Comparing the Efficacy and Efficiency of Human and Generative AI: Qualitative Thematic Analyses.

BACKGROUND: Qualitative methods are incredibly beneficial to the dissemination and implementation of new digital health interventions; however, these methods can be time intensive and slow down dissemination when timely knowledge from the data sources is needed in ever-changing health systems. Recent advancements in generative artificial intelligence (GenAI) and their underlying large language models (LLMs) may provide a promising opportunity to expedite the qualitative analysis of textual data, but their efficacy and reliability remain unknown. OBJECTIVE: The primary objectives of our study were to evaluate the consistency in themes, reliability of coding, and time needed for inductive and deductive thematic analyses between GenAI (ie, ChatGPT and Bard) and human coders. METHODS: The qualitative data for this study consisted of 40 brief SMS text message reminder prompts used in a digital health intervention for promoting antiretroviral medication adherence among people with HIV who use methamphetamine. Inductive and deductive thematic analyses of these SMS text messages were conducted by 2 independent teams of human coders. An independent human analyst conducted analyses following both approaches using ChatGPT and Bard. The consistency in themes (or the extent to which the themes were the same) and reliability (or agreement in coding of themes) between methods were compared. RESULTS: The themes generated by GenAI (both ChatGPT and Bard) were consistent with 71% (5/7) of the themes identified by human analysts following inductive thematic analysis. The consistency in themes was lower between humans and GenAI following a deductive thematic analysis procedure (ChatGPT: 6/12, 50%; Bard: 7/12, 58%). The percentage agreement (or intercoder reliability) for these congruent themes between human coders and GenAI ranged from fair to moderate (ChatGPT, inductive: 31/66, 47%; ChatGPT, deductive: 22/59, 37%; Bard, inductive: 20/54, 37%; Bard, deductive: 21/58, 36%). In general, ChatGPT and Bard performed similarly to each other across both types of qualitative analyses in terms of consistency of themes (inductive: 6/6, 100%; deductive: 5/6, 83%) and reliability of coding (inductive: 23/62, 37%; deductive: 22/47, 47%). On average, GenAI required significantly less overall time than human coders when conducting qualitative analysis (20, SD 3.5 min vs 567, SD 106.5 min). CONCLUSIONS: The promising consistency in the themes generated by human coders and GenAI suggests that these technologies hold promise in reducing the resource intensiveness of qualitative thematic analysis; however, the relatively lower reliability in coding between them suggests that hybrid approaches are necessary. Human coders appeared to be better than GenAI at identifying nuanced and interpretative themes. Future studies should consider how these powerful technologies can be best used in collaboration with human coders to improve the efficiency of qualitative research in hybrid approaches while also mitigating potential ethical risks that they may pose.

Postural Stability as a Measure of Fall Risk in Older People with and without HIV.

As the number of older people with HIV (PWH) grows, accidental falls and their associated negative health outcomes are of increasing concern. Fall risk can be measured using novel screening tools such as evaluating postural stability using force plate technology. The aims of this study were to test this technology to assess fall risk among older PWH. In a cross-sectional, observational study of people without HIV (PWoH) with a range of fall risk, participants underwent balance assessment using the validated BTrackS balance plate. Postural stability was compared by HIV serostatus. Multivariable linear regressions were used to examine the relationship between postural stability and validated measures of fall risk balance and frailty status. Among 34 PWH and 30 PWoH, all ≥50 years, postural stability was worse among PWH (35.4 cm vs. 28.3 cm, p = .07). In multivariable models, worse postural stability was associated with reporting a fall in the past 6 months (ß = 0.32, p = .004), worse fall efficacy (ß = 0.45, p < .001), and being frail or prefrail (ß = 0.26, p = .027). In multivariable models stratified by HIV serostatus, worse postural stability was significantly associated with worse fall efficacy (ß = 0.53, p < .01) and lower balance confidence (ß = -0.33, p =. 04) among PWH but not PWoH. Among older PWH and PWoH, worse postural stability was associated with validated measures of fall risk, including history of falls and poorer fall efficacy. Assessment of postural sway is a promising objective screening test for fall risk among older PWH.

Biopsychosocial phenotypes in people with HIV in the CHARTER cohort.

