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Effects of intensive lifestyle interventions with calorie-carbohydrate-restricted diet versus time-restricted eating on appetite and binge eating in type 2 diabetes: A randomized controlled trial.

The impact of intensive lifestyle interventions on appetite regulation and binge eating in individuals with type 2 diabetes (T2D) remains unclear. This study evaluated the effects of combined lifestyle interventions on appetite responses and binge eating in overweight or obese adults with T2D. In a randomized trial, 120 participants with T2D were allocated to three groups (n&#xa0;=&#xa0;40 each): (1) Calorie-carbohydrate restriction (CCR), (2) Time-restricted eating with CCR (TRE&#xa0;+&#xa0;CCR), or (3) Control. Intervention groups received structured exercise and behavioral education based on the Information-Motivation-Behavioral Skills model. Appetite perceptions (hunger, satiety, desire to eat, and prospective food consumption) and binge eating (Binge Eating Scale; BES and objective binge episodes) were evaluated at baseline, week 12, and week 24 using linear mixed models. Both CCR and TRE&#xa0;+&#xa0;CCR significantly improved subjective appetite compared with the control group at 12 and 24 weeks (all p&#xa0;<&#xa0;0.01). At 24 weeks, hunger decreased by -24.1&#x202f;mm (95% CI: -35.8, -12.5) in the CCR group and -32.7&#x202f;mm (95% CI: -44.2, -21.3) in the TRE&#xa0;+&#xa0;CCR group. Satiety also increased by 21.7&#x202f;mm (95% CI: 9.46, 33.9) and 29.4&#x202f;mm (95% CI: 17.4, 41.4), respectively. Significant reductions were observed for desire to eat and prospective food consumption. In contrast, changes in BES and objective binge episodes were not significantly different between groups at any time point. No significant differences were detected between the CCR and the TRE&#xa0;+&#xa0;CCR groups. Intensive lifestyle interventions incorporating CCR or TRE&#xa0;+&#xa0;CCR effectively reduced appetite in adults with T2D but did not significantly affect binge eating. Future research should target individuals with higher baseline BES scores to clarify potential benefits for binge eating behavior.

Humans

Longitudinal comparison of treat-to-target states and clinical outcomes in patients with late-onset versus early-onset systemic lupus erythematosus.

OBJECTIVE: We compared demographic and clinical characteristics between patients with late-onset (LO) and early-onset (EO) systemic lupus erythematosus (SLE) and examined their longitudinal associations with treatment targets and long-term outcomes, irreversible organ damage accrual and health-related quality of life (HRQoL). METHODS: We analyzed prospectively collected data from patients enrolled in the Asia Pacific Lupus Collaboration cohort. Patients diagnosed with SLE at age >50 years were classified as LO-SLE and compared with those diagnosed at age &#x2264;50 years (EO-SLE). Longitudinal associations with treatment targets (LLDAS and DORIS remission), organ damage accrual (SLICC/ACR Damage Index), and HRQoL (SF36v2 physical and mental component summary (PCS and MCS) scores) were examined using multivariable multilevel logistic, recurrent-event survival, and linear mixed-effects models, respectively. Disease activity, flares, medication exposure, and other clinical characteristics were also compared between groups. RESULTS: Among 3,917 patients studied, 346 (8.8%) had LO-SLE. Compared with EO-SLE, patients with LO-SLE had lower disease activity, lower glucocorticoid and immunosuppressant exposure, and higher attainment of treatment targets; LO-SLE was associated with higher odds of attaining LLDAS (OR: 2.33 (1.66, 3.28)) and DORIS remission (OR: 2.22 (1.45, 3.38)). However, they were at a greater risk of damage accrual (HR:1.82 (1.50, 2.21)) and lower PCS scores, meaning poorer physical health (regression coefficient (RC) = -3.63 (-4.58, -2.68)) but not MCS (RC= 0.68 (-.50, 1.86)). CONCLUSION: Despite higher attainment of treatment targets, patients with LO-SLE experienced greater damage accrual and poorer physical health, suggesting that disease activity targets alone may not fully capture outcome risk in LO-SLE.

Journal Article

Safety, tolerability, pharmacokinetics, and pharmacodynamics of oral JMKX003002 in Chinese healthy participants: a randomized, double-blind, placebo-controlled, single- and multiple-ascending dose, and food-effect phase I clinical trial.

OBJECTIVE: To evaluate the safety, tolerability, pharmacokinetics (PK), and pharma-codynamics (PD) of the sodium-hydrogen exchanger 3 (NHE3) inhibitor JMKX003002 in Chinese healthy participants. PATIENTS AND METHODS: This phase I, randomized, double-blind, placebo-controlled study included a single-ascending dose (SAD) study with seven cohorts (1&#x2009;mg [n&#x2009;=&#x2009;4] and 5, 20, 50, 75, 100, or 125&#x2009;mg [n&#x2009;=&#x2009;8]), a food-effect (FE) study with six sequence groups (25&#x2009;mg twice daily, n&#x2009;=&#x2009;4), and a multiple-ascending dose (MAD) study with two cohorts (10&#x2009;mg or 20&#x2009;mg twice daily, n&#x2009;=&#x2009;10). RESULTS: JMKX003002 was well-tolerated, with mostly mild treatment-related adverse events. One Grade 3 diarrhoea occurred in each of the 50&#x2009;mg and 125&#x2009;mg groups. No serious adverse events were reported, and no participants discontinued or withdrew due to treatment-emergent adverse events. Most plasma samples were below the limit of quantification (0.2&#x2009;ng/mL), with only transient detection of low concentrations, indicating low systemic exposure. JMKX003002 was primarily excreted in&#xa0;stool (79.9% recovered) and was undetectable in urine. The PD results consistently showed decreased urinary sodium and phosphorus, along with increased stool sodium and phosphorus, compared to baseline across all three studies. One day after discontinuation, stool sodium and phosphorus remained elevated relative to baseline in the MAD study. Mixed-effects model analysis in the FE study demonstrated significant food effect on stool sodium and phosphorus excretion. CONCLUSION: JMKX003002 exhibited favorable safety and tolerability with minimal systemic exposure. It effectively increased sodium and phosphorus excretion in stool. These promising findings warrant further investigation of JMKX003002 to evaluate its clinical benefits. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2300070473). Registered on April 13, 2023; prospectively registered.

