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PubMed2026

Patient experiences of diagnostic uncertainty in musculoskeletal care: a systematic review of qualitative studies.

BACKGROUND: Diagnosis plays a central role in musculoskeletal care. However, establishing a clear diagnosis is often challenging, and diagnostic uncertainty is common. OBJECTIVES: To explore patient experiences of diagnostic uncertainty in musculoskeletal care. METHODS: Five databases (CINAHL, Embase, MEDLINE, AMED, Web of Science) were searched from inception to October 2025. Qualitative studies involving semi-structured interviews with adults receiving care for MSK conditions were included. Methodological quality was appraised using the Joanna Briggs Institute Qualitative Checklist. Data were synthesised using thematic synthesis, and confidence in findings was assessed using the Grading of Recommendations Assessment, Development, and Evaluation Confidence in the Evidence from Reviews of Qualitative Research approach (GRADE-CERQual). RESULTS: Twenty-six studies involving 462 participants were included. Critical appraisal identified 23 studies with varying methodological limitations; all studies were included in the synthesis. Nine descriptive themes were synthesised into three analytical themes: (1) patient expectations and perceived meanings of a diagnosis and interpretations of diagnostic uncertainty; (2) the multi-dimensional experience of diagnostic uncertainty; and (3) the role of contextual factors, particularly communication and the therapeutic relationship, in shaping experiences of diagnostic uncertainty. Using GRADE-CERQual, confidence in these themes was rated as low, moderate and very low, respectively. CONCLUSION: Diagnostic uncertainty is a subjective and multi-dimensional experience shaped in part by patients' expectations and the meanings attributed to diagnosis. Its impact spans predominantly cognitive and affective domains and may influence clinical presentation. Patient-centred communication and strong therapeutic relationships may support patients in navigating diagnostic uncertainty in musculoskeletal care.

Adult↗

PubMed2026

Effects of sub-anesthetic doses of esketamine on immune function and postoperative negative emotions in acoustic neuroma patients: a randomized clinical trial.

BACKGROUND: Patients undergoing acoustic neuroma (AN) surgery often experience postoperative negative emotions, including anxiety, depression, and immune function suppression. This trial evaluated whether perioperative sub-anesthetic esketamine improves early postoperative negative emotions and immune function. METHODS: In this single-center, double-blind, randomized trial, 84 patients scheduled for AN surgery were assigned to esketamine (n = 42) or placebo (n = 42). The esketamine cohort received a continuous intravenous infusion of esketamine at 0.2 mg·kg-1·h-1 during anesthesia, followed by 1 mg·kg-1 esketamine as an adjuvant in patient-controlled intravenous analgesia (PCIA). The placebo group received saline. The primary outcome was the incidence of depression on postoperative day (POD1), defined as a Hospital Anxiety and Depression Scale-Depression subscale (HADS-D) score > 7. RESULTS: Seventy-seven patients completed the study (39 in the esketamine group, 38 in the placebo group). Esketamine significantly reduced the incidence of depression at POD1 (7.7% versus 31.6%; relative risk 0.24, 95% CI: 0.08-0.80, p = 0.008) and POD3 (0.0% versus 15.8%, relative risk 0.00, 95% CI: 0.00-0.47, p = 0.031) compared with placebo. The incidences of anxiety on POD1 and 3 and sleep disturbances on POD1 were also significantly reduced (p < 0.05). Notably, no significant differences were observed between the two groups in terms of immune function, postoperative pain scores, or intraoperative morphine equivalent. Adverse events did not differ between the groups. CONCLUSION: Perioperative sub-anesthetic esketamine reduced postoperative depression and anxiety, and improve sleep quality after AN surgery, without significant effects on early immune function or acute postoperative analgesia. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2400084537.

Humans↗

PubMed2026

Efficacy and safety of Ruxolitinib-based combination therapy in the patients with Myelofibrosis (MF): a systematic review and meta-analysis.

