PLoS ONE Alerts: Non-Clinical Medicine

Breaking the News or Fueling the Epidemic? Temporal Association between News Media Report Volume and Opioid-Related Mortality

2009-11-18T08:00:00Z

Background

Historical studies of news media have suggested an association between reporting and increased drug abuse. Period effects for substance use have been documented for different classes of legal and illicit substances, with the suspicion that media publicity may have played major roles in their emergence. Previous analyses have drawn primarily from qualitative evidence; the temporal relationship between media reporting volume and adverse health consequences has not been quantified nationally. We set out to explore whether we could find a quantitative relationship between media reports about prescription opioid abuse and overdose mortality associated with these drugs. We assessed whether increases in news media reports occurred before or after increases in overdose deaths.

Methodology/Principal Findings

Our ecological study compared a monthly time series of unintentional poisoning deaths involving short-acting prescription opioid substances, from 1999 to 2005 using multiple cause-of-death data published by the National Center for Health Statistics, to monthly counts of English-language news articles mentioning generic and branded names of prescription opioids obtained from Google News Archives from 1999 to 2005. We estimated the association between media volume and mortality rates by time-lagged regression analyses. There were 24,272 articles and 30,916 deaths involving prescription opioids during the seven-year study period. Nationally, the number of articles mentioning prescription opioids increased dramatically starting in early 2001, following prominent coverage about the nonmedical use of OxyContin. We found a significant association between news reports and deaths, with media reporting preceding fatal opioid poisonings by two to six months and explaining 88% (p<0.0001, df 78) of the variation in mortality.

Conclusions/Significance

While availability, structural, and individual predispositions are key factors influencing substance use, news reporting may enhance the popularity of psychoactive substances. Albeit ecological in nature, our finding suggests the need for further evaluation of the influence of news media on health. Reporting on prescription opioids conforms to historical patterns of news reporting on other psychoactive substances.

Postmortem Analyses Unveil the Poor Efficacy of Decontamination, Anti-Inflammatory and Immunosuppressive Therapies in Paraquat Human Intoxications

2009-09-25T07:00:00Z

Background

Fatalities resulting from paraquat (PQ) self-poisonings represent a major burden of this herbicide. Specific therapeutic approaches have been followed to interrupt its toxic pathway, namely decontamination measures to prevent PQ absorption and to increase its excretion from organism, as well as the administration of anti-inflammatory and immunosuppressive drugs. Until now, none of the postmortem studies resulting from human PQ poisonings have assessed the relationship of these therapeutic measures with PQ toxicokinetics and related histopathological lesions, these being the aims of the present study.

Methodology/Principal Findings

For that purpose, during 2008, we collected human fluids and tissues from five forensic autopsies following fatal PQ poisonings. PQ levels were measured by gas chromatography-ion trap mass spectrometry. Structural inflammatory lesions were evaluated by histological and immunohistochemistry analysis. The samples of cardiac blood, urine, gastric and duodenal wall, liver, lung, kidney, heart and diaphragm, showed quantifiable levels of PQ even at 6 days post-intoxication. Structural analysis showed diffused necrotic areas, intense macrophage activation and leukocyte infiltration in all analyzed tissues. By immunohistochemistry it was possible to observe a strong nuclear factor kappa-B (NF-κB) activation and excessive collagen deposition.

Conclusions/Significance

Considering the observed PQ levels in all analyzed tissues and the expressive inflammatory reaction that ultimately leads to fibrosis, we conclude that the therapeutic protocol usually performed needs to be reviewed, in order to increase the efficacy of PQ elimination from the body as well as to diminish the inflammatory process.

Early In-Hospital Mortality following Trainee Doctors' First Day at Work

2009-09-23T07:00:00Z

Background

There is a commonly held assumption that early August is an unsafe period to be admitted to hospital in England, as newly qualified doctors start work in NHS hospitals on the first Wednesday of August. We investigate whether in-hospital mortality is higher in the week following the first Wednesday in August than in the previous week.

Methodology

A retrospective study in England using administrative hospital admissions data. Two retrospective cohorts of all emergency patients admitted on the last Wednesday in July and the first Wednesday in August for 2000 to 2008, each followed up for one week.