Neuropsychiatric complications such as neurocognitive impairment and depression are common in people with HIV despite viral suppression on antiretroviral therapy, but these conditions are heterogeneous in their clinical presentations and associated disability. Identifying novel biopsychosocial phenotypes that account for neurocognitive performance and depressive and functional symptoms will better reflect the complexities encountered in clinical practice and may have pathological and therapeutic implications. We classified 1580 people with HIV based on 17 features, including 7 cognitive domains, 4 subscales of the Beck depression inventory-II, 5 components of the patient's assessment of own functioning inventory, and dependence in instrumental and basic activities of daily living. A two-stage clustering procedure consisting of dimension reduction with self-organizing maps and Mahalanobis distance-based k-means clustering algorithms was applied to cross-sectional data. Baseline demographic and clinical characteristics were compared between the phenotypes, and their prediction on the biopsychosocial phenotypes was evaluated using multinomial logistic regression. Four distinct phenotypes were identified. Participants in Phenotype 1 overall did well in all domains. Phenotype 2 had mild-to-moderate depressive symptoms and the most substance use disorders. Phenotype 3 had mild-to-moderate cognitive impairment, moderate depressive symptoms, and the worst daily functioning; they also had the highest proportion of females and non-HIV conditions that could affect cognition. Phenotype 4 had mild-to-moderate cognitive impairment but with relatively good mood, and daily functioning. Multivariable analysis showed that demographic characteristics, medical conditions, lifetime cocaine use disorder, triglycerides, and non-antiretroviral therapy medications were important variables associated with biopsychosocial phenotype. We found complex, multidimensional biopsychosocial profiles in people with HIV that were associated with different risk patterns. Future longitudinal work should determine the stability of these phenotypes, assess factors that influence transitions from one phenotype to another, and characterize their biological associations.

AI as a Medical Device Adverse Event Reporting in Regulatory Databases: Protocol for a Systematic Review.

BACKGROUND: The reporting of adverse events (AEs) relating to medical devices is a long-standing area of concern, with suboptimal reporting due to a range of factors including a failure to recognize the association of AEs with medical devices, lack of knowledge of how to report AEs, and a general culture of nonreporting. The introduction of artificial intelligence as a medical device (AIaMD) requires a robust safety monitoring environment that recognizes both generic risks of a medical device and some of the increasingly recognized risks of AIaMD (such as algorithmic bias). There is an urgent need to understand the limitations of current AE reporting systems and explore potential mechanisms for how AEs could be detected, attributed, and reported with a view to improving the early detection of safety signals. OBJECTIVE: The systematic review outlined in this protocol aims to yield insights into the frequency and severity of AEs while characterizing the events using existing regulatory guidance. METHODS: Publicly accessible AE databases will be searched to identify AE reports for AIaMD. Scoping searches have identified 3 regulatory territories for which public access to AE reports is provided: the United States, the United Kingdom, and Australia. AEs will be included for analysis if an artificial intelligence (AI) medical device is involved. Software as a medical device without AI is not within the scope of this review. Data extraction will be conducted using a data extraction tool designed for this review and will be done independently by AUK and a second reviewer. Descriptive analysis will be conducted to identify the types of AEs being reported, and their frequency, for different types of AIaMD. AEs will be analyzed and characterized according to existing regulatory guidance. RESULTS: Scoping searches are being conducted with screening to begin in April 2024. Data extraction and synthesis will commence in May 2024, with planned completion by August 2024. The review will highlight the types of AEs being reported for different types of AI medical devices and where the gaps are. It is anticipated that there will be particularly low rates of reporting for indirect harms associated with AIaMD. CONCLUSIONS: To our knowledge, this will be the first systematic review of 3 different regulatory sources reporting AEs associated with AIaMD. The review will focus on real-world evidence, which brings certain limitations, compounded by the opacity of regulatory databases generally. The review will outline the characteristics and frequency of AEs reported for AIaMD and help regulators and policy makers to continue developing robust safety monitoring processes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/48156.

Alzheimer-Type Cerebral Amyloidosis in the Context of HIV Infection: Implications for a Proposed New Treatment Approach.