BACKGROUND: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm. Although Ruxolitinib, a JAK1/2 inhibitor, remains the cornerstone of MF treatment, it does not reverse disease progression, and resistance frequently emerges. These limitations have prompted investigation into combination therapies targeting pathways beyond the JAK-STAT axis. This meta-analysis aims to evaluate the efficacy and safety of Ruxolitinib-based combination therapies in patients with MF. METHODS: We conducted a systematic search of databases for studies published through August 1, 2025. Thirteen distinct Ruxolitinib-based combination regimens were included. Primary efficacy endpoints were ≥35% spleen volume reduction at 24 weeks (SVR35) and ≥50% reduction in total symptom score (TSS50). Safety endpoints focused on the incidence of grade 3/4 thrombocytopenia and anemia. Subgroup analyses were performed based on prior JAK inhibitor exposure and therapeutic mechanism of action. RESULTS: A total of 19 studies comprising 1,088 patients were included in the meta-analysis. Among JAK inhibitor-naïve patients, the combination of Ruxolitinib with Selinexor demonstrated the highest efficacy (SVR35: 92%; TSS50: 78%), followed by Ruxolitinib plus BMS-986158 (SVR35: 90%). For patients with prior JAK inhibitor exposure, Ruxolitinib plus Siremadlin (SVR35: 45%) showed notable activity. CONCLUSION: For JAK inhibitor-naïve patients, Ruxolitinib-based combination regimens demonstrated satisfactory clinical responses and the potential for meaningful disease control. For patients with prior JAK inhibitor exposure, the addition of combination therapy drugs may further enhance the efficacy. Personalized treatment selection remains essential, as therapeutic efficacy is significantly influenced by prior JAK inhibitor exposure.

Humans↗

PubMed2026

Effect of urinary catheter securement band on meatal pressure injury in male intensive care patients: A randomized controlled trial.

OBJECTIVES: To investigate the effectiveness of a urinary catheter securement band in preventing meatal pressure injury (meatal-PI) in male ICU patients, and to identify associated risk factors and the timing of injury development. METHODS: A total of 248 adult male ICU patients were randomly allocated to an intervention group (n = 124) or a control group (n = 124) between December 2024 and April 2025. The intervention group received a catheter securement band in addition to standard care, while the control group received standard care alone. Meatal-PI was evaluated daily using a structured monitoring form and a validated staging system. RESULTS: The incidence of meatal-PI was significantly lower in the intervention group (6.5%) compared with the control group (16.1%) (p = 0.016). Multivariate analysis identified catheter securement, use of silicone catheters, higher Braden Scale scores, and shorter ICU length of stay as independent protective factors, while advanced age was associated with increased risk. Additional factors significantly associated with meatal-PI included comorbidities, higher device burden, latex catheter use, dry skin, lower Glasgow Coma Scale and Braden scores, sedation, and perineal oedema (p < 0.001). CONCLUSIONS: The use of a catheter securement band significantly reduces the incidence of meatal-PI in male ICU patients. Incorporating catheter securement devices into routine nursing care, prioritising silicone catheter use, and performing regular meatal assessments may enhance patient safety by reducing the risk of device-related pressure injuries. Further research comparing different catheter securement methods across diverse patient populations is warranted. IMPLICATIONS FOR CLINICAL PRACTICE: The use of catheter securement bands may reduce the incidence of meatal-PI in male ICU patients. Incorporating standardized catheter stabilization strategies into routine intensive care nursing practice may enhance patient safety and support pressure injury prevention efforts.

Humans↗

PubMed2026

The clinical relevance of regional lymph node microarchitecture in oesophageal cancer patients - Results from the UK MRC OE02 trial.

BACKGROUND: In oesophageal cancer (OeC) patients, neoadjuvant chemotherapy followed by surgery improves survival. Anti-tumour immune responses are mediated by lymph node (LN) microarchitecture. We investigated whether neoadjuvant chemotherapy and/or presence of tumour changes LN microarchitecture, and whether such changes are associated with survival. METHODS: Microarchitectural features (lymphocytes, germinal centres (GermC), histiocytes) were quantified morphometrically in 433 LNs from 333 OE02 trial patients (165 neoadjuvant chemotherapy+surgery (CS), 168 surgery alone (S)). Features were compared between tumour-negative (LNneg) and tumour-positive LN (LNpos) by treatment group. Associations with clinicopathological variables and overall survival (OS) were evaluated. RESULTS: LNneg GermC density was lower in CS patients than in S patients (median: 1% vs 2%; p = 0.0004). No other microarchitectural features differed by treatment group or LN status (LNneg vs LNpos). Low histiocyte content in LNneg and LNpos was associated with improved OS in S patients only (HR:0.67, 95%CI: 0.46-0.97, p = 0.03). Multivariable analysis confirmed the independent prognostic significance of LNneg histiocytes (HR:0.62, 95%CI: 0.42-0.9, p = 0.01). CONCLUSION: These findings suggest that LN microarchitecture may be a biomarker for treatment-related immune modulation and prognosis in patients with resectable OeC. These findings warrant independent validation and further investigation to determine whether LN microarchitectural features could inform personalised therapeutic strategies.

