Alcohol Sales and Risk of Serious AssaultJoel G, Ray; Rahim, Moineddin; Chaim M, Bell; Deva, Thiruchelvam; Maria Isabella, Creatore; Piotr, Gozdyra; Michael, Cusimano; Donald A, Redelmeier
doi: 10.1371/journal.pmed.0050104pmid: 18479181
Background Alcohol is a contributing cause of unintentional injuries, such as motor vehicle crashes. Prior research on the association between alcohol use and violent injury was limited to survey-based data, and the inclusion of cases from a single trauma centre, without adequate controls. Beyond these limitations was the inability of prior researchers to comprehensively capture most alcohol sales. In Ontario, most alcohol is sold through retail outlets run by the provincial government, and hospitals are financed under a provincial health care system. We assessed the risk of being hospitalized due to assault in association with retail alcohol sales across Ontario. Methods and Findings We performed a population-based case-crossover analysis of all persons aged 13 years and older hospitalized for assault in Ontario from 1 April 2002 to 1 December 2004. On the day prior to each assault case's hospitalization, the volume of alcohol sold at the store in closest proximity to the victim's home was compared to the volume of alcohol sold at the same store 7 d earlier. Conditional logistic regression analysis was used to determine the associated relative risk (RR) of assault per 1,000 l higher daily sales of alcohol. Of the 3,212 persons admitted to hospital for assault, nearly 25% were between the ages of 13 and 20 y, and 83% were male. A total of 1,150 assaults (36%) involved the use of a sharp or blunt weapon, and 1,532 (48%) arose during an unarmed brawl or fight. For every 1,000 l more of alcohol sold per store per day, the relative risk of being hospitalized for assault was 1.13 (95% confidence interval (CI) 1.02–1.26). The risk was accentuated for males (1.18, 95% CI 1.05–1.33), youth aged 13 to 20 y (1.21, 95% CI 0.99–1.46), and those in urban areas (1.19, 95% CI 1.06–1.35). Conclusions The risk of being a victim of serious assault increases with alcohol sales, especially among young urban men. Akin to reducing the risk of driving while impaired, consideration should be given to novel methods of preventing alcohol-related violence.
Decreased Brain Volume in Adults with Childhood Lead ExposureKim M, Cecil; Christopher J, Brubaker; Caleb M, Adler; Kim N, Dietrich; Mekibib, Altaye; John C, Egelhoff; Stephanie, Wessel; Ilayaraja, Elangovan; Richard, Hornung; Kelly, Jarvis; Bruce P, Lanphear
doi: 10.1371/journal.pmed.0050112pmid: 18507499
Background Although environmental lead exposure is associated with significant deficits in cognition, executive functions, social behaviors, and motor abilities, the neuroanatomical basis for these impairments remains poorly understood. In this study, we examined the relationship between childhood lead exposure and adult brain volume using magnetic resonance imaging (MRI). We also explored how volume changes correlate with historic neuropsychological assessments. Methods and Findings Volumetric analyses of whole brain MRI data revealed significant decreases in brain volume associated with childhood blood lead concentrations. Using conservative, minimum contiguous cluster size and statistical criteria (700 voxels, unadjusted p < 0.001), approximately 1.2% of the total gray matter was significantly and inversely associated with mean childhood blood lead concentration. The most affected regions included frontal gray matter, specifically the anterior cingulate cortex (ACC). Areas of lead-associated gray matter volume loss were much larger and more significant in men than women. We found that fine motor factor scores positively correlated with gray matter volume in the cerebellar hemispheres; adding blood lead concentrations as a variable to the model attenuated this correlation. Conclusions Childhood lead exposure is associated with region-specific reductions in adult gray matter volume. Affected regions include the portions of the prefrontal cortex and ACC responsible for executive functions, mood regulation, and decision-making. These neuroanatomical findings were more pronounced for males, suggesting that lead-related atrophic changes have a disparate impact across sexes. This analysis suggests that adverse cognitive and behavioral outcomes may be related to lead's effect on brain development producing persistent alterations in structure. Using a simple model, we found that blood lead concentration mediates brain volume and fine motor function.
