Moderate Baseline Research Articles

Kidney Outcomes with GLP-1RAs, SGLT2 Inhibitors, DPP-4 Inhibitors, and Sulfonylureas in Type 2 Diabetes and Moderate Cardiovascular Risk

Background: Chronic kidney disease (CKD) is a serious diabetes-related complication. While guidelines recommend use of sodium-glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists to mitigate cardiorenal risk in high-risk patients, the benefit of early initiation of these agents relative to other commonly prescribed glucose-lowering agents in patients at lower baseline cardiovascular disease (CVD) risk remains less clear. Methods: This retrospective observational study emulated an idealized target trial using claims data from OptumLabs® Data Warehouse to test the comparative association of treatment with a dipeptidyl peptidase-4 (DPP-4) inhibitor, SGLT2 inhibitor, GLP-1 receptor agonist, or sulfonylurea on a primary kidney composite outcome of incident CKD stages 3-5, kidney failure, or need for kidney replacement therapy (KRT) in patients with type 2 diabetes (T2D) and moderate CVD risk. A secondary composite outcome included all components of the primary composite outcome plus death. Results: A total of 364,714 adults ≥21 years of age initiating treatment with a DPP-4 inhibitor (N=78,843), GLP-1 receptor agonist (N=42,049), SGLT2 inhibitor (N=45,466), or sulfonylurea (N=198,356) were identified. Relative to DPP-4 inhibitor, SGLT2 inhibitor (HR: 0.71; 95% CI: 0.67-0.74; P˂0.001) and GLP-1 receptor agonist (HR: 0.87; 95% CI: 0.83-0.92; P˂0.001) treatment was superior for the primary composite outcome. Similarly, SGLT2 inhibitor (HR: 0.69; CI: 0.66-0.73) and GLP-1 receptor agonist (HR: 0.86; CI: 0.82-0.91) treatment was associated with risk reductions for the primary outcome relative to sulfonylurea treatment. When comparing SGLT2 inhibitor to GLP-1 receptor agonist therapy, SGLT2 inhibitors were superior for the primary composite outcome (HR: 0.81; 95% CI: 0.75-0.76; P˂0.001). Similar findings were observed for the secondary composite outcome across all comparisons. Conclusions: SGLT2 inhibitors and GLP-1 receptor agonists were superior to DPP-4 inhibitors and sulfonylurea for preventing kidney complications in a T2D population with moderate baseline CVD risk.

Three-Year Clinical Outcomes in Geographic Atrophy: An Analysis of 18,712 Patient Eyes

Methods: Retrospective analysis of 18,712 eyes with GA using the CorEvitas Vestrum Health Retina Database. Results: Mean age at index was 78.6 years (SD = 7.9) and mean visual acuity (VA) was 67.5 letters (SD = 13.0, Snellen equivalent 20/45). 18.9% of eyes developed nAMD within 36 months. Eyes with fellow-eye nAMD developed nAMD at over twice the rate of eyes with fellow-eye GA (relative risk 2.34, 95% CI [2.20, 2.49]). Mean VA of eyes that did not develop nAMD declined by 12.4 letters (95% CI [12.0, 12.9]) within 36 months. Older age and moderate baseline visual impairment (VA < 20/40 to 20/100) independently correlated with accelerated rate of decline. Eyes of patients in the oldest quartile with moderate visual impairment experienced the worst outcomes, losing an average of 19.7 letters over 36 months (95% CI [18.1, 21.3]). By 36 months, 70% of eyes had vision below threshold for driving (VA ≤ 20/40), 42% had low vision (VA ≤ 20/70), and 23% were legally blind (VA ≤ 20/200). Conclusions: GA is associated with significant disease burden. Eyes with GA lose an average of two to three lines of VA within 36 months of follow up. Older age and moderate baseline visual impairment independently correlate with poorer visual outcomes. Presence of nAMD in the fellow eye is associated with twofold higher risk of exudative conversion within 36 months.

