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Nevin Manimala Statistics

A Meta-Analysis of Levofloxacin for Contacts of Multidrug-Resistant Tuberculosis

NEJM Evid. 2024 Dec 18:EVIDoa2400190. doi: 10.1056/EVIDoa2400190. Online ahead of print.

ABSTRACT

BACKGROUND: Data from randomized trials evaluating the effectiveness of tuberculosis (TB) preventive treatment for contacts of multidrug-resistant (MDR)-TB are lacking. Two recently published randomized trials that did not achieve statistical significance provide the opportunity for a meta-analysis.

METHODS: We conducted combined analyses of two phase 3 trials of levofloxacin MDR-TB preventive treatment – Levofloxacin for the Prevention of Multidrug-Resistant Tuberculosis (VQUIN) trial and the Levofloxacin preventive treatment in children exposed to MDR-TB (TB-CHAMP) trial. Following MDR-TB household exposure, VQUIN enrolled mainly adults in Vietnam; TB-CHAMP enrolled mainly young children in South Africa. Random assignment in both trials was 1:1 at the household level to daily levofloxacin or placebo for 6 months. The primary outcome was incident TB by 54 weeks. We estimated the treatment effect overall using individual participant data meta-analysis.

RESULTS: The VQUIN trial (n=2041) randomly assigned 1023 participants to levofloxacin and 1018 participants to placebo; TB-CHAMP (n=922) assigned 453 participants to levofloxacin and 469 participants to placebo. Median age was 40 years (interquartile range 28 to 52 years) in VQUIN and 2.8 years (interquartile range 1.3 to 4.2 years) in TB-CHAMP. Overall, 8 levofloxacin-group participants developed TB by 54 weeks versus 21 placebo-group participants; the relative difference in cumulative incidence was 0.41 (95% confidence interval [CI] 0.18 to 0.92; P=0.03). No association was observed between levofloxacin and grade 3 or above adverse events (risk ratio 1.07, 95% CI 0.70 to 1.65). Musculoskeletal events of any grade occurred more frequently in the levofloxacin group (risk ratio 6.36, 95% CI 4.30 to 9.42), but not among children under 10 years of age. Overall, four levofloxacin-group participants and three placebo-group participants had grade 3 events.

CONCLUSIONS: In this meta-analysis of two randomized trials, levofloxacin was associated with a 60% relative reduction in TB incidence among adult and child household MDR-TB contacts, but with an increased risk of musculoskeletal adverse events. (Funded by the Australian National Health and Medical Research Council, UNITAID, and others.).

PMID:39693627 | DOI:10.1056/EVIDoa2400190

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When and Why Adults Abandon Lifestyle Behavior and Mental Health Mobile Apps: Scoping Review

J Med Internet Res. 2024 Dec 18;26:e56897. doi: 10.2196/56897.

ABSTRACT

BACKGROUND: With 1 in 3 adults globally living with chronic conditions and the rise in smartphone ownership, mobile health apps have become a prominent tool for managing lifestyle-related health behaviors and mental health. However, high rates of app abandonment pose challenges to their effectiveness.

OBJECTIVE: We explored the abandonment of apps used for managing physical activity, diet, alcohol, smoking, and mental health in free-living conditions, examining the duration of app use before abandonment and the underlying reasons.

METHODS: A scoping review was conducted based on the PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) guidelines and eligibility criteria were designed according to the SPIDER (Sample, Phenomenon of Interest, Design, Evaluation, Research type) framework. In total, 4 databases were searched (MEDLINE, Scopus, Embase, and PsycINFO) to identify quantitative and qualitative studies with outcome measures related to app abandonment in adults with free-living conditions, including reasons for abandonment and duration of use, for mobile apps related to WHO (World Health Organization) modifiable health behaviors and mental health. The included studies’ risk of bias was appraised based on the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) and COREQ (Consolidated Criteria for Reporting Qualitative Research) checklists. To enable data synthesis across different methodologies, app domains, demographic data, and outcome measures were categorized. Results are presented in 2 sections: quantitatively in a scatterplot to understand when users abandon apps and qualitatively through basic qualitative content analysis to identify the underlying reasons.

