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Personalized Patient Data and Behavioral Nudges to Improve Adherence to Chronic Cardiovascular Medications: A Randomized Pragmatic Trial

JAMA. 2024 Dec 2. doi: 10.1001/jama.2024.21739. Online ahead of print.

ABSTRACT

IMPORTANCE: Poor medication adherence is common. Text messaging is increasingly used to change patient behavior but often not rigorously tested.

OBJECTIVE: To compare different types of text messaging strategies with usual care to improve medication refill adherence among patients nonadherent to cardiovascular medications.

DESIGN, SETTING, AND PARTICIPANTS: Patient-level randomized pragmatic trial between October 2019 to April 2022 at 3 US health care systems, with last follow-up date of April 11, 2023. Adult (18 to <90 years) patients were eligible based on diagnosis of 1 or more cardiovascular condition(s) and prescribed medication to treat the condition. Patients who did not opt out and had a 7-day refill gap were randomized to 1 of 4 study groups.

INTERVENTION(S): Generic text message refill reminders (generic reminder); behavioral nudge text refill reminders (behavioral nudge); behavioral nudge text refill reminders plus a fixed-message chatbot (behavioral nudge + chatbot); usual care.

MAIN OUTCOMES AND MEASURES: Primary outcome was refill adherence based on pharmacy data using proportion of days covered at 12 months. Secondary outcomes were clinical events of emergency department visits, hospitalizations, and mortality.

RESULTS: Among 9501 enrolled patients, baseline characteristics across the 4 groups were comparable (mean age, 60 years; 47% female [n = 4351]; 16% Black [n = 1517]; 49% Hispanic [n = 4564]). At 12 months, the mean proportion of days covered was 62.0% for generic reminder, 62.3% for behavioral nudge, 63.0% for behavioral nudge + chatbot, and 60.6% for usual care (P = .06). In adjusted analysis, when compared with usual care, mean proportion of days covered was 2.2 percentage points (95% CI, 0.3-4.2; P = .02) higher for generic reminder, 2.0 percentage points (95% CI, 0.1-3.9; P = .04) higher for behavioral nudge, and 2.3 percentage points (95%, 0.4-4.2; P = .02) higher for behavioral nudge + chatbot, none of which were statistically significant after multiple comparisons correction. There were no differences in clinical events between study groups.

CONCLUSIONS AND RELEVANCE: Text message reminders targeting patients who delay refilling their cardiovascular medications did not improve medication adherence based on pharmacy refill data or reduce clinical events at 12 months. Poor medication adherence may be due to multiple factors. Future interventions may need to be designed to address the multiple factors influencing adherence.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03973931.

PMID:39621340 | DOI:10.1001/jama.2024.21739

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β-Blocker Use and Delayed Onset and Progression of Huntington Disease

JAMA Neurol. 2024 Dec 2. doi: 10.1001/jamaneurol.2024.4108. Online ahead of print.

ABSTRACT

IMPORTANCE: Huntington disease (HD) is characterized by motor, cognitive, and psychiatric decline. β-Blockers may play a therapeutic role by decreasing enhanced sympathetic tone in HD.

OBJECTIVE: To evaluate the impact of β-blockers on the timing of motor diagnosis onset and progression of HD symptoms.

DESIGN, SETTING, AND PARTICIPANTS: This observational, longitudinal multicenter study used the Enroll-HD platform database (initiated September 2011 to present), including propensity score-matched cohorts of patients with premanifest HD (preHD) and early motor-manifest HD (mmHD) who were either users or nonusers of β-blockers. Participants included patients with genetically confirmed preHD (n = 4683 eligible participants) or mmHD (n = 3024 eligible participants) who were taking a β-blocker and were matched to similar non-β-blocker users.

EXPOSURE: Uninterrupted use of a β-blocker for more than 1 year.

MAIN OUTCOMES AND MEASURES: For PreHD: risk of receiving a motor diagnosis of HD over time. For mmHD: progression rate of total motor score, total functional capacity score, and the symbol digit modalities test. Post hoc analyses were performed to test additional clarifying hypotheses after the primary analyses were completed.

