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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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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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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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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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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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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'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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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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Intravenous Lidocaine for Gut Function Recovery

To the Editor Dr Paterson and colleagues conducted a randomized clinical trial to evaluate the effect of perioperative IV lidocaine on return of gut function after elective minimally invasive colon resection. I was surprised by the lack of discussion regarding the observed difference in postoperative opioid consumption between the lidocaine and placebo groups and its potential impact on the study’s findings.

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An adaptive multiarm randomised trial of biomedical and psychosocial interventions to improve convalescence following severe acute malnutrition in sub-Saharan Africa: Co-SAM trial protocol

Introduction
Children discharged from hospital following management of complicated severe acute malnutrition (SAM) have a high risk of mortality, readmission and failed nutritional recovery. Current management approaches fail to sufficiently promote convalescence after inpatient nutritional rehabilitation. Novel interventions during the post-discharge period could enhance convalescence to help children survive and thrive.

Methods and analysis
The Co-SAM trial is an adaptive, multicountry, phase III, individually randomised clinical trial, based on the principles that (i) interacting biological and social factors drive multimorbidity in children with SAM, and (ii) both medical and psychosocial interventions may therefore ameliorate underlying causal pathways to reduce morbidity and mortality and improve recovery. Children aged 6–59 months with complicated SAM, who have stabilised and started the transition to ready-to-use therapeutic food (RUTF), will be enrolled and randomised to one of five trial arms (standard-of-care alone; antimicrobials; reformulated RUTF; psychosocial support; or a combination of all strategies). Standard-of-care, which is provided in all trial arms, includes RUTF until nutritional recovery (defined as weight-for-height Z-score >–2, mid-upper arm circumference >12.5 cm and oedema-free since the last study visit), and other management recommended in WHO guidelines. The 12-week antimicrobial package provides daily co-formulated rifampicin and isoniazid (with pyridoxine) and 3 days of azithromycin monthly. The reformulated RUTF, which incorporates medium-chain triglycerides and hydrolysed protein to increase nutrient bioavailability and reduce metabolic stress, is provided at the same dose and duration as standard RUTF. The 12-week psychosocial package includes caregiver problem-solving therapy, educational modules, peer support groups and child play. The combined arm includes all interventions. Children start their intervention package prior to hospital discharge, with follow-up data collection in study clinics at 2, 4, 6, 8, 12 and 24 weeks. The primary composite outcome is death, hospitalisation or failed nutritional recovery within 24 weeks post-randomisation. An interim analysis will allow unpromising arms to be dropped, while the final analysis will be conducted when 1266 children have completed the study. Embedded process evaluation and laboratory substudies will explore the mechanisms of action of the interventions.

Ethics and dissemination
The trial has been approved by ethics committees in Zimbabwe, Zambia, Kenya and UK. Dissemination will be via community advisory boards in each country; Ministries of Health; and dialogue with policymakers including UNICEF.

Trial registration number
Clinicaltrials.gov: NCT05994742; Pan African Clinical Trials Registry: PACTR202311478928378.

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Cost-effectiveness of massed versus spaced trauma-focused treatment as first-line treatment for post-traumatic stress disorder in adults with multiple trauma exposure: protocol for a single-blind non-inferiority randomised controlled trial

Introduction
Post-traumatic stress disorder (PTSD) is a serious disorder that burdens individuals and society. The current standard of first-line treatment for PTSD is spaced trauma-focused treatment (S-TFT), involving weekly sessions. While effective, S-TFT may take relatively long to complete, especially in patients exposed to multiple potentially traumatic events (PTEs). Massed trauma-focused treatment (M-TFT), involving increased session frequency, potentially results in faster symptom reduction and restoration of quality of life, as well as in a reduction of societal costs. However, M-TFT is not recommended as first-line treatment. This paper describes the research protocol of a single-blind, multicentre randomised controlled trial (RCT) aimed at investigating: (1) the clinical and cost-effectiveness of M-TFT versus S-TFT in employed, multiply traumatised patients who seek first-line treatment for PTSD and (2) predictive and moderating factors related to treatment response.

Methods and analysis
186 participants are recruited from five centres and will be included if they are ≥18 years old, meet criteria for a Diagnostic and Statistical Manual of Mental Disorders Fifth Edition PTSD diagnosis based on ≥two PTEs, seek treatment for the first time and are employed. Patients with specified comorbid disorders and insufficient Dutch language proficiency are excluded. Participants are randomised to 800 min of either M-TFT or S-TFT. M-TFT consists of two once-weekly preparatory sessions, 10 twice-daily sessions of prolonged exposure, eye movement desensitisation and reprocessing therapy for 2 weeks and two once-weekly closing sessions. S-TFT consists of weekly sessions of one of five evidence-based treatment interventions. Outcomes are assessed at baseline and at 7 weeks, 17 weeks, 6 months and 9 months after baseline. Primary outcomes are clinical effectiveness in terms of PTSD symptom severity and cost-effectiveness based on quality of life measures and societal costs. Data will be analysed with linear mixed models.

Ethics and dissemination
This study protocol was approved by the Medical Ethics Review Board of the Amsterdam University Medical Center (NL86057.018.24). Participants will provide informed consent before enrolment in the trial. Results will be published in peer-reviewed journals and will be released to clinicians, patient groups and the general community.

Trial registration number
This protocol is registered at Overview of Medical Research in the Netherlands (OMON; trial register number 56960) and ClinicalTrials.gov (NCT06700590).

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Preventive Effects of Prasugrel on Cerebrovascular Events Following Percutaneous Coronary Intervention

Stroke, Ahead of Print. BACKGROUND:Dual antiplatelet drug administration is recommended after percutaneous coronary intervention (PCI) stent placement. Although prasugrel, a newer P2Y12 inhibitor, reportedly suppresses cardiovascular events more effectively than the traditional agent clopidogrel, its preventive effects on cerebrovascular disorders remain a topic of ongoing debate. This study aimed to examine the cerebrovascular efficacy and safety of post-PCI prasugrel and clopidogrel using extensive real-world data in Japan.METHODS:Using the CLIDAS (Clinical Deep Data Accumulation System) database, 7412 post-PCI patients who received dual antiplatelet therapy between April 2013 and March 2019 were identified. The primary end point was defined as the incidence of any stroke, while secondary end points included individual ischemic and hemorrhagic cerebrovascular events. The incidence of cerebrovascular events was compared between the prasugrel (2.5–3.75 mg daily; n=2219) and clopidogrel (75 mg daily; n=5193) groups using propensity-score inverse probability of treatment weighting and Fine and Gray models to account for competing risks.RESULTS:Within 1 year after PCI, the prasugrel group had a significantly lower incidence of cerebrovascular events (subdistribution hazard ratio, 0.46 [95% CI, 0.24–0.91];P=0.027) than the clopidogrel group. The subgroup analyses did not show significant differences in the incidence of ischemic (subdistribution hazard ratio, 0.54 [95% CI, 0.25–1.14];P=0.11) and hemorrhagic cerebrovascular events (subdistribution hazard ratio, 0.30 [95% CI, 0.084–1.10];P=0.070) between the use of prasugrel and clopidogrel. One-year health care costs between patients treated with prasugrel and those treated with clopidogrel showed no significant differences.CONCLUSIONS:Our data suggest that post-PCI prasugrel use was associated with lower cerebrovascular events compared with the use of clopidogrel in combination with aspirin. Further research is necessary to substantiate the potential of prasugrel in lowering cerebrovascular risks after post-PCI while upholding a satisfactory safety profile.

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