Laboratory Creation of a Highly Transmissible H5N1 Influenza Virus: Balancing Substantial Risks and Real Benefits.
Ann Intern Med. 2012 Jan 26;
Authors: Pavia AT
Abstract
Controversy erupted when influenza researchers announced that they had created an H5N1 influenza virus that was transmissible between ferrets. The controversy escalated when the National Science Advisory Board for Biosecurity (NSABB) recommended that the work be published but recommended significant voluntary redactions. The responses to the NSABB action and to the research itself have been polarized. A readily transmitted H5N1 virus could be extraordinarily lethal; therefore, the risk for accidental release is significant, and deliberate misuse of the data to create a biological weapon is possible. However, the knowledge gained by these and future experiments under appropriate safeguards is likely to allow critical understanding of influenza transmission and virulence. It would be irresponsible to adopt either extreme solution: to prevent and censor the research or to allow unlimited distribution without careful review by an independent group, such as the NSABB.
PMID: 22282172 [PubMed - as supplied by publisher]
Engineered H5N1: A Rare Time for Restraint in Science.
Ann Intern Med. 2012 Jan 26;
Authors: Inglesby TV
Abstract
Two scientific teams have recently engineered the H5N1 virus to make it readily transmissible between ferrets. Given that ferrets are considered the most reliable animal surrogate for human influenza infection, the newly engineered H5N1 strain is probably transmissible between humans as well. The potential consequences of an engineered human transmissible H5N1 strain are stunning. Although seasonal flu infects as much as 20% of the world’s population-more than 1 billion persons-each year, only a small fraction of those with seasonal flu dies, most often the oldest, youngest, and sickest. If the newly engineered strain were to escape the laboratory (either by design or by accident) and spread as widely as seasonal flu with anywhere near the current confirmed H5N1 human case-fatality rate, it could endanger the lives of hundreds of millions of persons. The possible benefits of this work do not justify taking such risks. As clinicians, we have a stake in this issue with our responsibilities for the diagnosis and treatment of influenza. We embrace the principle of free and open exchange of scientific information, but we also believe in the principle of “first, do no harm.” These 2 principles have come into a moment of rare conflict. It seems most reasonable and prudent to request that the involved scientific community and its institutions exercise restraint by restricting dissemination of the experimental results and discontinuing work on the engineered H5N1 strains. If a highly compelling case is made for continued work on this strain despite the risks, the work should be controlled and should merit the greatest scrutiny.
PMID: 22282173 [PubMed - as supplied by publisher]
Antiretroviral Medication and HIV Prevention: New Steps Forward and New Questions.
Ann Intern Med. 2012 Jan 16;
Authors: Mayer KH, Krakower D
Abstract
During the past 2 years, several pivotal clinical trials have proven that the use of antiretrovirals by HIV-infected and at-risk uninfected persons can decrease the probability of HIV being transmitted sexually. The initial chemoprophylaxis studies evaluated tenofovir administered topically or orally (with or without emtricitabine). However, multiple questions remain. Some subsequent primary prevention studies did not replicate the results of the initial studies, raising questions about differences in the behaviors of participants in each study (in particular about medication adherence), as well as whether pharmacologic or local mucosal factors might explain the variable efficacy estimates. Other antiretrovirals and delivery systems are being evaluated to maximize the efficacy of primary chemoprophylactic approaches. At present, increasing access to antiretroviral treatment globally is a priority, because expanding access to medication that can prevent morbidity and mortality is itself an important public health goal and may reasonably be expected to decrease HIV incidence. However, for treatment as prevention to be maximally effective, increases in HIV testing, health care workers, and infrastructure are needed, in addition to medications and laboratory support for clinical monitoring. A combination of approaches is needed to most quickly decrease the current trends in HIV incidence, including early diagnosis and initiation of treatment for HIV-infected persons. These approaches can be coupled with appropriately tailored interventions for populations at greatest risk for infection (for example, men who have sex with men and sex workers), including male circumcision, behavioral interventions, and chemoprophylaxis. However, a substantial gap exists between current expenditures and unmet needs, which suggests that mobilization of political will is needed for this combination approach to be successful.
PMID: 22250077 [PubMed - as supplied by publisher]
High doses of vitamin d to reduce exacerbations in chronic obstructive pulmonary disease: a randomized trial.
