Cost-effectiveness of rabies post-exposure prophylaxis in the context of very low rabies risk: A decision-tree model based on the experience of France

IntroductionBenefit-risk of different anti-rabies post-exposure prophylaxis (PEP) strategies after scratches or bites from dogs with unknown rabies status is unknown in very low rabies risk settings.Design and settingA cost-effectiveness analysis in metropolitan France using a decision-tree model and input data from 2001 to 2011.PopulationA cohort of 2807 patients, based on the mean annual number of patients exposed to category CII (minor scratches) or CIII (transdermal bite) dog attacks in metropolitan France between 2001 and 2011.InterventionsFive PEP strategies: (A) no PEP for CII and CIII; (B) vaccine only for CIII; (C) vaccine for CII and CIII; (D) vaccine+ rabies immunoglobulin (RIG) only for CIII; and (E) vaccine for CII and vaccine+ RIG for CIII.Main outcomes measuresThe number of deaths related to rabies and to traffic accidents on the way to anti-rabies centers (ARC), effectiveness in terms of years of life gained by reducing rabies cases and avoiding traffic accidents, costs, and incremental cost-effectiveness ratios (ICER) associated with each strategy.ResultsStrategy E led to the fewest rabies cases (3.6 × 10⁻⁸) and the highest costs (€1,606,000) but also to 1.7 × 10⁻³ lethal traffic accidents. Strategy A was associated with the most rabies cases (4.8 × 10⁻⁶), but the risk of traffic accidents and costs were null; therefore, strategy A was the most effective and the least costly. The sensitivity analysis showed that, when the probability that a given dog is rabid a given day (P_A) was >1.4 × 10⁻⁶, strategy D was more effective than strategy A; strategy B became cost-effective (i.e. ICER vs strategy A <3 × French Gross Domestic Product per capita) when P_A was > 1.4 × 10⁻⁴.ConclusionsIn the metropolitan France's very low rabies prevalence context, PEP with rabies vaccine, administered alone or with RIG, is associated with significant and unnecessary costs and unfavourable benefit-risk ratios regardless to exposure category.     

Involving community stakeholders to increase park use and physical activity

ObjectiveThe aim of this study is to describe implementation of a randomized controlled trial of community-based participatory research (CBPR) approaches to increase park use and physical activity across 33 diverse neighborhoods in Los Angeles.MethodsFifty parks were randomly assigned based on park size, facilities and programs, and neighborhood socio-demographic characteristics to: park director (PD, 17 parks); PD and park advisory board of interested community members (PD + PAB, 16 parks); and no-intervention control (17 parks) arms. Between 2007 and 2012, PDs and PABs from the 33 intervention parks participated in community engagement, baseline assessment, marketing training, intervention design and implementation, and follow-up assessment.ResultsIntervention parks (PD and PD + PAB) invested in new and diversified signage, promotional items, outreach or support for group activities like fitness classes and walking clubs, and various marketing strategies. Scaling up CBPR methods across parks in 33 diverse neighborhoods was challenging. Working with departmental management and established structures for community input (PABs) and park policy (PDs) facilitated implementation and sustainability.ConclusionScaling up CBPR methods across diverse communities involved tradeoffs. CBPR is useful for tailoring research and enhancing community impact and sustainability, but more work is needed to understand how to conduct multi-site trials across diverse settings using CBPR.     

Levels and sources of volatile organic compounds including carbonyls in indoor air of homes of Puertollano,the most industrialized city in central Iberian Peninsula. Estimation of health risk