RESULTS: Eighteen eligible studies (525,824 participants) published between 2014 and 2022, predominantly from the United States, Canada, the United Kingdom, and Germany, were identified. Findings revealed a curvilinear pattern of app abandonment, with sharper abandonment soon after acquisition, followed by a slowing rate of abandonment over time. Taken together, a median of 70% of users discontinued use within the first 100 days. The abandonment rate appeared to vary by app domain, with apps focusing on alcohol and smoking exhibiting faster abandonment, and physical activity and mental health exhibiting longer usage durations. In total, 22 unique reasons for abandonment were organized into six categories: (1) technical and functional issues, (2) privacy concerns, (3) poor user experience, (4) content and features, (5) time and financial costs, and (6) evolving user needs and goals.

CONCLUSIONS: This study highlights the complex nature of health app abandonment and the need for an improved understanding of user engagement over time, underscoring the importance of addressing various factors contributing to abandonment, from technical issues to evolving user needs. Our findings also emphasize the need for longitudinal studies and a consistent definition of app abandonment to better understand and mitigate this phenomenon, thereby enhancing the effectiveness of health apps in supporting public health initiatives.

PMID:39693620 | DOI:10.2196/56897

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User Experience and Extended Technology Acceptance Model in Commercial Health Care App Usage Among Patients With Cancer: Mixed Methods Study

J Med Internet Res. 2024 Dec 18;26:e55176. doi: 10.2196/55176.

ABSTRACT

BACKGROUND: The shift in medical care toward prediction and prevention has led to the emergence of digital health care as a valuable tool for managing health issues. Aiding long-term follow-up care for cancer survivors and contributing to improved survival rates. However, potential barriers to mobile health usage, including age-related disparities and challenges in user retention for commercial health apps, highlight the need to assess the impact of patients’ abilities and health status on the adoption of these interventions.

OBJECTIVE: This study aims to investigate the app adherence and user experience of commercial health care apps among cancer survivors using an extended technology acceptance model (TAM).

METHODS: The study enrolled 264 cancer survivors. We collected survey results from May to August 2022 and app usage records from the app companies. The survey questions were created based on the TAM.

RESULTS: We categorized 264 participants into 3 clusters based on their app usage behavior: short use (n=77), medium use (n=101), and long use (n=86). The mean usage days were 9 (SD 11) days, 58 (SD 20) days, and 84 (SD 176) days, respectively. Analysis revealed significant differences in perceived usefulness (P=.01), interface satisfaction (P<.01), equity (P<.01), and utility (P=.01) among the clusters. Structural equation modeling indicated that perceived ease-of-use significantly influenced perceived usefulness (β=0.387, P<.01), and both perceived usefulness and attitude significantly affected behavioral intention and actual usage.

CONCLUSIONS: This study showed the importance of positive user experience and clinician recommendations in facilitating the effective usage of digital health care tools among cancer survivors and contributing to the evolving landscape of medical care.

PMID:39693615 | DOI:10.2196/55176

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Antibiotic Use and Subsequent Cognitive Decline and Dementia Risk in Healthy Older Adults

Neurology. 2025 Jan 14;104(1):e210129. doi: 10.1212/WNL.0000000000210129. Epub 2024 Dec 18.

ABSTRACT

BACKGROUND AND OBJECTIVES: Antibiotics rapidly reduce intestinal bacterial diversity, leading to dysbiosis that persists for months to years. Although emerging evidence from retrospective and claims-based studies has linked dysbiosis to cognitive function, prospective data are lacking. We aim to examine the prospective association of antibiotics with cognitive aging among initially healthy older adults.

