Acupuncture for substance use disorders: a protocol of systematic review and meta-analysis of randomised controlled trials

Introduction
Substance use disorders (SUDs) are common and highly disabling, causing serious long-term harm to people’s health. Despite the existence of evidence-based interventions for treating SUDs, many individuals remain symptomatic regardless of treatment, and relapse is common. Acupuncture has been examined for the treatment of SUDs, but available evidence is mixed. This comprehensive systematic review and meta-analysis aims to provide updated evidence which will include both English and Chinese studies to investigate the effectiveness and safety of different types of acupuncture for the treatment of alcohol, tobacco and illicit drug use disorders.

Methods and analysis
This protocol is guided by the Preferred Reporting Items for Systematic Reviews and Meta Analysis Protocols. A thorough search for relevant studies in multiple electronic databases (PubMed, Embase, PsycINFO, Cochrane Library, China National Knowledge Infrastructure, VIP, Wan-fang and China Biomedical Database) and clinical trial registries will be conducted. Population-Intervention-Comparator-Outcomes-Study design criteria will be adopted for study inclusion. Only randomised controlled trials analysing the efficacy and safety of acupuncture for SUDs will be included. Two reviewers will independently conduct the study selection, data extraction and quality assessment, and disagreements will be solved by a third senior reviewer or by contacting study authors. Frequency and quantity of substance use, abstinence rate, withdrawal symptoms, treatment drop-out and relapse rates are primary outcomes. Functional status, health-related quality of life and adverse events are secondary outcomes. The risk of bias and quality of evidence will be assessed by the revised Cochrane risk-of-bias tool for randomised trials and guidelines of the Grading of Recommendations Assessment, Development and Evaluation working group, respectively. When sufficient data is available, subgroup analyses will be performed to further compare the differences in the primary and secondary outcomes based on the type of substance use, acupuncture, co-intervention status, comparison group, measurement tools, length of follow-up, risk of bias of included studies and countries of studies conducted.

Ethics and dissemination
No private information is used in the entire process of the systematic review. Therefore, ethical approval is not required. Findings of the proposed systematic review will be published in a peer-reviewed journal and/or disseminated through conference presentations.

Protocol registration number
The protocol has been archived in the Prospero repository (PROSPERO 2024 CRD42024566389).

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Spiritual care for prevention of psychological disorders in critically ill patients: study protocol of a feasibility randomised controlled pilot trial

Introduction
A significant number of critically ill patients who survive their illness will experience new sequelae or a worsening of their baseline health status following their discharge from the hospital. These consequences may be physical, cognitive and/or psychological and have been labelled postintensive care syndrome (PICS). Prior research has demonstrated that spiritual care aligned with a specific creed during hospitalisation in the intensive care unit (ICU), as part of a comprehensive care plan, may be an effective strategy for preventing psychological sequelae in surviving critically ill patients. However, there is a gap in clinical literature regarding the effectiveness of generalist spiritual care in preventing psychological sequelae associated with PICS. This pilot study aims to explore the feasibility of implementing a generalist spiritual care strategy in the ICU and to evaluate its preliminary effectiveness in preventing anxiety and depression symptoms and post-traumatic stress disorder in critically ill patients.

Methods and analysis
This is a single-site, feasibility randomised controlled pilot trial of a generalist spiritual care intervention compared with the current standard of care. A total of 30 adults who are critically ill and have undergone invasive mechanical ventilation for a minimum of 72 hours without alterations in consciousness will be randomly assigned to either the spiritual care group or the usual care group at a ratio of 1:1. The primary outcome will be the feasibility and acceptability of the spiritual care strategy in critically ill patients. Secondary aims include evaluating the differences in anxiety and depression symptoms and post-traumatic stress disorder between the spiritual care group and the usual care control group at 3 months after ICU discharge. Subjects will be followed up until 3 months post-ICU discharge.

