PLoS Medicine: New Articles

Engaging Men in Prevention and Care for HIV/AIDS in Africa

2012-02-07T22:00:00Z

by Edward J. Mills, Chris Beyrer, Josephine Birungi, Mark R. Dybul

Clostridium: Transmission difficile?

2012-02-07T22:00:00Z

by Stephan Harbarth, Matthew H. Samore

Characterisation of Clostridium difficile Hospital Ward–Based Transmission Using Extensive Epidemiological Data and Molecular Typing

2012-02-07T22:00:00Z

by A. Sarah Walker, David W. Eyre, David H. Wyllie, Kate E. Dingle, Rosalind M. Harding, Lily O'Connor, David Griffiths, Ali Vaughan, John Finney, Mark H. Wilcox, Derrick W. Crook, Tim E. A. Peto

Background

Clostridium difficile infection (CDI) is a leading cause of antibiotic-associated diarrhoea and is endemic in hospitals, hindering the identification of sources and routes of transmission based on shared time and space alone. This may compromise rational control despite costly prevention strategies. This study aimed to investigate ward-based transmission of C. difficile, by subdividing outbreaks into distinct lineages defined by multi-locus sequence typing (MLST).

Methods and Findings

All C. difficile toxin enzyme-immunoassay-positive and culture-positive samples over 2.5 y from a geographically defined population of ∼600,000 persons underwent MLST. Sequence types (STs) were combined with admission and ward movement data from an integrated comprehensive healthcare system incorporating three hospitals (1,700 beds) providing all acute care for the defined geographical population. Networks of cases and potential transmission events were constructed for each ST. Potential infection sources for each case and transmission timescales were defined by prior ward-based contact with other cases sharing the same ST. From 1 September 2007 to 31 March 2010, there were means of 102 tests and 9.4 CDIs per 10,000 overnight stays in inpatients, and 238 tests and 15.7 CDIs per month in outpatients/primary care. In total, 1,276 C. difficile isolates of 69 STs were studied. From MLST, no more than 25% of cases could be linked to a potential ward-based inpatient source, ranging from 37% in renal/transplant, 29% in haematology/oncology, and 28% in acute/elderly medicine to 6% in specialist surgery. Most of the putative transmissions identified occurred shortly (≤1 wk) after the onset of symptoms (141/218, 65%), with few >8 wk (21/218, 10%). Most incubation periods were ≤4 wk (132/218, 61%), with few >12 wk (28/218, 13%). Allowing for persistent ward contamination following ward discharge of a CDI case did not increase the proportion of linked cases after allowing for random meeting of matched controls.

Conclusions

In an endemic setting with well-implemented infection control measures, ward-based contact with symptomatic enzyme-immunoassay-positive patients cannot account for most new CDI cases.

Please see later in the article for the Editors' Summary

Prevalence, Distribution, and Impact of Mild Cognitive Impairment in Latin America, China, and India: A 10/66 Population-Based Study

2012-02-07T22:00:00Z

by Ana Luisa Sosa, Emiliano Albanese, Blossom C. M. Stephan, Michael Dewey, Daisy Acosta, Cleusa P. Ferri, Mariella Guerra, Yueqin Huang, K. S. Jacob, Ivonne Z. Jiménez-Velázquez, Juan J. Llibre Rodriguez, Aquiles Salas, Joseph Williams, Isaac Acosta, Maribella González-Viruet, Milagros A. Guerra Hernandez, Li Shuran, Martin J. Prince, Robert Stewart

Background

Rapid demographic ageing is a growing public health issue in many low- and middle-income countries (LAMICs). Mild cognitive impairment (MCI) is a construct frequently used to define groups of people who may be at risk of developing dementia, crucial for targeting preventative interventions. However, little is known about the prevalence or impact of MCI in LAMIC settings.

Methods and Findings

Data were analysed from cross-sectional surveys established by the 10/66 Dementia Research Group and carried out in Cuba, Dominican Republic, Peru, Mexico, Venezuela, Puerto Rico, China, and India on 15,376 individuals aged 65+ without dementia. Standardised assessments of mental and physical health, and cognitive function were carried out including informant interviews. An algorithm was developed to define Mayo Clinic amnestic MCI (aMCI). Disability (12-item World Health Organization disability assessment schedule [WHODAS]) and informant-reported neuropsychiatric symptoms (neuropsychiatric inventory [NPI-Q]) were measured. After adjustment, aMCI was associated with disability, anxiety, apathy, and irritability (but not depression); between-country heterogeneity in these associations was only significant for disability. The crude prevalence of aMCI ranged from 0.8% in China to 4.3% in India. Country differences changed little (range 0.6%–4.6%) after standardization for age, gender, and education level. In pooled estimates, aMCI was modestly associated with male gender and fewer assets but was not associated with age or education. There was no significant between-country variation in these demographic associations.

