Investing in the future: lessons learnt from communicating the results of HSV/ HIV intervention trials in South Africa

<p>Abstract</p> <p>Background</p> <p>Communicating the results of randomised controlled trials may present challenges for researchers who have to work with communities and policy-makers to anticipate positive outcomes, while being aware that results may show no effect or harm.</p> <p>Methods</p> <p>We present a case study from the perspective of researchers in South Africa about the lessons learnt from communicating the results of four trials evaluating treatment for herpes simplex virus type 2 (HSV-2) as a new strategy for HIV prevention.</p> <p>Results</p> <p>We show that contextual factors such as misunderstandings and mistrust played an important role in defining the communications response. Use of different approaches in combination was found to be most effective in building understanding, credibility and trust in the research process. During the communication process, researchers acted beyond their traditional role of neutral observers and became agents of social change. This change in role is in keeping with a global trend towards increased communication of research results and presents both opportunities and challenges for the conduct of future research.</p> <p>Conclusions</p> <p>Despite disappointing trial results which showed no benefit of HSV-2 treatment for HIV prevention, important lessons were learnt about the value of the communication process in building trust between researchers, community members and policy-makers, and creating an enabling environment for future research partnerships.</p

An Economic Evaluation of Home Management of Malaria in Uganda: An Interactive Markov Model

BACKGROUND: Home management of malaria (HMM), promoting presumptive treatment of febrile children in the community, is advocated to improve prompt appropriate treatment of malaria in Africa. The cost-effectiveness of HMM is likely to vary widely in different settings and with the antimalarial drugs used. However, no data on the cost-effectiveness of HMM programmes are available. METHODS/PRINCIPAL FINDINGS: A Markov model was constructed to estimate the cost-effectiveness of HMM as compared to conventional care for febrile illnesses in children without HMM. The model was populated with data from Uganda, but is designed to be interactive, allowing the user to adjust certain parameters, including the antimalarials distributed. The model calculates the cost per disability adjusted life year averted and presents the incremental cost-effectiveness ratio compared to a threshold value. Model output is stratified by level of malaria transmission and the probability that a child would receive appropriate care from a health facility, to indicate the circumstances in which HMM is likely to be cost-effective. The model output suggests that the cost-effectiveness of HMM varies with malaria transmission, the probability of appropriate care, and the drug distributed. Where transmission is high and the probability of appropriate care is limited, HMM is likely to be cost-effective from a provider perspective. Even with the most effective antimalarials, HMM remains an attractive intervention only in areas of high malaria transmission and in medium transmission areas with a lower probability of appropriate care. HMM is generally not cost-effective in low transmission areas, regardless of which antimalarial is distributed. Considering the analysis from the societal perspective decreases the attractiveness of HMM. CONCLUSION: Syndromic HMM for children with fever may be a useful strategy for higher transmission settings with limited health care and diagnosis, but is not appropriate for all settings. HMM may need to be tailored to specific settings, accounting for local malaria transmission intensity and availability of health services

Swiss residents' speciality choices – impact of gender, personality traits, career motivation and life goals

BACKGROUND: The medical specialities chosen by doctors for their careers play an important part in the development of health-care services. This study aimed to investigate the influence of gender, personality traits, career motivation and life goal aspirations on the choice of medical speciality. METHODS: As part of a prospective cohort study of Swiss medical school graduates on career development, 522 fourth-year residents were asked in what speciality they wanted to qualify. They also assessed their career motivation and life goal aspirations. Data concerning personality traits such as sense of coherence, self-esteem, and gender role orientation were collected at the first assessment, four years earlier, in their final year of medical school. Data analyses were conducted by univariate and multivariate analyses of variance and covariance. RESULTS: In their fourth year of residency 439 (84.1%) participants had made their speciality choice. Of these, 45 (8.6%) subjects aspired to primary care, 126 (24.1%) to internal medicine, 68 (13.0%) to surgical specialities, 31 (5.9%) to gynaecology & obstetrics (G&O), 40 (7.7%) to anaesthesiology/intensive care, 44 (8.4%) to paediatrics, 25 (4.8%) to psychiatry and 60 (11.5%) to other specialities. Female residents tended to choose G&O, paediatrics, and anaesthesiology, males more often surgical specialities; the other specialities did not show gender-relevant differences of frequency distribution. Gender had the strongest significant influence on speciality choice, followed by career motivation, personality traits, and life goals. Multivariate analyses of covariance indicated that career motivation and life goals mediated the influence of personality on career choice. Personality traits were no longer significant after controlling for career motivation and life goals as covariates. The effect of gender remained significant after controlling for personality traits, career motivation and life goals. CONCLUSION: Gender had the greatest impact on speciality and career choice, but there were also two other relevant influencing factors, namely career motivation and life goals. Senior physicians mentoring junior physicians should pay special attention to these aspects. Motivational guidance throughout medical training should not only focus on the professional career but also consider the personal life goals of those being mentored

