Subgroup Of Participants Research Articles

Low-density lipoprotein cholesterol goal attainment with "inclisiran first" versus usual care in patients with atherosclerotic cardiovascular disease

Abstract Background Rapid and sustained attainment of guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals is critical for patients with atherosclerotic cardiovascular disease (ASCVD). In VICTORION-INITIATE, inclisiran administered twice-yearly by a healthcare professional earlier in the treatment pathway allowed more patients with ASCVD to achieve and sustain LDL-C goals vs current usual care (UC). Purpose To evaluate cumulative LDL-C exposure in the overall population and LDL-C goal attainment and safety in subgroups of participants (type of ASCVD, timing of ASCVD event, and history of statin intolerance) who received an "inclisiran first" implementation strategy (IF; adding inclisiran immediately on failure to achieve LDL-C <70 mg/dL [1.8 mmol/L] with maximally tolerated statins) compared with UC. Methods VICTORION-INITIATE was a 330-day, prospective, pragmatically designed trial that randomised participants 1:1 (stratified by insurance status) to IF (open-label inclisiran 284 mg at Days 0, 90 and 270 plus UC) or UC alone (lipid management directed by treating physician’s discretion). The study took place at 45 sites across 20 states in the USA. Treating physicians had access to LDL-C measurements and were encouraged to intensify treatment per clinical practice guidelines. This prespecified subgroup analysis evaluated LDL-C goal attainment by timing of the most recent ASCVD event (<1 year/≥1 year prior to consent), ASCVD subtype (coronary heart disease [CHD], peripheral arterial disease [PAD], and cerebrovascular disease [CVD]) and statin intolerance status. Cumulative LDL-C exposure over time in the overall population and safety by subgroup were also evaluated. Results Of 450 patients randomised to IF or UC, 11.1% and 84.2% had an ASCVD event <1 year or ≥1 year prior to consent, respectively; 91.8%, 18.2% and 14.7% had a history of CHD, CVD or PAD, and 25.8% were statin intolerant. Cumulative exposure to LDL-C to Day 330 was lower in patients treated with IF vs UC (mean time-adjusted LDL-C: 42.4 mg/dL vs 90.7 mg/dL, Figure). Significantly more patients who received IF achieved LDL-C goals of <70 mg/dL and <55 mg/dL at Day 330 vs UC, irrespective of subgroup (Table). Across subgroups, the incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs were similar between IF and UC (IF: 52.6−71.2%, UC: 46.2−66.0% and IF: 10.7−28.3%, UC: 11.4−22.2%, respectively). Conclusions Participants with ASCVD and LDL-C >70 mg/dL who received IF had lower cumulative LDL-C exposure over the study period than those treated with UC. IF resulted in rapid and sustained achievement of LDL-C goals regardless of ASCVD subtype, event timing and statin intolerance. The safety profile of IF was consistent across the subgroups analysed.

Differing needs for Advance Care Planning in the Veterans Health Administration: use of latent class analysis to identify subgroups to enhance Advance Care Planning via Group Visits for veterans

BackgroundAdvance Care Planning via Group Visits (ACP-GV) is a patient-centered intervention facilitated by a clinician using a group modality to promote healthcare decision-making among veterans. Participants in the group document a “Next Step” to use in planning for their future care needs. The next step may include documentation of preferences in an advance directive, discussing plans with family, or anything else to fulfill their ACP needs. This evaluation seeks to determine whether there are identifiable subgroups of group participants with differing needs prior to delivery of the ACP-GV program and, if so, to use information about the subgroups to enhance the program offered to veterans in United States Department of Veterans Affairs (VA) healthcare settings.MethodsWe conducted a secondary analysis of national data from a quality improvement evaluation. Patient- and provider-level data from administrative healthcare records for VA users in all 50 states, territories, and the District of Columbia provides data on veterans attending ACP-GV during federal fiscal years 2018–2022 (N = 26,857). Latent class analysis seeks to identify the various subgroups of veterans based on their level of ACP self-efficacy before attending ACP-GV and any demographic differences across the resulting subgroups of veterans attending ACP-GV. ACP self-efficacy is derived from seven items obtained from a participant worksheet used during the group.ResultsAnalysis revealed two distinct groups of veterans, distinguishable by their pre-ACP-GV levels of one aspect of ACP self-efficacy: prior knowledge of ACP. Veterans with higher prior knowledge of ACP are associated with an identified next step focused on checking their current AD status and updating it, and veterans with lower ACP prior knowledge are associated with identifying a next step to discuss ACP more fully with family. Differences in age, sex, race, ethnicity, and marital status exist across subgroups of veterans.ConclusionGreater attention must be paid to ACP and veterans’ prior knowledge of ACP to consistently encourage annual review and status updates.

