Wide Confidence Intervals Research Articles

Accelerated, physics-inspired inference of skeletal muscle microstructure from diffusion-weighted MRI.

Muscle health is a critical component of overall health and quality of life. However, current measures of skeletal muscle health take limited account of microstructural variations within muscle, which play a crucial role in mediating muscle function. To address this, we present a physics-inspired, machine learning-based framework for the non-invasive estimation of microstructural organization in skeletal muscle from diffusion-weighted MRI (dMRI) in an uncertainty-aware manner. To reduce the computational expense associated with direct numerical simulations of dMRI physics, a polynomial meta-model is developed that accurately represents the input/output relationships of a high-fidelity numerical model. This meta-model is used to develop a Gaussian process (GP) model that provides voxel-wise estimates and confidence intervals of microstructure organization in skeletal muscle. Given noise-free data, the GP model accurately estimates microstructural parameters. In the presence of noise, the diameter, intracellular diffusion coefficient, and membrane permeability are accurately estimated with narrow confidence intervals, while volume fraction and extracellular diffusion coefficient are poorly estimated and exhibit wide confidence intervals. A reduced-acquisition GP model, consisting of one-third the diffusion-encoding measurements, is shown to predict parameters with similar accuracy to the original model. The fiber diameter and volume fraction estimated by the reduced GP model is validated via histology, with both parameters accurately estimated, demonstrating the capability of the proposed framework as a promising non-invasive tool for assessing skeletal muscle health and function.

Postural alignment is impaired in adults with severe mobility limitations after an acquired brain injury: an observational study

Background: Postural alignment impairments can be observed after acquired brain injury (ABI) and may be more prevalent in people with greater mobility impairment. However, investigations of postural alignment are limited by the lack of an evaluated method of assessment. This study examined postural alignment differences between healthy adults and adults with ABI, and evaluated repeatability of a new kinematic method for measuring postural alignment. Methods: Observational study of 14 adults with ABI who were non-ambulant at eight weeks post-injury, and 14 healthy adults. 3D kinematic data were recorded using motion capture technology in sitting and standing, on two separate days. A new Postural Alignment and Dispersion (PAD) score quantified average body segment displacements from the base of support (BoS) in the transverse plane. The two groups’ PAD scores were compared. Repeatability of the PAD score between days was evaluated using intraclass correlation coefficients (ICCs). Major findings: Greater postural alignment deviations were observed after ABI, including marked deficits in frontal and sagittal planes. ICCs ranged moderate (0.614) to excellent (0.945). Wide confidence intervals (CIs) for some ICCs indicated that repeatability of PAD scores could not be assured for all sitting and standing conditions. Conclusions: Postural alignment impairments occur in multiple planes after ABI and can be pronounced in people with severe mobility impairment. Evidence is needed to determine if addressing postural alignment impairments affects functional progress after ABI. PAD score measurement requires further evaluation to determine how repeatability can be optimised.

Doppler ultrasound surveillance of recently formed haemodialysis arteriovenous fistula: the SONAR observational cohort study.