Conclusions

An algorithm-derived diagnosis of aMCI showed few sociodemographic associations but was consistently associated with higher disability and neuropsychiatric symptoms in addition to showing substantial variation in prevalence across LAMIC populations. Longitudinal data are needed to confirm findings—in particular, to investigate the predictive validity of aMCI in these settings and risk/protective factors for progression to dementia; however, the large number affected has important implications in these rapidly ageing settings.

Please see later in the article for the Editors' Summary

Effects of Two Commercial Electronic Prescribing Systems on Prescribing Error Rates in Hospital In-Patients: A Before and After Study

2012-01-31T22:00:00Z

by Johanna I. Westbrook, Margaret Reckmann, Ling Li, William B. Runciman, Rosemary Burke, Connie Lo, Melissa T. Baysari, Jeffrey Braithwaite, Richard O. Day

Background

Considerable investments are being made in commercial electronic prescribing systems (e-prescribing) in many countries. Few studies have measured or evaluated their effectiveness at reducing prescribing error rates, and interactions between system design and errors are not well understood, despite increasing concerns regarding new errors associated with system use. This study evaluated the effectiveness of two commercial e-prescribing systems in reducing prescribing error rates and their propensities for introducing new types of error.

Methods and Results

We conducted a before and after study involving medication chart audit of 3,291 admissions (1,923 at baseline and 1,368 post e-prescribing system) at two Australian teaching hospitals. In Hospital A, the Cerner Millennium e-prescribing system was implemented on one ward, and three wards, which did not receive the e-prescribing system, acted as controls. In Hospital B, the iSoft MedChart system was implemented on two wards and we compared before and after error rates. Procedural (e.g., unclear and incomplete prescribing orders) and clinical (e.g., wrong dose, wrong drug) errors were identified. Prescribing error rates per admission and per 100 patient days; rates of serious errors (5-point severity scale, those ≥3 were categorised as serious) by hospital and study period; and rates and categories of postintervention “system-related” errors (where system functionality or design contributed to the error) were calculated. Use of an e-prescribing system was associated with a statistically significant reduction in error rates in all three intervention wards (respectively reductions of 66.1% [95% CI 53.9%–78.3%]; 57.5% [33.8%–81.2%]; and 60.5% [48.5%–72.4%]). The use of the system resulted in a decline in errors at Hospital A from 6.25 per admission (95% CI 5.23–7.28) to 2.12 (95% CI 1.71–2.54; p<0.0001) and at Hospital B from 3.62 (95% CI 3.30–3.93) to 1.46 (95% CI 1.20–1.73; p<0.0001). This decrease was driven by a large reduction in unclear, illegal, and incomplete orders. The Hospital A control wards experienced no significant change (respectively −12.8% [95% CI −41.1% to 15.5%]; −11.3% [−40.1% to 17.5%]; −20.1% [−52.2% to 12.4%]). There was limited change in clinical error rates, but serious errors decreased by 44% (0.25 per admission to 0.14; p = 0.0002) across the intervention wards compared to the control wards (17% reduction; 0.30–0.25; p = 0.40). Both hospitals experienced system-related errors (0.73 and 0.51 per admission), which accounted for 35% of postsystem errors in the intervention wards; each system was associated with different types of system-related errors.

Conclusions

Implementation of these commercial e-prescribing systems resulted in statistically significant reductions in prescribing error rates. Reductions in clinical errors were limited in the absence of substantial decision support, but a statistically significant decline in serious errors was observed. System-related errors require close attention as they are frequent, but are potentially remediable by system redesign and user training. Limitations included a lack of control wards at Hospital B and an inability to randomize wards to the intervention.

Please see later in the article for the Editors' Summary

A New Year at PLoS Medicine: Maintaining a Focus on the World's Health Priorities and Identifying the Gaps

The PLoS Medicine Editors — 2012-01-31T22:00:00Z

by The PLoS Medicine Editors

Hitting Hotspots: Spatial Targeting of Malaria for Control and Elimination

2012-01-31T22:00:00Z

by Teun Bousema, Jamie T. Griffin, Robert W. Sauerwein, David L. Smith, Thomas S. Churcher, Willem Takken, Azra Ghani, Chris Drakeley, Roly Gosling

The Role of Health Systems Factors in Facilitating Access to Psychotropic Medicines: A Cross-Sectional Analysis of the WHO-AIMS in 63 Low- and Middle-Income Countries

2012-01-31T22:00:00Z

by Ryan McBain, Daniel J. Norton, Jodi Morris, M. Taghi Yasamy, Theresa S. Betancourt

Background

Neuropsychiatric conditions comprise 14% of the global burden of disease and 30% of all noncommunicable disease. Despite the existence of cost-effective interventions, including administration of psychotropic medicines, the number of persons who remain untreated is as high as 85% in low- and middle-income countries (LAMICs). While access to psychotropic medicines varies substantially across countries, no studies to date have empirically investigated potential health systems factors underlying this issue.