Adult

Preoperative Olanzapine and Quality of Recovery after Ambulatory Surgery: A Randomized Clinical Trial.

BACKGROUND: Postdischarge nausea and vomiting negatively impact recovery after surgery. Preoperative administration of 10&#x2009;mg olanzapine decreases postdischarge nausea and vomiting but increases sedation. No data are available on the impact of olanzapine on global quality of recovery. METHODS: This was a single-center, randomized, double-blind, placebo-controlled trial in female patients 18 to 50 yr old undergoing ambulatory surgery during general anesthesia. Participants received 5&#x2009;mg oral olanzapine or placebo in addition to antiemetic prophylaxis with dexamethasone and ondansetron. The primary outcome was Quality of Recovery-40 (QoR-40) on postoperative day (POD) 1. Secondary outcomes included QoR-40 on POD 2, postdischarge nausea (any and severe) through POD 2, and postanesthesia care unit length of stay. QoR-40 analyses used mixed-effects models adjusted for baseline preoperative QoR-40 scores. The group differences and corresponding 95% CI are reported. RESULTS: A total of 384 participants received olanzapine (n = 191) or placebo (n = 193). Compared with placebo, olanzapine was associated with higher QoR-40 scores on POD 1 (difference, 9.0 points; 95% CI, 6.1 to 11.8; P < 0.001). The POD 2 difference was 4.8 points (95% CI, 2.0 to 7.6; nominal P = 0.001), and this secondary outcome remained significant after false discovery rate correction. Olanzapine was associated with lower odds of any nausea (odds ratio [OR], 0.43; 95% CI, 0.28 to 0.66) and severe nausea (OR, 0.26; 95% CI, 0.14 to 0.48) on POD 1. On POD 2, olanzapine was associated with lower odds of any nausea (OR, 0.48; 95% CI, 0.30 to 0.76), but not severe nausea (OR, 0.65; 95% CI, 0.30 to 1.40). Postanesthesia care unit length of stay did not differ between groups. The significance of these prespecified secondary outcomes was unchanged after false discovery rate correction. CONCLUSIONS: When combined with dexamethasone and ondansetron, a single preoperative dose of 5&#x2009;mg olanzapine improved global quality of recovery after discharge from ambulatory surgery.

Humans

The effect of dietetic counseling combined with digital tools intervention on hemodynamic markers in Greek adults: The GATEKEEPER Study.

BACKGROUND AND AIM: Hypertension is a leading cardiovascular risk factor with substantial global impact on morbidity, mortality, and healthcare costs. While lifestyle interventions remain central to management, mHealth technologies offer promising adjunctive support, though their clinical effectiveness remains uncertain. This study evaluated whether combining dietetic counseling with digital tools improves hemodynamic markers in adults aged &#x2265;55 years with increased cardiometabolic risk. METHODS AND RESULTS: This 3-month RCT (NCT05031299) included 954 adults with at least one metabolic syndrome risk factor, allocated 1:1:1 to Standard Care (dietetic counseling), Platform (counseling plus web-based platform), or Platform&#xa0;+&#xa0;Devices (counseling plus platform plus wearables). Outcomes included anthropometrics, lifestyle characteristics, blood pressure, pulse pressure, and estimated pulse wave velocity, analyzed using linear mixed-effects models adjusted for age and sex. All groups improved over 3 months. Waist circumference decreased by -6.29, -4.92, and -4.69&#xa0;cm across Standard Care, Platform, and Platform&#xa0;+&#xa0;Devices groups respectively, and systolic blood pressure declined by -4.84 to -7.15&#xa0;mmHg across groups. The Platform&#xa0;+&#xa0;Devices group showed greater increases in physical activity (94.62 MET-min/week; 95% CI 66.49 to 122.76) and greater reductions in pulse pressure (-3.90&#xa0;mmHg; -6.58 to -1.22) versus Standard Care. Weight loss was associated with lower odds of hypertension (OR 0.4; 95% CI 0.2-0.7), greater likelihood of hypertension reversal (OR 3.6; 1.2-10.3), and higher probability of achieving normal pulse pressure (OR 1.8; 1.1-3.1). CONCLUSIONS: Dietary lifestyle intervention improved cardiometabolic outcomes, with limited added benefit from digital tools. Weight loss was the primary driver of hemodynamic improvement.

Aged

Association Between Statin Use and Dry Eye Disease: A Systematic Review and Meta-Analysis.

