• 2009-2010 INFLUENZA SEASON; INFLUENZA ACTIVITY REMAINED AT APPROXIMATELY AT THE SAME LEVELS AS WEEK 8

  Synopsis:

  1. 174 (5.1%) specimens tested by U.S. World Health Organization (WHO) and National Respiratory and Enteric Virus Surveillance System (NREVSS) collaborating laboratories and reported to CDC/Influenza Division were positive for influenza.
  2. All subtyped influenza A viruses reported to CDC were 2009 influenza A (H1N1) viruses.
  3. The proportion of deaths attributed to pneumonia and influenza (P&I) was below the epidemic threshold.
  4. No influenza-associated pediatric deaths were reported.
  5. The proportion of outpatient visits for influenza-like illness (ILI) was 1.9% which is below the national baseline of 2.3%. Three of 10 regions (Regions 4, 7, and 9) reported ILI at or above region-specific baseline levels.
  6. No states reported widespread influenza activity, five states reported regional influenza activity, Puerto Rico and six states reported local influenza activity, Guam, and 33 states reported sporadic influenza activity, the U.S. Virgin Islands and six states reported no influenza activity, and the District of Columbia did not report.

   

• PLAVIX (CLOPIDOGREL) HAS REDUCED EFFECTIVENESS IN PATIENTS WHO ARE POOR METABOLIZERS OF THE DRUG
  FDA notified healthcare professionals and patients that a Boxed Warning has been added to the prescribing information for Plavix, an anti-blood clotting medication. The Boxed Warning in the drug label will include information to:

  1. Warn about reduced effectiveness in patients who are poor metabolizers of Plavix. Poor metabolizers do not effectively convert Plavix to its active form in the body.
  2. Inform healthcare professionals that tests are available to identify genetic differences in CYP2C19 function.
  3. Advise healthcare professionals to consider use of other anti-platelet medications or alternative dosing strategies for Plavix in patients identified as poor metabolizers.

  Plavix is given to reduce the risk of Heart attack, unstable Angina, Stroke, and cardiovascular death in patients with Cardiovascular Disease. Plavix works by decreasing the activity of blood cells called platelets, making platelets less likely to form blood clots. A data summary and additional information for healthcare professionals and patients are provided in the linked Drug Safety Communication.

   
• BLOOD TRANSFUSION FOR PREVENTING STROKE IN PEOPLE WITH SICKLE CELL DISEASE

  Authors  Hirst Ceri, Wang Winfred C

  Review Group  Cochrane Cystic Fibrosis and Genetic Disorders Group

  Abstract  In sickle cell disease (SCD), a common inherited haemoglobin disorder, abnormal haemoglobin distorts red blood cells, causing anaemia, vaso-occlusion and dysfunction in most body organs. Stroke affects around 10% of children with sickle cell anaemia and recurrence is likely. Chronic blood transfusion dilutes the sickled red blood cells, reducing the risk of vaso-occlusion and stroke. However, side effects can be severe.

  Objectives:

  To assess risks and benefits of chronic blood transfusion regimens in people with SCD to prevent first stroke or recurrences.

  Search strategy:

  We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and conference proceedings.Last search of the Group's Trials Register: 22 May 2009.

  Selection criteria:

  Randomised and quasi-randomised controlled trials comparing blood transfusion as prophylaxis for stroke in people with SCD to alternative or no treatment.

  Data collection and analysis:

  Both authors independently assessed trial quality and extracted data.

  Main results:

  Searches identified two eligible trials. One compared a chronic transfusion regimen for maintaining sickle haemoglobin lower than 30% with standard care in 130 children with SCD judged (through transcranial doppler ultrasonography) as high-risk for first stroke. During the trial, 11 children in the standard care group suffered a stroke compared to one in the transfusion group. This 92% relative risk reduction meant the trial was terminated early. Thirty months treatment was planned, but median follow up was 21.1 months. The transfusion group had a high complications rate: iron overload; alloimmunisation; and transfusion reactions. The second trial investigated risk of stroke when transfusion was stopped after at least 30 months. The trial closed early due to a significant difference in risk of stroke between participants who stopped transfusion and those who continued (for whom it was deemed unsafe to recommend discontinuation), as measured by abnormal velocities on Doppler examinations, OR 0.02 (95% CI 0.00 to 0.43). No trials were identified investigating transfusion for preventing recurrence of stroke.

  Authors' conclusions:

  These trials demonstrated a significantly reduced risk of stroke in participants receiving regular blood transfusions. Data from a follow-up trial indicate individuals may revert to former risk status if transfusion is discontinued. Degree of risk must be balanced against the burden of chronic transfusions. Further research is required examining the use of transfusion in preventing secondary stroke, and further defining risk factors for stroke, to avoid unnecessarily starting children on blood transfusions.

  Implications  The STOP trial demonstrated a 90% relative reduction in risk of first stroke in high-risk children receiving regular blood transfusions, over a median follow up time of 21.1 months (STOP 1998). This must be balanced against the adverse effects and costs of a chronic transfusion regimen. The STOP 2 trial found that it is not safe to discontinue transfusion therapy, even after 30 months of treatment, in these high risk individuals (STOP 2 2005). No randomised controlled trials were found regarding prevention of secondary stroke by blood transfusion in people with sickle cell disease.

  Citation  Hirst C, Wang WC. Blood transfusion for preventing stroke in people with sickle cell disease. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD003146. DOI: 10.1002/14651858.CD003146.

   

• CURRENT USE OF ASPIRIN AND ANTITHROMBOTIC AGENTS IN PATIENTS WITH ATHEROTHROMBOTIC DISEASE
  Summary  About 25% of outpatients with vascular disease or at risk for it did not take aspirin, and 15% did not take any antithrombotic medication.

  Basis for Study "Despite its proven efficacy, low cost, and wide availability, aspirin remains underused." As part of the Reduction of Atherothrombosis for Continued Health Registry, the authors identified predictors of aspirin use in outpatients with atherothrombosis.

  Detailed Summary of Study  Demographic information and data on aspirin use were collected from 25,686 outpatients with atherothrombosis or at least three risk factors for it.

  Results/Body  Aspirin use was more likely in men, whites, patients age <65 and residents of the Midwest. About two thirds of the aspirin users took low-dose aspirin. Antithrombotic use was more common in whites, patients with atrial fibrillation or vascular disease, patients taking" other risk-reducing medications" and patients being treated by cardiologists. Antithrombotic use was less likely in women, smokers and diabetics.

  Sources & Other Links <> Cannon CP, Rhee KE, Califf RM, Boden WE, Hirsch AT, Alberts MJ, Cable G, Shao M, Ohman EM, Steg PG, Eagle KA, Bhatt DL; REACH Registry Investigators. Current use of aspirin and antithrombotic agents in the United States among outpatients with atherothrombotic disease (from the REduction of Atherothrombosis for Continued Health [REACH] Registry). Am J Cardiol. 2010 Feb 15;105(4):445-52

   
• EVEN SLIGHT REDUCTIONS IN DIETARY SALT COULD SUBSTANTIALLY REDUCE CARDIOVASCULAR DISEASE

  Summary "Modest reductions in dietary salt could substantially reduce cardiovascular events and medical costs and should be a public health target."

  Basis for Study  The authors projected the impact that lowering dietary salt levels would have on the incidence of cardiovascular disease in America.

  Detailed Summary of Study  The incidence of coronary heart disease, stroke, and myocardial infarction was estimated assuming a reduction in dietary salt intake by up to 3 g per day (1,200 mg sodium/day). The authors also examined the efficacy of salt reduction in various groups, compared the impact with that of other public-health efforts, and compared the cost-effectiveness of salt reduction vs. treatment of hypertension with medications.

  Results/Body "Reducing dietary salt by 3 g per day is projected to reduce the annual number of new cases of CHD by 60,000 to 120,000, stroke by 32,000 to 66,000, and myocardial infarction by 54,000 to 99,000 and to reduce the annual number of deaths from any cause by 44,000 to 92,000." It would save"194,000 to 392,000 quality-adjusted life-years and $10 billion to $24 billion in health care costs annually." Benefits were seen in all the groups analyzed, and salt reduction was found to be a more cost-effective way to reduce blood pressure than antihypertensive medications.  "The cardiovascular benefits of reduced salt intake are on par with the benefits of population-wide reductions in tobacco use, obesity, and cholesterol levels."

  Sources & Other Links  Bibbins-Domingo K, Chertow GM, Coxson PG, Moran A, Lightwood JM, Pletcher MJ, Goldman L. Projected effect of dietary salt reductions on future cardiovascular cisease. N Engl J Med. 2010 Feb 18;362(7):590-599

   

• SEVERELY OBESE TEENS LOSE MORE WEIGHT WITH GASTRIC BANDING THAN LIFESYTLE INTERVENTION
  Summary  Severely obese adolescents who underwent laparoscopic adjustable gastric banding lost significantly more weight, reduced their risk of metabolic syndrome and improved their quality of life compared to those who took part in a lifestyle intervention. However, revision operations were common in the surgical group.

  Basis for Study  This prospective randomized trial from Australia compared the outcomes of these two treatments in severely obese teens.

  Detailed Summary of Study  Subjects age 14 to 18 with a BMI >35 underwent gastric banding (n = 25) or took part in a supervised lifestyle intervention (n = 25). Weight loss, metabolic syndrome, insulin resistance, quality of life and adverse events was noted after 2 years in 24 of the gastric banding patients and 18 of the lifestyle intervention participants.

  Results/Body "Twenty-one (84%) in the gastric banding and 3 (12%) in the lifestyle groups lost more than 50% of excess weight, corrected for age. "Mean weight loss was 34.6 kg in the gastric banding group and 3.0 kg in the lifestyle intervention group. 9 of the 25 patients in the gastric banding group had metabolic syndrome before surgery and none had it at follow-up; corresponding figures for the lifestyle group were 10/25 at baseline and 4/18 at follow-up."The gastric banding group experienced improved quality of life with no perioperative adverse events. However, 8 operations (33%) were required in 7 patients for revisional procedures either for proximal pouch dilatation or tubing injury during follow-up."

  Sources & Other Links  O'Brien PE, Sawyer SM, Laurie C, Brown WA, Skinner S, Veit F, Paul E, Burton PR, McGrice M, Anderson M, Dixon JB. Laparoscopic adjustable gastric banding in severely obese adolescents: a randomized trial. JAMA. 2010 Feb 10;303(6):519-26.

   

• LONGER NEEDLES SHOULD BE USED WHEN GIVING HEPATITIS B VACCINE TO OBESE ADOLESCENTS
  Summary  Obese adolescents who received the hepatitis B vaccine using a 1.5-inch needle had significantly higher antibody titers than those immunized with a 1-inch needle.

  Basis for Study  The authors determined whether a shorter needle’s inability to penetrate the deltoid fat pad in obese adolescents could account for their lower antibody titers.

  Detailed Summary of Study <> Obese adolescents were randomized to receive the hepatitis B vaccine using a 1-inch or a 1.5-inch needle. Antibody titers were compared after vaccination.

  Results/Body <> Median titers were 189.8 mIU/mL with the 1-inch needle and 345.4 mIU/mL with the 1.5-inch needle."Needle length accounts for a significant portion of the discrepancy in immune response to HBV vaccine that is seen among those with obesity."

  Sources & Other Links  Middleman AB, Anding R, Tung C. Effect of needle length when immunizing obese adolescents with hepatitis B vaccine. Pediatrics. 2010 Feb 8. [Epub ahead of print].

   

• ORAL BISPHOSPHAONATES; ONGOING SAFETY REVIEW OF ATYPICAL SUBTROCHANTERIC FEMUR FRACTURES
  FDA notified healthcare professionals and patients that at this point, the data that FDA has reviewed have not shown a clear connection between bisphosphonate use and a risk of atypical subtrochanteric femur fractures. FDA is working with outside experts, including members of the recently convened American Society of Bone and Mineral Research Subtrochanteric Femoral Fracture Task Force, to gather more information and evaluate the issue further.

  FDA recommends that healthcare professionals follow the recommendations in the drug label when prescribing oral bisphosphonates.

  Patients should continue taking oral bisphosphonates unless told by their healthcare professional to stop. Patients should talk to their healthcare professional if they develop new hip or thigh Pain or have any concerns with their medications.

  [03/10/2010 - Drug Safety Communication: Ongoing safety review of oral bisphosphonates and atypical subtrochanteric femur fractures - FDA]

   

• WINRHO SDF (Rho(D) IMMUNE GLOBULIN INTRAVENOUS (HUMAN): RISK OF INTRAVASCULAR HEMOLYSIS IN PATIENTS WITH IMMUNE THROMBOCYTOPENIC PURPURA
  Cangene, Baxter and FDA notified healthcare professionals that cases of intravascular hemolysis (IVH) and its complications, including fatalities, have been reported in patients treated for immune thrombocytopenic purpura (ITP) with WinRho SDF. IVH can lead to clinically compromising anemia and multi-system organ failure including acute respiratory distress syndrome. Serious complications including severe anemia, acute renal insufficiency, renal failure and disseminated intravascular coagulation have also been reported. Fatal outcomes associated with IVH and its complications have occurred most frequently in patients of advanced age (age over 65) with co-morbid conditions.

  The Boxed Warning informs healthcare professionals that:

  1. Patients should be closely monitored in a health care setting for at least eight hours after adminstration
  2. A dipstick urinalysis should be performed at baseline, 2 hours, 4 hours after administration and prior to the end of the monitoring.
  3. patients should be alerted to and monitor for signs and symptoms of IVH, including back pain, shaking chills, fever, ad discolored urine or hematuria.  Absence of these signs ad/or symptoms of IVH within eight hours do not indicate IVH cannot occur subsequently
  4. If signs and/or symptoms of IVH are present or if IVH is suspected after WinRho administration, post-treatment laboratory tests should be performed including plasma hemoglobin, urinalysis, haptoglobin, LDH and plasm bilirubin (direct and indirect).

   
• INSULIN-SENSITIZING DRUGS FOR WOMEN WITH POLYCYSTIC OVARY SYNDROME

  Authors  Tang Thomas, Lord Jonathan M, Norman Robert J, Yasmin Ephia, Balen Adam H

  Review Group  Cochrane Menstrual Disorders and Subfertility Group

  Abstract  Polycystic ovary syndrome (PCOS) is characterised by anovulation, hyperandrogaenemia and insulin resistance. Hyperinsulinaemia is associated with an increase in cardiovascular risk and the development of diabetes mellitus. If insulin sensitising agents such as metformin are effective in treating features of PCOS, then they could have wider health benefits than just treating the symptoms of the syndrome.

  Objectives:

  To assess the effectiveness of insulin sensitising drugs in improving reproductive outcomes and metabolic parameters for women with PCOS and menstrual disturbance.

  Search strategy:

  We searched the Cochrane Menstrual Disorders & Subfertility Group trials register (searched September 2008), the Cochrane Central Register of Controlled Trials (Cochrane Library, third Quarter 2008), CINAHL (searched September 2008), MEDLINE (January 1966 to September 2008), and EMBASE (January 1985 to September 2008). All searches were rerun 13 August 2009 17 RCTs were located and await classification.

  Selection criteria:

  Randomised controlled trials which investigated the effect of insulin sensitising drugs compared with either placebo or no treatment, or compared with an ovulation induction agent.

  Data collection and analysis:

  Thirty one trials (2537 women) were included for analysis, 27 of them using metformin and involving 2150 women.

  Main results:

  There is no evidence that metformin improves live birth rates whether it is used alone (Pooled OR = 1.00, 95% CI 0.16 to 6.39) or in combination with clomiphene (Pooled OR = 1.48, 95% CI 1.12 to 1.95). However, clinical pregnancy rates are improved for metformin versus placebo (Pooled OR = OR 3.86, 95% C.I. 2.18 to 6.84) and for metformin and clomiphene versus clomiphene alone (Pooled OR =1.48, 95% C.I. 1.12 to 1.95) ). In the studies that compared metformin and clomiphene alone, there was no evidence of an improved live birth rate (OR= 0.67, 95% CI 0.44 to 1.02) but the pooled OR resulted in improved clinical pregnancy rate in in the clomiphene group (OR = 0.63 , 95% 0.43 to 0.92), although there was significant heterogeneity.There is also evidence that ovulation rates are improved with metformin in women with PCOS for metformin versus placebo (Pooled OR 2.12, 95% CI 1.50 to 3.0) and for metformin and clomiphene versus clomiphene alone (Pooled OR = 3.46, 95% CI 1.97 to 6.07).Metformin was also associated with a significantly higher incidence of gastrointestinal disturbance, but no serious adverse effects were reported.

  Authors' conclusions:

  In agreement with the previous review, metformin is still of benefit in improving clinical pregnancy and ovulation rates. However, there is no evidence that metformin improves live birth rates whether it is used alone or in combination with clomiphene, or when compared with clomiphene. Therefore, the use of metformin in improving reproductive outcomes in women with PCOS appears to be limited.

  Implications  In agreement with the previous review, metformin is still of benefit in improving clinical pregnancy and ovulation rates. However, there is no evidence that metformin improves live births whether it is used alone or in combination with clomiphene. In addition, metformin has limited effect on weight loss and metabolic parameters (insulin and the lipid profiles), especially in obese women with PCOS. Therefore, the use of metformin in improvement of reproductive outcomes or in reducing the risk of developing metabolic syndrome in women with PCOS appears to be limited. Furthermore, obesity poses a significant negative impact on the pregnancy outcomes Legro 2007. Hence, anovulatory obese women with PCOS should be advised to undergo life-style changes before fertility treatment (The Thessaloniki ESHRE/ASRM sponsored PCOS consensus workshop group, 2007) ESHRE/ASRM 2008.

  Citation  Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD003053. DOI: 10.1002/14651858.CD003053.pub3.

   

• GLUCOSAMINE THERAPY FOR TREATING OSTEOARTHRITIS
  Authors Towheed Tanveer, Maxwell Lara, Anastassiades Tassos P, Shea Beverley, Houpt JB, Welch Vivian, Hochberg Marc C, Wells George A

  Review Group  Cochrane Musculoskeletal Group

  Abstract Osteoarthritis (OA) is a common form of arthritis and is often associated with significant disability and impaired quality of life. This is an update of a Cochrane review first published in 2001 and previously updated in 2005.

  Objectives:

  To review randomized controlled trials (RCTs) evaluating the effectiveness and toxicity of glucosamine in OA.

  Search strategy:

  We searched CENTRAL and the Cochrane Database of Systematic Reviews (The Cochrane Library), MEDLINE, PREMEDLINE, EMBASE, AMED, ACP Journal Club, DARE (to January 2008); contacted content experts, and handsearched reference lists and pertinent review articles.

  Selection criteria:

  RCTs evaluating the effectiveness and safety of glucosamine in OA.

  Data collection and analysis:

  Data abstraction was performed independently by two review authors and investigators were contacted for missing data.

  Main results:

  This update includes 25 studies with 4963 patients. Analysis restricted to studies with adequate allocation concealment failed to show any benefit of glucosamine for pain (based on a pooled measure of different pain scales) and WOMAC pain, function and stiffness subscales; however, it was found to be better than placebo using the Lequesne index (standardized mean difference (SMD) -0.54; 95% confidence interval (CI) -0.96 to -0.12). Collectively, the 25 RCTs favoured glucosamine with a 22% (change from baseline) improvement in pain (SMD -0.47; 95% CI -0.72 to -0.23) and a 11% (change from baseline) improvement in function using the Lequesne index (SMD -0.47; 95% CI -0.82 to -0.12). However, the results were not uniformly positive and the reasons for this remain unexplained. WOMAC pain, function and stiffness outcomes did not reach statistical significance.RCTs in which the Rotta preparation of glucosamine was compared to placebo found glucosamine superior for pain (SMD -1.11; 95% CI -1.66 to -0.57) and function (Lequesne index SMD -0.47; 95% CI -0.82 to -0.12). Pooled results for pain (SMD -0.05; 95% CI -0.15 to 0.05) and function using the WOMAC index (SMD -0.01; 95% CI -0.13 to 0.10) in those RCTs using a non-Rotta preparation of glucosamine did not reach statistical significance. Two RCTs using the Rotta preparation showed that glucosamine was able to slow radiological progression of OA of the knee over a three-year period (mean difference (MD) 0.32; 95% CI 0.05 to 0.58).Glucosamine was as safe as placebo in terms of the number of participants reporting adverse reactions (relative risk ratio 0.99; 95% CI 0.91 to 1.07).

  Authors' conclusions:

  Pooled results from studies using a non-Rotta preparation or adequate allocation concealment failed to show benefit in pain and WOMAC function while those studies evaluating the Rotta preparation showed that glucosamine was superior to placebo in the treatment of pain and functional impairment resulting from symptomatic OA.

  Implications  The previous review from 2005, with 20 studies and 2570 participants, showed that glucosamine sulphate taken orally in amounts of 1500 mg/day produced a 28% (per cent change from baseline) benefit in pain and an increase in function of 21% (per cent change in Lequesne Index from baseline) in osteoarthritis, without side effects.If only the best designed studies are included, the benefit in pain and WOMAC function is no longer present; as shown in this update which includes 25 studies and 4963 patients. Inclusion of five new studies reduces the overall benefit on pain to 22% and function to 11% in the Lequesne Index. Pooled results from studies using a non-Rotta preparation or adequate allocation concealment failed to show benefit in pain and WOMAC function, while those studies evaluating the Rotta preparation showed that glucosamine was superior to placebo in the treatment of pain and functional impairment resulting from symptomatic OA. WOMAC outcomes of pain and function showed a superiority of glucosamine over placebo for only the Rotta preparation of glucosamine.Some studies suggest the Rotta preparation of glucosamine sulfate may slow radiological progression of OA of the knee over a three-year period. The ability of glucosamine to improve symptoms and delay radiological progression of OA affecting other joint sites also needs further research.Glucosamine was as safe as placebo.

  Citation  Towheed T, Maxwell L, Anastassiades TP, Shea B, Houpt JB, Welch V, Hochberg MC, Wells GA. Glucosamine therapy for treating osteoarthritis. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD002946. DOI: 10.1002/14651858.CD002946.pub2.

   
• INFLUENZA VACCINE MAY NOT BE BENEFICIAL IN PATIENTS WITH CYSTIC FIBROSIS

  Authors  Dharmaraj Poonam, Smyth Rosalind L

  Review Group  Cochrane Cystic Fibrosis and Genetic Disorders Group

  Abstract  Viral respiratory tract infections in people with cystic fibrosis (CF) have a deteriorating effect on their lung function and disease progression. Annual influenza vaccination is therefore commonly recommended for people with CF.

