A Retrospective Repeated Cross-Sectional Study

[Posted 3/Oct/2025]

AUDIENCE: Family Medicine, Infectious Disease

KEY FINDINGS: Medicare beneficiaries aged 65 years and older with HIV in the USA were more likely to receive opioid prescriptions and have OUD indicators than matched beneficiaries without HIV. Findings could help guide clinical opioid prescription guidelines and public health surveillance among this vulnerable ageing population.

BACKGROUND: There is longstanding concern that people with HIV receive prescription opioids at higher rates and have a disproportionate burden of opioid use disorder (OUD) compared with their counterparts without HIV. We aimed to evaluate trends of opioid prescriptions and indicators of OUD in an understudied but growing population of older adults with HIV.

DETAILS: For this retrospective repeated cross-sectional study, authors constructed annual cohorts through a nationally representative sample of fee-for-service Medicare beneficiaries aged 65 years and older in the USA with Part D coverage (ie, prescription drug) enrolled between Jan 1, 2008, and Dec 31, 2021. Beneficiaries were eligible for inclusion in each cross-sectional cohort if they had reached the age of 65 years by Jan 1 of the calendar year and had 1 year of continuous Medicare enrolment in Part A (inpatient hospital care), B (outpatient care), and D. Beneficiaries with HIV were matched in a 1:3 ratio to beneficiaries without HIV on age, sex, race or ethnicity, US state, and dual eligibility status (Medicare and Medicaid). The main outcomes were receipt of at least one opioid prescription and any indicator of OUD (ie, formal diagnosis, medication for OUD, or opioid-related or emergency department visits) during each calendar year. Generalised estimating equations were used to estimate odds ratios (ORs) of each outcome, comparing matched beneficiaries with or without HIV. Due to data availability, our analysis of indicators of OUD was restricted to 2008-16. Across all years, 163,429 beneficiaries with HIV and 490,287 beneficiaries without HIV were included (475,516 [72.7%] were male, 178,200 [27.3%] were female; 305,776 [46.8%] were non-Hispanic White, 238,172 [36.4%] were Black [or African American], 84,128 [12.9%] were Hispanic, 8964 [1.4%] were Asian or Pacific Islander, and 16,676 [2.6%] were other races or ethnicities). During 2008-21, 57,373 (35.1%) of 163,429 people with HIV and 138,547 (28.3%) of 490,287 people without HIV received at least one opioid prescription. During 2008-16, 2408 (3.1%) of 76,637 people with HIV and 2831 (1.2%) of 229,911 people without HIV had any indicator of OUD. Across all analysed years, beneficiaries with HIV had significantly increased odds of receiving at least one opioid prescription (OR 1.38, 95% CI 1.36-1.39) and having indicators of OUD (2.61, 2.47-2.76) compared with their matched counterparts without HIV.

Copyright © The Author(s). Elsevier Ltd. All rights reserved.

Source: Shiau, S., Drago, F., Kinkade, C. W., et al. (2024). Prescription Opioid Use and Opioid Use Disorder Among Older Adults With HIV in the USA From 2008 to 2021: A Retrospective Repeated Cross-Sectional Study. The Lancet Primary Care. 2025; 1(3): 100017. Published: September, 2025. DOI: 10.1016/j.lanprc.2025.100017.

[Posted 10/Oct/2025]

AUDIENCE: Neurology, Internal Medicine

KEY FINDINGS: Having a family history of PD predicts slower progression of cognitive decline and caudate dopaminergic degeneration, and less FOG compared with those without a family history independent of PRS. Taken together, information on family history could be used as a proxy for the clinical heterogeneity of PD.

BACKGROUND: Evidence suggests that either family history or polygenic risk score (PRS) is associated with developing Parkinson disease (PD). However, little is known about the longitudinal prognosis of PD according to family history and higher PRS.