Relationships Among COVID-19-Related Service Uptake, HIV Status, Drug Use, and COVID-19 Antibody Status Among HIV Testing Intervention Participants in KwaZulu-Natal, South Africa

People living with HIV (PLWH) and people who use drugs are vulnerable populations who may face barriers to accessing health services and may have irregularities in immune function. People with undiagnosed HIV infection may be particularly likely to have compromised immune function. However, research about whether/how HIV status is related to COVID-19-related health outcomes has been equivocal, and research on the predictors of COVID-19-related health service access/uptake has been limited in Sub-Saharan African settings. Among 470 participants of a peer-recruitment-based HIV-testing intervention in KwaZulu-Natal, we examined whether HIV status and/or hard drug use were associated with uptake of COVID-19 testing and vaccination, and whether they moderated the relationship between COVID-19 vaccination status and COVID-19 IgG antibody status. Women were significantly more likely than men to report testing for COVID-19 (OR = 1.84; p = 0.002) and being vaccinated (OR = 1.79; p = 0.002). Neither HIV status nor drug use was associated with likelihood of getting tested or vaccinated. Vaccinated participants (90% of whom obtained vaccines more than 6 months before the study) were significantly more likely to test positive for COVID-19 IgG antibodies (OR = 6.86; p < 0.0005). This relationship held true for subgroups of PLWH and participants with previously undiagnosed/uncontrolled HIV infection, and was not moderated by HIV status or hard drug use. These findings may suggest that both people who use drugs and PLWH were served as well as other people by KwaZulu-Natal’s COVID-19 response. However, gender-based disparities in COVID-19 service uptake suggest that special care should be taken during future COVID-19 outbreaks or other new epidemics to improve access to related healthcare services among men in this region.

Combined association between dietary antioxidant quality score and leisure-time physical activity on sleep pattern in cancer survivors: a cross-sectional study of NHANES database.

This study aimed to explore the combined association between the dietary antioxidant quality score (DAQS) and leisure-time physical activity on sleep patterns in cancer survivors. Data of cancer survivors were extracted from the National Health and Nutrition Examination Surveys (NHANES) database in 2007-2014 in this cross-sectional study. Weighted multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of DAQS and leisure-time physical activity on sleep patterns. The combined association was also assessed in subgroups of participants based on age, and use of painkillers and antidepressants. Among the eligible participants, 1,133 had unhealthy sleep patterns. After adjusting for covariates, compared to low DAQS level combined with leisure-time physical activity level <600 MET·min/week, high DAQS level combined with leisure-time physical activity ≥600 MET·min/week was associated with lower odds of unhealthy sleep patterns (OR=0.41, 95%CI: 0.23-0.72). Additionally, the association of high DAQS level combined with high leisure-time physical activity with low odds of unhealthy sleep patterns was also significant in <65 years old (OR=0.30, 95%CI: 0.13-0.70), non-painkiller (OR=0.39, 95%CI: 0.22-0.71), non-antidepressant (OR=0.49, 95%CI: 0.26-0.91) and antidepressant (OR=0.11, 95%CI: 0.02-0.50) subgroups. DAQS and leisure-time physical activity had a combined association on sleep patterns in cancer survivors. However, the causal associations of dietary nutrient intake and physical activity with sleep patterns in cancer survivors needs further clarification.

The relationship between BMI and depression: a cross-sectional study

IntroductionMental health problems, especially depressive symptoms, are becoming increasingly prominent, posing a significant risk to public health. Changes in the body mass index (BMI) may impact an individual’s mental health, however, the relationship between BMI and depressive symptoms is unclear. The purpose of this study was to investigate the association between BMI and depressive symptoms.MethodsUsing a multi-stage sampling method, 10,686 adults in Longgang District, Shenzhen City, Guangdong Province, China, were selected for participation in this study. Surveys were distributed in 2020 and 2021 to measure participant demographic data and health. Binary logistic regression, restricted cubic spline regression, and subgroup analyses were performed to explore the relationship between BMI and depressive symptoms.ResultsThe results showed a U-shaped relationship between BMI and depression. Both obesity and underweight increased the risk of depression among the participants, especially in subgroups of participants who were young, highly educated, single and employed.ConclusionThese findings suggest that adults should try to maintain a normal body weight as a way to prevent depression and maintain their physical and mental health.