Ethics and dissemination
The Ethics Committee for Medical Sciences of Pontificia Universidad Católica de Chile (#220111005) and the Ethics Committee of Servicio de Salud Metropolitano Sur Oriente approved the study. Pontificia Universidad Católica de Chile funded the study (project number 105699/DPCC2021). The findings will be widely disseminated through peer-reviewed publications, academic conferences, local community-based presentations, partner organisations and the Chilean Intensive Care Society.

Trial registration number
NCT06048783.

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Efficacy and safety of dynamic neuromuscular stabilisation in treating chronic non-specific low back pain: a systematic review and meta-analysis protocol

Introduction
Chronic non-specific low back pain (CNLBP) stands as a predominant factor contributing to disability worldwide. In the recent past, the sphere of medical research has witnessed a burgeoning interest in exploring the therapeutic potential of dynamic neuromuscular stabilisation (DNS) techniques for this condition. Despite the growing body of evidence, a comprehensive synthesis evaluating the effectiveness and safety of these interventions remains absent. This study, therefore, seeks to rigorously assess the therapeutic value and safety profile of DNS techniques in the management of CNLBP.

Methods and analysis
We will explicitly follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for conducting the systematic review. Our search strategy will encompass both English and Chinese databases, extending from their inception through March 2024. Specifically, we will explore the Web of Science, PubMed, Embase and the Cochrane Library for English literature, while for Chinese studies, we will delve into the Chinese National Knowledge Infrastructure, the Chinese Science and Technology Periodical Database (VIP), the Wan Fang Database and the China Biology Medicine disc. The outcome metrics we will assess include clinical efficacy, pain (assessed using the Visual Analogue Scale (VAS) and Numerical Pain Rating Scale (NPRS)) and functional disability (evaluated using the Oswestry Disability Index (ODI) and Roland-Morris Disability Questionnaire (RMDQ)) and the incidence of adverse reactions. Our focus will be on identifying randomised controlled trials that assess the efficacy of DNS training in the treatment of CNLBP. The data extracted from these trials will be synthesised through a comprehensive meta-analysis to elucidate the effectiveness of this intervention. When applying the Grading of Recommendations Assessment, Development and Evaluation framework to assess the included studies, we may encounter several challenges, for example, the variability in outcome measurements, the sample sizes of the included studies and the heterogeneity of the study populations. We will pay particular attention to these potential limitations to ensure the accuracy and reliability of the evaluation.

Ethical considerations and dissemination
Given that our research does not engage human or animal subjects nor does it handle any personal patient data, the requirement for ethical approval is bypassed. We aim to share the insights gleaned from this study through publication in reputable peer-reviewed journals and presentation at professional conferences, ensuring broad and impactful dissemination of our findings.

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Effects of Intensive Blood Pressure Lowering on Brain Swelling in Thrombolyzed Acute Ischemic Stroke: The ENCHANTED Results

Stroke, Ahead of Print. BACKGROUND:Cerebral swelling in relation to cytotoxic edema is a predictor of poor outcome in acute ischemic stroke (AIS) and elevated blood pressure (BP) promotes its development. Whether intensive BP-lowering treatment reduces cerebral swelling is uncertain. We aimed to determine whether intensive BP lowering reduces the severity of cerebral swelling after thrombolysis for AIS.METHODS:A secondary analysis of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study), a partial factorial, international, multicenter, open-label, blinded end point, randomized controlled trial of alteplase dose and levels of BP control in thrombolyzed patients with AIS. Participants were randomly assigned to intensive (systolic target 130–140 mm Hg within 1 hour; maintained for 72 hours) or guideline-recommended (systolic target

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Standalone Middle Meningeal Artery Embolization Versus Conservative Management for Nontraumatic Subdural Hematoma