TOPIC: This systematic review and meta-analysis evaluated the literature-pooled association between statins and dry eye disease (DED). CLINICAL RELEVANCE: Statins, a common treatment modality for dyslipidemia, have been proposed as a potential contributor to DED via their activity in meibomian gland epithelial cells. However, single studies show mixed evidence, and there remains an unmet clinical need to clarify whether statin exposure is associated with DED. METHODS: This review was reported in accordance with the Preferred Reporting Items for Systematic Reviews of Interventions (PRISMA) 2020 statement and was registered a priori on PROSPERO (CRD420251238004). Ovid MEDLINE, Embase, CINAHL, Web of Science, CENTRAL, and the reference lists of relevant reviews were searched from inception to November 2025 for studies reporting the association between statin use and DED. Random-effects meta-analysis using inverse-variance weighting was conducted to pool effect estimates as odds ratios with 95% confidence intervals (CIs). Study risk of bias was appraised using the ROBINS-E tool, and the certainty of the evidence was reported using the GRADE framework. RESULTS: Six observational studies were included in the meta-analysis (n = 560,821; 356,012/559,141 [63.7%] statin users). The pooled analysis revealed a significant positive association between statins and DED (odds ratio 1.09, 95% CI 1.05-1.13, P < .001), with an absolute risk difference of 10.2 more DED cases per 1000 (95% CI 5.5 more to 15.2 more). This result was derived from very low-certainty evidence given limitations in study design and serious inconsistency. Subgroup and sensitivity analyses for risk of bias (P = .123), method of outcome ascertainment (P = .737), type of effect estimate (P = .496), and leave-one-out analyses showed no evidence of effect modification and demonstrated consistent direction of association across studies. CONCLUSION: Statin use was associated with a small but statistically significant increase in DED, limited by very low-certainty evidence. Physicians should monitor for and educate patients on ocular surface symptoms in patients using statins with pre-existing DED risk factors. Future studies should use standardized DED diagnostic criteria to investigate the impact of statin dose, type, and duration to better characterize this potential association.

Humans

Long-term microbiome and clinical effects of a microbiome-guided personalized diet versus low-FODMAP diet in irritable bowel syndrome: A 12-month follow-up randomized controlled trial.

Dietary therapy is central to irritable bowel syndrome (IBS) management, yet the long-term durability of the low-FODMAP diet (LFD), and of microbiome-guided personalization, remains unclear. We assessed the long-term clinical and gut-microbiome effects of a microbiome-guided personalized diet (PD) compared with a standard LFD in adults meeting Rome IV criteria for IBS. In this multicenter, open-label randomized controlled trial with blinded outcome assessment, participants who completed a 6-week dietary intervention (PD or LFD) were followed at 6 and 12 months without further dietary intervention. Outcomes included the IBS Severity Scoring System (IBS-SSS), IBS Quality of Life (IBS-QOL), and the Hospital Anxiety and Depression Scale (HADS); gut microbiota were profiled by 16S rRNA sequencing. Longitudinal changes were evaluated using linear mixed-effects models, responder analyses, PERMANOVA, and PERMDISP. Both diets reduced IBS-SSS at 6 weeks. PD maintained symptom improvement at 6 and 12 months (-82.0 and -78.3 points from baseline), whereas LFD benefits regressed by 12 months (+29.3 points; between-group p&#x2009;=&#x2009;0.001). At 12 months, IBS-SSS responder rates were higher with PD than LFD (62.5% vs 34.5%; absolute risk difference&#x2009;+28.0%, 95% CI 4.2-47.7; Fisher p&#x2009;=&#x2009;0.029), and IBS-QOL, HADS-anxiety, and HADS-depression showed more favourable trajectories with PD. PD was associated with sustained Shannon alpha-diversity gains (+0.488 at 6 weeks;&#x2009;+0.205 at 12 months; both p&#x2009;<&#x2009;0.01). A modest between-group beta-diversity difference at 6 months (R2&#x2009;=&#x2009;0.035; p&#x2009;=&#x2009;0.011) was not significant at 12 months. This hypothesis-generating follow-up suggests more durable benefit with PD; larger trials powered for long-term clinical and microbiome outcomes are warranted.

Humans

Qualitative evidence of service user experiences and perspectives on long-acting injectable buprenorphine for opioid treatment - a scoping review.

BACKGROUND: There is substantial literature on opioid treatment program (OTP) formulations and how they relate to the pharmacotherapy service user experience. As a newer formulation, less is known about service user experiences of long-acting injectable buprenorphine (LAIB). The aim of this scoping review is to map the qualitative evidence and gaps in the literature on service user experiences and perspectives of LAIB. METHODS: Our search strategy included Medline, Embase, PsycINFO, CINAHL, Scopus and Web Science, and citation chaining, from January 2016 to June 2025. Studies were included if reporting qualitative descriptions of LAIB service user experiences of treatment for opioid dependence, inclusive of qualitative, mixed methods (description of qualitative data only), case reports and English language. Articles were screened by two reviewers. A living experience first author led the analysis using inductive coding and thematic analysis, to produce a descriptive summary of synthesised findings alongside key study characteristics and quality appraisal, adhering to the Systematic reviews and Meta-Analysis for Scoping Reviews (PRISMA-ScR) checklist. RESULTS: After screening 838 titles/abstracts and reviewing 150 full texts, 40 studies met the eligibility criteria. All were conducted in high income countries, principally the US (n=12); Australia (n=10); and England and Wales (n=9). We identified five themes: Navigating LAIB treatment; Embodied and relational effects of LAIB; Impact and role of the service provider; Narratives of harm reduction and recovery; Stigma and criminalisation. LAIB was commonly experienced as increasing convenience, stability and freedom from daily supervised dosing, enabling improved work, travel, privacy and social participation. Reduced clinic/dosing contact often lessened enacted stigma and treatment burden. However, experiences were heterogenous. Some participants described injection-site discomfort, uncertainty about dose adequacy, reduced flexibility once injected, and ambivalence about LAIB effects. There was inconsistency in LAIB service user reports on service connection, isolation and psychosocial support. Treatment experiences were strongly shaped by provider practices. CONCLUSIONS: Findings underscore the need for integrated, flexible, harm-reduction oriented and person-centred LAIB treatment models that prioritise choice, autonomy and therapeutic relationships to maximise benefit for service users. However, evidence of LAIB service user experiences is concentrated in high-income countries, and the absence of perspectives from low- and middle-income country settings represents a substantial gap in the evidence base.