Reverse transcriptase inhibitors (RTIs) are currently broadly prescribed for the treatment of HIV infection but are also thought to prevent Alzheimer's disease (AD) progression by protecting against amyloidosis. Our study evaluates the hypothesis that reverse transcriptase inhibitors protect against Alzheimer-type brain amyloidogenesis in the context of HIV infection. We compiled a case series of participants from a prospective study of the neurological consequences of HIV infection at the HIV Neurobehavioral Research Program (HNRP) who had serial neuropsychological and neurological assessments and were on RTIs. Two participants had gross and microscopic examination and immunohistochemistry of the brain at autopsy; one was assessed clinically for Alzheimer's disease by cerebrospinal fluid (CSF) analysis of phosphorylated-Tau, Total-Tau and Aß42. Additionally, a larger cohort of 250 autopsied individuals was evaluated for presence of amyloid plaques, Tau, and related pathologies. Three older, virally suppressed individuals with HIV who had long-term treatment with RTIs were included in analyses. Two cases demonstrated substantial cerebral amyloid deposition at autopsy. The third case met clinical criteria for AD based on a typical clinical course and CSF biomarker profile. In the larger cohort of autopsied individuals, the prevalence of cerebral amyloidosis among people with HIV (PWH) was greater for those on RTIs. Our study showed that long-term RTI therapy did not protect against Alzheimer-type brain amyloidogenesis in the context of HIV infection in these patients. Given the known toxicities of RTIs, it is premature to recommend them to individuals at risk or with Alzheimer's disease who do not have HIV infection.

Detecting Algorithmic Errors and Patient Harms for AI-Enabled Medical Devices in Randomized Controlled Trials: Protocol for a Systematic Review.

BACKGROUND: Artificial intelligence (AI) medical devices have the potential to transform existing clinical workflows and ultimately improve patient outcomes. AI medical devices have shown potential for a range of clinical tasks such as diagnostics, prognostics, and therapeutic decision-making such as drug dosing. There is, however, an urgent need to ensure that these technologies remain safe for all populations. Recent literature demonstrates the need for rigorous performance error analysis to identify issues such as algorithmic encoding of spurious correlations (eg, protected characteristics) or specific failure modes that may lead to patient harm. Guidelines for reporting on studies that evaluate AI medical devices require the mention of performance error analysis; however, there is still a lack of understanding around how performance errors should be analyzed in clinical studies, and what harms authors should aim to detect and report. OBJECTIVE: This systematic review will assess the frequency and severity of AI errors and adverse events (AEs) in randomized controlled trials (RCTs) investigating AI medical devices as interventions in clinical settings. The review will also explore how performance errors are analyzed including whether the analysis includes the investigation of subgroup-level outcomes. METHODS: This systematic review will identify and select RCTs assessing AI medical devices. Search strategies will be deployed in MEDLINE (Ovid), Embase (Ovid), Cochrane CENTRAL, and clinical trial registries to identify relevant papers. RCTs identified in bibliographic databases will be cross-referenced with clinical trial registries. The primary outcomes of interest are the frequency and severity of AI errors, patient harms, and reported AEs. Quality assessment of RCTs will be based on version 2 of the Cochrane risk-of-bias tool (RoB2). Data analysis will include a comparison of error rates and patient harms between study arms, and a meta-analysis of the rates of patient harm in control versus intervention arms will be conducted if appropriate. RESULTS: The project was registered on PROSPERO in February 2023. Preliminary searches have been completed and the search strategy has been designed in consultation with an information specialist and methodologist. Title and abstract screening started in September 2023. Full-text screening is ongoing and data collection and analysis began in April 2024. CONCLUSIONS: Evaluations of AI medical devices have shown promising results; however, reporting of studies has been variable. Detection, analysis, and reporting of performance errors and patient harms is vital to robustly assess the safety of AI medical devices in RCTs. Scoping searches have illustrated that the reporting of harms is variable, often with no mention of AEs. The findings of this systematic review will identify the frequency and severity of AI performance errors and patient harms and generate insights into how errors should be analyzed to account for both overall and subgroup performance. TRIAL REGISTRATION: PROSPERO CRD42023387747; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=387747. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/51614.

Correction: Cingulate transcranial direct current stimulation in adults with HIV.

[This corrects the article DOI: 10.1371/journal.pone.0269491.].