Principal Findings

The odds of death for patients admitted on the first Wednesday in August was 6% higher (OR 1.06, 95% CI 1.00 to 1.15, p = 0.05) after controlling for year, gender, age, socio-economic deprivation and co-morbidity. When subdivided into medical, surgical and neoplasm admissions, medical admissions admitted on the first Wednesday in August had an 8% (OR 1.08, 95% CI 1.01 to 1.16, p = 0.03) higher odds of death. In 2007 and 2008, when the system for junior doctors' job applications changed, patients admitted on Wednesday August 1^st had 8% higher adjusted odds of death than those admitted the previous Wednesday, but this was not statistically significant (OR 1.08, 95% CI 0.95 to 1.23, p = 0.24).

Conclusions

We found evidence that patients admitted on the first Wednesday in August have a higher early death rate in English hospitals compared with patients admitted on the previous Wednesday. This was higher for patients admitted with a medical primary diagnosis.

Empirical Study of Data Sharing by Authors Publishing in PLoS Journals

2009-09-18T07:00:00Z

Background

Many journals now require authors share their data with other investigators, either by depositing the data in a public repository or making it freely available upon request. These policies are explicit, but remain largely untested. We sought to determine how well authors comply with such policies by requesting data from authors who had published in one of two journals with clear data sharing policies.

Methods and Findings

We requested data from ten investigators who had published in either PLoS Medicine or PLoS Clinical Trials. All responses were carefully documented. In the event that we were refused data, we reminded authors of the journal's data sharing guidelines. If we did not receive a response to our initial request, a second request was made. Following the ten requests for raw data, three investigators did not respond, four authors responded and refused to share their data, two email addresses were no longer valid, and one author requested further details. A reminder of PLoS's explicit requirement that authors share data did not change the reply from the four authors who initially refused. Only one author sent an original data set.

Conclusions

We received only one of ten raw data sets requested. This suggests that journal policies requiring data sharing do not lead to authors making their data sets available to independent investigators.

First Things First: Effectiveness and Scalability of a Basic Prehospital Trauma Care Program for Lay First-Responders in Kampala, Uganda

2009-09-11T07:00:00Z

Background

We previously showed that in the absence of a formal emergency system, lay people face a heavy burden of injuries in Kampala, Uganda, and we demonstrated the feasibility of a basic prehospital trauma course for lay people. This study tests the effectiveness of this course and estimates the costs and cost-effectiveness of scaling up this training.

Methods and Findings

For six months, we prospectively followed 307 trainees (police, taxi drivers, and community leaders) who completed a one-day basic prehospital trauma care program in 2008. Cross-sectional surveys and fund of knowledge tests were used to measure their frequency of skill and supply use, reasons for not providing aid, perceived utility of the course and kit, confidence in using skills, and knowledge of first-aid. We then estimated the cost-effectiveness of scaling up the program.

At six months, 188 (62%) of the trainees were followed up. Their knowledge retention remained high or increased. The mean correct score on a basic fund of knowledge test was 92%, up from 86% after initial training (n = 146 pairs, p = 0.0016). 97% of participants had used at least one skill from the course: most commonly haemorrhage control, recovery position and lifting/moving and 96% had used at least one first-aid item. Lack of knowledge was less of a barrier and trainees were significantly more confident in providing first-aid. Based on cost estimates from the World Health Organization, local injury data, and modelling from previous studies, the projected cost of scaling up this program was $0.12 per capita or $25–75 per life year saved. Key limitations of the study include small sample size, possible reporter bias, preliminary local validation of study instruments, and an indirect estimate of mortality reduction.

Conclusions

Lay first-responders effectively retained knowledge on prehospital trauma care and confidently used their first-aid skills and supplies for at least six months. The costs of scaling up this intervention to cover Kampala are very modest. This may be a cost-effective first step toward developing formal emergency services in Uganda other resource-constrained settings. Further research is needed in this critical area of trauma care in low-income countries.

