Stephen J. Kerr

Introduction: Metabolic dysfunction‐associated steatohepatitis (MASH) is more common in people with HIV and associated with systemic inflammation and extrahepatic complications, including cognitive impairment. While cross‐sectional studies suggest an association between MASH and worse cognitive outcomes, its impact on longitudinal cognitive trajectories in people with HIV remains unclear. Methods: This prospective study included people with HIV aged≥50 years from HIV‐NAT, Bangkok, Thailand, between 2015 and 2024. MASLD and MASH were identified at baseline using the FibroScan‐AST (FAST) score. Cognitive function was assessed using the Thai‐validated Montreal Cognitive Assessment (MoCA) at baseline and a follow‐up visit. A multivariate linear mixed model was used to determine the difference in changes in MoCA scores between participants with and without baseline MASH. Results: Among 291 participants (60.5% male; median age 54.4 years), 60 (20.6%) met criteria for MASH at baseline. Over a median follow‐up of 5.9 years, baseline MASLD was not associated with cognitive decline, whereas participants with baseline MASH showed a significantly greater cognitive decline between ages 50 and 80 years, after adjusting for age, sex, body mass index, education level, employment status, smoking, alcohol consumption, diabetes, hypertension, duration of HIV acquisition and exposure to efavirenz. Participants with MASH showed a mean MoCA decline of –4.79 (95% CI –7.49 to –2.09), compared with –0.94 (95% CI –2.20 to –0.32) among those without MASH ( p ‐interaction = 0.007). Conclusions: MASH is a significant predictor of steeper cognitive decline in older people with HIV, independent of traditional metabolic and HIV‐related risk factors. These findings suggest that early identification and management of MASH may help mitigate cognitive decline in ageing HIV care.

Purpose: This national study examined longitudinal changes in perceived feedback quality during phased rollout of a mobile entrustable professional activity-based feedback application across Thai College of Emergency Physicians-accredited emergency medicine residency programs and explored institutional, contextual, and application use variables associated with perceived feedback quality. Method: This national, multisite prospective observational study (December 2019-September 2020) included 135 faculty and 357 residents from accredited Thai emergency medicine residency programs. The application was implemented in 3 phases: notifications, feedback guide/self-reflection prompts, and dashboard. Participants completed Feedback in the Emergency Room across 5 domains (timeliness, specificity, communication, action plan, feedback culture) using 5-point Likert-type items. Scores were converted to Percent of Maximum Possible (POMP; 0-100; higher scores indicate higher perceived feedback quality). Linear mixed-effects models estimated changes in domain and total Feedback in the Emergency Room POMP scores over time; total score models assessed associations with institutional, contextual, and application use variables. Results: Faculty-reported overall perceived feedback quality did not change significantly at 3 months but increased at 6 months (4.03 POMP; 95% CI, 1.99-6.07) and 9 months (3.57; 95% CI, 1.02-6.11). Resident-reported overall scores did not change significantly. In resident models, dashboard review (always: 2.54; 95% CI, 0.18-4.89; sometimes: 2.21; 95% CI, 0.32-4.09), and resident rules (1.78; 95% CI, 0.09-3.48) were associated with higher scores; absence of formal feedback strategies was associated with lower scores (−2.00; 95% CI, −3.87 to −0.13). Conclusions: During implementation of a mobile entrustable professional activity-based feedback application, faculty reported modest improvements in perceived feedback quality, whereas resident perceptions remained stable. Digital tools may support feedback processes when aligned with institutional context. Future studies should link feedback to encounters and evaluate mechanisms and downstream educational outcomes using designs that strengthen causal inference.

Background: Anti-tuberculosis drug-induced hepatotoxicity (DIH) is a common complication among people living with HIV (PLWH), potentially leading to treatment interruptions. Objective: To determine the incidence of DIH and identify risk factors in Thai and Filipino PLWH on tuberculosis (TB) treatment, compared with those with TB mono-infection. Methods: We conducted a cohort study of Thai and Filipino adults with active TB using retrospective data from Thailand (2000–2024) and prospective data from the Philippines (2024). DIH was defined as AST or ALT ≥3 times the upper limit of normal. Logistic regression was used to assess DIH risk factors among PLWH; TB treatment outcomes were compared by DIH status. Results: Among 222 participants (138 PLWH, 84 HIV-negative), median age was 38 years, 63% were male, and median body mass index (BMI) was 18.2 kg/m ² . DIH occurred in 13.8% of PLWH and 9.5% of HIV-negative individuals ( P = 0.35), with median onset at 10 and 3 weeks, respectively. Among PLWH, hepatitis C co-infection (aOR 5.84, 95% CI 1.51–22.55, P = 0.01) and lower BMI (aOR 0.78/kg/m ² , 95% CI 0.63–0.97, P = 0.03) were independently associated with DIH. Dolutegravir use showed a non-significantly lower DIH risk (OR 0.51, 95%CI, 0.18 – 1.42). TB treatment success was similar between those with and without DIH (92.6% vs 90.3%); mortality was slightly higher with DIH (3.7% vs 1.5%). Conclusions: Hepatitis C co-infection and low BMI are key risk factors for DIH among PLWH receiving TB treatment. Despite these risks, DIH did not significantly impact treatment outcomes.