Coronary artery calcium score and other risk factors in patients at moderate and high risk of cancer therapy-related cardiovascular toxicity

BackgroundThe presence and burden of coronary artery calcium (CAC) is a strong predictor of cardiovascular events. Current guidelines of the European Society of Cardiology (ESC) for cardio-oncology do not recommend the use of the CAC score to determine the status of risk in cancer patients. The aim of this study is to evaluate the presence and burden of CAC on cardiac tomography and the distribution of the cardiovascular toxicity risk factors in patients with moderate and high baseline risk of cancer therapy-related cardiovascular toxicity.MethodsThe study prospectively included cancer patients, diagnosed and qualified for systemic treatment with anthracycline chemotherapy. Clinical data and blood samples were collected from all patients. Additionally, the echocardiography and coronary computed tomography (CCTA) with the calculation of the coronary artery calcium (CAC) score were performed.ResultsA total of 80 patients (mean age 60.5 years, 75 female) were included in the study. The majority of patients (62, 77.5%) had breast cancer, 11 (13.8%) were diagnosed with sarcoma, and 7 (8.8%) with lymphoma. There were 42 (52.5%) patients classified as having moderate (MR) and 38 (47.5%) as having high risk (HR) of cancer therapy-related cardiovascular toxicity according to current ESC guidelines. In comparison with moderate risk, high risk patients were older and more likely to have hypertension, hyperlipidaemia and chronic kidney disease. The mean coronary artery calcium score was significantly higher in the HR group (150.4 vs. 24.8; p = 0.000). Furthermore, cardiac biomarkers were also higher in high-risk patients (p = 0.000). In echocardiographic parameters global longitudinal strain (GLS) was lower (p = 0.012), and diastolic dysfunction was more common in the HR group. However, the left ventricle ejection fraction (LVEF) was similar in the MR and HR groups.ConclusionsIn patients at high and moderate risk for cancer therapy-related cardiovascular toxicity, cardiovascular toxicity risk factors were common and more prevalent in the high-risk group. The coronary artery calcium score was also significantly higher in the high-risk group. Assessing the presence and burden of coronary artery calcium is an attractive option to assess additional cardiovascular risk in cancer patients.

Efficacy and safety of filgotinib in patients with moderately active rheumatoid arthritis and an inadequate response to methotrexate.

Clinical trials restricted to moderately active RA are limited. Filgotinib is approved for treating moderate to severe active RA. This post hoc analysis assessed efficacy and safety of filgotinib in moderately active RA. In FINCH 1, patients with active moderate to severe RA and inadequate response to methotrexate received filgotinib 200 mg or 100 mg (FIL200/FIL100) once daily, adalimumab 40 mg every 2 weeks, or placebo, all with methotrexate (n = 1,755). This subgroup analysis was conducted in patients with a moderate baseline Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP; >3.2 to ≤ 5.1; n = 425 [24.2%]). A higher proportion of patients achieved DAS28-CRP <2.6, Clinical Disease Activity Index (CDAI) remission (≤2.8), low disease activity (LDA) (DAS28-CRP ≤3.2 or CDAI ≤10), and American College of Rheumatology (ACR20/50/70) responses with FIL200 and FIL100 vs placebo at Weeks 12 and 24. Week 12 ACR20 response rates (primary end point) were 77.9%, 67.8%, and 43.8%, respectively. ∼75% of patients achieved DAS28-CRP LDA by week 24 with either filgotinib dose. FIL200 and FIL100 elicited greater improvements in patient-reported outcomes than placebo. The efficacy of filgotinib, maintained through week 52, was comparable to that of adalimumab. Frequency of adverse events (AEs) was similar with filgotinib and adalimumab. Infections were the most common AEs; incidence rates were 40-53% in active treatment groups. In this subpopulation with moderately active RA, the efficacy and safety of filgotinib were similar to those in the overall FINCH 1 population (patients with active moderate to severe RA). NCT02889796.

Effect of defocus incorporated multiple segments (DIMS) spectacle lenses on myopia progression in children: a retrospective analysis in a German real-life clinical setting

ObjectivesThis retrospective analysis evaluates the treatment success of “Defocus Incorporated Multiple Segments” (DIMS) spectacle lenses in a real-life clinical setting in Germany.Materials and methodsAxial length (AL) and objective refraction of 166 eyes treated with DIMS at baseline and 12-month follow-up were analyzed. Annual AL growth rate within the range of physiological growth rate was considered a successful treatment. Myopia progression of ≥ -0.5 D/yr accounted as treatment success. Differences in percentages of treatment success of subgroups depending on baseline AL and age against treatment success of the total population were investigated.ResultsConsidering all eyes, treatment success regarding AL growth and myopia progression was achieved in 46% and 65%, respectively. Male eyes with moderate AL showed treatment success in a higher proportion (73%, p < 0.01; 89%, p < 0.01); eyes with high AL showed treatment success in a lower proportion (25%, p < 0.01; 51%, n.s.). Female eyes showed the same trend but without statistical significance (moderate AL: 49%; 68%; high AL: 40%; 62%). Younger children showed treatment success in a lower proportion (male: 11%, p < 0.01; 38%, p < 0.05; female: 25%, p < 0.01; 42%, p < 0.01). Older children showed treatment success in a higher proportion (male: 60%, p < 0.05; 78% p < 0.05; female: 53%, n.s.; 77% p < 0.05).ConclusionsEyes with moderate baseline AL and of older children showed treatment success after 12 months of DIMS treatment. Eyes with a high baseline AL and of younger children showed treatment success in a smaller proportion, therefore combination treatment should be considered. In future studies, males and females should be assessed separately.

