Combined impact of healthy lifestyle factors on risk of asthma, rhinoconjunctivitis and eczema in school children: ISAAC phase III

Background Asthma is not the key focus of prevention strategies. A Healthy Lifestyle Index (HLI) was developed to examine the combined effect of modifiable lifestyle factors on asthma, rhinoconjunctivitis and eczema using data from the International Study of Asthma and Allergies in Childhood (ISAAC) phase III. Methods Information on symptoms of asthma, rhinoconjunctivitis, eczema and several lifestyle factors was obtained from children aged 6–7 years through written questionnaires. The HLI combined five lifestyle factors: no parental smoking, child’s adherence to Mediterranean diet, child’s healthy body mass index, high physical activity and non-sedentary behaviour. The association between the HLI and risk of asthma, rhinoconjunctivitis and eczema was evaluated using multilevel mixed-effects logistic regression models. Findings Data of 70 795 children from 37 centres in 19 countries were analysed. Each additional healthy lifestyle factor was associated with a reduced risk of current wheeze (OR 0.87, 95% CI 0.84 to 0.89), asthma ever (OR 0.89, 95% CI 0.87 to 0.92), current symptoms of rhinoconjunctivitis (OR 0.95, 95% CI 0.92 to 0.97) and current symptoms of eczema (OR 0.92, 95% CI 0.92 to 0.98). Theoretically, if associations were causal, a combination of four or five healthy lifestyle factors would result into a reduction up to 16% of asthma cases (ranging from 2.7% to 26.3 % according to region of the world). Conclusions These findings should be interpreted with caution given the limitations to infer causality from cross-sectional observational data. Efficacy of interventions to improve multiple modifiable lifestyle factors to reduce the burden asthma and allergy in childhood should be assessed

The impact of the method of consent on response rates in the ISAAC time trends study.

BACKGROUND: Centres in Phases I and III of the International Study of Asthma and Allergies in Childhood (ISAAC) programme used the method of consent (passive or active) required by local ethics committees. METHODS: Retrospectively, relationships between achieved response rates and method of consent for 13-14 and 6-7-year-olds (adolescents and children, respectively), were examined between phases and between English and non-English language centres. RESULTS: Information was obtained for 113 of 115 centres for adolescents and 72/72 centres for children. Both age groups: most centres using passive consent achieved high response rates (>80% adolescents and >70% children). English language centres using active consent showed a larger decrease in response rate. Adolescents: seven centres changed from passive consent in Phase I to active consent in Phase III (median decrease of 13%), with five centres showing lower response rates (as low as 34%). Children: no centre changed consent method between phases. Centres using active consent had lower median response rates (lowest response rate 45%). CONCLUSION: The requirement for active consent for population school-based questionnaire studies can impact negatively on response rates, particularly English language centres, thus adversely affecting the validity of the data. Ethics committees need to consider this issue carefully.Revisión por pare

Attractive targeted sugar bait phase III trials in Kenya, Mali, and Zambia.

BACKGROUND: Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) target night-time indoor biting mosquitoes and effectively reduce malaria transmission in rural settings across Africa, but additional vector control tools are needed to interrupt transmission. Attractive targeted sugar baits (ATSBs) attract and kill mosquitoes, including those biting outdoors. Deployment of ATSBs incorporating the insecticide dinotefuran was associated with major reductions in mosquito density and longevity in Mali. The impact of this promising intervention on malaria transmission and morbidity now needs to be determined in a range of transmission settings. METHODS/DESIGN: We will conduct three similar stand-alone, open-label, two-arm, cluster-randomized, controlled trials (cRCTs) in Mali, Kenya, and Zambia to determine the impact of ATSB + universal vector control versus universal vector control alone on clinical malaria. The trials will use a "fried-egg" design, with primary outcomes measured in the core area of each cluster to reduce spill-over effects. All household structures in the ATSB clusters will receive two ATSBs, but the impact will be measured in the core of clusters. Restricted randomization will be used. The primary outcome is clinical malaria incidence among children aged 5-14 years in Mali and 1-14 years in Kenya and Zambia. A key secondary outcome is malaria parasite prevalence across all ages. The trials will include 76 clusters (38 per arm) in Mali and 70 (35 per arm) in each of Kenya and Zambia. The trials are powered to detect a 30% reduction in clinical malaria, requiring a total of 3850 person-years of follow-up in Mali, 1260 person-years in Kenya, and 1610 person-years in Zambia. These sample sizes will be ascertained using two seasonal 8-month cohorts in Mali and two 6-month seasonal cohorts in Zambia. In Kenya, which has year-round transmission, four 6-month cohorts will be used (total 24 months of follow-up). The design allows for one interim analysis in Mali and Zambia and two in Kenya. DISCUSSION: Strengths of the design include the use of multiple study sites with different transmission patterns and a range of vectors to improve external validity, a large number of clusters within each trial site, restricted randomization, between-cluster separation to minimize contamination between study arms, and an adaptive trial design. Noted threats to internal validity include open-label design, risk of contamination between study arms, risk of imbalance of covariates across study arms, variation in durability of ATSB stations, and potential disruption resulting from the COVID-19 pandemic. TRIAL REGISTRATION: Zambia: ClinicalTrials.gov NCT04800055 . Registered on March 15, 2021 Mali: ClinicalTrials.gov NCT04149119 . Registered on November 4, 2019 Kenya: ClinicalTrials.gov NCT05219565 . Registered on February 2, 2022