The optimal second-line therapy for older adults with type 2 diabetes mellitus: protocol for a systematic review and network meta-analysis using individual participant data (IPD).

BACKGROUND: Due to increasing life expectancy, almost half of people with type 2 diabetes are aged 65 years or over worldwide. When metformin alone does not control blood sugar, the choice of which second-line therapy to prescribe next is not clear from currently available evidence. The existence of frailty and comorbidities in older adults further increases the complexity of medical decision-making. As only a relatively small proportion of trials report results separately for older adults, the relative efficacy and safety of second-line therapies in older adults with type 2 diabetes mellitus are unknown and require further investigation. This individual participant data (IPD) network meta-analysis evaluates the relative efficacy and safety of second-line therapies on their own or in combination in older adults with type 2 diabetes mellitus. METHODS: All relevant published and unpublished trials will be identified. Studies published prior to 2015 will be identified from two previous comprehensive aggregate data network meta-analyses. Searches will be conducted in CENTRAL, MEDLINE, and EMBASE from 1st January 2015 onwards, and in clinicaltrials.gov from inception. Randomised controlled trials with at least 100 estimated older adults (≥ 65 years) receiving at least 24 weeks of intervention that assess the effects of glucose-lowering drugs on mortality, glycemia, vascular and other comorbidities outcomes, and quality of life will be eligible. The screening and data extraction process will be conducted independently by two researchers. The quality of studies will be assessed using the Cochrane risk of bias tool 2. Anonymised IPD of all eligible trials will be requested via clinical trial portals or by contacting the principal investigators or sponsors. Received data will be reanalysed where necessary to standardise outcome metrics. Network meta-analyses will be performed to determine the relative effectiveness of therapies. DISCUSSION: With the increasing number of older adults with type 2 diabetes worldwide, an IPD network meta-analysis using data from all eligible trials will provide new insights into the optimal choices of second-line antidiabetic drugs to improve patient management and reduce unnecessary adverse events and the subsequent risk of comorbidities in older adults. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021272686.

Social Determinants and Consequences of Pain: Toward Multilevel, Intersectional, and Life Course Perspectives.

Despite wide endorsement of a biopsychosocial framework for pain, social aspects of pain remain rarely addressed in the context of pain prevention and management. In this review, we aim to 1) examine the broad scope of social determinants and consequences of pain and their interactions across multiple levels of organization, and 2) provide a framework synthesizing existing concepts and potential areas for future work on social aspects of pain, drawing upon socioecological, intersectional, and life course approaches. Integrating interdisciplinary theory and evidence, we outline pathways through which multilevel social factors and pain may affect each other over time. We also provide a brief summary of intrapersonal aspects of pain, which are thought to operate at the interface between individuals and the social context. Progressing from micro- to macrolevel factors, we illustrate how social determinants of pain can directly or indirectly contribute to pain experiences, expression, risk, prognosis, and impact across populations. We consider 1) at the interpersonal level, the roles of social comparison, social relatedness, social support, social exclusion, empathy, and interpersonal conflict; 2) at the group or community level, the roles of intimacy groups, task groups, social categories, and loose associations; and 3) at the societal level, the roles of political, economic, and cultural systems, as well as their policies and practices. We present examples of multilevel consequences of pain across these levels and discuss opportunities to reduce the burden and inequities of pain by expanding multilevel social approaches in pain research and practice. PERSPECTIVE: Despite wide endorsement of a biopsychosocial framework for pain, social aspects of pain are often unclearly defined, hindering their use in pain prevention, management, and research. We summarize the scope of social aspects of pain and provide a framework synthesizing existing concepts and potential areas for future work.

The impact of intimate partner violence on PrEP adherence among U.S. Cisgender women at risk for HIV.