  Objectives:

  To assess the effectiveness of influenza vaccination for people with CF.

  Search strategy:

  We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and hand searching of relevant journals and abstract books of conference proceedings. We also contacted the companies which market the influenza vaccines used in the trials to obtain further information about randomized controlled trials. Date of the most recent search of the Cystic Fibrosis Trials Register: 05 March 2009.

  Selection criteria:

  All randomized and quasi-randomized trials (published or unpublished) comparing any influenza vaccine with a placebo or with another type of influenza vaccine.

  Data collection and analysis:

  Two authors independently assessed study quality and extracted data. Additional information was obtained by contacting the investigators when it was indicated.

  Main results:

  Four studies enrolling a total of 179 participants with CF (143 (80%) were children aged 1 to 16 years) were included in this review. There was no study comparing a vaccine to a placebo or a whole virus vaccine to a subunit or split virus vaccine. Two studies compared an intranasal applied live vaccine to an intramuscular inactivated vaccine and the other two studies compared a split virus to a subunit vaccine and a virosome to a subunit vaccine (all intramuscular). The incidence of all reported adverse events was high depending on the type of influenza vaccine. The total adverse event rate ranged from 48 out of 201 participants (24%) for the intranasal live vaccine to 13 out of 30 participants (43%) for the split virus vaccine. With the limitation of a statistical low power there was no significant difference between the study vaccinations. None of the events were severe. All study influenza vaccinations generated a satisfactory serological antibody response. No study reported other clinically important benefits.

  Authors' conclusions:

  There is currently no evidence from randomized studies that influenza vaccine given to people with CF is of benefit to them. There remains a need for a well-constructed clinical study, that assesses the effectiveness of influenza vaccination on important clinical outcome measures.

  Implications  According to some national recommendations and the practice in many units caring for people with CF, it is advisable to vaccinate people with CF against influenza annually. Evidence from randomized controlled studies to support this recommendation in people with CF is lacking and clinicians must make judgments on the benefits and risks of this therapy in people with CF. The cost of annual influenza vaccination may also be considered before implementing changes to current practice. In the UK in 2008 annual influenza vaccination cost 3.55 (excluding VAT) per patient per year (RLCH Pharmacy 2009).

  Citation  Dharmaraj P, Smyth RL. Vaccines for preventing influenza in people with cystic fibrosis. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD001753. DOI: 10.1002/14651858.CD001753.pub2.

   

• IN ACUTE NECK STRAIN, CYCLOBENZAPRINE, IBUPROFEN, OR BOTH RELIEVE PAIN EQUALLY WELL
  There is little benefit to routinely using or adding cyclobenzaprine to NSAIDs for ED patients with acute cervical strain."

  Basis for Study  This randomized controlled trial compared the effectiveness of the NSAID ibuprofen, the centrally acting muscle relaxant cyclobenzaprine (Flexeril®), or both, in ED patients with acute neck strain.

  Detailed Summary of Study  Adult ED patients with cervical strain after a motor vehicle accident or a fall were randomized to receive ibuprofen (800 mg; n = 20), cyclobenzaprine (5 mg; n = 21) or both (n = 20) three times a day for 7 days. Pain relief and adverse events were compared.

  Results/Body  No significant differences were found between the treatments in terms of pain relief or adverse events.

  Sources & Other Links  Khwaja SM, Minnerop M, Singer AJ. Comparison of ibuprofen, cyclobenzaprine or both in patients with acute cervical strain: a randomized controlled trial. CJEM. 2010 Jan;12(1):39-44.

   

• 2009-2010 INFLUENZA SEASON ACTIVITY REMAINS AT APPROXIMATELY THE SAME LEVELS AS WEEK 6.
  185 (4.4%) specimens tested by U.S. World Health Organization (WHO) and National Respiratory and Enteric Virus Surveillance System (NREVSS) collaborating laboratories and reported to CDC/Influenza Division were positive for influenza.

  All subtyped influenza A viruses reported to CDC were 2009 influenza A (H1N1) viruses.

  The proportion of deaths attributed to pneumonia and influenza (P&I) was below the epidemic threshold.

  Three influenza-associated pediatric deaths were reported. One death was associated with 2009 influenza A (H1N1) virus infection and two deaths were associated with an influenza A virus for which the subtype was undetermined.

  The proportion of outpatient visits for influenza-like illness (ILI) was 1.8% which is below the national baseline of 2.3%. Three of 10 regions (Regions 1, 4, and 7) reported ILI above region-specific baseline levels.

  No states reported widespread influenza activity, three states reported regional influenza activity, Puerto Rico and eight states reported local influenza activity, the District of Columbia, Guam, and 35 states reported sporadic influenza activity, the U.S. Virgin Islands and four states reported no influenza activity.

   
• FDA CLEARS NEW TEST FOR OVARIAN CANCER WHICH CAN HELP IDENTIFY POTENTIAL MALIGNANCIES AND GUIDE SURGICAL DECISIONS
  
  The U.S. Food and Drug Administration today cleared a test that can help detect ovarian cancer in a pelvic mass that is already known to require surgery. The test, called OVA1, helps patients and health care professionals decide what type of surgery should be done and by whom.
  
  OVA1 identifies some women who will benefit from referral to a gynecological oncologist for their surgery, despite negative results from other clinical and radiographic tests for ovarian cancer. If other test results suggest cancer, referral to an oncologist is appropriate even with a negative OVA1 result.
  
  OVA1 should be used by primary care physicians or gynecologists as an adjunctive test to complement, not replace, other diagnostic and clinical procedures.
  
  OVA1 uses a blood sample to test for levels of five proteins that change due to ovarian cancer. The test combines the five separate results into a single numerical score between 0 and 10 to indicate the likelihood that the pelvic mass is benign or malignant.
  
  OVA1 is intended only for women, 18 years and older, who are already selected for surgery because of their pelvic mass. It is not intended for ovarian cancer screening or for a definitive diagnosis of ovarian cancer. Interpreting the test result requires knowledge of whether the woman is pre- or post-menopausal.
  
  The American College of Obstetricians and Gynecologists and the Society of Gynecologic Oncologists published recommendations in 2002 for the role of generalist obstetrician-gynecologists in the early detection of ovarian cancer, which included a recommendation of patient referral to a gynecological oncologist when specific indicators of malignancy are present.
  
  These recommendations and later reports indicate that patients with ovarian cancer have improved survival when the surgery is performed by gynecologic oncologists as opposed to general gynecologists or surgeons.
  
  “Tests such as OVA1 personalize and improve public health by providing patients and health care providers with more information to support medical decisions that impact survival rates and reduce surgical complications,” said Jeffrey Shuren, M.D., J.D., acting director of the FDA’s Center for Devices and Radiological Health.
  
  The FDA reviewed a study of 516 patients, including 269 evaluated by non-gynecological oncologists, which compared OVA1 results with biopsy results. When combined with pre-surgical information, such as radiography and other laboratory tests, results from the OVA1 tests identified additional patients who might benefit from oncology referral who were not identified using pre-surgical information alone.
  
  OVA1 is developed by Vermillion Inc., headquartered in Fremont, Calif., in conjunction with researchers at The Johns Hopkins University in Baltimore.

   

• COLCHICINE MARKETED AS COLCRYS NOW FDA APPROVED
  
  FDA notified healthcare professionals of the approval of the first single-ingredient oral colchicine product, Colcrys, for the treatment of familial Mediterranean fever (FMF) and acute gout flares and of two previously uncharacterized safety concerns associated with the use of colchicine. Oral colchicine has been used for many years as an unapproved drug with no FDA-approved prescribing information, dosage recommendations, or drug interaction warnings.
  
  FDA analyzed safety data for colchicine from adverse events reported to the Agency, the published literature, and company-sponsored pharmacokinetic and drug interaction studies. This analysis revealed cases of fatal colchicine toxicity reported in certain patients taking standard therapeutic doses of colchicine and concomitant medications that interact with colchicine, such as clarithromycin. These reports suggest that drug interactions affecting the gastrointestinal absorption and/or hepatic metabolism of colchicine play a central role in the development of colchicine toxicity. Data submitted supporting the safety and efficacy of Colcrys in acute gout flares demonstrated that a substantially lower dose of colchicine was as effective as the higher dose traditionally used. Moreover, patients receiving the lower dose experienced significantly fewer adverse events compared to the higher dose.
  
  Based on this information, FDA has included important safety considerations in the approved prescribing information to assure safe use of Colcrys and is providing background information, a data summary and recommendations in this alert.

• UNAPPROVED USE OF RELENZA (ZANAMIVIR) VIA NEBULIZATION/MECHANICAL VENTILATION CAN BE ASSOCIATED WITH FATAL OUTCOME

• LHRH AGONISTS FOR ADJUVANT THERAPY OF EARLY BREAST CANCER IN PREMENOPAUSAL WOMEN

• IN NEWLY DIAGNOSED CANCER PATIENTS PROGNOSIS AFFECTS INFORMATION RECALL BETTER THAN AGE

  Summary  In newly diagnosed cancer patients, prognosis is a better indicator of information recall than age.

  Basis for Study/Article  This study identified variables affecting information recall in patients newly diagnosed with cancer.

  Detailed Summary of Study  The study comprised 260 cancer patients seeing an oncologist for the first time. The visits were audiotaped, and patients were later asked to recall details about their diagnosis, prognosis and treatment. The amount and accuracy of their recall were checked against the recordings.

  Results/Body  Prognosis had a strong influence on recall. Patients with a poorer prognosis remembered less information, but regardless of the prognosis, patients given more information about prognosis remembered less. Older patients remembered less information than younger ones, but only when a large amount of information given.

  Sources & Other Links  Jansen J, et al. Does age really matter? Recall of information to newly patients with cancer. J Clin Oncol 2008;Oct 20 [olbp]Article Link (JCO)

   

• HIGH DOSES OF VITAMIN B DON'T SLOW COGNITIVE DECLINE IN ALZHEIMER'S DISEASE
  Summary  This randomized controlled trial found that high doses of vitamin B don’t slow cognitive decline in patients with mild to moderate Alzheimer’s disease.

  Basis for Study/Article  This multicenter trial assessed whether vitamin B supplements, by decreasing homocysteine levels, could slow the progression of Alzheimer’s disease.

  Detailed Summary of Study  Patients with mild to moderate Alzheimer’s disease (MMSE score 14-26) were randomized to receive high-dose folate (5 mg/day), vitamin B6 (25 mg/day) and vitamin B12 (1 mg/day) (n = 202) or placebo (n = 138) for 18 months. Change from baseline was assessed using the cognitive subscale of the Alzheimer Disease Assessment Scale.

  Results/Body  Patients taking the vitamins had lower homocysteine levels than those in the placebo group, but there were no significant differences between the groups in terms of cognitive function. The patients taking vitamins had “a higher quantity of adverse events involving depression.”

  Sources & Other Links  Aisen PS, et al. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA. 2008 Oct 15;300(15):1774-83. Article Link (NCBI)

   

• PHENYTOIN AND FOSPHENYTOIN ALERT
  FDA is investigating new preliminary data regarding a potential increased risk of serious skin reactions including Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) from phenytoin therapy in Asian patients positive for a particular human leukocyte antigen (HLA) allele, HLA-B*1502. This allele occurs almost exclusively in patients with ancestry across broad areas of Asia, including Han Chinese, Filipinos, Malaysians, South Asian Indians, and Thais. Because fosphenytoin is a prodrug and is converted to phenytoin after administration, any concern regarding this association is also applicable to fosphenytoin. Phenytoin and fosphenytoin are used to control tonic-clonic (grand mal) and complex-partial seizures in epilepsy.

  A recent FDA Information for Healthcare Professionals sheet (12/12/2007), described an increased risk of SJS/TEN with another antiepileptic drug, carbamazepine, in Asian ancestry patients with the HLA-B*1502 allele.

  The FDA is working to identify additional information to evaluate the possible risk of SJS/TEN from phenytoin and fosphenytoin in patients with HLA-B*1502. Until the evaluation is completed, healthcare providers who are considering the use of phenytoin or fosphenytoin should be aware of the risks and benefits described in the current prescribing information for this drug.

  Because this new data suggests a possible association between HLA-B*1502 and phenytoin or fosphenytoin-induced SJS/TEN, and because of the known association between phenytoin and SJS/TEN, healthcare providers should consider avoiding phenytoin and fosphenytoin as alternatives for carbamazepine in patients who test positive for HLA-B*1502.

   
• GINKGO EVALUATION OF MEMORY (GEM) STUDY FAILS TO SHOW BENEFIT IN PREVENTING DEMENTIA IN THE ELDERLY

  In this news release written by the National Institute on Aging, the dietary supplement Ginkgo biloba was found to be ineffective in reducing the development of dementia and Alzheimer's disease in older people, according to a study published in the "Journal of the American Medical Association.  To read more, visit:

  nia.nih.gov/Alzheimers/ResearchInformation/NewsReleases/PR20081119ginkgo.htm

   
• PSYCHOSOCIAL AND PHARMACOLOGICAL TREATMENTS VERSUS PHARMACOLOGICAL TREATMENTS FOR OPIOD DETOXIFICATION

  Authors  Amato L, Minozzi S, Davoli M, Vecchi S, Ferri MMF, Mayet S.

  Review Group  Cochrane Drugs and Alcohol Group

  Abstract  Different pharmacological approaches aimed at opioid detoxification are effective. Nevertheless a majority of patients relapse to heroin use, and relapses are a substantial problem in the rehabilitation of heroin users. Some studies have suggested that the sorts of symptoms which are most distressing to addicts during detoxification are psychological rather than physiological symptoms associated with the withdrawal syndrome.

  Objectives

  To evaluate the effectiveness of any psychosocial plus any pharmacological interventions versus any pharmacological alone for opioid detoxification, in helping patients to complete the treatment, reduce the use of substances and improve health and social status.

  Search strategy

  We searched the Cochrane Drugs and Alcohol Group trials register (27 February 2008). Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2008), PUBMED (1996 to February 2008); EMBASE (January 1980 to February 2008); CINAHL (January 2003-February 2008); PsycINFO (1985 to April 2003) and reference list of articles.

  Selection criteria

  Randomised controlled trials which focus on any psychosocial associated with any pharmacological intervention aimed at opioid detoxification. People less than 18 years of age and pregnant women were excluded.

  Data collection and analysis

  Three reviewers independently assessed trials quality and extracted data.

  Main results

  Nine studies involving people were included. These studies considered five different psychosocial interventions and two substitution detoxification treatments: Methadone and Buprenorphine. The results show promising benefit from adding any psychosocial treatment to any substitution detoxification treatment in terms of completion of treatment relative risk (RR) 1.68 (95% confidence interval (CI) 1.11 to 2.55), use of opiate RR 0.82 (95% CI 0.71 to 0.93), results at follow-up RR 2.43 (95% CI 1.61 to 3.66), and compliance RR 0.48 (95% CI 0.38 to 0.59).

  Authors' conclusions

  Psychosocial treatments offered in addition to pharmacological detoxification treatments are effective in terms of completion of treatment, use of opiate, results at follow-up and compliance. Although a treatment, like detoxification, that exclusively attenuates the severity of opiate withdrawal symptoms can be at best partially effective for a chronic relapsing disorder like opiate dependence, this type of treatment is an essential step prior to longer-term drug-free treatment and it is desirable to develop adjunct psychosocial approaches that might make detoxification more effective. Limitations to this review are imposed by the heterogeneity of the assessment of outcomes. Because of lack of detailed information no meta analysis could be performed to analyze the results related to several outcomes.

  Implications  Psychosocial treatments offered in addition to pharmacological detoxification treatments are effective in term of completion of treatment, use of opiate, results at follow-up and compliance. Although a treatment, like detoxification, that exclusively attenuates the severity of opiate withdrawal symptoms can be at best partially effective for a chronic relapsing disorder like opiate dependence, this form of treatment is an essential step prior to longer-term drug-free treatment and it is desirable to develop adjunct psychosocial approaches that might make detoxification more effective.

  Citation  Amato L, Minozzi S, Davoli M, Vecchi S, Ferri MMF, Mayet S. Psychosocial and pharmacological treatments versus pharmacological treatments for opioid detoxification. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD005031. DOI: 10.1002/14651858.CD005031.pub2.

   

• NOVEMBER 12, 2008
  Update of Safety Review Follow-up to the October 1, 2007 - Early Communication about the Ongoing Safety Review of Bisphosphonates

  Bisphosphonates marketed as Alendronate (Fosamax, Fosamax Plus D)
  Etidronate (Didronel)
  Ibandronate (Boniva)
  Pamidronate (Aredia)
  Risedronate (Actonel, Actonel W/Calcium)
  Tiludronate (Skelid)
  Zoledronic acid (Reclast, Zometa)

  On October 1, 2007, FDA announced that it was reviewing safety data that raised concerns about a potential increased risk for atrial fibrillation in patients treated with a bisphosphonate drug http://www.fda.gov/cder/drug/early_comm/bisphosphonates.htm. An article and an accompanying letter to the editor in the May 3, 2007, issue of The New England Journal of Medicine described increased rates of serious atrial fibrillation in two different studies of women ages 65 to 89 years old with osteoporosis treated with the bisphosphonates, Reclast and Fosamax. Data available to FDA at that time, including data from the NDA approval of Reclast for osteoporosis, showed an increased risk of serious atrial fibrillation and this risk was reflected in the Reclast labeling. After our review, based on the data available at this time, healthcare professionals should not alter their prescribing patterns for bisphosphonates and patients should not stop taking their bisphosphonate medication.

  On October 1, 2007, FDA began requesting placebo-controlled clinical trial information from the sponsors of alendronate, ibandronate, risedronate, and zoledronic acid in order to explore the potential risk for atrial fibrillation in male and female patients treated with these bisphosphonate drugs.

  The data submitted by the four sponsors included data on 19,687 bisphosphonate-treated patients and 18,358 placebo-treated patients who were followed for 6 months to 3 years.

  The occurrence of atrial fibrillation was rare within each study, with most studies containing 2 or fewer events. The absolute difference in event rates between each of the bisphosphonate and placebo arms varied from 0-3 per 1,000.

  One large study of zoledronic acid showed a statistically significant increase in the rate of serious atrial fibrillation events. However, across all studies, no clear association between overall bisphosphonate exposure and the rate of serious or non-serious atrial fibrillation was observed. Increasing dose or duration of bisphosphonate therapy was also not associated with an increased rate of atrial fibrillation.

  The FDA is aware of discordant results from the literature and from other epidemiological studies about the incidence and clinical course of atrial fibrillation in patients taking bisphosphonates. FDA is exploring the feasibility of conducting additional epidemiologic studies to examine this issue. In addition, FDA is continuing to monitor post-market reports of atrial fibrillation in patients who have taken bisphosphonates.

  Bisphosphonates are a class of drugs used primarily to increase bone mass and reduce the risk for fracture in patients with osteoporosis. Bisphosphonates are also used to slow bone turnover in patients with Paget’s disease of the bone and to treat bone metastases and lower elevated levels of blood calcium in patients with cancer. There are 7 FDA-approved bisphosphonates: alendronate (Fosamax, Fosamax Plus D), etidronate (Didronel), ibandronate (Boniva), pamidronate (Aredia), risedronate (Actonel, Actonel W/Calcium), tiludronate (Skelid), and zoledronic acid (Reclast, Zometa).

  This follow-up communication is in keeping with FDA’s commitment to inform the public about its ongoing safety reviews of drugs.

  The FDA urges both healthcare professionals and patients to report side effects from the use of bisphosphonates to the FDA's MedWatch Adverse Event Reporting program.

   

   
• CLASS 1 RECALL

  VIBE Technologies, Vibrational Integrated Bio-photonic Energizer (VIBE) Machine Multi-Frequency Field Generator

  Product:

  Vibrational Integrated Bio-photonic Energizer (VIBE) Machine Multi-Frequency Electromagnetic Field Generator

  This product was manufactured and distributed from November 16, 2002 through March 19, 2008.

  Use:

  The company’s labeling reported that the device could be used to treat or cure medical conditions and diseases such as:

  •		cancer
  •		depression
  •		infection
  •		pain

  The firm has failed to provide FDA with any evidence to support these claims.

  Recalling Firm:

  VIBE Technologies
  2329 W. 10th St
  Greeley, Colorado 80634-3527

  Reason for Recall:

  This device has not been approved by FDA, lacks safety and effectiveness data, and is not manufactured under current good manufacturing practices.

  Public Contact:

  Customers or other individuals that have been treated with this device may contact VIBE Technologies at 1-970-356-9594.

  FDA District:

  Denver

  FDA Comment:

  On October 1, 2008, the company sent a certified letter to each customer who purchased the device to stop using it. The letter also included:

  •		a warning label to be permanently placed on the VIBE Machine stating that it is not a medical device and should not be used as one.
  •		an updated operation manual/users’ guide that contains no medical conditions or treatment claims.
  •		a certification to be signed by the user and returned to the company acknowledging that they: ›   received the letter. ›   attached the warning label on the device, and ›   understand that the VIBE Machine does not affect the structure or function of the human or animal body.
  •		a request that the user certify that they will: ›   not promote the VIBE Machine as a medical device. ›   remove any medical claims from their individual websites, and ›   destroy any VIBE literature making medical claims.
  •		a warning that failure to sign and return the certification will result in the company refusing to service their machine.

  Class 1 recalls are the most serious type of recall and involve situations in which there is a reasonable probability that use of the product will cause serious injury or death.

  Health care professionals and consumers may report adverse reactions or quality problems experienced with the use of this product to the FDA's MedWatch Adverse Event Reporting program either online, by regular mail or by FAX.

   
• FDA ALERT

  Serious Complications Associated with Transvaginal Placement of Surgical Mesh in Repair of Pelvic Organ Prolapse and Stress Urinary Incontinence - Issued: October 20, 2008

  Dear Healthcare Practitioner:

  This is to alert you to complications associated with transvaginal placement of surgical mesh to treat Pelvic Organ Prolapse (POP) and Stress Urinary Incontinence (SUI). Although rare, these complications can have serious consequences. Following is information regarding the adverse events that have been reported to the FDA and recommendations to reduce the risks.

  Nature of the Problem

  Over the past three years, FDA has received over 1,000 reports from nine surgical mesh manufacturers of complications that were associated with surgical mesh devices used to repair POP and SUI. These mesh devices are usually placed transvaginally utilizing tools for minimally invasive placement.