Stroke, Ahead of Print. BACKGROUND:Recent randomized control trials have demonstrated the efficacy and safety of middle meningeal artery embolization (MMAE) as an adjunct to conventional management for patients with nonacute subdural hematoma (SDH); however, a large majority of trial participants received surgical evacuation as part of the standard of care. Thus, the efficacy and safety of standalone MMAE compared with conservative management (CM) for patients with nonsurgical SDH are unclear.METHODS:This was a retrospective cohort study of the 2019 to 2021 Nationwide Readmissions Database in the United States. Patients with nonsurgical nontraumatic SDH were identified, and MMAE patients were matched with similar CM patients using propensity score matching calculated from demographics, comorbidities, and initial hospitalization outcomes. Patients were followed up to 300 days. The primary end point was composite surgical rescue or death, and secondary end points included surgical rescue and all-cause mortality by 180 days.RESULTS:24 465 patients with nonsurgical nontraumatic SDH were identified; 2228 (9.1%) underwent MMAE. After propensity score matching, 6675 patients remained in the CM group and 2217 in the MMAE group. At 180 days, MMAE patients had a significantly lower risk of surgery or death compared with CM (8.2% versus 10.9%; relative risk, 0.75 [95% CI, 0.59–0.96];P=0.022) and lower risk of death (1.1% versus 3.0%; relative risk, 0.38 [95% CI, 0.17–0.86];P=0.020). Rates of surgical rescue among MMAE and CM patients at 180 days were similar (7.1% versus 8.4%; relative risk, 0.85 [95% CI, 0.63–1.14];P=0.27). Time-to-event analyses for the entire 300-day study follow-up period confirmed that while MMAE was associated with a lower cumulative risk of all-cause mortality (hazard ratio, 0.55 [95% CI, 0.35–0.87];P=0.010), it was not associated with a different risk of surgical rescue (hazard ratio, 1.00 [95% CI, 0.76–1.31];P=1.00).CONCLUSIONS:Standalone MMAE may be beneficial for patients with nonsurgical nontraumatic SDH by reducing the long-term risk of all-cause mortality.

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Teens and opioids postsurgery (TOPS): protocol for a prospective observational study describing associations between sleep deficiency and opioid use following outpatient surgery in adolescents

Introduction
The opioid crisis is a significant burden on adolescent public health in the USA. Medical use of prescription opioids is a pathway via which adolescents transition to opioid misuse, opioid use disorder and overdose. More than half of all opioids prescribed to adolescents are for pain management following surgery. Yet, little is known about the critical period following surgery during which adolescents initiate opioid misuse or the modifiable mechanisms (such as sleep deficiency) contributing to this process. This prospective observational study will broaden our knowledge by examining associations between sleep deficiency and opioid use and misuse following surgery. We will also examine behavioural, psychological, family and social factors linking sleep deficiency with opioid use and misuse.

Methods and analysis
Adolescents (10–19 years) undergoing outpatient orthopaedic surgery, along with one parent, will be recruited from two paediatric hospitals, for a sample of 400 dyads. Adolescents will be assessed at six timepoints. Before surgery, participants will undergo comprehensive multimodal sleep assessments (sleep surveys and actigraphy). Participants will also report on previous substance use, pain intensity and psychosocial, family and social factors. Adolescents will then be closely monitored over the first 14 days following surgery using ecological momentary assessment methods to capture real-time, naturalistic, daily data on sleep, opioid use, pain and psychological factors (including mood, affect and subjective response to opioid use). Opioid use (total number of doses and duration) will be measured with an innovative electronic medication monitoring device following surgery. Follow-up assessments at 3 months, 6 months, 12 months and 24 months will track the development of opioid misuse over time. Our primary outcomes include opioid use during the immediate 14 days following surgery and the presence of opioid misuse at 24 months after surgery. Multilevel mediation models will determine associations between predictor variables and acute postsurgical opioid use. We will apply modern machine learning algorithms to develop and validate models predicting adolescent prescription opioid misuse at 24 months from surgery.