BACKGROUND: Cisgender women account for 1 in 5 new HIV infections in the United States, yet remain under-engaged in HIV prevention. Women experiencing violence face risk for HIV due to biological and behavioral mechanisms, and barriers to prevention, such as challenges to Pre-Exposure Prophylaxis for HIV Prevention (PrEP) adherence. In this analysis, we aim to characterize intimate partner violence (IPV) among cisgender heterosexual women enrolled in a PrEP demonstration project and assess the associations with PrEP adherence. METHODS: Adherence Enhancement Guided by Individualized Texting and Drug Levels (AEGiS) was a 48-week single-arm open-label study of PrEP adherence in HIV-negative cisgender women in Southern California (N = 130) offered daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). From 6/2016 to 10/2018, women completed a survey reporting HIV risk behavior and experiences of any IPV (past 90-days) and IPV sub-types (past-year, lifetime) and biological testing for HIV/STIs at baseline, and concentrations of tenofovir-diphosphate (TFV-DP) in dried blood spots at weeks 4, 12, 24, 36, and 48. Outcomes were TFV-DP concentrations consistent with ≥ 4 or ≥ 6 doses/week at one or multiple visits. Multivariable logistic regression models were conducted to examine associations. RESULTS: Past-90-day IPV was reported by 34.4% of participants, and past-year and lifetime subtypes reported by 11.5-41.5%, and 21.5-52.3%, respectively. Women who engaged in sex work and Black women were significantly more likely to report IPV than others. Lifetime physical IPV was negatively associated with adherence at ≥ 4 doses/week at ≥ 3 of 5 visits, while other relationships with any IPV and IPV sub-types were variable. CONCLUSION: IPV is an indication for PrEP and important indicator of HIV risk; our findings suggest that physical IPV may also negatively impact long-term PrEP adherence. CLINICAL TRIALS REGISTRATION: NCT02584140 (ClinicalTrials.gov), registered 15/10/2015.

User Experience of Persons Using Ingestible Sensor-Enabled Pre-Exposure Prophylaxis to Prevent HIV Infection: Cross-Sectional Survey Study.

Background: A digital health technology's success or failure depends on how it is received by users. objectives: We conducted a user experience (UX) evaluation among persons who used the Food and Drug Administration-approved Digital Health Feedback System incorporating ingestible sensors (ISs) to capture medication adherence, after they were prescribed oral pre-exposure prophylaxis (PrEP) to prevent HIV infection. We performed an association analysis with baseline participant characteristics, to see if "personas" associated with positive or negative UX emerged. Methods: UX data were collected upon exit from a prospective intervention study of adults who were HIV negative, prescribed oral PrEP, and used the Digital Health Feedback System with IS-enabled tenofovir disoproxil fumarate plus emtricitabine (IS-Truvada). Baseline demographics; urine toxicology; and self-report questionnaires evaluating sleep (Pittsburgh Sleep Quality Index), self-efficacy, habitual self-control, HIV risk perception (Perceived Risk of HIV Scale 8-item), and depressive symptoms (Patient Health Questionnaire-8) were collected. Participants with ≥28 days in the study completed a Likert-scale UX questionnaire of 27 questions grouped into 4 domain categories: overall experience, ease of use, intention of future use, and perceived utility. Means and IQRs were computed for participant total and domain subscores, and linear regressions modeled baseline participant characteristics associated with UX responses. Demographic characteristics of responders versus nonresponders were compared using the Fisher exact and Wilcoxon rank-sum tests. Results: Overall, 71 participants were enrolled (age: mean 37.6, range 18-69 years; n=64, 90% male; n=55, 77% White; n=24, 34% Hispanic; n=68, 96% housed; and n=53, 75% employed). No demographic differences were observed in the 63 participants who used the intervention for ≥28 days. Participants who completed the questionnaire were more likely to be housed (52/53, 98% vs 8/10, 80%; P=.06) and less likely to have a positive urine toxicology (18/51, 35% vs 7/10, 70%; P=.08), particularly methamphetamine (4/51, 8% vs 4/10, 40%; P=.02), than noncompleters. Based on IQR values, ≥75% of participants had a favorable UX based on the total score (median 3.78, IQR 3.17-4.20), overall experience (median 4.00, IQR 3.50-4.50), ease of use (median 3.72, IQR 3.33-4.22), and perceived utility (median 3.72, IQR 3.22-4.25), and ≥50% had favorable intention of future use (median 3.80, IQR 2.80-4.40). Following multipredictor modeling, self-efficacy was significantly associated with the total score (0.822, 95% CI 0.405-1.240; P<.001) and all subscores (all P<.05). Persons with more depressive symptoms reported better perceived utility (P=.01). Poor sleep was associated with a worse overall experience (-0.07, 95% CI -0.133 to -0.006; P=.03). Conclusions: The UX among persons using IS-enabled PrEP (IS-Truvada) to prevent HIV infection was positive. Association analysis of baseline participant characteristics linked higher self-efficacy with positive UX, more depressive symptoms with higher perceived utility, and poor sleep with negative UX.

