Tag: nevin manimala

BMJ Open. 2023 Aug 1;13(8):e075736. doi: 10.1136/bmjopen-2023-075736.

ABSTRACT

INTRODUCTION: Friedreich ataxia (FA) is the most common hereditary ataxia in Europe, characterised by progressively worsening movement and speech impairments with a typical onset before the age of 25 years. The symptoms affect the patients’ health-related quality of life (HRQoL) and psychosocial health. FA leads to an increasing need for care, associated with an economic burden. Little is known about the impact of FA on daily lives and HRQoL. To fill that gap, we will assess patient-reported, psychosocial and economic outcomes using momentary data assessment via a mobile health application (app).

METHODS AND ANALYSIS: The PROFA Study is a prospective observational study. Patients with FA (n=200) will be recruited at six European study centres (Germany, France and Austria). We will interview patients at baseline in the study centre and subsequently assess the patients’ health at home via mobile health app. Patients will self-report ataxia severity, HRQoL, speech and hearing disabilities, coping strategies and well-being, health services usage, adverse health events and productivity losses due to informal care on a daily to monthly basis on the app for 6 months. Our study aims to (1) validate measurements of HRQoL and psychosocial health, (2) assess the usability of the mobile health app, and (3) use descriptive and multivariate statistics to analyse patient-reported and economic outcomes and the interaction effects between these outcomes. Insights into the app’s usability could be used for future studies using momentary data assessments to measure outcomes of patients with FA.

ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethics Committee of the University Medicine of Greifswald, (BB096/22a, 26 October 2022) and from all local ethics committees of the participating study sites. Findings of the study will be published in peer-reviewed journals, presented at relevant international/national congresses and disseminated to German and French Patient Advocacy Organizations.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05943002); Pre-results.

PMID:37527887 | DOI:10.1136/bmjopen-2023-075736

Res Synth Methods. 2023 Aug 1. doi: 10.1002/jrsm.1660. Online ahead of print.

ABSTRACT

Missing data complicates statistical analyses in multi-site studies, especially when it is not feasible to centrally pool individual-level data across sites. We combined meta-analysis with within-site multiple imputation for one-step estimation of the average causal effect (ACE) of a target population comprised of all individuals from all data-contributing sites within a multi-site distributed data network, without the need for sharing individual-level data to handle missing data. We considered two orders of combination and three choices of weights for meta-analysis, resulting in six approaches. The first three approaches, denoted as RR + metaF, RR + metaR and RR + std, first combined results from imputed data sets within each site using Rubin’s rules and then meta-analyzed the combined results across sites using fixed-effect, random-effects and sample-standardization weights, respectively. The last three approaches, denoted as metaF + RR, metaR + RR and std + RR, first meta-analyzed results across sites separately for each imputation and then combined the meta-analysis results using Rubin’s rules. Simulation results confirmed very good performance of RR + std and std + RR under various missing completely at random and missing at random settings. A direct application of the inverse-variance weighted meta-analysis based on site-specific ACEs can lead to biased results for the targeted network-wide ACE in the presence of treatment effect heterogeneity by site, demonstrating the need to clearly specify the target population and estimand and properly account for potential site heterogeneity in meta-analyses seeking to draw causal interpretations. An illustration using a large administrative claims database is presented.

PMID:37527843 | DOI:10.1002/jrsm.1660

Stat Med. 2023 Aug 1. doi: 10.1002/sim.9862. Online ahead of print.

ABSTRACT

Natural history of hepatitis B or C is comprised of multiple milestones such as liver cirrhosis and liver cancer. To fully characterize its natural course, semicompeting risks represent a common problem where liver cirrhosis and liver cancer are both of interest, but only the former may be censored by the latter. Copula, frailty and multistate models serve as well-established analytics for semicompeting risks. Here, we cast the semicompeting risks in a mediation framework, with liver cirrhosis as a mediator and liver cancer as an outcome. We define the indirect and direct effects as the effects of an exposure on the liver cancer incidence mediated and not mediated through liver cirrhosis, respectively. With the estimands derived as conditional probabilities, we derive respective expressions under the copula, frailty, and multistate models. Next, we propose estimators based on nonparametric maximum likelihood or U-statistics and establish their asymptotic results. Numerical studies demonstrate that the efficiency of copula models leads to potential bias due to model misspecification. Moreover, the robustness of frailty models is accompanied by a loss in efficiency, and multistate models balance the efficiency and robustness. We demonstrate the utility of the proposed methods by a hepatitis study, showing that hepatitis B and C lead to a higher incidence of liver cancer by increasing liver cirrhosis incidence. Thus, mediation modeling provides a unified framework that accommodates various semicompeting risks models.