Arteriovenous fistulas are considered the best option for haemodialysis provision, but as many as 30% fail to mature or suffer early failure. To assess the feasibility of performing a randomised controlled trial that examines whether, by informing early and effective salvage intervention of fistulas that would otherwise fail, Doppler ultrasound surveillance of developing arteriovenous fistulas improves longer-term arteriovenous fistula patency. A prospective multicentre observational cohort study (the 'SONAR' study). Seventeen haemodialysis centres in the UK. Consenting adults with end-stage renal disease who were scheduled to have an arteriovenous fistula created. Participants underwent Doppler ultrasound surveillance of their arteriovenous fistulas at 2, 4, 6 and 10 weeks after creation, with clinical teams blinded to the ultrasound surveillance findings. Fistula maturation at week 10 defined according to ultrasound surveillance parameters of representative venous diameter and blood flow (wrist arteriovenous fistulas: ≥ 4 mm and > 400 ml/minute; elbow arteriovenous fistulas: ≥ 5 mm and > 500 ml/minute). Mixed multivariable logistic regression modelling of the early ultrasound scan data was used to predict arteriovenous fistula non-maturation by 10 weeks and fistula failure at 6 months. A total of 333 arteriovenous fistulas were created during the study window (47.7% wrist, 52.3% elbow). By 2 weeks, 37 (11.1%) arteriovenous fistulas had failed (thrombosed), but by 10 weeks, 219 of 333 (65.8%) of created arteriovenous fistulas had reached maturity (60.4% wrist, 67.2% elbow). Persistently lower flow rates and venous diameters were observed in those fistulas that did not mature. Models for arteriovenous fistulas' non-maturation could be optimally constructed using the week 4 scan data, with fistula venous diameter and flow rate the most significant variables in explaining wrist fistula maturity failure (positive predictive value 60.6%, 95% confidence interval 43.9% to 77.3%), whereas resistance index and flow rate were most significant for elbow arteriovenous fistulas (positive predictive value 66.7%, 95% confidence interval 48.9% to 84.4%). In contrast to non-maturation, both models predicted fistula maturation much more reliably [negative predictive values of 95.4% (95% confidence interval 91.0% to 99.8%) and 95.6% (95% confidence interval 91.8% to 99.4%) for wrist and elbow, respectively]. Additional follow-up and modelling on a subset (n = 192) of the original SONAR cohort (the SONAR-12M study) revealed the rates of primary, assisted primary and secondary patency arteriovenous fistulas at 6 months were 76.5, 80.7 and 83.3, respectively. Fistula vein size, flow rate and resistance index could identify primary patency failure at 6 months, with similar predictive power as for 10-week arteriovenous fistula maturity failure, but with wide confidence intervals for wrist (positive predictive value 72.7%, 95% confidence interval 46.4% to 99.0%) and elbow (positive predictive value 57.1%, 95% confidence interval 20.5% to 93.8%). These models, moreover, performed poorly at identifying assisted primary and secondary patency failure, likely because a subset of those arteriovenous fistulas identified on ultrasound surveillance as at risk underwent subsequent successful salvage intervention without recourse to early ultrasound data. Although early ultrasound can predict fistula maturation and longer-term patency very effectively, it was only moderately good at identifying those fistulas likely to remain immature or to fail within 6 months. Allied to the better- than-expected fistula patency rates achieved (that are further improved by successful salvage), we estimate that a randomised controlled trial comparing early ultrasound-guided intervention against standard care would require at least 1300 fistulas and would achieve only minimal patient benefit. This trial is registered as ISRCTN36033877 and ISRCTN17399438. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR135572) and is published in full in Health Technology Assessment; Vol. 28, No. 24. See the NIHR Funding and Awards website for further award information.

Fluid balance versus weighing: A comparison in ICU patients: A single center observational study.

The fluid balance is a critical parameter in intensive care units (ICU) as it provides information about the patient's volume status. However, the accuracy of fluid balance measurements is often compromised due to the complexity and repetition of actions involved. Additionally, the fluid balance could be recalculated for insensible fluid loss. Weighing is an alternative method to estimate the patient's volume status. Built-in scales in beds make patient weighing easier and less time-consuming, allowing clinicians to intervene more quickly on existing treatments. This study compares fluid balance, and body weight changes over time in ICU patients. Furthermore, it seeks to determine the degree of congruence between the fluid balance corrected for insensible fluid loss and daily body weight in ICU patients. A single-center observational study was conducted in an ICU of a university hospital. All consecutive patients admitted to a bed with an integrated weighing scale were eligible. Exclusion criteria were (1) body weight ≥254,4 kilograms; (2) oral nutrition; (3) a flush catheter or balance; (4) only a single weight measurement; (5) delta body weight change of ≥5kg in 12 hours. Weights and fluid balances were obtained every 12 hours. We obtained 2282 measurements (n = 187 patients). The correlation between weight and fluid balance was weak (r = 0.274). After adjusting the fluid balance for insensible fluid loss, the correlation remained weak (r = 0,268). Bland Altman analysis revealed a wide confidence interval for both the fluid balance and corrected fluid balance versus weight. This study shows a weak correlation between weight and fluid balance. Therefore, when monitoring the volume status in the ICU, fluid balance and weight should both be taken into account. This two-pronged approach is crucial because it provides more control over erroneous fluid balance or weighing measurements.

