Bilateral visual acuity decline in males with choroideremia: a pooled, cross-sectional meta-analysis

Background Choroideremia is a rare inherited retinal disease that leads to blindness. Visual acuity (VA) is a key outcome measure in choroideremia treatment studies, but VA decline rates change with age. An accurate understanding of the natural deterioration of VA in choroideremia is important to assess the treatment effect of new therapies in which VA is the primary outcome measure. We conducted a meta-analysis of data on individuals with choroideremia to determine the rate of VA deterioration between the better- and worse-seeing eye (BSE and WSE, respectively). Methods Data were collected from the prospective Natural History of the Progression of Choroideremia (NIGHT) study (613 eyes, baseline data only), studies included in a recent meta-analysis, and studies identified in a targeted literature search performed on March 25, 2020, including individual best-corrected VA (BCVA) and age data in male individuals with choroideremia. Best-corrected VA decline rates (measured by logMAR units) by age and trends in BCVA decline rates in the BSE and WSE were evaluated. Results Data from 1037 males (1602 eyes; mean age, 41.8 years) were included. Before and after an age cutoff of 33.8 years, BCVA decline rates for the WSE were 0.0086 and 0.0219 logMAR per year, respectively. Before and after an age cutoff of 39.1 years, BCVA decline rates for the BSE were 0.00001 and 0.0203 logMAR per year, respectively. Differences in absolute BCVA and decline rates increased between the 2 eyes until age ~ 40; thereafter, differences in absolute BCVA and decline rates were similar between eyes. Conclusions Using the largest choroideremia data set to date, this analysis demonstrates accelerated BCVA decline beginning between 30 and 40 years of age. Disparate interocular progression rates were observed before the transition age, with similar interocular progression rates after the transition age.

Hypokalemia Measurement and Management in Patients With Status Asthmaticus on Continuous Albuterol

OBJECTIVE: Status asthmaticus is commonly treated in pediatric patients by using continuous albuterol, which can cause hypokalemia. The primary aim of this study was to determine if serial potassium monitoring is necessary by examining treatment frequency of hypokalemia. METHODS: This retrospective analysis was performed in 185 pediatric patients admitted with status asthmaticus requiring continuous albuterol between 2017 and 2019. All patients were placed on intravenous fluids containing potassium. The primary outcome measure was the treatment of hypokalemia in relation to the number of laboratory draws for potassium levels. The secondary outcome measure was hypokalemia frequency and relation to the duration and initial dose of continuous albuterol. RESULTS: Included were 156 patients with 420 laboratory draws (average, 2.7 per patient) for potassium levels. The median lowest potassium level was 3.40 mmol/L (interquartile range, 3.2–3.7). No correlation was found between initial albuterol dose and lowest potassium level (P = .52). Patients with hypokalemia had a mean albuterol time of 12.32 (SD, 15.76) hours, whereas patients without hypokalemia had a mean albuterol time of 11.50 (SD, 12.53) hours (P = .29). Potassium levels were treated 13 separate times. CONCLUSIONS: The number of laboratory draws for potassium levels was high in our cohort, with few patients receiving treatment for hypokalemia beyond the potassium routinely added to maintenance fluids. Length of time on albuterol and dose of albuterol were not shown to increase the risk of hypokalemia. Serial laboratory measurements may be decreased to potentially reduce health care costs, pain, and anxiety surrounding needlesticks.