  The most frequent complications included erosion through vaginal epithelium, infection, pain, urinary problems, and recurrence of prolapse and/or incontinence. There were also reports of bowel, bladder, and blood vessel perforation during insertion. In some cases, vaginal scarring and mesh erosion led to a significant decrease in patient quality of life due to discomfort and pain, including dyspareunia.

  Treatment of the various types of complications included additional surgical procedures (some of them to remove the mesh), IV therapy, blood transfusions, and drainage of hematomas or abscesses.

  Specific characteristics of patients at increased risk for complications have not been determined. Contributing factors may include the overall health of the patient, the mesh material, the size and shape of the mesh, the surgical technique used, concomitant procedures undertaken (e.g. hysterectomy), and possibly estrogen status.

  Recommendations

  Physicians should:

  Obtain specialized training for each mesh placement technique, and be aware of its risks.

  Be vigilant for potential adverse events from the mesh, especially erosion and infection.

  Watch for complications associated with the tools used in transvaginal placement, especially bowel, bladder and blood vessel perforations.

  Inform patients that implantation of surgical mesh is permanent, and that some complications associated with the implanted mesh may require additional surgery that may or may not correct the complication.

  Inform patients about the potential for serious complications and their effect on quality of life, including pain during sexual intercourse, scarring, and narrowing of the vaginal wall.

  Additional patient information can be found on the following FDA Consumer website at http://www.fda.gov/cdrh/consumer/surgicalmesh-popsui.html.

   
• ANXIETY PLAYS A KEY ROLE IN DEPRESSION

  Summary Anxiety plays a key role in depression, although anxiety symptoms differ with varying levels of depression. "The relationship between anxiety-related symptoms and depression should be considered in the assessment of depression and evaluation of treatment strategies and outcome."

  Basis for Study/Article  The authors explored the effect that anxiety-related symptoms have in major depression.

  Detailed Summary of Study  Using data from four clinical trials, the authors analyzed the relationship between patient scores on the Hamilton Anxiety Rating Scale and the Hamilton Depression Rating Scale.

  Results/Body  In general, anxiety symptoms increased with more severe depression. Anxious mood, tension, insomnia, concentration and memory problems and depressed mood were present at all levels of depression, but anxiety-related somatic problems were present only with more severe depression.

  Sources & Other Links  Vaccarino AL, et al. Symptoms of anxiety in depression: assessment of item performance of the Hamilton Anxiety Rating Scale in patients with depression. Depress Anxiety. 2008 Sep 17. Article Link (NCBI)

   

• METHYLXANTHINE TREATMENT FOR APNEA IN PRETERM INFANT

  Authors  Henderson-Smart David J, Steer Peter A

  Review Group  Cochrane Neonatal Group

  Abstract  Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and bradycardia that may be severe enough to require resuscitation including use of positive pressure ventilation. Methylxanthines (such as caffeine or theophylline) have been used to stimulate breathing and prevent apnea and its consequences.

  Objectives

  To determine the effects of methylxanthine treatment on the incidence of apnea and the use of intermittent positive pressure ventilation (IPPV), and other clinically important effects in preterm infants with recurrent apnea.

  Search strategy

  Searches were made of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2007), the Oxford Database of Perinatal Trials, MEDLINE (1966 to January 2008), EMBASE (1982 - January 2008), previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal hand searching mainly in the English language.

  Selection criteria

  All trials utilizing random or quasi-random patient allocation in which methylxanthine (theophylline or caffeine) was compared with placebo or no treatment for apnea in preterm infants were included.

  Data collection and analysis

  Methodological quality was assessed independently by the two review authors. Data were extracted independently by the two review authors. Treatment effects were expressed as relative risk (RR) and risk difference (RD) and their 95% confidence intervals, using a fixed effect model. For significant results, the inverse of the risk difference (1/RD) was used to calculate the number needed to treat (NNT).

  Main results

  The results of five trials that enrolled a total of 192 preterm infants with apnea indicate that methylxanthine therapy leads to a reduction in apnea and use of IPPV in the first two to seven days. There are insufficient data to adequately evaluate side effects and no data to examine effects within different gestational age groups. There are no data in the included studies that examine long-term effects.

  Authors' conclusions

  Methylxanthines are effective in reducing the number of apneic attacks and the use of mechanical ventilation in the two to seven days after starting treatment. In view of its lower toxicity, caffeine would be the preferred drug. The effects of methylxanthines on long-term outcomes will be addressed in data from the trial awaiting assessment (CAP Trial 2006).

  Implications  Methylxanthines are effective in reducing the number of apneic attacks in the short-term and in reducing the use of mechanical ventilation. In view of its lower toxicity, caffeine would be the preferred drug. In included studies, the safety of methylxanthine therapy is uncertain, especially in terms of lack of long-term growth and neurodevelopment outcomes.

  Citation  Henderson-Smart DJ, Steer PA. Methylxanthine treatment for apnea in preterm infants. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD000140. DOI: 10.1002/14651858.CD000140.

   

• ARIPIPRAZOLE VERSUS TYPICAL ANTIPSYCHOTIC DRUGS FOR SCHIZOPHRENIA

  Authors  Bhattacharjee Jayanti, El-Sayeh Hany George G

  Review Group  Cochrane Schizophrenia Group

  Abstract  Aripiprazole is a relatively new antipsychotic drug, said to be the prototype of a new third generation of antipsychotics; the so-called dopamine-serotonin system stabilisers. In this review we examine how the efficacy and tolerability of aripiprazole differs from that of typical antipsychotics.

  Objectives

  To evaluate the effects of aripiprazole compared with other typical antipsychotics for people with schizophrenia and schizophrenia-like psychoses.

  Search strategy

  We searched the Cochrane Schizophrenia Group Trials Register (November 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. We inspected references of all identified studies for further trials. We contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information.

  Selection criteria

  We included all randomised trials comparing aripiprazole with typical antipsychotics in people with schizophrenia or schizophrenia-like psychosis.

  Data collection and analysis

  We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model. We have contacted representatives of Bristol Myers Squibb pharmaceuticals (UK) for additional data.

  Main results

  We included nine randomised trials involving 3122 people comparing aripiprazole with typical antipsychotic drugs. None of the studies reported on relapse - our primary outcome of interest. Attrition from studies was high and data reporting poor. Participants given aripiprazole were comparable to those receiving typical drugs in improving global state and mental state. Aripiprazole provided a significant advantage over typical antipsychotics in terms of fewer occurrences of extra-pyramidal symptom (n=968, 3 RCT, RR 0.46 CI 0.3 to 0.9, NNT 13 CI 17 to 10), and particularly akathisia (n=897, 3 RCT, RR 0.39 CI 0.3 to 0.6, NNT 11 CI 14 to 9). Fewer participants given aripiprazole developed hyperprolactinaemia (n=300, 1 RCT, RR 0.07 CI 0.03 to 0.2, NNT 2 CI 3 to 1). Aripiprazole presented a lesser risk of sinus tachycardia (n=289, 1 RCT, RR 0.09 CI 0.01 to 0.8, NNT 22 CI 63 to 13) and blurred vision (n=308, 1 RCT, RR 0.19 CI 0.1 to 0.7, NNT 14 CI 25 to 10); but enhanced risk of occurrence of dizziness (n=957, 3 RCT, RR 1.88 CI 1.1 to 3.2, NNH 20 CI 33 to 14) and nausea (n=957, 3 RCT, RR 3.03 CI 1.5 to 6.1, NNH 17 CI 25 to 13). Attrition rates were high in both groups, although significantly more participants in the aripiprazole group completed the study in the long term (n=1294, 1 RCT, RR 0.81 CI 0.8 to 0.9 NNT 8 CI 5 to 14).

  Authors' conclusions

  Aripiprazole differs little from typical antipsychotic drugs with respect to efficacy, however it presents significant advantages in terms of tolerability. Clearly reported pragmatic short, medium and long term randomised controlled trials are required to replicate and validate these findings and determine the position of aripiprazole in everyday clinical practice.

  Implications

  1.		For people with schizophrenia Aripiprazole is not clearly more or less effective than typical antipsychotics in terms of improving global outcomes or mental state. However it confers a significant advantage over older drugs in terms of fewer occurrences of extra-pyramidal symptom related adverse events, but it is more likely to cause dizziness and nausea. Hyperprolactinaemia and associated complications of unpleasant breast pain and secretion and osteoporosis do not seem to be a significant concern with aripiprazole; while they remain adverse effects commonly seen with the older drugs. There appears to be a lesser chance of developing sinus tachycardia whilst taking aripiprazole even though it does not present any significant advantages over the typical drugs in causing QTc abnormalities.
  2.		For clinicians Aripiprazole appears to be as efficacious and effective as the comparator typical antipsychotic drugs in the included studies. It presents a significantly favourable adverse effect profile when compared to the older drugs. This suggests a significant advantage over typical drugs in ensuring compliance. However aripiprazole has been compared to haloperidol, perphenazine, and chlorpromazine in the studies included in this review and a sensitivity analysis could not be conducted due to lack of adequate relevant data; it cannot therefore be definitively concluded that it is as effective as or better tolerated than all typical antipsychotic drugs at various dose ranges. More studies are needed to replicate and validate these findings.
  3.		For managers/policy makers No data has emerged about service outcomes. Data about economic outcomes are minimal and insignificant. Even though aripiprazole appears to be an efficacious and effective drug there is inadequate data about medium and long-term outcomes. In the context of finite resources, the lack of good quality data leaves managers and policy makers with difficult decisions to make.

  Citation  Bhattacharjee J, El-Sayeh HGG. Aripiprazole versus typical antipsychotic drugs for schizophrenia. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD006617. DOI: 10.1002/14651858.CD006617.pub3.

   

• WHICH SHORT-CHAIN CARBS ARE THE VILLAINS IN IBS?
  
  Researchers challenged IBS patients with dietary fructose, fructans, and glucose.
  
  Malabsorption of fructose and other short-chain carbohydrates is thought to produce symptoms of irritable bowel syndrome (IBS). Common dietary sources of fructose include fruits, honey, and high-fructose corn syrup. Some carbohydrates, such as fructo-oligosaccharides (fructans) and galactosaccharides (e.g., raffinose), cannot be absorbed by humans.
  
  Now, in a double-blind, randomized, crossover trial, researchers have assessed the effects of fructose and fructans (alone or in combination) as dietary triggers of IBS symptoms. Twenty-five patients with known fructose malabsorption were challenged by graded-dose introduction of fructose, fructans, the combination, or a glucose control administered as drinks with meals for a 2-week test period, followed by a 10-day washout period.
  
  In a dose-dependent manner, fructose reproduced IBS symptoms in 70% of patients, fructans reproduced symptoms in 77%, and the combination induced symptoms in 79%. Only 14% of those challenged with glucose showed IBS symptoms (P≤0.002).
  
  Comment: Up to 40% of patients with IBS have been shown to absorb fructose incompletely (JW Gastroenterol Sep 28 2007). In this study, IBS symptoms were induced by either fructose or fructans, indicating that symptoms are reproduced by the bowel’s response to delivery of undigested carbohydrates to the colon and distal small bowel. These data supply more evidence to suggest that carbohydrate malabsorption plays a role in the pathogenesis of IBS symptoms. Douglas K. Rex, MD

   

• NICONTINIC ACID – THE NEW OLD WONDER DRUG
  Many patients with coronary heart disease (CHD) or its equivalent will need a >50% reduction in low-density lipoprotein (LDL) cholesterol to achieve the LDL goal of <100 mg/dl. There are also patients with what the National Cholesterol Education Program calls “atherogenic dyslipidemia,” which includes a nasty metabolic stew of elevated triglycerides, low high-density lipoprotein (HDL) cholesterol, prothrombotic and proinflammatory states, and a preponderance of small, dense LDL particles, which are highly atherogenic and strongly predict cardiovascular events (Slide1)¹ Moreover, all of the processes involved in atherogenesis can be exacerbated by insulin resistance and/or the metabolic syndrome (Slide 2).²
  
  There are numerous treatments that, to varying degrees, affect atherogenic dyslipidemia (Slide 3). While statins have dramatic effects on LDL cholesterol, they have little impact on the overall atherogenic lipoprotein profile (ALP). Interventions that improve ALP include fat weight loss, exercise, and good control of diabetes. One therapy that is particularly effective at improving ALP is nicotinic acid.² (When the biological significance of nicotinic acid was recognized, there was a desire to distinguish it from nicotine; thus, it was named niacin from the words “nicotinic acid vitamin.”)
  
  In recent years, niacin has gained recognition as an atheroprotective agent, in part because of its capacity to lower plasma levels of cholesterol, triglycerides, and very-low- and low-density lipoproteins. Also, of currently approved drugs, niacin is the most effective at raising HDL cholesterol levels. However, there have been concerns, too, that niacin might increase insulin resistance and have adverse effects on blood glucose levels.
  
  Combination Therapy
  
  Current guidelines recommend consideration of combination drug therapy to achieve optimal low-density LDL cholesterol lowering and broader lipid-altering effects when treating hypercholesterolemic patients at high risk for atherosclerotic cardiovascular events.¹ Because statins and niacin have potentially complementary actions, several studies have evaluated combination regimens.
  
  For example, investigators sought to determine whether intensive lipid therapy with a niacin-containing regimen would have a beneficial effect on cardiovascular disease, despite any increase in plasma glucose and insulin resistance in subjects with the metabolic syndrome. They evaluated 3 years of treatment with slow-release niacin plus simvastatin (N+S) on both angiographic and clinical outcomes in 160 subjects with coronary artery disease (CAD) and low levels of HDL from the HDL-Atherosclerosis Treatment Study (HATS).³
  
  Treating atherogenic dyslipidemia with combination therapy led to substantial benefits in terms of stenosis progression and clinical events, independently of whether the patient had metabolic syndrome or was insulin resistant. During the 3-year period, the beneficial effect of niacin in combination with simvastatin appeared to offset a modest adverse effect of niacin on glucose metabolism and insulin resistance in higher risk patients, “as long as careful attention is paid to glycemic control.”
  
  In another study, niacin extended release (niacin-ER) plus lovastatin was comparable to atorvastatin 10 mg and more effective than simvastatin 20 mg in reducing LDL cholesterol.⁴ The combination also was more effective in increasing HDL cholesterol than either atorvastatin or simvastatin and provided greater global improvements in non-HDL cholesterol, triglycerides, and lipoprotein(a) (Slide 4).
  
  Recently, investigators evaluated ezetimibe/simvastatin (E/S) plus niacin-ER in patients with type IIa or IIb hyperlipidemia.⁵ In this 24-week multicenter, double-blind study, 1,220 patients were randomized to treatment with E/S (10/20 mg/day), the same range of E/S per day plus niacin (titrated to 2 g/day), or niacin alone (titrated to 2 g/day).
  
  Coadministration of E/S with niacin-ER resulted in numerous beneficial effects (Slide 5), including significantly greater reductions in LDL cholesterol, non-HDL cholesterol, triglycerides, apolipoprotein B, and lipid/lipoprotein ratios, compared with either agent alone (p < 0.001). The combination increased levels of apolipoprotein A-I and HDL cholesterol significantly more than E/S (p < 0.001), and reduced high-sensitivity C-reactive protein levels significantly more than niacin alone (p = 0.005). The three-drug regimen was generally well tolerated aside from some niacin-associated flushing.
  
  Safety of Combo Rx
  
  In a recent State-of-the-Art paper for JACC, Davidson and Robinson reviewed the safety of aggressive lipid management.⁶ In a pooled analysis, ezetimibe + simvastatin 80 mg on average resulted in a 57% reduction in LDL, and ezetimibe + atorvastatin 80 mg in 60% reduction in LDL.⁷ E/S resulted in a similar rate of treatment-related discontinuation as simvastatin monotherapy. No differences in muscle-related adverse events were found between 4,558 subjects receiving E/S and 2,563 subjects who received simvastatin alone in this analysis of 17 12-week trials. Hepatic enzyme elevations ≥3x ULN on two or more occasions occurred in 1.4% of 925 ezetimibe + statin-treated subjects compared with 0.4% of 936 statin-only subjects. However, hospitalization for hepatic events was no higher for ezetimibe + statin combinations than for statin monotherapy.
  
  How does the addition of niacin to a statin effect safety endpoints? As mentioned, HATS randomized 160 subjects to placebo or to simvastatin + niacin (mean doses of simvastatin 13 mg and niacin 2.4 g). No cases of persistent ALT or CK elevations were found, and no cases of myopathy or rhabdomyolysis were reported. The ongoing AIM-HIGH trial will evaluate whether the addition of niacin-ER to simvastatin will result in a cardiovascular risk reduction greater than expected based on the degree of LDL lowering.
  
  Safety data also were recently published from both the OCEANS and SEACOAST studies evaluating niacin-ER and simvastatin.^8,9 Combination therapy was consistent with the safety profile of each individual component.
  
  In April 2008, investigators published the results of adverse events reported to the U.S. Food and Drug Administration (FDA).¹⁰ The analyses demonstrated that niacin-ER has a significantly better safety profile compared with other niacin formulations and compares favorably with other commonly used lipid-altering drugs, including statins and fibrates. In addition, analyses of FDA adverse event reports of the pill combining lovastatin and niacin-ER suggest that the safety of combination therapy to comparable with the safety of each of the drugs alone.
  
  At about the same time, Goldberg and Jacobson reported the results of an extensive literature review evaluating the effects of niacin on glucose control in patients with dyslipidemia.¹¹ They found that niacin (≤2.5 g/d), alone or in combination with statins, has only modest, transient or reversible effects on plasma glucose, and these effects are “typically amenable to adjustments in oral hypoglycemic regimens without discontinuing niacin.”
  
  What about triple-drug combination therapy? In the previously mentioned study of E/S with or without niacin therapy, triple therapy was generally well tolerated and showed a safety profile consistent with prior experience using these agents alone or in combination. This suggests that E/S plus niacin-ER may be an option in patients at high risk for CHD including those with diabetes, metabolic syndrome, and obesity, in whom polypharmacy otherwise might be a concern. The rates of serious adverse events were comparable for all treatment arms, and there were no statistically significant differences in muscle, liver, and gastrointestinal adverse events.
  
  Also, the Davidson and Robinson paper cited one study that formally evaluated the safety of triple therapy. A moderate dose of lovastatin (40 mg) was combined with niacin 200 mg and colestipol 20 g and evaluated in a crossover trial in 29 middle-aged men with CHD. This regimen resulted in 54-60% reduction in LDL, depending on the niacin formulation. Only 21% of subjects reported the regimen was "very easy" to take, although 79% thought it was "fairly easy." The primary adverse effects were cutaneous, which were less when sustained-release niacin formulations were used. No data on laboratory abnormalities or musculoskeletal complaints were reported.
  
  This interview features H. Robert Superko, MD, FACC, renowned for his work in metabolic heart disease diagnosis and treatment as well as research and publications on the effects of lipoprotein subclasses. He discusses the mechanism of action of nicotinic acid, new formulations that are increasing the interest in niacin therapy, and the value of using nicotinic acid in combination therapy.
  
  Source
  Content provided by the American College of Cardiology Foundation
  
  [Cardiosource CME link for American College of Cardiology members]

   

• TO MAINTAIN WEIGHT LOSS, EXERCISE EVEN MORE
  
  Women who maintained a 10% weight loss during a 2-year study had better eating habits and more leisure-time physical activity than did those who regained weight lost during the first 6 months.
  
  Experts generally recommend a minimum of 30 minutes of moderate-intensity activity on most days of the week (150 minutes weekly), but substantially more exercise probably is necessary to lose weight and to keep it off. Investigators randomized 191 overweight and obese women who were attending a weight-loss clinic into four groups: high or moderate energy expenditure (2000 vs. 1000 kcal/week) in the form of vigorous- or moderate-intensity exercise. Participants also were instructed to maintain a prescribed, reduced-caloric intake; all received intensive weight-loss counseling, regular group visits, and periodic telephone contact. Previous data from this study showed that average 12-month weight losses of 10% and 8% from baseline were associated with high and moderate amounts of exercise, respectively (JW Womens Health Nov 18 2003).
  
  At 24 months, each group had regained on average about half the weight lost during the first 6 months. However, the 47 women who maintained weight loss of ≥10% had increased their leisure-time physical activity from baseline by a mean of 1515 kcal weekly — substantially more than did women whose weight returned to or exceeded baseline (mean of 480 kcal weekly). No group maintained all of the eating behavior improvements seen at 6 months; however, at 24 months, women who kept their weight at least 10% below baseline retained more of the recommended eating behaviors than did other participants.
  
  Comment: Once again, a study illustrates the difficulty of losing weight and keeping it off — even among highly motivated women enrolled in a weight-loss clinic and given significant support and resources (each participant received a treadmill). As backsliding occurred, the women regained weight. Those who sustained 10% weight losses during 2 years engaged in a level of physical activity that was approximately twice the typical public health recommendation. Considering the difficulty that overweight adults have in maintaining substantial weight loss, healthcare providers should continue to take a proactive stance toward minimizing weight gain in children and young adults, while also promoting more physical activity for all. Wendy S. Biggs, MD 

   

• PERSONALIZED MEDICINE FOR QUITTING SMOKING
  
  Another step toward personalized medicine
  
  Assessing polymorphisms of cytochrome P450 (CYP) enzymes that metabolize bupropion might help to predict efficacy for smoking cessation (JW Psychiatry Nov 19 2007), but the cost-benefit ratio of testing has not seemed dramatic. Because people who metabolize nicotine rapidly have low between-cigarette nicotine levels and poor success in quitting smoking with nonpharmacologic treatments, these researchers investigated whether a marker of nicotine metabolism rate (NMR) would predict quit rates. In a 10-week study, 414 smokers (average, 1 pack/day) were randomized to counseling plus bupropion or placebo. NMR was measured by the ratio of trans-3´-hydroxycotinine to cotinine, two sequential metabolites of nicotine via CYP2A6.
  Among the slowest nicotine metabolizers (bottom NMR quartile), bupropion and placebo recipients had the same rate of smoking abstinence (32%) at the end of the trial and similar rates of maintenance of abstinence at 6-month follow-up. In contrast, among the fastest nicotine metabolizers (top NMR quartile), bupropion was associated with significantly higher rates than placebo for quitting at the end of treatment (34% vs. 10%; odds ratio, 4.84) and for maintenance at 6 months (27% vs. 8%; OR, 4.48).
  