Humans↗

PubMed2026

Assessing the Frequency of VEXAS-Related Canonical UBA1 Mutations in Myelodysplastic Syndrome Patients.

OBJECTIVES: Somatic mutations in the UBA1 gene cause VEXAS syndrome, which presents with inflammatory and hematological symptoms. Case studies show a strong overlap between VEXAS and myelodysplastic syndrome (MDS). Recognizing VEXAS is important for differential diagnosis in patients with both inflammation and MDS, as accurate identification guides treatment. The study focuses on determining how often canonical UBA1 mutations linked to VEXAS occur in MDS patients. METHODS: Patients diagnosed with MDS were enrolled in the study, and genomic DNA was isolated from bone marrow FFPE samples. Molecular analysis was performed using a specifically designed ARMS-PCR approach. Additionally, protein-protein interaction (PPI) studies combined with bioinformatic analyses were carried out to explore potential links between UBA1 and pyroptosis. RESULTS: Among the 149 MDS patients analyzed, none exhibited high-Variant Allele Frequency (VAF) the canonical UBA1 point mutations linked to VEXAS syndrome. PPI analysis revealed a possible association between UBA1 and the NLRP3 inflammasome component. CONCLUSIONS: Expanding the sample size and using targeted NGS or ddPCR would improve mutation detection sensitivity and could reveal UBA1 canonical and non-canonical variants and more accurately estimate the frequency of VEXAS-related mutations in the MDS population.

Humans↗

PubMed2026

Quality of life and gender identity in females with congenital adrenal hyperplasia after genital restoration surgery: A single-center experience.

BACKGROUND: Legislation restricting surgical interventions in children with differences of sex development (DSD) has intensified debate about female genital restoration surgery (FGRS) in patients with congenital adrenal hyperplasia (CAH). Long-term patient-reported outcomes are needed regarding the optimal timing of surgery. OBJECTIVE: We aimed to assess health-related quality of life (HRQoL), gender identity, and family satisfaction regarding surgical timing and outcome in females with CAH following genital restoration surgery. STUDY DESIGN: Cross-sectional survey of CAH patients who underwent surgery between January 2007 to December 2016 at our institution. Validated instruments (KINDL questionnaire for HRQoL, Utrecht Gender Dysphoria Scale, UGDS) and structured telephone interviews were employed. RESULTS: Data on HRQoL was available for 25 patients (self- and/or parent-reported) out of 56 eligible patients (45% response rate). Median age at first surgery was 6 months (range: 3-137 months). Patients' age at time of participation ranged from 2 to 28 years. All had 21-hydroxylase deficiency (92% salt-wasting form) with Prader grades ranging from II-V. Wound dehiscence requiring secondary suturing occurred in 15% of patients with primary surgery at our center, while only one (4%) patient developed vaginal stenosis after early primary vaginoplasty. Two additional patients (8%) with prior outside surgery required vaginal revision after FGRS at age 12. HRQoL scores were comparable to healthy reference populations across most age groups. Children aged 3-6 and adolescents and young adults showed no significant difference from reference values, while children aged 7-13 showed a slight elevation. None of five patients ≥14 years demonstrated gender dysphoria (all UGDS scores <40, threshold ≥40). 14 patients and families were also interviewed by telephone. All preferred early surgical timing. No family expressed regret about the decision or preferred delayed surgery. DISCUSSION: This study provides validated intermediate-term patient- and parent-reported outcomes after FGRS in CAH. Key limitations include the small sample size, single-center design, and young age of most patients. Selection bias may exist, though participating families included those who underwent revision surgery. The absence of a non-operated comparison group reflects current clinical reality, as nearly all CAH patients with urogenital sinus underwent surgical correction. CONCLUSIONS: Females with CAH reported normal HRQoL and a comfortable female gender identity after early FGRS. The patients and their families expressed a preference for early surgery. However, there is need for longer-term follow-up to assess sexual function and reproductive outcomes as well comparison of outcomes with a non-operated group.

Humans↗

PubMed2025

Effect of transcutaneous vagus nerve stimulation in hemodialysis patients: A randomized controlled trial.