Ethics and dissemination
This study was approved by Advarra’s Center for Institutional Review Board Intelligence (CIRBI) (Protocol 00072049), which serves as the single IRB of record for this multisite study.

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Wise or wide (WoW) study protocol: a national, multicentre, prospective, randomised and controlled, parallel group, non-inferiority study to compare single-staged versus two-staged excisions of thin invasive (<=1.0 mm) melanoma

Background
Sweden has one of the highest incidence rates of cutaneous melanoma globally, and the incidence is rapidly increasing. Melanoma mortality is linked to the thickness of the primary tumour, with thicker melanomas having a poorer prognosis. Thin invasive melanomas (≤1.0 mm Breslow thickness) have excellent prognosis. Traditionally, the surgical approach for melanoma involves a two-step procedure of a diagnostic excision followed by a wide local excision (WLE) with 10 mm clinical margins. The WLE aims to remove potential microsatellites and residual melanoma, which in theory would prevent loco-regional recurrence and could improve survival. However, recent research questions the necessity of WLE for thin invasive melanomas, given their favourable prognosis, minimal risk of microsatellitosis and low rates of residual melanoma found in WLE tissue specimens.

Methods and analysis
This multicentre, non-inferiority, randomised controlled trial seeks to enrol 2486 patients with thin invasive melanomas that are completely excised with ≥1.5 mm histopathological margins following the diagnostic excision. Patients will be randomly assigned to either a control group that will undergo a WLE with 10 mm clinical margins according to current clinical routine or an experimental group without a WLE. The primary and secondary endpoints are recurrence-free survival at 5 and 10 years, respectively, with tertiary aims including postoperative complications, scar quality, patient satisfaction and quality of life, healthcare resource utilisation as well as differences in biomarkers of recurrent and non-recurrent melanomas. Patients will be assessed at clinical follow-up visits at 3 months as well as at 1, 2, 3, 5 and 10 years.

Ethics and dissemination
Approval of this study was obtained from the Swedish Ethical Review Authority (2024-03274-01). The findings of the study will be presented at international scientific meetings and published in peer-reviewed academic journals.

Trial registration number
NCT06363591.

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Longitudinal analysis of proinflammatory and anti-inflammatory cytokines in the cerebrospinal fluid and peripheral blood of treatment-naïve first-episode psychosis patients, and their correlation with psychosis severity and cognitive impairment in sub-Saharan Africa

Background
Inflammation is indicated as one of the factors that play a role in the development of schizophrenia, with several studies having found considerable inconsistencies in their results. Few have investigated the role of inflammation in primary psychosis in blood and cerebrospinal fluids simultaneously, the aim of this study being to investigate the expression of blood and cerebrospinal fluid inflammatory cytokines in treatment-naive first-episode psychotic participants.

Methods and analysis
This is a combined cross-sectional and prospective observational study, which is currently taking place in Durban, South Africa, will recruit 60 participants (30 cases and 30 matched controls). The primary objective is to describe baseline CSF and longitudinal expression/levels of inflammatory cytokines in the blood in persons diagnosed with first-episode psychosis (FEP) for 12 months. The secondary objective is to describe the associations between inflammatory cytokines and psychosis severity, neurocognitive performance, antipsychotic response and metabolic changes at different time points (baseline, 3, 6 and 12 months).

Interventions
We will collect the sociodemographic details of all participants, and the Positive and Negative Symptoms Scale, Patient Health Questionnaire-9, Childhood Trauma Scale, Repeatable Battery for the Assessment of Neuropsychological Status Update, metabolic markers and inflammatory markers (venous blood and lumbar puncture cerebrospinal fluid) for those with FEP. Data from matched controls will only be collected at one point and no follow-ups (cross-sectional).

Ethics and dissemination
The study protocol has been approved by the University of KwaZulu-Natal Biomedical Research Ethics Committee (BREC/00004714/2022). The study is nested in an ongoing study titled the burden of HIV and Psychosis in an African setting: a longitudinal study of HIV-infected and non-infected patients with First-Episode Psychosis (BREC 571/18). The results will be actively disseminated through peer-reviewed journal publications and conference presentations.