Effect of combination treatment with glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors on incidence of cardiovascular and serious renal events: population based cohort study

ObjectiveTo determine whether the combined use of glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors is associated with a decreased risk of major adverse cardiovascular events and serious...

Fixed width confidence interval estimation for general continuous responses under a response adaptive design

. A fixed width confidence interval for the treatment difference is obtained under heteroscedastic normal responses following a response adaptive allocation targeting Neyman optimum allocation. The developed procedure is further extended for general location-scale model based responses under a compound response adaptive allocation. The developed procedures are studied theoretically and are supported empirically assuming various response models. A real data study is also provided following the proposed procedure for the purpose of illustration.

Modelling the replacement of red and processed meat with plant-based alternatives and the estimated effect on insulin sensitivity in a cohort of Australian adults

Dietary guidelines are increasingly promoting plant-based diets, limits on red meat consumption, and plant-based sources of protein for health and environmental reasons(1). It is unclear how the resulting food substitutions associate with insulin resistance, a risk factor for type 2 diabetes. Here, we modelled the replacement of red and processed meat with plant-based alternatives and the estimated effect on insulin sensitivity. We included 783 participants (55% female) from the Childhood Determinants of Adult Health (CDAH) study, a population-based cohort of Australians. In adulthood, diet was assessed at three time points using food frequency questionnaires: CDAH-1 (2004–06), CDAH-2 (2009–11), and CDAH-3 (2017–19). The median follow-up duration was 13 years. The cumulative average intake of each food group was calculated to reflect habitual consumption. Insulin sensitivity (%) was estimated from fasting glucose and insulin concentrations at CDAH-3 (aged 39–49 years) using homeostasis model assessment. Applying the partition model(2), we simulated the replacement of one food group with another by including both in the model simultaneously (e.g., red meat and legumes), along with potential confounders and energy intake. The difference between parameter estimates (i.e., regression coefficients and variances) and their covariance were used to estimate the “substitution” effect. We report the simulated percentage point change in log-transformed insulin sensitivity for a 1 serve/day lower intake of one food group with a 1 serve/day higher intake of another food group. Replacing red meat with a combination of plant-based alternatives was associated with higher insulin sensitivity (β = 0·10, 95% CI 0·04–0·16). Adjustment for waist circumference attenuated this association by 61·4%. On an individual basis, replacing red meat with legumes (β = 0·12, 95% CI 0·02–0·21), nuts and seeds (β = 0·15, 95% CI 0·06–0·23), or whole grains (β = 0·11, 95% CI 0·04–0·17) was likewise associated with higher insulin sensitivity. Point estimates were similar when replacing processed meat with plant-based alternatives, but more uncertain due to wide confidence intervals. Our modelling suggests that habitually replacing red meat, and possibly processed meat, with plant-based alternatives may associate with higher insulin sensitivity, and thus, a lower risk of type 2 diabetes. Abdominal adiposity was identified as a potentially important mediator in this relationship. In relation to insulin sensitivity, our findings support the recommendation to choose plant-based sources of protein at the expense of red meat consumption.

Pelvic floor disorders and impact on sexual function: a cross-sectional study among non-sexually active and sexually active women.