Improved Health Outcomes in Patients with Systemic Lupus Erythematosus Following Early Belimumab Initiation Without Prior Immunosuppressant Use: A Real-World Descriptive Study.

Patients with systemic lupus erythematosus (SLE) have variable treatment pathways, including antimalarials, glucocorticoids, immunosuppressants, and/or biologics. This study describes differences in clinical outcomes when initiating belimumab (BEL) before and after immunosuppressant use. This real-world, retrospective cohort study (GSK Study 217536) used de-identified administrative claims data from January 2015 to December 2022 in the Komodo Health Database. Adults with moderate/severe SLE initiating BEL (index date) were identified from January 2017 to May2022, allowing a ≥ 24-month baseline period. Patients were stratified into those initiating BEL before immunosuppressant use (no immunosuppressant use within 24months before index) and those initiating BEL after immunosuppressant use (one immunosuppressant used within 24months before index). Oral glucocorticoid (OGC) use, SLE flares, new organ damage, and all-cause healthcare resource utilization (HCRU) were analyzed descriptively over a 24-month follow-up. Baseline SLE severity was similar for patients initiating BEL before (n = 2295) versus after (n = 4114) immunosuppressant use (moderate, 83.1% vs 79.0%; severe, 16.8% vs 21.0%). Patients initiating BEL before versus after immunosuppressant use had lower SLE flare rates and OGC use. Post-index, patients initiating BEL before versus after immunosuppressant use discontinued their OGC sooner (moderate baseline SLE, 4.5 vs 8.9months; severe baseline SLE, 6.2 vs 11.6months). Patients initiating BEL before versus after immunosuppressant use had lower SLE flare rates per person-year at all time points (especially severe flare rates in patients with severe baseline SLE, 0.70 vs 1.48 through 24months post-index). Median time to new organ damage occurrence was longer in patients initiating BEL before versus after immunosuppressant use (moderate baseline SLE, 32.1 vs 26.7months; severe baseline SLE, 22.7 vs 21.6months). All-cause HCRU was similar between cohorts. These results suggest that patients initiating BEL before versus after immunosuppressant use had more favorable outcomes.

Parasympathetic regulation and support from family and friends predict prosocial development in U.S. Mexican-origin adolescents.

Both parasympathetic nervous system regulation and receipt of social support from close relationships contribute to prosocial development, although few studies have examined their combined influences in adolescence and particularly within racially and ethnically minoritized populations. In this longitudinal study of 229 U.S. Mexican-origin adolescents (48% female-identifying), youths reported on receipt of social support from family and friends from 10 to 16 years, had their baseline respiratory sinus arrhythmia (RSA) measured at 17 years, reported their prosocial behavior and completed the Mind in the Eyes test to assess cognitive empathy at 17 and 19 years, and reported their prosocial civic behavior (i.e., community activity) at 19 years. Family social support predicted prosocial behavior at 17 years, and friend social support predicted prosocial civic behavior at 19 years. Compared to youths with lower or higher baseline RSA, youths with moderate RSA reported more prosocial civic behavior, had greater cognitive empathy, and tended to report more general prosocial behavior at 19 years. The quadratic association between baseline RSA and cognitive empathy was stronger for youths with greater family social support. These findings are the first to extend the evidence that moderate baseline parasympathetic nervous system activity supports prosocial development into late adolescence and with the U.S. Mexican-origin community, and these findings address calls for more integrative biopsychosocial studies of prosociality. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Silk-Derived Protein-4 Versus Vehicle Control in Treating Patients With Moderate to Severe Dry Eye Disease: A Randomized Clinical Trial

