Dominance,Politics, and Physiology: Voters' Testosterone Changes on the Night of the 2008 United States Presidential Election

Background

Political elections are dominance competitions. When men win a dominance competition, their testosterone levels rise or remain stable to resist a circadian decline; and when they lose, their testosterone levels fall. However, it is unknown whether this pattern of testosterone change extends beyond interpersonal competitions to the vicarious experience of winning or losing in the context of political elections. Women''s testosterone responses to dominance competition outcomes are understudied, and to date, a clear pattern of testosterone changes in response to winning and losing dominance competitions has not emerged.

Methodology/Principal Findings

The present study investigated voters'' testosterone responses to the outcome of the 2008 United States Presidential election. 183 participants provided multiple saliva samples before and after the winner was announced on Election Night. The results show that male Barack Obama voters (winners) had stable post-outcome testosterone levels, whereas testosterone levels dropped in male John McCain and Robert Barr voters (losers). There were no significant effects in female voters.

Conclusions/Significance

The findings indicate that male voters exhibit biological responses to the realignment of a country''s dominance hierarchy as if they participated in an interpersonal dominance contest.     

Cholinesterase Inhibitors and Hospitalization for Bradycardia: A Population-Based Study

Background

Cholinesterase inhibitors are commonly used to treat dementia. These drugs enhance the effects of acetylcholine, and reports suggest they may precipitate bradycardia in some patients. We aimed to examine the association between use of cholinesterase inhibitors and hospitalization for bradycardia.

Methods and Findings

We examined the health care records of more than 1.4 million older adults using a case-time-control design, allowing each individual to serve as his or her own control. Case patients were residents of Ontario, Canada, aged 67 y or older hospitalized for bradycardia between January 1, 2003 and March 31, 2008. Control patients (3∶1) were not hospitalized for bradycardia, and were matched to the corresponding case on age, sex, and a disease risk index. All patients had received cholinesterase inhibitor therapy in the 9 mo preceding the index hospitalization. We identified 1,009 community-dwelling older persons hospitalized for bradycardia within 9 mo of using a cholinesterase inhibitor. Of these, 161 cases informed the matched analysis of discordant pairs. Of these, 17 (11%) required a pacemaker during hospitalization, and six (4%) died prior to discharge. After adjusting for temporal changes in drug utilization, hospitalization for bradycardia was associated with recent initiation of a cholinesterase inhibitor (adjusted odds ratio [OR] 2.13, 95% confidence interval [CI] 1.29–3.51). The risk was similar among individuals with pre-existing cardiac disease (adjusted OR 2.25, 95% CI 1.18–4.28) and those receiving negative chronotropic drugs (adjusted OR 2.34, 95% CI 1.16–4.71). We found no such association when we replicated the analysis using proton pump inhibitors as a neutral exposure. Despite hospitalization for bradycardia, more than half of the patients (78 of 138 cases [57%]) who survived to discharge subsequently resumed cholinesterase inhibitor therapy.

Conclusions

Among older patients, initiation of cholinesterase inhibitor therapy was associated with a more than doubling of the risk of hospitalization for bradycardia. Resumption of therapy following discharge was common, suggesting that the cardiovascular toxicity of cholinesterase inhibitors is underappreciated by clinicians. Please see later in the article for the Editors'' Summary     

Is Drug Treatment for Dementia Followed Up in Primary Care? A Swedish Study of Dementia Clinics and Referring Primary Care Centres

Purpose

It is largely unknown how the medical treatment of patients diagnosed with dementia is followed up in primary care. Therefore, we studied patient medical records from two dementia clinics and from the referring primary care centres.

Methods

A retrospective study of 241 patients was conducted from April to October 2011 in north west Stockholm, Sweden. Over half (51.5%) of the patients had Alzheimer’s disease (AD), the remainder had mixed AD/vascular dementia (VaD). Eighty-four medical reports from primary care (35% of the study group) were analysed at follow-up 18 months after diagnosis.

Results

All four dementia drugs available on the Swedish market (three cholinesterase inhibitors [donepezil, rivastigmine and galantamine] and memantine) were prescribed at the two dementia clinics. The most commonly used dementia drug was galantamine. There were differences between the two dementia clinics in preference and combination of drugs and of treatment given to male and female patients. At follow-up, 84% were still on dementia medication. Drug use was followed up by the general practitioners (GPs) in two-thirds of the cases. Eighteen per cent of the GPs’ medical records made no reference to the patient’s dementia or treatment even though dementia drugs were included in the list of medications prescribed.