METHODS: We leveraged data from prospective follow-up and observational extension of ASPirin in Reducing Events in the Elderly, a completed randomized trial of community-based Australian older adults. Among participants whose prescription records were available and without dementia during the first 2 years of follow-up, we identified any or repeated antibiotic use based on the Anatomical Therapeutic Chemical code (J01). We assessed the associations of antibiotic use during the first 2 years with longitudinal changes in standardized composite and domain-specific cognitive scores (global cognition, episodic memory, language and executive function, and psychomotor speed) using linear mixed models, and with incident, clinically adjudicated dementia (Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition criteria) and incident cognitive impairment, no dementia (CIND, without a dementia trigger but with significant, nontransient decline), using Cox proportional hazard models.

RESULTS: Over a median of 4.7 years after the second follow-up visit, we documented 461 dementia and 2,576 CIND cases among 13,571 participants (mean age ± SD 75.0 ± 4.1 years, 54.3% female). Compared with nonuse, antibiotic use was not associated with increased risks for dementia (hazard ratio [HR] 1.03; 95% CI 0.84-1.25), CIND (HR 1.02; 95% CI 0.94-1.11), or subsequent declines in cognitive scores, after adjusting for sociodemographic, lifestyle factors, family history of dementia, baseline cognitive function, and medications known to affect cognition. There were also no associations according to the cumulative frequency of antibiotic use, long-term use, specific antibiotic classes (e.g., beta-lactams, tetracyclines, and sulfonamides), and subgroups defined by risk factors.

DISCUSSION: Among initially healthy older adults, any or repeated antibiotic use was not associated with incident dementia, CIND, or accelerated cognitive decline. Although prescription data may not reflect the actual use, we examined the frequency of antibiotics within a defined period to capture the extent and duration of antibiotic exposure. Our results do not support an association between antibiotic-associated gut microbiome disruption and dementia risk.

PMID:39693592 | DOI:10.1212/WNL.0000000000210129

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Prevalence of Diabetic Retinopathy and Dilated Fundus Examinations by Metropolitan Status from 2017-2021: An Assessment of the Behavioral Risk Factor Surveillance System

Ophthalmic Epidemiol. 2024 Dec 18:1-4. doi: 10.1080/09286586.2024.2434247. Online ahead of print.

ABSTRACT

PURPOSE: Diabetic eye disease, namely diabetic retinopathy (DR), remains a leading cause of preventable blindness worldwide. Research has shown that treatment for diabetes and eye care was disrupted during the pandemic – with disparities between urban and rural populations being unknown. Thus, we aimed to assess the prevalence of reported rates of DR and dilated fundus exams from 2017 to 2021.

METHODS: We performed a cross-sectional analysis using data from the Behavioral Risk Factor Surveillance System (BRFSS). Among US residents with diabetes, we calculated the rates of DR and annual dilated fundus exams – overall and by metropolitan statistical area (MSA) – measuring differences using X2 tests.

RESULTS: In 2017, the rate of DR was 19.78% among US residents reporting diabetes, which increased to the highest rate in 2018 at 22.19% before dropping to the lowest rates in 2019 and 2020 (18.44%). These annual changes were statistically significant (p < .001), but we found no significant differences by MSA status. Each year, nearly ⅔ of all individuals reported receiving dilated fundus examinations which peaked in 2019 at 71.5%. These annual deviations, as well as deviations by MSA were statistically significant (p < .001).

CONCLUSION: Although populations outside of an MSA experienced an increase in dilated fundus examinations, the national prevalence of DR continues to rise. Further research into sociodemographic and cultural factors influencing diabetic eye disease and access to ophthalmic care will be crucial for the prevention of DR and improving vision outcomes.

PMID:39693586 | DOI:10.1080/09286586.2024.2434247

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Prediction of Hepatocellular Carcinoma After Hepatitis C Virus Sustained Virologic Response Using a Random Survival Forest Model

JCO Clin Cancer Inform. 2024 Dec;8:e2400108. doi: 10.1200/CCI.24.00108. Epub 2024 Dec 18.

ABSTRACT

PURPOSE: Postsustained virologic response (SVR) screening following clinical guidelines does not address individual risk of hepatocellular carcinoma (HCC). Our aim is to provide tailored screening for patients using machine learning to predict HCC incidence after SVR.