INTRODUCTION: Transcutaneous auricular vagus nerve stimulation (tVNS) has shown potential in neurological, autoimmune, and cardiovascular disorders, but its effects on HD patients remain unclear. This study aimed to evaluate the efficacy and safety of tVNS in HD patients. METHODS: We conducted a randomized controlled clinical trial on patients receiving HD ≥6 months. The tVNS group received stimulation for 1 h during the first 2 h of HD sessions, three times weekly for 8 weeks, while the control group received standard care. The primary outcomes were dialysis efficiency (Single-pool Kt/V, Sp Kt/V) and dialysis-related symptoms (Dialysis Symptom Index, DSI), assessed every 4 weeks. Secondary outcomes included pain and fatigue scores, physical performance, Hemodialysis Comfort Scale, hemoglobin levels, Mini-Mental State Examination, and anxiety and depression scores, measured at baseline and 8 weeks after intervention. RESULTS: A total of 63 patients were enrolled in the study, with 32 patients assigned to the tVNS group and 31 patients to the control group. At 8 weeks, the tVNS group showed significant improvements in Sp Kt/V (1.31 ± 0.11 vs. 1.25 ± 0.10, p = 0.02), and DSI (12.09 ± 5.84 vs. 16.26 ± 5.27, p = 0.004), as well as reductions in pain and fatigue, and increases in physical function, comfort, and hemoglobin. However, there were no statistically significant changes observed in cognitive function, anxiety, or depression. CONCLUSIONS: tVNS could improve dialysis efficiency, symptoms, and physical function in HD patients, indicating it may have a role as a complementary therapy.

Humans↗

PubMed2025

Global epidemiology of diabetes and prediabetes in lean or non-obese patients with NAFLD: a systematic review and meta-analysis.

BACKGROUND: The presence of diabetes increases the risk of adverse outcomes of patients with non-alcoholic fatty liver disease (NAFLD) even in those with lean or non-obese NAFLD. However, the epidemiological data regarding the prevalence of diabetes and prediabetes in lean or non-obese NAFLD populations remain limited. We assessed the global epidemiology of diabetes and prediabetes in lean or non-obese patients with NAFLD. METHODS: Published studies were searched in PubMed, EMBASE, Cochrane Library, and Web of Science databases from the inception of the databases to October 2024. The pooled global prevalence of diabetes or prediabetes in patients with NAFLD was evaluated using random-effects meta-analysis. Subgroup meta-analysis and meta-regression were used to investigate potential sources of heterogeneity. RESULTS: A total of 54 studies involving 146,714 patients with non-obese or lean NAFLD were included. The pooled global prevalence of diabetes among patients with lean or non-obese NAFLD was 15.6% (95% CI 10.8%-22.7%). Studies from South America reported the highest prevalence (41.3%, CI 39.1%-43.5%). Meta-regression models showed that geographic region and mean age (p < 0.05) were associated with the were associated with the prevalence of diabetes, jointly accounting for 51.61% of the heterogeneity. The global prevalence of prediabetes among patients with lean or non-obese NAFLD was 22.9% (95% CI 12.5%-41.9%) with the highest prevalence reported in studies from Europe (34.4%, CI 23.0%-51.4%). Meta-regression models showed that geographic region and country (p < 0.05) were associated with the prevalence of prediabetes, jointly accounting for 73.65% of the heterogeneity. CONCLUSION: The pooled global prevalence of diabetes and prediabetes were 15.6% and 22.9% in lean or non-obese patients with NAFLD, respectively. These findings suggest the importance of diabetes screening in these patients.

Humans↗

PubMed2026

Plasma proteome profiling identifies XPNPEP3 as a novel biomarker associated with metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes mellitus.