Pelvic floor disorders are common and associated with impaired sexual function in women. To assess women with pelvic floor disorders and describe factors associated with not being sexually active and those associated with sexual function in sexually active women. A cross-sectional study was conducted that included nonpregnant women with symptoms of pelvic floor disorders who were referred to the urogynecologic and surgical outpatient clinic at 2 Norwegian university hospitals: St Olavs Hospital, Trondheim University Hospital, and the University Hospital of Northern Norway, Tromsø. Women answered a questionnaire anonymously. Pelvic Organ Prolapse Incontinence Sexual Questionnaire-IUGA Revised. Of 157 respondents, 111 (71%) reported being sexually active (with or without a partner), and 46 (29%) reported not being sexually active. As compared with sexually active women, not sexually active women were older (mean ± SD, 60.2 ± 13.3 vs 51 ± 12.1 years; P < .001), more were menopausal (78% vs 47%, P = .001), and more had symptom debut <1year (31% vs 9%, P < .001). They reported more distress related to pelvic floor disorders, especially pelvic organ prolapse. In a multivariate logistic regression analysis, menopausal women and women with symptom debut <1year were 4 times more likely to be not sexually active than premenopausal women (odds ratio, 4.0; 95% CI, 1.7-9.2) and women with symptom debut ≥1year (odds ratio, 4.0; 95% CI, 1.5-10.7). In sexually active women, colorectal-anal distress was negatively associated with 5 of 6 domains of sexual function: arousal/orgasm (ß = -0.36; 95% CI, -0.02 to -0.005), partner related (ß = -0.28; 95% CI, -0.01 to -0.002), condition specific (ß = -0.39; 95% CI, -0.002 to -0.009), global quality (ß = -0.23; 95% CI, -0.02 to -0.002), and condition impact (ß = -0.34; 95% CI, -0.02 to -0.006). Health care professionals should discuss sexual function in patients with pelvic floor disorders, especially menopausal women and women with colorectal-anal symptoms. The study used condition-specific measures and recruited women from 2 university hospitals with wide range of age. Limitations include the small sample size and wide confidence intervals. The number of women who considered themselves not sexually active was low, and item nonresponse levels among these women where somewhat high. Of 625 eligible women, 200 (32%) answered the questionnaire. Sexual health and sexual function are still surrounded with taboo, and some women were probably not comfortable answering the questions. Menopausal women and women with recent onset of symptoms of pelvic floor disorders are more likely to be sexually inactive, and colorectal-anal symptoms have the most negative impact on sexual function in sexually active women.

Evaluating screening for autism spectrum disorder using cluster randomization

We evaluated the rate of autism spectrum disorder (ASD) in a group invited to a screening program compared to the rates in two groups who received usual care. The population eligible for screening was all children in Iceland registered for their 30-month well-child visits at primary healthcare centers (PHCs) from March 1, 2016, to October 31, 2017 (N = 7173). The PHCs in the capital area of Reykjavik were the units of cluster randomization. Nine PHCs were selected for intervention (invited group), while eight PHCs received usual care (control group 1). PHCs outside the capital area were without randomization (control group 2). An interdisciplinary team, including a pediatrician contributing with physical and neurological examination, a psychologist evaluating autism symptoms using a diagnostic instrument, and a social worker interviewing the parents, reached a consensus on the clinical diagnosis of ASD according to the ICD-10 diagnostic system. Children in the population were followed up for at least two years and 119 cases were identified. The overall cumulative incidence of ASD was 1.66 (95% confidence interval (CI): 1.37, 1.99). In the invited group the incidence rate was 2.13 (95% CI: 1.60, 2.78); in control group 1, the rate was 1.83 (95% CI: 1.31, 2.50); and in control group 2, the rate was 1.02 (95% CI: 0.66, 1.50). Although the rate of ASD was higher in the invited group than in the control groups, the wide confidence intervals prevented us from concluding definitively that the screening detected ASD more readily than usual care.

Neuromuscular Control and Resistance Training for People With Chronic Low Back Pain: A Randomized Controlled Trial.

OBJECTIVE: To determine if adding lumbar neuromuscular control retraining exercises to a 12-week program of strengthening exercises had greater effect for improving disability than 12 weeks of strengthening exercises alone in people with chronic low back pain (LBP). DESIGN: Single-center, participant- and assessor-blinded, comparative effectiveness randomized controlled trial. METHODS: Sixty-nine participants (31 females; 29 males; mean age: 46.5 years) with nonspecific chronic LBP were recruited for a 12-week program involving lumbar extension neuromuscular retraining in addition to resistance exercises (intervention) or 12 weeks of resistance exercises alone (control). The primary outcome measure was the Oswestry Disability Index. Secondary outcome measures included the Numeric Rating Scale, Tampa Scale for Kinesiophobia, Pain Self-Efficacy Questionnaire, and the International Physical Activity Questionnaire. Outcomes were measured at baseline, 6 weeks, and 12 weeks. RESULTS: Forty-three participants (22 control, 21 intervention) completed all outcome measures at 6 and 12 weeks. Fourteen participants were lost to follow-up, and 12 participants discontinued due to COVID-19 restrictions. Both groups demonstrated clinically important changes in disability, pain intensity, and kinesiophobia. The difference between groups with respect to disability was imprecise and not clinically meaningful (mean difference, -4.4; 95% CI: -10.2, 1.4) at 12 weeks. Differences in secondary outcomes at 6 or 12 weeks were also small with wide confidence intervals. CONCLUSIONS: Adding lumbar neuromuscular control retraining to a series of resistance exercises offered no additional benefit over resistance exercises alone over a 12-week period. J Orthop Sports Phys Ther 2024;54(5):1-10. Epub 18 March 2024. doi:10.2519/jospt.2024.12349.