In this study the safety and efficacy of silk-derived protein 4 (SDP-4), also known as amlisimod, eye drops against a vehicle control formulation in patients with moderate to severe dry eye disease (DED) was assessed. SDP-4 is a novel, naturally derived, anti-inflammatory wetting agent that enhances coating on the ocular surface. Exploratory Phase 2, 12- and 8-week, serial cohort, multicenter, double-masked, randomized, vehicle-controlled study. In the first cohort (N = 305), patients were randomized 1:1:1:1 to SDP-4 (0.1%, 1%, 3% wt./wt.) or vehicle control and dosed 2 times per day (BID), while in the second cohort patients were randomized 1:1 with 1% wt./wt. SDP-4, the best performing formulation from the first cohort, or vehicle control BID (N = 151). Diagnosed DED patients were treated in the United States between April 2019 and May 2021. The first cohort of subjects had moderate to severe baseline symptoms, while the second cohort had moderate baseline symptoms to study the impact of baseline symptoms on SDP-4 performance. Key sign and symptom end points were mean change from baseline in TBUT and total SANDE score (0-100 visual analog scale) throughout the study. SDP-4 (1%) significantly increased TBUT vs the vehicle control (P < .05) at days 28 and 56 in the first cohort, and patient symptomatology from baseline was reduced by 46% based on subject reported SANDE VAS scores at day 84. Patients with more severe baseline DED symptoms experienced a significantly greater amount of relief than when compared to patients with moderate DED (P < .05). All treatment groups were well tolerated with a 2.6% total discontinuation rate. To the best of our knowledge, this was the first-in-human use of SDP-4 in a clinical trial. SDP-4 is a first-in-class protein ingredient that offers a safe and multi-modal treatment approach for alleviating severe DED symptoms within a novel formulation.

Transforming Veteran Rehabilitation Care: Learnings from a Remote Digital Approach for Musculoskeletal Pain.

While musculoskeletal pain (MSP) stands as the most prevalent health condition among Veterans, timely and high-quality care is often hindered due to access barriers. Team Red, White & Blue (Team RWB), a nonprofit organization dedicated to promoting a healthier lifestyle among Veterans, aimed to assess innovative approaches to veteran care. This is a single-arm pilot study investigating the feasibility, clinical outcomes, engagement, and satisfaction of a remote multimodal digital care program among Veterans with MSP. The impact of deployment experience on outcomes was explored as a secondary aim. From 75 eligible Veterans, 61 started the program, reporting baseline pain frequently comorbid with mental distress. Program acceptance was suggested by the high completion rate (82%) and engagement levels, alongside high satisfaction (9.5/10, SD 1.0). Significant improvements were reported in all clinical outcomes: pain (1.98 points, 95%CI 0.13; 3.84, p = 0.036); mental distress, with those reporting at least moderate baseline depression ending the program with mild symptoms (8.50 points, 95%CI: 6.49; 10.51, p = 0.012); daily activity impairment (13.33 points, 95%CI 1.31; 25.34, p = 0.030). Deployed Veterans recovered similarly to their counterparts. Overall, the above results underscore the potential of a remote digital intervention to expand Veterans' access to timely MSP care.

Association Between Greater Social Vulnerability and Delayed Glaucoma Surgery

PurposeTiming of surgical intervention in glaucoma is crucial to preserving sight. While ocular characteristics that increase surgical risk are known, the impact of neighborhood-level social risk factors such as the Social Vulnerability Index (SVI) and Area Deprivation Index (ADI) on time to glaucoma surgery is unknown. The objective of this study was to evaluate the association between SVI or ADI scores and the timing of glaucoma surgical intervention. DesignRetrospective cohort study. MethodsAdult subjects with open-angle glaucoma were identified from the Bascom Palmer Glaucoma Repository using International Classification of Disease-10 codes. Subject demographics, ocular characteristics, and standard automated perimetry (SAP) data were extracted. Geocoded data were obtained using subject residences and American Community Survey data. Univariable and multivariable time-to-event survival analyses using accelerated failure time (AFT) models were completed to evaluate whether geocoded SVI and ADI scores accelerated or delayed time to glaucoma surgery from initial glaucoma diagnosis in the electronic health record. ResultsA total of 10,553 eyes from 6,934 subjects were evaluated, of which 637 eyes (6.0%) from 568 subjects (8.2%) underwent glaucoma surgery. Mean age was 68.3±13.5 years, with 57.9% female, 21.5% Black, and 34.5% Hispanic subjects. Mean follow-up time was 5.0±2.1 years, with time to surgery of 3.2±1.9 years. Multivariable AFT models demonstrated that higher mean intraocular pressure (time ratio (TR) 0.27 per 5 mmHg higher; 95% CI: 0.23-0.31, p<0.001), faster SAP rate of progression (TR 0.74 per 0.5 dB/year faster; 95% CI: 0.69-0.78, p<0.001), moderate (TR 0.69; 95% CI: 0.56-0.85, p<0.001) or severe baseline severity (TR 0.39; 95% CI: 0.32-0.47, p<0.001), and thinner central corneal thickness (TR 0.85 per 50µm thinner; 95% CI: 0.77-0.95, p=0.003) all accelerated time to surgery. In contrast, overall SVI delayed surgery (TR 1.11 per 25% increase; 95% CI: 1.03-1.20, p=0.006). Specifically, SVI Themes 1 (TR 1.08; 95% CI: 1.01-1.17, p=0.037) and 4 (TR 1.11; 95% CI: 1.03-1.19, p=0.006) were significant. Patients from the most deprived neighborhoods (highest national ADI quartile) had a 68% increase in time to surgery compared to the least deprived quartile (TR 1.68; 95% CI: 1.20-2.36, p=0.002). ConclusionsResidence in areas with higher SVI or ADI scores was associated with delayed glaucoma surgery after controlling for demographic and ocular parameters. Awareness of such disparities can guide initiatives aimed at achieving parity in health outcomes.

