Estimating the prevalence of persistent symptoms after SARS-CoV-2 infection (post-COVID-19 syndrome): a regional cross-sectional study protocol

Introduction
The COVID-19 pandemic, driven by the SARS-CoV-2 virus, has had a significant global impact, with over 775 million cases reported and more than 7 million deaths as of July 2024. In Chile, approximately 5.4 million people have been infected, with a substantial proportion experiencing persistent symptoms known as post-COVID-19 syndrome. This study aims to estimate the prevalence of post-COVID-19 syndrome in Punta Arenas, Chile, and to explore the associated symptoms, mainly focusing on psychological, physical and molecular impacts on the affected population.

Methods and analysis
This cross-sectional study will use stratified random sampling to select a representative sample of 282 adults from Punta Arenas. Participants eligible for the study are those who had tested positive for SARS-CoV-2 by reverse transcription-quantitative PCR between July 2022 and July 2023. Data collection will include comprehensive clinical assessments, psychological evaluations and laboratory analyses of inflammatory biomarkers. Standardised instruments will be used to ensure consistency and reliability in measuring persistent symptoms. Statistical analyses will include descriptive statistics, regression models and subgroup analyses to identify risk factors and the prevalence of post-COVID-19 syndrome.

Ethics and dissemination
The Human Research Ethics Committee of the Clinical Hospital of the University of Chile approved the study protocol (Memorandum No 007/2023). We will present the results in peer-reviewed publications and national and international professional and academic meetings.

Trial registration number
NCT05855382.

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Effect of subanaesthetic dose of esketamine induction on quality of recovery from general anaesthesia in abdominal surgery: a propensity-score-matched retrospective study

Objectives
Subanaesthetic doses of esketamine may attenuate the opioid-induced cough reflex and prevent intraoperative haemodynamic fluctuations. This study aims to evaluate the effect of subanaesthetic doses of esketamine on the quality of recovery in patients who underwent abdominal surgery.

Design
Retrospective cohort study using propensity score matching (PSM) methodology.

Setting
A tertiary academic hospital.

Participants
Patients who underwent abdominal surgery under general anaesthesia with tracheal intubation between 20 December 2022 and 30 April 2023, were retrospectively reviewed. Patients were assigned to the esketamine or control group based on whether they received a subanaesthetic dose of esketamine.

Primary and secondary outcome measures
The primary outcome was extubation time (T1). Secondary outcomes included post-anaesthesia care unit (PACU) observation time (T2), total PACU time (T3), postoperative pain at multiple time points and adverse events including respiratory depression, hypertension and others.

Results
A total of 2177 patients underwent abdominal surgery. After PSM, 1196 patients were analysed, 598 in each group. Esketamine significantly reduced the extubation time compared with the control group (20.00 vs 23.00 min, p=0.001). Total PACU time was shorter in the esketamine group than in the control group (62 vs 66 min, p=0.015), although PACU observation time did not show a significant difference. Compared with the control group, the esketamine group had a lower incidence of severe postoperative pain immediately after extubation (0.33% vs 2.01%, p=0.007) and respiratory depression (2.68% vs 5.35%, p=0.027), but a higher incidence of hypertension (9.53% vs 6.35%, p=0.042). There were no other significant differences in adverse events between the two groups.

Conclusions
The use of subanaesthetic doses of esketamine for induction of anaesthesia in patients undergoing abdominal surgery may shorten the extubation time and reduce the incidence of postoperative complications.

Trial registration number
ChiCTR2300072154.

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Correlation between postprandial hypotension and post-induction hypotension in the elderly: a protocol for a prospective cohort study

Introduction
Post-induction hypotension (PIH) is particularly common in elderly patients undergoing general anaesthesia and is associated with severe postoperative complications. Autonomic nervous system (ANS) dysfunction is a potential risk factor for significant haemodynamic fluctuations during general anaesthesia in elderly patients. Tools to identify ANS are currently lacking in perioperative clinical practice. Postprandial hypotension (PPH) is closely linked to ANS dysfunction and is also common among elderly individuals. Therefore, this study aims to explore the relationship between PPH and PIH in elderly patients undergoing non-cardiac surgery. By examining this correlation, we hope to better understand the factors contributing to PIH and explore the potential role of PPH in predicting PIH.