LAIB

Effects of an internet-based combined exercise and cognitive-behavioral therapy intervention on endocannabinoid system biomarkers and physical fitness in adults with mild-to-moderate depression: a SONRIE randomized controlled trial.

BACKGROUND: This SONRIE randomized controlled trial (NCT05849792) examined the effects of a 12-week combined physical exercise and internet-based cognitive-behavioral therapy (iCBT) intervention on endocannabinoid system (ES) biomarkers and physical fitness in adults with mild-to-moderate depression. METHODS: Eighty adults were randomly assigned 1:1 to an intervention (IG) or control (CG) group. Outcomes included nine ES biomarkers (2-arachidonoylglycerol, 2-AG; anandamide, AEA; seven analogues) and physical fitness, including cardiorespiratory fitness (CRF; 6-minute walking test) and muscular strength. Measurements were taken at baseline, post-intervention and 8-week follow-up. Primary analysis performed 2&#x2009;&#xd7;&#x2009;3 repeated-measures ANOVA on completers; mixed-effects intention-to-treat model as sensitivity analysis. RESULTS: No significant time &#xd7; group interaction was detected for any ES biomarker, including 2-AG (F(2,88)&#x2009;=&#x2009;0.17, p&#x2009;=&#x2009;0.844) and AEA (F(2,88)&#x2009;=&#x2009;1.20, p&#x2009;=&#x2009;0.306); both groups showed comparable within-group decreases in 2-AG, 2-LG and 2-OG. The intervention significantly improved CRF [between-group difference&#x2009;+&#x2009;81.6&#xa0;m at 12 weeks (F(2,78)&#x2009;=&#x2009;7.88, p&#x2009;=&#x2009;0.001)], exceeding the established minimal clinically important difference. None of the exploratory muscular fitness outcomes reached statistical significance; the arm curl test showed a borderline non-significant interaction (F(2,78)&#x2009;=&#x2009;2.83, p&#x2009;=&#x2009;0.065). CONCLUSION: A 12-week internet-based combined exercise and iCBT intervention significantly improved CRF in adults with mild-to-moderate depression. We did not find evidence of an intervention-specific effect on plasma ES biomarkers. These findings support the inclusion of internet-delivered exercise and psychological interventions in comprehensive treatment strategies for depression. TRIAL REGISTRATION: ClinicalTrials.gov NCT05849792 (registered 6 May 2023).

Humans

Low-burden metrics for monitoring healthy diets among nonpregnant females aged 15 to 49 years: a multicountry validation analysis using quantitative 24-hour dietary intake data.

BACKGROUND: Limited nationally representative quantitative dietary intake data and a lack of consensus on lower-burden tools and metrics hinder high-frequency monitoring of healthy diets globally. OBJECTIVES: This study aimed to evaluate the comparative construct validity and potential complementarity of low-burden metrics of a healthy diet among nonpregnant females aged 15 to 49 y. METHODS: Quantitative 24-h dietary intake data collected from 77,118 adolescent and adult females across 27 countries were used to construct low-burden metrics and reference metrics of dietary intake. Associations between mean-standardized low-burden measures or indicators and reference metrics were assessed using linear and logistic mixed-effect models, with Spearman's &#x3c1; used for survey-level rank correlations. Test characteristics identified low-burden indicators best differentiated adherence to reference indicators. RESULTS: An indicator reflecting nonconsumption of sweet foods and/or sweet beverages was most robustly associated with greater adherence to <10% energy from free sugars in upper-middle-income countries {odds ratio [OR] [95% confidence interval (CI)]: 5.35 [5.05, 5.66]}. Food group diversity score (FGDS) was most strongly associated with and differentiated higher mean adequacy ratio of micronutrients [&#x3b2; of 1-standard deviation (SD) change: &#x223c;11 percentage points (9, 12); &#x3c1;: 0.79], whereas noncommunicable disease-Protect score best reflected consumption of &#x2265;400 g/d of fruits and vegetables [range OR of 1-SD changes (95% CI): 2.56-3.01 (2.40, 3.13) in lower-middle and high-income countries, respectively; &#x3c1;: 0.56]. FGDS and Global Diet Quality Score Positive were most consistently associated with achieving &#x2265;25 g/d of fiber and &#x2265;3510 mg/d of potassium across contexts. CONCLUSIONS: Low-burden data collection tools yield valid metrics, enabling high-frequency monitoring of healthy diets across contexts. Specifically, avoiding sweet foods and/or sweet beverages is an indicator for adherence to WHO free sugar guidelines among nonpregnant females in upper-middle-income countries, whereas metrics reflecting nutritious food group diversity strongly reflect better micronutrient adequacy and adherence to WHO guidelines for fruits and vegetables, fiber, and potassium intakes within and across contexts.

