JAMA Internal Medicine

Mission Statement: To advance the equitable, person-centered, and evidence-based practice of internal medicine through publication of scientifically rigorous, innovative, and inclusive research, review, and commentary that informs dialogue and action with clinical, public health, and policy impact.

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Ventilation strategies used during anaesthesia for electroconvulsive therapy: scoping review protocol

Background
Electroconvulsive therapy (ECT) is an established treatment for depression and mania, with its therapeutic effect deriving from the induced seizure rather than the electrical stimulus itself. Anaesthetic agents are routinely used to reduce procedural discomfort, requiring assisted ventilation. However, these agents may raise the seizure threshold, necessitating higher stimulus doses and potentially increasing adverse effects. Although various strategies have been explored, pre-ECT hyperventilation—despite its known ability to lower the seizure threshold—remains insufficiently investigated. This review aims to examine the various ventilation approaches employed during anaesthesia for ECT, assess how hyperventilation has been applied to augment ECT, explore their impact on clinical outcomes and identify the outcome parameters most frequently investigated in ECT studies.

Methods
The reporting of the scoping review will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. A comprehensive literature search will be conducted in Medline, EMBASE, Scopus and PsycINFO. Grey literature, along with national and international guidelines, will also be included. Studies investigating any form of ventilation during anaesthesia for ECT will be included. An information specialist and a medical librarian will support the development and refinement of the search strategy. Two reviewers will independently screen eligible studies and perform data extraction according to predefined headings. Disagreements will be resolved by a third reviewer. Data will be organised under the following headings: details of the included studies, ventilation strategies investigated, outcome measures studied. Results will be presented narratively and in table form and discussed in relation to the relevant literature.

Ethics and dissemination
Ethical approval is not necessary, as the review synthesises evidence from the existing literature. The results will be disseminated through publication in a peer-reviewed journal and presentation at relevant academic conferences. Findings will also be shared with ECT clinicians to support clinical awareness and inform practice.

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Dextrans as anticoagulants and antiplatelet agents: protocol for a scoping review

Introduction
Haemostasis, a process involving platelet activation, platelet aggregation and coagulation, poses intricate clinical challenges for clinicians. There remains significant national variability in thromboprophylaxis protocols, which are used in 77–82% of surgical cases in Australia. There is also increasing concern focused on the development of antiplatelet resistance. Given an apparent lack of standardised approaches to haemostasis, these decisions frequently require clinician discretion and can result in suboptimal outcomes. To optimise patient management, all available therapeutic agents should be considered. Current standards may need to be revised accordingly.
Dextrans are polysaccharides with perioperative significance in haemostasis. Although the proposed mechanisms of dextran action are multifactorial, these agents may have a significant impact in cases of trauma, reconstructive surgery, transplantation and vascular surgery. However, a suspected deficit in the quality of the literature, and therefore clinical standardisation, raises concerns for optimal incorporation into practice.
Accordingly, we plan to examine both peer-reviewed articles and ‘grey’ literature that considers the indications, efficacy and complications associated with the clinical use of dextrans to promote haemostasis. The primary objective of this scoping review will be to analyse and map the existing literature on the use of dextrans in both operative and non-operative settings and provide insight that will bridge the current knowledge gap and guide future research initiatives.

Methods and analysis
The study and literature search will be performed in accordance with recommendations adapted for scoping reviews in alignment with Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews standards. A thorough and systematic investigation will be undertaken across several electronic databases, including EMBASE, the Cochrane Library and MEDLINE; additional studies will be accessed and examined by reference tracking. All relevant research published before 11 March 2024 will be reviewed for appropriateness of inclusion. Two researchers will perform data screening and extraction of relevant information. Study observations will be presented in a descriptive manner using a mixed methods and narrative approach.

Ethics and dissemination
Ethics approval was not required for this study. The results will be disseminated through publication in open-access peer-reviewed journals, established professional networks and conference presentations.

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Comparative efficacy and acceptability of nonpharmacological interventions for sleep disturbance among pregnant women: protocol for a systematic review and network meta-analysis

Introduction
Sleep disturbance is prevalent in pregnancy and can result in significant adverse outcomes for women and their infants. Numerous clinical trials of various nonpharmacotherapies for preventing or treating sleep disturbances have been conducted previously; however, previous systematic reviews with direct comparisons have failed to demonstrate the best options for different kinds of treatments. This systematic review and network meta-analysis (NMA) aims to explore the comparative efficacy and acceptability of nonpharmacological interventions for sleep disturbances in pregnancy and to assist clinical decision-making through ranking interventions concerning critical clinical outcomes.