Methods and Findings

This study uses a cross-sectional sample of 63 LAMICs and country regions to identify key health systems components associated with access to psychotropic medicines. Data from countries that completed the World Health Organization Assessment Instrument for Mental Health Systems (WHO-AIMS) were included in multiple regression analyses to investigate the role of five major mental health systems domains in shaping medicine availability and affordability. These domains are: mental health legislation, human rights implementations, mental health care financing, human resources, and the role of advocacy groups. Availability of psychotropic medicines was associated with features of all five mental health systems domains. Most notably, within the domain of mental health legislation, a comprehensive national mental health plan was associated with 15% greater availability; and in terms of advocacy groups, the participation of family-based organizations in the development of mental health legislation was associated with 17% greater availability. Only three measures were related with affordability of medicines to consumers: level of human resources, percentage of countries' health budget dedicated to mental health, and availability of mental health care in prisons. Controlling for country development, as measured by the Human Development Index, health systems features were associated with medicine availability but not affordability.

Conclusions

Results suggest that strengthening particular facets of mental health systems might improve availability of psychotropic medicines and that overall country development is associated with affordability.

Please see later in the article for the Editors' Summary

Adult Mortality Attributable to Preventable Risk Factors for Non-Communicable Diseases and Injuries in Japan: A Comparative Risk Assessment

2012-01-24T22:00:00Z

by Nayu Ikeda, Manami Inoue, Hiroyasu Iso, Shunya Ikeda, Toshihiko Satoh, Mitsuhiko Noda, Tetsuya Mizoue, Hironori Imano, Eiko Saito, Kota Katanoda, Tomotaka Sobue, Shoichiro Tsugane, Mohsen Naghavi, Majid Ezzati, Kenji Shibuya

Background

The population of Japan has achieved the longest life expectancy in the world. To further improve population health, consistent and comparative evidence on mortality attributable to preventable risk factors is necessary for setting priorities for health policies and programs. Although several past studies have quantified the impact of individual risk factors in Japan, to our knowledge no study has assessed and compared the effects of multiple modifiable risk factors for non-communicable diseases and injuries using a standard framework. We estimated the effects of 16 risk factors on cause-specific deaths and life expectancy in Japan.

Methods and Findings

We obtained data on risk factor exposures from the National Health and Nutrition Survey and epidemiological studies, data on the number of cause-specific deaths from vital records adjusted for ill-defined codes, and data on relative risks from epidemiological studies and meta-analyses. We applied a comparative risk assessment framework to estimate effects of excess risks on deaths and life expectancy at age 40 y. In 2007, tobacco smoking and high blood pressure accounted for 129,000 deaths (95% CI: 115,000–154,000) and 104,000 deaths (95% CI: 86,000–119,000), respectively, followed by physical inactivity (52,000 deaths, 95% CI: 47,000–58,000), high blood glucose (34,000 deaths, 95% CI: 26,000–43,000), high dietary salt intake (34,000 deaths, 95% CI: 27,000–39,000), and alcohol use (31,000 deaths, 95% CI: 28,000–35,000). In recent decades, cancer mortality attributable to tobacco smoking has increased in the elderly, while stroke mortality attributable to high blood pressure has declined. Life expectancy at age 40 y in 2007 would have been extended by 1.4 y for both sexes (men, 95% CI: 1.3–1.6; women, 95% CI: 1.2–1.7) if exposures to multiple cardiovascular risk factors had been reduced to their optimal levels as determined by a theoretical-minimum-risk exposure distribution.

Conclusions

Tobacco smoking and high blood pressure are the two major risk factors for adult mortality from non-communicable diseases and injuries in Japan. There is a large potential population health gain if multiple risk factors are jointly controlled.

Please see later in the article for the Editors' Summary

Effect of Sanitation on Soil-Transmitted Helminth Infection: Systematic Review and Meta-Analysis

2012-01-24T22:00:00Z

by Kathrin Ziegelbauer, Benjamin Speich, Daniel Mäusezahl, Robert Bos, Jennifer Keiser, Jürg Utzinger

Background

In countries of high endemicity of the soil-transmitted helminth parasites Ascaris lumbricoides, Trichuris trichiura, and hookworm, preventive chemotherapy (i.e., repeated administration of anthelmintic drugs to at-risk populations) is the main strategy to control morbidity. However, rapid reinfection of humans occurs after successful deworming, and therefore effective preventive measures are required to achieve public health goals with optimal efficiency and sustainability.