Conclusions

The results indicate that the Swedish guidelines for treatment of cognitive symptoms in AD are being followed in primary care. However, documentation of follow-up of drug treatment was sometimes insufficient, which calls for development of guidelines for complete medical records and medication lists.     

Quality of reporting of bioequivalence trials comparing generic to brand name drugs: a methodological systematic review

Background

Generic drugs are used by millions of patients for economic reasons, so their evaluation must be highly transparent.

Objective

To assess the quality of reporting of bioequivalence trials comparing generic to brand-name drugs.

Methodology/Principal Findings

PubMed was searched for reports of bioequivalence trials comparing generic to brand-name drugs between January 2005 and December 2008. Articles were included if the aim of the study was to assess the bioequivalency of generic and brand-name drugs. We excluded case studies, pharmaco-economic evaluations, and validation dosage assays of drugs. We evaluated whether important information about funding, methodology, location of trials, and participants were reported. We also assessed whether the criteria required by the Food and Drug Administration (FDA) and the European Medicine Agency (EMA) to conclude bioequivalence were reported and that the conclusions were in agreement with the results. We identified 134 potentially relevant articles but eliminated 55 because the brand-name or generic drug status of the reference drug was unknown. Thus, we evaluated 79 articles. The funding source and location of the trial were reported in 41% and 56% of articles, respectively. The type of statistical analysis was reported in 94% of articles, but the methods to generate the randomization sequence and to conceal allocation were reported in only 15% and 5%, respectively. In total, 65 articles of single-dose trials (89%) concluded bioequivalence. Of these, 20 (31%) did not report the 3 criteria within the limits required by the FDA and 11 (17%) did not report the 2 criteria within the limits required by the EMA.

Conclusions/Significance

Important information to judge the validity and relevance of results are frequently missing in published reports of trials assessing generic drugs. The quality of reporting of such trials is in need of improvement.     

Opportunity Cost for Early Treatment of Chagas Disease in Mexico

Background

Given current neglect for Chagas disease in public health programs in Mexico, future healthcare and economic development policies will need a more robust model to analyze costs and impacts of timely clinical attention of infected populations.

Methodology/Principal Findings

A Markov decision model was constructed to simulate the natural history of a Chagas disease cohort in Mexico and to project the associated short and long-term clinical outcomes and corresponding costs. The lifetime cost for a timely diagnosed and treated Chagas disease patient is US$ 10,160, while the cost for an undiagnosed individual is US$ 11,877. The cost of a diagnosed and treated case increases 24-fold from early acute to indeterminate stage. The major cost component for lifetime cost was working days lost, between 44% and 75%, depending on the program scenario for timely diagnosis and treatment.

Conclusions/Significance

In the long term, it is cheaper to diagnose and treat chagasic patients early, instead of doing nothing. This finding by itself argues for the need to shift current policy, in order to prioritize and attend this neglected disease for the benefit of social and economic development, which implies including treatment drugs in the national formularies. Present results are even more relevant, if one considers that timely diagnosis and treatment can arrest clinical progression and enhance a chronic patient''s quality of life.     

The Cost and Impact of the Interim Federal Health Program Cuts on Child Refugees in Canada

Introduction

On June 30, 2012, Interim Federal Health Program (IFHP) funding was cut for refugee claimant healthcare. The potential financial and healthcare impacts of these cuts on refugee claimants are unknown.

Methods

We conducted a one-year retrospective chart review spanning 6 months before and after IFHP funding cuts at The Hospital for Sick Children, a tertiary care children''s hospital in Toronto. We analyzed emergency room visits characteristics, admission rates, reasons for admission, and financial records including billing from Medavie Blue Cross.

Results

There were 173 refugee children visits to the emergency room in the six months before and 142 visits in the six months after funding cuts. The total amount billed to the IFHP program during the one-year of this study was $131,615. Prior to the IFHP cuts, 46% of the total emergency room bills were paid by IFHP compared to 7% after the cuts (p<0.001).

Interpretation

After the cuts to the IFHP, The Hospital for Sick Children was unable to obtain federal health coverage for the vast majority of refugee claimant children registered under the IFHP. This preliminary analysis showed that post-IFHP cuts healthcare costs at the largest tertiary pediatric institution in the country increased.     

The political gender gap: gender bias in facial inferences that predict voting behavior

Background

Throughout human history, a disproportionate degree of political power around the world has been held by men. Even in democracies where the opportunity to serve in top political positions is available to any individual elected by the majority of their constituents, most of the highest political offices are occupied by male leaders. What psychological factors underlie this political gender gap? Contrary to the notion that people use deliberate, rational strategies when deciding whom to vote for in major political elections, research indicates that people use shallow decision heuristics, such as impressions of competence solely from a candidate''s facial appearance, when deciding whom to vote for. Because gender has previously been shown to affect a number of inferences made from the face, here we investigated the hypothesis that gender of both voter and candidate affects the kinds of facial impressions that predict voting behavior.