Investigation of FF-MAS oxysterole’s role in follicular development and its relation to hedgehog signal pathway

The Hedgehog signaling pathway plays a crucial role in folliculogenesis; however, the association between FF-MAS oxysterol activity in folliculogenesis and the Hedgehog signaling pathway has not been revealed. The evaluation of FF-MAS activity in polycystic ovary syndrome (PCOS) with folliculogenesis disorder might provide a new approach to tackle follicular and oocyte maturation failure. The question is: does FF-MAS oxysterol affect granulosa cell (GC) proliferation? If so, is this effect facilitated through the Hedgehog pathway? To answer these questions, GCs were isolated from follicle fluids obtained from patients undergoing oocyte retrieval during in vitro fertilization (IVF) treatment. After the isolated GCs were incubated in different cell culture media, the levels of Hedgehog pathway components (SMO, Gli1) were measured by using immunohistochemical methods, cytoELISA, and qRT-PCR. Meanwhile, cell proliferation rates were determined. Significant increases (p < 0.001) in SMO and Gli1 expressions and cell proliferation were observed in the FF-MAS-treated subgroups of both PCOS and male factor participants compared to the FF-MAS deficient subgroup. Remarkably, FF-MAS positively affected the pathway components despite the pathway inhibitor cyclopamine. Although the increase in Hedgehog pathway components was slightly higher in the male factor group (MF), it was not statistically significant. In our study, we demonstrated for the first time the molecular effect of FF-MAS on human GCs in folliculogenesis. Since FF-MAS is already used in assisted reproductive techniques in animals and is known to be synthesized in the human body, it could be considered a new approach in human IVF treatments.

Projecting the benefit of vericiguat in PARADIGM-HF and DAPA-HF populations: Insights from the VICTORIA trial.

The VICTORIA trial demonstrated a significant reduction in the primary composite outcome of heart failure (HF) hospitalization or cardiovascular death with vericiguat relative to placebo in high-risk HF. This study aimed to contextualize treatment effects of vericiguat in populations with varying risk profiles simulated from the PARADIGM-HF and DAPA-HF trials. Subgroups of VICTORIA participants (n=5050) were generated to simulate PARADIGM-HF and DAPA-HF trial populations. The PARADIGM-HF-eligible population excluded participants not meeting left ventricular ejection fraction (LVEF), estimated glomerular filtration rate (eGFR), and minimal dose criteria and those with high predicted probability of run-in failure. The DAPA-HF-eligible population excluded those not meeting LVEF and eGFR criteria or with recent (<30days) HF hospitalization. The time-to-first-event analysis was performed using an unadjusted Cox proportional hazards model. A total of 1982 (39.2%) and 2543 (50.4%) VICTORIA participants were respectively deemed eligible for PARADIGM-HF and DAPA-HF. Vericiguat was associated with numerically larger reductions in the primary outcome of HF hospitalization or cardiovascular death in populations simulated from PARADIGM-HF [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.72-0.99] and DAPA-HF (HR 0.82, 95% CI 0.71-0.94) compared with the overall VICTORIA trial (HR 0.90). Significant reduction in HF hospitalization with vericiguat was also observed in the DAPA-HF-eligible population (HR 0.83, 95%CI 0.73-0.95) and with a nominal reduction in the PARADIGM-HF-eligible population (HR 0.86, 95% CI 0.74-1.01). A trend towards enhanced efficacy of vericiguat in populations simulated from PARADIGM-HF and DAPA-HF was observed. These findings support further exploration of vericiguat in lower-risk HF populations as is being investigated in the ongoing VICTOR (a study of vericiguat in participants with chronic heart failure with reduced ejection fraction) trial.

Serum metabolite signature of the modified Mediterranean-DASH intervention for neurodegenerative delay (MIND) diet.