Methods and Findings

We conducted a systematic review and meta-analysis to assess the effect of sanitation (i.e., access and use of facilities for the safe disposal of human urine and feces) on infection with soil-transmitted helminths. PubMed, Embase, ISI Web of Science, and the World Health Organization Library Database were searched without language restrictions and year of publication (search performed until December 31, 2010). Bibliographies of identified articles were hand-searched. All types of studies reporting data on sanitation availability (i.e., having access at own household or living in close proximity to sanitation facility), or usage, and soil-transmitted helminth infections at the individual level were considered. Reported odds ratios (ORs) of the protective effect of sanitation on soil-transmitted helminth infections were extracted from the papers or calculated from reported numbers. The quality of published studies was assessed with a panel of criteria developed by the authors. Random effects meta-analyses were used to account for observed heterogeneity. Thirty-six publications, consisting of 39 datasets, met our inclusion criteria. Availability of sanitation facilities was associated with significant protection against infection with soil-transmitted helminths (OR = 0.46 to 0.58). Regarding the use of sanitation, ORs of 0.54 (95% confidence interval [CI] 0.28–1.02), 0.63 (95% CI 0.37–1.05), and 0.78 (95% CI 0.60–1.00) were determined for T. trichiura, hookworm, and A. lumbricoides, respectively. The overall ORs, combining sanitation availability and use, were 0.51 (95% CI 0.44–0.61) for the three soil-transmitted helminths combined, 0.54 (95% CI 0.43–0.69) for A. lumbricoides, 0.58 (95% CI 0.45–0.75) for T. trichiura, and 0.60 (95% CI 0.48–0.75) for hookworm.

Conclusions

Despite a number of limitations (e.g., most studies used a cross-sectional design and were of low quality, with potential biases and considerable heterogeneity), our results reveal that sanitation is associated with a reduced risk of transmission of helminthiases to humans. Access to improved sanitation should be prioritized alongside preventive chemotherapy and health education to achieve a durable reduction of the burden of helminthiases.

Please see later in the article for the Editors' Summary

Challenging Medical Ghostwriting in US Courts

2012-01-24T22:00:00Z

by Xavier Bosch, Bijan Esfandiari, Leemon McHenry

Ensemble Modeling of the Likely Public Health Impact of a Pre-Erythrocytic Malaria Vaccine

2012-01-17T22:00:00Z

by Thomas Smith, Amanda Ross, Nicolas Maire, Nakul Chitnis, Alain Studer, Diggory Hardy, Alan Brooks, Melissa Penny, Marcel Tanner

Background

The RTS,S malaria vaccine may soon be licensed. Models of impact of such vaccines have mainly considered deployment via the World Health Organization's Expanded Programme on Immunization (EPI) in areas of stable endemic transmission of Plasmodium falciparum, and have been calibrated for such settings. Their applicability to low transmission settings is unclear. Evaluations of the efficiency of different deployment strategies in diverse settings should consider uncertainties in model structure.

Methods and Findings

An ensemble of 14 individual-based stochastic simulation models of P. falciparum dynamics, with differing assumptions about immune decay, transmission heterogeneity, and treatment access, was constructed. After fitting to an extensive library of field data, each model was used to predict the likely health benefits of RTS,S deployment, via EPI (with or without catch-up vaccinations), supplementary vaccination of school-age children, or mass vaccination every 5 y. Settings with seasonally varying transmission, with overall pre-intervention entomological inoculation rates (EIRs) of two, 11, and 20 infectious bites per person per annum, were considered. Predicted benefits of EPI vaccination programs over the simulated 14-y time horizon were dependent on duration of protection. Nevertheless, EPI strategies (with an initial catch-up phase) averted the most deaths per dose at the higher EIRs, although model uncertainty increased with EIR. At two infectious bites per person per annum, mass vaccination strategies substantially reduced transmission, leading to much greater health effects per dose, even at modest coverage.

Conclusions

In higher transmission settings, EPI strategies will be most efficient, but vaccination additional to the EPI in targeted low transmission settings, even at modest coverage, might be more efficient than national-level vaccination of infants. The feasibility and economics of mass vaccination, and the circumstances under which vaccination will avert epidemics, remain unclear. The approach of using an ensemble of models provides more secure conclusions than a single-model approach, and suggests greater confidence in predictions of health effects for lower transmission settings than for higher ones.

Please see later in the article for the Editors' Summary

Trends in Resource Utilization by Children with Neurological Impairment in the United States Inpatient Health Care System: A Repeat Cross-Sectional Study

2012-01-17T22:00:00Z

by Jay G. Berry, Annapurna Poduri, Joshua L. Bonkowsky, Jing Zhou, Dionne A. Graham, Chelsea Welch, Heather Putney, Rajendu Srivastava

Background

Care advances in the United States (US) have led to improved survival of children with neurological impairment (NI). Children with NI may account for an increasing proportion of hospital resources. However, this assumption has not been tested at a national level.

