Nevin Manimala

Telemed J E Health. 2024 Mar 7. doi: 10.1089/tmj.2023.0554. Online ahead of print.

ABSTRACT

Background: The COVID-19 pandemic significantly increased telehealth adoption. Rural communities experience challenges relating to telehealth, including a shortage of clinicians, low health literacy, mistrust of medicine, and limited technology access, yet rural perceptions have not been a subject of robust study. The setting of this study was a rural Midwestern family medicine clinic within an academic health system. Methods: Surveys were given to all patients of age 18 or older visiting the clinic over a one-week period. Those who expressed interest were contacted for a semistructured interview. Descriptive statistics and chi-square testing were used to analyze survey results for significant relationships, while interview transcripts were analyzed for themes. Results: Of respondents, 27% indicated prior telehealth use and were more likely to prefer telehealth visits (p = 0.03). Perceptions of telehealth were sorted into themes, including scope of care, convenience, and technology. Telehealth was preferred for discussing test results or mental health. Barriers such as travel time and transportation access favored telehealth. Although more convenient, telehealth was found to be less effective for relationship building. The absence of physical examination during phone visits was a concern. Phone visits were more prevalent due to failure of video-based technology. Conclusions: Despite the potential to address these unique challenges in rural communities, telehealth acceptance is poor. Barriers such as accessibility of technology can be improved through governmental and health systemwide measures. Future work can help develop interventions that counter negative perceptions of telehealth while increasing interest and uptake in rural communities.

PMID:38452338 | DOI:10.1089/tmj.2023.0554

J Clin Oncol. 2024 Mar 7:JCO2302182. doi: 10.1200/JCO.23.02182. Online ahead of print.

ABSTRACT

PURPOSE: The US Food and Drug Administration (FDA) approved talazoparib with enzalutamide for first-line treatment of patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).

PATIENTS AND METHODS: The approval was based on the HRR gene-mutated (HRRm) population of TALAPRO-2, a randomized, double-blind trial that randomly assigned 1,035 patients with mCRPC to receive enzalutamide with either talazoparib or placebo. Two cohorts enrolled sequentially: an all-comer population (Cohort 1), followed by an HRRm-only population (Cohort 2). The independent primary end points were radiographic progression-free survival (rPFS) per blinded independent central review (BICR) in Cohort 1 (all-comers) and in the combined HRRm population (all HRRm patients from Cohorts 1 and 2). Overall survival (OS) was a key secondary end point.

RESULTS: A statistically significant improvement in rPFS by BICR was demonstrated in both the all-comers cohort and the combined HRRm population, with hazard ratio (HR) of 0.63 (95% CI, 0.51 to 0.78; P < .0001) and 0.45 (95% CI, 0.33 to 0.61; P < .0001), respectively. In an exploratory analysis of the 155 patients with BRCA-mutated (BRCAm) mCRPC, rPFS HR was 0.20 (95% CI, 0.11 to 0.36). In the non-HRRm/unknown stratum of Cohort 1 (n = 636), the rPFS HR was 0.70 (95% CI, 0.54 to 0.89). OS was immature.

CONCLUSION: Despite a statistically significant rPFS improvement in the all-comer cohort, FDA did not consider the magnitude of rPFS clinically meaningful in the context of the broad indication, combination treatment, and safety profile. Approval was therefore limited to patients with HRRm mCRPC, for whom there was a statistically significant and clinically meaningful improvement in rPFS and favorable OS results. This represents the first approval for the first-line treatment of patients with HRRm mCRPC.

PMID:38452327 | DOI:10.1200/JCO.23.02182

Psychiatr Pol. 2023 Oct 16:1-22. doi: 10.12740/PP/OnlineFirst/169912. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to investigate incidences of stigmatisation and discrimination by selected health professionals against patients with HIV/AIDS and HCV, and to assess how these affected feelings in both groups.

METHODS: The study involved 160 patients – 80 diagnosed with HIV/AIDS in the baseline group and 80 with HCV in the comparison group. Patients were recruited from among patients treated in two outpatient clinics of the University Hospital in Krakow.

