Osteoporosis (OP) is a systemic skeletal disorder that increases fragility and susceptibility to fractures. Despite the availability of teriparatide for the treatment of patients with acute fractures with better efficacy, its long-term daily injection and high cost limit its broader use among a wider patient population, especially for those living in low- and middle-income countries. This study aims to evaluate the efficacy of a novel sequential treatment with teriparatide daily for 6 months followed by denosumab every 6 months for another 18 months, in comparison with denosumab monotherapy every 6 months for 24 months, in reducing the risk of fractures in patients with newly diagnosed osteoporotic fractures. The study will also explore the possible difference between two sequential treatments (shifting to denosumab treatment at 6 or 12 months) in their effect on increasing bone mineral density (BMD).

This study is designed as a multicentre, open-label, randomised controlled trial among 2478 patients with newly diagnosed osteoporotic fractures from 58 hospitals across China. Participants will be randomly assigned in a 10:10:1 ratio to three treatment groups: 24 months of denosumab monotherapy, early sequential treatment (teriparatide for 6 months followed by denosumab for 18 months) and late sequential treatment (teriparatide for 12 months followed by denosumab for 12 months). The primary outcome is the incidence of vertebral fractures over 24 months of treatment. Secondary outcomes include changes in BMD at the lumbar spine, total hip and femoral neck, changes in bone turnover markers (β-carboxy-terminal telopeptide of type 1 collagen and procollagen type 1 N-terminal propeptide), treatment adherence and cost-effectiveness. Follow-up assessments are scheduled at 3, 6, 9, 12, 18 and 24 months post-randomisation for primary and secondary outcomes, and biannually afterwards for the primary outcome.

The study protocol has been registered on ClinicalTrials.gov and has received ethical approval from the Peking Union Medical College Hospital Medical Science Research Ethics Committee (1-22PJ939). The findings will be disseminated through peer-reviewed scientific journals.

NCT05866029.

Peritoneal dialysis (PD) is a widely used renal replacement therapy for chronic kidney disease patients, yet malnutrition remains a common complication linked to poor outcomes. Nearly 40% of PD patients in China are malnourished, with serum albumin levels below 35 g/L. Amino acid-based peritoneal dialysis solutions (AA-PDS), which replace glucose with amino acids as the osmotic agent, have been used globally for decades to improve nutrition and reduce peritoneal damage, but they were introduced to mainland China only in 2022. This study aims to evaluate the efficacy and safety of AA-PDS in improving nutritional status and clinical outcomes among malnourished PD patients in mainland China, providing a potential new therapeutic option for this population.

This multicentre, open-label, prospective, parallel-controlled study will enrol patients with end-stage kidney disease who were stable on PD for more than 3 months. A total of 500 eligible patients will be divided into the intervention group undergoing PD once every morning using 2.0 L of amino acid (15) PD solution and the control group using conventional PD solution (lactate) in a 4:1 ratio based on their willingness and clinical needs. Our primary outcome is serum albumin, while other nutritional indicators, including serum prealbumin, serum transferrin, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and ultrafiltration volumes are considered secondary outcomes. Information such as demographics, clinical and biochemical characteristics, examination indicators, anthropometry measurements and Subjective Global Assessment scores will be collected at baseline, 1 month, 3 month and 6 month follow-up. Statistical analysis will be conducted using SAS V.9.4 or higher versions. All statistical tests are conducted through the two-tailed test, and a p value≤0.05 will be considered statistically significant. The description of quantitative indicators will be used in calculating the number of cases, mean, SD, median and IQR method. The classification indicators will be used to describe the number of cases and percentages (frequency and frequency rate).

This multicentre study obtained ethical approval from the lead ethics committee at the First Affiliated Hospital of Zhejiang Chinese Medical University (approval no.: 2024-KLS-379-02). Additionally, each participating site provided local ethical approval or a formal waiver, as required by their institutional policies. The results will be reported in a peer-reviewed journal and a relevant academic conference.

ChiCTR2400090896.

Acute pain following pulmonary surgery can affect the recovery process of patients. The use of intrathecal morphine (ITM) injections offers a long-lasting analgesic effect, but its clinical application remains controversial. This study aims to investigate the impact of combining bupivacaine with ITM injections on the quality of postoperative recovery in patients who have undergone pulmonary surgery.