DETAILS: From the Parkinson's Progression Markers Initiative database, 395 patients with PD who followed up for more than 2 years were grouped into those with family history within first-degree, second-degree, and third-degree relatives (N = 127 [32.2%]) vs those without (N = 268 [67.8%]). The PRS of 386 patients was computed using whole-genome sequencing data. Longitudinal assessment of motor, cognition, and imaging based on dopaminergic degeneration was conducted during the regular follow-up period. Effects of family history, PRS, or both on longitudinal changes of cognition, motor severity, and nigrostriatal degeneration were tested using a linear mixed model. The risk of freezing of gait (FOG) according to family history was assessed using the Kaplan-Meier analysis and Cox regression models. During a median follow-up of 9.1 years, PD with positive family history showed a slower decline of caudate dopamine transporter uptake (ß estimate of family history x time = 0.02, 95% CI = 0.002-0.036, p = 0.027). Family history of PD and higher PRS were independently associated with a slower decline of Montreal Cognitive Assessment (ß estimate of family history x time = 0.12, 95% CI = 0.02-0.22, p = 0.017; ß estimate of PRS x time = 0.09, 95% CI = 0.03-0.16, p = 0.006). In those 364 patients without FOG at baseline, PD with positive family history had a lower risk of FOG (hazard ratio of family history = 0.57, 95% CI = 0.38-0.84, p = 0.005).

Copyright © American Academy of Neurology. All Rights Reserved.

Source: Park, M. and Lee, Y. (2025). Association of Family History and Polygenic Risk Score With Longitudinal Prognosis in Parkinson Disease. Neurology Genetics. 2025; Published: October, 2025. DOI: 10.1212/NXG.0000000000200115.

[Posted 9/Oct/2025]

AUDIENCE: Gastroenterology, Internal Medicine

KEY FINDINGS: Elevated DUOX2 signalling contributes to epithelial barrier dysfunction, microbiome alterations and subclinical inflammation. Butyrate and HDAC inhibitors reversed these effects, indicating that DUOX2 may be a therapeutic target in IBD.

BACKGROUND: Inflammatory bowel diseases (IBDs) are characterised by dysbiosis and a leaky gut. The NADPH oxidase dual oxidase 2 (DUOX2) is upregulated in patients with IBD, yet its role in driving the disease remains unclear. Authors interrogated the functional consequences of epithelial DUOX2 activity for the host and microbiome.

DETAILS: DUOX2 function was studied in mice with epithelial-specific DUOX2 overactivation (vTLR4), inactivation (vTLR4 DUOXA IEC-KO) and wild-type controls. Authors assessed the effect of dysbiosis on DUOX2 signalling and intestinal permeability (FITC-dextran, serum zonulin, bacterial translocation) with germ-free (GF) mice engrafted with IBD or healthy microbiota. RNA sequencing of colonic mucosa and microbiota and faecal metabolomics were used to characterise the host-microbe interface. Mechanistic studies were conducted in mouse colonoids, IBD biopsies and patient serum samples. DUOX2 activity increased permeability and bacterial translocation and induced subclinical inflammation in vTLR4 mice. GF vTLR4 mice had increased DUOX2 activity and permeability but no subclinical inflammation. In patients with IBD, DUOX2 expression was positively associated with plasma zonulin levels and negatively associated with ZO-1 expression. Engraftment of GF mice with IBD stool increased DUOX2 activity and triggered low-grade inflammation and permeability defects in mice. DUOX2 activity functionally altered the microbiome, reduced butyrate metabolism and promoted proinflammatory and pro-oncogenic bacterial metabolites. Butyrate and histone deacetylase (HDAC) inhibitors blocked DUOX2 activation and reversed its effects.

Copyright © BMJ Publishing Group Ltd & British Society of Gastroenterology. All rights reserved.

Source: Hazime, H., Ducasa, G. M., Santander, A. M., et al. (2025). DUOX2 Activation Drives Bacterial Translocation and Subclinical Inflammation in IBD-Associated Dysbiosis. dysbiosisGut. 2025; 74: 1589-1601. Published: October, 2025. DOI: 10.1136/gutjnl-2024-334346.