RESULTS: Incidents of stigmatisation and discrimination were observed significantly more often in the HIV/AIDS group compared to the HCV group. According to the patients, incidents of stigmatisation and discrimination on the part of medical staff occur due to fear and a sense of threat from infection with the viruses. The experience of stigmatisation and discrimination by patients manifests itself in the impediment or denial of healthcare services by medical professionals. Some of the medical staff blamed the patients for the infection, expressed disrespect and verbal aggression towards them, and treated them worse when they found out about the infection. Their emotional state depended on the nature of the relationship with the medical staff triggered by stigmatisation and discrimination.

CONCLUSIONS: Stigmatisation and discrimination by medical staff against patients were, according to the respondents, linked to fear of infection but confirmation of this relationship would require further research. In the course of these cases, patients experienced pejorative verbal evaluation, impediment or denial of health services, which could have specific health consequences. These types of attitudes had a negative impact on their emotional state.

PMID:38452318 | DOI:10.12740/PP/OnlineFirst/169912

Rheumatology (Oxford). 2024 Mar 7:keae140. doi: 10.1093/rheumatology/keae140. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate cancer risk in rheumatoid arthritis (RA) patients treated with tocilizumab/sarilumab, abatacept, or rituximab compared with those who received tumour necrosis factor inhibitors (TNFi) and compared with biological disease-modifying anti-rheumatic drugs (bDMARD) naïve RA patients.

METHODS: Nationwide registry-based cohort study of RA patients initiating treatment with tocilizumab/sarilumab, abatacept, rituximab, TNFi, and bDMARD-naive patients their second type of conventional synthetic DMARD (csDMARD). Patients were identified in DANBIO and followed for cancer from 2006-2020. Patients could contribute multiple treatments, with person years (PYRS), deaths, and cancers allocated to each treatment group in a ‘latest type of treatment’ manner. Inverse probability of treatment weighting and weighted cause-specific Cox models were used to calculate hazard ratios (HRs) for cancer in each tocilizumab/sarilumab, abatacept, and rituximab group compared with TNFI and bDMARD naïve groups, respectively.

RESULTS: In total, 21 982 treatment initiations, 96 475 PYRS, and 1423 cancers were identified. There were no statistically significant increased HRs for overall cancer in tocilizumab/sarilumab, abatacept, or rituximab treatment groups (HRs ranged from 0.7-1.1). More than five years of abatacept exposure showed a non-significantly increased HR compared with TNFi (HR 1.41, 95% confidence intervals CI 0.74-2.71). For hematological cancers, rituximab treatment showed non-significantly reduced HRs: vs TNFi (HR 0.09; 95%CI 0.00-2.06) and bDMARD-naïve (HR 0.13; 95%CI 0.00-1.89).

CONCLUSION: Treatment with tocilizumab/sarilumab, abatacept, or rituximab in RA patients was not associated with increased risks of cancer compared with TNFi-treated and with bDMARD-naïve RA patients in a real-world setting.

PMID:38452297 | DOI:10.1093/rheumatology/keae140

J Am Med Inform Assoc. 2024 Mar 7:ocae004. doi: 10.1093/jamia/ocae004. Online ahead of print.

ABSTRACT

OBJECTIVE: The timely initiation of renal replacement therapy (RRT) for acute kidney injury (AKI) requires sequential decision-making tailored to individuals’ evolving characteristics. To learn and validate optimal strategies for RRT initiation, we used reinforcement learning on clinical data from routine care and randomized controlled trials.

MATERIALS AND METHODS: We used the MIMIC-III database for development and AKIKI trials for validation. Participants were adult ICU patients with severe AKI receiving mechanical ventilation or catecholamine infusion. We used a doubly robust estimator to learn when to start RRT after the occurrence of severe AKI for three days in a row. We developed a “crude strategy” maximizing the population-level hospital-free days at day 60 (HFD60) and a “stringent strategy” recommending RRT when there is significant evidence of benefit for an individual. For validation, we evaluated the causal effects of implementing our learned strategies versus following current best practices on HFD60.

RESULTS: We included 3748 patients in the development set and 1068 in the validation set. Through external validation, the crude and stringent strategies yielded an average difference of 13.7 [95% CI -5.3 to 35.7] and 14.9 [95% CI -3.2 to 39.2] HFD60, respectively, compared to current best practices. The stringent strategy led to initiating RRT within 3 days in 14% of patients versus 38% under best practices.

DISCUSSION: Implementing our strategies could improve the average number of days that ICU patients spend alive and outside the hospital while sparing RRT for many.