PMID:37527841 | DOI:10.1002/sim.9862

Am J Vet Res. 2023 Aug 5:1-7. doi: 10.2460/ajvr.23.05.0099. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate antinociceptive efficacy of SC administration of hydromorphone hydrochloride and buprenorphine hydrochloride in ferrets (Mustela putorius furo).

ANIMALS: 14 healthy adult ferrets (6 neutered males, 8 spayed females).

METHODS: In a randomized, blind, controlled, complete crossover design, all 14 ferrets received a single, SC injection of hydromorphone low dose (0.1 mg/kg), hydromorphone high dose (0.2 mg/kg), buprenorphine low dose (0.02 mg/kg), buprenorphine high dose (0.04 mg/kg), or saline solution (0.2 mL/kg). Sedation and forelimb withdrawal latency from a noxious thermal stimulation were evaluated, and behavior was recorded for a total of 8 hours postinjection.

RESULTS: Compared to saline, administration of hydromorphone at 0.2 mg/kg resulted in an estimated increase of withdrawal latencies of 7.4 seconds (95% CI, 3.2 to 11.6) at 60 minutes, of 6.6 seconds (2.4 to 10.8) at 90 minutes, of 6.0 seconds (1.8 to 10.2) at 120 minutes, of 7.0 seconds (2.9 to 11.1) at 180 minutes, and of 4.5 seconds (0.5 to 8.6) at 240 minutes. These differences were statistically significant. Hydromorphone administered at a lower dose and buprenorphine at either dose did not increase withdrawal latencies compared to saline. Based on the sedation score used in this study, signs of sedation increased over time in a similar fashion with all treatments, including saline. Erratic dysphoric-like behaviors occurred in all groups except for saline.

CLINICAL RELEVANCE: SC administration of hydromorphone at a dose of 0.2 mg/kg provided antinociception from 1 to 4 hours postinjection. Further validation of sedation scores in ferrets is warranted.

PMID:37527831 | DOI:10.2460/ajvr.23.05.0099

J Am Med Dir Assoc. 2023 Jul 29:S1525-8610(23)00615-1. doi: 10.1016/j.jamda.2023.06.025. Online ahead of print.

ABSTRACT

OBJECTIVES: To better demonstrate the relationship between common eye diseases and the risk of dementia, we conducted a systematic review and meta-analysis of cohort studies to investigate the relationship between common eye diseases and dementia.

DESIGN: Systematic review and meta-analysis.

SETTING AND PARTICIPANTS: Patients with common eye diseases.

METHODS: We conducted a systematic search of articles published up to August 25, 2022, of online databases including PubMed, EMBASE, and Web of Science. We included cohort studies that evaluated the association of glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and cataracts with all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VaD). Relative risks (RRs) and 95% CIs were pooled using random effects model, and heterogeneity was assessed by the I² statistic. Subgroup analysis and sensitivity analysis were also performed.

RESULTS: In total, 25 studies were included in the meta-analysis, with a total of 11,410,709 participants. Pooled estimates suggested an increased risk of all-cause dementia associated with AMD (RR, 1.29; 95% CI, 1.13-1.48), glaucoma (RR, 1.16; 95% CI, 1.03-1.32), DR (RR, 1.40; 95% CI, 1.21-1.63), and cataract (RR,1.23; 95% CI, 1.09-1.40); an increased risk of AD associated with AMD (RR, 1.27; 95% CI, 1.06-1.52), glaucoma (RR, 1.18; 95% CI, 1.02-1.38), DR (RR, 1.21; 95% CI, 1.04-1.41), and cataracts (RR,1.22; 95% CI, 1.07-1.38). No association was observed between incident VaD and any eye diseases. The results of subgroup analyses were consistent with those in meta-analysis of DR and risk of all-cause dementia. Meta-regressions suggested geographic regions as potential sources of heterogeneity for the association between AMD and all-cause dementia, AMD and AD, glaucoma and dementia, glaucoma, and AD, respectively.

CONCLUSIONS AND IMPLICATIONS: AMD, glaucoma, DR, and cataract may be associated with an increased risk of all-cause dementia and AD, but not VaD. However, the results should be interpreted cautiously because of the high heterogeneity and unstable findings in some subgroup analyses.

PMID:37527793 | DOI:10.1016/j.jamda.2023.06.025

Appl Clin Inform. 2023 Aug 1. doi: 10.1055/a-2145-6980. Online ahead of print.

ABSTRACT

OBJECTIVE: Few community pharmacies have access to health information exchange (HIE) data. We conducted a first-of-its-kind usability evaluation of a HIE interface prototype (referred to throughout as the “HIE-Pioneer mock-up”) developed with pharmacists and pharmacy technicians to aid future implementation in community pharmacies.

