ACPM - JournalWatch: January 2006

January 2006
Compiled by Ryung Suh, MD
Resident, Pfizer Practicum Rotation in Health Policy and Preventive Medicine

Adamantane Resistance and Guidelines for Use of Antivirals
Statins Have “Neutral” Effect on Cancer
Attenuated Vaccine Against Severe Rotavirus Gastroenteritis
Relationship of Obesity to Morbidity and Mortality
Expert Reviews on Clostridium Difficile
Travel-Related Illness and Spectrum of Disease
2004 National Health Expenditures Hit 16.0%
Tuberculosis Control Guidelines
Aspirin Prevents Cardiovascular Disease in Healthy Adults

Adamantane Resistance and Guidelines for Use of Antivirals

The CDC has issued interim recommendations that adamantanes not be used during the rest of the 2005-06 influenza season. Resistance of influenza A viruses to adamantanes may occur spontaneously or emerge rapidly during treatment. A single point mutation in the codons for certain amino acids of the M2 protein can confer cross-resistance to both amantadine and rimantadine. Neither replication, transmission, nor virulence of adamantane-resistant influenza A viruses are impaired by the point mutations conferring resistance. From October 1, 2005 – January 14, 2006, a total of 123 influenza A viruses collected from 23 states were tested at CDC for adamantane resistance. Among the 120 influenza A (H3N2) viruses tested, 109 (91%) demonstrated the S31N substitution in the M2 protein that confers resistance to amantadine and rimantadine. Among the three influenza A (H1N1) viruses tested, none contained any mutations associated with resistance.

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm55d117a1.htm CDC. 2006. High levels of adamantane resistance among influenza A (H3N2) viruses and interim guidelines for use of antiviral agents – United States, 2005-06 influenza season. Morbidity and Mortality Weekly Report 55(Dispatch):1-2.

January 2005 Index

Statins Have “Neutral” Effect on Cancer

A meta-analysis of large-scale clinical trials of statins suggests that the cholesterol-lowering drug class has a neutral effect on cancer and cancer deaths. Seven recent retrospective studies had suggested that statins have a chemoprotective effect; but Dale et al. conducted a meta-analysis of 26 randomized controlled clinical trials of statins involving 86,936 participants. Statins failed to reduce the incidence of cancer (odds ratio 1.02, 95% CI) and failed to reduce cancer deaths (odds ratio 1.01, 95% CI). Furthermore, there were no reductions noted in any individual cancer type to include breast, colon, gastrointestinal tract, prostate, respiratory tract, or skin. The findings may discourage sponsors from pursuing large-scale trials seeking a cancer prevention claim for their statin products.

January 2005 Index

Attenuated Vaccine Against Severe Rotavirus Gastroenteritis

A randomized, double-blind, phase III trial of 63,225 healthy infants from 11 Latin American countries and Finland of two oral doses of live attenuated G1P[8] human rotavirus vaccine (HRV) or placebo at two and four months of age demonstrated vaccine efficacy of 85 percent (p<0.001) and reached 100 percent against more severe rotavirus gastroenteritis. Hospitalization for diarrhea was reduced by 42 percent (95% CI, 29% to 53%) and was not associated with increased risk of intussusception.

http://www.nejm.orgNew England Journal of Medicine. Vol 354 (No. 1), pp. 11-22. Guillermo M. Ruiz-Palacios et al. for the Human Rotavirus Vaccine Study Group.

January 2005 Index

Relationship of Obesity to Morbidity and Mortality

Abundant evidence links overweight and obesity with impaired health. However, controversies persist as to whether overweight and obesity have additional impacts on cardiovascular outcomes independent of their strong associations with established coronary risk factors, e.g., high blood pressure and high cholesterol level. The objective of this study was to assess the relationship of midlife body mass index with morbidity and mortality outcomes in older age among individuals without and with other major risk factors at baseline. A total of 17,643 subjects participated in the prospective study, with a mean follow-up of 32 years. Main outcome measures were hospitalization and mortality from CHD, cardiovascular disease, or diabetes, beginning at age 65 years. In multivariable analyses that included adjustment for systolic blood pressure and total cholesterol level, the odds ratio (95% confidence interval) for CHD death for obese participants compared with those of normal weight in the same risk category was 1.43 (0.33-6.25) for low risk and 2.07 (1.29-3.31) for moderate risk; for CHD hospitalization, the corresponding results were 4.25 (1.57-11.5) for low risk and 2.04 (1.29-3.24) for moderate risk. Results were similar for other risk groups and for cardiovascular disease, but stronger for diabetes. For individuals with no cardiovascular risk factors as well as for those with 1 or more risk factors, those who are obese in middle age have a higher risk of hospitalization and mortality from CHD, cardiovascular disease, and diabetes in older age than those who are normal weight.

http://jama.ama-assn.org/cgi/content/full/295/2/190 Yan LL, Daviglus ML, Liu K, Stamler J, Wang R, Pirzada A, Garside DB, Dyer AR, Van Horn L, Liao Y, Fries JF, Greenland P. 2006. Midlife body mass index and hospitalization and mortality in older age. JAMA 295:190-198.