Twenty nine organic air pollutants including carbonyl compounds, alkanes, aromatic hydrocarbons and terpenes were measured in the indoor environment of different houses together with the corresponding outdoor measurements in Puertollano, the most industrialized city in central Iberian Peninsula. VOCs were sampled during 8 weeks using Radiello^® passive samplers, and a questionnaire on potential VOCs sources was filled out by the occupants. The results show that formaldehyde and hexanal was the most abundant VOCs measured in indoor air, with a median concentration of 55.5 and 46.4 μg m⁻³, respectively followed by butanal (29.1 μg m⁻³), acetone (28.4 μg m⁻³) and acetaldehyde (21.4 μg m⁻³). After carbonyls, n-dodecane (13.1 μg m⁻³) and terpenes (α-pinene, 13.4 μg m⁻³ and limonene, 13.4 μg m⁻³) were the compounds with higher median concentrations. The indoor/outdoor (I/O) ratios demonstrated that sources in the indoor environment are prevailing for most of the investigated VOCs especially for limonene, α-pinene, hexanal, formaldehyde, pentanal, acetaldehyde, o-xylene, n-dodecane and acetone with I/O ratio >6. Multiple linear regressions were applied to investigate the indoor VOC determinants and Spearman correlation coefficients were used to establish common sources between VOCs. Finally, the lifetime cancer risk associated to formaldehyde, acetaldehyde and benzene exposure was estimated and they varied from 7.8 × 10⁻⁵ to 4.1 × 10⁻⁴ for formaldehyde, from 8.6 × 10⁻⁶ to 3.5 × 10⁻⁵ for acetaldehyde and from 2.0 × 10⁻⁶ to 1.5 × 10⁻⁵ for benzene. For formaldehyde, the attributed risk in most sampled homes was two orders of magnitude higher than the one (10⁻⁶) proposed as acceptable by risk management bodies.     

Molecular evolution of fever,thrombocytopenia and leukocytopenia virus (FTLSV) based on whole-genome sequences

FTLSV is a novel bunyavirus that was discovered in 2007 in the Henan province of China and has reported case fatality rates of up to 30%. Despite the high case fatality rate, knowledge of the evolution and molecular epidemiology of FTLSV is limited. In this study, detailed phylogenetic analyses were performed on whole-genome sequences to examine the virus's evolutionary rates, estimate dates of common ancestry, and determine the population dynamics and selection pressure for FTLSV. The evolutionary rates of FTLSV were estimated to be 2.28 × 10^− 4, 2.42 × 10^− 4 and 1.19 × 10^− 4 nucleotide substitutions/site/year for the S, M and L segments, respectively. The most recent ancestor of the viruses existed approximately 182–294 years ago. Evidence of RNA segment reassortment was found in FTLSV. A Bayesian skyline plot showed that after a period of genetic stability following high variability, the FTLSV population appeared to have contracted it. Selection pressures were estimated and revealed an abundance of negatively selected sites and sparse positively selected sites. These data will be valuable in understanding the evolution and molecular epidemiology of FTLSV, eventually helping to determine mechanisms of emergence and pathogenicity and the level of the virus's threat to public health.     

Voltammetric determination of vitamin B6 in food samples and dietary supplements

A simple and rapid voltammetric method based on the use of disposable screen-printed electrodes is proposed for the determination of vitamin B₆. The influence of the pH on the voltammetric response was analyzed. Estimation of the linear range (2.0 × 10⁻⁶/7.2 × 10⁻⁵ M), calibration function, limit of detection (1.5 × 10⁻⁶ M) and reproducibility was performed along with the determination of possible interferences from species present in real samples. The proposed analytical system was successfully applied for the determination of pyridoxine in multivitamin supplements, energy drinks and breakfast cereals by using the standard addition method.     

A systematic review and meta-analysis on the effects of yoga on weight-related outcomes