Background: The optimal surgical management of high‐grade parotid carcinoma confined to the superficial lobe remains controversial, with limited evidence comparing total and superficial parotidectomy in this setting. Objective: To compare oncologic outcomes and complications between total parotidectomy with postoperative radiotherapy (TP + PORT) and superficial parotidectomy with postoperative radiotherapy (SP + PORT). Study Design: Multicentre retrospective cohort study. Methods: Adult patients (> 18 years) with high‐grade parotid carcinoma confined to the superficial lobe treated between 2011 and 2023 were identified at tertiary centres. Exclusion criteria included preoperative facial nerve palsy, metastatic disease to the parotid gland, prior head and neck radiotherapy, receipt of concurrent chemoradiation and follow‐up < 12 months. Results: A total of 108 patients were included (TP + PORT, n = 63; SP + PORT, n = 45) with a median follow‐up of 53 months. Baseline characteristics were comparable except for older age and a higher proportion of Milan category VI cytology in the TP + PORT group ( p < 0.05). Local, regional and distant recurrence rates and mortality did not differ significantly between groups ( p = 0.55, 0.26, 1.00 and 0.36, respectively). All local recurrences occurred within 24 months (mean: 7.2 months). Age and positive resection margins were independent predictors of mortality ( p < 0.01). Five‐year overall survival was 73.0% in the TP + PORT group and 81.5% in the SP + PORT group. IPTW‐adjusted analyses confirmed no significant differences in recurrence or mortality between groups (hazard ratio for mortality, 0.78; 95% CI: 0.32–1.90; p = 0.59). Permanent facial nerve palsy was significantly more common after TP + PORT (14.3% vs. 2.2%, p < 0.001), while other complications were similar. Conclusion: Superficial parotidectomy with adequate margins followed by PORT achieves comparable oncologic outcomes with significantly fewer complications and may be preferred for high‐grade parotid carcinoma confined to the superficial lobe. Level of Evidence: 2d (JBI).

Objectives: To assess the association of the Cardio‐Ankle Vascular Index (CAVI) and ankle‐brachial index (ABI) with all‐cause mortality and major adverse cardiovascular events (MACE) in older people with HIV receiving long‐term antiretroviral therapy (ART) in Thailand. Methods: We conducted a prospective cohort study of 307 virologically suppressed participants aged ≥50 years who underwent baseline CAVI and ABI measurements. ABI was analysed both as a continuous variable and as a categorical variable using a cut‐off p = 0.004) but did not reach statistical significance for the composite outcome (aHR 1.64, 95% CI: 0.89–3.01, p = 0.112). However, when modelled as a continuous variable, each unit increase in CAVI was associated with an increased risk of composite outcome (aHR 1.29, 95% CI: 1.08–1.54, p = 0.004). Ever smoking, hypertension and elevated IL‐6 were significantly associated with increased risk of mortality and MACE. ABI < 0.9 was strongly associated with mortality (aHR 4.20, 95% CI: 1.43–12.27). Conclusions: In older people with HIV on long‐term ART, traditional cardiovascular risk, systemic inflammation (IL‐6) and low ABI (<0.9) were stronger predictors of mortality and MACE. CAVI demonstrated prognostic value for mortality and the composite outcome, suggesting a potential complementary role in cardiovascular risk assessment. Clinical trial registration: HIVNAT 006 (NCT00411983).