OBJECTIVE: To identify plasma protein differences between type 2 diabetes mellitus (T2DM) patients with and without metabolic dysfunction-associated steatotic liver disease (MASLD), and to evaluate the diagnostic potential of X-prolyl aminopeptidase 3 (XPNPEP3) for identifying MASLD in T2DM patients. METHODS: Twenty T2DM inpatients were categorized into groups with and without MASLD and their plasma samples were analyzed using data-independent acquisition mass spectrometry, followed by bioinformatics analysis to identify differentially expressed proteins. The cohort was then expanded to 84 patients, and plasma XPNPEP3 levels were validated by enzyme-linked immunosorbent assay. Correlation between XPNPEP3 and clinical indicators were evaluated, and diagnostic performance was determined via receiver operating characteristic (ROC) analysis. Immunohistochemistry was employed to compare hepatic XPNPEP3 expression between the two groups. RESULTS: Proteomic analysis identified 176 differentially expressed proteins, with XPNPEP3 exhibiting the most significant down-regulation by fold change. In the validation cohort, plasma XPNPEP3 was significantly lower in T2DM+MASLD versus T2DM alone. XPNPEP3 levels were negatively correlated with diabetes duration, liver function markers, and triglyceride levels, and was identified as an independent factor inversely associated with MASLD in T2DM.ROC analysis demonstrated strong diagnostic performance for XPNPEP3, further enhanced when combined with BMI and diabetes duration.  Immunohistochemistry confirmed reduced hepatic XPNPEP3 expression in T2DM+MASLD patients. CONCLUSIONS: Lower plasma XPNPEP3 is independently associated with MASLD in T2DM patients and demonstrates strong diagnostic potential, positioning XPNPEP3 as a promising biomarker for diagnosing MASLD in T2DM patients and a novel target for non-invasive diagnostic tool development.

Humans↗

PubMed2026

Nurse-led titration models of care for heart failure reduced ejection fraction: a systematic narrative review of characteristics, patient outcomes, and healthcare resource utilization.

AIMS: Nurse-led titration (NLT) models of care assist with delivery of guideline directed medical therapy for patients with heart failure with reduced ejection fraction (HFrEF). Effectiveness of NLT is established but there is limited information of characteristics of models, patient outcomes and healthcare resource utilization. To build upon the existing evidence by providing a systematic narrative review of the literature of NLT of medications for patients with HFrEF. This review syntheses characteristics of NLT models of care, patient outcomes and healthcare resource utilization. METHODS AND RESULTS: A systematic narrative literature review with systematic search strategy, identification of results, thematic analysis and narrative synthesis. A search was conducted from 2012 to 2025 in Medline, Cinahl complete, Embase and Cochrane. Sixteen studies of NLT models of care were identified from 1944 screened records. Characteristics of models of care were participation of nurses, multidisciplinary teams, follow-up and common features of service delivery. Patient outcomes of mortality were favourable for those that received NLT. There is some evidence of changes in healthcare resource utilization; studies in which the NLT groups received more HF nurse visits and greater HF medication use also reported reduced rehospitalizations. CONCLUSION: Findings reinforce the published benefits of NLT. Additional studies examining adverse events and quality-of-life outcomes are needed to strengthen the evidence base. Several studies suggest a shift in resource use with NLT, highlighting the need for an economic evaluation to inform a cost-effective model of care.

Humans↗

PubMed2026

Clopidogrel Versus Dual-Antiplatelet Therapy for Long-Term Maintenance After Coronary Stenting in Ischemic and Bleeding Birisk Patients With Acute Coronary Syndromes and Diabetes: A Prespecified Subgroup Analysis of the OPT-BIRISK Trial.

BACKGROUND: Among patients with acute coronary syndromes at both high bleeding and ischemic risk (birisk), extended clopidogrel monotherapy after 9 to 12 months of dual-antiplatelet therapy reduces bleeding without increasing ischemia. Whether this benefit extends to birisk patients with diabetes is unknown. METHODS: This prespecified subgroup analysis of the OPT-BIRISK (Optimal Antiplatelet Therapy for High Bleeding and Ischemic Risk Patients) trial included birisk patients with acute coronary syndrome who had completed 9 to 12 months of dual-antiplatelet therapy after percutaneous coronary intervention. Patients were then randomized 1:1 to 9 months of clopidogrel plus placebo versus clopidogrel plus aspirin. Outcomes were compared by diabetes status. The primary end point was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding at 9 months after randomization. The key secondary end point was major adverse cardiac and cerebral events, defined as a composite outcome of all-cause death, myocardial infarction, stroke, or clinically driven revascularization. RESULTS: Of 7758 patients, 4072 (52.5%) had diabetes. Clopidogrel monotherapy decreased Bleeding Academic Research Consortium type 2, 3, or 5 bleeding (2.1% versus 3.2%; hazard ratio [HR], 0.66 [95% CI, 0.45-0.97]) with no increase in major adverse cardiac and cerebral events (2.9% versus 3.6%; HR, 0.79 [95% CI, 0.56-1.12]) compared with clopidogrel plus aspirin in patients with diabetes. Outcomes were consistent in patients without diabetes, with no significant interactions by diabetes status. CONCLUSIONS: In birisk patients with acute coronary syndrome who were stable on dual-antiplatelet therapy with clopidogrel plus aspirin for 9 to 12 months after percutaneous coronary intervention, clopidogrel monotherapy for an additional 9 months reduced clinically relevant bleeding without increasing ischemic events compared with continued dual-antiplatelet therapy, irrespective of diabetes status. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT03431142.