IntroductionOverweight and obesity are among the most important modifiable risk factors for chronic diseases and premature death. The aim of this review was to systematically assess and analyze the effects of yoga on weight-related outcomes.MethodsMedline/PubMed, Scopus, and the Cochrane Library were screened through March 2015 for randomized controlled trials on yoga for weight-related outcomes in the general population or overweight/obese individuals. Risk of bias was assessed using the Cochrane risk of bias tool on the following domains: selection bias, performance bias, detection bias, attrition bias, reporting bias, and other bias.ResultsOut of 445 records identified during literature search, 30 trials with a total of 2173 participants were included. No effects on weight, body mass index, body fat percentage or waist circumference were found. In studies with healthy adult participants an effect of yoga compared to usual care was found regarding waist/hip ratio (SMD =‐ − 1.00; 95% CI =‐ − 1.44, − 0.55; p < 0.001). In studies with overweight/obese participants only, effects relative to usual care were found for body mass index (SMD = − 0.99; 95% CI = − 1.67, − 0.31; p = 0.004). Effects however were not robust against selection bias; and publication bias could not be ruled out. No intervention-related adverse events were reported.ConclusionsDespite methodological drawbacks, yoga can be preliminarily considered a safe and effective intervention to reduce body mass index in overweight or obese individuals.     

Molecular evolution of emerging Banna virus

Banna virus (BAV) is an emerging pathogen that causes human viral encephalitis and has been isolated from types of blood-sucking insects and mammals in Asia. However, there are no reported systematic studies that describe the origin and evolution of BAV. Here, a phylogenetic analysis of BAVs isolated from a variety of potential vectors and vertebrate hosts worldwide revealed that BAVs emerged in the beginning of the 20th century and do not exhibit a species barrier. The mean substitution rate of BAVs was 2.467 × 10^− 2 substitution/site/year (95% HPD, 1.093 × 10^− 3 to 5.628 × 10^− 2). The lineage is mainly composed of BAVs from high-latitude regions, which are the most recently emerged viruses with significantly higher substitution rates compared with the lineage comprised of the isolates from middle or low-latitude regions. The genetic differences between BAV strains are positively correlated with the geographic distribution. Strains from the same latitude regions are almost 100% identical, whereas the differences between strains from long distance regions with different latitudes could be > 60%. Our results demonstrate that BAV is an emerging virus at a stage that involves rapid evolution and has great potential for introduction into non-endemic areas. Thus, enhanced surveillance of BAV is highly recommended worldwide.     

Pedometer-assessed physical activity of Singaporean youths

ObjectiveThe aim of the study was to investigate the pedometer-assessed physical activity of Singaporean youths using an objective measurement of physical activity.Methods and resultsPedometer step count was monitored over the entire week in 877 participants aged 9–18 years in three schooling cohorts [primary (age, 9–12 years; n = 150 males; 156 females), secondary (age, 13–16 years; n = 137 males; 138 females) and junior college (age, 17–18 years; n = 140 males; 156 females)] in Singapore during July to September 2009. Analyses identified significant main effects for step count taken outside of school compared to within school (mean (SD): 5568 (4796) vs. 3881 (3149), p < 0.05). However, no significant difference was found for steps accumulated within or outside school in boys and girls across the schooling levels (steps × sex × level interaction, p > 0.05). Step counts were not significantly different between weekdays or weekends (9719 (6063) vs. 9483 (8056), p > 0.05), across schooling levels and between male and female participants (sex × level and steps × level × sex interactions, all p > 0.05).ConclusionStep count decline is drastic for male adolescents after primary school but remains low across the schooling levels for female participants. Aggregated daily step count fell short by up to 35% of the 16,000 and 13,000 steps recommended respectively for male and female youths.     

Dating the origin and dispersal of Human Papillomavirus type 16 on the basis of ancestral human migrations

A major limitation when reconstructing the origin and evolution of HPV-16 is the lack of reliable substitution rate estimates for the viral genes. On the basis of the hypothesis of human HPV-16 co-divergence, we estimated a mean evolutionary rate of 1.47 × 10^− 7 (95% HPD = 0.64–2.47 × 10^− 7) subs/site/year for the viral LCR region. The results of a Bayesian phylogeographical analysis suggest that the currently circulating HPV-16 most probably originated in Africa about 110 thousand years ago (Kya), before giving rise to four known geographical lineages: the Asian/European lineage, which most probably originated in Asia a mean 38 Kya, and the Asian/American and two African lineages, which probably respectively originated about 33 and 27 Kya. These data closely reflect current hypotheses concerning modern human expansion based on studies of mitochondrial DNA phylogeny. The correlation between ancient human migration and the present HPV phylogeny may be explained by the co-existence of modes of transmission other than sexual transmission.     