Adverse pregnancy outcomes in pregnant women with chronic kidney disease: A systematic review and meta-analysis.

Chronic kidney disease (CKD) is associated with an increased risk of adverse pregnancy outcomes, but the risk at different stages of CKD (defined by estimated glomerular filtration rate, eGFR) compared with women without CKD has not been quantified in large cohorts. To quantify the association between CKD and adverse pregnancy outcomes according to CKD definition, CKD stage and presence or absence of diabetes. A systematic search of EMBASE and MEDLINE from inception to 5 January 2023. English-language randomised controlled trials as well as cohort and case-control studies investigating adverse pregnancy outcomes in pregnant women with CKD. Two reviewers conducted independent data extractions. A random-effects model was used to estimate risk. We included 19 studies with 3 251 902 women. Defining CKD using eGFR or serum creatinine produced results with greater effect size but wider confidence intervals. Compared with CKD stages 1-2, women with CKD stages 3-5 have a greater risk, but also greater imprecision in the risk estimate, of the following outcomes: pre-eclampsia (OR 55.18, 95% CI 2.63-1157.68, vs OR 24.74, 95% CI 1.75-348.70), preterm birth (OR 20.24, 95% CI 2.85-143.75, vs OR 8.18, 95% CI 1.54-43.46) and neonatal intensive care unit admission (OR 19.32, 95% CI 3.07-121.68, vs OR 9.77, 95% CI 2.49-38.39). Women with diabetic kidney disease, compared with women without diabetic kidney disease, have higher risks of maternal mortality, small-for-gestational-age neonates, pre-eclampsia and gestational hypertension. There is heterogeneity in the definition of CKD in pregnancy. Future studies should consider ways to standardise its definition and measurement in pregnancy.

Decreased circulating omega-3 fatty acids increase the risk of myocardial infarction: a two-sample Mendelian randomization study.

Many studies have shown that omega-3 fatty acids may play critical roles in cardiovascular diseases. Myocardial infarction (MI) typically results from a thrombotic occlusion of a coronary artery leading to myocardial ischemia. Thus, this study aims to examine the association between omega-3 fatty acids and MI. A two-sample Mendelian randomization study was used to explore the causal relationship between circulating omega-3 fatty acids and the risk of MI performed by MR-Egger regression, inverse-variance weighted (IVW), weighted median, and weighted mode. Five single-nucleotide polymorphisms strongly related to circulating omega-3 fatty acids were selected as instrumental variables from a published genome-wide association study (GWAS) meta-analysis including 13,544 subjects. We extracted summary data for the risk of MI from another GWAS meta-analysis including 171,875 individuals (43,676 cases and 128,199 controls). The genetically predicted lower circulating omega-3 increased the risk of myocardial infarction showed by the results of IVW [odds ratio (OR) = 1.224, 95% CI = 1.045-1.433, P = 0.012], weighted median method (OR = 1.171, 95% CI = 1.042-1.315, P = 0.008), and weighted mode (OR = 1.149, 95% CI = 1.002-1.317, P = 0.117), although the result of MR-Egger was not significant (OR = 0.950, 95% CI = 0.513-1.760, P = 0.880) with a wider confidence interval. The findings from our Mendelian randomization analysis suggest that the association between omega-3 fatty acid levels and MI is likely causal.