RESULTS: This study included 174 preHD β-blocker users (59 males; 115 females) with a mean age of 46.4 (SD, 13.1) years and a mean cytosine-adenine guanine repeat length of 41.1 (SD, 2.4) who were well matched to 174 preHD non-β-blocker users. The preHD β-blocker users showed a statistically significant reduction in the annualized hazard of receiving a motor diagnosis compared with nonusers (n = 174) (hazard ratio, 0.66; 95% CI, 0.46-0.94; P = .02). There were 149 mmHD β-blocker users (86 males; 60 females) with a mean age of 58.9 (SD, 11.3) years and a mean cytosine-adenine guanine repeat length of 42.0 (SD, 2.3) matched to 149 mmHD non-β-blocker users. The β-blocker users had a slower mean annualized worsening in total motor score (mean difference [MD], -0.45; 95% CI, -0.85 to -0.06; q = 0.025), total functional capacity score (MD, 0.10; 95% CI, 0.02-0.18; q = 0.025), and symbol digit modalities test (MD, 0.33; 95% CI, 0.10-0.56; q = 0.017) compared with matched nonusers.

CONCLUSIONS AND RELEVANCE: In this study, β-blocker use was associated with delayed motor onset in preHD and reduced the rate of worsening of symptoms in mmHD. These findings demonstrated that β-blockers may have a therapeutic role in HD but further studies are required.

PMID:39621338 | DOI:10.1001/jamaneurol.2024.4108

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Respiratory Benefits of Multisetting Air Purification in Children: A Cluster Randomized Crossover Trial

JAMA Pediatr. 2024 Dec 2. doi: 10.1001/jamapediatrics.2024.5049. Online ahead of print.

ABSTRACT

IMPORTANCE: Particulate matter exposure has been linked to impaired respiratory health in children, but the respiratory benefits of air purification have not been fully elucidated.

OBJECTIVES: To assess the respiratory health outcomes among children exposed to multisetting air purification vs sham purification.

DESIGN, SETTING, AND PARTICIPANTS: This cluster randomized, double-blind, crossover trial was conducted among healthy school-aged children (10-12 years) in China from April to December 2021. Data were analyzed from December 2021 to July 2024.

INTERVENTIONS: A multisetting (both in classrooms and bedrooms) air purification intervention compared with sham purification in a 2-stage intervention with more than 2 months (76 days) for each period and a washout period (88 days) to estimate the respiratory benefits of air purification.

MAIN OUTCOMES AND MEASURES: The primary outcomes were pulmonary function, airway inflammation markers, and metabolites in exhaled breath condensate (EBC) before and after the air purification intervention. Linear mixed-effects models were used to estimate the respiratory benefits of children related to air purification. Differential metabolites in EBC were identified using metabolomics analysis to explore their possible mediation roles.

RESULTS: A total of 79 children (38 male [48%]; mean [SD] age, 10.3 [0.5] years) were included in the statistical analyses. During the study period, the mean (SD) concentration of outdoor fine particulate matter (PM2.5) at the school site was 32.53 (24.06) μg/m3. The time-weighted personal PM2.5 concentration decreased by 45.14% during the true air purification period (mean [SD], 21.49 [8.72] μg/m3) compared with the sham air purification period (mean [SD], 39.17 [14.25] μg/m3). Air purification improved forced expiratory volume in 1 second by 8.04% (95% CI, 2.15%-13.93%), peak expiratory flow by 16.52% (95% CI, 2.76%-30.28%), forced vital capacity (FVC) by 5.73% (95% CI, 0.48%-10.98%), forced expiratory flow at 25% to 75% of FVC by 17.22% (95% CI, 3.78%-30.67%), maximal expiratory flow at 75% of FVC by 14.60% (95% CI, 0.35%-28.85%), maximal expiratory flow at 50% of FVC by 17.86% (95% CI, 3.65%-32.06%), and maximal expiratory flow at 25% of FVC by 18.22% (95% CI, 1.73%-34.70%). Fractional exhaled nitric oxide in the true air purification group decreased by 22.38% (95% CI, 2.27%-42.48%). Several metabolites in EBC (eg, L-tyrosine and β-alanine) were identified to mediate the effect of air purification on respiratory health.

CONCLUSIONS AND RELEVANCE: This randomized clinical trial provides robust and holistic evidence that indoor air purification notably improved pulmonary health in children, highlighting the importance of intensified indoor air purification in regions with high air pollution levels.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04835337.

PMID:39621320 | DOI:10.1001/jamapediatrics.2024.5049

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Physicochemistry and comparative metagenomics of a tropical estuary persistently inundated with anthropogenic pollutants

Folia Microbiol (Praha). 2024 Dec 2. doi: 10.1007/s12223-024-01227-3. Online ahead of print.