This multicentre, randomised, double-blind, controlled trial will enrol 254 patients undergoing elective lung surgery, who will be randomly assigned in a 1:1 ratio to either group IT (receiving an intrathecal injection of 3 mg bupivacaine and 0.25 mg morphine before general anaesthesia induction) or the control group (C group). The primary outcome includes postoperative recovery quality on day 1 (quality of recovery, QoR-15), with secondary outcomes encompassing postoperative recovery quality on days 2 and 3 (QoR-15), pain scores within 72 hours postoperatively, analgesic rescue, intraoperative haemodynamic parameters, opioid consumption, postoperative adverse reactions, recovery metrics, complications, chronic pain incidence and sleep quality.

The results will be disseminated through peer-reviewed publications. This study protocol (V.2.0, 30 October 2024) involves human participants and has been approved by the Ethics Committee of Affiliated Hospital of Yangzhou University (number 2024-08-02-2), Taicang Hospital Affiliated to Soochow University (number 2025 SR-041) and Yichang Central People’s Hospital (number 2024-513-02). Each individual who agrees to participate in the research will provide written informed consent after the objectives and procedures of this study are explained to them.

ChiCTR2400092935. Registered on 26 November 2024.

To estimate tuberculosis (TB) incidence trends in the high-altitude Xizang, China, and to explore the key intervention strategies on achieving the WHO 2030 TB control target.

We developed a susceptible–exposed–infectious–recovered transmission model using routinely reported TB surveillance data from 2004 to 2022. Scenario-based simulations were conducted to project future TB incidence under alternative intervention strategies. Model assumptions are as follows: (1) a stable population, (2) lifelong vaccine-induced immunity, (3) infectiousness of active TB cases, (4) relapse risk after recovery and (5) homogeneous mixing within the population.

Seven prefectures of Xizang Autonomous Region on the Tibetan Plateau, China.

An estimated population of approximately 3 million individuals residing in Xizang.

We assessed the epidemiological impact of four interventions implemented independently: increasing vaccine efficacy rate, reducing transmission rates of susceptible individuals, decreasing progression rate from latent TB infection to active disease and reducing relapse rate among successfully treated patients, compared with continuation of current control measures.

The estimated basic reproduction number (R₀ ) for TB in Xizang was 0.39 (95% CI 0.21 to 0.71) in the absence of additional interventions, which was the highest among all regions of China. Model simulations indicated that all four evaluated interventions were each likely to reduce TB incidence, but only reducing the latent-to-active TB progression had a substantial effect. A 50% reduction in the progression rate was predicted to lower TB incidence from 66.56 (62.00–70.11) to 40.54 (37.15–43.77) cases per 100 000 population, meeting the WHO 2030 TB control target.

Targeted management of individuals with latent TB infection should be strengthened to substantially reduce TB transmission in high-altitude areas.

Deep vein thrombosis (DVT) of the lower limbs has a significantly higher incidence among elderly populations than that observed in other types of fractures, prolonged immobilisation and the systemic inflammatory response triggered by preoperative pain are the main risk factors. Liposomal bupivacaine (LB) single-injection pericapsular nerve group (PENG) block has demonstrated effective analgesia both before and after surgery, while preserving motor function in patients with hip fracture. Although regional nerve block is a well-established component of preoperative multimodal analgesia, its potential role and underlying mechanisms in the prevention of DVT in elderly patients with hip fracture remain largely unexplored.

This study will be conducted as a double-blind, randomised, sham-controlled, prospective clinical trial. On admission, a total of 132 participants will be randomly assigned using block randomisation to receive either treatment group (LB single-injection PENG block) or sham group (saline solution single-injection PENG block). The primary outcome was the incidence of DVT, while secondary outcomes included perioperative inflammatory and immune-related stress levels and functional-based pain scores.

This study protocol complies with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 guidelines and has been approved by the Ethics Committee of Shunde Hospital, Guangzhou University of Traditional Chinese Medicine (Approval No KY-2025005). The raw data are planned to be made publicly available on the ResMan raw data–sharing platform (IPD sharing platform) of the Chinese Clinical Trial Registry in December 2027 and can be accessed at http://www.medresman.org.cn.