Methods and analysis
This is a prospective observational cohort study. 120 elderly Chinese patients aged ≥65 years and scheduled to undergo non-cardiac surgery under general anaesthesia at Peking Union Medical College Hospital (PUMCH) will be included. PPH assessments will include baseline pre-prandial records and blood pressure measurements immediately after meal completion, followed by every 5 min for 120 min. To evaluate PIH, blood pressure will be monitored from the patients’ entry into the operating room until 20 min after anaesthesia induction or the initiation of surgery. PIH is defined as systolic blood pressure of

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Identifying barriers and disparities in the healthcare of patients with alopecia areata: a mixed-methods analysis using claims data and qualitative interview data

Objectives
Alopecia areata (AA) is a chronic immune-related disease with non-scarring hair loss. Treatment may reduce disease activity but cannot cure. Even though AA can be very burdensome to patients, the German social act has categorised AA as a ‘lifestyle disease’ and treatment is not covered by statutory health insurances (SHI). We aimed to characterise the healthcare situation of patients with AA in Germany, including potential inequalities, and to derive recommendations for action.

Design
This mixed-methods study combined: (1) semistructured qualitative interviews with patients and dermatologists, analysed through qualitative content analysis and (2) claims data analyses of a large nationwide German SHI from 2016 to 2020. Both types of data were collected and analysed in parallel to enable integrated analysis. Consecutively, an expert panel derived recommendations for action.

Setting
Interviews were conducted online or via telephone.

Participants
Patients were recruited conveniently via a dermatological outpatient clinic, patient organisations and social media. Dermatologists were recruited from a nationwide network and the dermatological societies.

Primary and secondary outcome measures
Exploration of the healthcare situation of adult persons with AA in Germany, investigating potential barriers to adequate care and identifying potential inequalities of access to care.

Results
We interviewed 20 patients (mean age 40.7 years; 75.0% female) and 14 dermatologists (mean age 48.4 years, 50.0% female). SHI data included 4692 persons with AA in 2020 (prevalence 0.23%; mean age 55.8 years; 76.2% female). The lack of reimbursement was criticised by both patients and dermatologists. Though 57.5% of patients received at least one drug prescription, mostly topical therapies, access to approved systemic drugs was very low. Drugs were prescribed mostly by general practitioners (41.1%) and dermatologists (32.8%). Some patients were sceptical regarding the side effects of treatment and criticised exclusively symptomatic treatment. Patients reported an urge for information and exchange with others, as well as different ways of handling their disease, such as acceptance, and frustration or desperation. Patients living in urban areas received topical therapies more often than patients in rural areas. Furthermore, women were more likely to receive treatment than men. Recommendations for action include reimbursement of AA medication and developing a platform providing information on AA to physicians and patients.

Conclusions
The disease burden and frustration of patients with AA is high, mostly caused by limited treatment options and lack of reimbursement, limiting access to approved drugs such as Janus kinase inhibitors.
Through the mixed-methods design, we were able to combine patient experiences and quantitative data reflecting the reality of healthcare in Germany.

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Feasibility study protocol: implementing consultation-based high-quality palliative care services in intensive care units

Introduction
Critically ill patients in intensive care units (ICUs) receive life-sustaining treatments aimed at restoring or maintaining organ function. ICU admission often involves substantial multidimensional suffering that can burden patients, their families and surrogates. Multidisciplinary palliative care support can help alleviate their sufferings. In South Korea, however, palliative care has not yet been integrated into critical care settings, highlighting the need to explore the feasibility of its implementation within the ICU.

Methods and analysis
This study aims to test the feasibility of a consultation-based palliative care intervention in the ICU. The study will include 20 patients admitted to the ICU of a tertiary hospital due to sudden severe acute brain injury or progressive organ failure, along with their family caregivers. A palliative care team, comprising a social worker and a palliative care physician, will provide consultations to the ICU healthcare professionals based on the palliative care needs, following family counselling. Additional family meetings will be held if necessary. The primary outcomes will include participation rates, family counselling rates and study completion rates. The intervention’s potential impact will be assessed by changes in surrogate decision-making conflict, self-efficacy, depression and anxiety, post-decision regret and the experience of patient-centred and family-centred care. The demand and acceptability of the intervention will be assessed through semi-structured interviews with family surrogates, followed by qualitative analysis.

Ethics and dissemination
This study will be conducted in accordance with the Declaration of Helsinki and applicable national laws and regulations. The clinical study protocol, along with any protocol amendments and the informed consent form, has been approved by the Institutional Review Board of the Hospital (2404-111-1532). We plan to submit the study results for presentation at conferences and for publication in international peer-reviewed journals. Data will also be made available on request to participants, funding agencies and interested researchers.

Trial registration number
NCT06490835.

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The CHILL BONES (combining high-intensity impact loading and lifting with mind-body exercise for optimisation of nervous system and skeletal health) trial: protocol for a parallel-group, semi-randomised controlled trial

Introduction
Animal studies suggest that elevated sympathetic nervous system (SNS) activity can accelerate bone loss. However, this area has not been well researched in humans. High-intensity Resistance and Impact Training (HiRIT) is recognised as an effective treatment for osteoporosis and osteopenia. Alternate forms of exercise such as mind-body exercise may be used to modulate sympathetic activity, which could have an additive benefit for skeletal adaptation when used in conjunction with HiRIT. The aim of this study is to investigate whether the combination of mind-body exercise (Tai Chi) and HiRIT can be used to concurrently modulate SNS activity and improve skeletal health.