Humans

Prevalence of Slowly Expanding Lesions in Patients With Multiple Sclerosis: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Chronic active lesions (CALs) reflect chronic inflammation in multiple sclerosis (MS). Slowly expanding lesions (SELs) are CALs identified on conventional MRI by linear, concentric expansion over time, while paramagnetic rim lesions (PRLs) are CALs characterized by a paramagnetic rim on susceptibility-sensitive MRI. However, the prevalence of SELs and their overlap with PRLs remain unclear. The aims of this study were to (1) estimate the proportion of SELs among all T2 lesions and the proportion of patients with at least 1 SEL and (2) assess the proportion of SELs overlapping with PRLs. METHODS: We systematically searched PubMed, Scopus, Web of Science, and Embase on February 1, 2026, for studies evaluating SELs in MS. At least 2 authors independently assessed study eligibility. Primary outcomes were the pooled proportion of SELs among T2 lesions and the proportion of patients with at least 1 SEL. We estimated mean per-patient volumes of SELs and total T2 lesions and the proportion of SELs overlapping with PRLs. Random-effects generalized linear mixed-effects models and inverse-variance methods were used, with between-study heterogeneity assessed using &#x3c4;2 and I2 and robustness using sensitivity analyses. Univariable meta-regression explored heterogeneity. PROSPERO: CRD42024603778. RESULTS: Of 5,980 records, 20 studies comprising 4,786 patients with MS were included (mean age: 43.6 &#xb1; 6.3 years; 63.7% female). Sample sizes varied by outcome. SELs accounted for 14% (95% CI 10-21) of all T2 lesions, and 78% (67-85) of patients had at least 1 SEL. After sensitivity analysis, per-patient mean volumes were 1.42 mL (0.79-2.06) for SELs and 10.6 mL (8.53-12.67) for total T2 lesions. In total, 11% (6-20) of SELs overlapped with PRLs. In subgroup analyses, proportions of SELs were similar in relapsing-remitting and progressive MS (15%), but the proportion of patients with at least 1 SEL was higher in progressive MS. Between-study heterogeneity was high across analyses with no significant sources identified. DISCUSSION: Although SELs represent a minority of T2 lesions, most patients have at least 1 SEL and a subset overlaps with PRLs, suggesting a partial correspondence between these 2 imaging markers of chronic inflammatory activity. Limitations include possible publication bias, high unexplained heterogeneity, differences in SEL identification methods, and differences in MRI time point number/timing.

Humans

Association Between 24-Hour Blood Pressure and Rates of Retinal Nerve Fiber Layer Progression in Glaucoma: The Vascular Imaging in Glaucoma Study.

PURPOSE: Low systemic blood pressure (BP) has been implicated as a risk factor for glaucoma progression. The purpose of this study was to investigate the association between 24-hour BP and rates of retinal nerve fiber layer (RNFL) loss in eyes with primary open-angle glaucoma. DESIGN: Prospective cohort study. PARTICIPANTS: Seventy-nine eyes from 42 subjects with glaucoma (mean age, 68.5 &#xb1; 7.6 years) enrolled in the Vascular Imaging in Glaucoma Study at the Bascom Palmer Eye Institute. METHODS: Participants underwent 24-hour ambulatory BP monitoring at baseline. Follow-up evaluations were conducted at 4-month intervals and included ophthalmic examination, BP measurement, and peripapillary RNFL thickness measurement with spectral-domain optical coherence tomography. The association between BP and RNFL loss over time was assessed using linear mixed-effects models adjusted for age, sex, race, baseline RNFL thickness, central corneal thickness, and intraocular pressure. MAIN OUTCOME MEASURES: The effect of baseline 24-hour mean arterial pressure (MAP), systolic BP (SBP), and diastolic BP (DBP) on the rate of average RNFL loss over time. RESULTS: Eyes underwent an average of 13 &#xb1; 3 optical coherence tomography exams over 43 &#xb1; 10 months of follow-up. The mean rate of RNFL loss was -0.34 &#xb1; 0.64 &#xb5;m/y (median: -0.32; interquartile range: -0.66 to -0.04 &#xb5;m/y). After adjusting for confounding factors, every 10 mm Hg lower in 24-hour minimum MAP, SBP, and DBP was associated with -0.542 &#xb5;m/y (P < .001), -0.360 &#xb5;m/y (P = .003), and -0.458 &#xb5;m/y (P = .008) faster RNFL loss, respectively. Eyes in the lowest quartile of average 24-hour MAP (81-90 mm Hg) and minimum 24-hour DBP (35-47 mm Hg) experienced significantly faster progression compared to those in the highest quartile, with differences of -0.68 &#xb5;m/y (P = .017) and -0.63 &#xb5;m/y (P = .030), respectively. CONCLUSIONS: Lower systemic BP, especially minimum MAP, SBP, and DBP measured by 24-hour ambulatory BP monitoring, is associated with faster rates of RNFL loss in primary open-angle glaucoma eyes. 24-hour BP monitoring may help predict glaucoma patients at greater risk of progression.

Humans

A comparative systematic review of pharmacist education systems and pharmacy service quality in ASEAN-5: Indonesia, Malaysia, Thailand, the Philippines, and Singapore.