Methods and Findings

We conducted a study of 25,747,016 US hospitalizations of children recorded in the Kids' Inpatient Database (years 1997, 2000, 2003, and 2006). Children with NI were identified with International Classification of Diseases, 9th Revision, Clinical Modification diagnoses resulting in functional and/or intellectual impairment. We assessed trends in inpatient resource utilization for children with NI with a Mantel-Haenszel chi-square test using all 4 y of data combined. Across the 4 y combined, children with NI accounted for 5.2% (1,338,590) of all hospitalizations. Epilepsy (52.2% [n = 538,978]) and cerebral palsy (15.9% [n = 164,665]) were the most prevalent NI diagnoses. The proportion of hospitalizations attributable to children with NI did not change significantly (p = 0.32) over time. In 2006, children with NI accounted for 5.3% (n = 345,621) of all hospitalizations, 13.9% (n = 3.4 million) of bed days, and 21.6% (US$17.7 billion) of all hospital charges within all hospitals. Over time, the proportion of hospitalizations attributable to children with NI decreased within non-children's hospitals (3.0% [n = 146,324] in 1997 to 2.5% [n = 113,097] in 2006, p<.001) and increased within children's hospitals (11.7% [n = 179,324] in 1997 to 13.5% [n = 209,708] in 2006, p<0.001). In 2006, children with NI accounted for 24.7% (2.1 million) of bed days and 29.0% (US$12.0 billion) of hospital charges within children's hospitals.

Conclusions

Children with NI account for a substantial proportion of inpatient resources utilized in the US. Their impact is growing within children's hospitals. We must ensure that the current health care system is staffed, educated, and equipped to serve this growing segment of vulnerable children.

Please see later in the article for the Editors' Summary

A United Nations General Assembly Special Session for Mental, Neurological, and Substance Use Disorders: The Time Has Come

2012-01-17T22:00:00Z

by Judith K. Bass, Thomas H. Bornemann, Matthew Burkey, Sonia Chehil, Lenis Chen, John R. M. Copeland, William W. Eaton, Vijay Ganju, Erin Hayward, Rebecca S. Hock, Rubeena Kidwai, Kavitha Kolappa, Patrick T. Lee, Harry Minas, Flora Or, Giuseppe J. Raviola, Benedetto Saraceno, Vikram Patel

Monitoring the Introduction of Pneumococcal Conjugate Vaccines into West Africa: Design and Implementation of a Population-Based Surveillance System

2012-01-17T22:00:00Z

by Grant A. Mackenzie, Ian D. Plumb, Sana Sambou, Debasish Saha, Uchendu Uchendu, Bolanle Akinsola, Usman N. Ikumapayi, Ignatius Baldeh, Effua Usuf, Kebba Touray, Momodou Jasseh, Stephen R. C. Howie, Andre Wattiaux, Ellen Lee, Maria Deloria Knoll, Orin S. Levine, Brian M. Greenwood, Richard A. Adegbola, Philip C. Hill

What Will It Take to Eliminate Pediatric HIV? Reaching WHO Target Rates of Mother-to-Child HIV Transmission in Zimbabwe: A Model-Based Analysis

2012-01-10T22:00:00Z

by Andrea L. Ciaranello, Freddy Perez, Jo Keatinge, Ji-Eun Park, Barbara Engelsmann, Matthews Maruva, Rochelle P. Walensky, Francois Dabis, Jennifer Chu, Asinath Rusibamayila, Angela Mushavi, Kenneth A. Freedberg

Background

The World Health Organization (WHO) has called for the “virtual elimination” of pediatric HIV: a mother-to-child HIV transmission (MTCT) risk of less than 5%. We investigated uptake of prevention of MTCT (PMTCT) services, infant feeding recommendations, and specific drug regimens necessary to achieve this goal in Zimbabwe.

Methods and Findings

We used a computer model to simulate a cohort of HIV-infected, pregnant/breastfeeding women (mean age, 24 y; mean CD4, 451/µl; breastfeeding duration, 12 mo). Three PMTCT regimens were evaluated: (1) single-dose nevirapine (sdNVP), (2) WHO 2010 guidelines' “Option A” (zidovudine in pregnancy, infant nevirapine throughout breastfeeding for women without advanced disease, lifelong combination antiretroviral therapy for women with advanced disease), and (3) WHO “Option B” (pregnancy/breastfeeding-limited combination antiretroviral drug regimens without advanced disease; lifelong antiretroviral therapy with advanced disease). We examined four levels of PMTCT uptake (proportion of pregnant women accessing and adhering to PMTCT services): reported rates in 2008 and 2009 (36% and 56%, respectively) and target goals in 2008 and 2009 (80% and 95%, respectively). The primary model outcome was MTCT risk at weaning.The 2008 sdNVP-based National PMTCT Program led to a projected 12-mo MTCT risk of 20.3%. Improved uptake in 2009 reduced projected risk to 18.0%. If sdNVP were replaced by more effective regimens, with 2009 (56%) uptake, estimated MTCT risk would be 14.4% (Option A) or 13.4% (Option B). Even with 95% uptake of Option A or B, projected transmission risks (6.1%–7.7%) would exceed the WHO goal of less than 5%. Only if the lowest published transmission risks were used for each drug regimen, or breastfeeding duration were shortened, would MTCT risks at 95% uptake fall below 5%.

Conclusions

Implementation of the WHO PMTCT guidelines must be accompanied by efforts to improve access to PMTCT services, retain women in care, and support medication adherence throughout pregnancy and breastfeeding, to approach the “virtual elimination” of pediatric HIV in Zimbabwe.