Comparison of the applicability of seven calculation equations of glomerular filtration rate among elderly people in China

BackgroundAt present, estimated glomerular filtration rate (eGFR) remains the most frequently utilized parameter in the evaluation of kidney injury severity. Numerous equations have been formulated based on serum creatinine (Scr) or serum cystatin C (Cysc) levels. However, there is a lack of consensus regarding the efficacy of these equations in assessing eGFR, particularly for elderly individuals in China. This study aimed to evaluate the applicability of the MDRD, MDRDc, CKD-EPI series, BIS1, and FAS equations within the Chinese elderly population.MethodsA cohort of 298 elderly patients with measured GFR (mGFR) was enrolled. The patients were categorized into three subgroups based on their mGFR levels. The eGFR performance was examined, taking into account bias, interquartile range (IQR), accuracy P30, and root-mean-square error (RMSE). Bland–Altman plots were employed to verify the validity of eGFR.ResultsThe participants had a median age of 71 years, with 167 (56.0%) being male. Overall, no significant differences in bias were observed among the seven equations (P > 0.05). In terms of IQR, P30, and RMSE, the BIS1 equation demonstrated superior accuracy (14.61, 72.1%, and 13.53, respectively). When mGFR < 30 ml/min/1.73 m2, all equations underestimated the true GFR, with the highest accuracy reaching only 59%. Bland–Altman plots indicated that the BIS1 equation exhibited the highest accuracy, featuring a 95% confidence interval (CI) width of 52.37.ConclusionsThis study suggested that the BIS1 equation stands out as the most applicable for estimating GFR in Chinese elderly patients with normal renal function or only moderate decline. 2020NL-085-03, 2020.08.10, retrospectively registered.

Better tools for better estimates: improving approaches to handling missing data in Swiss cancer registries.

Various approaches have been used in the literature to handle missing vital status data in cancer registries. We aimed to compare these approaches to determine which led to the least biased estimates in typical analytic tasks of cancer registries. A simulation study was performed using data from the Swiss National Agency for Cancer Registration for six tumor types. First, 5%, 10% and 15% missingness in the vital status were introduced artificially in the complete data. Second, missing vital status data were handled by applying no, single or multiple imputations. Five-year overall survival estimates, relative survival or standardized incidence ratio were computed. Estimates were compared with the true value. Standardized incidence ratio estimates for colorectal cancer obtained with multiple imputation yielded least biased results (-0.06 to -0.04), but the widest confidence intervals. Single imputation was more biased (-0.32) than using no imputation at all (-0.21). A similar pattern was observed for overall survival and relative survival. This simulation study indicated that often used single imputation (sometimes referred to as simulating follow-up times) techniques to fill in missing vital status data are likely too biased to be useful in practice. Multiple imputation approaches yielded standardized incidence ratio, overall and relative survival estimates with the least bias, indicating reasonable performance that is likely to generalize to other settings.

A register and questionnaire study of long-term general health symptoms following SARS-CoV-2 vaccination in Denmark

Many individuals who refuse COVID-19 vaccination have concerns about long-term side effects. Here, we report findings on self-reported symptoms from a Danish survey- and register study. The study included 34,868 vaccinated primary course recipients, 95.8% of whom received mRNA vaccines, and 1,568 unvaccinated individuals. Participants had no known history of SARS-CoV-2 infection. Using g-computation on logistic regression, risk differences (RDs) for symptoms between vaccinated and unvaccinated persons were estimated with adjustments for possible confounders. Within six weeks after vaccination, higher risks were observed for physical exhaustion (RD 4.9%, 95% CI 1.1% to 8.4%), fever or chills (RD 4.4%, 95% CI 2.1% to 6.7%), and muscle/joint pain (RD 7.0%, 95% CI 3.1% to 10.7%), compared to unvaccinated individuals. Beyond twenty-six weeks, risks were higher among the vaccinated for sleeping problems (RD 3.0, 95% 0.2 to 5.8), fever or chills (RD 2.0, 95% CI 0.4 to 3.6), reduced/altered taste (RD 1.2, 95% CI 0.2 to 2.3) and shortness of breath (RD 2.6, 95% CI 0.9 to 4.0). However, when examining pre-omicron responses only, the difference for reduced/altered taste was significant. As expected, the risk of experiencing physical exhaustion, fever or chills, and muscle/joint pain was higher among persons who responded within six weeks of completing the primary course. No significant differences were observed for the 7-25-week period after vaccination. Associations for the period beyond 26 weeks must be interpreted with caution and in the context of undetected SARS-CoV-2 infection, wide confidence intervals, and multiple testing. Overall, we observe no concerning signs of long-term self-reported physical, cognitive, or fatigue symptoms after vaccination.