There is a lack of biomarkers of clinically important diets, such as the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet. Our study explored serum metabolites associated with adherence to the MIND diet. In 3,908 Atherosclerosis Risk in Communities (ARIC) study participants, we calculated a modified MIND diet score based on a 66-item self-reported food frequency questionnaire (FFQ). The modified score did not include berries and olive oil, as these items were not assessed in the FFQ. We used multivariable linear regression models in 2 subgroups of ARIC study participants and meta-analyzed results using fixed effects regression to identify significant metabolites after Bonferroni correction. We also examined associations between these metabolites and food components of the modified MIND diet. C-statistics evaluated the prediction of high modified MIND diet adherence using significant metabolites beyond participant characteristics. Of 360 metabolites analyzed, 27 metabolites (15 positive, 12 negative) were significantly associated with the modified MIND diet score (lipids, n = 13; amino acids, n = 5; xenobiotics, n = 3; cofactors and vitamins, n = 3; carbohydrates n = 2; nucleotide n = 1). The top 4 metabolites that improved the prediction of high dietary adherence to the modified MIND diet were 7-methylxanthine, theobromine, docosahexaenoate (DHA), and 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF). Twenty-seven metabolomic markers were correlated with the modified MIND diet. The biomarkers, if further validated, could be useful to objectively assess adherence to the MIND diet.

Effectiveness and safety of insulin glargine 300 U/mL in insulin-naïve individuals according to diabetes duration: Results from the REALI European pooled data analysis.

To evaluate the effectiveness and safety of insulin glargine 300 U/mL (Gla-300) initiation according to diabetes duration (DD). We analysed patient-level data from 2381 insulin-naïve individuals with type 2 diabetes (T2D), of whom 2349 (98.7%) were treated with Gla-300 for 24 weeks. Of the 2381 participants, 1048 (44.0%) had a DD of less than 8 years and 1333 (56.0%) had a DD of 8 years or longer. We further analysed the subgroups of participants having a DD of less than 4 years (N = 450), 4-8 years (N = 598), 8-12 years (N = 627) and 12 years or longer (N = 706). Mean ± standard deviation age was 60.2 ± 9.0 years in participants with a DD less than 8 years and 64.2 ± 8.8 years in those with a DD of 8 years or longer. At 24 weeks of Gla-300 therapy, HbA1c improved with a least-squares (LS) mean change from baseline of -1.88% (95% confidence interval [CI], -1.95 to -1.80) and -1.71% (95% CI, -1.77 to -1.65), respectively, resulting in a LS mean difference between groups of 0.17% (95% CI, 0.07 to 0.26; P = .0005). In the subgroup analysis, LS mean HbA1c reduction from baseline to week 24 was highest in participants with a DD of less than 4 years and lowest in participants with a DD of 12 years or longer. Overall, incidences of symptomatic and severe hypoglycaemia were low, irrespective of DD, without body weight changes. Gla-300 was effective and safe in insulin-naïve individuals with T2D, regardless of DD. Improvement in HbA1c was greater when Gla-300 was initiated in participants with a DD of less than 4 years, although the difference between the groups was modest.

A Bayesian beta-binomial piecewise growth mixture model for longitudinal overdispersed binomial data.

In a recent 12-week smoking cessation trial, varenicline tartrate failed to show significant improvements in enhancing end-of-treatment abstinence when compared with placebo among adolescents and young adults. The original analysis aimed to assess the average effect across the entire population using timeline followback methods, which typically involve overdispersed binomial counts. We instead propose to investigate treatment effect heterogeneity among latent classes of participants using a Bayesian beta-binomial piecewise linear growth mixture model specifically designed to address longitudinal overdispersed binomial responses. Within each class, we fit a piecewise linear beta-binomial mixed model with random changepoints for each study group to detect critical windows of treatment efficacy. Using this model, we can cluster subjects who share similar characteristics, estimate the class-specific mean abstinence trends for each study group, and quantify the treatment effect over time within each class. Our analysis identified two classes of subjects: one comprising high-abstinent individuals, typically young adults and light smokers, in which varenicline led to improved abstinence; and another comprising low-abstinent individuals for whom varenicline showed no discernible effect. These findings highlight the importance of tailoring varenicline to specific participant subgroups, thereby advancing precision medicine in smoking cessation studies.

Urine epidermal growth factor as a biomarker for kidney function recovery and prognosis in glomerulonephritis with severe kidney function impairment.