ABSTRACT

The physicochemistry, metabolic properties, and microbial community structure of a tropical estuary persistently inundated with anthropogenic pollutants were elucidated using diverse analytical tools and a shotgun metagenomics approach. The physicochemistry of the Awoye estuary surface water (AEW) and sediment (AES) revealed higher values in the sediment for most of the parameters analyzed, while aside from copper and zinc, the concentrations of the detected heavy metals (Cd, Cr, Pb, Fe, As, Ni, Hg, Mn, Se) in the water and sediment were higher than the acceptable thresholds. Hydrocarbon content analysis revealed increasingly high concentrations of high molecular weight polycyclic aromatic hydrocarbons (HMW PAHs) in the sediment. Structurally, the predominant taxa in the AEW metagenome are Proteobacteria (50.35%), Alphaproteobacteria (43.31%), Brevundimonas (49.96%), and Leptolyngbya boryana (14.93%), while in the sediment (AES) metagenome, Proteobacteria (53.03%), Gammaproteobacteria (28.66%), Azospirillum (6.51%), and Acidihalobacter prosperus (7.56%) were preponderant. Statistical analysis of the two microbiomes (AEW, AES) revealed significant statistical differences (P < 0.05) at all the hierarchical levels. Functional characterization of the two metagenomes revealed extensive adaptations of the sediment microbiome to various environmental stressors as evident in the high numbers of putative genes involved in the degradation of diverse classes of aromatic hydrocarbons, efflux, detoxification, and transport of heavy metals, and metabolism of organic/inorganic nutrients. Findings from this study revealed that the estuary sediment is the sink for most of the anthropogenic pollutants and harbors the more adapted microbiome that could serve as a potential bioresource for the bioremediation of the perturbed estuary.

PMID:39621289 | DOI:10.1007/s12223-024-01227-3

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Bioinformatics for the Structural Genomics of Poxviruses

Methods Mol Biol. 2025;2860:65-82. doi: 10.1007/978-1-0716-4160-6_5.

ABSTRACT

Poxviruses are large, complex viruses, and their host species are widespread across the tree of life. As a result, the bioinformatics analysis of their genomes can be complex. Here we show how a few helpful tools and strategies can be used to inform the analysis, leading to a better understanding of the structural properties of poxvirus genomes and to a more accurate quality control of, or comparison between, assembled sequences.

PMID:39621261 | DOI:10.1007/978-1-0716-4160-6_5

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Prevalence of Potentially Inappropriate Prescribing in Older Adults in Gulf Cooperation Council Countries: A Systematic Review and Meta-Analysis

J Epidemiol Glob Health. 2024 Dec 2. doi: 10.1007/s44197-024-00332-3. Online ahead of print.

ABSTRACT

INTRODUCTION: Potentially Inappropriate Prescribing (PIP) poses a significant risk to patient safety and associated with poor healthcare outcomes in Gulf Cooperation Council (GCC) countries. This study aimed to assess PIP prevalence and patterns in older adults across all care settings in GCC.

METHODS: A comprehensive search was conducted on six medical databases to identify studies assessing the PIP prevalence in older adults using validated criteria in GCC. Pooled prevalence estimates and odds ratios were calculated using STATA Software (version 16). Statistical heterogeneity was evaluated with the I² statistic, and publication bias was assessed using funnel plot symmetry and Egger’s regression test. The risk of bias was assessed using the JBI Prevalence Critical Appraisal Tool.

RESULTS: Fourteen eligible studies conducted over ten years included 18,647 patients. The median prevalence of PIP was 54.4% (IQR: 37.6-62.1%), higher in hospital settings (59.5%; IQR: 53.7-65.3%) compared to primary care (44.2%; IQR: 18.5-54.4%). Cardiovascular medications were the most common PIP (15,353 occurrences). Polypharmacy was significantly associated with PIP exposure (OR: 5.26; 95% CI: 2.33-11.84). The odds of PIP exposure were significantly increased among older individuals with chronic kidney disease (OR: 1.87; 95% CI: 1.19-2.54) and diabetes (OR: 1.74; 95% CI: 1.18-2.30).

CONCLUSION: This study highlights high PIP prevalence among older adults in GCC countries, particularly in hospital settings. Polypharmacy and certain chronic conditions were significantly associated with PIP exposure. These findings emphasize the need for targeted interventions to improve prescribing practices and medication safety.