Modulating Temporal and Spatial Oxygenation over Adherent Cellular Cultures

2009-09-03T07:00:00Z

Oxygen is a key modulator of many cellular pathways, but current devices permitting in vitro oxygen modulation fail to meet the needs of biomedical research. A microfabricated insert for multiwell plates has been developed to more effectively control the temporal and spatial oxygen concentration to better model physiological phenomena found in vivo. The platform consists of a polydimethylsiloxane insert that nests into a standard multiwell plate and serves as a passive microfluidic gas network with a gas-permeable membrane aimed to modulate oxygen delivery to adherent cells. Equilibration time is on the order of minutes and a wide variety of oxygen profiles can be attained based on the device design, such as the cyclic profile achieved in this study, and even oxygen gradients to mimic those found in vivo. The proper biological consequences of the device's oxygen delivery were confirmed in cellular models via a proliferation assay and western analysis of the upregulation of hypoxia inducible transcription factor-1α. These experiments serve as a demonstration for the platform as a viable tool to increase experimental throughput and permit novel experimental possibilities in any biomedical research lab.

Sources and Coverage of Medical News on Front Pages of US Newspapers

2009-09-02T07:00:00Z

Background

Medical news that appears on newspaper front pages is intended to reach a wide audience, but how this type of medical news is prepared and distributed has not been systematically researched. We thus quantified the level of visibility achieved by front-page medical stories in the United States and analyzed their news sources.

Methodology

Using the online resource Newseum, we investigated front-page newspaper coverage of four prominent medical stories, and a high-profile non-medical news story as a control, reported in the US in 2007. Two characteristics were quantified by two raters: which newspaper titles carried each target front-page story (interrater agreement, >96%; kappa, >0.92) and the news sources of each target story (interrater agreement, >94%; kappa, >0.91). National rankings of the top 200 US newspapers by audited circulation were used to quantify the extent of coverage as the proportion of the total circulation of ranked newspapers in Newseum.

Findings

In total, 1630 front pages were searched. Each medical story appeared on the front pages of 85 to 117 (67.5%–78.7%) ranked newspaper titles that had a cumulative daily circulation of 23.1 to 33.4 million, or 61.8% to 88.4% of all newspapers. In contrast, the non-medical story achieved front-page coverage in 152 (99.3%) newspaper titles with a total circulation of 41.0 million, or 99.8% of all newspapers. Front-page medical stories varied in their sources, but the Washington Post, Los Angeles Times, New York Times and the Associated Press together supplied 61.7% of the total coverage of target front-page medical stories.

Conclusion

Front-page coverage of medical news from different sources is more accurately revealed by analysis of circulation counts rather than of newspaper titles. Journals wishing to widen knowledge of research news and organizations with important health announcements should target at least the four dominant media organizations identified in this study.

Business Return in New Orleans: Decision Making Amid Post-Katrina Uncertainty

2009-08-26T07:00:00Z

Background

Empirical observations on how businesses respond after a major catastrophe are rare, especially for a catastrophe as great as Hurricane Katrina, which hit New Orleans, Louisiana on August 29, 2005. We analyzed repeated telephone surveys of New Orleans businesses conducted in December 2005, June 2006, and October 2007 to understand factors that influenced decisions to re-open amid post-disaster uncertainty.

Methodology/Principal Findings

Businesses in the group of professional, scientific, and technical services reopened the fastest in the near term, but differences in the rate of reopening for businesses stratified by type became indistinguishable in the longer term (around two years later). A reopening rate of 65% was found for all businesses by October 2007. Discriminant analysis showed significant differences in responses reflecting their attitudes about important factors between businesses that reopened and those that did not. Businesses that remained closed at the time of our third survey (two years after Katrina) ranked levee protection as the top concern immediately after Katrina, but damage to their premises and financing became major concerns in subsequent months reflected in the later surveys. For businesses that had opened (at the time of our third survey), infrastructure protection including levee, utility, and communications were the main concerns mentioned in surveys up to the third survey, when the issue of crime became their top concern.

Conclusions/Significance

These findings underscore the need to have public policy and emergency plans in place prior to the actual disaster, such as infrastructure protection, so that the policy can be applied in a timely manner before business decisions to return or close are made. Our survey results, which include responses from both open and closed businesses, overcome the “survivorship bias” problem and provide empirical observations that should be useful to improve micro-level spatial economic modeling of factors that influence business return decisions.