Methods and analysis
We will follow the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. Two reviewers will systematically search five major bibliographic databases (PubMed, Embase, Cochrane Library, Web of Science and Cumulative Index to Nursing and Allied Health Literature) and registries for published and unpublished randomised controlled trials (RCTs) of any nonpharmacological interventions for sleep disturbances from inception to 24 June 2025. To ensure the search is up to date, we will also perform an updated search up to the time of final analysis submission. Primary outcomes will consider efficacy (the overall mean change of any predefined sleep disturbances, including sleep quality, sleep duration and sleep-specific symptoms) and acceptability (all-cause discontinuation). The risk of bias of each included RCT will be assessed using the Cochrane Risk of Bias 2.0 Tool (RoB2). Traditional pairwise meta-analyses and NMAs will be performed to compare the efficacy and acceptability of different nonpharmacological interventions. Surface under the cumulative ranking curve for the outcomes of interest will be used to rank the competing interventions. The Grading of Recommendations, Assessment, Development and Evaluation system will be used to assess the quality of evidence associated with the main results.

Ethics and dissemination
This review is a secondary analysis of published data and, therefore, does not require ethical approval. The results will be disseminated in a peer-reviewed journal.

PROSPERO registration number
CRD42024546340.

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Assessing symptom improvement in patients with postural orthostatic tachycardia syndrome (POTS) following a 16-week structured exercise programme: a protocol for a randomised cross-over trial in a clinical outpatient setting

Introduction
Exercise training is recommended as a complementary treatment in postural orthostatic tachycardia syndrome (POTS) according to international guidelines. However, less is known regarding how exercise training could successfully be implemented in clinical practice in patients with POTS. Thus, in the current study, we aim to assess the effect of a 16-week tailored exercise training programme in POTS.

Methods and analysis
A total of 200 patients diagnosed with POTS will be recruited. The study will be conducted as a randomised cross-over study. POTS symptoms will be evaluated using the Malmö POTS Symptom Score, Orthostatic Hypotension Questionnaire and 36-item Short Form Health Survey. Haemodynamic parameters will be evaluated by orthostatic tests and maximum working capacity evaluated by bicycle exercise test. Symptoms, haemodynamic parameters and exercise capacity will be assessed before and after a 16-week training programme.

Ethics and dissemination
The study was approved by the Swedish ethical review authority (2022-03186-01) and all procedures will be performed in accordance with the Helsinki Declaration. Results will be made available to patients with POTS, healthcare professionals, the funders and other researchers in publicly available (open access) medical journals.

Trial registration details
NCT05554107, registered on 26 September 2022.

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Impact of employment support in different work environments on individuals with intellectual disability and their families from their own perspectives: protocol for a systematic review of qualitative evidence

Introduction
People with intellectual disability experience lower levels of employment than those with other disabilities and those without disability, and typically require support services to access and maintain employment. Reviews on employment support often focus on the perspectives of providers and employers, meaning that, thus far, the perspectives of people with intellectual disability and their family members have not been collated and synthesised. This review will address this evidence gap.

Methods and analysis
Six databases (CINAHL, EconLit, EMBASE, Medline Complete, PsychINFO, Web of Science) will be comprehensively searched for the last 20 years to identify English-language, peer-reviewed publications including primary qualitative data. Search results will be independently screened by three reviewers (CP, NM, SF). Backwards and forwards citation tracing will be used to identify any additional literature not found by the searches. A narrative summary of the included studies will be provided. Study characteristics such as research focus, design, setting and findings will be independently extracted by one reviewer, checked by a second. Methodological quality will be independently evaluated by two reviewers using the Critical Appraisal Skills Programme Qualitative Studies Checklist. Findings from the studies will be collated using thematic synthesis and a realist approach. Any disagreement during the review process will be resolved by a third reviewer.

Ethics and dissemination
Ethics approval is not required to conduct the planned systematic review of peer-reviewed, published articles because the research does not involve human participants. Findings will be published in a peer-reviewed journal, presented at leading disability conferences and disseminated via website postings and social media channels.