PMID:39621251 | DOI:10.1007/s44197-024-00332-3

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Evaluation of global warming effects on juvenile rainbow trout: focus on immunohistochemistry and osmoregulation

Fish Physiol Biochem. 2025 Feb;51(1):1-13. doi: 10.1007/s10695-024-01431-5. Epub 2024 Dec 2.

ABSTRACT

The negative effects of global warming also directly affect aquatic populations. Consequences such as evaporation due to chronic temperature increase, increase in salinity, and increase in stock density per unit volume are potential stress factors. While creating the trial design, an attempt was made to simulate the effects of global warming, especially on species living in salty and brackish water biotopes. In this study, changes in the gills of rainbow trout (Oncorhynchus mykiss) acclimated to 0, 20, and 38 ‰ of saline in the laboratory were examined histologically and immunohistochemically and blood serum osmolarity. In addition, the water temperature was changed, and experiments were carried out at 16, 19, and 22 °C for each salinity group in parallel with the increase in salinity. However, to simulate the decrease in water volume and intensive stocking due to the potential impact of climate change, the study was carried out using 15 fishes in low-volume aquariums (45 L). Tap water that had been kept for at least 3 days was used in the aquariums. To protect the water quality, independent aquariums with sponge filters were used, and since the aim was to keep dissolved oxygen low, no ventilation system other than the sponge filter was used. In order to minimize the deterioration in water quality during the trial, a 15% water change was performed by performing a bottom flush every 4 days and water of the same temperature and salinity was added as much as the reduced volume. In addition, since increasing stock density due to temperature increase and water decrease will cause the amount of dissolved oxygen to decrease, pure oxygen was not entered into any tank throughout the experiment, and the concentration was requested to be at a low level (7 ± 0.13 mg/L) in all groups. The trials were terminated at the end of the 71st day. Increased serum osmolarity values were observed due to the increase in salinity, and the highest serum osmolarity value was measured at 644 mOsm/kg in the 38 ‰ salinity group. Differences between the groups were found to be statistically significant (p < 0.05). It was observed that the number of cells containing Na+/K+-ATPase increased depending on salinity. Also, the number of chloride cells reached the maximum level in the 38 ‰ salinity group. Due to increasing salt levels, an increase in mucus cells, limited onset hyperplasia, aneurysm, lamellar separation, and necrosis were observed in the gill tissue.

PMID:39621246 | DOI:10.1007/s10695-024-01431-5

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Correlation between adult trauma center status and radiology resident performance on trauma cases in the WIDI SIM exam

Emerg Radiol. 2024 Dec 2. doi: 10.1007/s10140-024-02302-5. Online ahead of print.

ABSTRACT

PURPOSE: To assess whether adult trauma center status influences radiology resident performance on trauma cases in the Emergent/Critical Care Imaging SIMulation (WIDI SIM) exam.

MATERIALS AND METHODS: This retrospective study analyzed 29,290 WIDI SIM exam scores from 110 adult trauma cases across 55 radiology residency programs. Residents were categorized by training level-R1 (n = 17,801), R2 (n = 9,136), R3 (n = 1,826), R4 (n = 527)-and by their program’s adult trauma center designation: Level 1 (n = 20,121), Level 2 (n = 1,870), Level 3 (n = 1,029), Level 4 (n = 487), and no trauma designation (n = 5,834). A Generalized Linear Mixed Model with a negative binomial distribution was used to evaluate the effect of trauma center status on resident performance, adjusting for resident level, imaging modality, and case specialty.

RESULTS: After adjusting for confounding variables, there was no statistically significant difference in resident scores based on adult trauma center status (p > 0.05 for all trauma levels compared to no trauma designation). Resident level significantly influenced performance, with higher-level residents scoring better than R1 residents (p < 0.001 for R2-R4). Imaging modality and case specialty also significantly affected scores. Residents performed better on MR, US, and XR modalities compared to CT (p ≤ 0.002), and scored lower on chest, cardiovascular, musculoskeletal, and neuro cases compared to abdominopelvic cases (p < 0.001).

CONCLUSION: Adult trauma center status did not significantly impact radiology resident performance on trauma cases in the WIDI SIM exam. Resident training level, imaging modality, and case specialty were significant factors influencing performance. These findings suggest that resident education and exposure to diverse imaging modalities and specialties are more critical determinants of diagnostic accuracy than the trauma center designation of their training program.