Please see later in the article for the Editors' Summary

The Inadequate Treatment of Pain: Collateral Damage from the War on Drugs

2012-01-10T22:00:00Z

by Jason W. Nickerson, Amir Attaran

Trends in Compulsory Licensing of Pharmaceuticals Since the Doha Declaration: A Database Analysis

2012-01-10T22:00:00Z

by Reed Beall, Randall Kuhn

Background

It is now a decade since the World Trade Organization (WTO) adopted the “Declaration on the TRIPS Agreement and Public Health” at its 4th Ministerial Conference in Doha. Many anticipated that these actions would lead nations to claim compulsory licenses (CLs) for pharmaceutical products with greater regularity. A CL is the use of a patented innovation that has been licensed by a state without the permission of the patent title holder. Skeptics doubted that many CLs would occur, given political pressure against CL activity and continued health system weakness in poor countries. The subsequent decade has seen little systematic assessment of the Doha Declaration's impact.

Methods and Findings

We assembled a database of all episodes in which a CL was publically entertained or announced by a WTO member state since 1995. Broad searches of CL activity were conducted using media, academic, and legal databases, yielding 34 potential CL episodes in 26 countries. Country- and product-specific searches were used to verify government participation, resulting in a final database of 24 verified CLs in 17 nations. We coded CL episodes in terms of outcome, national income, and disease group over three distinct periods of CL activity. Most CL episodes occurred between 2003 and 2005, involved drugs for HIV/AIDS, and occurred in upper-middle-income countries (UMICs). Aside from HIV/AIDS, few CL episodes involved communicable disease, and none occurred in least-developed or low-income countries.

Conclusions

Given skepticism about the Doha Declaration's likely impact, we note the relatively high occurrence of CLs, yet CL activity has diminished markedly since 2006. While UMICs have high CL activity and strong incentives to use CLs compared to other countries, we note considerable countervailing pressures against CL use even in UMICs. We conclude that there is a low probability of continued CL activity. We highlight the need for further systematic evaluation of global health governance actions.

Please see later in the article for the Editors' Summary

Long-Term Survival in a Large Cohort of Patients with Venous Thrombosis: Incidence and Predictors

2012-01-10T22:00:00Z

by Linda E. Flinterman, Astrid van Hylckama Vlieg, Suzanne C. Cannegieter, Frits R. Rosendaal

Background

Venous thrombosis is a common disease with a high mortality rate shortly after the event. However, details on long-term mortality in these patients are lacking. The aim of this study was to determine long-term mortality in a large cohort of patients with venous thrombosis.

Methods and Findings

4,947 patients from the Multiple Environmental and Genetic Assessment study of risk factors for venous thrombosis (MEGA study) with a first nonfatal venous thrombosis or pulmonary embolism and 6,154 control individuals without venous thrombosis, aged 18 to 70 years, were followed up for 8 years. Death and causes of death were retrieved from the Dutch death registration. Standardized mortality ratios (SMRs) were calculated for patients compared with control individuals. Several subgroups were studied as well.736 participants (601 patients and 135 controls) died over a follow-up of 54,948 person-years. The overall mortality rate was 22.7 per 1,000 person-years (95% CI 21.0–24.6) for patients and 4.7 per 1,000 person-years (95% CI 4.0–5.6) for controls. Patients with venous thrombosis had a 4.0-fold (95% CI 3.7–4.3) increased risk of death compared with controls. The risk remained increased up to 8 years after the thrombotic event, even when no additional comorbidities were present. The highest risk of death was found for patients with additional malignancies (SMR 5.5, 95% CI 5.0–6.1). Main causes of death were diseases of the circulatory system, venous thrombosis, and malignancies. Main limitation was a maximum age of 70 at time of inclusion for the first event. Therefore results can not be generalized to those in the highest age categories.

Conclusions

Patients who experienced a first venous thrombosis had an increased risk of death which lasted up to 8 years after the event, even when no comorbidities were present at time of thrombosis. Future long-term clinical follow-up could be beneficial in these patients.

Please see later in the article for the Editors' Summary

Disclosure of Investigators' Recruitment Performance in Multicenter Clinical Trials: A Further Step for Research Transparency

2011-12-27T22:00:00Z

by Rafael Dal-Ré, David Moher, Christian Gluud, Shaun Treweek, Jacques Demotes-Mainard, Xavier Carné

Violent Crime, Epilepsy, and Traumatic Brain Injury

2011-12-27T22:00:00Z

by Jan Volavka

Poor Diet in Shift Workers: A New Occupational Health Hazard?

The PLoS Medicine Editors — 2011-12-27T22:00:00Z

by The PLoS Medicine Editors

Risk of Violent Crime in Individuals with Epilepsy and Traumatic Brain Injury: A 35-Year Swedish Population Study

2011-12-27T22:00:00Z

by Seena Fazel, Paul Lichtenstein, Martin Grann, Niklas Långström

Background

Epilepsy and traumatic brain injury are common neurological conditions, with general population prevalence estimates around 0.5% and 0.3%, respectively. Although both illnesses are associated with various adverse outcomes, and expert opinion has suggested increased criminality, links with violent behaviour remain uncertain.