Expectations for Recovery Important in the Prognosis of Whiplash InjuriesLena W, Holm; Linda J, Carroll; J. David, Cassidy; Eva, Skillgate; Anders, Ahlbom
doi: 10.1371/journal.pmed.0050105pmid: 18479182
Background Individuals' expectations on returning to work after an injury have been shown to predict the duration of time that a person with work-related low back pain will remain on benefits; individuals with lower recovery expectations received benefits for a longer time than those with higher expectations. The role of expectations in recovery from traumatic neck pain, in particular whiplash-associated disorders (WAD), has not been assessed to date to our knowledge. The aim of this study was to investigate if expectations for recovery are a prognostic factor after experiencing a WAD. Methods and Findings We used a prospective cohort study composed of insurance claimants in Sweden. The participants were car occupants who filed a neck injury claim (i.e., for WAD) to one of two insurance companies between 15 January 2004 and 12 January 2005 ( n = 1,032). Postal questionnaires were completed shortly (average 23 d) after the collision and then again 6 mo later. Expectations for recovery were measured with a numerical rating scale (NRS) at baseline, where 0 corresponds to “unlikely to make a full recovery” and 10 to “very likely to make a full recovery.” The scale was reverse coded and trichotomised into NRS 0, 1–4, and 5–10. The main outcome measure was self-perceived disability at 6 mo postinjury, measured with the Pain Disability Index, and categorised into no/low, moderate, and high disability. Multivariable polytomous logistic regression was used for the analysis. There was a dose response relationship between recovery expectations and disability. After controlling for severity of physical and mental symptoms, individuals who stated that they were less likely to make a full recovery (NRS 5–10), were more likely to have a high disability compared to individuals who stated that they were very likely to make a full recovery (odds ratio (OR) 4.2 (95% confidence interval (CI) 2.1 to 8.5). For the intermediate category (NRS 1–4), the OR was 2.1 (95% CI 1.2 to 3.2). Associations between expectations and disability were also found among individuals with moderate disability. Conclusions Individuals' expectations for recovery are important in prognosis, even after controlling for symptom severity. Interventions designed to increase patients' expectations may be beneficial and should be examined further in controlled studies.
Pharmacy Refill Adherence Compared with CD4 Count Changes for Monitoring HIV-Infected Adults on Antiretroviral TherapyGregory P, Bisson; Robert, Gross; Scarlett, Bellamy; Jesse, Chittams; Michael, Hislop; Leon, Regensberg; Ian, Frank; Gary, Maartens; Jean B, Nachega
doi: 10.1371/journal.pmed.0050109pmid: 18494555
Background World Health Organization (WHO) guidelines for monitoring HIV-infected individuals taking combination antiretroviral therapy (cART) in resource-limited settings recommend using CD4 + T cell (CD4) count changes to monitor treatment effectiveness. In practice, however, falling CD4 counts are a consequence, rather than a cause, of virologic failure. Adherence lapses precede virologic failure and, unlike CD4 counts, data on adherence are immediately available to all clinics dispensing cART. However, the accuracy of adherence assessments for predicting future or detecting current virologic failure has not been determined. The goal of this study therefore was to determine the accuracy of adherence assessments for predicting and detecting virologic failure and to compare the accuracy of adherence-based monitoring approaches with approaches monitoring CD4 count changes. Methodology and Findings We conducted an observational cohort study among 1,982 of 4,984 (40%) HIV-infected adults initiating non-nucleoside reverse transcriptase inhibitor-based cART in the Aid for AIDS Disease Management Program, which serves nine countries in southern Africa. Pharmacy refill adherence was calculated as the number of months of cART claims submitted divided by the number of complete months between cART initiation and the last refill prior to the endpoint of interest, expressed as a percentage. The main outcome measure was virologic failure defined as a viral load > 1,000 copies/ml (1) at an initial assessment either 6 or 12 mo after cART initiation and (2) after a previous undetectable (i.e., < 400 copies/ml) viral load (breakthrough viremia). Adherence levels outperformed CD4 count changes when used to detect current virologic failure in the first year after cART initiation (area under the receiver operating characteristic (ROC) curves (AUC) were 0.79 and 0.68 (difference = 0.11; 95% CI 0.06 to 0.16; χ 2 = 20.1) respectively at 6 mo, and 0.85 and 0.75 (difference = 0.10; 95% CI 0.05 to 0.14; χ 2 = 20.2) respectively at 12 mo; p < 0.001 for both comparisons). When used to detect current breakthrough viremia, adherence and CD4 counts were equally accurate (AUCs of 0.68 versus 0.67, respectively (difference = 0.01; 95% CI −0.06 to 0.07); χ 2 = 0.1, p > 0.5). In addition, adherence levels assessed 3 mo prior to viral load assessments were as accurate for virologic failure occurring approximately 3 mo later as were CD4 count changes calculated from cART initiation to the actual time of the viral load assessments, indicating the potential utility of adherence assessments for predicting future, rather than simply detecting current, virologic failure. Moreover, combinations of CD4 count and adherence data appeared useful in identifying patients at very low risk of virologic failure. Conclusions Pharmacy refill adherence assessments were as accurate as CD4 counts for detecting current virologic failure in this cohort of patients on cART and have the potential to predict virologic failure before it occurs. Approaches to cART scale-up in resource-limited settings should include an adherence-based monitoring approach.