The Dynamic Interest in Topics within the Biomedical Scientific Community

2009-08-07T07:00:00Z

The increase in the size of the scientific community created an explosion in scientific production. We have analyzed the dynamics of biomedical scientific output during 1957–2007 by applying a bibliometric analysis of the PubMed database using different keywords representing specific biomedical topics. With the assumption that increased scientific interest will result in increased scientific output, we compared the output of specific topics to that of all scientific output. This analysis resulted in three broad categories of topics; those that follow the general trend of all scientific output, those that show highly variable output, and attractive topics which are new and grow explosively. The analysis of the citation impact of the scientific output resulted in a typical longtail distribution: the majority of journals and articles are of very low impact. This distribution has remained unchanged since 1957, although the interests of scientists must have shifted in this period. We therefore analyzed the distribution of articles in top journals and lower impact journals over time for the attractive topics. Novelty is rewarded by publication in top journals. Over time more articles are published in low impact journals progressively creating the longtail distribution, signifying acceptance of the topic by the community. There can be a gap of years between novelty and acceptance. Within topics temporary novelty is created with new subtopics. In conclusion, the longtail distribution is the foundation of the scientific output of the scientific community and can be used to examine different aspects of science practice.

The Impact of National Institutes of Health Funding on U.S. Cardiovascular Disease Research

2009-07-29T07:00:00Z

Background

Intense interest surrounds the recent expansion of US National Institutes of Health (NIH) budgets as part of economic stimulus legislation. However, the relationship between NIH funding and cardiovascular disease research is poorly understood, making the likely impact of this policy change unclear.

Methods

The National Library of Medicine's PubMed database was searched for articles published from 1996 to 2006, originating from U.S. institutions, and containing the phrases “cardiolog,” “cardiovascular,” or “cardiac,” in the first author's department. Research methodology, journal of publication, journal impact factor, and receipt of NIH funding were recorded. Differences in means and trends were tested with t-tests and linear regression, respectively, with P≤0.05 for significance.

Results

Of 117,643 world cardiovascular articles, 36,684 (31.2%) originated from the U.S., of which 10,293 (28.1%) received NIH funding. The NIH funded 40.1% of U.S. basic science articles, 20.3% of overall clinical trials, 18.1% of randomized-controlled, and 12.2% of multicenter clinical trials. NIH-funded and total articles grew significantly (65 articles/year, P<0.001 and 218 articles/year, P<0.001, respectively). The proportion of articles receiving NIH funding was stable, but grew significantly for basic science and clinical trials (0.87%/year, P<0.001 and 0.67%/year, P = 0.029, respectively). NIH-funded articles had greater journal impact factors than non NIH-funded articles (5.76 vs. 3.71, P<0.001).

Conclusions

NIH influence on U.S. cardiovascular research expanded in the past decade, during the period of NIH budget doubling. A substantial fraction of research is now directly funded and thus likely sensitive to budget fluctuations, particularly in basic science research. NIH funding predicts greater journal impact.

Quality of Pharmaceutical Advertisements in Medical Journals: A Systematic Review

2009-07-22T07:00:00Z

Background

Journal advertising is one of the main sources of medicines information to doctors. Despite the availability of regulations and controls of drug promotion worldwide, information on medicines provided in journal advertising has been criticized in several studies for being of poor quality. However, no attempt has been made to systematically summarise this body of research. We designed this systematic review to assess all studies that have examined the quality of pharmaceutical advertisements for prescription products in medical and pharmacy journals.