Association of overweight and obesity with health status, weight management, and exercise behaviors among individuals with type 2 diabetes mellitus or with cardiometabolic risk factors

James R Gavin, III1, Helena W Rodbard2, Kathleen M Fox3, Susan Grandy4 for the SHIELD Study Group1Emory University School of Medicine, Atlanta, GA, USA; 2Endocrine and Metabolic Consultants, Rockville, MD, USA; 3Strategic Healthcare Solutions, LLC, Monkton, MD, USA; 4AstraZeneca LP, Wilmington, DE, USAObjectives: This investigation evaluated the role of obesity in health status and behaviors for weight management and exercise among individuals with type 2 diabetes mellitus (T2DM) or cardiometabolic risk factors.Methods: Self-reported health status, exercise behaviors, and weight management were assessed in the SHIELD study for respondents with T2DM or high risk (HR) for diabetes (ie, ≥3 of the following: abdominal obesity, body mass index [BMI] ≥28 kg/m2, self-reported diagnosis of dyslipidemia, hypertension, or history of cardiovascular disease). Respondents were stratified into three BMI categories: <25 kg/m2 (underweight or normal weight), 25.0−29.9 kg/m2 (overweight), and ≥30 kg/m2 (obese), with comparisons made using analysis of variance. Comparisons between T2DM and HR were made using chi-square tests.Results: T2DM (n = 3,918) and HR (n = 5,464) groups were similar for age (mean = 59 years), race (≥85% white), and obesity. Overweight (31%) or obese T2DM (18%) respondents were significantly less likely to report excellent health compared with overweight or obese HR respondents (42% and 30%, respectively), p < 0.001. There were no differences between T2DM and HR groups for exercise behaviors. More obese respondents (20% T2DM, 21% HR) were “contemplating exercising”, and fewer (21%−23%) were currently “exercising regularly” compared with overweight and normal weight respondents, p < 0.001. More obese respondents (78% T2DM, 83% HR) attempted weight management than normal (28%−35%) or overweight (57%−61%) respondents, p < 0.001.Conclusions: Obesity was negatively associated with self-perception of current health, exercising regularly, and weight maintenance for those with or at risk for diabetes.Keywords: overweight, obesity, type 2 diabetes mellitus, exercise, weight managemen

Association of severity of primary open-angle glaucoma with serum vitamin D levels in patients of African descent.

PurposeTo study the relationship between primary open-angle glaucoma (POAG) in a cohort of patients of African descent (AD) and serum vitamin D levels.MethodsA subset of the AD and glaucoma evaluation study III (ADAGES III) cohort, consisting of 357 patients with a diagnosis of POAG and 178 normal controls of self-reported AD, were included in this analysis. Demographic information, family history, and blood samples were collected from all the participants. All the subjects underwent clinical evaluation, including visual field (VF) mean deviation (MD), central cornea thickness (CCT), intraocular pressure (IOP), and height and weight measurements. POAG patients were classified into early and advanced phenotypes based on the severity of their visual field damage, and they were matched for age, gender, and history of hypertension and diabetes. Serum 25-Hydroxy (25-OH) vitamin D levels were measured by enzyme-linked immunosorbent assay (ELISA). The association of serum vitamin D levels with the development and severity of POAG was tested by analysis of variance (ANOVA) and the paired t-test.ResultsThe 178 early POAG subjects had a visual field MD of better than -4.0 dB, and the 179 advanced glaucoma subjects had a visual field MD of worse than -10 dB. The mean (95% confidence interval [CI]) levels of vitamin D of the subjects in the control (8.02 ± 6.19 pg/ml) and early phenotype (7.56 ± 5.74 pg/ml) groups were significantly or marginally significantly different from the levels observed in subjects with the advanced phenotype (6.35 ± 4.76 pg/ml; p = 0.0117 and 0.0543, respectively). In contrast, the mean serum vitamin D level in controls was not significantly different from that of the subjects with the early glaucoma phenotype (p = 0.8508).ConclusionsIn this AD cohort, patients with advanced glaucoma had lower serum levels of vitamin D compared with early glaucoma and normal subjects

Effect of a Multidisciplinary Team Approach to Eradicate Central Line Associated Blood-Stream Infections (CLABSI)