Introduction: Frailty is highly prevalent among older people with HIV (PWH), driven by multimorbidity and HIV‐associated accelerated ageing. We investigated frailty transitions and associated factors over a 5‐year follow‐up period in an ageing cohort of PWH in Thailand. Methods: We conducted a prospective cohort study among PWH aged ≥50 years in Bangkok, Thailand, between May 2015 and June 2024. Frailty phenotypes were assessed at baseline and at 5 years of follow‐up using the Fried frailty phenotype, including unintentional weight loss, low physical activity, exhaustion, weak grip strength and slow walking speed. Multinomial logistic regression was performed to identify factors associated with frailty progression and reversibility over follow‐up. Results: Among 324 participants enrolled (63% male; median age of 54 [IQR, 52−59] years), 158 (49%) were robust, 153 (47%) were pre‐frailty and 13 (4%) were frailty at baseline. Over 5 years, 111 participants (34%) experienced frailty worsening, 158 (49%) remained stable and 55 (17%) demonstrated frailty reversal. Among 158 PWH who were robust at baseline, 75 (47%) remained robust, 57 (36%) transitioned to pre‐frailty and 26 (16%) progressed to frailty. Notably, among those frail at baseline ( N = 13), 65% improved to pre‐frailty or robustness. Low physical activity was the most common frailty component at baseline, while weak grip strength was the most predominant frailty phenotype at year 5. In multivariable analysis, multimorbidity (adjusted odds ratio [aOR] 3.09, 95% confidence interval [CI]: 1.42−6.72, p = 0.004), antiretroviral therapy (ART) duration>20 years (aOR 1.82, 95% CI: 1.08−3.06, p = 0.025) and baseline vitamin D deficiency (aOR 1.85, 95% CI: 1.10−3.10, p = 0.019) were independently associated with increased frailty over the 5‐year follow‐up. Conversely, multimorbidity (aOR 0.44, 95% CI: 0.44 [0.23−0.84], p = 0.013) and CD4 counts< 500 cells/mm ³ (aOR 0.25, 95% CI: 0.10−0.62, p = 0.003) were associated with a lower likelihood of frailty reversal. Conclusions: Frailty among PWH aged ≥50 years in Thailand was common and highly dynamic, with over half of frail participants improving over 5 years. Multimorbidity, prolonged ART exposure and vitamin D deficiency were key predictors of frailty progression, whereas CD4< 500 cells/mm ³ and multimorbidity reduced the likelihood of frailty reversal. These findings highlight frailty as modifiable and support integrating routine frailty screening and geriatric‐informed care into long‐term HIV services. Clinical Trial Registration: NCT00411983

Objectives: Access to the frontal sinus after receiving angled Draf 2a frontal sinusotomy remains challenging, while adequate postoperative irrigation is essential in managing chronic inflammatory sinus disease. This study compared frontal sinus irrigation distribution between the angled Draf 2a and Carolyn's window approaches, a modification of Draf 2a which removes the nasofrontal beak by drilling to permit direct 0° endoscopic access. Methods: Fresh human cadaver heads underwent sequential dissection with angled Draf 2a followed by Carolyn's window approach. Each cavity was irrigated using a 250 mL high‐pressure squeeze bottle filled with 1/1000 10% fluorescein‐labeled water in the Frankfort horizontal position. Fluid irrigation was recorded using an endoscope placed within the frontal sinus. Blinded grading of fluid distribution was performed using a 0–4 scale: 0 (nasal cavity only), 1 (frontal recess), 2 (medial half), 3 (lateral half), and 4 (complete lavage). Scores were compared between two surgical approaches. Results: Eight cadaveric specimens (16 frontal sinuses) were evaluated. Compared with angled Draf 2a frontal sinusotomy, Carolyn's window approach achieved a greater distribution: grade 1 (50.0% vs. 0%), grade 2 (31.3% vs. 0%), grade 3 (6.3% vs. 43.8%), and grade 4 (12.5% vs. 56.3%). The median (IQR) distribution grade following angled Draf 2a frontal sinusotomy was 1.5 (1, 2), and 4 (3, 4) for the Carolyn's window approach ( p < 0.01). Conclusion: Carolyn's window significantly enhances frontal sinus irrigation compared to angled Draf 2a by improving access and distribution. This technique is robust for enhancing postoperative topical therapy in chronic frontal sinus disease. Level of Evidence: N/A.