Methodology/Principal Finding

Male and female voters judged a series of male and female political candidates on how competent, dominant, attractive and approachable they seemed based on their facial appearance. Then they saw a series of pairs of political candidates and decided which politician they would vote for in a hypothetical election for President of the United States. Results indicate that both gender of voter and candidate affect the kinds of facial impressions that predict voting behavior. All voters are likely to vote for candidates who appear more competent. However, male candidates that appear more approachable and female candidates who appear more attractive are more likely to win votes. In particular, men are more likely to vote for attractive female candidates whereas women are more likely to vote for approachable male candidates.

Conclusions/Significance

Here we reveal gender biases in the intuitive heuristics that voters use when deciding whom to vote for in major political elections. Our findings underscore the impact of gender and physical appearance on shaping voter decision-making and provide novel insight into the psychological foundations underlying the political gender gap.     

NIH disease funding levels and burden of disease

Background

An analysis of NIH funding in 1996 found that the strongest predictor of funding, disability-adjusted life-years (DALYs), explained only 39% of the variance in funding. In 1998, Congress requested that the Institute of Medicine (IOM) evaluate priority-setting criteria for NIH funding; the IOM recommended greater consideration of disease burden. We examined whether the association between current burden and funding has changed since that time.

Methods

We analyzed public data on 2006 NIH funding for 29 common conditions. Measures of US disease burden in 2004 were obtained from the World Health Organization''s Global Burden of Disease study and national databases. We assessed the relationship between disease burden and NIH funding dollars in univariate and multivariable log-linear models that evaluated all measures of disease burden. Sensitivity analyses examined associations with future US burden, current and future measures of world disease burden, and a newly standardized NIH accounting method.

Results

In univariate and multivariable analyses, disease-specific NIH funding levels increased with burden of disease measured in DALYs (p = 0.001), which accounted for 33% of funding level variation. No other factor predicted funding in multivariable models. Conditions receiving the most funding greater than expected based on disease burden were AIDS ($2474 M), diabetes mellitus ($390 M), and perinatal conditions ($297 M). Depression ($719 M), injuries ($691 M), and chronic obstructive pulmonary disease ($613 M) were the most underfunded. Results were similar using estimates of future US burden, current and future world disease burden, and alternate NIH accounting methods.

Conclusions

Current levels of NIH disease-specific research funding correlate modestly with US disease burden, and correlation has not improved in the last decade.     

Funding source and research report quality in nutrition practice-related research

Background

The source of funding is one of many possible causes of bias in scientific research. One method of detecting potential for bias is to evaluate the quality of research reports. Research exploring the relationship between funding source and nutrition-related research report quality is limited and in other disciplines the findings are mixed.

Objective

The purpose of this study is to determine whether types of funding sources of nutrition research are associated with differences in research report quality.

Design

A retrospective study of research reporting quality, research design and funding source was conducted on 2539 peer reviewed research articles from the American Dietetic Association''s Evidence Analysis Library® database.

Results

Quality rating frequency distributions indicate 43.3% of research reports were rated as positive, 50.1% neutral, and 6.6% as negative. Multinomial logistic regression results showed that while both funding source and type of research design are significant predictors of quality ratings (χ2 = 118.99, p<0.001), the model''s usefulness in predicting overall research report quality is little better than chance. Compared to research reports with government funding, those not acknowledging any funding sources, followed by studies with University/hospital funding were more likely to receive neutral vs positive quality ratings, OR = 1.85, P <0.001 and OR = 1.54, P<0.001, respectively and those that did not report funding were more likely to receive negative quality ratings (OR = 4.97, P<0.001). After controlling for research design, industry funded research reports were no more likely to receive a neutral or negative quality rating than those funded by government sources.

Conclusion

Research report quality cannot be accurately predicted from the funding source after controlling for research design. Continued vigilance to evaluate the quality of all research regardless of the funding source and to further understand other factors that affect quality ratings are warranted.     

Dopaminergic and serotonergic drug use: a nationwide register-based study of over 1,300,000 older people

Objective

To investigate the use of dopaminergic and serotonergic drugs in elderly people.