Introduction: CLABSI remains a significant problem in the intensive care unit. Hypothesis: A multimodal approach for the insertion and care of CVC will prevent CLABSI. Methods: A Critical Care Operations Committee was formed to transform care in 8 intensive care units (ICU) in an academic medical center in 9/2004. One goal was to reduce CLABSI. Using evidence based medicine, a clinical practice guideline was developed that incorporated the use of maximum barrier precautions, chlorhexidine skin preparation, avoidance of the femoral insertion site, dedicated catheter cart, a check list, the tracking of high risk CVC, anti-septic or antimicrobial impregnated catheters, a recommendation to use ultrasound guidance when inserting CVC in the internal jugular vein, daily determination of the need for the CVC and treatment of CLABSI as a critical event.CLABSI were adjudicated by the hospital epidemiologist and CVC days were tracked. Rates of CLABSI were followed from 9/2004 through 7/2011. The Spearman correlation coefficient was used for statistical evaluation. A p Results: CLABSI rates (per 1000 catheter-days) declined dramatically from 2004 to 2011 (p Conclusions: A multimodal approach to CVC insertion and care reduces CLABSI by over 90%. Our ultimate goal is the complete eradication of CRBSI in our institution

Using biomarkers to predict TB treatment duration (Predict TB): a prospective, randomized, noninferiority, treatment shortening clinical trial

Background : By the early 1980s, tuberculosis treatment was shortened from 24 to 6 months, maintaining relapse rates of 1-2%. Subsequent trials attempting shorter durations have failed, with 4-month arms consistently having relapse rates of 15-20%. One trial shortened treatment only among those without baseline cavity on chest x-ray and whose month 2 sputum culture converted to negative. The 4-month arm relapse rate decreased to 7% but was still significantly worse than the 6-month arm (1.6%, P<0.01).  We hypothesize that PET/CT characteristics at baseline, PET/CT changes at one month, and markers of residual bacterial load will identify patients with tuberculosis who can be cured with 4 months (16 weeks) of standard treatment.Methods: This is a prospective, multicenter, randomized, phase 2b, noninferiority clinical trial of pulmonary tuberculosis participants. Those eligible start standard of care treatment. PET/CT scans are done at weeks 0, 4, and 16 or 24. Participants who do not meet early treatment completion criteria (baseline radiologic severity, radiologic response at one month, and GeneXpert-detectable bacilli at four months) are placed in Arm A (24 weeks of standard therapy). Those who meet the early treatment completion criteria are randomized at week 16 to continue treatment to week 24 (Arm B) or complete treatment at week 16 (Arm C). The primary endpoint compares the treatment success rate at 18 months between Arms B and C.Discussion: Multiple biomarkers have been assessed to predict TB treatment outcomes. This study uses PET/CT scans and GeneXpert (Xpert) cycle threshold to risk stratify participants. PET/CT scans are not applicable to global public health but could be used in clinical trials to stratify participants and possibly become a surrogate endpoint. If the Predict TB trial is successful, other immunological biomarkers or transcriptional signatures that correlate with treatment outcome may be identified. TRIAL REGISTRATION: NCT02821832

A Randomized Placebo-Controlled Phase 3 Trial of an Antisense Oligonucleotide, Drisapersen, in Duchenne Muscular Dystrophy

This 48-week, randomized, placebo-controlled phase 3 study (DMD114044; NCT01254019) evaluated efficacy and safety of subcutaneous drisapersen 6 mg/kg/week in 186 ambulant boys aged ≥5 years, with Duchenne muscular dystrophy (DMD) resulting from an exon 51 skipping amenable mutation. Drisapersen was generally well tolerated, with injection-site reactions and renal events as most commonly reported adverse events. A nonsignificant treatment difference (P = 0.415) in the change from baseline in six-minute walk distance (6MWD; primary efficacy endpoint) of 10.3 meters in favor of drisapersen was observed at week 48. Key secondary efficacy endpoints (North Star Ambulatory Assessment, 4-stair climb ascent velocity, and 10-meter walk/run velocity) gave consistent findings. Lack of statistical significance was thought to be largely due to greater data variability and subgroup heterogeneity. The increased standard deviation alone, due to less stringent inclusion/exclusion criteria, reduced the statistical power from pre-specified 90% to actual 53%. Therefore, a post-hoc analysis was performed in 80 subjects with a baseline 6MWD 300-400 meters and ability to rise from floor. A statistically significant improvement in 6MWD of 35.4 meters (P = 0.039) in favor of drisapersen was observed in this subpopulation. Results suggest that drisapersen could have benefit in a less impaired population of DMD subjects

The effectiveness of early lens extraction with intraocular lens implantation for the treatment of primary angle-closure glaucoma (EAGLE) : study protocol for a randomized controlled trial

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