Neurocognition and its predictors in a linguistically and culturally diverse cohort of people with HIV.

Objective: HIV/AIDS disproportionately affects Black and Latino people in the United States, yet there is a lack of research on predictors of neurocognitive outcomes in these groups. We examined neurocognitive performance and its key predictors across White, Black, and Latino people with HIV (PWH). Method: Participants included 586 PWH of White, Black, and Latino (English- and Spanish-speaking) background. Neurocognition was assessed via demographically-adjusted Fluid Cognition Composite T-scores from the NIH-Toolbox cognition battery, and individual tests comprising this composite. Predictors examined included sociodemographic and HIV disease characteristics, and medical, psychiatric and substance comorbidities. Results: Compared to White PWH, English-speaking Latino PWH had lower T-scores on the Fluid Cognition Composite, as well as Flanker Inhibition and Picture Sequence Memory tests. While there were no other significant group differences on Fluid Cognition, both Latino PWH language groups performed worse than Black PWH on Flanker Inhibition, and Black PWH performed worse than White PWH on List Sorting. Separate multivariable linear regression models by ethnic/racial/language group showed that significant correlates of worse Fluid Cognition included depressive symptoms among White PWH; hepatitis C co-infection among Black PWH; hypertension among English-speaking Latino PWH; and higher estimated duration of HIV disease and depressive symptoms in Spanish-speaking Latino PWH. Conclusions: Findings suggest worse neurocognition among English-speaking Latino PWH compared to Whites. Predictors of neurocognitive function among PWH differ across ethnic/racial and language groups. Consideration of these HIV disease characteristics and comorbidities may be valuable in developing targeted culturally-relevant interventions aimed at ameliorating neurocognitive dysfunction among diverse PWH.

The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.

Disparities in Metabolic Syndrome and Neurocognitive Function Among Older Hispanics/Latinos with Human Immunodeficiency Virus.

Neurocognitive impairment and metabolic syndrome (MetS) are prevalent in persons with HIV (PWH). We examined disparities in HIV-associated neurocognitive function between Hispanic and non-Hispanic White older PWH, and the role of MetS in explaining these disparities. Participants included 116 community-dwelling PWH aged 50-75 years enrolled in a cohort study in southern California [58 Hispanic (53% Spanish speaking) and 58 age-comparable non-Hispanic White; overall group: age: M = 57.9, standard deviation (SD) = 5.7; education (years): M = 13, SD = 3.4; 83% male, 58% AIDS, 94% on antiretroviral therapy]. Global neurocognition was derived from T-scores adjusted for demographics (age, education, sex, ethnicity, language) on a battery of 10 cognitive tests. MetS was ascertained via standard criteria that considered central obesity, and fasting elevated triglycerides, low high-density lipoprotein cholesterol and elevated glucose, or medical treatment for these conditions. Covariates examined included sociodemographic, psychiatric, substance use and HIV disease characteristics. Compared with non-Hispanic Whites, Hispanics showed worse global neurocognitive function (Cohen's d = 0.56, p < 0.05) and had higher rates of MetS (38% vs. 56%, p < 0.05). A stepwise regression model including ethnicity and significant covariates showed Hispanic ethnicity was the sole significant predictor of worse global neurocognition (B = -3.82, SE = 1.27, p < 0.01). A model also including MetS showed that both Hispanic ethnicity (B = -3.39, SE = 1.31, p = 0.01) and MetS (B = -2.73, SE = 1.31, p = 0.04) were independently associated with worse neurocognition. In conclusion, findings indicate that increased MetS is associated with worse neurocognitive function in both Hispanic and non-Hispanic White older PWH, but does not explain neurocognitive disparities. MetS remains an important target for intervention efforts to ameliorate neurocognitive dysfunction among diverse older PWH.