CONCLUSION: We developed and validated a practical and interpretable dynamic decision support system for RRT initiation in the ICU.

PMID:38452293 | DOI:10.1093/jamia/ocae004

Harv Rev Psychiatry. 2024 Mar-Apr 01;32(2):58-62. doi: 10.1097/HRP.0000000000000392.

ABSTRACT

Since the inclusion of gender identity disorder in the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III), psychiatry and the broader medical field have made substantial alterations in their recognition of and respect for transgender and gender diverse (TGD) identities. As this recognition continues to expand, psychiatrists should be aware of both historical harm and current best care practices, especially in light of psychiatric morbidity in TGD populations relative to the general population. This article contextualizes the history of psychiatry’s engagement with TGD patients and presents the gender minority stress and resilience model to frame the mental health disparities experienced by TGD people. We envision a role for psychiatry that goes beyond gatekeeping gender-affirming hormone therapy and surgeries. Instead, we should invest in equitable care across the continuum of mental health needs. We provide an overview of existing literature to help characterize psychiatric epidemiology for this population, with the goal of offering guidance on how psychiatrists can deliver responsive and high-quality care for TGD people. Some key areas of proposed clinical improvement include culturally tailoring interventions for substance use disorders, reducing medical trauma in acute psychiatric care settings, and better understanding the interplay of psychopharmacology and gender-affirming hormone therapy.

PMID:38452285 | DOI:10.1097/HRP.0000000000000392

J Evol Biol. 2024 Mar 7:voae025. doi: 10.1093/jeb/voae025. Online ahead of print.

ABSTRACT

Members of the genus Clivia show considerable variation in flower pigmentation and morphology. Such variation is effected by mutations that emerge in candidate flower development genes over time. Besides population history, mutations can further illuminate the effects of demographic events in populations in addition to population genetic parameters including selection, recombination, and linkage disequilibrium (LD). The current study aimed to find sequence variants in two anthocyanin biosynthetic genes (DFR and bHLH) of Clivia miniata and use the data to assess population genetic factors from a random collection of orange/red- and yellow-flowered specimens. Overall, average nucleotide diversity in the two anthocyanin genes was moderate (π = 0.00646), whereas haplotypes differed significantly (Hd ≥ 0.9). Gene evolution was seemingly driven by mutations (CmiDFR) or recombination (CmibHLH001). LD decayed swiftly within the analyzed gene regions and supported the feasibility of assessing trait-variant associations via the association/linkage mapping approach. In the end, most associations were found to be spurious, but one haplotype in CmibHLH001 showed a promising correlation to the orange/red flower phenotype in Clivia specimens. In all, the present study is the first to measure gene-level diversity in C. miniata – data that had never been reported so far. Further, the study also identified allelic and haplotypic variants that may be beneficial in future association genetic studies of Clivia. Such studies, however, consider large diverse populations to control for statistical bias intrinsic to the analysis of small datasets.

PMID:38452247 | DOI:10.1093/jeb/voae025

J Gerontol A Biol Sci Med Sci. 2024 Mar 7:glae077. doi: 10.1093/gerona/glae077. Online ahead of print.

ABSTRACT

Alzheimer’s disease is strongly linked to metabolic abnormalities. We aimed to distinguish amyloid-positive people who progressed to cognitive decline from those who remained cognitively intact. We performed untargeted metabolomics of blood samples from amyloid-positive individuals, before any sign of cognitive decline, to distinguish individuals who progressed to cognitive decline from those who remained cognitively intact. A plasma-derived metabolite signature was developed from Supercritical Fluid chromatography coupled with high-resolution mass spectrometry (SFC-HRMS) and nuclear magnetic resonance (NMR) metabolomics. The two metabolomics datasets were analyzed by Data Integration Analysis for Biomarker discovery using Latent approaches for Omics studies (DIABLO), to identify a minimum set of metabolites that could describe cognitive decline status. NMR or SFC-HRMS data alone cannot predict cognitive decline. However, among the 320 metabolites identified, a statistical method that integrated the two datasets enabled identification of a minimal signature of 9 metabolites (3-hydroxybutyrate, citrate, succinate, acetone, methionine, glucose, serine, sphingomyelin d18:1/C26:0 and triglyceride C48:3) with a statistically significant ability to predict cognitive decline more than 3 years before decline. This metabolic fingerprint obtained during this exploratory study may help to predict amyloid-positive individuals who will develop cognitive decline. Due to the high prevalence of brain amyloid-positivity in older adults, identifying adults who will have cognitive decline will enable the development of personalized and early interventions.