  Comment: People who slowly metabolize nicotine seem to have no need for bupropion; they get good results with behavioral methods alone. Rapid metabolizers have poorer results and higher relapse rates with counseling alone, presumably because their nicotine levels drop swiftly, leading to intense craving. Nicotine supplements also might not be helpful because they will be eliminated too rapidly.
  
  Nicotine metabolism, but not bupropion metabolism, is dependent on CYP3A4; genotyping of this enzyme would predict outcomes only weakly because various environmental factors and unidentified alleles influence the enzyme’s activity. Measuring metabolism of both bupropion and nicotine might be useful in predicting responders to bupropion. Steven Dubovsky, MD 
   
• RANDOMIZED COMPARISON OF GUAIAC-BASED VS. IMMUNOCHEMICAL FOBT  Douglas K. Rex, MD 
  
  Immunochemical FOBT’s better sensitivity but lower specificity for detecting cancer and advanced adenomas (compared with guaiac-based FOBT) led to similar positive predictive values for the two test types.
  
  The Joint Colorectal Cancer Screening Guideline recommends that fecal occult blood testing (FOBT) be performed using immunochemical methods rather than guaiac-based methods (JW Gastroenterol Apr 4 2008). However, direct comparisons between the two test types have been performed only in patients at high risk for, or previously diagnosed with, colorectal cancer (CRC).
  Now, investigators have prospectively compared the performance of guaiac-based FOBT (Hemoccult II) and immunochemical FOBT (OC-Sensor) in a general screening population. A random sample of 20,623 older Dutch adults (age range, 50-75) underwent CRC screening with one of the two types of tests. A standard cutoff of 100 ng/mL was used for immunochemical FOBT. Positive results on either type of FOBT were verified with colonoscopy.
  
  The proportion of completed tests was significantly higher for immunochemical FOBT than for guaiac-based FOBT (6157 vs. 4836). A total of 456 individuals had positive FOBT results; the positivity rate was higher with immunochemical FOBT than with guaiac-based FOBT (5.5% vs. 2.4%; P<0.01). Immunochemical FOBT detected cancer and advanced adenomas more often than did guaiac-based FOBT (24 vs. 11 cases and 121 vs. 46 cases, respectively). However, immunochemical FOBT was 2.3% less specific than was guaiac-based FOBT for detecting cancer and 1.3% less specific for detecting advanced adenomas.
  
  Comment: Immunochemical FOBT’s better sensitivity but lower specificity for detecting cancer and advanced adenomas (compared with guaiac-based FOBT) led to similar positive predictive values for the two test types. Although wider use of immunochemical FOBT would result in more colonoscopies, it would also lead to the detection of substantially more neoplasias, and the positive predictive value would be comparable to that seen with guaiac-based FOBT. The study’s authors could not explain the higher number of completed immunochemical tests, but this finding indicates a strong patient preference for immunochemical FOBT. Overall, these results support the Joint Colorectal Cancer Screening Guideline recommendations to abandon older guaiac-based cards in favor of immunochemical FOBT.
   
• OTC COUGH AND COLD MEDICINES - PRODUCT LABELS BEING MODIFIED TO STATE "DO NOT USE" IN CHILDREN UNDER 4 YEARS OF AGE 10/09/2008
  
  FDA notified healthcare professionals and consumers that the Consumer Healthcare Products Association (CHPA) is voluntarily modifying the product labels for consumers of over the counter (OTC) cough and cold medicines to state "do not use" in children under 4 years of age. FDA supports CHPA members to help prevent and reduce misuse and to better inform consumers about the safe and effective use of these products for children. FDA continues to assess the safety and efficacy of these products and to revise its OTC list of approved ingredients and amounts for these medicines. Parents and care givers should adhere to the dosage instructions and warnings on the label that accompanies OTC cough and cold medications before giving the product to children, and should consult their healthcare professionals if they have any questions or concerns.
   
  GALLBALDDER DISEASE AND USE OF TRANSDERMAL VERSUS ORAL HORMONE REPLACEMENT THERAPY IN POSTMENOPAUSAL WOMEN: PROSPECTIVE COHORT STUDY
  
  Bette Liu, clinical epidemiologist¹, Valerie Beral, professor of epidemiology¹, Angela Balkwill, statistical programmer¹, Jane Green, clinical research scientist¹, Siân Sweetland, statisticial epidemiologist¹, Gillian Reeves, statistical epidemiologist¹, for the Million Women Study Collaborators ¹ Epidemiology Unit, University of Oxford, Oxford OX3 7LF Correspondence to: B Liu Bette.Liu@ceu.ox.ac.uk
  
  Objective To determine whether transdermal compared with oral use of hormone replacement therapy reduces the risk of gallbladder disease in postmenopausal women.
  
  Design Prospective cohort study (Million Women Study).
  
  Setting Women registered with the National Health Service (NHS) in England and Scotland.
  
  Participants 1 001 391 postmenopausal women (mean age 56) recruited between 1996 and 2001 from NHS breast screening centers and followed by record linkage to routinely collected NHS hospital admission data for gallbladder disease.
  
  Main outcome measures Adjusted relative risk and standardized incidence rates of hospital admission for gallbladder disease or cholecystectomy according to use of hormone replacement therapy.
  
  Results During follow-up 19 889 women were admitted for gallbladder disease; 17 190 (86%) had a cholecystectomy. Compared with never users of hormone replacement therapy, current users were more likely to be admitted for gallbladder disease (relative risk 1.64, 95% confidence interval 1.58 to 1.69) but risks were substantially lower with transdermal therapy than with oral therapy (relative risk 1.17, 1.10 to 1.24 v 1.74, 1.68 to 1.80; heterogeneity P<0.001). Among women using oral therapy, equine oestrogens were associated with a slightly greater risk of gallbladder disease than estradiol (relative risk 1.79, 1.72 to 1.87 v 1.62, 1.54 to 1.70; heterogeneity P<0.001) and higher doses of estrogen increased the risk more than lower doses: for equine estrogens >0.625 mg, 1.91 (1.78 to 2.04) v ≤0.625 mg, 1.76 (1.68 to 1.84); heterogeneity P=0.02; estradiol >1 mg, 1.68 (1.59 to 1.77) v ≤1 mg, 1.44 (1.31 to 1.59); heterogeneity P=0.003. The risk of gallbladder disease decreased with time since stopping therapy (trend P=0.004). Results were similar taking cholecystectomy as the outcome. Standardized hospital admission rates per 100 women over five years for cholecystectomy were 1.1 in never users, 1.3 with transdermal therapy, and 2.0 with oral therapy.
  
  Conclusion Gallbladder disease is common in postmenopausal women and use of hormone replacement therapy increases the risk. Use of transdermal therapy rather than oral therapy over a five year period could avoid one cholecystectomy in every 140 users.

   

• CONTINUOUS GLUCOSE MONITORING IN TYPE 1 DIABETES Allan S. Brett, MD
  
  Published in Journal Watch General Medicine September 30, 2008

  Continuous monitoring helped lower HbA_1c levels in patients who were older than 24, but not in children, adolescents, or younger adults.
  
  Continuous glucose monitoring devices, which measure interstitial glucose via subcutaneous sensors, now are available commercially. To determine the value of such devices, 322 adults and children with type 1 diabetes (glycosylated hemoglobin [HbA_1c] level, 7%–10%) were randomized to continuous glucose monitoring or to conventional monitoring (fingerstick testing ≥4 times daily). Three prespecified age subgroups were enrolled: 8 to 14 years, 15 to 24 years, and 25 or older. Patients used either insulin pumps or multiple daily insulin injections and were instructed on adjusting insulin doses according to monitoring results.
  
  Among patients who were 25 or older, mean HbA_1c concentration decreased by a mean of 0.5 percentage points at 26 weeks in the continuous monitoring group but remained unchanged in the conventional monitoring group — a significant difference. In contrast, among younger patients, continuous monitoring did not lower mean HbA_1c levels more than conventional monitoring did. Continuous monitoring improved most secondary endpoints in the oldest patients and some endpoints (e.g., proportion of subjects with HbA levels <7% at 26 weeks) in the youngest patients, but among 15- to 24-year-olds, no significant differences emerged. Within the continuous monitoring groups, those in the 15- to 24-year-old group were less adherent to sensor use than were older or younger patients. Rates of hypoglycemia were similar with continuous and conventional monitoring in all age groups.
  
  Comment: Not surprisingly, continuous glucose monitoring was most effective in patients who were 25 or older and was no better than conventional monitoring in adolescents and very young adults. Continuous monitoring is expensive, has some accuracy limitations, and requires patient motivation. Although this method is appealing theoretically, the extent to which it will improve long-term clinical outcomes remains to be determined.

   

• DECONGENSTANTS AND ANTIHISTAMINES FOR ACUTE OTITIS MEDIA IN CHILDREN

  Authors  Coleman Cassie, Moore Michael

  Review Group  Cochrane Acute Respiratory Infections Group

  Abstract  Acute otitis media (AOM) is a common and important source of morbidity in children, although the majority of cases resolve spontaneously. While frequently recommended, decongestant and antihistamine therapy is of unclear benefit. Objectives To determine the efficacy of decongestant and antihistamine therapy in children with AOM on outcomes of AOM resolution, symptom resolution, medication side effects, and complications of AOM.Search strategy In this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 2); MEDLINE (January 2004 to May 2007); and EMBASE (July 2003 to May 2007).Selection criteria Randomized controlled trials (RCTs) evaluating decongestant or antihistamine treatment for children with AOM were included. Patient-oriented outcomes were considered most relevant. Data collection and analysis: The review authors independently evaluated studies for inclusion, performed validity assessments and completed data extraction. Dichotomous data were pooled to generate relative risks; homogeneity was assessed using approximate chi-square tests. Main results No new studies were included following this updated search. Fifteen trials involving 2695 people were included. Only the combined decongestant-antihistamine group demonstrated statistically lower rates of persistent AOM at the two week period (fixed relative risk (RR) 0.76; 95% confidence interval (CI) 0.60 to 0.96; number needed to treat (NNT) 10). No benefit was found for early cure rates, symptom resolution, prevention of surgery or other complications. There was a five to eight -fold increased risk of side effects for those receiving an intervention, which reached statistical significance for all decongestant groupings. Validity sub analyses demonstrated that lower quality studies found benefit, while analysis of those studies with higher validity scores found no benefit of treatment. Authors' conclusions Given lack of benefit and increased risk of side effects, these data do not support the use of decongestant treatment in children with AOM. There was a small statistical benefit from combination medication use but the clinical significance is minimal and study design may be biasing the results. Thus, the routine use of antihistamines for treating AOM in children cannot be recommended.

  Implications  This review did not find sufficient statistical or clinical benefit to decongestant, antihistamine or combination therapy for AOM. Treatment groups, however, experienced an increased risk of side effects. The current evidence suggests that decongestants and/or antihistamines not be routinely used to treat children with AOM.

  Citation  Coleman C, Moore M. Decongestants and antihistamines for acute otitis media in children. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD001727. DOI: 10.1002/14651858.CD001727.pub4.

   

• RECOMMENDATIONS FOR TREATING LOW BONE DENSITY/OSTEOPOROSIS TO PREVENT FRACTURES
   

  Summary  The American College of Physicians has made four recommendations for treating low bone density/osteoporosis in an attempt to prevent fractures: 1) Patients with osteoporosis and those who have had fragility fractures should receive pharmacologic treatment; 2) Clinicians should consider pharmacologic treatment of patients at risk for developing osteoporosis; 3) Pharmacologic treatment should be based on a risk/benefit assessment in individual patients; 4) More research in needed to evaluate treatments for osteoporosis.

  Basis for Study/Article  The American College of Physicians “developed this guideline to present the available evidence on various pharmacologic treatments to prevent fracture in men and women with low bone density or osteoporosis.”

  Detailed Summary of Study  The authors conducted a literature search for relevant articles and analyzed the data.

  Results/Body  1) Patients with osteoporosis and those who have had fragility fractures should receive pharmacologic treatment (strong recommendation, high-quality evidence); 2) Clinicians should consider pharmacologic treatment of patients at risk for developing osteoporosis (weak recommendation, moderate-quality evidence); 3) Pharmacologic treatment should be based on a risk/benefit assessment in individual patients (strong recommendation, moderate-quality evidence); 4) More research in needed to evaluate treatments for osteoporosis.

  Sources & Other Links  Qaseem A, et al. Pharmacologic treatment of low bone density or osteoporosis to prevent fractures: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2008 Sep 16;149(6):404-15.

  Article Link (NCBI)

   

• FEMORAL NECK STRENGTH IS HIGHER IN BOYS; INTENSITY OF ACTIVITY PREDICTS STRENGTH
   

  Summary  In 9-year-olds, the intensity of physical activity is a predictor of femoral neck strength, although it does not fully account for the greater bone strength in boys. “Daily vigorous physical activity for at least approximately 25 minutes seems to improve femoral neck bone health in children.”

  Basis for Study/Article This study from Portugal examined whether the intensity and duration of physical activity affected femoral neck strength and the bone mineral density of the femoral neck, lumbar spine and total body in children.

  Detailed Summary of Study  DEXA scans were done in 143 girls and 150 boys (mean age 9.7 years), and their physical activity was assessed using accelerometry. Compressive, bending and impact strengths were calculated.

  Results/Body  Gender differences of 9% for compressive strength, 10% for bending strength and 9% for impact strength were found. Vigorous physical activity was “the main physical activity predictor of femoral neck strength but did not explain gender differences.” The most active boys (top 50%) had higher values on all the strength ratings than the least active (bottom 25%) boys. In girls, the only difference between the most active (top 25%) and least active (bottom 25%) groups was bending strength. Physical activity did not affect lumbar spine strength.

  Sources & Other Links  Sardinha LB, et al. Objectively measured physical activity and bone strength in 9-year-old boys and girls. Pediatrics. 2008 Sep;122(3):e728-36.

  Article Link (NCBI)

   

• ON SCREENING COLONOSCOPY, BLACK PATIENTS HAVE HIGHER RISK OF POLYPS >9 mm
   

  Summary  This multicenter study found that on screening colonoscopy of asymptomatic patients, the prevalence of polyps larger than 9 mm is 7.7% in black patients vs. 6.2% in white patients. Although the prevalence of proximal polyps <9 mm was similar between the races, the incidence was higher in blacks older than 60.

  Basis for Study/Article Black patients have a higher incidence of colorectal cancer and a higher mortality rate. This trial compared screening colonoscopy findings in asymptomatic black vs. white patients.

  Detailed Summary of Study  The study comprised 80,061 white patients and 5,464 black patients undergoing screening colonoscopy at 67 adult GI practice sites. The prevalence and location of polyps larger than 9 mm were recorded.

  Results/Body  The prevalence of polyps larger than 9 mm was 7.7% in black patients vs. 6.2% in white patients; adjusted odds ratios were 1.16 for black men and 1.62 for black women. The prevalence of proximal polyps <9 mm was similar between the groups, but they were more common in black patients older than 60.

  Sources & Other Links  Lieberman DA, et al. Prevalence of colon polyps detected by colonoscopy screening in asymptomatic black and white patients. JAMA. 2008;300(12):1417-22.

  Article Link (NCBI)

   

• FDA APPROVES UPDATED LABELING FOR PSORIASIS DRUG RAPTIVA
  Safety concerns drove labeling changes

  The U.S. Food and Drug Administration today announced labeling changes, including a Boxed Warning, to highlight the risks of life-threatening infections, including progressive multifocal leukoencephalopathy (PML), with the use of Raptiva (efalizumab). The labeling changes are based on the FDA's post-market surveillance. The FDA is also requiring the submission of a Risk Evaluation and Mitigation Strategy (REMS), which will include a Medication Guide for patients and a timetable for assessment of the REMS.

  Raptiva is a once-weekly injection approved for adults with moderate to severe plaque psoriasis who are candidates for systemic (whole body) therapy or phototherapy to control their psoriasis.

  The FDA's Office of Surveillance and Epidemiology, charged by the Agency with monitoring drugs once approved for the marketplace, has received reports of serious infections leading to hospitalizations, and deaths in some cases, in patients using Raptiva.

  The now-required Boxed Warning will highlight the risk of bacterial sepsis, viral meningitis, invasive fungal disease, progressive multifocal leukoencephalopathy and other opportunistic infections.

  Additionally, Raptiva's label will be updated to include data from juvenile animal studies in mice (age equivalent to a 1-14 year old human). These data indicate a potential risk for the permanent suppression of the immune system with repeat administration of Raptiva in this age group. Raptiva is not approved for children under 18 years of age.

  "As part of FDA's monitoring of the life-cycle of approved products, the agency received reports of serious infections in some patients taking Raptiva. These reports led to our decision to highlight these risks in the drugs labeling," said Janet Woodcock, the FDA's director of the Center for Drug Evaluation and Research. "Doctors and other prescribers should carefully evaluate and weigh the risk/benefit profile of Raptiva for patients who would be more susceptible to these risks."

  Raptiva works by suppressing the immune system to reduce psoriasis flare-ups, however by suppressing the body's natural defense system, it can also increase the risk of serious infections and malignancies in patients.

  Patients identified to begin therapy with Raptiva should have received all their age-appropriate vaccinations before starting the drug. Vaccinations should not be administered to patients taking Raptiva because immunity to the vaccination virus may not be conferred.

  Patients taking Raptiva should be educated about recognizing the signs and symptoms of infection, PML (confusion, dizziness or loss of balance, difficulty talking or walking, and vision problems), anemia (dizziness upon standing, weakness or jaundice), thrombocytopenia (bruising, bleeding gums, pin-point sized red or purple dots under the skin), or the worsening of their psoriasis or arthritis. Signs of a nervous system disorder include sudden onset of numbness, tingling or weakness in the arms, legs or face.

  If any of these signs appear, Raptiva patients should seek immediate medical attention. Patients with pre-existing infections or who have a compromised immune system should notify their health care professional before beginning treatment with Raptiva.

  Because reports of these adverse events were received voluntarily from populations of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to the drug's use.

  One report of PML in a Raptiva-treated patient came from an ongoing post-marketing epidemiological study of patients with psoriasis.

  Health care professionals should monitor patients treated with Raptiva for the signs and symptoms of these adverse events and also instruct patients to report any such signs and symptoms to them without delay.

  Consumers and health care professionals can report adverse events to the FDA's MedWatch program at 800-FDA-1088, by mail at MedWatch, HF-2, FDA, 5600 Fishers Lane, Rockville, MD 20852-9787, or online at www.fda.gov/medwatch/report.htm.

  Raptiva was approved in 2003. It is manufactured by Genentech, Inc. of San Francisco, Calif.

   
• SEQUENTIAL THERAPY MAY BE EFFECTIVE FOR DRUG-RESISTANT H. PYLORI

  Summary  Sequential therapy consisting of 10 days of a PPI, with amoxicillin for the first 5 days and clarithromycin and tinidazole for the second 5 days, may be an effective way to treat infection with H. pylori, which is increasingly becoming resistant to standard medications.

  Basis for Study/Article  This article examines the effectiveness of various treatment strategies for H. pylori infection, given that “the rate of treatment failure associated with established drug regimens has increased at a rapid rate.”

  Detailed Summary of Study  H. pylori is becoming increasingly resistant to clarithromycin and metronidazole. The authors reviewed the effectiveness of standard regimens vs. sequential therapy for H. pylori infection.

  Results/Body  A large recent U.S. randomized trial showed that “triple therapy” (7 to 10 days of a PPI plus clarithromycin and amoxicillin) has an H. pylori eradication rate of 78%. The eradication rate for “quadruple therapy” (bismuth, metronidazole, tetracycline, and a PPI) was 87.7% in a 1999 study, before resistance became widespread. In contrast, sequential therapy—10 days of a standard-dose PPI b.i.d., with amoxicillin (1 g b.i.d.) for the first 5 days and clarithromycin (500 mg b.i.d.) and tinidazole (500 mg b.i.d.) for the second 5 day—showed higher eradication rates in several studies, with acceptable adherence rates. It was even effective in patients with infection that was resistant to clarithromycin. The authors also discuss the limited role of treatment with levofloxacin and rifabutin.

  Sources & Other Links  Vakil N, et al. Sequential therapy for Helicobacter pylori: time to consider making the switch? JAMA. 2008 Sep 17;300(11):1346-7.

   
• IN OLDER WOMEN, HOSPITALIZATION FOR NONSPECIFIC CHEST PAIN DOUBLES RISK FOR CAD EVENT

  Summary  In postmenopausal women, hospital admission for nonspecific chest pain doubles the risk for a coronary artery disease event in the next 5 to 7 years. These women are “candidates for aggressive risk factor treatment.” Hormone replacement therapy does not affect the risk of either hospitalization for nonspecific chest pain or a subsequent CAD event.

  Basis for Study/Article  The authors explored whether being hospitalized for nonspecific chest pain is associated with a woman’s risk of suffering a CAD event.

  Detailed Summary of Study  This study comprised 9,427 women in the Women’s Health Initiative Estrogen-Alone study (follow-up, 7.1 years) and 15,105 women in the Women’s Health Initiative Estrogen Plus Progestin trial (follow-up, 5.6 years). They were postmenopausal (age 50 to 79) and did not have cardiovascular disease at baseline. Hospital admissions for nonspecific chest pain and subsequent CAD events were recorded.

  Results/Body  322 women in the Estrogen-Alone study and 249 in the Estrogen Plus Progestin trial were hospitalized for nonspecific chest pain. They had double the risk of subsequent nonfatal CAD events, including nonfatal MI (2.3% vs. 1.7%; hazard ratio 2.1), revascularization (3.5% vs. 2.6%; hazard ratio 1.99), and hospitalization for angina (3.7% vs. 2.3%; hazard ratio 2.39).

  Sources & Other Links  Robinson JG, et al. Cardiovascular risk in women with nonspecific chest pain (from the Women’s Health Initiative Hormone Trials). Am J Cardiol. 2008 Sep 15;102(6):693-9.  Article Link (NCBI)

   

• OTC COUGH AND COLD MEDICINES - PRODUCT LABELS BEING MODIFIED TO STATE "DO NOT USE" IN CHILDREN UNDER 4 YEARS OF AGE

  MedWatch - The FDA Safety Information and Adverse Event Reporting Program

  FDA notified healthcare professionals and consumers that the Consumer Healthcare Products Association (CHPA) is voluntarily modifying the product labels for consumers of over the counter (OTC) cough and cold medicines to state "do not use" in children under 4 years of age. FDA supports CHPA members to help prevent and reduce misuse and to better inform consumers about the safe and effective use of these products for children. FDA continues to assess the safety and efficacy of these products and to revise its OTC list of approved ingredients and amounts for these medicines. Parents and care givers should adhere to the dosage instructions and warnings on the label that accompanies OTC cough and cold medications before giving the product to children, and should consult their healthcare professionals if they have any questions or concerns.