Predicting cardiovascular events with fluoropyrimidine chemotherapy using a standard cardiovascular risk calculator.

Fluoropyrimidine chemotherapy is important for treatment of many solid tumours but is associated with cardiotoxicity. The relationship of fluoropyrimidine-associated cardiotoxicity (FAC) with conventional cardiovascular (CV) risk factors is poorly understood, and standard cardiovascular risk scores are not validated in this context. Single-centre retrospective study of patients treated with fluoropyrimidine chemotherapy using electronic health records for cardiovascular risk factors (and calculation of QRISK3 score), cancer treatment, and clinical outcomes. FAC was defined by cardiovascular events during or within 3months of fluoropyrimidine treatment, and Cox regression was used to assess associations of CV risk and cancer treatment with FAC. One thousand eight hundred ninety-eight patients were included (45% male; median age 64years), with median follow up 24.5 (11.5-48.3months); 52.7% of patients were at moderate or high baseline CV risk (QRISK3 score >10%) Cardiovascular events occurred in 3.1% (59/1898)-most commonly angina (64.4%, 38/59) and atrial fibrillation (13.6%, 8/59), with 39% events during cycle one of treatment. In univariable analysis, QRISK3 score >20% was significantly associated with incident FAC (HR 2.25, 95% CI 1.11-4.93, P=0.03). On multivariable analysis, beta-blocker use (HR 1.04, 95% CI 1.00-1.08, P=0.04) and higher BMI (HR 2.33, 95% CI 1.04-5.19, P=0.04) were independently associated with incident CV events. Thirty-two of the 59 patients with FAC were subsequently rechallenged with fluoropyrimidine chemotherapy, with repeat CV events in 6% (2/32). Incident FAC did not affect overall survival (P=0.50). High BMI and use of beta-blockers are associated with risk of CV events during fluoropyrimidine chemotherapy. QRISK3 score may also play a role in identifying patients at high risk of CV events during fluoropyrimidine chemotherapy. Re-challenge with further fluoropyrimidine chemotherapy can be considered in patients following CV events during prior treatment.

Association of Baseline Hepatitis B Virus DNA and On-Treatment Risk of Cirrhosis and Hepatocellular Carcinoma.