The Multicenter, Two-Cohort, Phase II NEPTUNES Study

[Posted 8/Oct/2025]

AUDIENCE: Oncology

KEY FINDINGS: Nivolumab 1 mg/kg + ipilimumab 3 mg/kg is an active treatment in ImS+ pretreated mCRPC. Nivolumab 3 mg/kg + ipilimumab 1 mg/kg has less toxicity but may have lower efficacy. HII is a promising prospectively tested predictive biomarker in prostate cancer that could be integrated into future trials.

BACKGROUND: Efficacy of immune checkpoint inhibitors in unselected patients with metastatic castration-resistant prostate cancer (mCRPC) is limited. The NEPTUNES study evaluated combination nivolumab and ipilimumab in patients with immunogenic signature-positive (ImS+) mCRPC.

DETAILS: This open-label, 2-cohort, phase II trial enrolled patients with ImS+ mCRPC progressing on >=1 previous line of treatment. ImS+ was defined by (1) mismatch repair deficiency (MMRD); (2) DNA damage repair gene loss; and/or (3) high inflammatory infiltrate (HII). Patients received four doses of nivolumab 1 mg/kg + ipilimumab 3 mg/kg (C1) or nivolumab 3 mg/kg + ipilimumab 1 mg/kg (C2) followed by nivolumab 480 mg once every 4 weeks up to 10 cycles. The primary end point was composite response rate (CRR) assessed radiologically, biochemically, and by reduction of circulating tumor cells. Secondary end points included toxicity, progression-free survival, overall survival, and duration of response. Between May 2018 and June 2022, 35 (C1) and 36 (C2) patients commenced treatment. The CRR in C1 was 14/35 (40%, 90% CI, 26% to 55%) and in C2 was 9/36 (25%, 90% CI, 14% to 40%). The overall CRR was 23/71 (32%, 90% CI, 23% to 43%). Response rates were higher in patients with MMRD (7/10), BRCA2 loss (4/8), and HII ± other ImS+ features (13/30). Duration of response for patients with HII without other ImS+ features, DNA repair gene loss without MMRD, and MMRD was 2.6, 17.3, and 10 months, respectively. Grade 3 to 4 treatment-related adverse events occurred in 22/35 (63%) in C1 and 12/36 (33%) patients in C2. There were no treatment-related deaths.

Copyright © American Society of Clinical Oncology. All rights reserved.

Source: Leone, G., Wong, Y. N. S., Jones, R. J., et al. (2025). Nivolumab and Ipilimumab for Metastatic Castration-Resistant Prostate Cancer With an Immunogenic Signature: The Multicenter, Two-Cohort, Phase II NEPTUNES Study. Journal of Clinical Oncology. 2025; 43(28): 3070-3080. Published: October 1, 2025. DOI: 10.1200/JCO-24-02637.

[Posted 30/Sep/2025]

AUDIENCE: Internal Medicine, Nursing

KEY FINDINGS:

• DPP-4 inhibitors offer a safer alternative to meglitinides in T2D patients with Stage 5 CKD with lower severe renal outcomes and hypoglycemia risk.
• Hypoglycemia risk is lower with DPP-4i due to glucose-dependent insulinotropic action.
• DPP-4i are weight neutral, helpful in normal or lower BMI patients.
• Renoprotection mechanisms of DPP-4i may involve GLP-1 dependent pathways and antifibrotic effects but need further study.
• Observational data with residual confounding; randomized trials needed for conclusive evidence.
• Cost and access issues may influence DPP-4i use in some settings.

BACKGROUND: Managing hyperglycemia in type 2 diabetes (T2D) patients with advanced chronic kidney disease (CKD) is complex due to altered drug metabolism and risk of adverse events. Conventional treatments like metformin pose risks due to renal excretion; sulphonylureas and pioglitazone involve metabolites renally cleared raising hypoglycemia and fluid retention risks. Meglitinide repaglinide is preferred in this setting due to hepatic metabolism and flexible dosing. DPP-4 inhibitors (DPP-4i) offer a safer profile with low hypoglycemia risk and weight neutrality, but data on their safety and efficacy in Stage 5 CKD remain scarce.