METHODS: Community pharmacists and pharmacy technicians were recruited to complete usability evaluations with the HIE-Pioneer mock-up. Each usability evaluation lasted up to 60 mins. System usability scale (SUS) scores were collected from each participant following each usability evaluation session and summarized with descriptive statistics. Usability evaluation videos were reviewed for common usability attributes, such as the impact of identified usability problems, learnability, and efficiency. Time on task, task success rates, and prototype utilization were also recorded.

RESULTS: Sixteen total participants completed usability testing across three community pharmacies. The average SUS score was 69.7 (scale 0 – 100, where 100 is the best), with pharmacists on average reporting higher satisfaction than technicians (74.1 vs. 65.3, respectively). Altogether, we identified 23 distinct usability problems. Key problems identified included needed clarification in tool label names and accessibility of HIE links within existing workflow. Overall, the usability of the HIE-Pioneer mock-up generally fostered pharmacy professionals’ ease of learning and efficiency.

CONCLUSION: Our study identified key areas, and potential solutions, to improve the usability of the HIE-Pioneer mock-up. Overall, pharmacy professionals viewed the HIE-Pioneer mock-up positively, with good satisfaction ratings. The HIE-Pioneer mock-up provides a blueprint for future HIE implementation in community pharmacy settings, which would increase community pharmacy teams’ access to HIE data nationwide. Community pharmacy access to bi-directional HIE is expected to improve communication amongst more healthcare professionals involved in patient care and equip pharmacy professionals with needed information for improved clinical decision making.

PMID:37527792 | DOI:10.1055/a-2145-6980

Am J Perinatol. 2023 Aug 1. doi: 10.1055/a-2145-7636. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the effect of non-reassuring fetal heart rate (NRFHR) patterns in labor on the postnatal renal function of neonates with a prenatal diagnosis of Congenital Anomalies of the Kidney and Urinary Tract (CAKUT).

STUDY DESIGN: A retrospective cohort study was conducted in a single tertiary referral center between 2012 and 2020. All cases with a prenatal diagnosis of CAKUT were extracted, and their fetal, maternal, obstetrical, and neonatal characteristics were analyzed. Cases of multiple gestations, preterm delivery, small for gestational age, major associated malformations or genetic aberrations, and pre-labor acute obstetrical events were excluded from the analysis. The study group was comprised of patients who experienced NRFHR during labor. The control groups included (1) patients who had a trial of labor with a normal fetal heart rate pattern and (2) patients who delivered by elective cesarean section (CS). The primary outcome was abnormal serum creatinine levels in the perinatal period. For statistical purposes, the CAKUT cases were classified into a low and high estimated risk for an abnormal postnatal renal outcome. A subgroup analysis of the results was performed accordingly.

RESULTS: 256 fetuses were diagnosed prenatally with CAKUT during the study period. Of them, 214 (83%) women underwent a trial of labor, and forty-two patients (17%) underwent an elective Cesarean Section. Of the patients who underwent a trial of labor, 21/214 (9.8%) experienced NRFHR during labor. No statistically significant between-group differences were found in maternal and fetal characteristics. NRFHR patterns were not associated with a deterioration in neonatal serum creatinine compared to those with normal fetal monitoring or those born by an elective CS.

CONCLUSION: NRFHR patterns during labor and delivery did not impair neonatal renal function status in fetuses diagnosed prenatally with low and high-risk CAKUT. Delivery can be managed according to standard obstetrical guidelines.

PMID:37527788 | DOI:10.1055/a-2145-7636

Thromb Haemost. 2023 Aug 1. doi: 10.1055/a-2145-7238. Online ahead of print.

ABSTRACT

BACKGROUND: Cancer associated venous thromboembolism (Ca-VTE) treatment with anticoagulation is associated with bleeding complications and there are limited data on risk factors. Current models do not provide accurate bleeding risk prediction.

METHODS: UK Clinical Practice Research Datalink data (2008-2020) was used to generate a cohort of patients with anticoagulant initiation for first Ca-VTE. Patients were observed up to 180 days for significant bleeding including major bleeding, and clinically relevant non-major bleeding requiring hospitalisation (CRNMB-H). A scoring scheme was developed from subdistribution hazard ratios, and its discrimination (expressed by the C-statistic) estimated from cross-validation.