Genetic analysis of human rhinovirus species A to C detected in patients with acute respiratory infection in Kumamoto prefecture,Japan 2011–2012

We performed detailed genetic analysis of the VP4/VP2 coding region in human rhinovirus species A to C (HRV-ABC) strains detected in patients with a variety of acute respiratory infections in Kumamoto, Japan in the period 2011–12. The phylogenetic tree and evolutionary timescale were obtained by the Bayesian Markov chain Monte Carlo method. Phylogenetic analyses showed that the present HRV-A, -B, and -C strains belonged to 25, 4, and 18 genotypes, respectively. Some new genotypes were confirmed as prevalent strains of HRV-C. An ancestor of the present HRV-ABCs could be dated back to about 20,000 years ago. The present HRV-A and -C strains have wide genetic divergence (pairwise distance >0.2) with rapid evolutionary rates (around 7 × 10⁻⁴ to 4 × 10⁻³ substitutions/site/year). Over 100 sites were found to be under negative selection, while no positively selected sites were found in the analyzed region. No evidence of recombination events was found in this region of the present strains. Our results indicate that the present HRV strains have rapidly evolved and subsequently diverged over a long period into multiple genotypes.     

A first step to assess harm and benefit in clinical trials in one scale

ObjectiveTo develop a simple system to assess benefit and harm of treatment on a single scale. Harm and benefit signals from trials need to be placed in the proper perspective to decide on the value of a treatment. Several systems have been developed for assessment, but few attempt to incorporate both benefit and risk in the same metric while retaining enough simplicity to aid patients and clinicians in their decision making.Study Design and SettingWe designed a very simple 3 × 3 table (Outcome Measures in Rheumatology [OMERACT] 3 × 3) that comprises three ranks for both beneficial and harm outcomes: for benefit, these are “none,” “substantial,” and “(near) remission”; for harm, these are “none,” “severe,” and “(near) death.” Patients are ranked both for benefit and harm and subsequently counted in a 3 × 3 table.ResultsThe system was feasible when applied to one trial dataset (patient-level information) and a meta-analysis. To become applicable as a tool, several issues need to be resolved in further development, especially the definitions and cutoffs for the ranks.ConclusionA simple 3 × 3 table to rank both benefit and harm outcomes is feasible. For rheumatology this will be further developed in the context of the OMERACT initiative.     

Diet quality is lower among adults with a BMI ≥40 kg m−2 or a history of weight loss surgery

BackgroundPoor diet is a major public health issue requiring strategies to support improvements. Nutrition knowledge influences eating behaviours, yet few studies have examined relationships with diet quality. The current study aimed to explore relationships between demographic characteristics, nutrition knowledge, and diet quality using the Australian Recommended Food Score (measuring diet variety).MethodsAdults 18–60 years completed a 210-item survey including questions on demographics, health, nutrition knowledge, and diet. Statistical analysis used chi-square tests, linear and multiple regression, adjusted for covariates.Results480 respondents with a mean (SD) age 39.1 ± 11.6 years (18% male) completed all questions. Overall diet quality scores were high (ARFS 39.5 ± 9 points). Nutrition knowledge (p < 0.001) and BMI (p < 0.001) were positively associated with ARFS. ARFS scores were higher for those with higher nutrition knowledge scores (ARFS 42 ± 8 points) and of lower BMI (ARFS 40 ± 8 points) compared to those with lower knowledge (ARFS 37 ± 11) and higher BMI (ARFS 35 ± 10 points). Those with BMI ≥ 40 kg·m⁻² and weight loss surgery reported the lowest diet quality (ARFS 31 ± 10 points).ConclusionDiet quality was highest among those with high nutrition knowledge and lower BMI. Those with a BMI ≥ 40 kg·m⁻², particularly those with past weight loss surgery reported the lowest diet quality, despite comparable levels of nutrition knowledge. It remains unclear which factors explain the variation in diet quality in the weight loss surgery group and this deserves further attention given the growing popularity of weight loss surgery.     