Interventions to improve latent and active tuberculosis treatment completion rates in underserved groups in low incidence countries: a scoping review.

BACKGROUND: People in underserved groups have higher rates of tuberculosis (TB) and poorer treatment outcomes compared with people with no social risk factors. OBJECTIVES: This scoping review aimed to identify interventions that improve TB treatment adherence or completion rates. ELIGIBILITY CRITERIA: Studies of any design focusing on interventions to improve adherence or completion of TB treatment in underserved populations in low incidence countries. SOURCES OF EVIDENCE: MEDLINE, Embase and Cochrane CENTRAL were searched (January 2015 to December 2023). CHARTING METHODS: Piloted data extraction forms were used. Findings were tabulated and reported narratively. Formal risk of bias assessment or synthesis was not undertaken. RESULTS: 47 studies were identified. There was substantial heterogeneity in study design, population, intervention components, usual care and definition of completion rates. Most studies were in migrants or refugees, with fewer in populations with other risk factors (eg, homelessness, imprisonment or substance abuse). Based on controlled studies, there was limited evidence to suggest that shorter treatment regimens, video-observed therapy (compared with directly observed therapy), directly observed therapy (compared with self-administered treatment) and approaches that include tailored health or social support beyond TB treatment may lead to improved outcomes. This evidence is mostly observational and subject to confounding. There were no studies in Gypsy, Roma and Traveller populations, or individuals with mental health disorders and only one in sex workers. Barriers to treatment adherence included a lack of knowledge around TB, lack of general health or social support and side effects. Facilitators included health education, trusted relationships between patients and healthcare staff, social support and reduced treatment duration. CONCLUSIONS: The evidence base is limited, and few controlled studies exist. Further high-quality research in well-defined underserved populations is needed to confirm the limited findings and inform policy and practice in TB management. Further qualitative research should include more people from underserved groups.

Longitudinal analysis of CSF HIV RNA in untreated people with HIV: Identification of CSF controllers.

Interindividual variation of human immunodeficiency virus (HIV) RNA setpoint in cerebrospinal fluid (CSF) and its determinants are poorly understood, but relevant for HIV neuropathology, brain reservoirs, viral escape, and reseeding after antiretroviral interruptions. Longitudinal multicentric study on demographic, clinical, and laboratory correlates of CSF HIV RNA in 2000 follow-up visits from 597 people with HIV (PWH) off antiretroviral therapy (ART) and with plasma HIV RNA > the lower limit of quantification (LLQ). Factors associated with CSF control (CSFC; CSF HIV RNA < LLQ while plasma HIV RNA > LLQ) and with CSF/plasma discordance (CSF > plasma HIV RNA > LLQ) were also assessed through mixed-effects models. Posthoc and sensitivity analyses were performed for persistent CSFC and ART-naïve participants, respectively. Over a median follow-up of 2.1 years, CSF HIV RNA was associated with CD4+ and CD8+ T cells, CSF leukocytes, blood-brain barrier (BBB) integrity, biomarkers of iron and lipid metabolism, serum globulins, past exposure to lamivudine, and plasma HIV RNA (model p < 0.0001). CSFC (persistent in 7.7% over 3 years) and CSF/plasma discordance (persistent in <0.01% over 1 year) were variably associated with the same parameters (model p < 0.001). Sensitivity analyses confirmed most of the previous associations in participants never exposed to ART. Persistent CSFC was associated with higher CD4+ T-cell count nadir (p < 0.001), lower serum globulins (p = 0.003), and lower CSF leukocytes (p < 0.001). Without ART, one in 13 PWH had persistently undetectable CSF HIV RNA, while persistent CSF/plasma discordance was extremely rare over years. Immune responses, inflammation, BBB permeability, and iron and lipid metabolism were all associated with HIV replication in CSF.

The impacts of rising vapour pressure deficit in natural and managed ecosystems.