PMID:39621241 | DOI:10.1007/s10140-024-02302-5

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Mechanistic modeling of social conditions in disease-prediction simulations via copulas and probabilistic graphical models: HIV case study

Health Care Manag Sci. 2024 Dec 2. doi: 10.1007/s10729-024-09694-3. Online ahead of print.

ABSTRACT

As social and economic conditions are key determinants of HIV, the United States ‘National HIV/AIDS Strategy (NHAS)’, in addition to care and treatment, aims to address mental health, unemployment, food insecurity, and housing instability, as part of its strategic plan for the ‘Ending the HIV Epidemic’ initiative. Although mechanistic models of HIV play a key role in evaluating intervention strategies, social conditions are typically not part of the modeling framework. Challenges include the unavailability of coherent statistical data for social conditions and behaviors. We developed a method, combining undirected graphical modeling with copula methods, to integrate disparate data sources, to estimate joint probability distributions for social conditions and behaviors. We incorporated these in a national-level network model, Progression and Transmission of HIV (PATH 4.0), to simulate behaviors as functions of social conditions and HIV transmissions as a function of behaviors. As a demonstration for the potential applications of such a model, we conducted two hypothetical what-if intervention analyses to estimate the impact of an ideal 100% efficacious intervention strategy. The first analysis modeled care behavior (using viral suppression as proxy) as a function of depression, neighborhood, housing, poverty, education, insurance, and employment status. The second modeled sexual behaviors (number of partners and condom-use) as functions of employment, housing, poverty, and education status, among persons who exchange sex. HIV transmissions and disease progression were then simulated as functions of behaviors to estimate incidence reductions. Social determinants are key drivers of many infectious and non-infectious diseases. Our work enables the development of decision support tools to holistically evaluate the syndemics of health and social inequity.

PMID:39621234 | DOI:10.1007/s10729-024-09694-3

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Comparison of On-Label Treatment Persistence in Real-World Patients with Psoriatic Arthritis Receiving Guselkumab Versus Subcutaneous Interleukin-17A Inhibitors

Adv Ther. 2024 Dec 2. doi: 10.1007/s12325-024-03042-1. Online ahead of print.

ABSTRACT

INTRODUCTION: Psoriatic arthritis (PsA) is a chronic, multidomain, inflammatory disease requiring long-term treatment. Guselkumab, a fully human interleukin [IL]-23p19-subunit inhibitor, and the IL-17A inhibitors (IL-17Ai) ixekizumab and secukinumab are approved by the US Food and Drug Administration (FDA) for adults with active PsA. Real-world data evaluating on-label treatment persistence is an important consideration for patients.

METHODS: This retrospective claim-based analysis (IQVIA PharMetrics® Plus) included adults with PsA receiving guselkumab or their first subcutaneous (SC) IL-17Ai (ixekizumab/secukinumab) per FDA label (“on-label”) between July 14, 2020, and June 30, 2022. Baseline demographic and disease characteristics were collected in the 12 months preceding the index date (date of first guselkumab or SC IL-17Ai claim); follow-up extended through the earlier of the end of continuous insurance eligibility or end of data availability. Baseline characteristics were balanced between the cohorts by propensity score weighting (standardized mortality ratio [SMR]). Discontinuation was defined as a gap 2 × the FDA-approved maintenance dosing interval (guselkumab:112 days; SC IL-17Ai: 56 days); on-label persistence in the weighted cohorts was assessed using Kaplan-Meier curves and compared with a Cox proportional hazards model.

RESULTS: Weighted demographic and disease characteristics were well balanced between the cohorts (guselkumab: N = 910, mean age = 50.4 years, 60.4% female; SC IL-17Ai: N = 2740, mean age = 50.2, 59.4% female). At 12 months, the guselkumab cohort was 1.85 × more likely to remain persistent with on-label therapy vs the SC IL-17Ai cohort (p < 0.001); median time to discontinuation was not reached for guselkumab and was 12.3 months for SC IL-17Ai. At 3, 6, 9, and 12 months, persistence rates in the weighted cohorts were higher with guselkumab than with SC IL-17Ai (p < 0.001).

CONCLUSION: In this real-world claims data analysis in adults with PsA, on-label persistence rates were statistically significantly higher with guselkumab, as early as 3 months, with ~ 2 × greater likelihood of persistence at 12 months relative to SC IL-17Ai.

PMID:39621228 | DOI:10.1007/s12325-024-03042-1