Prognostication in glomerulonephritis with severe kidney function impairment is critical for evaluating the benefit-to-risk ratio of immunosuppression. We hypothesized that the urine biomarker epidermal growth factor (EGF) could have good discrimination powerto identify subjects who might ultimatelyrecover kidney function. We included 82 subjects with glomerulonephritis and severe kidney function impairment at admission (estimated glomerular filtration rate [eGFR] ≤ 30mL/min/1.73m2): 58 with lupus nephritis (LN) and 24 with ANCA-associated vasculitis (AAV). Thirty-five subjects requiredkidney replacement therapy (KRT) at presentation. Urine epidermal growth factor was measured and corrected by urine creatinine (uEGF/Cr) and the population was analyzed by uEGF/Cr tertiles. The primary outcome was time to recovery of eGFR ≥ 30mL/min/1.73m2 and time to recovery of kidney function with dialysis independence in those with initial KRT. Forty-four (54%) participants met the primary outcome of recovery of eGFR ≥ 30mL/min/1.73m2. The 6-month recovery rates were 93%, 57%, and 0% for participants in the highest, middle, and lowest uEGF/Cr tertile, respectively. Recovery of thekidney function was faster and ledto a higher post-therapy eGFR in the highest uEGF/Cr tertile. In the ROC analysis,uEGF/Cr was a predictor of recovery with an area under the curve (AUC) of 0.92 (95% CI 0.87-0.98), and a cutoff of 2.60ng/mg had 100% sensitivity to detect patients who recovered kidney function. In the subgroup of participants with initial KRT,the cut-off of uEGF/Cr of 2.0ng/mg had 100% sensitivity to detect participants who recovered kidney function with dialysis independence by 6months. Urine EGF/Cr is a promising biomarker to aid in the prediction of recovery of kidney function in glomerulonephritis with severe kidney function impairment.

The researcher's guide to selecting biomarkers in mental health studies.

Clinical mental health researchers may understandably struggle with how to incorporate biological assessments in clinical research. The options are numerous and are described in a vast and complex body of literature. Here we provide guidelines to assist mental health researchers seeking to include biological measures in their studies. Apart from a focus on behavioral outcomes as measured via interviews or questionnaires, we advocate for a focus on biological pathways in clinical trials and epidemiological studies that may help clarify pathophysiology and mechanisms of action, delineate biological subgroups of participants, mediate treatment effects, and inform personalized treatment strategies. With this paper we aim to bridge the gap between clinical and biological mental health research by (1) discussing the clinical relevance, measurement reliability, and feasibility of relevant peripheral biomarkers; (2) addressing five types of biological tissues, namely blood, saliva, urine, stool and hair; and (3) providing information on how to control sources of measurement variability.

Trajectories of Breastfeeding-Related Thoughts and Attitudes Among Low-Income Smoke-Exposed Pregnant Women: A Latent Class Growth Analysis.

Psychosocial predictors of breastfeeding and changes in those factors during pregnancy, along with the relationship of those changes with both breastfeeding and smoke use and exposure, are not well explored. The aim of this study was to identify distinct trajectories of psychosocial determinants of breastfeeding and smoking in pregnant women. We used a longitudinal study design and data from a randomized controlled trial conducted among smoke-exposed pregnant women and their infants. Participants were recruited early in pregnancy and were surveyed at ≤ 16 and 32 weeks gestation, delivery, 3 and 6 months postpartum for breastfeeding intentions, initiation, continuation, and smoke use and exposure. Psychosocial variables associated with breastfeeding were measured at baseline and 32 weeks gestation using the Mitra index, a structured questionnaire that assesses barriers and facilitators of breastfeeding intentions. Latent class growth analysis was performed using Mitra scores to identify distinct subgroups of participants with different trajectories. Sociodemographic characteristics, breastfeeding, and tobacco smoke use and exposure were compared across classes. Three or four trajectories were identified for each of the six Mitra scores. Trajectories for all Mitra scores were associated with breastfeeding intention and initiation. Overall, Mitra, knowledge, self-efficacy, social support, and time barrier classes all differed by tobacco smoke use or exposure. Trajectories of breastfeeding knowledge, self-efficacy, social support, and time to breastfeed/social barriers are associated with tobacco smoke use and exposure during pregnancy. Encouragement to breastfeed and to cease and avoid tobacco smoke should start early in pregnancy, focusing on these determinants to improve health outcomes.

Bone Marrow Adiposity Alterations in Postmenopausal Women With Type 2 Diabetes Are Site-Specific.