BACKGROUND: The global transition toward patient-centered pharmaceutical care has exposed structural disparities in ASEAN pharmacy workforce training and deployment. This review examines four research questions: how pharmacy education systems and accreditation standards differ across Indonesia, Malaysia, Thailand, the Philippines, and Singapore (collectively, the ASEAN-5); the extent to which pre-registration education influences clinical service scope and professional confidence; how education reform and regulatory change have shaped pharmacist clinical roles; and what barriers and enablers exist for regional qualification harmonization. METHODS: A systematic literature review following PRISMA 2020 was conducted. Searches of PubMed/MEDLINE and Scopus, supplemented by grey literature, were completed in May 2026. Of 78 unique records screened, 46 studies published between 2005 and 2026 met inclusion criteria. Quality appraisal used an adapted Mixed Methods Appraisal Tool; synthesis employed narrative thematic analysis. RESULTS: The five countries represent four structurally distinct pharmacy education architectures: Thailand's standardized six-year Doctor of Pharmacy with dual specialization tracks; four-year Bachelor of Pharmacy programmes in Malaysia and the Philippines with institutional variation; Indonesia's clinically underdeveloped system despite rapid expansion; and Singapore's four-year Bachelor of Pharmacy followed by a nationally mandated one-year pre-registration pathway. Evidence links deeper clinical training to broader practice scope, higher confidence, and improved patient outcomes. Reform produced uneven results: Thailand's PharmD transition improved clinical recognition but exposed deployment paradoxes; Singapore achieved the strongest training-to-practice alignment; Indonesia's health insurance reforms were not absorbed by an underprepared workforce; the Philippines lacks a national competency framework. No binding mutual recognition arrangement was identified; divergent qualification structures, incompatible accreditation systems, and an asymmetric evidence base remain the primary barriers. DISCUSSION: These findings indicate that clinical service scope is bounded less by national policy ambition than by the depth and clinical orientation of the pre-registration education that precedes it, and that credentialing reforms which outpace a health system's capacity to absorb new clinical roles, or the reverse, do not by themselves translate into expanded practice. CONCLUSIONS: Pharmacy education across the ASEAN-5 remains nationally distinct and clinically uneven. Clinical service scope is directly bounded by pre-registration education quality. No country has fully closed the education-practice gap. Regional harmonization requires national-level educational reform as a prerequisite.

Humans

Perioperative analgesic efficacy of ultrasound-guided erector spinae plane block and posterior transversus abdominis plane block in paediatric patients undergoing open pyeloplasty: A prospective randomised trial.

PURPOSE: Open pyeloplasty in the paediatric population involves extensive tissue dissection and manipulation, resulting in significant postoperative pain. Ultrasound-guided fascial plane blocks have emerged as an important component of multimodal analgesia in abdominal surgeries. This study compared the analgesic efficacy of ultrasound-guided Erector spinae plane block (ESP) and posterior transversus abdominis plane (pTAP) block in children undergoing open pyeloplasty. METHODS: It is a prospective, randomised, double-blind study conducted at a single paediatric centre in a tertiary care hospital in Asia from January 2022 to June 2023. 40 ASA I-II children were randomised to receive either the ESP block (Group E) or the pTAP block (Group T). Both groups received 0.4 ml/kg, 0.2% ropivacaine with 1 mcg/kg dexmedetomidine. Children with an allergy to local anaesthetics, cardiac, renal or hepatic dysfunction and local site infection were excluded. The primary outcome was cumulative 24 h postoperative acetaminophen consumption. Secondary outcomes included the effects on intraoperative hemodynamics, perioperative opioid consumption, FLACC and Watcha scores, time to first rescue analgesia, and any block-related complications. RESULTS: Weight-normalised 24 h postoperative acetaminophen consumption was significantly lower in the ESP group (13.5 &#xb1; 4.7 mg/kg) compared to the pTAP group (25.4 &#xb1; 8.3 mg/kg), with a mean difference of -12 mg/kg (p < 0.001, 95%CI -16 to -7.6). The median time to first rescue analgesia was significantly longer in the ESP group (18 h [95% CI, 18-24]) than in the TAP group (9 h [95% CI, 6-12]), p < 0.001. Although FLACC scores were significantly lower in the ESP group at 30 min and 12 h postoperatively, the overall longitudinal analysis using a linear mixed-effects model showed no significant difference in the trend of FLACC scores over time between the two groups. There were no block-related complications. CONCLUSION: Ultrasound-guided ESPB provides better, longer-lasting analgesia than posterior TAP block in children undergoing open pyeloplasty. Hence, it may serve as an effective component of multimodal pain management in paediatric open pyeloplasty. CTRI REGISTRATION (CTRI/2022/04/041876) DATED 13/04/2022): https://ctri.nic.in/Clinicaltrials/rmaindet.php?trialid=67747&EncHid=42257.14515&modid=1&compid=19.

Humans

Comparison of Adult Tracheostomy Outcomes Before and After Implementation of a Dedicated Tracheostomy Team.