  Read the entire 2008 MedWatch Safety Summaries, including a link to the FDA Press Release regarding the above issue at:

  Snapshot as on GMT: Fri Oct 10 04:50:38 2008

   
• BRAIN SEROTONIN TRANSPORTER BINDING VARIES WITH THE SEASONS

  Summary  Brain serotonin transporter binding varies with the seasons, with higher levels during periods of less sunshine. “Since higher serotonin transporter density is associated with lower synaptic serotonin levels, regulation of serotonin transporter density by season is a previously undescribed physiologic mechanism that has the potential to explain seasonal changes in normal and pathologic behaviors.”

  Basis for Study/Article  “Brain serotonin is involved in the regulation of physiologic functions, such as mating, feeding, energy balance, and sleep.” This study from Canada examined whether brain serotonin transporter binding varies depending on the amount of daily sunshine.

  Detailed Summary of Study  Regional serotonin transporter binding potential values were obtained from 88 drug-naïve healthy volunteers by PET scanning over 4 years. Levels were then correlated with sunshine levels.

  Results/Body  Serotonin transporter binding levels were higher in all brain regions scanned during the fall and winter, when there was less sunlight.

  Sources & Other Links  Praschak-Rieder N, et al. Seasonal variation in human brain serotonin transporter binding. Arch Gen Psychiatry. 2008 Sep;65(9):1072-8.  Article Link (NCBI)

   

• SURGERY VERSUS PRIMARY ENDOCRINE THERAPY FOR OPERABLE PRIMARY BREAST CANCER IN ELDERLY WOMEN (70 YEARS PLUS)

  Authors  Hind Daniel, Wyld Lynda, Beverley Catherine, Reed Malcolm W

  Review Group  Cochrane Breast Cancer Group

  Abstract  Several studies have evaluated the clinical effectiveness of endocrine therapy alone in women aged 70 years or over and who are fit for surgery. ObjectivesTo identify and review the evidence from randomised trials comparing primary endocrine therapy (endocrine therapy alone) to surgery, with or without adjuvant endocrine therapy, in the management of women aged 70 years or over with operable breast cancer. Search strategy For this update, the Cochrane Breast Cancer Group Specialised Register was searched 13th November 2007 using the codes for "early breast cancer", "endocrine therapy", "psychosocial" or "surgery". Selection criteria Randomised trials comparing primary endocrine therapy with surgery, with or without adjuvant endocrine therapy, in the management of women aged 70 years or over with early breast cancer and who are fit for surgery.Data collection and analysis Studies were assessed for eligibility and quality, and data from published trials were extracted by two independent reviewers. Hazard ratios were derived for time-to-event outcomes, where possible, and a fixed-effect model was used for meta-analysis. Toxicity and quality-of-life data were extracted, where present. Where outcome data were not available, trialists were contacted and unpublished data requested.Main resultsSeven eligible trials were identified of which six had published time-to-event data and one was published only in abstract form with no usable data. The quality of the allocation concealment was adequate in three studies and unclear in the remainder. In each case the endocrine therapy used was tamoxifen.Data, based on an estimated 869 deaths in 1571 women, were unable to show a statistically significant difference in favour of either surgery or primary endocrine therapy in respect of overall survival. However, there was a statistically significant difference in terms of progression-free survival, which favoured surgery with or without endocrine therapy.The hazard ratios (HR) for overall survival were: 0.98 (95% confidence interval (CI) 0.74 to 1.30, P value 0.9) for surgery alone versus primary endocrine therapy; 0.86 (95% CI 0.73 to 1.00, P value 0.06) for surgery plus endocrine therapy versus primary endocrine therapy. The HRs for progression-free survival were: 0.55 (95% CI 0.39 to 0.77, P value 0.0006) for surgery alone versus primary endocrine therapy; 0.65 (95% CI 0.53 to 0.81, P value 0.0001) for surgery plus endocrine therapy versus primary endocrine therapy (each comparison based on only one trial). Tamoxifen-related adverse effects included hot flushes, skin rash, vaginal discharge, indigestion, breast pain, sleepiness, headache, vertigo, itching, hair loss, cystitis, acute thrombophlebitis, nausea, and indigestion. Surgery-related adverse effects included paresthesia on the ipsilateral arm and lateral thoracic wall in those who had axillary clearance. One study suggested that those undergoing surgery suffered more psychosocial morbidity at three months postsurgery, although this difference had disappeared by two years.Authors' conclusions Primary endocrine therapy should only be offered to women with oestrogen receptor (ER) positive tumours who are unfit for or who refuse surgery. In a cohort of women with significant co-morbid disease and ER-positive tumours it is possible that primary endocrine therapy may be a superior option to surgery. Trials are needed to evaluate the clinical effectiveness of aromatase inhibitors as primary therapy for an infirm older population with ER-positive tumours.

  Implications  Primary endocrine therapy should only be offered to women with ER-positive tumours who are unfit for, or who refuse, surgery. In a cohort of women with reduced life expectancy, due to significant co-morbid disease, and ER-positive tumours, primary endocrine therapy may be an appropriate treatment choice.

  Citation  Hind D, Wyld L, Beverley C, Reed MW. Surgery versus primary endocrine therapy for operable primary breast cancer in elderly women (70 years plus). Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD004272. DOI: 10.1002/14651858.CD004272.pub2.

   
• IN OLDER WOMEN WITH OSTEOPOROSIS, TIBOLONE REDUCES FRACTURE AND CANCER RISK BUT DOUBLES RISK OF STROKES

  Summary  In older women with osteoporosis, tibolone reduces the risk of fracture, breast cancer, and colon cancer, but it doubles the risk of stroke. Because of the increased risk of stroke, this trial was stopped early.

  Basis for Study/Article  This study examined the effects of tibolone, a synthetic hormone used in HRT, on the risk of fractures, breast cancer, colon cancer, and CV disease in postmenopausal women with osteoporosis.

  Detailed Summary of Study  4,538 women age 60 to 85 (BMD T-score of -2.5 or less at hip or spine, or T-score -2.0 or less and radiographic evidence of vertebral fracture) were randomized to receive tibolone (1.25 mg/day) or placebo. Annual spine radiographs were taken to assess for vertebral fractures, and other fractures, breast cancer, and CV events were also recorded over a median follow-up of 34 months.

  Results/Body  The rate of vertebral fracture was 70/1,000 person-years in the tibolone group vs. 126 in the placebo group (relative hazard 0.55), and the rate of nonvertebral fracture was 122 vs. 166 (relative hazard 0.74). The tibilone group had lower rates of invasive breast cancer (relative hazard 0.32) and colon cancer (relative hazard 0.31). However, the rate of stroke in the tibolone group was more than double that in the placebo group (relative hazard 2.19), and because of this the study was stopped early. The rate of CHD and VTE did not differ between the groups.

  Sources & Other Links  Cummings SR, et al. The effects of tibolone in older postmenopausal women. N Engl J Med. 2008 Aug 14;359(7):697-708.  Article Link (NCBI)

   

• COST-EFFECTIVENESS OF PPI THERAPY ALONG WITH LOW-DOSE ASPIRIN DEPENDS ON PATIENT'S RISK OF GI BLEEDING

  Summary  In patients at average risk for upper GI bleeding, taking a PPI along with low-dose, long-term aspirin is cost-effective if the drug is purchased OTC. At prescription cost, it would be cost-effective only in patients at high risk for upper GI bleeding.

  Basis for Study/Article  Because of the risk of upper GI bleeding in patients taking long-term low-dose aspirin for CV protection, proton pump inhibitors are often prescribed as well. This study looked at the cost-effectiveness of taking a PPI and low-dose aspirin vs. aspirin alone.

  Detailed Summary of Study  The authors created a statistical model comparing the life-long costs of the two regimens. Variables tested were patient age (range 50 to 80), risk for upper GI bleeding, PPI effectiveness and PPI cost per year (range $250 to $1,400).

  Results/Body  In patients at average risk for upper GI bleeding, taking a PPI along with aspirin was cost-effective in terms of its cost per life-year saved if the drug was purchased OTC. At prescription cost, it was cost-effective only in patients at high risk for upper GI bleeding.

  Sources & Other Links Saini S, et al. Cost-effectiveness of proton pump inhibitor cotherapy in patients taking long-term, low-dose aspirin for secondary cardiovascular prevention. Arch Intern Med. 2008 Aug 11;168(15):1684-90.

  Article Link (NCBI)

   

• TOPICAL GABAPENTIN REDUCES PAIN IN WOMEN WITH VULVODYNIA

  Summary  Topical gabapentin significantly decreases pain and improves sexual function in many women with vulvodynia.

  Basis for Study/Article  This retrospective study assessed the role of topical gabapentin in the treatment of vulvodynia.

  Detailed Summary of Study  The authors reviewed the outcomes of 51 women using 2% to 6% topical gabapentin to treat vulvodynia (19 generalized, 32 localized). 35 women were available for evaluation after at least 8 weeks of treatment.

  Results/Body  After treatment, the mean pain score was reduced from 7.26 to 2.49 on a scale of 0 to 10. 28 of the 35 women had at least a 50% drop in pain scores. Sexual function improved in 17 of the 20 evaluable women with localized vulvodynia. 14% of patients discontinued treatment.

  Sources & Other Links  Boardman L, et al. Topical gabapentin in the treatment of localized and generalized vulvodynia. Obstet Gynecol. 2008 Sep;112(3):579-85.  Article Link (NCBI)

   

• HIGH VITAMIN D LEVELS PROTECT AGAINST TYPE 2 DIABETES

  Summary  This 22-year follow-up study showed that high vitamin D levels protect against type 2 diabetes. The effect was less marked in women, who as a group had lower vitamin D levels than men.

  Basis for Study/Article  This study from Finland examined whether high vitamin D levels decrease the risk of developing type 2 diabetes.

  Detailed Summary of Study  The researchers combined and analyzed the data from two case-control studies showing that high vitamin D levels protects against type 2 diabetes. Information on vitamin D levels was collected between 1973 and 1980 in subjects aged 40 to 74 year who did not have diabetes. Cases of diabetes were then recorded over 22 years of follow-up. Incidence rates were calculated based on the subject’s vitamin D level at baseline.

  Results/Body  Men with the highest vitamin D levels had a lower risk of type 2 diabetes (relative odds between highest and lowest levels, 0.28). Overall, women had lower vitamin D levels than men, and the relative odds for developing type 2 diabetes between the highest and lowest levels was 1.14.

  Sources & Other Links  Knekt P, et al. Serum vitamin D and subsequent occurrence of type 2 diabetes. Epidemiology. 2008 Sep;19(5):666-71.

  Article Link (NCBI)

   

• HOME INTRAVENOUS ANTIBIOTICS FOR CYSTIC FIBROSIS

  Authors  Balaguer Albert, Gonz&aacute;lez de Dios Javier

  Review Group  Cochrane Cystic Fibrosis and Genetic Disorders Group

  Abstract  Background: Recurrent endobronchial infection in cystic fibrosis (CF) requires treatment with intravenous antibiotics for several weeks usually in hospital, affecting health costs and quality of life for patients and their families. Objectives: To determine whether home intravenous antibiotic therapy in CF is as effective as inpatient intravenous antibiotic therapy and if it is preferred by individuals or families or both. Search strategy: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search of the Group's Trials Register: April 2008. Selection criteria: Randomized and quasi-randomized controlled studies of intravenous antibiotic treatment for adults and children with CF at home compared to in hospital. Data collection and analysis: The authors independently selected studies for inclusion in the review, assessed methodological quality of each study and extracted data using a standardised form. Main results: Seventeen studies were identified by the searches. Only one study could be included which reported results from 17 participants aged 10 to 41 years with an infective exacerbation of Pseudomonas aeruginosa. All their 31 admissions (18 hospital and 13 at home after two to four days of hospital treatment) were analysed as independent events. Outcomes were measured at 0, 10 and 21 days after initiation of treatment. Home participants underwent fewer investigations than hospital participants (P < 0.002) and general activity was higher in the home group. No significant differences were found for clinical outcomes, adverse events, complications or change of intravenous lines, or time to next admission. Home participants received less low-dose home maintenance antibiotic.  Quality of life measures showed no significant differences for dyspnoea and emotional state, but fatigue and mastery were worse for home participants, possibly due to a higher general activity and need of support. Personal, family, sleeping and eating disruptions were less important for home than hospital admissions.  Home therapy was cheaper for families and the hospital. Indirect costs were not determined.  Authors' conclusions: Current evidence is restricted to a single randomized clinical trial. It suggests that, in the short term, home therapy does not harm individuals, entails fewer investigations, reduces social disruptions and can be cost-effective. There were both advantages and disadvantages in terms of quality of life. The decision to attempt home treatment should be based on the individual situation and appropriate local resources. More research is urgently required.

  Implications The current evidence is too limited to draw conclusions for practice. The limited evidence available is from participants who commenced treatment in hospital and suggests that, in the short term, home therapy is associated with less social disruption and no serious adverse events. The decision to commence home therapy should be based on the individual and be co-ordinated from units with appropriate outpatient resources.

  Citation  Balaguer A, Gonz&aacute;lez de Dios J. Home intravenous antibiotics for cystic fibrosis. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD001917. DOI: 10.1002/14651858.CD001917.pub2.

   

• CLINICAL/DEMOGRAPHIC DETAILS, TREATMENT HISTORY DOES NOT APPEAR TO HELP IN CHOOSING A SECOND-LINE ANTIDEPRESSANT

  Summary  "Clinical, demographic, and treatment history were of little value in recommending one medication vs. another as a second-step treatment for major depressive disorder."

  Basis for Study/Article  This study identified characteristics of patients who responded to a second-line antidepressant after initial treatment with citalopram (Celexa®) failed to produce remission of major depressive disorder.

  Detailed Summary of Study  The 41-center study comprised 727 patients age 18 to 75 with major depressive disorder that did not remit with citalopram. The second-line treatments given were sustained-release bupropion (Wellbutrin®; 150 mg/day, titrated to 400 mg/day), sertraline (Zoloft®; 50 mg/day, titrated to 200 mg/day), and extended-release venlafaxine (Effexor®; 37.5 mg/day, titrated to 375 mg/day). Depressive symptoms were rated using 3 scales. Factors increasing and decreasing the odds of remission were identified.

  Results/Body  Factors increasing the odds of remission were white race, employed status, cohabiting or married status, private insurance, no suicide attempts, and a prior response to citalopram (including intolerance). Factors decreasing the odds of remission were greater Axis I psychiatric disorder comorbidity and concurrent substance abuse. Intolerance of the second-line treatment was more likely in patients with suicide attempts or intolerance to citalopram; it was less likely in Hispanics.

  Sources & Other Links  Rush AJ, et al. Selecting among second-step antidepressant medication monotherapies: predictive value of clinical, demographic, or first-step treatment features. Arch Gen Psychiatry. 2008 Aug;65(8):870-80.  Article Link (NCBI)

   

• EATING NUTS, CORN POPCORN, SEEDS DOESN'T APPEAR TO INCREASE THE INCIDENCE OF DIVERTICULOSIS
  Summary  This long-term study found that eating nuts, corn, popcorn and seeds doesn’t increase the incidence of diverticulosis or diverticular disease. “The recommendation to avoid these foods to prevent diverticular complications should be reconsidered.”

  Basis for Study/Article <> This large prospective study evaluated the traditional belief that eating nuts, corn, popcorn and seeds can cause diverticular disease.

  Detailed Summary of Study  Dietary and medical information was collected over an 18-year period from 47,228 men aged 40 to 75 (participants in the Health Professionals Follow-up Study) who did not have diverticulosis, cancer or inflammatory bowel disease at baseline.

  Results/Body  During follow-up there were 801 cases of diverticulitis and 383 cases of diverticular bleeding. Men who ate popcorn and nuts at least twice a week were less likely to have diverticulitis than those who ate them less than once a month (hazard ratios 0.72 for popcorn, 0.80 for nuts). No link was found between corn consumption and diverticulitis or between nut, corn or popcorn consumption and diverticular bleeding or uncomplicated diverticulosis.

  Commentary  The tradition based medicine approach of repeating this long standing “ wisdom” of avoiding various dietary compounds to prevent diverticulitis has never been proven, but continues to be popular folklore. This study doesn’t fully evaluate this issue; but certainly calls it into question. Overall, healthcare providers should not advise patients to make dietary changes which are completely unsupported by facts.

  Grant E. Fraser M.D.
  MedAlert Editor

  Sources & Other Links  Strate LL, et al. Nut, corn, and popcorn consumption and the incidence of diverticular disease. JAMA. 2008 Aug 27;300(8):907-14.  Article Link (NCBI

   

• INFANT FORMULA MANUFACTURED IN CHINA: HEALTH INFORMATION ADVISORY DUE TO REPORTS OF POSSIBLE CONTAMNATION WITH MELAMINE
   

  FDA issued a Health Information Advisory to consumers and healthcare professionals regarding milk-based infant formula manufactured in China. The Chinese manufactured infant formula may be contaminated with melamine. Melamine artificially increases the protein profile of milk and can cause kidney diseases. Currently, no Chinese manufacturers of infant formula have fulfilled the requirements to sell this product in the United States. FDA officials are investigating whether or not infant formula manufactured in China is being sold in specialty markets which serve the Asian community. Caregivers should not feed infant formula manufactured in China to infants and should replace any product from China with an appropriate infant formula manufactured in the United States. Individuals should contact their health care professional if they have questions regarding their infant's health or if they note changes in their infant's health status.

  Read the entire 2008 MedWatch Safety Summary, including a link to the FDA Health Information Advisory regarding the above issue:

  http://www.fda.gov/medwatch/safety/2008/safety08.htm#formulaChina
  or Snapshot as on GMT: Mon Sep 15 06:40:39 2008

   

• TUMOR NECROSIS FACTOR-ALPHA BLOCKERS: DELAYS IN DIAGNOSIS OF FUNGAL AND OTHER OPPORTUNISTIC INFECTION

  ^*Tumor necrosis factor-alpha blockers (TNF blockers), Cimzia (certolizumab pegol), Enbrel (etanercept), Humira (adalimumab), and Remicade (infliximab)^{* *}Audience: ^*Rheumatological, gastroenterological and infectious disease healthcare professionals.

  FDA notified healthcare professionals that pulmonary and disseminated histoplasmosis, coccidioidomycosis, blastomycosis and other opportunistic infections are not consistently recognized in patients taking tumor necrosis factor- blockers (TNF blockers). This has resulted in delays in appropriate treatment, sometimes resulting in death. For patients taking TNF blockers who present with signs and symptoms of possible systemic fungal infection, such as fever, malaise, weight loss, sweats, cough, dypsnea, and/or pulmonary infiltrates, or other serious systemic illness with or without concomitant shock, healthcare professionals should ascertain if patients live in or have traveled to areas of endemic mycoses. For patients at risk of histoplasmosis and other invasive fungal infections, clinicians should consider empiric antifungal treatment until the pathogen(s) are identified.

  Read the complete MedWatch 2008 Safety summary, including links to the Information for Healthcare Professionals page, FDA press release and previous MedWatch alert on these products, at:

  www.fda.gov/medwatch/safety/2008/safety08.htm#TNF2
  or Snapshot as on GMT: Fri Sep 5 04:59:23 2008

   
• HIGH FISH OIL INTAKE REDUCES ATHEROSCLEROSIS IN JAPANESE, JAPANESE-AMERICANS AND WHITE MEN

  Summary  Compared with Japanese-American and white men, Japanese men in their forties have twice the level of marine-derived omega-3 fatty acids and have the lowest levels of atherosclerosis.

  Basis for Study/Article  The authors compared the intake and effects of marine-derived omega-3 fatty acids in Japanese, Japanese-American and white men age 40 to 49.

  Detailed Summary of Study  Intake of marine-derived omega-3 fatty acids, intima-media thickness of the carotid artery, coronary artery calcification and serum fatty acids were assessed in 281 men born and living in Japan, 281 men born in Japan and living in the U.S., and 306 white men born and living in the U.S. All were age 40 to 49.

  Results/Body  The Japanese men had the lowest levels of atherosclerosis; the level was similar in the other two groups. The Japanese men also had double the level of marine-derived omega-3 fatty acids compared to the other two groups. The Japanese men had a significant inverse association of fatty acids with intima-media thickness that was not explained by traditional CV risk factors. This association was not found in the other two groups.

  Sources & Other Links  Sekikawa A, et al. Marine-derived omega-3 fatty acids and atherosclerosis in Japanese, Japanese-American, and white men: a cross-sectional study. J Am Coll Cardiol. 2008 Aug 5;52(6):417-24.  Article Link (NCBI)

   

• OBSTRUCTIVE SLEEP APNEA WORSENS INSULIN RESISTANCE AND GLUCOSE TOLERANCE IN POLYCYSTIC OVARY SYNDROME

  Summary  Sleep apnea worsens insulin resistance and glucose tolerance in women with polycystic ovary syndrome.

  Basis for Study/Article  The authors investigated whether obstructive sleep apnea, which has been linked to metabolic dysfunction, affects insulin resistance and glucose tolerance in women with polycystic ovary syndrome.

  Detailed Summary of Study  52 women with PCOS and 21 women without PCOS matched for age and BMI underwent an overnight sleep study and a 75-g oral glucose tolerance test.

  Results/Body  56% of the PCOS women and 19% of the controls were found to have sleep apnea. Impaired glucose tolerance and insulin resistance were more common in the women with PCOS and sleep apnea vs. those with PCOS but without sleep apnea. “Insulin resistance and glucose tolerance were highly correlated with the presence and severity” of sleep apnea.

  Sources & Other Links  Tasali E, et al. Impact of obstructive sleep apnea on insulin resistance and glucose tolerance in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2008 Jul 22.  Article Link (NCBI)

   

• ALOE VERA EFFECTIVE FOR THE TREATMENT OF ORAL LICHEN PLANUS

  Aloe Vera apears to be an effective, inexpensive, well-tolerated treatment for oral lichen planus.  Oral lichen planus affects 1% to 2% of the populartion.  Treatment options inlcude stroids, tacrolimus, retinoids,  Fifty-four (54)

   

• GROWTH HORMONE REDUCES HIV-ASSOCIATED ABDOMINAL FAT ACCUMULATION

  Summary  This randomized controlled trial found that in HIV-positive patients receiving antiretroviral therapy, low-dose growth hormone reduces abdominal fat accumulation, truncal obesity, triglycerides, and diastolic blood pressure, but 2-hour glucose levels are increased.