Physician practices related to use of BMI-for-age and counseling for childhood obesity prevention: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Screening for obesity and providing appropriate obesity-related counseling in the clinical setting are important strategies to prevent and control childhood obesity. The purpose of this study is to document pediatricians (PEDs) and general practitioners (GPs) with pediatric patients use of BMI-for-age to screen for obesity, confidence in explaining BMI, access to referral clinics, and characteristics associated with screening and counseling to children and their caregivers.</p> <p>Methods</p> <p>The authors used 2008 DocStyles survey data to examine these practices at every well child visit for children aged two years and older. Counseling topics included: physical activity, TV viewing time, energy dense foods, fruits and vegetables, and sugar-sweetened beverages. Chi-square tests were used to examine differences in proportions and logistic regression to identify characteristics associated with screening and counseling.</p> <p>Results</p> <p>The final analytic sample included 250 PEDs and 621 GPs. Prevalence of using BMI-for-age to screen for obesity at every well child visit was higher for PEDs than GPs (50% vs. 22%, χ2 = 67.0, p ≤ 0.01); more PEDs reported being very/somewhat confident in explaining BMI (94% vs. GPs, 87%, p < 0.01); more PEDs reported access to a pediatric obesity specialty clinic for referral (PEDs = 65% vs. GPs = 42%, χ2 = 37.5, p ≤ 0.0001).</p> <p>In general, PEDs reported higher counseling prevalence than GPs. There were significant differences in the following topics: TV viewing (PEDs, 79% vs. GPs, 61%, χ2 = 19.1, p ≤ 0.0001); fruit and vegetable consumption (PEDs, 87% vs. GPs, 78%, χ2 = 6.4, p ≤ 0.01). The only characteristics associated with use of BMI for GPs were being female (OR = 2.3, 95% CI = 1.5-3.5) and serving mostly non-white patients (OR = 1.8, 95% CI = 1.1-2.9); there were no significant associations for PEDs.</p> <p>Conclusions</p> <p>The findings for use of BMI-for-age, counseling habits, and access to a pediatric obesity specialty clinic leave room for improvement. More research is needed to better understand why BMI-for-age is not being used to screen at every well child visit, which may increase the likelihood overweight and obese patients receive counseling and referrals for additional services. The authors also suggest more communication between PEDs and GPs through professional organizations to increase awareness of existing resources, and to enhance access and referral to pediatric obesity specialty clinics.</p

Similar efficacy and safety of artemether-lumefantrine (Coartem®) in African infants and children with uncomplicated falciparum malaria across different body weight ranges

<p>Abstract</p> <p>Background</p> <p>Artemisinin-based combination therapy, including artemether-lumefantrine (AL), is currently recommended for the treatment of uncomplicated <it>Plasmodium falciparum </it>malaria. The objectives of the current analysis were to compare the efficacy and safety of AL across different body weight ranges in African children, and to examine the age and body weight relationship in this population.</p> <p>Methods</p> <p>Efficacy, safety and pharmacokinetic data from a randomized, investigator-blinded, multicentre trial of AL for treatment of acute uncomplicated <it>P. falciparum </it>malaria in infants and children in Africa were analysed according to body weight group.</p> <p>Results</p> <p>The trial included 899 patients (intent-to-treat population 886). The modified intent-to-treat (ITT) population (n = 812) comprised 143 children 5 to < 10 kg, 334 children 10 to < 15 kg, 277 children 15 to < 25 kg, and 58 children 25 to < 35 kg. The 28-day PCR cure rate, the primary endpoint, was comparable across all four body weight groups (97.2%, 98.9%, 97.8% and 98.3%, respectively). There were no clinically relevant differences in safety or tolerability between body weight groups. In the three AL body weight dosing groups (5 to < 15 kg, 15 to < 25 kg and 25 to < 35 kg), 80% of patients were aged 10-50 months, 46-100 months and 90-147 months, respectively.</p> <p>Conclusion</p> <p>Efficacy of AL in uncomplicated falciparum malaria is similar across body weight dosing groups as currently recommended in the label with no clinically relevant differences in safety or tolerability. AL dosing based on body weight remains advisable.</p

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Effects of shared medical appointments on quality of life and cost-effectiveness for patients with a chronic neuromuscular disease. Study protocol of a randomized controlled trial