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Patient Portals—Balancing Workload and Opportunity

Soon after the earliest email systems were developed in the late 1960s, electronic messages began to pile up. The onslaught of messages surprised early adopters and spurred the development of message management systems from which modern email applications descended. Sixty years later, health care email has arrived in earnest with the development of patient portal messaging systems. And despite the history, the recent growth of patient portal messaging has caught clinicians and health systems by surprise. As health care systems struggle to adapt, understanding the scale of portal messaging and its potential impacts on clinicians and patients is crucial for designing and implementing effective solutions.

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Complexity and Challenges of Measuring PrEP Adherence—Reply

In Reply On behalf of my coauthors, we appreciate the Letter by Garcia-Martinez and colleagues, which was written in response to our article published in JAMA Internal Medicine. Our study used pharmacy claims data to assess the degree to which patients of different physician specialties were more or less likely to pick up their initial HIV preexposure prophylaxis (PrEP) prescription across the US population.

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Counternarrative Poetry and Medicine

Physicians’ best medical advice for care does not always align with patients’ wishes. While many causes of this harmful and costly discordance are postulated, poor communication of shared goals tops many lists. In “Planning Our Escape,” poetry becomes a window into better understanding a patient’s refusal of treatment by offering a moving counternarrative to uncompromising medical advice. The speaker describes a friend with “thigh sarcoma” whose doctors “floated the idea of amputation,” after which he “floated up to visit” for a week spent outdoors instead. The implied clinical narrative of hospital confinement, surgery, and the resulting physical impairment is countered by the poem’s story of a lively friendship characterized by unfettered activity that clearly informs the “escape” of the poem’s title. That the speaker joins his friend in his escapist impulse, changing the friend’s habitual response to questions about his life from “planning my escape” to “planning our escape,” both shows respect for his friend’s autonomy and betrays a hint of his own contrarian wish to be free of medicine’s demands. Without ever explicitly endorsing his friend forgoing potentially lifesaving treatment, evident in the poem’s heart-wrenching conclusion is an openness to empathizing with him that could serve as a crucial basis for reconsideration. Poetry, in its capacity to embrace both the finality of the image of 2 friends searching for something lost (on another backpacking trip to Hiroshima, Japan) and the ironic hope of later sharing sake with “friends we made that night and never saw again,” beautifully engages the challenges of leaving against medical advice.

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Omission of axillary lymph node dissection in patients with breast cancer with axillary pathological complete response confirmed by stained region lymph node biopsy after neoadjuvant systemic therapy (SrLNB study): study protocol for a single-arm, single-centre, phase-II trial

Introduction
Given that axillary lymph node dissection (ALND) may not contribute to local control or survival and could lead to increased arm morbidity, axillary de-escalation procedures have replaced ALND in patients achieving axillary pathologic complete response (apCR) after neoadjuvant systemic therapy (NST). However, the application of targeted lymph node biopsy, one of the de-escalation procedures, remains limited due to a lack of long-term follow-up studies.

Methods and analysis
This prospective, single-arm, open-label, non-inferiority, single-centre phase II trial targets breast cancer patients initially diagnosed with axillary metastasis who achieved apCR after NST. The study aims to validate the oncological safety of stained region lymph node biopsy (SrLNB) procedure. SrLNB is a novel de-escalation axillary surgery, which was developed and tested in our preliminary study. The primary endpoint of this trial is the 3-year invasive disease-free survival (iDFS). Secondary endpoints include local-regional recurrence, incidence of breast cancer-related lymphoedema and patient-reported outcomes. The 3-year iDFS in patients undergoing ALND is expected to be approximately 90%, with a non-inferiority margin of 10%, a significance level of 0.05, power of 0.8 and a loss-to-follow-up rate of 10%. The planned enrolment is 92 patients. The trial was initiated on 11 September 2023, with the first patient enrolled on 25 September 2023, and is scheduled to end in 2026.