Ann Intern Med. 2012 Jan 17;156(2):105-14
Authors: Lehouck A, Mathieu C, Carremans C, Baeke F, Verhaegen J, Van Eldere J, Decallonne B, Bouillon R, Decramer M, Janssens W
Abstract
Background: Low serum 25-hydroxyvitamin D (25-[OH]D) levels have been associated with lower FEV(1), impaired immunologic control, and increased airway inflammation. Because many patients with chronic obstructive pulmonary disease (COPD) have vitamin D deficiency, effects of vitamin D supplementation may extend beyond preventing osteoporosis. Objective: To explore whether supplementation with high doses of vitamin D could reduce the incidence of COPD exacerbations. Design: Randomized, single-center, double-blind, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00666367) Setting: University Hospitals Leuven, Leuven, Belgium. Patients: 182 patients with moderate to very severe COPD and a history of recent exacerbations. Intervention: 100 000 IU of vitamin D supplementation or placebo every 4 weeks for 1 year. Measurements: The primary outcome was time to first exacerbation. Secondary outcomes were exacerbation rate, time to first hospitalization, time to second exacerbation, FEV(1), quality of life, and death. Results: Mean serum 25-(OH)D levels increased significantly in the vitamin D group compared with the placebo group (mean between-group difference, 30 ng/mL [95% CI, 27 to 33 ng/mL]; P < 0.001). The median time to first exacerbation did not significantly differ between the groups (hazard ratio, 1.1 [CI, 0.82 to 1.56]; P = 0.41), nor did exacerbation rates, FEV(1), hospitalization, quality of life, and death. However, a post hoc analysis in 30 participants with severe vitamin D deficiency (serum 25-[OH]D levels <10 ng/mL) at baseline showed a significant reduction in exacerbations in the vitamin D group (rate ratio, 0.57 [CI, 0.33 to 0.98]; P = 0.042). Limitation: This was a single-center study with a small sample size. Conclusion: High-dose vitamin D supplementation in a sample of patients with COPD did not reduce the incidence of exacerbations. In participants with severe vitamin D deficiency at baseline, supplementation may reduce exacerbations. Primary Funding Source: Applied Biomedical Research Program, Agency for Innovation by Science and Technology (IWT-TBM).
Cardiovascular mortality in women with obstructive sleep apnea with or without continuous positive airway pressure treatment: a cohort study.
Ann Intern Med. 2012 Jan 17;156(2):115-22
Authors: Campos-Rodriguez F, Martinez-Garcia MA, de la Cruz-Moron I, Almeida-Gonzalez C, Catalan-Serra P, Montserrat JM
Abstract
Background: Obstructive sleep apnea (OSA) is a risk factor for cardiovascular death in men, but whether it is also a risk factor in women is unknown. Objective: To investigate whether OSA is a risk factor for cardiovascular death in women and assess whether continuous positive airway pressure (CPAP) treatment is associated with a change in risk. Design: Prospective, observational cohort study. Setting: 2 sleep clinics in Spain. Patients: All women consecutively referred for suspected OSA between 1998 and 2007. Intervention: Every woman had a diagnostic sleep study. Women with an apnea-hypopnea index (AHI) less than 10 were the control group. Obstructive sleep apnea was diagnosed when the AHI was 10 or higher (classified as mild to moderate [AHI of 10 to 29] or severe [AHI ≥30]). Patients with OSA were classified as CPAP-treated (adherence ≥4 hours per day) or untreated (adherence <4 hours per day or not prescribed). Participants were followed until December 2009. Measurements: The end point was cardiovascular death. Results: 1116 women were studied (median follow-up, 72 months [interquartile range, 52 to 88 months]). The control group had a lower cardiovascular mortality rate (0.28 per 100 person-years [95% CI, 0.10 to 0.91]) than the untreated groups with mild to moderate OSA (0.94 per 100 person-years [CI, 0.10 to 2.40]; P = 0.034) or severe OSA (3.71 per 100 person-years [CI, 0.09 to 7.50]; P < 0.001). Compared with the control group, the fully adjusted hazard ratios for cardiovascular mortality were 3.50 (CI, 1.23 to 9.98) for the untreated, severe OSA group; 0.55 (CI, 0.17 to 1.74) for the CPAP-treated, severe OSA group; 1.60 (CI, 0.52 to 4.90) for the untreated, mild to moderate OSA group; and 0.19 (CI, 0.02 to 1.67) for the CPAP-treated, mild to moderate OSA group. Limitation: The study was observational and not randomized, and OSA was diagnosed by 2 different methods. Conclusion: Severe OSA is associated with cardiovascular death in women, and adequate CPAP treatment may reduce this risk. Primary Funding Source: None.
Virtual autopsy as an alternative to traditional medical autopsy in the intensive care unit: a prospective cohort study.