OBJECTIVE: (A) Determine patient and institutional factors associated with increased length of stay (LOS) and complications of tracheostomy, (B) Develop data-driven quality improvement in tracheostomy care. DESIGN: Mixed methods protocol used cross-sectional survey assessing institutional trends in tracheostomy-specific care. Retrospective chart review compared tracheostomy patient outcomes prior to and during implementation of a multidisciplinary tracheostomy care team and standardized guidelines. PARTICIPANTS: Patients undergoing tracheostomy from January 2019 to December 2021 at a tertiary hospital. METHODS: Patient factors, procedure type and indication, tracheostomy tube size, management timeline, insurance, and disease severity using Acute Physiology and Chronic Health Evaluation II (APACHE II) score were analyzed for associations with LOS and adverse events. Multivariate analyses controlled for APACHE II score and payer source. LOS and complications were compared between patients before and during implementation of multidisciplinary tracheostomy care team and standardized guidelines. RESULTS: Three-hundred and eighteen patients met criteria with a 21.7% complication rate, average LOS of 24 days (SD&#x2009;=&#x2009;28.523), and median LOS post-tracheostomy of 14 days (IQR 7, 29). Departments without standardized protocols had greater LOS (F[1,316]&#x2009;=&#x2009;28.706, P&#x2009;<&#x2009;.001]) and complication odds (OR&#x2009;=&#x2009;2.92, P&#x2009;=&#x2009;.015, 95% CI[1.231, 6.930]). Larger tracheostomy tube size was linked to increased LOS (&#x3b2;&#x2009;=&#x2009;.253, t(314)&#x2009;=&#x2009;4.741, P&#x2009;<&#x2009;.001, 95% CI[4.137, 10.081]). Delays from ventilation discontinuation to cuffless tube exchange and decannulation correlated with increased LOS (&#x3b2;&#x2009;=&#x2009;.406, t(184)&#x2009;=&#x2009;6.321, P&#x2009;<&#x2009;.001, 95% CI[.928, 1.771]); (&#x3b2;&#x2009;=&#x2009;.554, t(129)&#x2009;=&#x2009;7.625, P&#x2009;<&#x2009;.001, 95% CI[1.008, 1.715]). When focusing on a single department, comparing 2019 patients to 2021 patients (pre- and post-guideline and care team), overall, LOS decreased from 33.08 to 30.83 days (P&#x2009;=&#x2009;.586). When excluding patients discharged on a ventilator, the 2019 group had average LOS of 37.938 days versus 33.41 days in 2021 (P&#x2009;=&#x2009;.344). CONCLUSIONS: Standardized tracheostomy care guidelines and multidisciplinary care teams are critical to improving institutional outcomes. Data-driven approaches to quality improvement ensure efficient and targeted methods to improving patient care. LEVEL OF EVIDENCE: 4.

Humans

HPV circulating tumor DNA as a potential prognostic and predictive biomarker in head and neck squamous cell carcinoma: a systematic review.

PURPOSE: Human papillomavirus circulating tumor DNA (HPVctDNA) has emerged as a promising prognostic biomarker in HPV-related head and neck squamous cell carcinoma (HNSCC). This systematic review aimed to synthesize current evidence on the diagnostic accuracy and prognostic value of HPVctDNA in HNSCC management. MATERIAL/METHODS: We systematically reviewed a PubMed-indexed database of studies published between January 2012 and September 2025. Eligible studies were assessed for design, primary tumor site and stage, treatment modality, HPVctDNA detection method, diagnostic accuracy (sensitivity and specificity), and reported clinical endpoints. Descriptive syntheses were performed; sensitivity and specificity were standardized to proportions and summarized as median values per group. RESULTS: A total of 60 studies, including 8,234 patients were analyzed, of which 41 (68.3%) focused exclusively on oropharyngeal squamous cell carcinoma (OPSCC) and 17 (28.3%) included mixed HPV-related HNSCC subsites and HPV-positive cancers of unknown primary. The median follow-up across the included studies was 23&#xa0;months. Among the included studies, 19 were retrospective (31.7%) and 33 were prospective (55.0%), with a small proportion of cross-sectional and randomized clinical trials. Overall, 40 (66.7%) evaluated the role of HPVctDNA in a curative setting. Plasma was the most common sample type, analyzed in 55 studies (91.7%), while 5 studies also included saliva. Detection methods varied: 40 employed droplet digital PCR (ddPCR), 16 used quantitative PCR (qPCR) and 4 applied NGS-based assays. Most of these studies (38, 63.3%) evaluated the prognostic utility of HPVctDNA, while only 4 (6.7%) assessed HPVctDNA in a screening or diagnostic setting. Regarding diagnostic accuracy, the median sensitivity across evaluable studies was 91.1%, while the median specificity was 99.4%. In OPSCC-only cohorts, the median sensitivity and specificity were 89.4% and 99.4%, respectively. Dynamic changes in HPVctDNA levels during or after treatment were consistently associated with outcomes: clearance or sustained negativity correlated with higher response rates, improved progression-free survival and overall survival, while persistent positivity or increasing levels predicted disease progression and recurrence. CONCLUSIONS: HPVctDNA demonstrates high diagnostic and prognostic accuracy in HPV-related HNSCC, especially OPSCC, supporting its use for prognosis, treatment monitoring and early detection of recurrence. However, prospective interventional studies are still required to demonstrate that HPVctDNA-guided treatment decisions improve clinical outcomes before routine implementation.

Humans

Soft Tissue Volume Augmentation at Single Implant Sites Applying Collagen Matrices or Connective Tissue Grafts: 10-Year Follow-Up of a Randomized Controlled Trial.