National Institutes of Health Stroke Scale as an Outcome in Stroke Research: Value of ANCOVA Over Analyzing Change From Baseline

National Institutes of Health Stroke Scale (NIHSS), measured a few hours to days after stroke onset, is an attractive outcome measure for stroke research. NIHSS at the time of presentation (baseline NIHSS) strongly predicts the follow-up NIHSS. Because of the need to account for the baseline NIHSS in the analysis of follow-up NIHSS as an outcome measure, a common and intuitive approach is to define study outcome as the change in NIHSS from baseline to follow-up (ΔNIHSS). However, this approach has important limitations. Analyzing ΔNIHSS implies a very strong assumption about the relationship between baseline and follow-up NIHSS that is unlikely to be satisfied, drawing into question the validity of the resulting statistical analysis. This reduces the precision of the estimates of treatment effects and the power of clinical trials that use this approach to analysis. ANCOVA allows for the analysis of follow-up NIHSS as the dependent variable while adjusting for baseline NIHSS as a covariate in the model and addresses several challenges of using ΔNIHSS outcome using simple bivariate comparisons (eg, a t test, Wilcoxon rank-sum, linear regression without adjustment for baseline) for stroke research. In this article, we use clinical trial simulations to illustrate that variability in NIHSS outcome is less when follow-up NIHSS is adjusted for baseline compared to ΔNIHSS and how a reduction in this variability improves the power. We outline additional, important clinical and statistical arguments to support the superiority of ANCOVA using the final measurement of the NIHSS adjusted for baseline over, and caution against using, the simple bivariate comparison of absolute NIHSS change (ie, delta).

Distance to first symptoms measured by the 6-min walking test differentiates between treatment success and failure in patients with degenerative lumbar disorders

Purpose The smartphone-based 6-min walking test (6WT) is an established digital outcome measure in patients undergoing surgery for degenerative lumbar disorders (DLD). In addition to the 6WTs primary outcome measure, the 6-min walking distance (6WD), the patient’s distance to first symptoms (DTFS) and time to first symptoms (TTFS) can be recorded. This is the first study to analyse the psychometric properties of the DTFS and TTFS. Methods Forty-nine consecutive patients (55 ± 15.8 years) completed the 6WT pre- and 6 weeks (W6) postoperative. DTFS and TTFS were assessed for reliability and content validity using disease-specific patient-reported outcome measures. The Zurich Claudication Questionnaire patient satisfaction subscale was used as external criterion for treatment success. Internal and external responsiveness for both measures at W6 was evaluated. Results There was a significant improvement in DTFS and TTFS from baseline to W6 (p < 0.001). Both measures demonstrated a good test–retest reliability (β = 0.86, 95% CI 0.81–0.90 and β = 0.83, 95% CI 0.76–0.87, both p < 0.001). The DTFS exceeded the 6WD capability to differentiate between satisfied (82%) and unsatisfied patients (18%) with an AUC of 0.75 (95% CI 0.53–0.98) vs. 0.70 (95% CI 0.52–0.90). The TTFS did not demonstrate meaningful discriminative abilities. Conclusion Change in DTFS can differentiate between satisfied and unsatisfied patients after spine surgery. Digital outcome measures on the 6WT metric provide spine surgeons and researchers with a mean to assess their patient’s functional disability and response to surgical treatment in DLD.

Burden and outcome of neonatal surgical conditions in Nigeria: A countrywide multicenter cohort study

Background: Despite a decreasing global neonatal mortality, the rate in sub-Saharan Africa is still high. The contribution and the burden of surgical illness to this high mortality rate have not been fully ascertained. This study is performed to determine the overall and disease-specific mortality and morbidity rates following neonatal surgeries; and the pre, intra, and post-operative factors affecting these outcomes. Methods: This was a prospective observational cohort study; a country-wide, multi-center observational study of neonatal surgeries in 17 tertiary hospitals in Nigeria. The participants were 304 neonates that had surgery within 28 days of life. The primary outcome measure was 30-day postoperative mortality and the secondary outcome measure was 30-day postoperative complication rates. Results: There were 200 (65.8%) boys and 104 (34.2%) girls, aged 1-28 days (mean of 12.1 ± 10.1 days) and 99(31.6%) were preterm. Sepsis was the most frequent major postoperative complication occurring in 97(32%) neonates. Others were surgical site infection (88, 29.2%) and malnutrition (76, 25.2%). Mortality occurred in 81 (26.6%) neonates. Case-specific mortalities were: gastroschisis (14, 58.3%), esophageal atresia (13, 56.5%) and intestinal atresia (25, 37.2%). Complications significantly correlated with 30-day mortality (p <0.05). The major risk predictors of mortality were apnea (OR=10.8), severe malnutrition (OR =6.9), sepsis (OR =7. I), deep surgical site infection (OR=3.5), and re-operation (OR=2.9). Conclusion: Neonatal surgical mortality is high at 26.2%. Significant mortality risk factors include prematurity, apnea, malnutrition, and sepsis.