Aged↗

PubMed2026

Cost-Effectiveness of Electronic Patient-Reported Outcome Measure Interventions in Cancer: Systematic Review and Parameter Extraction for Economic Modeling.

BACKGROUND: Complex digital interventions that integrate electronic patient-reported outcome measures (ePROM) into clinical practice in cancer have the potential to improve quality of life, increase survival, and reduce health resource use and costs. Such systems can help patients with cancer self-manage chemotherapy symptoms, reduce clinicians' workloads through automated decision support, and resolve problems earlier. However, more research on the cost-effectiveness of ePROM monitoring is needed. OBJECTIVE: This paper comprises two complementary components: (1) a systematic literature review summarizing and evaluating the quantitative and qualitative evidence related to the cost-effectiveness of ePROM monitoring and (2) a health economic model parameter extraction. We also conducted supplementary targeted searches and scoping to provide context to our findings. METHODS: We searched Ovid (including MEDLINE and Embase), Scopus, and the International Health Technology Assessment Database for original English-language papers published on or before March 2025 using search strings that combined terms related to ePROMs, health economics, and cancer/oncology. We included papers reporting health economic-related outcomes for ePROM interventions designed for adult cancer populations and excluded screening tools and conference abstracts. RESULTS: We included 34 publications from 27 unique studies and identified and analyzed 26 ePROM-integrated interventions within these. Most (23/26) of the included interventions explicitly described some form of alert handling and automated decision support based on remote ePROM monitoring. Of the 34 publications, 5 presented full cost-effectiveness analysis results, of which 3 were highly uncertain and lacked clear differences in costs and health outcomes between ePROMs and standard care; conversely, 2 presented strong evidence of cost-effectiveness due to quality-of-life improvements, reduced hospitalizations, and potentially more autonomy in health-related travel (eg, ePROM-monitored patients can drive or walk to the hospital instead of using taxis or ambulances). A further 5 publications reported partial health economic results (eg, cost-consequence and budget impact), of which 1 detected no difference in strategies; in contrast, 4 reported lower health resource use and costs of ePROMs, mainly due to hospitalization reductions. Overall, 12 of the 27 studies included a qualitative component but mostly focused on user experience and design-related themes; only 2 of these addressed economic-specific themes (eg, changes in workflow and resource use due to ePROM implementation and integration), indicating some potential for time saving due to ePROM monitoring. CONCLUSIONS: Some ePROM-integrated interventions demonstrated cost-effectiveness in cancer care, but the evidence base remains limited. Where evidence does exist, cost-effectiveness appears driven by reduced hospitalization and improved quality of life. Qualitative research within the included studies rarely addressed economic questions. We provide a detailed parameter extraction for use in future economic modeling and recommend research priorities, including quantitative mapping of ePROM symptom data onto health resource use patterns, and qualitative work exploring how ePROM implementation affects clinical workloads and patient-perspective costs.