Recent studies suggest an inverse relationship between baseline levels of hepatitis B virus (HBV) DNA and on-treatment risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). However, data are limited to Asian cohorts, and it is unclear if similar associations hold true for non-Asians with CHB. We aimed to evaluate association of baseline HBV DNA with long-term risks of cirrhosis and HCC among a predominantly non-Asian cohort of CHB patients in the USA. Using longitudinal data from the national Veterans Affairs database, we evaluated the risk of cirrhosis or HCC among adults with non-cirrhotic CHB who are on continuous antiviral therapy, stratified by moderate levels of baseline HBV DNA (4.00 - 6.99 log10 IU/mL) vs. high levels of baseline HBV DNA (7.00 log10 IU/mL or higher). Propensity score weighting was applied, and competing risks cumulative incidence functions and Cox proportional hazards models were utilized. Among 1,129 non-cirrhotic CHB patients (41% non-Hispanic White, 36% African American, mean age 57.0 years, 62.2% hepatitis B e antigen (HBeAg) positive), 585 had moderate levels of baseline HBV DNA and 544 had high HBV DNA. After propensity score weighting, no significant difference in risk of cirrhosis was observed between moderate vs. high baseline HBV DNA (4.55 vs. 5.22 per 100 person-years, hazard ratio (HR): 0.87, 95% confidence interval (CI): 0.69 - 1.09, P = 0.22), but risk of HCC was significantly higher in patients with moderate vs. high baseline HBV DNA (0.84 vs. 0.69 per 100 person-years, HR: 1.33, 95% CI: 1.09 - 1.62, P < 0.01). Among a national cohort of predominantly non-Asian US veterans with non-cirrhotic CHB on antiviral therapy, moderate levels of baseline HBV DNA was associated with higher risk of HCC than high HBV DNA.

Ixekizumab Demonstrates Rapid and Consistent Efficacy for Patients with Psoriatic Arthritis, Regardless of Psoriasis Severity.

Skin involvement in patients with psoriatic arthritis (PsA) worsens the severity and burden of disease. Ixekizumab (IXE), a selective interleukin (IL)-17A antagonist, was compared to placebo (PBO) in the SPIRIT-P1 (NCT01695239) and SPIRIT-P2 (NCT02349295) studies in patients with PsA and evidence of plaque psoriasis. This post hoc analysis reports musculoskeletal, skin, and nail outcomes through week24 in patients from SPIRIT-P1 and SPIRIT-P2, stratified by mild, moderate, or psoriasis at baseline. This post hoc analysis pooled patients from SPIRIT-P1 and SPIRIT-P2 who were randomly assigned to PBO or IXE 80mg every 4weeks (Q4W) or every 2weeks (Q2W). Efficacy outcomes were analyzed through week24 by baseline psoriasis severity, defined by percent body surface area (BSA) affected; mild = BSA < 3%, moderate = 3% ≤ BSA ≤ 10%, severe = BSA > 10%. The primary outcomes assessed were the proportion of patients achieving American College of Rheumatology (ACR)20, ACR50, and ACR70 responses. Secondary outcomes included musculoskeletal, disease activity, skin and nail, and health-related quality-of-life measures. Similar proportions of patients achieved ACR20/ACR50/ACR70 over time across all severity subgroups and treatment arms. More than one-third of IXE-treated patients achieved ACR20 at week4, or ACR50 at week24, with no significant differences according to psoriasis severity at baseline. Disease activity outcomes were similar through week24 with both IXEQ4W and IXEQ2W, regardless of psoriasis severity at baseline. There were no significant differences over 24weeks in the proportions of IXE-treated patients with mild, moderate, or severe baseline psoriasis who achieved Minimal Disease Activity (MDA). Across all severity subgroups, IXE demonstrated Psoriasis Area Severity Index100 response as early as week4, and approximately one-third of IXE-treated patients achieved total skin clearance at week24. IXE demonstrated rapid and consistent efficacy in joint, skin, and nail for patients with PsA, regardless of baseline psoriasis severity. SPIRIT-P1 (NCT01695239), SPIRIT-P2 (NCT02349295).

Trajectories of cognitive function among people aged 45 years and older living with diabetes in China: Results from a nationally representative longitudinal study (2011~2018).

Diabetes is associated with decline of cognitive function. Exploring different trajectories of cognitive function occurring in people with diabetes is important to improved prognosis. This study aimed to investigate differential patterns of trajectories of cognitive function and baseline determinants of trajectory group membership utilizing data from middle-aged and older Chinese adults with diabetes. Participants of the Chinese Health And Retirement Longitudinal Study (CHARLS) aged 45 years and above received biennial assessments between 2011 and 2018. The primary outcome was overall cognitive function score operationalized as sum of mental intactness and episodic memory scores derived from the Telephone Interview of Cognitive Status (TICS). A weighted growth mixture model was used to estimate cognitive function trajectories of CHARLS participants with diabetes, and baseline factors associated with trajectory group membership were investigated with weighted multinomial logistic regression. Data from 1,463 participants with diabetes aged 45 years and above were analyzed, a three-group trajectory model showed the best fit for overall cognitive scores: low baseline, linear declining (22.1%); moderate baseline, linear declining (37.5%) and high-stable (40.3%). Older participants, females, participants with low education, with nighttime sleep <6 h, without daytime napping habits, and with depressive symptoms were at a higher risk of unfavorable cognitive function trajectories. We identified heterogeneous trajectories of cognitive function among middle-aged and older people living with diabetes in China. Socially vulnerable groups including females, rural residents, and those with low education were at a higher risk for unfavorable trajectories. In health programs aimed at preventing and mitigating cognitive decline in individuals with diabetes more attention should be given to vulnerable groups. Reduced nighttime sleep, lack of daytime napping, and depressive symptoms appear to be modifiable risk factors.