Adecuación de la utilización de benzodiazepinas en ancianos desde la oficina de farmacia. Un estudio de colaboración médico-farmacéutico

AimsTo improve the use of benzodiazepines (BZD) in the elderly by a pharmacist-physician collaboration, and to insure that BZD are effective, safe, and used as long as necessary.DesignA single blind controlled study was conducted on 11 pharmacies in the Community of Valencia.SettingEleven pharmacies in the Community of Valencia.ParticipantsPatients older than 65 years treated with BZD attending the participating pharmacies.InterventionsInterviews and pharmaceutical care for a year.Main measurementdetection of duplications, adverse drug reactions, drug interactions and measuring the effectiveness of the treatment.ResultsWe studied 314 patients, randomised to control or intervention and who used 346 BZD. The majority (67 %) of patients used BZD for more than 1 year. Only 5 % patients with anxiety knew the duration of treatment should be one month. Long-acting BZD were used by 20 % of the patients, 76 % used medium-acting (39 % lorazepam and 37 % other BZD) and 4 % short-acting BZD. A total of 132 drug interactions were detected and 278 adverse drug reactions: 32 % memory loss, 21 % drowsiness, 12 % lack of coordination, 8.3 % dizziness and confusion, 8,3 % disorientation and 10 % others. A total of 426 pharmacist interventions were performed, 30 accepted by the doctor and 78 were resolved at the end of the year of study. Eleven per cent of cases were considered satisfactory in the control group and 30 % in the intervention group.ConclusionThe use of benzodiazepines in the Community of Valencia exceeds the recommendations of the Spanish Medicines Agency.     

Molecular epidemiology and evolutionary dynamics of Echovirus 3 serotype

Echovirus 3 (E3) serotype has been related with several neurologic diseases, although it constitutes one of the rarely isolated serotypes, with no report of epidemics in Europe. The aim of the present study was to provide insights into the molecular epidemiology and evolution of this enterovirus serotype, while an E3 strain was isolated from sewage in Greece, four years after the initial isolation of the only reported E3 strain in the same geographical region.Phylogenetic analysis of the complete VP1 genomic region of that E3 strain and of those available in GenBank suggested three main genogroups that were further subdivided into seven subgenogroups. Further evolutionary analysis suggested that VP1 genomic region of E3 was dominated by purifying selection, as the vast majority of genetic diversity presumably occurred through synonymous nucleotide substitutions and the substitution rate for complete and partial VP1 sequences was calculated to be 8.13 × 10⁻³ and 7.72 × 10⁻³ substitutions/site/year respectively. The partial VP1 sequence analysis revealed the composite epidemiology of this serotype, as the strains of the three genogroups presented different epidemiological characteristics.     

Molecular evolution of attachment glycoprotein (G) gene in human respiratory syncytial virus detected in Japan 2008–2011

We investigated the evolution of the C-terminal 3rd hypervariable region of G gene in the prevalent human respiratory syncytial virus (RSV) subgroups A (RSV-A) and B (RSV-B) in Japan in 2008–2011. Phylogenetic analysis and the evolutionary timescale was obtained by the Bayesian Markov Chain Monte Carlo method. All 38 RSV-A strains detected were classified into genotype NA1 and the 17 RSV-B strains detected belonged to genotypes BA and GB2. NA1 subdivided around 1998 in the present phylogenetic tree. Genotype BA subdivided around 1994. The evolutionary rates for RSV-A and RSV-B were estimated at 3.63 × 10⁻³ and 4.56 × 10⁻³ substitutions/site/year, respectively. The mean evolutionary rate of RSV-B was significantly faster than that of RSV-A during all seasons. The pairwise distance was relatively short (less than 0.06). In addition, some unique sites under positive selection were found. The results suggested that this region of the RSV strains rapidly evolved with some unique amino acid substitutions due to positive pressure.     

