Alcohol attributable burden of incidence of cancer in eight European countries based on results from prospective cohort study

To compute the burden of cancer attributable to current and former alcohol consumption in eight European countries based on direct relative risk estimates from a cohort study.

Design Combination of prospective cohort study with representative population based data on alcohol exposure.

Setting Eight countries (France, Italy, Spain, United Kingdom, the Netherlands, Greece, Germany, Denmark) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Participants 109 118 men and 254 870 women, mainly aged 37-70.

Main outcome measures Hazard rate ratios expressing the relative risk of cancer incidence for former and current alcohol consumption among EPIC participants. Hazard rate ratios combined with representative information on alcohol consumption to calculate alcohol attributable fractions of causally related cancers by country and sex. Partial alcohol attributable fractions for consumption higher than the recommended upper limit (two drinks a day for men with about 24 g alcohol, one for women with about 12 g alcohol) and the estimated total annual number of cases of alcohol attributable cancer.

Results If we assume causality, among men and women, 10% (95% confidence interval 7 to 13%) and 3% (1 to 5%) of the incidence of total cancer was attributable to former and current alcohol consumption in the selected European countries. For selected cancers the figures were 44% (31 to 56%) and 25% (5 to 46%) for upper aerodigestive tract, 33% (11 to 54%) and 18% (−3 to 38%) for liver, 17% (10 to 25%) and 4% (−1 to 10%) for colorectal cancer for men and women, respectively, and 5.0% (2 to 8%) for female breast cancer. A substantial part of the alcohol attributable fraction in 2008 was associated with alcohol consumption higher than the recommended upper limit: 33 037 of 178 578 alcohol related cancer cases in men and 17 470 of 397 043 alcohol related cases in women.

Conclusions In western Europe, an important proportion of cases of cancer can be attributable to alcohol consumption, especially consumption higher than the recommended upper limits. These data support current political efforts to reduce or to abstain from alcohol consumption to reduce the incidence of cancer.

source: BMJ

Vision Loss In Macular Degeneration Slowed Using Unique Encapsulated Cell Therapy

A phase 2 clinical trial for the treatment of a severe form of age-related macular degeneration, called geographic atrophy (GA), has become the first study to show the benefit of a therapy to slow the progression of vision loss for this disease. The results highlight the benefit of the use of a neurotrophic factor to treat GA and provide hope to nearly one million Americans suffering from GA.

The multi-center research team, including Kang Zhang, M.D., Ph.D., of the University of California, San Diego, Shiley Eye Center, the lead author of the paper and one of the leading investigators in the study, found that long-term delivery of ciliary neurotrophic factor (CNTF) served to re-nourish the retina and stop or slow the loss of visual acuity caused by the disorder. The results were recently published online in the Proceedings of National Academy of Sciences (PNAS).

According to Zhang—professor of ophthalmology and human genetics at the UCSD School of Medicine and director of UCSD’s Institute of Genomic Medicine—there is currently no effective treatment for dry AMD or GA, though there is a very big need. “This could open the door to long-term treatment of dry AMD, using a simple surgical procedure.”

Age-related macular degeneration, or AMD, is a leading cause of vision loss in Americans age 60 and older. It is a disease that causes cells in the macula—the part of the eye that allows us to see in fine detail—to die. There are two forms of the disorder, wet and dry AMD. GA is considered the end stage of dry AMD, where central vision is lost.

According to the National Eye Institute, wet AMD occurs when abnormal blood vessels behind the retina start to grow under the macula. These new blood vessels tend to be very fragile and often leak blood and fluid. The blood and fluid raise the macula from its normal place at the back of the eye, resulting in rapid loss of central version. There is currently a very effective therapy for wet AMD. Dry AMD occurs when the light-sensitive cells in the macula slowly break down, gradually blurring central vision in the affected eye.

In the trial, high-dose CNTF was delivered to 27 GA patients using encapsulated cell therapy (ECT). Another 24 patients received either a sham surgery (12) or a low-dose of CNTF (12). CNTF affects survival and differentiation of cells in the nervous system, including retinal cells. CNTF has been shown to retard the loss of photoreceptor cells in many animal models of retinal degeneration.

The ECT utilized a capsule that contains genetically engineered cells to continuously produce CNTF over a 12-month period. The CNTF-secreting capsule was implanted in the back of the study subject’s eye. The implant allows the CNTF molecules to diffuse into the eye tissue, while keeping out antibodies and immune cells that would attack and destroy the CNTF-producing cells.

There was a statistically significant difference in the change of the total macular volume in the eyes of study participants at the 12-month point, versus baseline in the high-dose group, according to Zhang. “In addition, all but one of the patients in the high dose group, or 96.3 percent, maintained stabilized vision, compared to only 75% of the patients in the sham-treatment group.”

The patients treated with a high dose of CNTF also showed an increase in retinal thickness as early as four months after implant, an increase that correlated to the stabilization of vision.

source: macular degeneration research

Can We Prevent Transmission of Drug-Resistant Bacteria in Hospitals?

Two large studies on active screening for drug-resistant bacteria produced strikingly different results.

How to limit the spread of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) in the healthcare environment remains unclear. This issue was recently addressed in two large clinical studies.

In a cluster-randomized trial involving 18 U.S. adult intensive care units (ICUs), Huskins and colleagues (with partial industry support) examined the effect of MRSA and VRE surveillance. In the 10 intervention ICUs, patients known or found to have MRSA or VRE colonization or infection were managed with contact precautions; all other patients received care with universal gloving pending the results of the screening studies. In the eight control ICUs, standard institutional protocols for managing MRSA and VRE were followed. Routinely scheduled surveillance cultures were obtained in all ICUs, but results were reported only for the intervention ICUs.