Methods

We analyzed data on age, sex and dispensed drugs for individuals aged ≥65 years registered in the Swedish Prescribed Drug Register from July to September 2008 (n = 1 347 564; 81% of the total population aged ≥65 years in Sweden). Main outcome measures were dopaminergic (enhancing and/or lowering) and serotonergic (enhancing and/or lowering) drugs and combinations of these.

Results

Dopaminergic and serotonergic drugs were used by 5.6% and 13.2% the participants, respectively. Female gender was related to use of both dopaminergic and, particularly, serotonergic drugs. Higher age was associated with use of dopamine lowering drugs and serotonergic drugs, whereas the association with use of dopamine enhancing drugs declined in the oldest old. The occurrence of combinations of dopaminergic and serotonergic drugs was generally low, with dopamine lowering + serotonin lowering drug the most common combination (1.6%). Female gender was associated with all of the combinations of dopaminergic and serotonergic drugs, whereas age showed a mixed pattern.

Conclusion

Approximately one out of ten older patients uses serotonergic drugs and one out of twenty dopaminergic drugs. The frequent use of dopaminergic and serotonergic drugs in the elderly patients is a potential problem due to the fact that aging is associated with a down-regulation of both these monoaminergic systems. Future studies are needed for evaluation of the impact of these drugs on different cognitive and emotional functions in old age.     

Size and usage patterns of private TB drug markets in the high burden countries

Background

Tuberculosis (TB) control is considered primarily a public health concern, and private sector TB treatment has attracted less attention. Thus, the size and characteristics of private sector TB drug sales remain largely unknown.

Methodology/Principal Findings

We used IMS Health data to analyze private TB drug consumption in 10 high burden countries (HBCs), after first mapping how well IMS data coverage overlapped with private markets. We defined private markets as any channels not used or influenced by national TB programs. Private markets in four countries – Pakistan, the Philippines, Indonesia and India – had the largest relative sales volumes; annually, they sold enough first line TB drugs to provide 65–117% of the respective countries'' estimated annual incident cases with a standard 6–8 month regimen. First line drug volumes in five countries were predominantly fixed dose combinations (FDCs), but predominantly loose drugs in the other five. Across 10 countries, these drugs were available in 37 (loose drug) plus 74 (FDCs) distinct strengths. There were 54 distinct, significant first line manufacturers (range 2–11 per country), and most companies sold TB drugs in only a single study country. FDC markets were, however, more concentrated, with 4 companies capturing 69% of FDC volume across the ten countries. Among second line drugs, fluoroquinolones were widely available, with significant volumes used for TB in India, Pakistan and Indonesia. However, certain WHO-recommended drugs were not available and in general there were insufficient drug volumes to cover the majority of the expected burden of multidrug-resistant TB (MDR-TB).

Conclusions/Significance

Private TB drug markets in several HBCs are substantial, stable, and complicated. This calls for appropriate policy and market responses, including expansion of Public-Private Mix (PPM) programs, greater reach, flexibility and appeal of public programs, regulatory and quality enforcement, and expansion of public MDR-TB treatment programs.     

Tamoxifen Enhances the Hsp90 Molecular Chaperone ATPase Activity

Background

Hsp90 is an essential molecular chaperone that is also a novel anti-cancer drug target. There is growing interest in developing new drugs that modulate Hsp90 activity.

Methodology/Principal Findings

Using a virtual screening approach, 4-hydroxytamoxifen, the active metabolite of the anti-estrogen drug tamoxifen, was identified as a putative Hsp90 ligand. Surprisingly, while all drugs targeting Hsp90 inhibit the chaperone ATPase activity, it was found experimentally that 4-hydroxytamoxifen and tamoxifen enhance rather than inhibit Hsp90 ATPase.

Conclusions/Significance

Hence, tamoxifen and its metabolite are the first members of a new pharmacological class of Hsp90 activators.     

Prescription drugs associated with reports of violence towards others

Context

Violence towards others is a seldom-studied adverse drug event and an atypical one because the risk of injury extends to others.

Objective

To identify the primary suspects in adverse drug event reports describing thoughts or acts of violence towards others, and assess the strength of the association.

Methodology

From the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) data, we extracted all serious adverse event reports for drugs with 200 or more cases received from 2004 through September 2009. We identified any case report indicating homicide, homicidal ideation, physical assault, physical abuse or violence related symptoms.

Main Outcome Measures

Disproportionality in reporting was defined as a) 5 or more violence case reports, b) at least twice the number of reports expected given the volume of overall reports for that drug, c) a χ2 statistic indicating the violence cases were unlikely to have occurred by chance (p<0.01).