U.S. Law Enforcement Officers’ Stress, Job Satisfaction, Job Performance, and Resilience: A National Sample

The current study examined reports of perceived stress, job satisfaction, and job performance ratings in a longitudinal study of 684 officers participating in the Officer Safety and Wellness (OSAW) Initiative. Structural equation models were estimated to examine direct effects and, in subsequent analyses, the moderating effects of officer resilience and agency wellness programming on both the stress-job satisfaction association and the job satisfaction-job performance association. Surveys were administered annually, with job performance assessed both in terms of a self-rating and a self-report of supervisory rating at each officer’s last performance review. Officers’ stress (wave 1) was negatively associated with job satisfaction (wave 2), which in turn was positively associated with supervisory ratings of job performance (wave 3). These associations remained significant among officers reporting low to moderate baseline resilience but the association between job satisfaction and performance dissipated among officers with high resilience. Stress was negatively related to job satisfaction for officers who had easy access to agency-based wellness programs, whether they had concerns about stigma or used the programs, or not. The association between stress and job performance varied according to program access, use, and concerns about stigma associated with use. Administrators and policymakers striving to retain a high-performance police workforce may consider these results in recruiting as well as academy and in-service wellness training and program decisions.

Patients with High Pre-Operative Physical Activity Take Longer to Return to Baseline

Patients with end-stage osteoarthritis are recommended to engage in physical activity (PA) to reduce pain and improve function but may avoid PA due to joint pain. Our goal was to investigate patient-reported outcomes and objective mobility metrics (step counts) in total hip arthroplasty (THA) patients as a function of pre-operative PA levels. In total, 1647 patients enrolled in a multicenter prospective cohort study investigating a smartphone-based care management platform for self-directed rehabilitation that underwent THA and were included in analysis. The entire cohort’s step count was divided into quartiles to categorize patients with low, moderate, and high baseline PA. Outcomes including pain, EQ-5D-5L, HOOS JR, and step counts were compared according to activity group by ANOVA. Pre-operative pain scores were lowest, with smallest improvements, in the high-baseline PA group. Low-PA patients demonstrated the greatest improvements in EQ-5D-5L, while changes in EQ-VAS, HOOS JR, and satisfaction were similar between groups. Low- and moderate-PA patients increased physical activity by six weeks, reaching 180% and 114% of pre-operative steps; high-PA patients did not return to full step counts until one-year post-operation. Patients who perform high levels of PA undergoing THA report lower levels of pain and higher function pre-operatively but may appreciate less improvement in PA up to one year post-operatively. These results may be helpful in appropriate counseling of patient expectations prior to surgery.

Delivery of a post-natal neonatal jaundice education intervention improves knowledge among mothers at Jinja Regional Referral Hospital in Uganda.

Neonatal jaundice (NNJ) is a major contributor to childhood morbidity and mortality. As many infants are discharged by 24 hours of age, mothers are key in detecting severe forms of jaundice. Mothers with limited knowledge of NNJ have a hard time identifying these infants who could go on to have the worst outcomes. This study aimed to determine the effect of a jaundice education package delivered to mothers prior to hospital discharge on maternal knowledge after discharge. This was a before and after interventional study involving an education package delivered through a video message and informational voucher. At 10-14 days after discharge, participants were followed up via telephone to assess their post-intervention knowledge. A paired t-test was used to determine the effectiveness of the intervention on knowledge improvement. Linear regression was used to determine predictors of baseline knowledge and of change in knowledge score. Of the 250 mothers recruited, 188 were fit for analysis. The mean knowledge score was 10.02 before and 14.61 after the intervention, a significant difference (p<0.001). Factors determining higher baseline knowledge included attendance of 4 or more antenatal visits (p < 0.001), having heard about NNJ previously (p < 0.001), having experienced an antepartum illness (p = 0.019) and higher maternal age (p = 0.015). Participants with poor baseline knowledge (β = 7.523) and moderate baseline knowledge (β = 3.114) had much more to gain from the intervention relative to those with high baseline knowledge (p < 0.001). Maternal knowledge of jaundice can be increased using a simple educational intervention, especially in settings where the burden of detection often falls on the mother. Further study is needed to determine the impact of this intervention on care seeking and infant outcomes.