ChiCTR2500100799.

To assess the association between ambient ozone (O₃) exposure and semen quality among men with unhealthy behaviours and low income.

A case-control study was conducted from February 2024 to January 2025, in which male participants aged 18–45 years were recruited from Foshan, and following propensity score matching, a total of 820 participants were included in the final analysis.

The evaluated the association between O₃ exposure during the 70–90 days, 10–14 days, 0–9 days and 0–90 days prior to semen collection and semen quality using stepwise conditional logistic regression analyses, and restricted cubic splines were incorporated into the models.

O₃ exposure during the 70–90 days and 0–90 days preceding semen sample collection was significantly associated with an increased risk of low semen quality, with ORs of 1.020 (95% CI 1.003 to 1.039) and 1.056 (95% CI 1.008 to 1.108), respectively. Additionally, O₃ exposure during the 0–90-days period showed a significant positive association with abnormal sperm concentration. A non-linear relationship between O₃ exposure and sperm concentration was also observed. Notably, O₃ exposure during the 0–9 days before semen collection was inversely associated with the risk of low semen quality. Subgroup analyses across age, lifestyle factors and socioeconomic strata revealed no significant effect modifications.

This study found that O₃ exposure during the 70–90 days and 0–90 days before sampling was associated with reduced semen quality in men with unhealthy behaviours and low income.

Atrial fibrillation (AF), with a prevalence of 1–2%, is the most common cardiac arrhythmia. AF is associated with a fivefold increased risk of cardioembolic events; approximately 20% of all strokes are caused by AF. Pulmonary vein isolation (PVI) has become the first-line treatment for AF. However, PVI cannot eliminate the residual stroke risk. Current guidelines recommend that anticoagulation be continued in this specific group of patients, regardless of the presence or absence of AF. In this large AF population post-PVI, who are considered to be in an earlier stage of AF, it is unknown whether left atrial appendage closure (LAAC) offers an alternative to direct oral anticoagulant (DOAC) therapy.

The trial will be a prospective, randomised, multicentre non-inferiority study comparing two treatment strategies in AF patients after atrial ablation. Patients will be randomly assigned to either percutaneous LAAC (group A) or DOAC treatment (group B) in a 1:1 ratio; both sequential and concomitant planned ablation with or without LAAC are accepted. Randomisation will be conducted using web-based randomisation software. A total of 1012 participants (506 patients per group) will be enrolled. The primary effectiveness measure will be the occurrence of any of the specified events within 24 months after randomisation: stroke/transient ischaemic attack/systemic thromboembolism, cerebral haemorrhage, other major haemorrhages (Bleeding Academic Research Consortium ≥2), cardiovascular mortality and all-cause mortality.

The study was approved by the Ethical Review Board of Shanghai Chest Hospital, China (KS(Y)20287). Written informed consent will be obtained from all participants. The trial will follow the Declaration of Helsinki and Good Clinical Practice. Confidentiality will be maintained with anonymised, securely stored data. Findings will be disseminated through peer-reviewed publications and conferences.

ChiCTR2000036538.

Chronic non-specific low back pain (CNLBP) is a multifactorial disease involving physical dysfunction and psychological distress. Acupuncture and mindfulness-based stress reduction (MBSR) are two non-pharmacological therapies recommended by guidelines, which have been proven effective in improving the clinical symptoms of CNLBP. However, the efficacy of their combined use has yet to be explored. This study aims to explore whether the combination of acupuncture and MBSR would have different synergistic effects in patients with CNLBP compared with acupuncture or MBSR alone.