Sample size determination for interval estimation of the prevalence of a sensitive attribute under non-randomized response models.

A sufficient number of participants should be included to adequately address the research interest in the surveys with sensitive questions. In this paper, sample size formulas/iterative algorithms are developed from the perspective of controlling the confidence interval width of the prevalence of a sensitive attribute under four non-randomized response models: the crosswise model, parallel model, Poisson item count technique model and negative binomial item count technique model. In contrast to the conventional approach for sample size determination, our sample size formulas/algorithms explicitly incorporate an assurance probability of controlling the width of a confidence interval within the pre-specified range. The performance of the proposed methods is evaluated with respect to the empirical coverage probability, empirical assurance probability and confidence width. Simulation results show that all formulas/algorithms are effective and hence are recommended for practical applications. A real example is used to illustrate the proposed methods.

Assessment of a screening tool to aid home-based identification of adolescents (aged 10-14) living with HIV in Zambia and South Africa: HPTN 071 (PopART) study.

The HPTN071 (PopART) for Youth (P-ART-Y) study evaluated the acceptability and uptake of a community-level combination HIV prevention package including universal testing and treatment (UTT) among young people in Zambia and South Africa. We determined whether a four-question primary care level screening tool, validated for use in clinical settings, could enhance community (door-to-door) identification of undiagnosed HIV-positive younger adolescents (aged 10-14) who are frequently left out of HIV interventions. Community HIV-care Providers (CHiPs) contacted and consented adolescents in their homes and offered them participation in the PopART intervention. CHiPs used a four question-screening tool, which included: history of hospital admission; recurring skin problems; poor health in last 3 months; and death of at least one parent. A "yes" response to one or more questions was classified as being "at risk" of being HIV-positive. Rapid HIV tests were offered to all children. Data were captured through an electronic data capture device from August 2016 to December 2017. The sensitivity, specificity, positive predictive value and negative predictive value were estimated for the screening tool, using the rapid HIV test result as the gold standard. In our 14 study sites, 33,710 adolescents aged 10-14 in Zambia and 8,610 in South Africa participated in the study. About 1.3% (427/33,710) and 1.2% (106/8,610) self-reported to be HIV positive. Excluding the self-reported HIV-positive, we classified 11.3% (3,746/33,283) of adolescents in Zambia and 17.5% (1,491/8,504) in South Africa as "at risk". In Zambia the estimated sensitivity was 35.3% (95% CI 27.3%-44.2%) and estimated specificity was 88.9% (88.5%-89.2%). In South Africa the sensitivity was 72.3% (26.8%-94.9%) and specificity was 82.5% (81.6-83.4%). The sensitivity of the screening tool in a community setting in Zambia was low, so this tool should not be considered a substitute for universal testing where that is possible. In South Africa the sensitivity was higher, but with a wide confidence interval. Where universal testing is not possible the tool may help direct resources to adolescents more likely to be living with undiagnosed HIV. Clinical Trial Number: NCT01900977.

Comparison of statistical methods used to meta-analyse results from interrupted time series studies: an empirical study

BackgroundThe Interrupted Time Series (ITS) is a robust design for evaluating public health and policy interventions or exposures when randomisation may be infeasible. Several statistical methods are available for the analysis and meta-analysis of ITS studies. We sought to empirically compare available methods when applied to real-world ITS data.MethodsWe sourced ITS data from published meta-analyses to create an online data repository. Each dataset was re-analysed using two ITS estimation methods. The level- and slope-change effect estimates (and standard errors) were calculated and combined using fixed-effect and four random-effects meta-analysis methods. We examined differences in meta-analytic level- and slope-change estimates, their 95% confidence intervals, p-values, and estimates of heterogeneity across the statistical methods.ResultsOf 40 eligible meta-analyses, data from 17 meta-analyses including 282 ITS studies were obtained (predominantly investigating the effects of public health interruptions (88%)) and analysed. We found that on average, the meta-analytic effect estimates, their standard errors and between-study variances were not sensitive to meta-analysis method choice, irrespective of the ITS analysis method. However, across ITS analysis methods, for any given meta-analysis, there could be small to moderate differences in meta-analytic effect estimates, and important differences in the meta-analytic standard errors. Furthermore, the confidence interval widths and p-values for the meta-analytic effect estimates varied depending on the choice of confidence interval method and ITS analysis method.ConclusionsOur empirical study showed that meta-analysis effect estimates, their standard errors, confidence interval widths and p-values can be affected by statistical method choice. These differences may importantly impact interpretations and conclusions of a meta-analysis and suggest that the statistical methods are not interchangeable in practice.