Non-linear association of baseline viral load with on-treatment hepatocellular carcinoma risk in chronic hepatitis B

ObjectiveThe association between baseline pretreatment serum HBV DNA levels and on-treatment hepatocellular carcinoma (HCC) risk remains controversial in patients with chronic hepatitis B (CHB). We aimed to investigate the association...

Latent Change Trajectories in Mood During Focused CBT Enhanced for Eating Disorders Are Associated With Global Eating Pathology at Posttreatment and Follow-Up Among Individuals With Bulimia Nervosa Spectrum Disorders: A Preliminary Examination

Bulimia nervosa (BN) is characterized by recurrent loss of control over eating (LOC) and inappropriate compensatory behaviors. Although cognitive-behavioral therapy (CBT) is efficacious for BN, many patients continue to experience symptoms at posttreatment. One potential driver of this low treatment response may be low mood, which maintains BN symptoms through negative reinforcement. Thus, it is important to understand how mood changes over enhanced cognitive-behavioral therapy (CBT-E) and whether these changes are associated with improved treatment outcomes. Participants (N = 56) with BN-spectrum eating disorders (EDs) received 16 sessions of the focused version of CBT-E. The Eating Disorder Examination (EDE) was used to measure ED symptoms (global ED pathology, frequency of binge episodes, and compensatory behaviors) at pre- and posttreatment. Latent growth mixture modeling (LGMM) of affective ratings via digital self-monitoring identified latent growth classes. Kruskal–Wallis H tests examined the effect of trajectory of change in mood on pre- to posttreatment symptom change. LGMM yielded a four-class model that best fit the data representing distinct mood trajectories over the course of treatment: (a) highest baseline mood, linear improving; (b) moderate baseline mood, stable; (c) moderate baseline mood, quadratic worsening; and (d) lowest baseline mood, quadratic improving. Participants who demonstrated worsening mood over treatment (i.e., individuals in the “moderate baseline mood, quadratic worsening” class) had significantly higher EDE global scores at posttreatment and follow-up compared to participants with stable mood across treatment. Change in LOC eating frequency and compensatory behaviors across treatment did not significantly differ by mood class. The main effect of mood class or interaction effect between time and mood class on objective binge episodes, subjective binge episodes, and compensatory behaviors was not significant. There were no significant differences in global ED pathology at either posttreatment or follow-up for any other class comparisons. These results suggest that certain trajectories of change in mood during treatment are particularly associated with change in pre- to posttreatment EDE global score. If replicated, our findings could suggest that future iterations of CBT-E should target mood early in treatment in order to maximize reductions in global eating pathology.

Baseline symptom severity and efficacy of Silexan in patients with anxiety disorders: A symptom-based, patient-level analysis of randomized, placebo-controlled trials.

The influence of baseline severity on the efficacy of Silexan, a proprietary essential oil from Lavandula angustifolia, in anxiety disorders has not been investigated in a pooled dataset. We report on an individual patient data analysis of all five double-blind, randomized, placebo-controlled trials with Silexan in anxiety disorders. Eligible participants received Silexan 80mg/d or placebo for 10 weeks. Analyses were based on the Hamilton Anxiety Rating Scale (HAMA), its psychic and somatic anxiety subscores, and the Clinical Global Impressions (CGI) scale. To correlate baseline severity with outcome, patients were segregated into mild, moderate, and severe cases. Altogether 1,172 patients (Silexan, n=587; placebo, n=585) were analyzed. For the HAMA total score, we found a significant association between the score at baseline and the treatment effect of Silexan versus placebo at week 10 (p<0.001). HAMA items from the somatic domain scored lower at baseline and showed less improvement than items from the psychic domain, particularly in patients with mild or moderate baseline symptoms. For CGI item 2 (global improvement), significant efficacy favoring Silexan were observed in mild, moderate, and severe baseline symptom severity. Although significant improvements were found for all subsets, the more severe the initial symptoms, the greater the treatment effects documented by the HAMA. Overall this analysis confirms that Silexan is an effective treatment option in early or mild stages of anxiety disorder. Given its favorable safety profile, Silexan can thus fill a therapeutic gap in the treatment of (subsyndromal) anxiety disorders.