AIM: To compare up to 10&#x2009;years clinical, profilometric and patient-reported outcomes of implant sites previously augmented using a volume-stable collagen matrix (VCMX) or connective tissue graft (SCTG) in the aesthetic zone. METHODS: The original non-inferiority randomized controlled trial (RCT) enrolled 20 patients who received soft tissue volume augmentation with VCMX or SCTG at single implant sites. Clinical assessments and standardized measurements were performed at baseline after crown insertion and at 6&#x2009;months, 1, 3, 5, 7.5, and 10&#x2009;years. The primary outcome was mucosal thickness. Secondary outcomes included marginal bone levels (MBL), probing depth (PD), bleeding on probing (BOP), plaque control record, Pink Aesthetic Score (PES), OHIP-14 and buccal profilometric changes. Group comparisons were performed using mixed-effects and generalized estimating equation (GEE) models, which account for within-patient correlations due to repeated measurements and allow inclusion of all available data without requiring imputation for missing observations. RESULTS: Of the 20 originally enrolled patients, 10 (5 in the SCTG group and 5 in the VCMX group) were available for re-examination at 10&#x2009;years. The adjusted between-group difference in mucosal thickness was -0.02&#x2009;mm (95% CI -0.99 to 0.96). As the lower bound of the confidence interval remained above the prespecified non-inferiority margin of -1&#x2009;mm, non-inferiority of VCMX was shown. Buccal contour changes were comparable during the early follow-up, while a trend toward a greater long-term contour decrease was observed in group VCMX (-0.31&#x2009;mm [95% CI, -0.65 to 0.03]; p&#x2009;=&#x2009;0.07). Mean PES values were 10.6 in the SCTG group and 9.6 in the VCMX group, with no significant between-group differences (p&#x2009;=&#x2009;0.45). Both groups revealed high levels of oral health-related quality of life, with low median OHIP-14 scores (SCTG, 0.0; VCMX, 1.0; p&#x2009;=&#x2009;0.26). CONCLUSION: These preliminary long-term findings showed no clinically relevant differences between SCTG and VCMX in terms of clinical, profilometric and patient-reported outcomes. While SCTG remains the reference standard, VCMX represents a less invasive alternative but with a slight tendency toward greater long-term contour reduction. CLINICAL SIGNIFICANCE: Volume-stable collagen matrices serve as a viable alternative to autogenous connective tissue grafts for peri-implant soft tissue volume augmentation, particularly in patients seeking a reduced morbidity, without compromising long-term clinical or aesthetic outcomes. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00017484.

Humans

Nurse-led attribution remodeling training based on the Neuman systems model to enhance resilience, adaptive coping, and attributional style in women newly diagnosed with breast cancer: A randomized controlled trial.

BACKGROUND: Psychological interventions for patients with breast cancer often overlook the critical role of maladaptive attributional style in shaping their adjustment. Therefore, the need for theory-driven, scalable interventions that target cognitive restructuring, particularly during the vulnerable post-diagnosis period, is clear. OBJECTIVE: To evaluate the effectiveness of a nurse-led attribution remodeling training intervention grounded in the Neuman systems model for improving resilience, adaptive coping, and attributional style among women newly diagnosed with breast cancer. DESIGN: A randomized controlled trial. SETTING: A tertiary general hospital. PARTICIPANTS: A total of 130 eligible women newly diagnosed with breast cancer were recruited between March and November 2024. METHODS: A two-arm parallel-group randomized controlled trial was conducted. Participants were randomly assigned to receive either attribution remodeling training plus routine nursing (n&#xa0;=&#xa0;65) or routine nursing only (n&#xa0;=&#xa0;65). The nurse-led attribution remodeling training intervention, delivered via a blended model of in-person sessions and continued support through the WeChat mobile platform, was designed to systematically reshape maladaptive attributions into more adaptive ones. Resilience (primary indicator), coping strategy (i.e., confrontation, avoidance, resignation), and attributional style (secondary indicators) were assessed at baseline and at 1, 3, and 6&#xa0;months post-baseline. A linear mixed model was used to analyze the effects of group, time, and group-by-time interactions. Effect sizes (Cohen's D) were calculated based on the means and standard deviations. RESULTS: At the 6-month follow-up, the intervention group had better outcomes than the control group in terms of resilience (mean difference: 1.49, 95% confidence interval: 0.37, 2.61), confrontation coping (3.35 [2.33, 4.37]), and adaptive attributional style (4.16 [3.87, 4.45]). Avoidance coping showed a small increase (0.82 [0.22, 1.42]), whereas resignation coping decreased (-1.66 [-2.49, -0.83]). Group effects and group-by-time interactions were statistically significant for all outcomes. Effect sizes at 6&#xa0;months ranged from small for resilience (D&#xa0;=&#xa0;0.28) and avoidance coping (D&#xa0;=&#xa0;0.26) to moderate for confrontation coping (D&#xa0;=&#xa0;0.60) and resignation coping reduction (D&#xa0;=&#xa0;-0.51), and large for attributional style (D&#xa0;=&#xa0;0.94). CONCLUSIONS: Attribution remodeling training is a promising and effective theory-based intervention that can enhance psychological adaptation in women newly diagnosed with breast cancer. By strengthening key defense mechanisms, as conceptualized by the Neuman systems model, the program is effective, scalable, and nurse-deliverable for psycho-oncology care, bridging a critical gap in supportive cancer care and empowering nurses as primary psychological support providers. REGISTRATION: ChiCTR2000031827, registered prospectively on April 11, 2020, www.Chictr.or.cn.

Humans