Methods and Findings

Studies were identified via searching electronic databases, web library, search engine and reviewing citations (1950 – February 2006). Only articles published in English and examined the quality of information included in pharmaceutical advertisements for prescription products in medical or pharmacy journals were included. For each eligible article, a researcher independently extracted the data on the study methodology and outcomes. The data were then reviewed by a second researcher. Any disagreements were resolved by consensus. The data were analysed descriptively. The final analysis included 24 articles. The studies reviewed advertisements from 26 countries. The number of journals surveyed in each study ranged from four to 24 journals. Several outcome measures were examined including references and claims provided in advertisements, availability of product information, adherence to codes or guidelines and presentation of risk results. The majority of studies employed a convenience-sampling method. Brand name, generic name and indications were usually provided. Journal articles were commonly cited to support pharmaceutical claims. Less than 67% of the claims were supported by a systematic review, a meta-analysis or a randomised control trial. Studies that assessed misleading claims had at least one advertisement with a misleading claim. Two studies found that less than 28% of claims were unambiguous clinical claims. Most advertisements with quantitative information provided risk results as relative risk reduction. Studies were conducted in 26 countries only and then the generalizability of the results is limited.

Conclusions

Evidence from this review indicates that low quality of journal advertising is a global issue. As information provided in journal advertising has the potential to change doctors' prescribing behaviour, ongoing efforts to increase education about drug promotion are crucial. The results from our review suggest the need for a global pro-active and effective regulatory system to ensure that information provided in medical journal advertising is supporting the quality use of medicines.

Expression of the Bcl-2 Protein BAD Promotes Prostate Cancer Growth

2009-07-13T07:00:00Z

BAD, a pro-apoptotic protein of the Bcl-2 family, has recently been identified as an integrator of several anti-apoptotic signaling pathways in prostate cancer cells. Thus, activation of EGFR, GPCRs or PI3K pathway leads to BAD phosphorylation and inhibition of apoptosis. Increased levels of BAD in prostate carcinomas have also been reported. It appears contradictory that instead of limiting expression of pro-apoptotic protein, prostate cancer cells choose to increase BAD levels while keeping it under tight phosphorylation control. Analysis of the effect of BAD on prostate cancer xenografts has shown that increased BAD expression enhances tumor growth, while knockdown of BAD expression by shRNA inhibits tumor growth. Tissue culture experiments demonstrated that increased BAD expression stimulates proliferation of prostate cancer cells. These results suggest that increased expression of BAD provides a proliferative advantage to prostate tumors, while BAD dephosphorylation increases sensitivity of prostate cancer cells to apoptosis. Combination of proliferative and apoptotic properties prompts prostate cancer cells to be “addicted” to increased levels of phosphorylated BAD. Thus, kinases that phosphorylate BAD are plausible therapeutic targets; while monitoring BAD phosphorylation could be used to predict tumor response to treatments.

Categorizing Patients in a Forced-Choice Triad Task: The Integration of Context in Patient Management

2009-06-11T07:00:00Z

Background

Studies of experts' problem-solving abilities have shown that experts can attend to the deep structure of a problem whereas novices attend to the surface structure. Although this effect has been replicated in many domains, there has been little investigation into such effects in medicine in general or patient management in particular.

Methodology/Principal Findings

We designed a 10-item forced-choice triad task in which subjects chose which one of two hypothetical patients best matched a target patient. The target and its potential matches were related in terms of surface features (e.g., two patients of a similar age and gender) and deep features (e.g., two diabetic patients with similar management strategies: a patient with arthritis and a blind patient would both have difficulty with self-injected insulin). We hypothesized that experts would have greater knowledge of management categories and would be more likely to choose deep matches. We contacted 130 novices (medical students), 11 intermediates (medical residents), and 159 experts (practicing endocrinologists) and 15, 11, and 8 subjects (respectively) completed the task. A linear mixed effects model indicated that novices were less likely to make deep matches than experts (t(68) = −3.63, p = .0006), while intermediates did not differ from experts (t(68) = −0.24, p = .81). We also found that the number of years in practice correlated with performance on diagnostic (r = .39, p = .02), but not management triads (r = .17, p = .34).

Conclusions

We found that experts were more likely than novices to match patients based on deep features, and that this pattern held for both diagnostic and management triads. Further, management and diagnostic triads were equally salient for expert physicians suggesting that physicians recognize and may create management-oriented categories of patients.