Bone marrow adiposity (BMAT) alterations in patients with type 2 diabetes mellitus (T2DM) may contribute to adverse bone effects. Characterization of BMAT content and composition in patients with well-controlled T2DM. This cross-sectional study included 2 groups of postmenopausal women: one with T2DM and the other without. The proton density fat fraction (PDFF) of the lumbar spine and proximal femur, comprising the femoral head, neck, and diaphysis, was assessed using chemical shift-based water-fat separation imaging (WFI). Magnetic resonance imaging with spectroscopy (1H-MRS) was performed in a subgroup of participants to confirm the PDFF measurements and determine the apparent lipid unsaturation level (aLUL) at the L3 vertebrae and femoral neck. The association of imaging-based PDFFs and aLUL between diabetes groups was investigated by adjusting for confounding factors using a linear mixed model. Among 199 participants, patients with T2DM (n = 29) were significantly heavier (P < .001) and had a higher bone mineral density (BMD) (P < .001 for all sites) than nondiabetic patients (n = 170). When PDFFs were compared after adjusting for age, body mass index (BMI), and BMD, the femoral head WFI-based PDFF was lower in patients with T2DM (mean [standard error] 88.0% [0.7] vs 90.6% [0.3], P < .001). Moreover, the aLUL at the L3 vertebrae was lower in patients with T2DM (n = 16) than in without (n = 97) (mean [standard error] 3.9% [0.1] vs 4.3% [0.1], P = .02). The content and composition of BMAT are modified in postmenopausal women with T2DM and these changes occur at specific sites.

Efficacy of Brodalumab in Patients with Psoriasis and Risk Factors for Treatment Failure: A Review of Post Hoc Analyses.

Factors such as obesity, alcohol consumption, and tobacco use are associated with both increased psoriasis severity and inadequate response to systemic and biologic therapies. Obesity is linked to chronic inflammation, which can contribute to psoriasis pathogenesis. Fixed-dose therapies may have reduced efficacy in patients with a higher body mass index, while weight-based dosing can increase the burden of drug-specific side effects. Alcohol and nicotine from tobacco have also been shown to stimulate keratinocyte and immune cell proliferation and production of proinflammatory cytokines. While these risk factors are prevalent among patients with moderate-to-severe psoriasis, their influence on treatment outcomes may be overlooked when evaluating therapeutic options. Brodalumab is a fully human interleukin-17 receptorA antagonist approved for the treatment of moderate-to-severe psoriasis. In this review, we describe the lifestyle-related risk factors associated with decreased response to treatment. We further summarize the post hoc analyses of brodalumab in participant subgroups with moderate-to-severe psoriasis and a history of prior biologic failure, obesity, and alcohol or tobacco use from two phase 3 clinical trials (AMAGINE-2 and AMAGINE-3; ClinicalTrials.gov identifiers: NCT01708603 and NCT01708629, respectively). Our review of clinical trial and real-world data suggests that brodalumab is an efficacious and safe treatment option for patients with lifestyle factors that increase the likelihood of treatment failure, allowing them to achieve skin clearance and improve quality of life.

Efficacy of KarXT on negative symptoms in acute schizophrenia: A post hoc analysis of pooled data from 3 trials

BackgroundCurrently approved antipsychotics do not adequately treat negative symptoms (NS), which are a major determinant of functional disability in schizophrenia. KarXT, an M1 /M4 preferring muscarinic receptor agonist, has shown efficacy as a broad-spectrum monotherapy for the treatment of schizophrenia in participants with acute psychosis. Post hoc analyses evaluated the possibility that NS improve independently of positive symptoms with KarXT in a subgroup of participants with moderate-to-severe NS and no predominance of positive symptoms. MethodsData were pooled from the three pivotal trials of KarXT monotherapy in people with schizophrenia with an acute exacerbation of psychosis. All 3 studies used similar 5-week randomized, double-blind, placebo-controlled designs (modified intention-to-treat sample N = 640). PANSS criteria proposed in the literature identified a subset of study participants (n = 64) with prominent NS. ResultsKarXT was significantly better than placebo on PANSS Marder Negative Factor Scores in the full sample (p < .001; Cohen's d = 0.42) and more so in the prominent NS subgroup (p < .001; Cohen's d = 1.18). Further, the KarXT effect in the NS subgroup remained significant after accounting for changes in positive symptoms, depression/anxiety, disorganization, and hostility. ConclusionsParticipants with prominent NS revealed greater improvement of NS following KarXT therapy than the full sample that persisted after accounting for positive and other symptoms. While these findings must be interpreted with caution, they are consistent with the possibility that NS improvements associated with KarXT are not secondary to improvements in other symptom domains and support further investigation in larger, stable outpatient studies.