Methods and Findings

We combined Swedish population registers from 1973 to 2009, and examined associations of epilepsy (n = 22,947) and traumatic brain injury (n = 22,914) with subsequent violent crime (defined as convictions for homicide, assault, robbery, arson, any sexual offense, or illegal threats or intimidation). Each case was age and gender matched with ten general population controls, and analysed using conditional logistic regression with adjustment for socio-demographic factors. In addition, we compared cases with unaffected siblings.Among the traumatic brain injury cases, 2,011 individuals (8.8%) committed violent crime after diagnosis, which, compared with population controls (n = 229,118), corresponded to a substantially increased risk (adjusted odds ratio [aOR] = 3.3, 95% CI: 3.1–3.5); this risk was attenuated when cases were compared with unaffected siblings (aOR = 2.0, 1.8–2.3). Among individuals with epilepsy, 973 (4.2%) committed a violent offense after diagnosis, corresponding to a significantly increased odds of violent crime compared with 224,006 population controls (aOR = 1.5, 1.4–1.7). However, this association disappeared when individuals with epilepsy were compared with their unaffected siblings (aOR = 1.1, 0.9–1.2). We found heterogeneity in violence risk by age of disease onset, severity, comorbidity with substance abuse, and clinical subgroups. Case ascertainment was restricted to patient registers.

Conclusions

In this longitudinal population-based study, we found that, after adjustment for familial confounding, epilepsy was not associated with increased risk of violent crime, questioning expert opinion that has suggested a causal relationship. In contrast, although there was some attenuation in risk estimates after adjustment for familial factors and substance abuse in individuals with traumatic brain injury, we found a significantly increased risk of violent crime. The implications of these findings will vary for clinical services, the criminal justice system, and patient charities.

Please see later in the article for the Editors' Summary

Cognitive Performance in Late Adolescence and the Subsequent Risk of Subdural Hematoma: An Observational Study of a Prospective Nationwide Cohort

2011-12-27T22:00:00Z

by Anna Nordström, Peter Nordström

Background

There are few identified risk factors for traumatic brain injuries such as subdural hematoma (SDH). The aim of the present study was to investigate whether low cognitive performance in young adulthood is associated with SDH later in life. A second aim was to investigate whether this risk factor was associated with education and physical fitness.

Methods and Findings

Word recollection, logical, visuospatial, and technical performances were tested at a mean age of 18.5 years in a prospective nation-wide cohort of 440,742 men. An estimate of global intelligence was calculated from these four tests. Associations between cognitive performance, education, physical fitness, and SDH during follow-up were explored using Cox regression analyses. During a median follow-up of 35 years, 863 SDHs were diagnosed in the cohort. Low global intelligence was associated with an increased risk of SDH during follow-up (hazard ratio [HR]: 1.33, per standard deviation decrease, 95% CI = 1.25–1.43). Similar results were obtained for the other measures of cognitive performance (HR: 1.24–1.33, p<0.001 for all). In contrast, a high education (HR: 0.27, comparing more than 2 years of high school and 8 years of elementary school, 95% CI = 0.19–0.39), and a high level of physical fitness (HR: 0.76, per standard deviation increase, 95% CI = 0.70–0.83), was associated with a decreased risk of suffering from a SDH.

Conclusions

The present findings suggest that reduced cognitive function in young adulthood is strongly associated with an increased risk of SDH later in life. In contrast, a higher level of education and a higher physical fitness were associated with a decreased risk of SDH.

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Worldwide Incidence of Malaria in 2009: Estimates, Time Trends, and a Critique of Methods

2011-12-20T22:00:00Z

by Richard E. Cibulskis, Maru Aregawi, Ryan Williams, Mac Otten, Christopher Dye

Background

Measuring progress towards Millennium Development Goal 6, including estimates of, and time trends in, the number of malaria cases, has relied on risk maps constructed from surveys of parasite prevalence, and on routine case reports compiled by health ministries. Here we present a critique of both methods, illustrated with national incidence estimates for 2009.

Methods and Findings

We compiled information on the number of cases reported by National Malaria Control Programs in 99 countries with ongoing malaria transmission. For 71 countries we estimated the total incidence of Plasmodium falciparum and P. vivax by adjusting the number of reported cases using data on reporting completeness, the proportion of suspects that are parasite-positive, the proportion of confirmed cases due to each Plasmodium species, and the extent to which patients use public sector health facilities. All four factors varied markedly among countries and regions. For 28 African countries with less reliable routine surveillance data, we estimated the number of cases from model-based methods that link measures of malaria transmission with case incidence. In 2009, 98% of cases were due to P. falciparum in Africa and 65% in other regions. There were an estimated 225 million malaria cases (5th–95th centiles, 146–316 million) worldwide, 176 (110–248) million in the African region, and 49 (36–68) million elsewhere. Our estimates are lower than other published figures, especially survey-based estimates for non-African countries.