Antigen Load and Viral Sequence Diversification Determine the Functional Profile of HIV-1–Specific CD8 + T CellsHendrik, Streeck; Zabrina L, Brumme; Michael, Anastario; Kristin W, Cohen; Jonathan S, Jolin; Angela, Meier; Chanson J, Brumme; Eric S, Rosenberg; Galit, Alter; Todd M, Allen; Bruce D, Walker; Marcus, Altfeld
doi: 10.1371/journal.pmed.0050100pmid: 18462013
Background Virus-specific CD8 + T lymphocytes play a key role in the initial reduction of peak viremia during acute viral infections, but display signs of increasing dysfunction and exhaustion under conditions of chronic antigen persistence. It has been suggested that virus-specific CD8 + T cells with a “polyfunctional” profile, defined by the capacity to secrete multiple cytokines or chemokines, are most competent in controlling viral replication in chronic HIV-1 infection. We used HIV-1 infection as a model of chronic persistent viral infection to investigate the process of exhaustion and dysfunction of virus-specific CD8 + T cell responses on the single-epitope level over time, starting in primary HIV-1 infection. Methods and Findings We longitudinally analyzed the polyfunctional epitope-specific CD8 + T cell responses of 18 patients during primary HIV-1 infection before and after therapy initiation or sequence variation in the targeted epitope. Epitope-specific CD8 + T cells responded with multiple effector functions to antigenic stimulation during primary HIV-1 infection, but lost their polyfunctional capacity in response to antigen and up-regulated programmed death 1 (PD-1) expression with persistent viremic infection. This exhausted phenotype significantly decreased upon removal of stimulation by antigen, either in response to antiretroviral therapy or by reduction of epitope-specific antigen load in the presence of ongoing viral replication, as a consequence of in vivo selection of cytotoxic T lymphocyte escape mutations in the respective epitopes. Monofunctionality increased in CD8 + T cell responses directed against conserved epitopes from 49% (95% confidence interval 27%–72%) to 76% (56%–95%) (standard deviation (SD) of the effect size 0.71), while monofunctionality remained stable or slightly decreased for responses directed against escaped epitopes from 61% (47%–75%) to 56% (42%–70%) (SD of the effect size 0.18) ( p < 0.05). Conclusion These data suggest that persistence of antigen can be the cause, rather than the consequence, of the functional impairment of virus-specific T cell responses observed during chronic HIV-1 infection, and underscore the importance of evaluating autologous viral sequences in studies aimed at investigating the relationship between virus-specific immunity and associated pathogenesis.
Impact of Round-the-Clock, Rapid Oral Fluid HIV Testing of Women in Labor in Rural IndiaNitika Pant, Pai; Ritu, Barick; Jacqueline P, Tulsky; Poonam V, Shivkumar; Deborah, Cohan; Shriprakash, Kalantri; Madhukar, Pai; Marina B, Klein; Shakuntala, Chhabra
doi: 10.1371/journal.pmed.0050092pmid: 18462011
Background Testing pregnant women for HIV at the time of labor and delivery is the last opportunity for prevention of mother-to-child HIV transmission (PMTCT) measures, particularly in settings where women do not receive adequate antenatal care. However, HIV testing and counseling of pregnant women in labor is a challenge, especially in resource-constrained settings. In India, many rural women present for delivery without any prior antenatal care. Those who do get antenatal care are not always tested for HIV, because of deficiencies in the provision of HIV testing and counseling services. In this context, we investigated the impact of introducing round-the-clock, rapid, point-of-care HIV testing and counseling in a busy labor ward at a tertiary care hospital in rural India. Methods and Findings After they provided written informed consent, women admitted to the labor ward of a rural teaching hospital in India were offered two rapid tests on oral fluid and finger-stick specimens (OraQuick Rapid HIV-1/HIV-2 tests, OraSure Technologies). Simultaneously, venous blood was drawn for conventional HIV ELISA testing. Western blot tests were performed for confirmatory testing if women were positive by both rapid tests and dual ELISA, or where test results were discordant. Round-the-clock (24 h, 7 d/wk) abbreviated prepartum and extended postpartum counseling sessions were offered as part of the testing strategy. HIV-positive women were administered PMTCT interventions. Of 1,252 eligible women (age range 18 y to 38 y) approached for consent over a 9 mo period in 2006, 1,222 (98%) accepted HIV testing in the labor ward. Of these, 1,003 (82%) women presented with either no reports or incomplete reports of prior HIV testing results at the time of admission to the labor ward. Of 1,222 women, 15 were diagnosed as HIV-positive (on the basis of two rapid tests, dual ELISA and Western blot), yielding a seroprevalence of 1.23% (95% confidence interval (CI) 0.61%–1.8%). Of the 15 HIV test–positive women, four (27%) had presented with reported HIV status, and 11 (73%) new cases of HIV infection were detected due to rapid testing in the labor room. Thus, 11 HIV-positive women received PMTCT interventions on account of round-the-clock rapid HIV testing and counseling in the labor room. While both OraQuick tests (oral and finger-stick) were 100% specific, one false-negative result was documented (with both oral fluid and finger-stick specimens). Of the 15 HIV-infected women who delivered, 13 infants were HIV seronegative at birth and at 1 and 4 mo after delivery; two HIV-positive infants died within a month of delivery. Conclusions In a busy rural labor ward setting in India, we demonstrated that it is feasible to introduce a program of round-the-clock rapid HIV testing, including prepartum and extended postpartum counseling sessions. Our data suggest that the availability of round-the-clock rapid HIV testing resulted in successful documentation of HIV serostatus in a large proportion (82%) of rural women who were unaware of their HIV status when admitted to the labor room. In addition, 11 (73%) of a total of 15 HIV-positive women received PMTCT interventions because of round-the-clock rapid testing in the labor ward. These findings are relevant for PMTCT programs in developing countries.