An exponential rise in the atmospheric vapour pressure deficit (VPD) is among the most consequential impacts of climate change in terrestrial ecosystems. Rising VPD has negative and cascading effects on nearly all aspects of plant function including photosynthesis, water status, growth and survival. These responses are exacerbated by land-atmosphere interactions that couple VPD to soil water and govern the evolution of drought, affecting a range of ecosystem services including carbon uptake, biodiversity, the provisioning of water resources and crop yields. However, despite the global nature of this phenomenon, research on how to incorporate these impacts into resilient management regimes is largely in its infancy, due in part to the entanglement of VPD trends with those of other co-evolving climate drivers. Here, we review the mechanistic bases of VPD impacts at a range of spatial scales, paying particular attention to the independent and interactive influence of VPD in the context of other environmental changes. We then evaluate the consequences of these impacts within key management contexts, including water resources, croplands, wildfire risk mitigation and management of natural grasslands and forests. We conclude with recommendations describing how management regimes could be altered to mitigate the otherwise highly deleterious consequences of rising VPD.

Understanding the impacts of chronic pain on autistic adolescents and effective pain management: a reflexive thematic analysis adolescent-maternal dyadic study.

OBJECTIVE: Sensory elements are core features in chronic pain and autism, yet knowledge of the pain experience in autistic adolescents is limited. Little is known regarding how autistic adolescents experience chronic pain, manage their pain and perceive psychological treatment for their chronic pain. METHODS: Ten autistic adolescents (6 female, 3 male, and 1 self-identified as agender) with chronic pain and their mothers (n = 10) participated in semistructured interviews concerning their perceptions of living with chronic pain. Participants were recruited from U.K. pain management services. According to preference, interviews were conducted individually (n = 10) or dyadically (n = 10 participants across 5 dyads). Data were analyzed using inductive reflexive thematic analysis. RESULTS: Two themes were generated. Theme 1, "overstimulated and striving for control" described how adolescents' experience of heightened sensitivity enhanced adolescents' levels of anxiety and subsequent pain, illustrating a reciprocal relationship between anxiety, pain, and sensory elements. Theme 2, "not everyone fits the mold" captured how autistic adolescents positioned themselves as distinct from others due to the unique nature of being autistic and living with pain. This sense of difference negatively impacted adolescents' ability to engage with and benefit from the standard treatment for chronic pain. CONCLUSIONS: Findings suggest that autistic adolescents living with pain experience pain and face barriers to effective pain treatment. Our results identify the need for educational resources to facilitate clinicians to better understand the experience of autistic adolescents living with pain. In turn, such understanding may improve treatment and outcomes in this population.

Latent Profile Analysis of Cognitive Performance and Depressive Symptoms Among People with HIV.

Depression and cognitive impairment are prevalent conditions among people with HIV (PWH), likely attributable to shared causes and common risk factors. Identifying subtypes of PWH with similar patterns of neurocognitive impairment (NCI) and depressive symptoms may inform development of patient-centered interventions that target-specific profiles. This study aimed to (1) classify PWH based on patterns of domain-specific NCI and depression; and (2) determine the relationship between latent class membership and pertinent clinical characteristics. PWH (N = 580, 86.2% male, 57.1% non-Hispanic White, 69.2% unemployed) completed a comprehensive neuropsychological test battery assessing global and domain-specific cognition. Domain-specific NCI was classified as deficit score >0.5. Participants completed the Beck Depression Inventory-II (BDI-II), and domain-specific BDI-II scores reflecting cognitive, affective, and somatic symptoms were computed. Latent profile analysis (LPA) was used to determine latent subgroups of NCI and depression. The optimal LPA solution consisted of five classes: minimal NCI and minimal depression (Class 1), amnestic and minimal depression (Class 2), severe multi-domain NCI and moderate depression (somatic and affective; Class 3), mild NCI and mild depression (Class 4), and moderate multi-domain NCI and severe depression (Class 5). Despite similar levels of functional impairment, Class 5 had a significant psychiatric profile, whereas Class 3 had a complex medical profile (i.e., higher frailty index, higher medications, greater proportion of AIDS diagnosis). In contrast, Class 1 had the lowest medication use and frailty index, with similar HIV disease characteristics to Classes 3 and 5. Our results suggest there are multiple pathways to cognitive and functional impairment among PWH with co-occurring depression and cognitive impairment, and these groups may respond differently to interventions. Of note, our sample was majority non-Hispanic White and male, which is nonrepresentative of the US population of PWH. Future interventions should consider a more integrated, person-centered approach that addresses cognitive and emotional health to optimize health outcomes in PWH.