Conclusions

Estimates of malaria incidence derived from routine surveillance data were typically lower than those derived from surveys of parasite prevalence. Carefully interpreted surveillance data can be used to monitor malaria trends in response to control efforts, and to highlight areas where malaria programs and health information systems need to be strengthened. As malaria incidence declines around the world, evaluation of control efforts will increasingly rely on robust systems of routine surveillance.

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The Toxic Effects of Cigarette Additives. Philip Morris' Project Mix Reconsidered: An Analysis of Documents Released through Litigation

2011-12-20T22:00:00Z

by Marcia S. Wertz, Thomas Kyriss, Suman Paranjape, Stanton A. Glantz

Background

In 2009, the promulgation of US Food and Drug Administration (FDA) tobacco regulation focused attention on cigarette flavor additives. The tobacco industry had prepared for this eventuality by initiating a research program focusing on additive toxicity. The objective of this study was to analyze Philip Morris' Project MIX as a case study of tobacco industry scientific research being positioned strategically to prevent anticipated tobacco control regulations.

Methods and Findings

We analyzed previously secret tobacco industry documents to identify internal strategies for research on cigarette additives and reanalyzed tobacco industry peer-reviewed published results of this research. We focused on the key group of studies conducted by Phillip Morris in a coordinated effort known as “Project MIX.” Documents showed that Project MIX subsumed the study of various combinations of 333 cigarette additives. In addition to multiple internal reports, this work also led to four peer-reviewed publications (published in 2001). These papers concluded that there was no evidence of substantial toxicity attributable to the cigarette additives studied. Internal documents revealed post hoc changes in analytical protocols after initial statistical findings indicated an additive-associated increase in cigarette toxicity as well as increased total particulate matter (TPM) concentrations in additive-modified cigarette smoke. By expressing the data adjusted by TPM concentration, the published papers obscured this underlying toxicity and particulate increase. The animal toxicology results were based on a small number of rats in each experiment, raising the possibility that the failure to detect statistically significant changes in the end points was due to underpowering the experiments rather than lack of a real effect.

Conclusion

The case study of Project MIX shows tobacco industry scientific research on the use of cigarette additives cannot be taken at face value. The results demonstrate that toxins in cigarette smoke increase substantially when additives are put in cigarettes, including the level of TPM. In particular, regulatory authorities, including the FDA and similar agencies elsewhere, could use the Project MIX data to eliminate the use of these 333 additives (including menthol) from cigarettes.

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A Comprehensive Framework for Human Resources for Health System Development in Fragile and Post-Conflict States

2011-12-20T22:00:00Z

by Noriko Fujita, Anthony B. Zwi, Mari Nagai, Hidechika Akashi

Estimating the Burden of Malaria: The Need for Improved Surveillance

2011-12-20T22:00:00Z

by Ivo Mueller, Laurence Slutsker, Marcel Tanner

Sex-Specific Immunization for Sexually Transmitted Infections Such as Human Papillomavirus: Insights from Mathematical Models

2011-12-20T22:00:00Z

by Johannes A. Bogaards, Mirjam Kretzschmar, Maria Xiridou, Chris J. L. M. Meijer, Johannes Berkhof, Jacco Wallinga

Background

Sex-specific differences regarding the transmissibility and the course of infection are the rule rather than the exception in the epidemiology of sexually transmitted infections (STIs). Human papillomavirus (HPV) provides an example: disease outcomes differ between men and women, as does the potential for transmission to the opposite sex. HPV vaccination of preadolescent girls was recently introduced in many countries, and inclusion of boys in the vaccination programs is being discussed. Here, we address the question of whether vaccinating females only, males only, or both sexes is the most effective strategy to reduce the population prevalence of an STI like HPV.

Methods and Findings

We use a range of two-sex transmission models with varying detail to identify general criteria for allocating a prophylactic vaccine between both sexes. The most effective reduction in the population prevalence of infection is always achieved by single-sex vaccination; vaccinating the sex with the highest prevaccine prevalence is the preferred strategy in most circumstances. Exceptions arise only when the higher prevaccine prevalence is due to a substantially lower rate of natural immunity, or when natural immunity is lifelong, and a prolonged duration of infectiousness coincides with increased transmissibility. Predictions from simple models were confirmed in simulations based on an elaborate HPV transmission model. Our analysis suggests that relatively inefficient genital transmission from males to females might render male vaccination more effective in reducing overall infection levels. However, most existing HPV vaccination programs have achieved sufficient coverage to continue with female-only vaccination.

Conclusions

Increasing vaccine uptake among preadolescent girls is more effective in reducing HPV infection than including boys in existing vaccination programs. As a rule, directing prophylactic immunization at the sex with the highest prevaccine prevalence results in the largest reduction of the population prevalence.

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The Role of Group Dynamics in Scientific Inconsistencies: A Case Study of a Research Consortium

2011-12-13T22:00:00Z

by Judith G. M. Rosmalen, Albertine J. Oldehinkel