  Basis for Study/Article  “Antiretroviral therapy can be associated with visceral adiposity and metabolic complications, increasing cardiovascular risk.” Because reduced secretion of growth hormone has been proposed as a contributing factor, the authors examined the effects of GH administration on “body composition, glucose, and cardiovascular parameters” in this population.

  Detailed Summary of Study  56 HIV-positive patients with abdominal fat accumulation and reduced GH secretion were randomized to receive subcutaneous GH (average dose 0.33 mg/day) or placebo for 18 months. Outcomes were change in body composition (CT and DEXA scans), glucose levels, IGF-1, blood pressure and lipids.

  Results/Body  Compared to the placebo group, the GH group had significantly decreased visceral fat, truncal obesity, triglycerides and diastolic blood pressure; however, their 2-hour glucose levels on glucose tolerance testing increased. The number of adverse events did not differ significantly (23% for GH, 28% for placebo).

  Sources & Other Links  Lo J, et al. Low-dose physiological growth hormone in patients with HIV and abdominal fat accumulation: a randomized controlled trial. JAMA. 2008 Aug 6;300(5):509-19.  Article Link (NCBI)

   

• FATAL STROKES MORE COMMON IN PATIENTS WITH LOW VITAMIN D LEVELS

  Summary  In patients undergoing coronary angiography, low vitamin D levels are predictive of fatal stroke. “Vitamin D supplementation is a promising approach in the prevention of strokes.”

  Basis for Study/Article  This European study investigated whether vitamin D levels affect the risk for fatal stroke.

  Detailed Summary of Study  Levels of 25(OH)D and 1,25(OH)2D were measured in patients referred for coronary angiography (n = 3,299 and 3,315). Seasonal variations in vitamin D levels were corrected for statistically. Fatal strokes (ischemic and hemorrhagic) were recorded over a median follow-up of 7.75 years.

  Results/Body  During follow-up there were 42 fatal strokes, and low levels of 25(OH)D and 1,25(OH)2D were both independent predictors of fatal strokes. Patients who had a history of cerebrovascular disease at baseline also had lower vitamin D levels.

  Sources & Other Links  Pilz S, et al. Low vitamin D levels predict stroke in patients referred to coronary angiography. Stroke. 2008 Jul 17. [Epub ahead of print]  Article Link (NCBI)

   

• LOW-ENERGY FEMORAL SHAFT FRACTURES HAVE A DISTINCTIVE PATTERN IN ALENDRONATE (Fosamax®) USERS
  Summary  Low-energy femoral shaft fractures have a distinctive pattern in patients who take alendronate (Fosamax®).

  Basis for Study/Article  “Long-term alendronate use may overly suppress bone metabolism, limiting repair of microdamage and creating risk for insufficiency fractures.” The authors examined whether alendronate use changes the patterns of low-energy femoral shaft fractures.

  Detailed Summary of Study  The authors examined the records of 70 patients (59 women, 11 men; average age 74.7) admitted to their institution with low-energy femoral shaft fractures. Fracture patterns were compared between those taking alendronate (n = 25) and those not taking it (n = 45).

  Results/Body  19 (76%) of the alendronate patients and only 1 of the non-alendronate group had “a simple, transverse fracture with a unicortical beak in an area of cortical hypertrophy.” Duration of use was 6.9 years for alendronate users with this pattern vs. 2.5 years in alendronate users who did not; only one of the patients with this pattern had been taking alendronate for less than 4 years. The pattern “may result from propagation of a stress fracture whose repair is retarded by diminished osteoclast activity and impaired microdamage repair” resulting from long-term alendronate use.

  Sources & Other Links  Neviaser AS, et al. Low-energy femoral shaft fractures associated with alendronate use. J Orthop Trauma. 2008 May-Jun;22(5):346-50.  Article Link (NCBI)

   

• COMPARING LOW-CARBOHYDRATE, LOW-FAT, AND MEDITERRANEAN DIETS

  Summary  This 2-year trial found that “Mediterranean and low-carbohydrate diets may be effective alternatives to low-fat diets.” Physicians can use the particular strengths of the diets—the low-carb diet reduced lipids and the Mediterranean diet offered better glycemic control—to devise an effective plan for a specific patient.

  Basis for Study/Article  The authors compared the effects of the three diets in moderately obese patients.

  Detailed Summary of Study 322 patients with a mean BMI of 31 (mean age 52, 86% men) were randomized to one of three diets: low-fat, restricted-calorie; Mediterranean, restricted-calorie; or low-carbohydrate, without calorie restrictions. Adherence rates, food intake, weight loss and outcomes were recorded over 2 years.

  Results/Body <> Adherence rates were 95.4% at 1 year and 84.6% at 2 years. Mean weight loss was 2.9 kg for the low-fat group, 4.4 kg for the Mediterranean group and 4.7 kg for the low-carb group. In the 272 subjects who completed the intervention, the corresponding figures were 3.3, 4.6 and 5.5 kg. The subjects on the Mediterranean diet had the highest fiber intake and the highest ratio of monounsaturated to saturated fats. The low-carb group had the lower intake of carbohydrates and the highest intake of fat, protein and cholesterol. The ratio of total cholesterol to HDL decreased by 20% in the low-carb group and by 12% in the low-fat group. In the 36 diabetic patients, “changes in fasting plasma glucose and insulin levels were more favorable” in the Mediterranean group than in the low-fat group.

  Sources & Other Links  Shai I, et al. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med. 2008 Jul 17;359(3):229-41.ticle Link (NCBI)

   

• VIVITRO (Naltrexone) - SERIOUS INJECTION SITE REACTIONS COULD OCCUR

  MedWatch - The FDA Safety Information and Adverse Event Reporting Program

  FDA informed healthcare professionals of the risk of adverse injection site reactions in patients receiving naltrexone. Naltrexone is indicated for the treatment of alcohol dependence in patients who are able to abstain from alcohol in an outpatient setting prior to initiation of treatment. Naltrexone is administered as an intramuscular gluteal injection and should not be administered intravenously, subcutaneously, or inadvertently into fatty tissue. Physicians should instruct patients to monitor the injection site and contact them if they develop pain, swelling, tenderness, induration, bruising, pruritus, or redness at the injection site that does not improve or worsens within two weeks. Physicians should promptly refer patients with worsening injection site reactions to a surgeon. Read the FDA recommendations for healthcare professionals to consider regarding the use of Naltrexone injection.

  Read the entire MedWatch Safety Summary, including a link to the FDA Drug Information Page regarding this issue at: http://www.fda.gov/medwatch/safety/2008/safety08.htm#naltrexone
  or  Snapshot as on GMT: Wed Aug 13 04:52:34   2008

   
• ASTHMA IS LESS COMON IN CHILDREN WITH H.PYLORI COLONIZATION

  Summary  Asthma and other allergy symptoms are less common in children with H. pylori colonization.

  Basis for Study/Article  The authors assessed whether there is an association between childhood asthma and exposure to H. pylori.

  Detailed Summary of Study  The authors used data from 7,412 subjects in the National Health and Nutrition Examination Survey (1999-2000).

  Results/Body  “H. pylori seropositivity was inversely associated with onset of asthma before 5 years and current asthma in children aged 3-13 years.” It was also inversely related to recent wheezing, allergic rhinitis, dermatitis, eczema or rash. “These findings indicate new directions for research and asthma prevention.”

  Commentary  H. pylori infection is also likely a marker for a “dirtier” environment growing up. Although this association may indeed be causative, it would seem much more likely that it is simply a marker for being exposed to many environmental factors at an early age.

  Grant E. Fraser, M.D.
  MedAlert Editor

  Sources & Other Links <> Chen Y, et al. Helicobacter pylori colonization is inversely associated with childhood asthma. J Infect Dis. 2008 Aug 15;198(4):553-60. Article Link (NCBI)

   
• SUMATRIPTAN/NAPROXEN COMBINATION EFFECTIVE FOR EARLY MIGRAINE TREATMENT

  Summary  A fixed-dose combination of sumatriptan and naproxen aborts migraine if taken within 1 hour of onset.

  Basis for Study/Article  The authors examined the efficacy and safety of a fixed-dose combination of sumatriptan (85 mg) and naproxen (500 mg) for early treatment of migraine.

  Detailed Summary of Study  In two separate studies, adult patients (n = 576 and 535) were randomized to take either the sumatriptan/naproxen combination or placebo within 1 hour of migraine onset, while the pain was still mild. Pain relief and adverse events were recorded.

  Results/Body  2 hours after dosing, 52% and 51% of the sumatriptan/naproxen patients were pain-free vs. 17% and 15% of the control group. In the sumatriptan/naproxen patients, pain relief started as early as 30 minutes and lasted for 2 to 24 hours; they also had fewer migraine-associated symptoms than the control group. The most common adverse events were nausea (4% or less) and dizziness (2% or less).

  Sources & Other Links  Silberstein S, et al. Multimechanistic (sumatriptan-naproxen) early intervention for the acute treatment of migraine. Neurology. 2008 Jul 8;71(2):114-21.

  Article Link (NCBI)

   

• SIMVASTATIN USED WITH AMIODARONE ALERT

  The FDA is notifying the public of the risk of a rare condition of muscle injury called rhabdomyolysis, which can lead to kidney failure or death, when simvastatin is used with amiodarone. This risk is dose-related and increases when a dose of simvastatin greater than 20 mg per day is given with amiodarone. A revision of the simvastatin labeling in 2002 described an increased risk of rhabdomyolysis when amiodarone is taken with simvastatin doses greater than 20 mg daily. However, the FDA continues to receive reports of rhabdomyolysis in patients treated concurrently with amiodarone and simvastatin, particularly with simvastatin doses greater than 20 mg daily. Prescribers should be aware of the increased risk of rhabdomyolysis when simvastatin is prescribed with amiodarone, and they should avoid doses of simvastatin greater than 20 mg per day in patients taking amiodarone.

  This information reflects FDA's current analysis of data available to FDA concerning this drug. FDA intends to update this when additional information or analyses become available.

  Healthcare Professional Information Information for Healthcare ProfessionalsSimvastatin Prescribing (labeling) Information from Drugs@FDA Amiodarone Prescribing (labeling) Information from Drugs@FDA

  Other Information

  Simvastatin, Ezetimibe/Simvastatin, and Amiodaroneis marketed under these names: Simvastatin (marketed as Zocor and generics)Ezetimibe/Simvastatin (marketed as Vytorin)Niacin extended-release/Simvastatin (marketed as Simcor) Used with Amiodarone (Cordarone, Pacerone)

   

• AUGUST 2008 FDA PATIENT SAFETY NEWS VIDEO IS AVAILABLE NOW

  MedWatch - The FDA Safety Information and Adverse Event Reporting Program

  FDA Patient Safety News (PSN) is a monthly video news show for healthcare professionals. It covers significant safety alerts, recalls, new product approvals, and offers important tips on protecting patients. Read the complete stories and watch or download the video program at http://www.fda.gov/psn. You may have already received notification of some of these safety issues through the MedWatch list serve. However, many of these PSN stories contain video footage and demonstrations that may be especially useful to educators in healthcare facilities and academic institutions.

  Stories in the August 2008 edition include:

  Warning Added to Regranex (becaplermin) Label

  Use caution when treating diabetic foot and leg ulcers with Regranex in patients who have known malignancies...

  Cellcept and Myfortic Linked to Birth Defects and Fetal Loss

  Before prescribing these drugs, healthcare professionals should ensure that women are not pregnant and are using two effective forms of birth control...

  Possible Association between TNF Blockers and Cancer

  Ongoing safety reviews of Remicade, Enbrel, Humira, and Cimzia...

  Danger Giving Topical Thrombin Intravascularly

  ISMP recommends ways to reduce the risk of errors that can lead to extensive intravascular clotting and death...

  Potential Problems with Insulin Pens in Hospitals

  Insulin pen design and usage issues can present safety concerns...

  Nonoxynol 9 (N9) Contraceptives: No Protection against HIV and Other STDs

  Labeling warns that using nonoxynol 9 may increase the risk of contracting HIV/AIDS from an infected partner...

  For more "FDA Patient Safety News", visit http://www.fda.gov/psn. Please send any comments, questions or suggestions about the program to PSNews@fda.gov

   

• VIAPRO 375 MG CAPSULES -  VOLUNTARY RECALL DUE TO POTENTIAL HARMFUL ANALOG OF SILDENAFIL

  MedWatch - The FDA Safety Information and Adverse Event Reporting Program

  EG Labs, LLC, notified consumers and healthcare professionals not to buy or use Viapro 375 mg Capsules because one lot of the product was found to contain a potentially harmful undeclared ingredient, thio-methisosildenafil, an analog of sildenafil, a FDA approved product used to treat erectile dysfunction in men to enhance sexual performance. The undeclared ingredient may interact with nitrates found in some prescription drugs (such as nitroglycerin) and can lower blood pressure to dangerous levels. Consumers with diabetes, high blood pressure, high cholesterol, or heart disease often take products containing nitrates. Consumers who have this product should discontinue using it and consult their healthcare professional if they experience any problems that may be related to taking Viapro.

   

• ERYTHROPOIESIS STIMULATING AGENTS; PROCRIT, EPOGEN, AND ARANESP, - FDA CLARIFIES APPROVED CONDITIONS FOR USE OF ESAs IN PATIENT WITH CANCER- REVISES DOSING DIRECTIONS

  MedWatch - The FDA Safety Information and Adverse Event Reporting Program

  Amgen and FDA informed healthcare professionals of modifications to certain sections of the Boxed Warnings, Indications and Usage, and Dosage and Administration sections of prescribing information for Erythropoiesis Stimulating Agents (ESAs). The changes clarify the FDA-approved conditions for use of ESAs in patients with cancer and revise directions for dosing to state the hemoglobin level at which treatment with an ESA should be initiated. Additional revisions to prescribing information that ESAs are not intended for use in patients receiving myelosuppressive therapy when the expected outcome is cure and when to initiate and discontinue ESA dosing will be forthcoming. FDA continues to encourage healthcare professionals to discuss with their patients before starting or continuing therapy with ESAs, the benefits of treatment with ESAs and the potential and demonstrated risks of ESAs for thrombovascular events, shortened time to tumor progression or recurrence, and shortened survival time.

  Read the entire 2008 MedWatch Safety Summary, including a link to the FDA's Follow Up to an Ongoing Safety Review regarding this issue at:

  http://www.fda.gov/medwatch/safety/2008/safety08.htm#ESA2
   

   

• VACCINES FOR PREVENTING INFLUENZA IN HEALTHY CHILDREN

  Authors  Jefferson Tom, Rivetti Alessandro, Harnden Anthony, Di Pietrantonj Carlo, Demicheli Vittorio

  Review Group  Cochrane Acute Respiratory Infections Group

  Abstract  The consequences of influenza in children and adults are mainly absenteeism from school and work. However, the risk of complications is greatest in children and people over 65 years old. Objectives: To appraise all comparative studies evaluating the effects of influenza vaccines in healthy children; assess vaccine efficacy (prevention of confirmed influenza) and effectiveness (prevention of influenza-like illness) and document adverse events associated with influenza vaccines. Search strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, issue 3); OLD MEDLINE (1950 to 1965); MEDLINE (1966 to September 2007); EMBASE (1974 to September 2007); Biological Abstracts (1969 to September 2007); and Science Citation Index (1974 to September 2007).Selection criteria Randomized controlled trials (RCTs), cohort and case-control studies of any influenza vaccine in healthy children under 16 years of age. Data collection and analysis : Two review authors independently assessed trial quality and extracted data. Main results Fifty-one studies with 294,159 observations were included. Sixteen RCTs and 18 cohort studies were included in the analysis of vaccine efficacy and effectiveness. From RCTs, live vaccines showed an efficacy of 82% (95% confidence interval (CI) 71% to 89%) and an effectiveness of 33% (95% CI 28% to 38%) in children older than two compared with placebo or no intervention. Inactivated vaccines had a lower efficacy of 59% (95% CI 41% to 71%) than live vaccines but similar effectiveness: 36% (95% CI 24% to 46%). In children under two, the efficacy of inactivated vaccine was similar to placebo. Variability in study design and presentation of data was such that a meta-analysis of safety outcome data was not feasible. Extensive evidence of reporting bias of safety outcomes from trials of live attenuated vaccines impeded meaningful analysis. Authors' conclusions:  Influenza vaccines are efficacious in children older than two but little evidence is available for children under two. There was a marked difference between vaccine efficacy and effectiveness. No safety comparisons could be carried out, emphasizing the need for standardization of methods and presentation of vaccine safety data in future studies. It was surprising to find only one study of inactivated vaccine in children under two years, given current recommendations to vaccinate healthy children from six months old in the USA and Canada. If immunization in children is to be recommended as a public health policy, large-scale studies assessing important outcomes and directly comparing vaccine types are urgently required.

  Implications  National policies for the vaccination of healthy young children are based on very little evidence.

  Citation  Jefferson T, Rivetti A, Harnden A, Di Pietrantonj C, Demicheli V. Vaccines for preventing influenza in healthy children. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD004879. DOI: 10.1002/14651858.CD004879.pub3.

   

• IN SCIATICA, EARLY SURGERY HAS SHORT-TERM BUT NOT LONG-TERM BENEFITS OVER CONSERVATIVE CARE
   

  Summary  For sciatica due to lumbar disc herniation, this randomized controlled trial found that early surgery has short-term but not long-term benefits over conservative treatment.

  Basis for Study/Article  The authors of this multi-center Dutch trial compared early surgery vs. prolonged conservative treatment for sciatica.

  Detailed Summary of Study  Of 283 patients who had sciatica for 6 to 12 weeks, 141 were assigned to early surgery (89% had microdiscectomy) and 142 were assigned to 6 months of conservative treatment, with surgery if needed (44% of them eventually had surgery). Pain was assessed over 2 years of follow-up.

  Results/Body  Disability scores did not differ between the groups over 2 years. Leg pain improved more quickly in the early surgery group, but the difference was no longer significant by 6 months and continued to decrease over 2 years. Patient satisfaction fell slightly between 1 and 2 years; after 2 years 20% of patients reported an unsatisfactory outcome.

  Sources & Other Links  Peul WC, et al. Prolonged conservative care versus early surgery in patients with sciatica caused by lumbar disc herniation: two-year results of a randomised controlled trial. BMJ. 2008 Jun 14;336(7657):1355-8.  Article Link (NCBI)

   

• DIABETES INCREASES RISK OF HEARING LOSS

  Summary  Diabetes is an independent risk factor for hearing loss.

  Basis for Study/Article  The authors compared the prevalence of hearing impairment in adults with and without diabetes.

  Detailed Summary of Study  As part of the National Health and Nutrition Examination Survey, information was collected from 5,140 subjects (399 with type 1 or 2 diabetes) age 20 to 69 who underwent audiometry.

  Results/Body  The age-adjusted prevalence of at least mild low- or mid-frequency hearing loss was 21.3% in the diabetics vs. 9.4% in those without diabetes (adjusted odds ratio 1.82). The figures for high-frequency hearing loss were 54.1% vs. 32.0% (adjusted odds ratio 2.16). The higher figures for diabetics were not explained by risk factors for hearing loss such as noise exposure, ototoxic medication use or smoking.

  Sources & Other Links  Bainbridge KE, et al. Diabetes and hearing impairment in the United States: audiometric evidence from the National Health and Nutrition Examination Survey, 1999 to 2004. Ann Intern Med. 2008 Jul 1;149(1):1-10.

  Article Link (NCBI)

   

• SAFETY REVIEW ERYTHROPOIESIS-STIMULATING AGENTS (ESAs) EPOETIN ALFA (marketed as Procrit, Epogen) DARBEPOETIN ALFA (marketed as Aranesp)

  On April 22, 2008, FDA notified the manufacturer of Epogen/Procrit and Aranesp of its decision to require additional safety-related changes to the labeling for these products.

  Amgen submitted labeling supplements for Epogen/Procrit and Aranesp on May 22, 2008, following the March 13, 2008 Oncologic Advisory Committee’s recommendations to make additional safety-related changes to the labeling for these products. Amgen and FDA have agreed on many of these changes, including to replace the existing Patient Package Insert with a Medication Guide and to modify certain sections of the Boxed Warnings, Indications and Usage, and Dosage and Administration sections of package insert.

  These changes are intended to clarify the FDA-approved conditions for use of ESAs in patients with cancer and revise directions for dosing to state the hemoglobin level at which treatment with an ESA should not be initiated. While agreement was reached on the general concepts, Amgen and FDA have not reached agreement on specific wording on two points, including a warning statement that ESAs are not intended for use in patients receiving myelosuppressive therapy when the expected outcome is cure and statements regarding when to initiate and to discontinue ESA dosing. Labeling discussions concluded on July 15 and FDA issued a letter ordering the additional changes on July 30, 2008.

  FDA’s action to require these safety labeling changes follows the completion of the review of information received in November 2007 and December 2007 and are in keeping with the recommendations made at the March 13, 2008 Oncologic Drugs Advisory Committee meeting. Amgen has been ordered to make the additional changes under new authorities provided in the FDA Amendments Act of 2007 and has 5 days to appeal or 15 days to submit a supplement containing the labeling changes.

  FDA continues to encourage healthcare professionals to discuss with their patients before starting or continuing therapy with ESAs, the benefits of treatment with ESAs and the potential and demonstrated risks of ESAs for thrombovascular events, shortened time to tumor progression or recurrence, and shortened survival time.