METHODS: Using clinical data from 1,028 SVR patients, we developed an HCC prediction model using a random survival forest (RSF). Model performance was assessed using Harrel’s c-index and validated in an independent cohort of 737 SVR patients. Shapley additive explanation (SHAP) facilitated feature quantification, whereas optimal cutoffs were determined using maximally selected rank statistics. We used Kaplan-Meier analysis to compare cumulative HCC incidence between risk groups.

RESULTS: We achieved c-index scores and 95% CIs of 0.90 (0.85 to 0.94) and 0.80 (0.74 to 0.85) in the derivation and validation cohorts, respectively, in a model using platelet count, gamma-glutamyl transpeptidase, sex, age, and ALT. Stratification resulted in four risk groups: low, intermediate, high, and very high. The 5-year cumulative HCC incidence rates and 95% CIs for these groups were as follows: derivation: 0% (0 to 0), 3.8% (0.6 to 6.8), 26.2% (17.2 to 34.3), and 54.2% (20.2 to 73.7), respectively, and validation: 0.7% (0 to 1.6), 7.1% (2.7 to 11.3), 5.2% (0 to 10.8), and 28.6% (0 to 55.3), respectively.

CONCLUSION: The integration of RSF and SHAP enabled accurate HCC risk classification after SVR, which may facilitate individualized HCC screening strategies and more cost-effective care.

PMID:39693579 | DOI:10.1200/CCI.24.00108

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THERAPEUTIC REFRACTIVE VITRECTOMY (TRV) FOR THE MANAGEMENT OF VITREOUS FLOATERS AND OPACITIES (VFO) ASSESSED BY THE STANDARDIZED AND KINETIC ANATOMICAL AND FUNCTIONAL TESTING OF VITREOUS FLOATERS AND OPACITIES (SK VFO TEST)

Retina. 2024 Dec 16. doi: 10.1097/IAE.0000000000004373. Online ahead of print.

ABSTRACT

PURPOSE: Propose new terminology and evaluate the effectiveness of Therapeutic Refractive Vitrectomy (TRV) for selective removal of vitreous floaters and opacities (VFO) utilizing Standardized Kinetic Anatomical Functional Testing of VFO (SK VFO Test) and new ultra widefield (UWF) OCT imaging techniques.

METHODS: Retrospective analysis. Twenty eyes underwent TRV for symptomatic VFO. Pre-/post-TRV assessments: SK-VFO Test, including straylight measurements (HD Analyzer, Light Disturbance Analyzer, C-Quant) alongside non-contact imaging including a new UWF OCT to evaluate changes in vitreous anatomical and optical properties.

RESULTS: Post-TRV evaluations indicated objective changes in vitreous optical properties and subjective measures. Reduced straylight measurements: HDA 22%, LDA 54.4% (p=0.013), and C-Quant 7.8% (p=0.034). Patient reported outcomes statistically significantly improved (p=0.022). Corrected distance visual acuity (CDVA) changes were marginal. New UWF 26 mm with a 12 mm imaging window OCT facilitated detailed vitreous imaging, confirming status of posterior vitreous detachment (PVD) (100%). Post-TRV UWF and OCT imaging demonstrated restoration of vitreous clarity, confirmed presence of residual cortical vitreous and absence of new PVDs.

CONCLUSION: TRV is a significant contribution for therapeutic refractive surgery as a safe and effective approach to enhancing visual quality, correcting refractive and opaque vitreous anomalies. Improvement in CDVA was minimal representing limited effectiveness as a measure of comprehensive visual function. Improvements in objective straylight measures and imaging are in alignment with subjective symptom improvements post-TRV. This underscores the utility and value of new holistic evaluation methods beyond traditional metrics to assess the impact of TRV on visual function and quality of life.

PMID:39693577 | DOI:10.1097/IAE.0000000000004373

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Structural Commonalities Determined by Physicochemical Principles in the Complex Polymorphism of the Amyloid State of Proteins

Biochem J. 2024 Dec 18:BCJ20240602. doi: 10.1042/BCJ20240602. Online ahead of print.