PROSPERO registration number
CRD42024615393.

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Protocol for a multicentre, open-label, dose-escalation phase I/II study evaluating the tolerability, safety, efficacy and pharmacokinetics of repeated continuous intravenous PPMX-T003 in patients with aggressive natural killer cell leukaemia

Introduction
Aggressive natural killer cell leukaemia (ANKL) is a rare form of NK cell lymphoma with a very low incidence and poor prognosis. While multi-agent chemotherapy including L-asparaginase has been used to treat ANKL patients, they often cannot receive adequate chemotherapy at diagnosis due to liver dysfunction. PPMX-T003, a fully human monoclonal antibody targeting the transferrin receptor 1, shows promise in treating ANKL by helping patients recover from fulminant clinical conditions, potentially enabling a transition to chemotherapy. This study aimed to evaluate the tolerability, safety, efficacy, and pharmacokinetics of repeated continuous intravenous PPMX-T003 in patients with ANKL.

Methods and analysis
This multicentre, open-label, dose-escalation phase I/II study will be conducted at nine hospitals in Japan. Patients diagnosed with ANKL (whether as a primary or recurrent disease) and exhibiting abnormal liver function or hepatomegaly due to the primary disease will be included. The primary endpoint is the tolerability and safety of repeated continuous intravenous administration of PPMX-T003 in the first course, based on adverse events and dose-limiting toxicities. PPMX-T003 will be administered as a continuous intravenous infusion every 24 hours for five consecutive days, followed by a 2-day break. Pretreatment will be provided to minimise the risk of infusion-related reactions. Initial doses of PPMX-T003 will be 0.5, 1.0 or 2.0 mg/kg, with subsequent dose increases determined by the Data and Safety Monitoring Committee. The sample size is set at seven participants, with enrolment increased to up to 12 participants if dose-limiting toxicities occur, based on feasibility due to the rarity of ANKL. Descriptive statistics will summarise data according to initial dose, and pharmacokinetic analysis will be conducted based on administered dose.

Ethics and dissemination
This study was approved by the institutional review boards at participating hospitals. The results will be disseminated in peer-reviewed journals.

Trial registration number
jRCT2061230008 (jRCT); NCT05863234 (ClinicalTrials.gov).

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Identifying and reporting modifications to surgical innovation: a systematic review of IDEAL/IDEAL-D studies

Objectives
The Idea, Development, Evaluation, Assessment and Long-term follow-up (IDEAL) framework was designed to improve the quality of surgical research and evaluation of surgical innovation. It has become a widely cited tool for evaluating innovative devices and procedures, yet challenges remain concerning the definition and reporting of incremental innovative modifications, hindering evolution and evaluation of innovations and potentially risking patient safety. This systematic review examined IDEAL studies to identify such modifications and establish recent practices around modification reporting to inform the development of future guidance to facilitate safe, transparent and efficient surgical innovation.

Design
Systematic review and thematic synthesis of studies reporting surgical innovation.

Data sources
Web of Science and Scopus were searched in July 2023 using citation tools to identify studies following the IDEAL framework (citing any of 13 key IDEAL/IDEAL framework publications and guideline papers).

Eligibility criteria
Primary research studies of any design that involved invasive innovative devices or procedures.

Data extraction and synthesis
Study characteristics and verbatim text for all reported modifications, including contextual information, were extracted. Data were analysed and synthesised using thematic synthesis.

Results
Of 1071 records screened, 104 studies published between 2011–2023 were included (n=87 (83.6%) study reports; n=17 (16.3%) protocols). 425 modifications were reported in 76 (73.1%) studies, including modifications to procedures (n=283, 66.6%), devices (n=94, 22.1%) and patient selection (n=48, 11.3%). Procedure/device modifications included technical, non-technical and cessation (conversion to other procedures or abandonment). Modifications were most often reported within IDEAL stage 2a (n=30/44, 68.2%), whereas there was considerable variation across other stages, such as stage 0 (n=2/3, 66%) and stage 2b (n=4/12, 33.3%).

Conclusion
Reporting modifications is imperative for evaluating surgical innovation. However, this review found inconsistent approaches to reporting and describing modifications. Findings will inform the development of a checklist for reporting modifications that aims to complement the IDEAL framework and further promote shared learning, avoiding the repetition of harmful/ineffective modifications and enhancing patient safety.