Twelve Years' Experience with Direct-to-Consumer Advertising of Prescription Drugs in Canada: A Cautionary Tale

2009-05-27T07:00:00Z

Background

Direct-to-consumer advertising (DTCA) of prescription drugs is illegal in Canada as a health protection measure, but is permitted in the United States. However, in 2000, Canadian policy was changed to allow ‘reminder’ advertising of prescription drugs. This is a form of advertising that states the brand name without health claims. ‘Reminder’ advertising is prohibited in the US for drugs that have ‘black box’ warnings of serious risks. This study examines spending on DTCA in Canada from 1995 to 2006, 12 years spanning this policy shift. We ask how annual per capita spending compares to that in the US, and whether drugs with Canadian or US regulatory safety warnings are advertised to the Canadian public in reminder advertising.

Methodology/Principal Findings

Prescription drug advertising spending data were extracted from a data set on health sector spending in Canada obtained from a market research company, TNS Media Inc. Spending was adjusted for inflation and compared with US spending. Inflation-adjusted spending on branded DTCA in Canada grew from under CAD$2 million per year before 1999 to over $22 million in 2006. The major growth was in broadcast advertising, accounting for 83% of spending in 2006. US annual per capita spending was on average 24 times Canadian levels. Celebrex (celecoxib), which has a US black box and was subject to three safety advisories in Canada, was the most heavily advertised drug on Canadian television in 2005 and 2006. Of 8 brands with >$500,000 spending, which together accounted for 59% of branded DTCA in all media, 6 were subject to Canadian safety advisories, and 4 had US black box warnings.

Conclusions/Significance

Branded ‘reminder’ advertising has grown rapidly in Canada since 2000, mainly due to a growth in television advertising. Although DTCA spending per capita is much lower in Canada than in the US, there is no evidence of safer content or product choice; many heavily-advertised drugs in Canada have been subject to safety advisories. For governments searching for compromise solutions to industry pressure for expanded advertising, Canada's experience stands as a stark warning.

Systemic Inhibition of NF-κB Activation Protects from Silicosis

2009-05-25T07:00:00Z

Background

Silicosis is a complex lung disease for which no successful treatment is available and therefore lung transplantation is a potential alternative. Tumor necrosis factor alpha (TNFα) plays a central role in the pathogenesis of silicosis. TNFα signaling is mediated by the transcription factor, Nuclear Factor (NF)-κB, which regulates genes controlling several physiological processes including the innate immune responses, cell death, and inflammation. Therefore, inhibition of NF-κB activation represents a potential therapeutic strategy for silicosis.

Methods/Findings

In the present work we evaluated the lung transplant database (May 1986–July 2007) at the University of Pittsburgh to study the efficacy of lung transplantation in patients with silicosis (n = 11). We contrasted the overall survival and rate of graft rejection in these patients to that of patients with idiopathic pulmonary fibrosis (IPF, n = 79) that was selected as a control group because survival benefit of lung transplantation has been identified for these patients. At the time of lung transplantation, we found the lungs of silica-exposed subjects to contain multiple foci of inflammatory cells and silicotic nodules with proximal TNFα expressing macrophage and NF-κB activation in epithelial cells. Patients with silicosis had poor survival (median survival 2.4 yr; confidence interval (CI): 0.16–7.88 yr) compared to IPF patients (5.3 yr; CI: 2.8–15 yr; p = 0.07), and experienced early rejection of their lung grafts (0.9 yr; CI: 0.22–0.9 yr) following lung transplantation (2.4 yr; CI:1.5–3.6 yr; p<0.05). Using a mouse experimental model in which the endotracheal instillation of silica reproduces the silica-induced lung injury observed in humans we found that systemic inhibition of NF-κB activation with a pharmacologic inhibitor (BAY 11-7085) of IκBα phosphorylation decreased silica-induced inflammation and collagen deposition. In contrast, transgenic mice expressing a dominant negative IκBα mutant protein under the control of epithelial cell specific promoters demonstrate enhanced apoptosis and collagen deposition in their lungs in response to silica.

Conclusions

Although limited by its size, our data support that patients with silicosis appear to have poor outcome following lung transplantation. Experimental data indicate that while the systemic inhibition of NF-κB protects from silica-induced lung injury, epithelial cell specific NF-κB inhibition appears to aggravate the outcome of experimental silicosis.