DETAILS: Hung et al. conducted a nationwide Taiwanese cohort study (2012-2020) comparing renal outcomes in Stage 5 CKD patients with T2D starting either DPP-4i (n=5028) or meglitinides (n=2243). Stage 5 CKD was defined using erythropoiesis-stimulating agent (ESA) use as a surrogate for eGFR <15 mL/min/1.73 m². Propensity score matching adjusted for confounders. The primary composite outcome included renal replacement therapy (RRT), renal death, and kidney-related hospitalization. DPP-4i use was associated with a 14% lower risk of the primary composite renal outcome vs. meglitinides (HR 0.86; 95% CI 0.81-0.92), mainly through reduced need for RRT. Severe hypoglycemia risk was 41% lower in the DPP-4i group. The findings support the renal safety and possible benefits of DPP-4i over meglitinides in severe CKD. Limitations include observational design, ESA use as CKD surrogate, lack of clinical measurements, and limited generalizability due to homogeneous Taiwanese cohort.

Copyright © John Wiley & Sons, Inc. All rights reserved

Source: Ryden, M. (2025). Choosing Oral Antihyperglycaemic Drugs in People Living With Type 2 Diabetes and Severe Chronic Kidney Disease. Journal of Internal Medicine. 2025; 298(3): 149-151. Published: September, 2025. DOI: 10.1111/joim.70002.

A Prospective Interventional Study

[Posted 29/Sep/2025]

AUDIENCE: General Surgery, Internal Medicine, Hematology

KEY FINDINGS: Curettage remains optimal for thick, hyperkeratotic SKs, enabling histopathological confirmation. The 532 nm laser, preferred subjectively for convenience, may suit small, non-hyperkeratotic lesions but warrants further validation. Propane-butane cryotherapy offers a cost-effective alternative. The discordance between patient preferences (prioritizing convenience) and clinical efficacy underscores the need for personalized treatment strategies balancing outcomes, tolerability, and cosmetic expectations.

BACKGROUND: Seborrheic keratosis (SK) is the most prevalent benign skin tumor associated with aging, posing esthetic concerns and potential discomfort. The rising demand for cosmetic interventions prompts the exploration of effective removal methods. This study compares three treatment modalities: curettage, 532 nm laser, and propane-butane cryotherapy.

DETAILS: A prospective interventional clinical study was conducted with 30 subjects, treating 123 SK using curettage, 532 nm laser, and propane-butane cryotherapy. Randomized allocation and evaluations at 0, 4, 8, and 12 weeks were employed. Objective measures included clearance rates (assessed by a dermatologist) and blinded cosmetic ratings by 125 observers. Subjective outcomes encompassed patient-reported pain (VAS), side effects, satisfaction, and preferences. Curettage achieved the highest clearance rate (87.5% vs. laser: 55%, cryotherapy: 50%; p < 0.01). However, patients perceived complete healing most frequently with laser (90% vs. curettage: 87%, cryotherapy: 53%). Despite lower efficacy, 67% favored laser for future treatments, valuing minimal bleeding and no dressings. Observers rated curettage's cosmetic outcomes superior (50% vs. laser: 22.5%). Laser caused the fewest side effects (mean 0.93/lesion) but highest pain (VAS: 4.62 vs. cryotherapy: 3.85). Cryotherapy showed efficacy comparable to laser (50% vs. 55%) but more adverse events.

Copyright © Wiley Periodicals LLC. All rights reserved

Source: Timmermann, V., Krengel, S., Mrowka, P,, et al. (2024). Practical Approaches for Seborrheic Keratosis Treatment: Curettage Versus 532-nm Lithium Borate Laser Versus Cryotherapy: A Prospective Interventional Study. Lasers in Surgery and Medicine. 2025; 57(7): 581-589. Published: September, 2025. DOI: 10.1002/lsm.70042.