January 2005 Index

Expert Reviews on Clostridium Difficile

Pepin et al. (2005) discussed quinolones as a major risk for C. difficile diarrhea, and concluded that fluoroquinolones have emerged as the most important risk factor for C. difficile-associated colonic disease in Quebec. Warny et al. (2005) reported on C. difficile toxin production detected during a severe epidemic, and concluded that the epidemic may be caused by a strain of C. difficile that appears to hyperproduce toxins A and B. Broek et al. (2005) described C. difficile sampling/cytotoxicity assays, and concluded that a second sample is unnecessary when using the cytotoxicity assay to detect C. difficile toxin.

http://www.medscape.com/viewarticle/517802?src=search Bartlett JG. 2005. Clostridium difficile: December 2005. Expert reviews and commentary. MedScape Infectious Diseases, Online.

January 2005 Index

Travel-Related Illness and Spectrum of Disease

Analysis of clinician-based sentinel surveillance data for 17,353 ill returned travelers seen in travel or tropical-medicine clinics revealed significant regional differences in proportionate morbidity in 16 of 21 broad syndromic categories. Systemic febrile illness without localizing findings were most often seen in travelers returning from sub-Saharan Africa or Southeast Asia, acute diarrhea among those returning from south central Asia, and dermatological problems among those returning from the Caribbean or Central or South America. Regional differences were also noted for malaria, dengue, rickettsial infection, typhoid, and others. This suggests that diagnostic approaches and empiric therapies may be better guided by these travel destination-specific differences.

http://www.nejm.org New England Journal of Medicine. Vol 354 (No. 2), pp. 119-130. David O. Freedman, Leisa H. Weld, Phyllis E. Kozarsky, Tamara Fisk, Rachel Robins, Frank von Sonnenburg, Jay S. Keystone, Prativa Pandey, Martin Cetron.

January 2005 Index

2004 National Health Expenditures Hit 16.0%

National health expenditures for 2004 totaled $1.88 trillion, reaching 16.0% of gross domestic product and $6,280 per capita. The rise in health spending was 7.9%, suggesting a slowing of the rate of spending growth for both public and private payers. Hospital spending accounted for 30 percent of the aggregate increase between 2002 and 2004, and prescription drugs accounted for an 11 percent share. The rate of growth was the smallest since 2000, driven by slowdowns in spending for prescription drugs and hospitals.

January 2005 Index

Tuberculosis Control Guidelines

National guidelines for the investigation, diagnostic evaluation, and medical treatment of TB contacts have not been updated since 1976, although investigation and treatment of infected contacts is an important component of the US strategy for TB elimination. The CDC issued a statement providing expanded guidelines concerning investigation of TB exposure and transmission and prevention of future cases of TB through contact investigations. In addition to the topics discussed previously, these expanded guidelines also discuss multiple related topics (e.g., data management, confidentiality and consent, and human resources). These guidelines are intended for use by public health officials, but also are relevant to others who contribute to TB control efforts. Although the recommendations pertain to the US, they might be adaptable for use in other countries that adhere to guidelines issued by WHO, the International Union against Tuberculosis and Lung Disease, and national TB control programs.

http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5415a1.htm CDC. 2005. Guidelines for the investigation of contacts of persons with infectious tuberculosis. Recommendations from the National Tuberculosis Controllers Association and CDC. Morbidity and Mortality Weekly Report 54(RR15):1-37.

January 2005 Index

Aspirin Prevents Cardiovascular Disease in Healthy Adults

A meta-analysis of six prospective, randomized controlled trials (51,342 women and 44,114 men) found that low-dose aspirin is effective in preventing cardiovascular events, even among men and women without pre-existing cardiovascular disease. Aspirin also increases the risks of major bleeding and, thus, clinicians must weigh the relative risks and benefits before prescribing as primary prophylaxis. Mean duration of follow-up was 6.4 years, and aspirin doses ranged from 100 mg every other day to 500 mg daily. Among men, aspirin reduced the risk of major cardiovascular events by 14% (p=0.01) and of myocardial infarction by 32% (p=0.001); it increased the risk of hemorrhagic stroke by 69% (p=0.03). Among women, aspirin prophylaxis reduced the risk of a cardiovascular event by 12% (p=0.03) and reduced the risk of ischemic stroke by 24% (p=0.008). Aspirin did not appear to have an impact on cardiovascular or all-cause mortality among men or women. The study population was at very low risk, and the number needed to prevent one cardiovascular event over a mean of 6.4 years was 333 women and 270 men.

http://jama.ama-assn.org.lrc1.usuhs.edu/cgi/reprint/295/3/306 JAMA 2006;295:306-313. Jeffrey S. Berger, Maria C. Roncaglioni, Fausto Avanzini, Ierta Pangrazzi, Gianni Tognoni, David L. Brown.

January 2005 Index