Methods and analysis
The CHILL BONES trial is a semi-randomised controlled trial where consenting adults over 60 years, who have low bone mass (total hip, femoral neck and/or lumbar spine T-score

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Community burden of acute respiratory infections in Shanghai, a longitudinal cohort study in respiratory pathogens, China, 2024-2027

Purpose
We are conducting a longitudinal cohort study—the Community Burden of Acute Respiratory Infections in Shanghai—to assess age-stratified incidence, healthcare utilisation and risk factors of influenza virus, respiratory syncytial virus (RSV) and SARS-CoV-2 associated acute respiratory infections (ARIs) in Shanghai, China.

Participants
Study participants were enrolled by family doctors in all 47 community health services centres in Pudong New Area District, Shanghai, China. All permanent residents 6 months and older living in Pudong for at least 6 months were eligible for enrolment; residents who planned to leave Pudong for more than 1 month in the first study year were excluded. During enrolment, study staff conducted baseline assessments of sociodemographics, underlying medical conditions, vaccination history and household and self-rated health status. Study participants are being followed for ARIs for 3 years. Nasopharyngeal and oropharyngeal swab specimens are being obtained from suspected ARI cases. Influenza virus, RSV, SARS-CoV-2 and other respiratory pathogens are tested for by multiplex respiratory pathogen real-time quantitative PCR assays. Illness courses and clinical recoveries of ARI cases are assessed through weekly contact with ARI cases for 28 days post ascertainment.

Findings to date
Between 14 October 2024 and 22 November 2024, we enrolled 5387 community residents into the cohort, including 233 children aged from 6 months to 2 years, 278 preschool children aged 3–6 years, 575 school-age children aged 7–18 years, 2150 adults aged 19–64 years and 2151 older adults aged 65+years. All finished baseline assessment and started follow-up. Surveillance of ARI symptoms, collection of specimens and laboratory testing are ongoing.

Future plans
Findings from this study will be used to provide valuable scientific data to inform ongoing control efforts and future pandemic preparedness for respiratory diseases in China. Planned analyses include analysis of annual pathogen-specific incidence by age group and exploration of healthcare seeking behaviour and factors associated with ARIs and severe ARIs. We will also assess transmission dynamics of common respiratory pathogens in a household transmission subcohort.

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Interventional arterial chemotherapy versus sorafenib for advanced hepatocellular carcinoma in China: a health economic evaluation of open-label, randomised, phase 3 study

Objectives
This post hoc study aimed to evaluate the cost-effectiveness of hepatic artery infusion chemotherapy (HAIC) with fluorouracil, leucovorin and oxaliplatin (HAIC-FO) compared with sorafenib in patients with advanced hepatocellular carcinoma (HCC). The analysis was conducted from the perspective of Chinese payers.

Design
A cost-effectiveness analysis was performed using a Markov model derived from data obtained in the FOHAIC-1 trial (phase 3 randomised controlled trial; conducted 2017–2020).

Setting
The study was conducted in tertiary care centres in China.

Participants
The study included advanced HCC patients enrolled in the FOHAIC-1 trial. Inclusion criteria followed the trial protocols, with patients stratified by disease severity (including the presence of Vp4 portal vein tumour thrombus (PVTT) and high tumour burden).

Interventions
HAIC-FO (fluorouracil, leucovorin and oxaliplatin) was compared with sorafenib for cost and health outcomes.

Primary outcome measure
The primary outcome was the incremental cost-effectiveness ratio (ICER), calculated as the additional cost per quality-adjusted life year (QALY) gained.

Results
Sorafenib yielded 0.66 QALYs at a cost of $15 011.73, whereas HAIC-FO yielded 1.00 QALY at a cost of $18 470.98. The ICER of HAIC-FO compared with sorafenib was $10 235.56 per QALY, which was below the willingness-to-pay (WTP) threshold of $30 492.00 per QALY. Sensitivity analyses confirmed that HAIC-FO remained cost-effective across variable assumptions, with probabilistic sensitivity analysis showing a 99.9% probability of cost-effectiveness at the WTP threshold. Subgroup analyses demonstrated more favourable ICERs for patients with Vp4 PVTT ($7003.33 per QALY) and those with high tumour burden ($7382.86 per QALY).

Conclusions
HAIC-FO is a more cost-effective treatment for advanced HCC than sorafenib from the Chinese payer’s perspective, particularly in patients with Vp4 PVTT and/or high tumour burden. Further research is needed to explore long-term economic implications and real-world effectiveness data.