Results

We identified 1527 cases of violence disproportionally reported for 31 drugs. Primary suspect drugs included varenicline (an aid to smoking cessation), 11 antidepressants, 6 sedative/hypnotics and 3 drugs for attention deficit hyperactivity disorder. The evidence of an association was weaker and mixed for antipsychotic drugs and absent for all but 1 anticonvulsant/mood stabilizer. Two or fewer violence cases were reported for 435/484 (84.7%) of all evaluable drugs suggesting that an association with this adverse event is unlikely for these drugs.

Conclusions

Acts of violence towards others are a genuine and serious adverse drug event associated with a relatively small group of drugs. Varenicline, which increases the availability of dopamine, and antidepressants with serotonergic effects were the most strongly and consistently implicated drugs. Prospective studies to evaluate systematically this side effect are needed to establish the incidence, confirm differences among drugs and identify additional common features.     

Isoniazid,Pyrazinamide and Rifampicin Content Variation in Split Fixed-Dose Combination Tablets

Setting

In most developing countries, paediatric tuberculosis is treated with split tablets leading to potential inaccuracy in the dose delivery and drug exposure. There is no data on the quality of first-line drugs content in split fixed-dose combination tablets.

Objective

To determine Isoniazid, Pyrazinamide and Rifampicin content uniformity in split FDC tablets used in the treatment of childhood tuberculosis.

Design

Drug contents of 15 whole tablets, 30 half tablets and 36 third tablets were analysed by high performance liquid chromatography. The content uniformity was assessed by comparing drug content measured in split portions with their expected amounts and the quality of split portions was assessed applying qualitative specifications for whole tablets.

Results

All whole tablets measurements fell into the USP proxy for the three drugs. But a significant number of half and third portions was found outside the tolerated variation range and the split formulation failed the requirements for content uniformity. To correct for the inaccuracy of splitting the tablets into equal portions, a weight-adjustment strategy was used but this did not improve the findings.

Conclusion

In split tablets the content of the three drugs is non-uniform and exceeded the USP recommendations. There is an absolute need to make child-friendly formulations available for the treatment of childhood tuberculosis.     

Political Regimes,Political Ideology,and Self-Rated Health in Europe: A Multilevel Analysis

Background

Studies on political ideology and health have found associations between individual ideology and health as well as between ecological measures of political ideology and health. Individual ideology and aggregate measures such as political regimes, however, were never examined simultaneously.

Methodology/Principal Findings

Using adjusted logistic multilevel models to analyze data on individuals from 29 European countries and Israel, we found that individual ideology and political regime are independently associated with self-rated health. Individuals with rightwing ideologies report better health than leftwing individuals. Respondents from Eastern Europe and former Soviet republics report poorer health than individuals from social democratic, liberal, Christian conservative, and former Mediterranean dictatorship countries. In contrast to individual ideology and political regimes, country level aggregations of individual ideology are not related to reporting poor health.

Conclusions/Significance

This study shows that although both individual political ideology and contextual political regime are independently associated with individuals'' self-rated health, individual political ideology appears to be more strongly associated with self-rated health than political regime.     

Respiratory paradoxical adverse drug reactions associated with acetylcysteine and carbocysteine systemic use in paediatric patients: a national survey

Objective

To report pediatric cases of paradoxical respiratory adverse drug reactions (ADRs) after exposure to oral mucolytic drugs (carbocysteine, acetylcysteine) that led to the withdrawal of licenses for these drugs for infants in France and then Italy.

Design

The study followed the recommendations of the European guidelines of pharmacovigilance for medicines used in the paediatric population.

Setting

Cases voluntarily reported by physicians from 1989 to 2008 were identified in the national French pharmacovigilance public database and in drug company databases.

Patients

The definition of paradoxical respiratory ADRs was based on the literature. Exposure to mucolytic drugs was arbitrarily defined as having received mucolytic drugs for at least 2 days (>200 mg) and at least until the day before the first signs of the suspected ADR.

Results

The non-exclusive paradoxical respiratory ADRs reported in 59 paediatric patients (median age 5 months, range 3 weeks to 34 months, 98% younger than 2 years old) were increased bronchorrhea or mucus vomiting (n = 27), worsening of respiratory distress during respiratory tract infection (n = 35), dyspnoea (n = 18), cough aggravation or prolongation (n = 11), and bronchospasm (n = 1). Fifty-one (86%) children required hospitalization or extended hospitalization because of the ADR; one patient died of pulmonary oedema after mucus vomiting.

Conclusion

Parents, physicians, pharmacists, and drug regulatory agencies should know that the benefit risk ratio of mucolytic drugs is at least null and most probably negative in infants according to available evidence.