Humans↗

PubMed2025

Treatment preference for once-weekly versus once-daily DPP-4 inhibitors in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND/OBJECTIVE: Although once-weekly and once-daily DPP-4 inhibitors have gained widespread market recognition, patient preference differences remain a key focus. This meta-analysis compares treatment preferences for once-weekly versus once-daily DPP-4 inhibitors in T2DM, offering evidence to guide clinical decisions and healthcare policies. METHODS: PubMed, OVID, EBSCO, Web of Science, CNKI, Wanfang, and clinical trial registries were searched up to June 30, 2025. After screening literature against predefined criteria, a systematic review was conducted to compare the effects of once-weekly and once-daily DPP-4 inhibitors on the treatment preferences of patients with T2DM. RESULTS: 8 RCTs with 1,575 participants were analyzed. No significant difference in medication adherence and DTSQ total score between the once-weekly and once-daily groups (p > 0.05). HbA1c percentage (MD = -0.21, 95% CI [-0.42, -0.01], p < 0.05) decreased significantly with once-weekly dosing, while GA and FPG showed no change (p > 0.05), this suggests greater improvement in HbA1c percentage levels following a switch to once-weekly DPP-4 inhibitors. Once-weekly DPP-4 inhibitors showed higher musculoskeletal/connective tissue disorder risk (RR = 2.63; 95% CI [1.18, 5.83]), but no significant differences in other adverse events (p > 0.05). No significant differences in treatment burden between both groups (p > 0.05). CONCLUSION: No statistically significant association between treatment preferences for once-weekly versus once-daily DPP-4 inhibitors among T2DM patients and medication adherence, treatment satisfaction, glycemic level changes, safety, or treatment burden for these two dosing regimens. Further research is needed to elucidate the influence of physician prescribing behavior on these preferences.

Humans↗

PubMed2026

Clinical performance of monolithic and veneered zirconia three-unit posterior FDPs: A five-year multicenter randomized controlled trial.

AIM: This randomized controlled clinical study compared monolithic, partially veneered, and fully veneered zirconia FDPs over a 5-year period with respect to survival, technical and biological complications, and patient-reported outcome measures (PROMs). MATERIALS AND METHODS: Sixty-four patients requiring three-unit posterior FDPs were randomly allocated to monolithic (MONO-FDP), partially veneered (PV-FDP), or fully veneered (FV-FDP) groups. All FDPs were fabricated from 4 mol% Y₂O₃ partially stabilized zirconia (4Y-TZP). Follow-up examinations were conducted at baseline, 1, 3, and 5 years. Technical parameters were evaluated using modified USPHS criteria. Periodontal measurements (PPD, BOP, PI) and patient satisfaction were assessed at all time points. RESULTS: A total of 63 FDPs were evaluated at baseline, 57 at 3 years, and 54 at 5 years. Survival at 5 years was 94.7% for MONO-FDPs, 100% for FV-FDPs and 100% for PV-FDPs. Technical complications occurred exclusively in PV-FDP (33%) and FV-FDP (38%) groups and consisted of minor, polishable chipping; no chipping or fractures were recorded in MONO-FDPs (0%) with statistically significant difference between MONO-FDP and the other two groups (p ≤ 0.014). Biological parameters remained stable across all groups, with no significant differences in PPD, BOP, or PI. PV-FDPs and FV-FDPs tended to receive more favorable professional color ratings, whereas PROMs were similar among the groups. CONCLUSIONS: All three FDP designs-monolithic, partially veneered, and fully veneered-fabricated from 4Y-TZP zirconia demonstrated excellent 5-year clinical performance. Technical complications were limited to PV- and FV-FDPs and consisted of minor chipping. Biological outcomes and patient satisfaction were similar across groups. CLINICAL SIGNIFICANCE: The five-year outcomes suggest that veneered, partially veneered, and monolithic FDPs can be used with high clinical reliability; however, restorations incorporating veneering ceramic may present an elevated risk of ceramic chipping.

Humans↗

PubMed2026

Daily low-dose carboplatin or weekly carboplatin plus nab-paclitaxel for concurrent chemoradiotherapy in older patients with locally advanced non-small cell lung cancer (JCOG1914): A randomized phase 3 trial.

BACKGROUND: Daily low-dose carboplatin with concurrent thoracic radiotherapy is the standard treatment for older patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC) in Japan. METHODS: This open-label phase 3 trial was conducted at 38 institutions in Japan. Patients aged ≥ 75 years with LA-NSCLC were randomly assigned (1:1) to receive daily carboplatin (30 mg/m2) or weekly carboplatin (area under the curve, 2 mg·min/mL) plus nab-paclitaxel (30 mg/m2) with thoracic radiotherapy. Durvalumab maintenance therapy was recommended after treatment completion. The primary endpoint was overall survival, which was used to assess the non-inferiority of weekly carboplatin plus nab-paclitaxel compared to daily low-dose carboplatin. RESULTS: From December 2020 to March 2024, 124 patients were enrolled (carboplatin arm, 61 and carboplatin plus nab-paclitaxel arm, 63). In the planned interim analysis, the Bayesian predictive probability indicating the non-inferiority of carboplatin plus nab-paclitaxel compared with carboplatin in the final analysis was 8.0%, leading to early study termination for futility. The median overall survival was not estimable in the carboplatin arm; the estimated value in the carboplatin plus nab-paclitaxel arm was 26.1 months (hazard ratio, 1.56; 95% confidence interval, 0.79-3.11; p = 0.200). Two treatment-related and seven non-cancer-related deaths occurred in the carboplatin plus nab-paclitaxel arm. Patients in the carboplatin arm had better quality of life than those in the carboplatin plus nab-paclitaxel arm at 6 weeks (odds ratio, 0.39; 95% confidence interval, 0.18-0.81; p = 0.012). CONCLUSIONS: Daily low-dose carboplatin with concurrent thoracic radiotherapy remains the standard treatment for older patients with unresectable LA-NSCLC in Japan.