Insulin Efsitora versus Degludec in Type 2 Diabetes without Previous Insulin Treatment.

Insulin efsitora alfa (efsitora) is a new basal insulin designed for once-weekly administration. Data on safety and efficacy have been limited to small, phase 1 or phase 2 trials. We conducted a 52-week, phase 3, parallel-design, open-label, treat-to-target trial involving adults with type 2 diabetes who had not previously received insulin. Participants were randomly assigned in a 1:1 ratio to receive efsitora or degludec. The primary end point was the change in the glycated hemoglobin level from baseline to week 52; we hypothesized that efsitora would be noninferior to degludec (noninferiority margin, 0.4 percentage points). Secondary and safety end points included the change in the glycated hemoglobin level in subgroups of participants using and not using glucagon-like peptide-1 (GLP-1) receptor agonists, the percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter in weeks 48 through 52, and hypoglycemic episodes. A total of 928 participants underwent randomization (466 to the efsitora group and 462 to the degludec group). The mean glycated hemoglobin level decreased from 8.21% at baseline to 6.97% at week 52 with efsitora (least-squares mean change, -1.26 percentage points) and from 8.24% to 7.05% with degludec (least-squares mean change, -1.17 percentage points) (estimated treatment difference, -0.09 percentage points; 95% confidence interval [CI], -0.22 to 0.04), findings that showed noninferiority. Efsitora was noninferior to degludec with respect to the change in the glycated hemoglobin level in participants using and not using GLP-1 receptor agonists. The percentage of time that the glucose level was within the target range was 64.3% with efsitora and 61.2% with degludec (estimated treatment difference, 3.1 percentage points; 95% CI, 0.1 to 6.1). The rate of combined clinically significant or severe hypoglycemia was 0.58 events per participant-year of exposure with efsitora and 0.45 events per participant-year of exposure with degludec (estimated rate ratio, 1.30; 95% CI, 0.94 to 1.78). No severe hypoglycemia was reported with efsitora; six episodes were reported with degludec. The incidence of adverse events was similar in the two groups. In adults with type 2 diabetes who had not previously received insulin, once-weekly efsitora was noninferior to once-daily degludec in reducing glycated hemoglobin levels. (Funded by Eli Lilly; QWINT-2 ClinicalTrials.gov number, NCT05362058.).

Decoding heterogeneity in data-driven self-monitoring adherence trajectories in digital lifestyle interventions for weight loss: a qualitative study

BackgroundData-driven trajectory modeling approaches have been used to identify participant subgroups with differing responses to digital lifestyle interventions. Identifying contributing factors to different participant subgroups can inform tailored strategies to early “rescue” intervention non-responders. Self-monitoring (SM) is a central mechanism in lifestyle interventions for driving behavior change and can serve as an early indicator for later intervention response. This qualitative study aimed to compare SM experiences between intervention response subgroups and to identify contributing factors to intervention response subgroups in a 6-month digital lifestyle intervention for adults with overweight or obesity.ResultsParticipants were middle-aged (52.9 ± 10.2 years), mostly female (65%), and of Hispanic ethnicity (55%). Four major themes with emerged from the thematic analysis: Acceptance towards SM Technologies, Perceived SM Benefits, Perceived SM Barriers, and Responses When Facing SM Barriers. Participants across both subgroups perceived SM as positive feedback, aiding in diet and physical activity behavior changes. Both groups cited individual and technical barriers to SM, including forgetfulness, the burdensome SM process, and inaccuracy. The Responder Group displayed positive problem-solving skills that helped them overcome the SM barriers. In contrast, some in the Non-responder Group felt discouraged from SM. Both subgroups found diet SM particularly challenging, especially due to technical issues such as the inaccurate food database, the time-consuming food entry process in the Fitbit app.ConclusionsOur study indicates that qualitative analysis is valuable for translating data-driven findings to actionable intervention improvement strategies. Our findings may inform the development of practical SM improvement strategies in future digital lifestyle interventions for weight loss. Notably, building problem solving skills emerge as a key approach to prevent potential non-responders from intervention disengagement.