RESULTS: 15,749 patients with Ca-VTE and anticoagulant treatment were included. In total, 537 significant bleeding events, 161 major bleeds and 376 CRNMB-H were identified after adjudicated review in 4914 person-years of observation. Incidence rates of 3.3 and 7.7 per 100 person-years were noted for major bleeding and CRNMB-H. Independent predictors of significant bleeding were cancer of the bladder, central nervous system, cervix, kidney, melanoma, prostate and upper gastrointestinal tract. Overall C-statistic for significant bleeding was 0.70, and 0.76 and 0.67 for major bleeding and for CRNMB-H, respectively.

CONCLUSIONS: This risk score may identify patients at risk of significant bleeding, while also helping to determine treatment duration.

PMID:37527782 | DOI:10.1055/a-2145-7238

J Gynecol Obstet Hum Reprod. 2023 Jul 30:102637. doi: 10.1016/j.jogoh.2023.102637. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the evolution of endometriomas with or without medical treatment.

METHODS: This retrospective observational study was performed at the Gynaecological Center, Hôpital La Conception (Assistance Publique Hopitaux de Marseille). We reviewed clinical data of patients with at least one endometrioma diagnosed by magnetic resonance imaging (MRI) and at least one other MRI exam after more than three months. Patients were divided into groups receiving medical treatment and without medical treatment (high-dose progestins, low-dose progestins or combined contraceptives). The primary objective was to evaluate the evolution of endometriomas with or without hormonal treatment. The primary evaluation criterion was the diameter of the endometriomas, and the secondary evaluation criterion was the number of endometriomas for each patient observed. The secondary objective was to evaluate whether different categories of hormonal treatment have different efficacity in the evolution of endometriomas.

RESULTS: We included 68 patients, 39 (57,4%) with hormonal treatment and 29 (42,6%) without hormonal treatment. There were 105 total endometriomas identified at the first MRI, 52 in patients with hormonal treatment and 53 in patients without treatment. The mean diameter of the endometriomas in patients with hormonal treatment was 31,48 ± 18,1 mm at the first MRI and 23,60 ± 15,3 mm at the second MRI. The mean diameter of the endometriomas in patients without treatment was 33,57 ± 19,7 mm at the first MRI and 40,11 ± 25,7 mm at the second MRI (statistically significant difference, p = 0.01). The mean number of endometriomas in patients with treatment was 1,79 ± 1,1 at the first MRI and 1,18 ± 0,9 at the second MRI, while the mean number of endometriomas in patients without hormonal treatment was 1,38 ± 0,6 at the first MRI and 1,97 ± 1,5 at the second MRI (difference not statistically significant, p = 0.38). The subgroup analysis differentiated by category of hormonal treatment did not show statistically significant results.

CONCLUSIONS: The present study shows that there is a positive effect of hormonal treatment on reducing the diameter of endometriomas and also a significative increase in endometrioma size in the absence of treatment. There is no evidence of an advantage of a single category of hormonal treatment on this effect on endometriomas. Thus, any medical treatment could be proposed as a first-line therapy for endometriomas that would reduce the size of the endometrioma and thereby help to avoid surgical intervention.

PMID:37527765 | DOI:10.1016/j.jogoh.2023.102637

Neuropsychologia. 2023 Jul 30:108652. doi: 10.1016/j.neuropsychologia.2023.108652. Online ahead of print.

ABSTRACT

The current study examined whether adults with Developmental Dyslexia are impaired in learning linguistic regularities in a novel language, and whether this may be explained by a domain general deficit in the effect of sleep on consolidation. We compared online learning and offline consolidation of morphological regularities in individuals with Developmental Dyslexia (N = 40) and typical readers (N = 38). Participants learned to apply plural inflections to novel words based on morpho-phonological rules embedded in the input and learned to execute a finger motor sequence task. To test the effects of time and sleep on consolidation, participants were assigned into one of two sleep-schedule groups, trained in the evening or in the morning and tested 12 and 24 h later. Unlike typical readers, Dyslexic readers did not extract the morpho-phonological regularities during training and as a group they did not show offline gains in inflecting trained items 24 h after training, suggesting that the deficit in extraction of regularities during training may be related to the deficit in consolidation. The offline gains in dyslexic readers, were correlated with their prior phonological abilities, and were less affected by sleep than those of typical readers. Although no deficit was found in the consolidation of the motor task, dyslexic readers were again less successful in generating an abstract representation of the motor sequence, reflected in a difficulty to generalize the motor sequence knowledge acquired using one hand to the untrained hand. The results suggest that individuals with Developmental Dyslexia have a domain general deficit in extracting statistical regularities from an input. Within the language domain this deficit is reflected in reduced benefits of consolidation, particularly during sleep, perhaps due to reduced prior phonological abilities, which may impede the individual’s ability to extract the linguistic regularities during and after training and thus constrain the consolidation process.

PMID:37527734 | DOI:10.1016/j.neuropsychologia.2023.108652