An exploratory investigation of purging disorder

ObjectivePurging Disorder (PD) is an understudied pattern of behaviors within the Eating Disorder Not Otherwise Specified (EDNOS) category. Such categorization may suggest that PD is not clinically significant as other eating disorders. However, evidence has suggested that PD is associated with significant impairments in psychosocial functioning and well-being. Despite the apparent clinical significance of PD, it remains to be determined if PD is distinct from other clinically significant eating disorders. The present study sought to assess the phenomenology, clinical significance, and distinctiveness of PD.MethodGroup scores on measures of eating pathology, body image disturbance, and psychological correlates were compared using MANOVA among a female undergraduate sample (N = 94) meeting diagnostic criteria for PD (n = 20), Bulimia Nervosa (BN; n = 35), restrained eating (n = 18), and healthy controls (n = 21).ResultsOverall, results indicated the PD group reported less severe symptoms than BN but more severe symptoms than controls. The PD and restraint groups were similar on most variables (including subjective binge behavior), with the exception of perfectionism and hunger.DiscussionFindings support the conceptualization of PD as existing along a spectrum of bulimic spectrum disorders rather than as a distinct diagnostic category.     

Plaguicidas organofosforados y efecto neuropsicológico y motor en la Región del Maule,Chile

ObjectiveTo evaluate organophosphate pesticide exposure and neuropsychological and motor performance in agricultural and non-agricultural workers in the Maule Region in Chile.MethodAnalytic cross-sectional study in 93 exposed farm workers and 84 unexposed non-agricultural workers. A battery of four neuropsychological tests was administered together with a neuro-motor physical examination.ResultsOn the Weschler adult intelligence scale (WAIS-IV), exposed agricultural workers exhibited poorer performance than non-agricultural workers in verbal comprehension (β = −3.2; p = 0.034) and processing speed (β = −4.4; p = 0.036) and in the full scale (β = −4; p = 0.016), as well as in discrimination sensitivity (β = 1, p = 0,009), adjusted by years of schooling and/or age.ConclusionsWe suggest the development of policies and regulations for the control, sale and use of organophosphate pesticides and intervention strategies on safety measures aimed at the exposed population.     

Validity of the estimates of oral cholera vaccine effectiveness derived from the test-negative design

BackgroundThe test-negative design (TND) has emerged as a simple method for evaluating vaccine effectiveness (VE). Its utility for evaluating oral cholera vaccine (OCV) effectiveness is unknown. We examined this method's validity in assessing OCV effectiveness by comparing the results of TND analyses with those of conventional cohort analyses.MethodsRandomized controlled trials of OCV were conducted in Matlab (Bangladesh) and Kolkata (India), and an observational cohort design was used in Zanzibar (Tanzania). For all three studies, VE using the TND was estimated from the odds ratio (OR) relating vaccination status to fecal test status (Vibrio cholerae O1 positive or negative) among diarrheal patients enrolled during surveillance (VE =  (1 − OR)×100%). In cohort analyses of these studies, we employed the Cox proportional hazard model for estimating VE (=1 − hazard ratio)×100%).ResultsOCV effectiveness estimates obtained using the TND (Matlab: 51%, 95% CI:37–62%; Kolkata: 67%, 95% CI:57–75%) were similar to the cohort analyses of these RCTs (Matlab: 52%, 95% CI:43–60% and Kolkata: 66%, 95% CI:55–74%). The TND VE estimate for the Zanzibar data was 94% (95% CI:84–98%) compared with 82% (95% CI:58–93%) in the cohort analysis. After adjusting for residual confounding in the cohort analysis of the Zanzibar study, using a bias indicator condition, we observed almost no difference in the two estimates.ConclusionOur findings suggest that the TND is a valid approach for evaluating OCV effectiveness in routine vaccination programs.