Trial registration number
NCT03164382.

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Efficacy and acceptability of different blood flow restriction training interventions during the rehabilitation of military personnel with lower limb musculoskeletal injuries: protocol for a two-phase randomised controlled trial

Background
Musculoskeletal injury (MSKI) is the leading cause of medical downgrading and discharge within the UK military, with lower limb MSKI having the greatest incidence, negatively impacting operational readiness. Pain is a primary limiting factor to rehabilitation progress following MSKI. Heavy-load resistance training (RT; ie, loads >70% 1-repetition maximum) is traditionally used but may be contraindicated due to pain, potentially prolonging recovery and leading to failure of essential physical employment standards for UK military personnel. Low-load RT with blood flow restriction (BFR) can promote favourable morphological and physiological adaption, as well as elicit hypoalgesia in healthy and clinical populations (eg, post-operative), and has proven a viable option in military rehabilitation settings. The acceptability and tolerance of higher relative BFR pressures in persistent pain populations are unknown due to the complexity of presentation and the perception of discomfort experienced during BFR exercise. Greater relative pressures (ie, 80% limb occlusion pressure (LOP)) elicit a greater hypoalgesic response in pain-free individuals, but greater perceived discomfort which may not be tolerated in persistent pain populations. However, lower relative pressure (ie, 40% LOP) has elicited hypoalgesia in pain-free individuals, which therefore may be more clinically acceptable and tolerated in persistent pain populations. The primary aim of both randomised controlled trials (RCT) is to investigate the efficacy and acceptability of using high-frequency, low-load BFR-RT in UK military personnel with lower limb MSKI where persistent pain is the primary limiting factor for progression.

Methodology
The presented protocol is a two-phase RCT based within a military rehabilitation setting. Phase One is a 1-week RCT to determine the most efficacious and acceptable BFR-RT protocol (7x BFR-RT sessions over 5 days at 40% or 80% LOP; n=28). Phase Two is a 3-week RCT comparing the most clinically acceptable BFR pressure, determined by Phase One (21x BFR-RT sessions over 15 days; n=26) to usual care within UK Defence Rehabilitation residential rehabilitation practices. Outcomes will be recorded at baseline, daily and following completion of the intervention. The primary outcome will be the brief pain inventory. Secondary outcomes include blood biomarkers for inflammation and pain (Phase Two only), injury-specific outcome measures, lower extremity function scale, objective measures of muscle strength and neuromuscular performance, and pressure pain threshold testing.

Ethics and dissemination
The study is approved by the Ministry of Defence Research Ethics Committee (2318/MODREC/24) and Northumbria University. All study findings will be published in scientific peer-reviewed journals and presented at relevant scientific conferences.

Trial registration number
Registered with Clinical Trials. The registration numbers are as follows: NCT06621914 (Phase One) and NCT06621953 (Phase Two).

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'Shared efforts, brighter smiles: a protocol for a randomised controlled study on the effectiveness of a parent-child orofacial myofunctional therapy programme post-adenoidectomy

Introduction
Adenoid hypertrophy has a high prevalence in children, often causing early orofacial muscle dysfunction that worsens facial deformities over time. While adenoidectomy (AT) alleviates airway obstruction, it only partially addresses the condition, leaving persistent neuromuscular habits. Orofacial myofunctional therapy is necessary for post-AT recovery but faces challenges such as poor adherence and ineffective parent-child communication. Dyadic interventions, which actively involve both parents and children, have shown advantages in improving treatment adherence and enhancing orofacial muscle function. Evidence suggests that dyadic intervention addresses both the child’s recovery needs and the caregiving capacity of parents, offering a more comprehensive solution for long-term intervention. Therefore, our team developed a parent-child dyadic orofacial myofunctional therapy (PCD-OMT) programme, offering insights into its potential application in paediatric healthcare to support comprehensive family-centred care.

Method and analysis
This two-arm, parallel-design, randomised controlled trial will recruit 80 dyads whose children performed AT from two hospitals in Qingdao, China. Dyads will be randomly allocated to two arms. Dyads randomly assigned to the intervention group will receive the PCD-OMT programme. Dyads randomly assigned to the control group will receive regular care. The primary outcomes are orofacial myofunction in children and parental care abilities. The secondary outcomes are children’s engagement and parental functioning. A feasibility and acceptability process will be employed to evaluate the viability in clinical practice. Outcomes will be collected at three checkpoints: baseline (T0), postintervention (T1) and after a 12-week follow-up phase (T2).

Ethics and dissemination
This study was approved by the Ethics Committee of Medical College of Qingdao University (QDU-HEC-2023216). The results will be published in peer-reviewed publications and presented in international conferences.

Trial registration number
ChiCTR2400091466.

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