This protocol describes a randomised controlled trial with a 2x2 factorial design involving 120 CNLBP patients. Participants will be randomly allocated to four groups: (1) acupuncture, (2) MBSR, (3) acupuncture combined with MBSR, and (4) health education. The intervention period is 6 weeks. The outcome measurements will include the Visual Analogue Scale (VAS), Tactile Acuity Test, Short-form of McGill Pain Questionnairethe(SF-MPQ); Roland-Morris Functional Disability Questionnaire (RMDQ), Oswestry Disability Index(ODI), the Five Facet Mindfulness Questionnaire (FFMQ), the 21-item Depression Anxiety Stress Scales (DASS-21), the Regulatory Self-Efficacy Scale (RESE), the Beck Depression Inventory (BDI-II), the Beck Anxiety Inventory (BAI), the Fear-Avoidance Beliefs Questionnaire (FABQ) and the Pain Catastrophizing Scale (PCS);Pain Sensitivity Questionnaire(PSQ); Pittsburgh Sleep Quality Index(PSQI). All evaluations will be conducted at the baseline stage as well as 6 weeks and 4 months after the implementation of the intervention measures.

Ethics approval was obtained from the Ethics Committee of the Affiliated Rehabilitation Hospital of the Fujian University of Traditional Chinese Medicine (2024KY-041-04). The results of the study will be disseminated through peer-reviewed publications and at scientific conferences.

ITMCTR2025000764.

Concha-type microtia, classified as a milder form of microtia under Nagata’s classification, is characterised by the presence of more normal ear subunits compared with other types. The non-expanded auricular reconstruction using autologous rib cartilage is a standard procedure treating conchal microtia, and this operation typically comprises two stages. To maximise the utilisation of native auricular cartilage, the lower half of a patient’s ear is preserved as residual ear, which should be connected to the rib cartilage scaffold in this operation. However, it remains unclear whether this connection should be performed in the first-stage or second-stage surgery. Current literature lacks sufficient evidence to determine the safer and more effective approach. Thus, we plan to conduct this randomised controlled trial to formally compare the safety and efficacy of first-stage versus second-stage connection, hypothesising that second-stage connection may be a better choice since it may reduce skin cutting, operative risk and improve recovery.

This is a single-centre, randomised controlled trial comparing two surgical treatments. Based on sample size calculations, a total of 78 eligible patients will be randomised with a 1:1 allocation. The control group will be treated with connecting the residual ear with the framework in stage 1, while the experimental group will be treated with connecting the residual ear with the framework in stage 2.

The safety of the surgery will be evaluated based on the grade-A healing rate and the incidence of complications (infection, haematoma, flap or skin necrosis and cartilage scaffold exposure). Efficacy of the surgery will be assessed using the Patient and Observer Scar Assessment Scale (POSAS) and Glasgow Benefit Inventory (GBI) scores. Patients will be scheduled for follow-up 3–6 months after each surgery. Descriptive analyses will be performed to summarise baseline demographics. The incidence of grade-A healing and complications will be analysed using the ² test. GBI and POSAS scores of the two groups will be analysed using independent-samples t test. A p value

This study was approved by the Ethics Committee of Sichuan Provincial People’s Hospital (no. 2025-256-1) on 9 April 2025, and conformed to the Declaration of Helsinki. At the time of manuscript submission, patient recruitment began in April 2025 and is expected to continue until January 2027. Surgical procedures and follow-up will continue until February 2028. Trial results will be published in peer-reviewed journals and will be disseminated to the media and the public.

NCT06763991.

Due to the multisystemic nature of sickle cell disease (SCD), complications can occur together and thus discerning costs associated with individual complications requires a methodology that can estimate the costs of a given complication while accounting for the presence of other complications. In this study, we aimed to estimate period-based incremental costs associated with specific chronic complications in patients with SCD in England while accounting for multimorbidity.

All-cause primary and secondary care healthcare resource utilisation (HCRU) was obtained for a retrospective cohort of patients with SCD using Clinical Practice Research Datalink (CPRD) Aurum linked to Hospital Episode Statistics (HES) datasets. Annualised HCRU and costs were calculated, dividing patient-level events by patient-level time (in years) to obtain per person per year estimates. A series of generalised linear models were used with adjustment for demographic factors and proportion of follow-up time with each complication to estimate the costs associated with 10 chronic SCD-related complications of interest. For these costs, annual equivalent costs can be obtained by dividing by the median follow-up time of 4.74 years.

Patients with a diagnosis of SCD, with or without complications, in CPRD or HES with at least 12 months follow-up.

Period-based all-cause direct healthcare costs.