Humans↗

PubMed2026

Repeated scoring with the adult appendicitis score improves the sensitivity and the specificity of appendicitis diagnosis in patients with early equivocal signs of appendicitis: a secondary analysis.

PURPOSE: The utilization of computed tomography in the early stage of acute appendicitis may result in overdiagnosis and unnecessarily expose patients to ionising radiation. The Adult Appendicitis Score (AAS) can be used to select patients for imaging. Observation and re-scoring in the DIAMOND trial reduced the need for imaging. Now, we wanted to determine if the change in AAS (∆AAS) can serve as a diagnostic tool to select patients for imaging even more precisely. METHODS: Eighty-eight patients with early equivocal appendicitis participated in the observation arm of the DIAMOND trial. The data for these patients were reanalysed, and ∆AAS during the observation was calculated. The baseline AAS, final AAS, and the change in C-reactive protein (∆CRP) were selected as reference standards. RESULTS: Eighty-three patients with complete data were included in the analysis. The AUROC (Area Under the Receiver Operating Characteristic) values are as follows: ∆AAS, 0.932 (95% CI 0.868-0.996); baseline AAS, 0.629 (95% CI 0.498-0.760); final AAS, 0.936 (95% CI 0.886-0.987); and ∆CRP, 0.796 (95% CI 0.696-0.897). Using receiver operating characteristic curves, we established the thresholds for low (AAS ≤ -2), intermediate (AAS -1 to 0), and high (AAS ≥ 1) probability of appendicitis. The negative predictive value for the low-probability group and the positive predictive value for the high-probability group concerning acute appendicitis were 97% and 94%, respectively. CONCLUSION: Patients with equivocal signs of appendicitis may benefit from short observation and the calculation of ∆AAS to reduce overdiagnosis and exposure to excessive imaging. REGISTRATION: The DIAMOND trial was officially registered on ClinicalTrials.gov (NCT02742402) on April 13, 2016.

Adult↗

PubMed2026

Assessing perinatal depression identifying abilities among maternal and child health workers in rural China using smartphone-based virtual patients: a multi-center cross-sectional study.

OBJECTIVE: To assess rural maternal and child health (MCH) workers' virtual patients (VPs)-assessed performance in identifying perinatal depression (PND) using smartphone-based VPs, and to identify factors associated with this performance in rural Hunan, China. METHODS: A multicentre cross-sectional study was conducted in Hunan Province, China. A standardized questionnaire collected demographic and work-related characteristics of rural MCH workers. Smartphone-based VPs were used to assess PND identification performance in a simulated clinical scenario. An overall score ≥60 was used as a prespecified operational benchmark across consultation, ancillary assessment, diagnosis, management, and health education domains. Data were analyzed using SPSS 26.0. RESULTS: A total of 375 rural MCH workers participated, yielding an effective response rate of 90.4%. Only 25.9% met the prespecified operational benchmark for VP-assessed PND identification performance. The mean accuracy scores for consultation, ancillary assessment, diagnosis, management, and health education were 94%, 48%, 64%, 58%, and 74%, respectively. Complete consultation accuracy was higher among MCH workers from township health centers than among those from county-level MCH hospitals. MCH workers aged 18-39 years showed higher odds of complete diagnostic accuracy for PND than those aged ≥40 years. CONCLUSIONS: Smartphone-based VP assessment was feasible in rural MCH settings and revealed suboptimal PND identification performance. Mobile VPs may help identify frontline performance gaps and inform targeted training, but further validation against real-world clinical performance, or standardized patient encounters is needed before large-scale implementation. These findings may support targeted capacity-building for rural MCH workers and more equitable perinatal mental health care.

Humans↗