During the intervention period (March–August 2006), the mean incidence of MRSA and VRE colonization or infection events, adjusted for baseline incidence, was similar between the intervention and control ICUs (40.4 and 35.6 per 1000 patient-days at risk; P=0.35). The use of contact precautions, although marginally better in the intervention ICUs, was not optimal in either ICU group (appropriate glove use, 82% vs. 72% of contacts; appropriate gown use, 77% vs. 59%; hand hygiene after contact, 69% vs. 59%).

Jain and colleagues investigated the effectiveness of a “MRSA bundle” designed to reduce MRSA transmission in U.S. Veterans Affairs (VA) hospitals. This bundle involved surveillance for nasal MRSA colonization for all patients on admission, after transfer from one inpatient unit to another, and at hospital discharge; contact precautions for all patients with MRSA infection or colonization; hand hygiene; and a change in institutional culture to make prevention of MRSA transmission a responsibility for all healthcare workers.

From October 2007 (when the program was fully implemented in VA hospitals nationwide) through June 2010, the monthly rate of MRSA transmission decreased by 17% in ICUs and by 21% in non-ICUs. The monthly incidence of healthcare-associated MRSA infections in ICUs — which did not decrease significantly during the 2 years before bundle implementation — fell by 62%, with reductions noted for bloodstream infections, pneumonias, urinary tract infections, and skin and soft-tissue infections. A subset of hospitals reported on the incidence of healthcare-associated Clostridium difficile and VRE infections: During the study period, the rate of C. difficile infections did not change significantly in ICUs but decreased by 57% in non-ICUs; the rate of VRE infections fell by 100% in ICUs and by 70% in non-ICUs.

Comment: Huskins and colleagues’ results may have been affected by slow identification of colonized patients, as well as by poor adherence to recommended procedures (even with observers in the ICUs). Such lapses in adherence are consistent with the observations of many physicians and infection-control practitioners. Nonetheless, the study findings challenge the paradigm of performing surveillance and then instituting gown-and-glove precautions.

Whether the decrease in MRSA transmission in VA hospitals is attributable to the MRSA bundle is also unclear: The reduction is similar to that observed nationally between 2005 and 2008 (JW Infect Dis Aug 25 2010). Moreover, the fact that there was a concurrent comparable reduction in C. difficile and VRE transmission in VA hospitals suggests that the observed decrease in MRSA transmission might be attributable to greater emphasis on general infection-control measures (e.g., improved hand hygiene and strategies to decrease central line bloodstream infections and ventilator-associated pneumonias), rather than to the MRSA bundle. As noted by an editorialist, these studies underscore the importance of evaluating healthcare practices, including surveillance testing, to determine whether they achieve the expected results.

source:Journal Watch Infectious Diseases

Cardiac Troponin: Lowering the Threshold, Improving the Outcome

In a single-center study, detection of smaller elevations in troponin concentrations led to better management of acute coronary syndromes.

Many are concerned that lowering the cutoff value for myocardial necrosis on cardiac troponin tests will increase the number of false-positive results, thereby subjecting patients to unnecessary procedures. To assess the effect of lowering the diagnostic threshold, investigators used a sensitive assay to measure plasma troponin I concentrations in 2092 consecutive patients with suspected acute coronary syndromes (ACS) admitted to a single institution in Edinburgh, Scotland. Patients were stratified according to plasma troponin concentration (<0.05 ng/mL, 0.05–0.19 ng/mL, and 0.20 ng/mL). During a 6-month validation phase, the diagnostic troponin threshold for myocardial infarction (MI) was 0.20 ng/mL; during the following 6-month implementation phase, the diagnostic threshold was lowered to 0.05 ng/mL. Patients’ clinical characteristics were similar in both phases. Median follow-up after discharge was 453 days for the validation cohort and 451 days for the implementation cohort.

During both phases, patients with troponin concentrations below the MI threshold were less likely than those with troponin concentrations at or above it to be referred to a cardiologist, receive dual antiplatelet therapy, undergo coronary revascularization, or receive secondary preventive medications on discharge. When the MI threshold was lowered, the rates of these interventions increased significantly in the 8% of patients who newly received an MI diagnosis but remained unchanged in the 92% of patients whose MI status was unaffected.

During the validation phase, patients with troponin concentrations between 0.05 ng/mL and 0.19 ng/mL were significantly more likely than those with higher or lower concentrations to die or be readmitted with MI. When the MI threshold was lowered, the rate of death or MI decreased in patients who newly received an MI diagnosis (odds ratio, 0.42; P=0.01) but remained unchanged in those whose MI status was unaffected. Independent predictors of outcome were troponin concentration, history of ischemic heart disease, and age.

Comment: In this single-center study, lowering the diagnostic threshold for myocardial infarction was associated with significant improvements in the clinical care and outcomes of patients with suspected acute coronary syndromes. The findings demonstrate the value of sensitive troponin assays in the diagnosis of MI and the identification of high-risk patients.

source: Journal Watch Cardiology


Herpes Shedding Patterns Show Wide Risks for Transmission

Among patients seropositive for herpes simplex virus type 2, genital shedding is “likely universal,” regardless of symptoms, according to a JAMA study.

Researchers followed some 500 seropositive individuals for 2 months, during which the subjects collected daily swabs from the genital area. Rates of viral shedding were twice as high among symptomatic participants, but even asymptomatic subjects showed shedding on 10% of days. In addition, the number of virus copies shed was similar between symptomatic and asymptomatic participants.

The authors say their findings suggest that clinical management of seropositive — but asymptomatic — patients should include anticipatory guidance on recognizing genital symptoms as well as counseling on condom use, valacyclovir therapy, and the need to disclose serostatus to sexual partners.

Source: JAMA