Individual Difference Predictors of Attitudes toward Polyamorous Targets and Likelihood to Date a Polyamorous Partner in a Student Sample

An online survey was completed by a convenience sample of 495 students to assess attitude toward polyamorous targets as an outgroup using 0–100 feeling thermometers. Also assessed was the likelihood of dating a polyamorous partner. These two measures were only weakly related for women participants but modestly related for men participants. Overall, feeling thermometer averages were favorable (66%) but dating likelihood was very low, with 89% rating dating a polyamorous partner as unlikely. Women were slightly more favorable toward polyamorous targets than were men but target gender showed no effect (i.e., ratings of polyamorous men were the same as those of polyamorous women). However, men were slightly more willing to date a polyamorous partner than were women. In terms of personality and individual difference variables as predictors of attitudes, authoritarianism, erotophobia–erotophilia, and participant sexual orientation accounted for a quarter of the variance in feeling thermometer ratings of polyamorous targets. Specifically, those who had lower authoritarianism, were more comfortable with sexuality, and were sexual minority in orientation were likely to rate the polyamorous targets the most favorably. Individual difference variables did not predict willingness to date a polyamorous partner consistently across gender and sexual orientation participant subgroups; the most consistent predictors were sociosexuality and erotophobia–erotophilia. This study adds to our knowledge in a nascent area of sexual attitude and discrimination research—it demonstrates the differences between rating an outgroup person and attitude toward engaging with them personally. The latter appears to involve more complexity in terms of the relationship with personality and the type of social perceiver. More research is needed into the differentiation between general ratings of others who engage in non-mainstream, stigmatized sexual practices versus when the ratings involve personal involvement or behavior of the social perceiver (i.e., such as dating).

Self-report underestimates the frequency of the acute respiratory exacerbations of COPD but is associated with BAL neutrophilia and lymphocytosis: an observational study

RationaleResearch studies typically quantify acute respiratory exacerbation episodes (AECOPD) among people with chronic obstructive pulmonary disease (COPD) based on self-report elicited by survey questionnaire. However, AECOPD quantification by self-report could be inaccurate, potentially rendering it an imprecise tool for identification of those with exacerbation tendency.ObjectiveDetermine the agreement between self-reported and health records-documented quantification of AECOPD and their association with airway inflammation.MethodsWe administered a questionnaire to elicit the incidence and severity of respiratory exacerbations in the three years preceding the survey among current or former heavy smokers with or without diagnosis of COPD. We then examined electronic health records (EHR) of those with COPD and those without (tobacco-exposed persons with preserved spirometry or TEPS) to determine whether the documentation of the three-year incidence of moderate to very severe respiratory exacerbations was consistent with self-report using Kappa Interrater statistic. A subgroup of participants also underwent bronchoalveolar lavage (BAL) to quantify their airway inflammatory cells. We further used multivariable regressions analysis to estimate the association between respiratory exacerbations and BAL inflammatory cell composition with adjustment for covariates including age, sex, height, weight, smoking status (current versus former) and burden (pack-years).ResultsOverall, a total of 511 participants completed the questionnaire, from whom 487 had EHR available for review. Among the 222 participants with COPD (70 ± 7 years-old; 96% male; 70 ± 38 pack-years smoking; 42% current smoking), 57 (26%) reported having any moderate to very severe AECOPD (m/s-AECOPD) while 66 (30%) had EHR documentation of m/s-AECOPD. However, 42% of those with EHR-identified m/s-AECOPD had none by self-report, and 33% of those who reported m/s-AECOPD had none by EHR, suggesting only moderate agreement (Cohen’s Kappa = 0.47 ± 0.07; P < 0.001). Nevertheless, self-reported and EHR-identified m/s-AECOPD events were both associated with higher BAL neutrophils (ß ± SEM: 3.0 ± 1.1 and 1.3 ± 0.5 per 10% neutrophil increase; P ≤ 0.018) and lymphocytes (0.9 ± 0.4 and 0.7 ± 0.3 per 10% lymphocyte increase; P ≤ 0.041). Exacerbation by either measure combined was associated with a larger estimated effect (3.7 ± 1.2 and 1.0 ± 0.5 per 10% increase in neutrophils and lymphocytes, respectively) but was not statistically significantly different compared to the self-report only approach. Among the 184 TEPS participants, there were fewer moderate to very severe respiratory exacerbations by self-report (n = 15 or 8%) or EHR-documentation (n = 9 or 5%), but a similar level of agreement as those with COPD was observed (Cohen’s Kappa = 0.38 ± 0.07; P < 0.001).DiscussionWhile there is modest agreement between self-reported and EHR-identified m/s-AECOPD, events are missed by relying on either method alone. However, m/s-AECOPD quantified by self-report or health records is associated with BAL neutrophilia and lymphocytosis.