Ethics and dissemination
The trial protocol received approval from the Human Research Ethics Committee of The First Affiliated Hospital with Nanjing Medical University in May 2023 (No. 2023-SR-169). All participants will provide informed consent. The study results will be disseminated through international peer-reviewed scientific journals, presentations at international scientific conferences and public lectures.

Trial registration number
NCT05939830.

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Persistent Tissue-Level Hypoperfusion (No-Reflow) Negates the Clinical Benefit of Successful Thrombectomy

Stroke, Ahead of Print. BACKGROUND:Tissue-level hypoperfusion (no-reflow) persists in 30% of patients with seemingly successful upstream angiographic recanalization at thrombectomy. We investigated the clinical impact of the no-reflow phenomenon by comparing patients with no-reflow versus patients with varying degrees of angiographic recanalization.METHODS:In a post hoc pooled analysis of the EXTEND-IA (Endovascular Therapy for Ischemic Stroke With Perfusion-Imaging Selection) and EXTEND-IA TNK (Tenecteplase Versus Alteplase Before Thrombectomy for Ischemic Stroke) part 1 and 2 trials, clinical and radiological outcomes were compared between patients with (1) full angiographic recanalization with no-reflow (expanded Treatment in Cerebral Ischemia [eTICI] 2c3–NoReflow), defined as >15% reduction in relative cerebral blood flow or Volume within the infarct relative to a contralateral homolog on 24-hour-follow-up perfusion computed tomography or magnetic resonance imaging despite eTICI grade 2c-3 angiographic recanalization, (2) full angiographic recanalization and tissue reperfusion (eTICI 2c3–CompleteFlow), (3) partial angiographic recanalization (eTICI 2b), and (4) unsuccessful thrombectomy (eTICI 0-2a). The primary outcome, functional independence at 90 days, was investigated using a mixed effect logistic regression model, both unadjusted and adjusted for a priori-selected covariates, namely age, premorbid modified Rankin Scale, baseline National Institutes of Health Stroke Scale, and baseline core volume.RESULTS:Among 537 patients from the overall pooled cohort, 456 patients were included in the analysis. The mean age of the included patients was 71 years old, and 54% were male. A favorable outcome (90-day modified Rankin Scale score of 0–2 or return to baseline modified Rankin Scale) was observed in 43.33% (n=13/30) of patients with eTICI 2c3–NoReflow, 67.50% (n=81/120) of eTICI 2c3–CompleteFlow, 63.03% (n=150/238) of eTICI 2b, and 50.00% (n=34/68) of unsuccessful thrombectomy. In multivariable analysis, patients with eTICI 2c3–NoReflow had lower odds of favorable outcome compared with those with eTICI 2c3–CompleteFlow (adjusted odds ratio, 0.31 [95% CI, 0.12–0.77];P=0.01) and eTICI 2b (adjusted odds ratio, 0.40 [95% CI, 0.17–0.96];P=0.04) but not unsuccessful thrombectomy (adjusted odds ratio, 1.02 [95% CI, 0.38–2.73];P=0.97). Patients with eTICI 2c3–NoReflow had similar follow-up infarct volume to unsuccessful thrombectomy (β=−8.26 [95% CI, −27.38 to 10.86];P=0.40) and eTICI 2b (β=9.38 [95% CI, −7.33 to 26.09];P=0.27) but had larger infarcts compared with eTICI 2c3–CompleteFlow (β=18.85 [95% CI, 1.16–36.54];P=0.04).CONCLUSIONS:When no-reflow occurred, clinical and radiological outcomes in patients with full angiographic recanalization were similar to patients with unsuccessful thrombectomy. Preventing or reversing no-reflow has the potential to augment the clinical benefit of reperfusion treatment in ischemic stroke.

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