Contains fulltext : 96862.pdf (publisher's version ) (Open Access)BACKGROUND: Shared medical appointments are a series of one-to-one doctor-patient contacts, in presence of a group of 6-10 fellow patients. This group visits substitute the annual control visits of patients with the neurologist. The same items attended to in a one-to-one appointment are addressed. The possible advantages of a shared medical appointment could be an added value to the present management of neuromuscular patients. The currently problem-focused one-to-one out-patient visits often leave little time for the patient's psychosocial needs, patient education, and patient empowerment. METHODS/DESIGN: A randomized, prospective controlled study (RCT) with a follow up of 6 months will be conducted to evaluate the clinical and cost-effectiveness of shared medical appointments compared to usual care for 300 neuromuscular patients and their partners at the Radboud University Nijmegen Medical Center. Every included patient will be randomly allocated to one of the two study arms. This study has been reviewed and approved by the medical ethics committee of the region Arnhem-Nijmegen, The Netherlands. The primary outcome measure is quality of life as measured by the EQ-5D, SF-36 and the Individualized neuromuscular Quality of Life Questionnaire. The primary analysis will be an intention-to-treat analysis on the area under the curve of the quality of life scores. A linear mixed model will be used with random factor group and fixed factors treatment, baseline score and type of neuromuscular disease. For the economic evaluation an incremental cost-effectiveness analysis will be conducted from a societal perspective, relating differences in costs to difference in health outcome. Results are expected in 2012. DISCUSSION: This study will be the first randomized controlled trial which evaluates the effect of shared medical appointments versus usual care for neuromuscular patients. This will enable to determine if there is additional value of shared medical appointments to the current therapeutical spectrum. When this study shows that group visits produce the alleged benefits, this may help to increase the acceptance of this innovative and creative way of using one of the most precious resources in health care more efficiently: time. TRIAL REGISTRATION: DutchTrial Register http://www.trialregister.nlNTR1412

Lentiviral gene therapy for X-linked chronic granulomatous disease

Chronic granulomatous disease (CGD) is a rare inherited disorder of phagocytic cells. We report the initial results of nine severely affected X-linked CGD (X-CGD) patients who received ex vivo autologous CD34+ hematopoietic stem and progenitor cell-based lentiviral gene therapy following myeloablative conditioning in first-in-human studies (trial registry nos. NCT02234934 and NCT01855685). The primary objectives were to assess the safety and evaluate the efficacy and stability of biochemical and functional reconstitution in the progeny of engrafted cells at 12 months. The secondary objectives included the evaluation of augmented immunity against bacterial and fungal infection, as well as assessment of hematopoietic stem cell transduction and engraftment. Two enrolled patients died within 3 months of treatment from pre-existing comorbidities. At 12 months, six of the seven surviving patients demonstrated stable vector copy numbers (0.4–1.8 copies per neutrophil) and the persistence of 16–46% oxidase-positive neutrophils. There was no molecular evidence of either clonal dysregulation or transgene silencing. Surviving patients have had no new CGD-related infections, and six have been able to discontinue CGD-related antibiotic prophylaxis. The primary objective was met in six of the nine patients at 12 months follow-up, suggesting that autologous gene therapy is a promising approach for CGD patients

Variants in STXBP3 are Associated with Very Early Onset Inflammatory Bowel Disease, Bilateral Sensorineural Hearing Loss and Immune Dysregulation

Background and aims: Very early onset inflammatory bowel disease [VEOIBD] is characterized by intestinal inflammation affecting infants and children less than 6 years of age. To date, over 60 monogenic aetiologies of VEOIBD have been identified, many characterized by highly penetrant recessive or dominant variants in underlying immune and/or epithelial pathways. We sought to identify the genetic cause of VEOIBD in a subset of patients with a unique clinical presentation. Methods: Whole exome sequencing was performed on five families with ten patients who presented with a similar constellation of symptoms including medically refractory infantile-onset IBD, bilateral sensorineural hearing loss and, in the majority, recurrent infections. Genetic aetiologies of VEOIBD were assessed and Sanger sequencing was performed to confirm novel genetic findings. Western analysis on peripheral blood mononuclear cells and functional studies with epithelial cell lines were employed. Results: In each of the ten patients, we identified damaging heterozygous or biallelic variants in the Syntaxin-Binding Protein 3 gene [STXBP3], a protein known to regulate intracellular vesicular trafficking in the syntaxin-binding protein family of molecules, but not associated to date with either VEOIBD or sensorineural hearing loss. These mutations interfere with either intron splicing or protein stability and lead to reduced STXBP3 protein expression. Knock-down of STXBP3 in CaCo2 cells resulted in defects in cell polarity. Conclusion: Overall, we describe a novel genetic syndrome and identify a critical role for STXBP3 in VEOIBD, sensorineural hearing loss and immune dysregulation.info:eu-repo/semantics/publishedVersio

Policy challenges for the pediatric rheumatology workforce: Part II. Health care system delivery and workforce supply

The United States pediatric population with chronic health conditions is expanding. Currently, this demographic comprises 12-18% of the American child and youth population. Affected children often receive fragmented, uncoordinated care. Overall, the American health care delivery system produces modest outcomes for this population. Poor, uninsured and minority children may be at increased risk for inferior coordination of services. Further, the United States health care delivery system is primarily organized for the diagnosis and treatment of acute conditions. For pediatric patients with chronic health conditions, the typical acute problem-oriented visit actually serves as a barrier to care. The biomedical model of patient education prevails, characterized by unilateral transfer of medical information. However, the evidence basis for improvement in disease outcomes supports the use of the chronic care model, initially proposed by Dr. Edward Wagner. Six inter-related elements distinguish the success of the chronic care model, which include self-management support and care coordination by a prepared, proactive team