Social communication in fragile X syndrome: pilot examination of the Brief Observation of Social Communication Change (BOSCC)

Background Social communication is a key area of difficulty in fragile X syndrome (FXS) and there are not yet adequate outcome measurement tools. Appropriate outcome measures for FXS have been identified as a key area of research interest in order to evaluate future therapeutic trials. The Brief Observation of Social Communication Change-Minimally Verbal (BOSCC-MV), an outcome measure with strong psychometrics developed for autism spectrum disorder, has promise as an outcome measure to assess social communication change with FXS participants. Methods We examined the BOSCC-MV via central coders in this multi-site-trial to assess its appropriateness for FXS. Eighteen minimally verbal males ages 3–12 years were enrolled and assessed on two consecutive days and 7 participants completed a third visit 6 months later. We examined test-retest reliability, inter-rater reliability, and both convergent and divergent validity with standard clinical measures including the Autism Diagnostic and Observation Schedule-2, Vineland 3, Social Responsiveness Scale, and the Aberrant Behavior Checklist. Results The BOSCC-MV in FXS demonstrated strong inter-rater and test-retest reliability, comparable to previous trials in idiopathic ASD. Strong convergent validity was found with Autism Diagnostic Observation Schedule-2 and Vineland-3. Divergent validity was demonstrated between BOSCC-MV and unrelated measures. Conclusions The BOSCC-MV shows promise as a FXS social communication outcome measure, warranting further large-scale evaluation.

Using mHealth to promote parents’ brushing of preschool children’s teeth: a protocol for a randomized factorial trial using the Multi-phase Optimization Strategy (MOST)

Background Early childhood caries is a highly prevalent disease affecting young children. Parental brushing of children’s teeth is recommended during preschool years. Interventions to promote parental brushing of children’s teeth are assessed as a package in randomized clinical trials and the efficacy of separate components is not known. Methods and analysis The aim of this study is to develop an optimized behavior modification intervention to increase parents’ brushing of their pre-school children’s teeth using the multi-phase optimization strategy (MOST) guided by the Theory of Planned Behavior. Behavior change will be assessed by the percent reduction in children’s dental plaque index after 6 months and parents reporting of toothbrushing frequency. Two phases of MOST will be carried out. First, the preparation phase comprises the development of a conceptual framework, identifying candidate components, conducting a feasibility pilot study to assess the acceptability and the design features of three intervention components (motivational interviewing (MI), and two mobile health (mHealth) components: oral health promotion messages and storytelling videos delivered using WhatsApp messenger) in addition to setting an optimization objective. Second, the optimization phase constitutes a factorial trial assessing the three intervention components and developing the intervention by selecting the most effective components within the optimization constraint. Each component will be set at two levels: yes (the intervention is applied) and no (the intervention is not applied). A linear regression model will be used to assess the effect of the intervention components on the percent reduction in dental plaque index (primary outcome measure). The secondary outcome measure is the change in the frequency of parents’ brushing of the child’s teeth. The combination of components making up the new optimized intervention will be selected. Discussion This will be the first study to apply the MOST framework in the field of dentistry. The results of this study can guide the development of an optimized behavior modification interventions using mHealth and MI. Trial registration ClinicalTrials.gov, NCT04923581, Registered 11 June 2021.