  The FDA urges healthcare professionals to promptly report serious and unexpected adverse reactions associated with Epogen, Procrit and Aranesp to the FDA MedWatch reporting program, as described below.  Online at www.fda.gov/medwatch/report.htm

   

• DIETARY ADVICE IN PREGNANCY FOR PREVENTING GESTATIONAL DIABETES

  Authors  Tieu Joanna, Crowther Caroline A, Middleton Philippa

  Review Group  Cochrane Pregnancy and Childbirth Group

  Abstract  Gestational diabetes mellitus (GDM) is a form of diabetes that occurs during pregnancy which can result in significant adverse outcomes for mother and child both in the short and long term. The potential for adverse outcomes, in addition to the increasing prevalence of gestational diabetes worldwide, demonstrates the need to assess strategies, such as dietary advice, that might prevent gestational diabetes.ObjectivesTo assess the effects of dietary advice in preventing gestational diabetes mellitus.Search strategy. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (January 2008) and reference lists of retrieved articles.Selection criteria Quasi-randomised and randomised studies of dietary intervention for preventing glucose intolerance in pregnancy.Data collection and analysis: Two review authors independently conducted data extraction and quality assessment. We resolved disagreements through discussion or through a third author.Main resultsThree trials (107 women) were included in the review. One trial (25 pregnant women) analysed high-fibre diets with no included outcomes showing statistically significant differences. Two trials (82 pregnant women) assessed low glycaemic index (LGI) versus high glycaemic index diets for pregnant women. Women on the LGI diet had fewer large for gestational age infants (one trial; relative risk (RR) 0.09, 95% confidence interval (CI) 0.01 to 0.69), infants with lower ponderal indexes (two trials; weighted mean difference (WMD) -0.18, 95% CI -0.32 to -0.04, random-effects analysis) and lower maternal fasting glucose levels (two trials; WMD -0.28 mmol/L 95% CI -0.54 to -0.02, random-effects model). Results for women on the LGI diet on neonatal birth weight were not conclusive under a random-effects model (two trials; WMD -527.64 g, 95% CI -1119.20 to 63.92); however, on a fixed-effect model, women on the LGI diet gave birth to lighter babies (two trials; WMD -445.55 g, 95% CI -634.16 to -256.95). High heterogeneity was observed between the trials in most results and both were relatively small trials. One of these trials also included a standard exercise regimen for all participants.Authors' conclusionsWhile a low glycaemic index diet was seen to be beneficial for some outcomes for both mother and child, results from the review were inconclusive. Further trials with large sample sizes and longer follow up are required to make more definitive conclusions. No conclusions could be drawn from the high-fibre versus control-diet comparison since the trial involved did not report on many of the outcomes we prespecified.

  Implications  Overall, results were inconclusive due to the limited number of trials, participants and data provided in addition to high heterogeneity between trials. While the results were promising, the evidence is not sufficient to change clinical practice without further research on dietary intervention for the prevention of gestational diabetes mellitus (GDM) and its associated outcomes. One study in Australia suggests that dietary advice for low and high GI diets can be acceptable and affordable for women.

  Citation  Tieu J, Crowther CA, Middleton P. Dietary advice in pregnancy for preventing gestational diabetes mellitus. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD006674. DOI: 10.1002/14651858.CD006674.pub2.

• FDA ALERT [7/24/2008]: ABACAVIR (MARKETED AS ZIAGEN) AND ABACAVIR-CONTAINING MEDICATIONS

  Serious and sometimes fatal hypersensitivity reactions (HSR) caused by abacavir therapy are significantly more common in patients with a particular human leukocyte antigen (HLA) allele, HLA-B*5701. Abacavir HSR is a multi-organ syndrome characterized by 2 or more clinical signs or symptoms that can include fever, rash, gastrointestinal symptoms, respiratory symptoms and constitutional symptoms.

  FDA has reviewed data from 2 studies that support the recommendation for pre-therapy screening for the presence of the HLA-B*5701 allele and the selection of alternative therapy in positive subjects. Genetic tests for HLA-B*5701 are already available and all patients should be screened for the HLA-B*5701 allele before starting or restarting treatment with abacavir or abacavir-containing medications. Avoidance of abacavir therapy in HLA-B*5701 positive patients will significantly decrease the risk of developing clinically-suspected abacavir HSR. For HLA-B*5701-positive patients, treatment with an abacavir-containing regimen is not recommended and should be considered only under exceptional circumstances when the potential benefit outweighs the risk.

  Development of clinically-suspected abacavir HSR requires immediate and permanent discontinuation of abacavir therapy in all patients, including patients negative for HLA-B*5701. This new safety information will be reflected in updated product labeling.www.fda.gov/medwatch/report/hcp.htm

   
• PREDICTING ELDERLY WOMEN AT HIGH V S. LOW RISK FOR OSTEOPOROTIC FRACTURE

  Summary  A low ultrasound bone stiffness index at the heel and four clinical risk factors (age, history of fracture, recent fall, “failed chair test”) can be used together to predict which elderly women are at high risk for osteoporotic fracture.

  Basis for Study/Article  The authors of this Swiss study developed and tested a predictive rule to identify elderly women at high vs. low risk for osteoporotic fracture.

  Detailed Summary of Study  The authors used data from a prospective multicenter study (6,174 women age 70 to 85) assessing the predictive value of an ultrasound bone stiffness index at the heel. Statistical analysis was used to identify additional factors that were predictive of fracture.

  Results/Body  Risk factors for osteoporotic fracture were age >75 years, low stiffness index in the heel, history of fracture, a recent fall and “a failed chair test” (inability to rise from a chair three times in a row without using the arms). A scoring system incorporating these risk factors assigned 1,464 women to a low-risk group and 4,710 to a high-risk group. The rate of osteoporotic fracture was 6.1% for the high-risk group and 1.8% for the low-risk group. 90% of those who had an osteoporotic hip fracture were in the high-risk group.

  Sources & Other Links  Guessous I, et al. Osteoporotic fracture risk in elderly women: estimation with quantitative heel US and clinical risk factors. Radiology. 2008 Jul;248(1):179-84.

  Article Link (NCBI)

   
• IN NEWLY DIAGNOSED TYPE 2 DM, SHORT-TERM INSULIN THERAPY OUTPERFORMS OVRAL HYPOGLYCEMICS

  Summary  In patients with newly diagnosed diabetes, this randomized, multicenter trial found that short-term, intensive insulin therapy results in better beta-cell function and longer glycemic remission compared to oral hypoglycemics.

  Basis for Study/Article  This Chinese trial compared the effectiveness of intensive insulin therapy vs. oral hypoglycemics in terms of beta-cell function and diabetes remission rates in newly diagnosed diabetics.

  Detailed Summary of Study  382 patients ages 25 to 70 from 9 centers in China with a fasting plasma glucose level of 7.0 to 16.7 mmol/L were randomized to receive short-term therapy with insulin (continuous infusion or multiple daily injections) or oral hypoglycemics. Drug treatment was stopped after blood glucose levels were normal for 2 weeks. Glucose tolerance tests were done and blood glucose levels, insulin and proinsulin levels were measured at baseline, immediately after therapy, and 1 year after therapy.

  Results/Body  Compared with the oral hypoglycemic group, the patients who received early insulin treatment had significantly higher remission rates at 1 year (51.1% for continuous insulin, 44.9% for multiple daily insulin injections, 26.7% for oral hypoglycemics). More of the insulin group patients achieved their target blood glucose goals (97.1% of the continuous infusion group, 95.2% of the multiple injections group, 83.5% of the oral hypoglycemic group), and in less time (4.0 days, 5.6 days, 9.3 days). Beta-cell function improvements persisted at 1 year in the insulin group but declined significantly in the oral treatment group.

  Sources & Other Links  Weng J, et al. Effect of intensive insulin therapy on beta-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial. Lancet. 2008 May 24;371(9626):1753-60.  Article Link (NCBI)

   

• OLANZAPINE (Zyprexa®) USEFUL IN TREATING ANOREXIA NERVOSA

  Summary  In women with anorexia nervosa, this controlled trial found that olanzapine (Zyprexa®) promotes weight gain and reduces obsessive symptoms.

  Basis for Study/Article  The authors tested the utility of the atypical antipsychotic drug olanzapine in the treatment of women with anorexia nervosa.

  Detailed Summary of Study  34 women with anorexia nervosa were randomized to receive day hospital treatment plus either placebo or olanzapine (flexible dose). Weight and obsessive symptoms were recorded at baseline and after 10 weeks of treatment.

  Results/Body  Compared with the placebo group, the women taking olanzapine had a greater rate of weight gain, achieved their target weight earlier and had fewer obsessive symptoms. There were no differences in adverse events between the groups. The authors recommend that a large multicenter trial be conducted.

  Sources & Other Links  Bissada H, et al. Olanzapine in the treatment of low body weight and obsessive thinking in women with anorexia nervosa: a randomized, double-blind, placebo-controlled trial. Am J Psychiatry. 2008 Jun 16.

  Article Link (NCBI)

   

• WHICH PRESCHOOLERS WITH WHEEZE WILL DEVELOP PERSISTENT ASTHMA?

  Summary  Preschoolers with exercise-induced wheeze and a history of atopic disorders are much more likely to develop persistent asthma.

  Basis for Study/Article  The authors identified predictors of persistent asthma in preschoolers with wheeze.

  Detailed Summary of Study  Parents of preschoolers in Manchester, England, received questionnaires asking about their children’s respiratory symptoms five times between 1993 and 2004. At baseline the 628 children were <5 years old. Follow-up was at least 6 years.

  Results/Body  32% of the children had wheeze at baseline and 27% had it at the second time point. Predictors of persistent asthma were exercise-induced wheeze (odds ratio 3.94) and a history of atopic disorders (odds ratio 4.44). Children with both predictors had a 53.2% likelihood of developing asthma; the likelihood was 10.9% if neither was present.

  Sources & Other Links  Frank PI, et al. Long term prognosis in preschool children with wheeze: longitudinal postal questionnaire study 1993-2004. BMJ. 2008 Jun 21;336(7658):1423-6.

  Article Link (NCBI)

   

• OBSTRUCTIVE SLEEP APNEA IS COMMON IN WOMEN WITH NOCTURIA

  Summary  Obstructive sleep apnea is common in women with nocturia, and 88% of women with dilute nighttime urine have OSA. “We should consider a diagnosis of OSA in all patients with nocturia,” even those with daytime overactive bladder symptoms.

  Basis for Study/Article  The authors explored the association between obstructive sleep apnea and nocturia in women and tested urine samples to see whether urine concentration was predictive for sleep apnea.

  Detailed Summary of Study  21 women with nocturia (16 of them also had daytime overactive bladder) and 10 control subjects completed nocturia questionnaires, underwent a home sleep study and provided evening and morning urine samples.

  Results/Body  17 of the 21 women with nocturia (81%) were found to have sleep apnea (13 of the 16 with daytime overactive bladder and 4 of the 5 without) vs. 4 of the control group. “The presence of diluted nighttime urine in a patient with nocturia was 88% sensitive for the presence of OSA.”

  Sources & Other Links  Lowenstein L, et al. The relationship between obstructive sleep apnea, nocturia, and daytime overactive bladder syndrome in women. Am J Obstet Gynecol. 2008 May;198(5):598.e1-5.  Article Link (NCBI)

   

• HAVING 1/2 TO 1 ALCOHOLIC DRINK PER DAY PROTECTS AGAINST HIP FRACTURE

  Summary  This meta-analysis found that people who have 1/2 to 1 alcoholic drink per day have a lower risk of hip fracture compared to nondrinkers and heavier drinkers.

  Basis for Study/Article  The authors performed a literature review to assess the effects of moderate alcohol consumption on bone density and the risk of osteoporotic hip fracture.

  Detailed Summary of Study  Effect sizes were pooled for hip fracture and bone density, and results were synthesized for four outcomes: non-hip fracture, bone density loss over time, bone response to estrogen replacement, and bone remodeling.

  Results/Body  People who had 1/2 to 1 alcoholic drink per day had a lower risk of hip fracture compared to nondrinkers (relative risk 0.80); the relative risk was 1.39 for those who had more than 2 drinks a day. “A linear relationship existed between femoral neck bone density and alcohol consumption,” but “a precise range of beneficial alcohol consumption cannot be determined.”

  Sources & Other Links  Berg KM, et al. Association between alcohol consumption and both osteoporotic fracture and bone density. Am J Med. 2008 May;121(5):406-18. Article Link (NCBI)

   

• ADVERSE EVENTS ASSOCIATED WITH PCA AND INSULIN PUMPS IN ADOLESCENTS

  Summary  Over a 10-year period, there were 1,594 reports to the FDA of adverse events associated with adolescents’ use of insulin pumps (including 13 deaths) and 53 reports of adverse events associated with patient-controlled analgesia pumps. “Studies need to further identify safety problems in this age group.”

  Basis for Study/Article  After receiving five reports of deaths in adolescents associated with insulin pumps in 2005, the FDA conducted an assessment of the safety of insulin and PCA pumps in this population.

  Detailed Summary of Study  The authors reviewed reports submitted to the FDA from 1996 through 2005 about adverse events associated with use of insulin or PCA pumps by adolescents (ages 12 to 21). Demographics, type of adverse event, outcomes and contributing factors were analyzed.

  Results/Body  Over a 10-year period, there were 1,594 reports of adverse events associated with insulin pumps, including 13 deaths, 2 possible suicide attempts, and several reports of apparently device-related hyperglycemia or hypoglycemia. Some of the contributing factors were compliance problems, lack of education, “sports-related activities” and “dropping or damaging the pump.” In 82% of the events the patient was hospitalized. There were 53 reports of adverse events associated with PCA pumps. In half the patients received too much medication; “tampering and noncompliance were evident in some cases.”

  The authors suggest more studies on the safety of these devices in adolescents.

  Sources & Other Links  Cope J, et al. Adolescent use of insulin and patient-controlled analgesia pump technology: a 10-year Food and Drug Administration retrospective study of adverse events. Pediatrics. 2008 May;121(5):e1133-8.  Article Link (NCBI)

   
• DIABETES MELLITUS TYPE 2 AND ITS DURATION AFFECT COGNITIVE FUNCTION IN THE ELDERLY

  Summary  This prospective study found that community-dwelling older adults with diabetes mellitus type 2 and those with a longer duration of diabetes have a higher risk for cognitive decline.

  Basis for Study/Article  The authors assessed whether the presence of diabetes mellitus type 2 and its duration affect cognitive function in elderly men and women.

  Detailed Summary of Study  General cognition and verbal memory were assessed at baseline in 5,907 men (mean age 74.1) in the Physicians’ Health Study II and 6,326 women (mean age 71.9) in the Women’s Health Study. 553 men and 405 women had diabetes. Follow-up assessments were made 2 years after baseline; the women had a third assessment 4 years later.

  Results/Body  Diabetic subjects had significantly lower baseline scores. A longer duration of diabetes was significantly associated with lower scores at baseline and follow-up. Diabetic men and women had significantly greater cognitive decline at follow-up than those without diabetes.

  Sources & Other Links  Okereke OI, et al. Type 2 diabetes mellitus and cognitive decline in two large cohorts of community-dwelling older adults. J Am Geriatr Soc. 2008 Jun;56(6):1028-36. Article Link (NCBI)

   
• HOME BLOOD PRESSURE MEASUREMENT IS USEFUL AND SHOULD BE COVERED BY INSURANCE

  Summary  Home blood pressure measurement is useful in the management of hypertension and should be covered by medical insurance.

  Basis for Study/Article  This is a scientific statement from the American Hearth Association, the American Society of Hypertension and the Preventive Cardiovascular Nurses Association. The authors reviewed the evidence on the use of home blood pressure monitoring by hypertensive patients and made recommendations for such use.

  Results/Body  Home monitoring should be part of the management regimen in all patients with known or suspected hypertension. It can be useful in identifying “white-coat hypertension.” Patients should use oscillometric monitors that measure BP on the upper arm, and should be shown how to use them properly. Target BP is <135/85, or <130/80 in high-risk patients. Home monitoring “has the potential to improve the quality of care while reducing costs and should be reimbursed.”

  Sources & Other Links  Pickering TG, et al. Call to action on use and reimbursement for home blood pressure monitoring: executive summary: a joint scientific statement from the American Heart Association, American Society of Hypertension, and Preventive Cardiovascular Nurses Association. Hypertension. 2008 Jul;52(1):1-9.  Article Link (NCBI)

   

• DISTINGUISHING ORGANIC VS. MECHANICAL LOW BACK PAIN IN CHILDREN

  Summary 

  In children with short-term symptoms, a bone scan is particularly useful n distinguishing organic low back pain from mechanical back pain.

  Basis for Study/Article

  The authors identified "which combination of imaging modalities provides the most sensitive and specific screening protocol for children with low back pain."

  Detailed Summary of Study

  The authors reviewed the records of 100 children age 2 to 18 with low back pain without night pain or constitutional symptoms, examining the utility of the imaging studies that were done.

  Results/Body

  The hyperextension test and on x-ray had a negative predicative value of 0.81 and a sensitivity of 0.90.  For children with non-neurologic symptoms of <6 weeks duration, a bone scan had 100% negative predictive value and sensitivity; it is "the most useful screening test because it is accurate, accessible, inexpensive and unlikely to require sedation."  Mechanical back pain was most likely in children with painless hyperextension and negative AP, lateral and oblique lumbar x-rays and MRI.

  Sources & Other Links 

  Auerbach JD, et al, Streamlining the evaluation of low back pain in children.  Clin Orthop Relat Res.  2008 June 16.  Article-Link (NCBI)

   

• ALPHA-LINOLENIC ACID REDUCES RISK OF MYOCARDIAL INFARCTION

  (HealthDay News) - Increased omega-3 fatty acid alpha-linolenic acid (ALA) intake is associated with decreased risk of non-fatal acute MI, according to a Harvard School of Public Health case-control study of 1,819 patients with a 1st non-fatal acute MI and 1,819 controls.  In a separate report, increased omega-6- fatty ALA intake is associated with reduction in systolic and diastolic blood pressure, according to a Japanese study of 2,238 patients without known cardiovascular disease.  Authors concluded that these results lend support to current recommendations for increased ingestion of polyunsaturated fatty acid from vegetable sources. (PubMed)

   
• COFFEE RELATED TO A HEALTHIER HEART
  Heavy coffee drinking may lower risk of cardiovascular death. 

  Summary:  This long-term study found that people who drink six or more cups of coffee each day have lower risk of dying of cardiovascular disease.

  Basis for study/Article

  The authors explored the association between coffee and mortality (all-cause and disease-specific)

  Detailed Summary of Study

  As part of the prospective Health Professionals Follow-up Study and the Nurses' health Study, information was collected on self-reported coffee consumption and death rates for cancer and cardiovascular disease, and was recorded.  The participants were 41,736 men and 86,214 women who did not have cardiovascular disease or cancer at baseline.  Follow-up was 18 years in men and 24 years in women.  The six levels of coffee consumption were <1 cup per months, 1 cup per months to 4 cups per week, 5 to 7 cups per week, 2 or 3 cups a day, 4 or 5 cups a day and 6 or more cups a day.

  Results/Body

  At follow-up, 6,888 of the men had dies (2,049 due to cardiovascular disease, 2,491 due to cancer) and 11,095 of the women had died )2,368 due to cardiovascular disease, 5,011 due to cancer).  In men, the relative risks for al-cause mortality were 1.0, 1.07, 1.02, 0.97, 0.93, and 0.80 for the six levels of coffee consumption, after adjusting for age, smoking and other risk factors for cancer and CVD.  In women the figures were 1.0,0.98,0.3, 0.82, 0.74, and 0.83.  Most of the effect was due to a reduction in CVD mortality rather than cancer mortality.  "Decaffeinated coffee consumption was associated with a small reduction in all-cause and CVD mortality."

  Sources & Other Links

  Lopez-Garcia E, et al.  The relationship of coffee consumption with mortality.  Ann Intern Med. 2008 Jun 17;148(12):904-13

• MEDICAL GRADE HONEY; LAST RESORT FOR DRUG-RESISTANT INFECTIONS

  In vitro studies of bactericidal activity show that a 40% solution of of honey reproducibly killed all bacterial isolates tested, including MRSA, vancomycin-resistant E. faecium, and multidrung-resistant gram-negative rods.  42 healthy volunteers had small forearm patches of skin swabbed with honey and covered with polyurethane dressings for 2 days.  Compared with control skin patches on the same volunteers, honey-covered patches were culture-negative significatly more often.  Medical-grade honey is produced by bees in closed greenhouses.  Grocery-grade honey is not standardized and can be bacterially contaminated.  Medline (Journal Watch).

   
• ANGINA PREVENTION

1 year after MI, angina remains in 20% of patients

Summary

This multi-center study found that 1 year after myocardial infarction, 20% of patients still have angina.  The most significant associated factors are depressive symptoms, a history of CABG surgery, and a prior history of angina.

Detailed Summary of Study

Angina was assessed 1 year after MI in  1,957 patients at 19 hospitals.  Information was collected on demographics, clinical history, MI presentation and inpatient and outpatient treatment.

Results/Body

19.5% of the patients had angina 1 year after their MI.  Associated factors were younger age (relative risk per 10-year decrease, 1.19), nonwhite race/male gender (relative risk 1.50), prior history of angina (1.78), CABG (1.92), recurrent rest angina during hospital stay (1.54), continued smoking after MI (1.23), history of revascularization after the first hospitalization (1.37), and presence of new (1.96), persistent (1.88) or transient (1.77) depressive symptoms.

Sources & Other Links

Maddox TM, et al. Angina at 1 year after myocardial infarction; prevalence and associated findings.  Arch Intern Med. 2998 Jun23;168(12);1310-6  Article Link (NIBI)

• AVASTIN (BEVACIZUMAB) AND SUNITINIB MALATE ASSOCIATED HEMOLYTIC ANEMIA

• FDA PRELIMINARY PHN: POSSIBLE MALFUNCTION OF ELECTRONIC MEDICAL DEVICES CAUSED BY COMPUTED TOMOGRAPHY (CT) SCANNING

  FDA informed healthcare professionals of the possibility that x-rays used during CT examinations may cause some implanted and external electronic medical devices to malfunction. Most patients with electronic medical devices undergo CT scans without any adverse consequences. However, the Agency has received a small number of reports of adverse events in which CT scans may have interfered with electronic medical devices, including pacemakers, defibrillators, neurostimulators, and implanted or externally worn drug infusion pumps. FDA is continuing to investigate the issue and is working with the manufacturer to raise awareness in the healthcare community. See the FDA Public Health Notification for a description of adverse event reports and recommendations regarding reducing the potential risk to patients.

   

• DIABETES TYPE 1 & 2 CONTROL VIA THE DCCT AND UKPDS STUDIES-GROUND BREAKING HISTORY OF GLOBAL MEDICINE REVIEW

• DIETARY ADVICE IN PREGNANCY FOR PREVENTING GESTATIONAL DIABETES MELLITUS

• ANTIBIOTICS FOR ACUTE MAXILLARY SINUSITIS

• IS TYPE 2 DIABETES A RISK FACTOR FOR DEPRESSION?

  Summary  Depressed people are slightly more likely to develop type 2 diabetes, mostly because of lifestyle factors. Conversely, depression was less common in people with impaired fasting glucose levels and untreated type 2 diabetes than it was in people with normal fasting glucose levels and those with treated type 2 diabetes.