Background: Emerging evidence suggests that human cytomegalovirus (HCMV) infection is associated with tuberculosis (TB) disease. This study aimed to assess the relationship between the dynamics of HCMV markers and TB disease in people with human immunodeficiency virus (PWH). Methods: In a case-control study nested within a Thai HIV cohort, stored samples from people with HIV who were diagnosed with TB disease after antiretroviral therapy (ART) (cases) and TB-negative controls matched 1:2 on ART duration. HCMV DNA, immunoglobulin M (IgM), and immunoglobulin G (IgG) were measured at 3 timepoints: (i) 6–24 months before TB diagnosis (pre-TB visit), (ii) at TB diagnosis (TB visit), and (iii) 6–24 months after TB diagnosis (post-TB visit). Results: We enrolled 34 TB cases and 68 controls, the majority of whom were male (56% vs 60%). At the pre-TB visit, all participants were IgG seropositive, and there were no significant differences in the proportion with HCMV viremia or in HCMV IgM or IgG levels. At the TB diagnosis visit, the proportion of HCMV viremia was higher among TB cases compared with controls (34.5% vs 13.8%; P = .028). HCMV IgM geometric mean concentration (GMC) was higher in cases (0.17 vs 0.12 AU/mL; geometric mean ratio, 1.38 [95% confidence interval, 1.01–1.87]; P = .039). At the post-TB visit, HCMV viremia remained more frequent in cases (31.8% vs 4.5%; P = .006). Conclusions: HCMV viremia and serology measured 6–24 months before TB diagnosis in cases did not differ from those in matched controls. At TB diagnosis, people with HIV with TB had higher proportion of HCMV viremia and higher GMC of HCMV IgM, possibly reflecting HCMV reactivation due to TB disease.

Objective: To evaluate real‐world outcomes of dolutegravir (DTG)‐based first‐line antiretroviral therapy (ART) among people with HIV in Thailand, where baseline HIV‐1 RNA and resistance testing is not routinely available. Methods: This retrospective cohort study enrolled ART‐naive Thai people with HIV aged ≥15 years who initiated DTG‐based ART between 2020 and 2023 under the national Universal Health Coverage programme. People with HIV with ≥1 post‐baseline HIV viral load (VL) measurement were included. Virological non‐suppression (VNS) was defined as VL ≥1000 copies/mL after ≥6 months of ART. The primary outcome was the proportion achieving virological suppression (VL 3 (aSHR 2.11, 95% CI: 1.36–3.27) and residence in northern (aSHR 1.64, 95% CI: 1.12–2.40) or southern Thailand (aSHR 1.99, 95%: 1.30–3.04). Same‐day/rapid ART initiation, sex and WHO HIV clinical staging were not associated with VNS. Conclusions: Nationwide rollout of DTG‐based ART achieved excellent virological outcomes in Thailand. However, higher VNS risk among adolescents, individuals with advanced HIV disease and those in specific regions underscores the need for targeted interventions to improve treatment equity and long‐term viral suppression.

Background: The N-Acetyltransferase (NAT2) slow acetylator phenotype has been associated with a higher risk of isoniazid (INH)-induced hepatotoxicity. We investigated the association between NAT2 genotypes with inferred acetylator status, hepatotoxicity, and INH pharmacokinetics in Thai people living with HIV (PLWH) receiving INH-based Tuberculosis (TB) preventive or treatment regimens. Methods: In this prospective cohort study of Thai PLWH initiating INH-based regimens; NAT2 genotyping classified participants as slow (SA), intermediate (IA), or rapid acetylators (RA). Hepatotoxicity was defined as transaminase elevations more than 2.5 times the upper limit of normal (ULN). Multivariable logistic regression identified genotypes and factors associated with hepatotoxicity. A pharmacokinetic (PK) substudy assessed INH exposure across phenotypes. Results: Of 894 participants, 32.4% were SA, 41.2% IA, and 26.4% RA. Hepatotoxicity occurred in 10.9% overall and was highest in SA (15.2%). SA had increased hepatotoxicity risk versus RA (adjusted odds ratio [aOR] 2.43; 95% CI: 1.32–4.48). Genotypes NAT2*6A/*6A (aOR 1.84) and NAT2*7B/*7B (aOR 4.46) were associated with increased risk; NAT2*4/*4 was protective (aOR 0.33). Other independent risk factors included high baseline alanine aminotransferase (ALT), HCV co-infection, 2HRZE/4HR regimen (vs 1HP), and efavirenz-based antiviral therapy (vs dolutegravir). In the PK substudy (n = 93), INH exposure assessed by the area under the concentration time curve from 0 to 24 h, was significantly increased by approximately 2-fold in SA, regardless of anti-TB regimen. Conclusions: NAT2 SA phenotype, particularly *6A/*6A and *7B/*7B genotypes, is associated with an increased risk of anti-tuberculosis-induced hepatotoxicity and higher INH exposure in Thai PLWH. Incorporating NAT2-guided dosing may enhance safety of INH-containing regimens in PLWH.