Power outages and pediatric unintentional injury hospitalizations in New York State.

In the past decade, electrical power disruptions (outages) have increased in the United States, especially those attributable to weather events. These outages have a range of health impacts but are largely unstudied in children. Here, we investigated the association between outages and unintentional injury hospitalizations, a leading cause of childhood morbidity. The study setting was New York State (NYS) from 2017 to 2020. Outage exposure was defined as ≥10%, ≥20%, and ≥50% of customers from a power operating locality without power, ascertained from NYS Department of Public Service records and stratified by rural, urban non-New York City (NYC), and NYC regions. Outcome daily block group-level pediatric injury hospitalization data was from the Statewide Planning and Research Cooperative System (SPARCS). We leveraged a case-crossover study design with logistic conditional regression. We identified 23,093 unintentional injury hospitalizations in children <18 years with complete block group and exposure data. Most hospitalizations occurred in urban regions (90%), whereas outages were more likely in rural than urban areas. In urban non-NYC regions, outages ≥4 hours were associated with 30% increased odds of all-cause unintentional injury hospitalizations when ≥50% of customers were without power. Analyses by injury subtype revealed increasing point estimates as the proportion of customers exposed increased. These results, however, had wide confidence intervals. Outage exposure differed significantly across rural, urban non-NYC, and NYC regions across New York. Especially at the highest outage threshold, we observed an increased risk of pediatric unintentional injury hospitalizations.

Abstract TMP56: Accuracy of Dual-Energy Computed Tomography for Differentiation Between Cerebral Hemorrhage and Contrast Extravasation Following Mechanical Revascularization in Acute Ischemic Stroke: A Diagnostic Accuracy Meta-Analysis

Background: Mechanical revascularization has become an essential treatment for acute ischemic stroke patients. Post-treatment imaging frequently displays hyperdense regions, prompting concerns regarding possible cerebral hemorrhage. Dual-energy computed tomography (DECT), as an advanced imaging modality, offers the potential to discern between hemorrhage and harmless contrast leakage. Aim: This study aims to assess the diagnostic precision of DECT in distinguishing cerebral hemorrhage from contrast extravasation post-mechanical revascularization in acute ischemic stroke cases. Methods: A comprehensive search was performed for PubMed, EMBASE, and the Cochrane Library until January 2023. We focused on studies that focused on the diagnostic efficacy of DECT for this specific application. R software (version 4.0.3) coupled with mada package facilitated the analyses pooling metrics such as sensitivity, specificity, false-positive rate estimates, diagnostic odds ratio, and positive and negative Likelihood Ratios. These metrics were reported with a 95% Confidence Interval (CI). Results: Our analysis included 5 studies involving 241 patients. DECT demonstrated a pooled sensitivity of 94.5% (95% CI: 25.9% to 99.9%, I 2 =0%) and a specificity of 99% (95% CI: 77.3% to 100%, I 2 =0%). The false-positive rate was minimal at 1% (95% CI: 0% to 22.7%). The positive likelihood ratio was calculated as 98.94 (95% CI: 3.34 to 2929.22), while the negative likelihood ratio was 0.05 (95% CI: 0.001 to 2.21). The diagnostic odds ratio was substantial at 1795.17 (95% CI: 10.04 to 321055.24), signifying a robust performance of DECT in making the differentiation. Conclusion: While DECT manifests impressive accuracy in differentiating cerebral hemorrhage from contrast extravasation after mechanical revascularization in acute ischemic stroke cases, the wide confidence intervals signify a degree of uncertainty in these estimates. Nevertheless, given its high diagnostic metrics, DECT can substantially influence post-intervention evaluations, paving the way for more informed clinical decisions and potentially reducing patient adverse outcomes. However, further studies with larger sample sizes might help refine these diagnostic estimates.