  Basis for Study/Article  “Depressive symptoms are associated with development of type 2 diabetes, but it is unclear whether type 2 diabetes is a risk factor for elevated depressive symptoms.”

  Detailed Summary of Study  The researchers conducted two analyses of data from the Multi-Ethnic Study of Atherosclerosis, which comprised men and women age 45 to 84 who were enrolled in 2000-02 and followed up until 2004-05. The first analysis looked at the incidence of type 2 diabetes in 5,201 subjects who did not have diabetes at baseline, comparing the incidence in those with vs. without depressive symptoms. The second analysis looked at the incidence of depression in 4,847 subjects who were not depressed at baseline, comparing the incidence in those with vs. without diabetes. Depression was defined as use of antidepressants or a score of 16 on the Center for Epidemiologic Studies Depression Scale. Fasting glucose levels were defined as normal (<100 mg/dL), impaired (100 to 125 mg/dL) or type 2 diabetes (either receiving treatment or 126 mg/dL).

  Results/Body  In analysis 1, the incidence rate of type 2 diabetes was 22.0 per 1,000 person-years for those with depression and 16.6 for those without depression. This association was partially explained by lifestyle factors. In analysis 2, the incidence rate of depression was 36.8 per 1,000 person-years for those with normal fasting glucose levels, 27.9 for those with impaired levels, 31.2 for those with untreated diabetes and 61.9 for those with treated diabetes. Odds ratios for developing depression, compared to those with normal fasting glucose levels, were 0.79 for those with impaired levels, 0.75 for those with untreated diabetes and 1.54 for those with treated diabetes. The association remained significant after adjusting for multiple factors.

  Sources & Other Links  Golden SH, et al. Examining a bidirectional association between depressive symptoms and diabetes. JAMA. 2008 Jun 18;299(23):2751-9.  Article Link (NCBI)

   

• H. PYLORI INFECTIONS MAY TRIGGER SIDS

  Summary  This study from Norway found that H. pylori infection is significantly more common in SIDS victims and infants who die of infection. The authors hypothesize that such infection “may be involved as the triggering pathogen” for SIDS.

  Basis for Study/Article  The authors explored the proposed link between H. pylori infection and SIDS.

  Detailed Summary of Study  Immunoassay for the H. pylori antigen was performed in infants who died of various causes (122 SIDS victims; 17 infants who died of infection; 11 accidental or violent deaths) and 156 live controls.

  Results/Body  H. pylori was found in stool samples of 25% of the SIDS victims (p <0.001 vs. live controls), 53% of the babies who died of infection (p <0.001), 9% of accidental deaths (p = 0.6) and 8% of the live controls. In infants ages 1 to 5 months of age, the classic age for SIDS, 21 of the 67 SIDS victims tested positive for H. pylori vs. only 1 of the 68 live controls. “We hypothesize that H. pylori infection in infancy may be involved as the triggering pathogen for sudden death during the first five months after birth.”

  Sources & Other Links  Stray-Pederson A, et al. Helicobacter pylori antigen in stool is associated with SIDS and sudden infant deaths due to infectious disease. Pediatr Res. 2008 Jun 4. [Epub ahead of print] rticle Link (NCBI)

   

• ADDING SINGLE-DOSE DEXAMETHASONE TO ACUTE MIGRAINE TREATMENT LOWERS RECURRENCE RATE

  Summary  This meta-analysis found that adding a single dose of dexamethasone to standard abortive treatment for an acute migraine lowers the risk that the migraine will recur within 72 hours.

  Basis for Study/Article  The authors explored the role of parenteral dexamethasone in the treatment of acute migraine.

  Detailed Summary of Study  The authors analyzed the data from seven randomized controlled trials comparing the effects of standard abortive therapy for acute migraines plus either parenteral dexamethasone or placebo.

  Results/Body  Adding dexamethasone to the regimen did not improve pain relief, but it did reduce the risk of recurrence within 72 hours (relative risk 0.74) compared to placebo.

  Sources & Other Links <> Colman I, et al. Parenteral dexamethasone for acute severe migraine headache: meta-analysis of randomised controlled trials for preventing recurrence. BMJ. 2008 Jun 14;336(7657):1359-61.  Article Link (NCBI)

   

• VITAMIN D DEFICIENCY IS COMMON IN HEALTHY YOUNG CHILDREN

  Summary  Vitamin D deficiency (20 mg/mL) is common in otherwise healthy young children, and a third of the children with vitamin D deficiency had evidence of bone demineralization. Significant predictors of deficiency were breastfeeding without supplementation in infants and lower milk intake in children.

  Basis for Study/Article  The authors assessed the prevalence of vitamin D deficiency in healthy infants and toddlers and identified predictors of deficiency.

  Detailed Summary of Study  25-hydroxyvitamin D levels were measured in 380 healthy infants and toddlers at one urban clinic. Information was also collected on the children’s sun exposure, nutrition, and skin pigmentation and the parents’ health habits. Deficiency was defined as a level 20 mg/mL; the “accepted optimal threshold” was 30 mg/mL. For those found to have a deficiency, wrist and knee x-rays were taken to assess bone mineralization.

  Results/Body  12% of the children had a vitamin D deficiency; 40% had less than the optimal level. A third of the children with deficiency had radiographic evidence of bone demineralization and 7.5% had rachitic changes. In infants, breastfeeding without supplementation was a significant predictor of deficiency; in children, lower milk intake was a significant predictor. Skin pigmentation was not a predictor.

  Sources & Other Links  Gordon CM, et al. Prevalence of vitamin D deficiency among healthy infants and toddlers. Arch Pediatr Adolesc Med. 2008 Jun;162(6):505-12.

  Article Link (NCBI)

   
• CHILDREN WHO DRINK 100% FRUIT JUICE HAVE BETTER NUTRIENT INTAKE AND AREN'T OVERWEIGHT

  Summary  Children age 2 to 11 who drink 100% fruit juice have better nutrient intake and are not more likely to be overweight.

  Basis for Study/Article  The authors explored the impact of consumption of 100% fruit juice in terms of dietary intake and weight in children age 2 to 11 years.

  Detailed Summary of Study  The authors used data from the 1999-2002 National Health and Nutrition Examination Survey (n = 3,618 children). Mean daily intake of 100% fruit juice was 4.1 fluid ounces.

  Results/Body  Compared to those who didn’t drink 100% fruit juice, the children who did drink 100% fruit juice had significantly higher intakes of whole fruit, energy, carbohydrates, vitamin C, vitamin B6, potassium, riboflavin, magnesium, iron and folate. They had significantly less intake of total fat, saturated fatty acids, discretionary fat and added sugar. The amount of juice consumed did not affect the child’s weight or risk of being overweight.

  Sources & Other Links  Nicklas T, et al. Association between 100% juice consumption and nutrient intake and weight of children aged 2 to 11 years. Arch Pediatr Adolesc Med. 2008 Jun;162(6):557-65.  Article Link (NCBI)

   

• FDA RECALL

  FOR IMMEDIATE RELEASE -- Pompano Beach, FL – July 01, 2008 – Jack Distribution, LLC, 1501 Green Road Unit C Pompano Beach, Florida 33064 and its wholesale distributors G & N works, Inc., and Devine Distribution, Inc., announced today that they are conducting a voluntary nationwide recall of the following lot numbers of the company's supplement products sold under the brand names Rize 2 The Occasion and Rose 4 Her. (Rize 2 lot numbers CG-84 expires 11/10, GD-98 expires 08/10, CC-06 expires 06/10, 709 expires 09/10, CG-79 expires 11/10) (Rose 4 Her lot number CG-78 expires 11/10).

  Jack Distribution, LLC, is conducting this recall after being informed by representatives of the Food and Drug Administration (FDA) that lab analysis by FDA of Rize 2 and Rose 4 Her samples from lots manufactured and packaged in 2007 found the product contains potentially harmful, undeclared ingredients. FDA asserts that its chemical analysis revealed that these lots of Rize 2 The Occasion and Rose 4 Her contain thiomethisosildenafil, an analog of sildenafil, the active ingredient of a FDA-approved drug used for Erectile Dysfunction (ED). FDA maintains that this ingredient is close in structure to sildenafil and is expected to possess a similar pharmacological and adverse event profile. This undeclared chemical poses a potential threat to consumers because it may interact with nitrates found in some prescription drugs (such as nitroglycerin) and may lower blood pressure to dangerous levels.

  Consumers with diabetes, high blood pressure, high cholesterol, or heart disease often take nitrates. ED is a common problem in men with these conditions, and consumers may seek these types of products to enhance sexual performance.

  Customers who have this product in their possession should stop using it immediately and contact their physician if they have experienced any problems that may be related to taking this product.

  Any adverse events that may be related to the use of this product should be reported to the FDA's MedWatch Program by phone at 1-800-FDA-1088 or by fax at 1-800-FDA-0178 or by mail at MedWatch, HF-2, FDA, 5600 Fishers Lane, Rockville, MD 20852-9787.

  The company advises that any unused portions from these lot numbers be returned to the place of purchase for a full refund of purchase price. G & N Works and Devine Distribution are not shipping any Rize 2 or Rose 4 Her that is in stock while additional samples are being tested, they expect to begin shipping again in 2-4 weeks.

  Rize 2 and Rose 4 Her are sold in adult stores, vitamin & nutrition shops, convenience stores, and via the internet nationwide. The Rize 2 product is sold as a (single blister pack, three count bottles, twelve count bottles, and thirty count bottles. Rose 4 Her is only available in single blister packs and three count bottles.

  The Company is taking this voluntary action because it is committed and is always concerned with the health of persons who have consumed this product. The Company is reviewing the procedures and policies of all firms involved with the manufacture of the product to ensure that there will be no future issues with regard to Rize 2 and Rose 4 Her pills composition. The Company is working closely with the FDA in the recall process and is committed to the quality and integrity of its products. It sincerely regrets any inconvenience to consumers and its other customers.

  FDA notified healthcare professionals that a BOXED WARNING and Medication Guide are to be added to the prescribing information to strengthen existing warnings about the increased risk of developing tendinitis and tendon rupture in patients taking fluoroquinolones for systemic use.

  FOR IMMEDIATE RELEASE  Fluoroquinolones are associated with an increased risk of tendinitis and tendon rupture. This risk is further increased in those over age 60, in kidney, heart, and lung transplant recipients, and with use of concomitant steroid therapy. Physicians should advise patients, at the first sign of tendon pain, swelling, or inflammation, to stop taking the fluoroquinolone, to avoid exercise and use of the affected area, and to promptly contact their doctor about changing to a non-fluoroquinolone antimicrobial drug. Selection of a fluoroquinolone for the treatment or prevention of an infection should be limited to those conditions that are proven or strongly suspected to be caused by bacteria

   

• ALZHEIMER'S DISEASE IS NOW THE  6^th LEADING CAUSE OF DEATH

  Preliminary death statistics for 2006, released by CDC’s National Center for Health Statistics in early June 2008, found that Alzheimer’s Disease surpassed diabetes as the 6^th leading cause of death in the United States.  To view the press release, please visit: http://www.cdc.gov/media/pressrel/2008/r080611.htm.

   

• TRAUMATIC BRAIN INJURIES AMONG OLDER AMERICANS CAN RESULT FROM FALLS
  
  Traumatic brain injuries due to falls caused nearly 8,000 deaths and 56,000 hospitalizations in 2005 among Americans 65 and older, according to a new report from the Centers for Disease Control and Prevention released in the June issue of the Journal of Safety Research.  To learn more, please visit:  http://www.cdc.gov/ncipc/tbi/elder_fall.htm. 

   

• CAR CRASHES MORE COMMON IN PATIENTS WITH OBSTRUCTIVE SLEEP APNEA

  Summary Car accidents are more common in patients with obstructive sleep apnea/hypopnea, and they are also more likely to be injured in the crash.

  Basis for Study/Article  The authors of this Canadian study investigated the incidence and severity of car accidents in patients with obstructive sleep apnea.

  Detailed Summary of Study  Information on the number and severity of vehicle accidents was obtained from 783 patients (71% men, mean age 50 years) undergoing sleep studies for suspected obstructive sleep apnea. The figures were compared to those from 783 age- and sex-matched controls.

  Results/Body  Over a 3-year period the patients had 252 car crashes and the controls had 123. Relative risks were 2.6 for patients with mild OSA, 1.9 for those with moderate OSA and 2.0 for those with severe OSA. The crashes involving OSA patients were more likely to cause personal injury; corresponding relative risks were 4.8, 3.0 and 4.3. The patients whose sleep studies were negative did not have a significantly increased risk of being in a crash compared to the controls, nor were they more likely to be involved in accidents involving injury. 80% of the serious crashes (head-on collisions or accidents involving pedestrians or cyclists) occurred in the patients.

  Commentary  This data indeed is concerning for not only the frequency of accidents, but the evidence that major lapses in attention must have occurred to result in the higher severity of each accident. Doctors of OSA patients need to counsel their patients that this is a risk of OSA and consider this when recommending therapy for OSA.

  Grant E. Fraser, M.D.
  MedAlert Editor

  Sources & Other Links  Mulgrew AT, et al. Risk and severity of motor vehicle crashes in patients with obstructive sleep apnoea/hypopnoea. Thorax. 2008 Jun;63(6):536-41.  Article Link (NCBI)

   

• LONG-TERM EFFECTS OF DIET AND EXERCISE ON TYPE 2 DIABETES PREVENTION

  Summary  This study from China found that lifestyle changes (diet and exercise) can prevent or delay the onset of type 2 diabetes, but their effect on reducing the risk of cardiovascular disease and death remains unclear.

  Basis for Study/Article  The authors performed a follow-up analysis of their diabetes prevention study to assess the long-term effects of lifestyle changes. In the original multicenter study (1986–1992), 577 adults with impaired glucose tolerance were randomized to a control group or to one of three “lifestyle intervention groups” (diet, exercise, or both).

  Detailed Summary of Study  In this follow-up study, type 2 diabetes incidence, CVD incidence and mortality, and all-cause mortality were tracked in the original trial participants.

  Results/Body  At the 20-year follow-up, 80% of those who made lifestyle changes had developed type 2 diabetes vs. 93% of the control group. Those who made lifestyle changes had a 51% lower incidence of diabetes during the 6-year study and a 43% lower incidence at the 20-year follow-up, “controlled for age and clustering by clinic.” Average yearly incidence of diabetes was 7% for those who made lifestyle changes vs. 11% in the control group. Those who made lifestyle changes “spent an average of 3.6 fewer years with diabetes” vs. the control group. There were no differences between the groups in terms of rate of first CVD events, CVD mortality, and all-cause mortality, “but our study had limited statistical power to detect differences for these outcomes.”

  Sources & Other Links  Li G, et al. The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study. Lancet 2008 May 24;371(9626):1783-9.Article Link (NCBI)

   

• TEENS WITH PRIMARY AMENORRHEA AND PCOS ARE A DISTINCT SUBGROUP

  Summary  Teenage girls with polycystic ovarian syndrome that manifests as primary amenorrhea form a subgroup distinct from those with PCOS and oligomenorrhea or secondary amenorrhea. They have “increased features of the metabolic syndrome and higher androstenedione levels and may represent a more severe spectrum of a common condition.”

  Basis for Study/Article  This study compared the characteristics of teenage girls with PCOS manifested by primary amenorrhea vs. that manifested by secondary amenorrhea or oligomenorrhea.

  Detailed Summary of Study  At a Canadian pediatric endocrine clinic, clinical, laboratory and ultrasound results were collected from 9 adolescent girls with PCOS and primary amenorrhea and 18 with PCOS and secondary amenorrhea or oligomenorrhea.

  Results/Body  The girls with primary amenorrhea and PCOS had “older age at pubarche, higher androstenedione levels, greater prevalence of family history of obesity, a tendency toward no withdrawal bleeding in response to the progesterone challenge, and more features associated with the metabolic syndrome.”

  Sources & Other Links  Rachmiel M, et al. Primary amenorrhea as a manifestation of polycystic ovarian syndrome in adolescents: a unique subgroup? Arch Pediatr Adolesc Med. 2008 Jun;162(6):521-5.  Article Link (NCBI)

   

• MEN WITH LOWER VITAMIN D LEVELS HAVE A HIGHER RISK OF MYOCARDIAL INFARCTION

  Summary  This prospective study found that men with lower levels of vitamin D have a higher risk of myocardial infarction, with the degree of risk dependent on the level.

  Basis for Study/Article  The authors investigated whether low vitamin D levels raise the risk of coronary heart disease in men.

  Detailed Summary of Study  As part of the Health Professionals Follow-up Study, serum vitamin D levels (25-hydroxyvitamin D) were measured at baseline in 18,225 men age 40 to 75 who did not have cardiovascular disease. 10 years later, 454 of the men had developed nonfatal MI or fatal CHD. The authors compared vitamin D levels in those who did and did not develop heart disease.

  Results/Body  The risk of having an MI was 2.42 times higher in the men with low vitamin D levels (defined as 15 ng/mL), 1.43 times higher in those with levels 15 to 22.5 ng/mL, and 1.60 times higher in those with levels 22.6 to 29.9 ng/mL vs. those with “sufficient” levels (30 ng/mL). Adjusting for CV risk factors such as family history of MI, BMI, alcohol consumption, physical activity, lipid profile and others did not change the relationship.

  Sources & Other Links  Giovannucci E, et al. 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch Intern Med. 2008 Jun 9;168(11):1174-80.  Article Link (NCBI)

   

• IN YOUNG ADULTS, IBD HAS SERIOUS EFFECTS ON QUALITY OF LIFE, BODY IMAGE, AND SEXUAL FUNCTION

  Summary  In young adults, IBD has serious effects on quality of life, body image, and sexual function. “These issues need to be further addressed in both research & clinical settings.”

  Basis for Study/Article  The authors of this study from Australia explored how IBD affects quality of life, body image and sexual function in young adults.

  Detailed Summary of Study  The authors asked 183 patients (65% women, mean age 36 years) how IBD (mostly Crohn’s disease and ulcerative colitis) affected their lifestyle and body image.

  Results/Body  88% of the patients believed that IBD had affected their quality of life. 52% believed it had affected their relationship status; women were more likely to believe this, even though there was no actual difference in relationship status between men and women. 75% of women and half of men said it had affected their body image. 67% of women and 39% of men reported decreased libido due to IBD; 69% of those who had undergone surgery reported decreased libido vs. 49% of those who had not. 55% of patients reported decreased sexual activity since the onset of IBD symptoms: 87% attributed the decrease to feeling unwell, 48% to lower libido and 23% to concerns about their partner’s reaction.

  Sources & Other Links  Muller KR, et al. Female gender and surgery lead to greater perceived impact of inflammatory bowel disease (IBD) on body image and sexual function: a neglected issue. Presented at Digestive Disease Week, May 2008, abstract #944  Article Link (DOWNLOAD)

   

• GREEN TEA MAY IMPROVE HEART FUNCTION ACCORDING TO ONE NEW STUDY-MORE STUDIES NEEDED TO CONFIRM

  More evidence for the beneficial effect of green tea on risk factors for heart disease has emerged in a new study reported in the latest issue of European Journal of Cardiovascular Prevention and Rehabilitation. The study found that the consumption of green tea rapidly improves the function of (endothelial) cells lining the circulatory system; endothelial dysfunction is a key event in the progression of atherosclerosis.

  The study, performed by Dr Nikolaos Alexopoulos and colleagues at the 1st Cardiology Department, Athens Medical School in Greece, was a randomized trial involving the diameter measurement (dilatation) of the brachial artery of healthy volunteers on three separate occasions - after taking green tea, caffeine, and hot water (for a placebo effect). The measurements were taken at 30, 90 and 120 minutes after consumption. Dilatation of the brachial artery as a result of increased blood flow (following a brief period of ischemia of the upper limb) is related to endothelial function and is known to be an independent predictor of cardiovascular risk.2

  Results showed that endothelium-dependent brachial artery dilatation increased significantly after drinking green tea, with a peak increase of 3.9 per cent 30 minutes after consumption. The effect of caffeine consumption (or hot water) was not significant.

  While black tea has been associated with improved short and long-term endothelial performance, this is the first time that green tea has been shown to have a short-term beneficial effect on the large arteries. Another study has already shown that green tea reverses endothelial dysfunction in smokers.

  Green tea, which originates in China but is now consumed throughout the world, is made with pure leaves, and has undergone little oxidization during processing. The cardiovascular benefits of all teas - as well as dark chocolate and red wine - are attributed to the flavonoids they contain and their antioxidant activity.3 However, says investigator Dr. Charalambos Vlachopoulos, flavonoids in green tea are probably more potent antioxidants than in black tea because there has been no oxidization.

  "These findings have important clinical implications," says Dr Vlachopoulos. "Tea consumption has been associated with reduced cardiovascular morbidity and mortality in several studies. Green tea is consumed less in the Western world than black tea, but it could be more beneficial because of the way it seems to improve endothelial function. In this same context, recent studies have also shown potent anticarcinogenic effects of green tea, attributed to its antioxidant properties."

The Food and Drug Administration has approved Requip (ropinirole) to treat moderate to severe Restless Legs Syndrome (RLS). The drug was first approved for Parkinson’s disease in 1997.

Restless Legs Syndrome is a condition that affects about ten percent of the population. The disorder is characterized by an urge to move the legs, usually accompanied by or caused by uncomfortable leg sensations. For most people with the condition, symptoms begin or worsen during periods of rest or inactivity and are partially or totally relieved by movement. Symptoms typically worsen or occur only in the evening or at night, and can disturb sleep.

Requip was found to be effective for RLS in three randomized, double-blind placebo controlled studies in adults diagnosed with moderate to severe RLS. The studies measured effectiveness of the drug using the International Restless Leg Syndrome Scale, a patient rated scale that measures different aspects of RLS including severity of muscle movement and discomfort, sleep disturbance, mood and overall effect on quality of life. The Clinical Global Impression-Global Improvement scale was also used. This is an investigator rated scoring of improvement following treatment. All three studies demonstrated a statistically significant difference between the treatment group receiving Requip and the group receiving placebo.

Common side effects of Requip reported in clinical trials include nausea, headache, and vomiting. The label for the drug will also include a caution that Requip has been associated with sedating effects, including somnolence (sleepiness), and the possibility of falling asleep while engaged in activities of daily living, including operation of a motor vehicle. Syncope (fainting) or symptomatic hypotension (low blood pressure) may occur, particularly during initial treatment or dosing.