ABSTRACT

Advances in solid-state nuclear magnetic resonance (ssNMR) spectroscopy and cryogenic electron microscopy (cryoEM) have revealed the polymorphic nature of the amyloid state of proteins. Given the association of amyloid with protein misfolding disorders, it is important to understand the principles underlying this polymorphism. To address this problem, we combined computational tools to predict the specific regions of the sequence forming the β-spine of amyloid fibrils with the availability of 30, 83 and 24 amyloid structures deposited in the Protein Data Bank (PDB) and Amyloid Atlas (AA) for the amyloid β (Aβ) peptide, α-synuclein (αS), and the 4R isoforms of tau, associated with Alzheimer’s disease, Parkinson’s disease, and various tauopathies, respectively. This approach enabled a statistical analysis of sequences forming β-sheet regions in amyloid polymorphs. We computed for any given sequence residue n the fraction of PDB/AA structures in which that residue adopts a β-sheet conformation (Fβ(n)) to generate an experimental, structure-based profile of Fβ(n) vs n, which represents the β-conformational preference of any residue in the amyloid state. The peaks in the respective Fβ(n) profiles of the three proteins, corresponding to sequence regions adopting more frequently the β-sheet structural core in the various fibrillar structures, align very well with the peaks identified with five predictive algorithms (ZYGGREGATOR, TANGO, PASTA, AGGRESCAN, WALTZ). These results indicate that, despite amyloid polymorphism, sequence regions most often forming the structural core of amyloid have high hydrophobicity, high intrinsic β-sheet propensity and low electrostatic charge across the sequence, as rationalised and predicted by the algorithms.

PMID:39693572 | DOI:10.1042/BCJ20240602

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The Impact of the Advancing American Kidney Health Initiative on Search Patterns of Home Dialysis Options

R I Med J (2013). 2025 Jan 2;108(1):39-43.

ABSTRACT

The 2019 Advancing American Kidney Health (AAKH) initiative aims to increase utilization of home dialysis for end-stage kidney disease (ESKD), but its impact on public awareness is unknown. We analyzed Google Trends data from 2013-2021 to compare relative search volumes for “home dialysis”, “peritoneal dialysis”, and “home hemodialysis” in the United States (US) versus globally before versus after the July 2019 AAKH announcement. An interrupted time-series analysis found steady pre-AAKH increases in search interest across terms and locations. An immediate increase after AAKH occurred for all searches, greatest for home dialysis (+5.93 US, +11.2 global), but post-AAKH trends were flat or declining. Differences between US and global trends were not statistically significant. Despite goals to increase home dialysis use, AAKH has not impacted public information-seeking behaviors. Targeted patient education initiatives may be needed to increase awareness of home dialysis options.

PMID:39693534

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Community Emergency Medicine Clinicians’ Pediatric Sepsis Readiness

R I Med J (2013). 2025 Jan 2;108(1):30-34.

ABSTRACT

BACKGROUND/OBJECTIVE: Pediatric sepsis is a significant cause of morbidity and mortality in the United States, and its early recognition is crucial but challenging. This study assessed clinicians’ self-reported preparedness for recognizing and managing pediatric sepsis in the Rhode Island region.

METHODS: A cross-sectional, survey was developed and sent to community emergency medicine clinicians in greater Rhode Island. Results were analyzed using descriptive statistics.

RESULTS: Survey responses were received from 35 participants across 10 Emergency Departments. Ninety-seven percent (97%) felt confident managing adult sepsis with shock, but only 51% felt confident managing pediatric sepsis with shock. Lack of pediatric procedural experience and familiarity with pediatric dosing were barriers to providing care to pediatric patients with sepsis for 74.2% and 62.8% of participants, respectively.

CONCLUSION: Many community ED clinicians lack confidence in managing pediatric sepsis. Structured educational initiatives focused on clinical examination, procedural skills, and medication dosing may enhance confidence in managing these patients.

PMID:39693532