Ann Intern Med. 2012 Jan 17;156(2):123-30
Authors: Wichmann D, Obbelode F, Vogel H, Hoepker WW, Nierhaus A, Braune S, Sauter G, Pueschel K, Kluge S
Abstract
Background: Autopsy is an important educational and quality-control tool in the intensive care unit (ICU), but rates of traditional medical autopsies have declined worldwide. “Virtual” autopsy involving only advanced radiographic techniques might provide an alternative approach to postmortem examinations. Objective: To assess the value of postmortem multidetector computed tomography as an alternative to medical autopsy. Design: Prospective cohort study. (ClinicalTrials.gov registration number: NCT01040520) Setting: 9 ICUs in a single academic medical center. Consent for both medical and virtual autopsies was sought from the families of all consecutive patients who died in the ICU between 1 January and 30 June 2010. Clinical records were reviewed to determine whether unsuspected autopsy findings would have altered care if known (major diagnosis) or would not have altered care (minor diagnosis). Results: Of 285 patients, 47 underwent both virtual and medical autopsy. Of 196 clinical diagnoses made before death, 173 (88%) were identified by virtual autopsy and 183 (93%) by medical autopsy. Fourteen new major and 88 new minor diagnoses were detected by any autopsy method. The main diagnoses missed by virtual autopsy were cardiovascular events (9 of 72) and cancer (12 of 30). In contrast, medical autopsy missed 13 traumatic fractures and 2 pneumothoraces. Among 115 additional patients in whom only virtual autopsy was performed, 11 new major diagnoses were made. Limitation: Virtual autopsy was performed in only 57% of patients (n = 162); among this group, consent for traditional medical autopsy was obtained for only one third. Conclusion: Virtual autopsy may be useful for identifying diagnoses that traditionally have been identified by medical autopsy. This may also hold true, at least in part, for the educational aspect of medical autopsy (confirming antemortem clinical diagnoses). Further studies are required to confirm these preliminary results. Primary Funding Source: University Medical Center Hamburg-Eppendorf, Germany.
Background: Relatively little is known about why older persons develop long-term disability in community mobility. Objective: To identify the risk factors and precipitants for long-term disability in walking a quarter mile and driving a car. Design: Prospective cohort study from March 1998 to December 2009. Setting: Greater New Haven, Connecticut. Participants: 641 persons, aged 70 years or older, who were active drivers or nondisabled in walking a quarter mile. Persons who were physically frail were oversampled. Measurements: Candidate risk factors were assessed every 18 months. Disability in community mobility and exposure to potential precipitants, including illnesses or injuries leading to hospitalization or restricted activity, were assessed every month. Disability that lasted 6 or more consecutive months was considered long-term. Results: 318 (56.0%) and 269 (53.1%) participants developed long-term disability in walking and driving, respectively. Seven risk factors were independently associated with walking disability and 8 were associated with driving disability; the strongest associations for each outcome were found for older age and lower score on the Short Physical Performance Battery. The precipitants had a large effect on long-term disability, with multivariate hazard ratios for each outcome greater than 6.2 for hospitalization and greater than 2.4 for restricted activity. The largest differences in absolute risk were generally observed in participants with a specific risk factor who were subsequently hospitalized. Limitations: The observed associations may not be causal. The severity of precipitants was not assessed. The effect of the precipitants may have been underestimated because their exposure after the initial onset of disability was not evaluated. Conclusion: Long-term disability in community mobility is common among older persons. Multiple risk factors, together with subsequent precipitants, greatly increase the likelihood of long-term mobility disability. Primary Funding Source: National Institute on Aging, National Institutes of Health.
Wheeled mobility (wheelchair) service delivery: scope of the evidence.
Ann Intern Med. 2012 Jan 17;156(2):141-6
Authors: Greer N, Brasure M, Wilt TJ
Abstract
Identifying the appropriate wheelchair for a person who needs one has implications for both disabled persons and society. For someone with severe locomotive problems, the right wheelchair can affect mobility and quality of life. However, policymakers are concerned about the increasing demand for unnecessarily elaborate chairs. The Office of Inspector General, U.S. Department of Health and Human Services, issued 4 reports between 2009 and 2011 detailing fraud and misapplication of Medicare funds for powered wheelchairs, more than a decade after similar concerns were first raised by 4 contractors who process claims for durable medical equipment. Subsequent concerns have arisen about whether some impaired persons who need wheeled mobility devices may now be inappropriately denied coverage. A transparent, evidence-based approach to wheeled mobility service delivery (the matching of mobility-impaired persons to appropriate devices and supporting services) might lessen these concerns. This review describes the process of wheeled mobility service delivery for long-term wheelchair users with complex rehabilitation needs and presents findings from a survey of the literature (published and gray) and interviews with key informants. Recommended steps in the delivery process were identified in textbooks, guidelines, and published literature. Delivery processes shared many commonalities; however, no research supports the recommended approaches. A search of bibliographic databases through March 2011 identified 24 studies that evaluated aspects of wheeled mobility service delivery. Most were observational, exploratory studies designed to determine consumer use of and satisfaction with the process. The evidence base for the effectiveness of approaches to wheeled mobility service delivery is insufficient, and additional research is needed to develop standards and guidelines.
PMID: 22250145 [PubMed - in process]
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