PMID:38452244 | DOI:10.1093/gerona/glae077

Eur J Orthod. 2024 Apr 1;46(2):cjae011. doi: 10.1093/ejo/cjae011.

ABSTRACT

OBJECTIVES: The rapid advancement of Large Language Models (LLMs) has prompted an exploration of their efficacy in generating PICO-based (Patient, Intervention, Comparison, Outcome) queries, especially in the field of orthodontics. This study aimed to assess the usability of Large Language Models (LLMs), in aiding systematic review processes, with a specific focus on comparing the performance of ChatGPT 3.5 and ChatGPT 4 using a specialized prompt tailored for orthodontics.

MATERIALS/METHODS: Five databases were perused to curate a sample of 77 systematic reviews and meta-analyses published between 2016 and 2021. Utilizing prompt engineering techniques, the LLMs were directed to formulate PICO questions, Boolean queries, and relevant keywords. The outputs were subsequently evaluated for accuracy and consistency by independent researchers using three-point and six-point Likert scales. Furthermore, the PICO records of 41 studies, which were compatible with the PROSPERO records, were compared with the responses provided by the models.

RESULTS: ChatGPT 3.5 and 4 showcased a consistent ability to craft PICO-based queries. Statistically significant differences in accuracy were observed in specific categories, with GPT-4 often outperforming GPT-3.5.

LIMITATIONS: The study’s test set might not encapsulate the full range of LLM application scenarios. Emphasis on specific question types may also not reflect the complete capabilities of the models.

CONCLUSIONS/IMPLICATIONS: Both ChatGPT 3.5 and 4 can be pivotal tools for generating PICO-driven queries in orthodontics when optimally configured. However, the precision required in medical research necessitates a judicious and critical evaluation of LLM-generated outputs, advocating for a circumspect integration into scientific investigations.

PMID:38452222 | DOI:10.1093/ejo/cjae011

Scand J Pain. 2024 Mar 7;24(1). doi: 10.1515/sjpain-2023-0035. eCollection 2024 Jan 1.

ABSTRACT

OBJECTIVES: Pain catastrophizing in the aging population has not been studied in great detail. Existing investigations have reported conflicting results on the effects of age on pain catastrophizing in relation to pain responses. This study investigated the relationship between pain catastrophizing, and its individual components (rumination, magnification, and helplessness), and the responses to standardized experimental pain stimuli in old and young, healthy adults.

METHODS: Sixty-six volunteers (32 old: 65-87, 18 females; 34 young: 20-35, 17 females) participated in the study. Pain catastrophizing including the components of rumination, magnification, and helplessness was assessed with the pain catastrophizing scale (PCS). Experimental pain was induced by applying predefined pressure stimulations to the trapezius muscle. Pain intensity and unpleasantness were assessed using numerical rating scales. Pain catastrophizing levels and pain responses were statistically compared between the two age groups.

RESULTS: Elderly individuals reported significantly (p = 0.028) lower scores of pain catastrophizing (Med = 5; interquartile range [IQR] = 14) than younger individuals; this difference was driven by the significantly lower components of rumination (Med = 2; IQR = 4; p = 0.017) and helplessness (Med = 2; IQR = 7; p = 0.049). A larger proportion of young (57.8%) rated pain catastrophizing at high levels, with scores above the 75th percentile (Med = 20). Additionally, elderly reported the lowest pain intensity (Med = 5; p = 0.034) and pain unpleasantness (Med = 4.5; p = 0.011) responses to the experimental pressure stimuli. In the elderly group, pain unpleasantness was positively and significantly associated with pain catastrophizing (r _s = 0.416, p = 0.021), rumination (r _s = 0.42, p = 0.019), and helplessness (r _s = 0.434, p = 0.015), respectively. No associations were found in the young group.

CONCLUSIONS: Elderly reported lower PCSs than young adults. Rumination and helplessness were reduced in the elderly group. The elderly population showed positive correlations between catastrophizing levels and pain unpleasantness to standardized pressure pain stimuli. Results supported the view that elderly possess resilience over specific domains of pain catastrophizing that could counteract pain perception due to physiological decline.

PMID:38452201 | DOI:10.1515/sjpain-2023-0035