Of the 1271 patients with SCD included in the study, 49.9% (n=634) had at least one complication and of these 41.3% (n=262) had two or more complications either at baseline or during follow-up. Patients with complications had higher all-cause healthcare costs compared with patients without complications (mean (SD) annualised cost £16 058 (£21 488) vs £4399 (£6635)). Patients with complications had four times the number of annualised inpatient admissions (6.1 vs 1.5 admissions) and more than double the number of annualised bed days in hospital (8.3 vs 3.8 days) over a median 4.74 years of follow-up. Of the complications evaluated, end-stage renal disease had the highest estimated incremental cost of £252 083 (95% CI £214 478 to £283 745) over 4.74 years; this is in addition to the £18 547 period-based cost among patients with SCD without complications. Osteonecrosis was the most common complication with an estimated incremental cost of £27 399 (95% CI £6417 to £43 319) over the same period.

Estimating the cost of complications, while accounting for multimorbidity, is essential to determine the true direct cost of SCD. The modelling method presented in our study provides period-based estimates of cost and hospital admissions for individual complications in patients with SCD, accounting for multimorbidity. This approach can be used and extended to other diseases with multisystemic complications to estimate the direct HCRU and costs of individual complications.

Tuberculosis (TB) remains a globally concerning infectious disease, and significant challenges persist in attaining the 2030 targets set by the WHO. With the rapid advancements in computer-aided detection (CAD) technology, CAD-assisted Chest X-Ray (CAD-CXR) has been applied in TB patients triaging, but the practical application value of the CAD-CXR system in real-world primary healthcare settings in China for TB prevention and control has not been fully elucidated. This protocol reports a design of a cluster randomised controlled trial (CRCT), which aims to evaluate the effectiveness and clinical pathway of CAD-CXR in enhancing TB diagnostic yield in primary healthcare settings, thereby contributing to global TB elimination strategies.

Scheduled for September 2025, this CRCT will recruit 22 townships in Yichang of Hubei Province, China. These townships will be randomly allocated at a 1:1 ratio to either the CAD-CXR system intervention group or the control group. In the intervention group, healthcare providers will use the CAD-CXR analysis system to assist in TB screening, whereas the control group will rely solely on conventional CXR interpretation by radiologists. The primary outcome of the study is the TB diagnostic yield; the secondary outcomes include diagnostic delay duration and the accuracy of the CAD-CXR system. These metrics will be comprehensively evaluated to assess the effectiveness of the CAD-CXR intervention. Findings from this study are anticipated to offer evidence-based recommendations regarding the optimal application scenarios and implementation pathways for CAD-CXR.

This study was approved by the Ethics Committee of the Peking Union Medical College (CAMS&PUMC-IEC-2025-044). Findings of this study will be disseminated through traditional academic pathways, including peer-reviewed publications and conference presentations.

NCT06963606.

Frailty is a multidimensional concept of vulnerability closely associated with ageing and adverse health outcomes, including mortality, chronic diseases and functional impairments. Despite its clinical relevance, the conceptualisation of frailty remains challenging, highlighting the need to explore how it relates to general health decline over time.

To evaluate whether a Frailty Index is associated with subsequent decline in self-rated health (SRH) over 13 months in older adults.

Longitudinal cohort design.

A total of 660 community dwelling participants aged 65 and older from Canton Ticino, Southern Switzerland, were included. The follow-up period, conducted as part of the Corona Immunitas study, spanned from September 2020 to November 2021.

The Rockwood Frailty Index categorised participants into frail, prefrail and robust groups based on 30 variables across seven domains. SRH trajectories were analysed over time using linear mixed-effects models, adjusting for socio-demographic and health-related covariates.

From 660 participants, 41.5% were robust, 48.2% prefrail and 10.3% frail at baseline, with baseline mean SRH 4.22, 3.74 and 2.97, respectively. SRH declined over 13 months in all groups (β=–0.009, p

Frail individuals experience a more pronounced decline in SRH compared with robust and prefrail individuals, highlighting their heightened vulnerability. The Rockwood Frailty Index was associated with health deterioration over time and clearly distinguished between frailty states, supporting its use to identify older adults at higher risk of subsequent health decline and to inform early detection and prevention strategies in older populations.