PROSPERO registration number
CRD42023427704.

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Prevalence of low-level viremia in the treatment of chronic hepatitis B in China: a systematic review and meta-analysis

Objectives
Low-level viremia (LLV) is a risk factor affecting the prognosis of patients with chronic hepatitis B (CHB). The objective of this study was to systematically assess the prevalence of LLV, thereby providing robust evidence-based medical insights into effective clinical interventions and preventative measures against LLV.

Design
Systematic review and meta-analysis.

Data sources
A comprehensive literature search was conducted across various databases, including China National Knowledge Infrastructure, Wanfang Data (Wanfang), China Science And Technology Journal Database (VIP-CSTJ), China Biology Medicine disc (CBMdisc), PubMed, Embase, Web of Science and the Cochrane Library, spanning from the inception of these databases up to 5 January 2024.

Eligibility criteria
The research type included either a cross-sectional study or a cohort study focusing on the Chinese population, with the outcome being LLV. The languages were limited to both Chinese and English. Studies with any of the following were excluded: subjects with other comorbidities, original articles inaccessible or data unavailable, and duplicate publications.

Data extraction and synthesis
Literature management used EndNote X9.1, and an information extraction table was created using Microsoft Excel to record research information, including first author, year of publication and study type. The prevalence of LLV was assessed via meta-analysis. Meta-analyses were conducted in RStudio using the ‘metaprop ()’ function. Subgroup analysis and sensitivity analysis were used to identify sources of heterogeneity, and funnel plots and AS-Thompson tests were employed to evaluate publication bias.

Results
18 studies, encompassing a total sample of 9773 patients, were included in the analysis. Of these, 3336 patients were identified with LLV. The meta-analysis revealed that the prevalence of LLV among treated CHB patients stands at 33.6% (95% CI 30.2 to 37.0). The antigen status, antiviral treatment regimen (type of drugs and nucleos(t)ide analogues (NAs)), treatment duration, medication adherence and baseline hepatitis B virus DNA levels all affected the prevalence of LLV. Sensitivity analysis further corroborated the stability of these meta-analysis findings. The funnel plot and AS-Thompson test indicated no significant publication bias (t = –0.01, p=0.995).

Conclusions
The prevalence of LLV among CHB patients was established at 33.7% (95% CI 29.8% to 37.6%). Thus, it is imperative for clinical decision-makers to consider the various influencing factors of LLV when formulating treatment plans in order to mitigate any potential adverse outcomes.

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Understanding preconception care: a scoping review of knowledge, attitudes and practices among reproductive age individuals, healthcare workers and stakeholders in low- and middle-income countries

Objectives
This scoping review aims to map existing evidence on knowledge, attitudes and practices (KAP) and barriers to preconception care in low- and middle-income countries. The primary objective is to identify key gaps and research priorities to guide future efforts to improve maternal and child health.

Design
This review followed Arksey and O’Malley’s scoping review framework, with a comprehensive search across Medline, EMBASE, CINAHL and Scopus from inception to May 2025. Eligible studies included original research on preconception care (PCC), KAP in low- and middle-income countries (LMICs) without date restrictions. Two independent reviewers conducted screening in Covidence. Findings were presented in graphical, tabular and narrative formats, adhering to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols Extension for Scoping Reviews (PRISMA-ScR) standard.

Setting
The review focused on PCC studies conducted in LMICs across various healthcare settings, emphasising primary and secondary levels of care. The geographical scope was global but limited to LMICs as defined by World Bank criteria.

Result
A total of 62 studies were included in the review. Of these, 42 employed quantitative methods, 18 used qualitative approaches and 2 used a mixed-methods design. Regarding focus areas, 25 studies assessed knowledge, 14 assessed practices, 12 studies assessed KAP comprehensively and 10 assessed attitudes. Participants were mainly women of reproductive age (44 studies), with only five studies including men. Among healthcare providers, KAP varied, with midwives being the most frequently studied group. Stakeholders such as policymakers were notably under-represented. Identified barriers included limited training, cultural beliefs and inadequate policies. Facilitators highlighted were targeted education, spousal support and policy advocacy, emphasising the need for gender-sensitive and systemic interventions.

Conclusion
LMICs face complex challenges in utilising PCC, influenced by socioeconomic, cultural, and healthcare system factors. To address these challenges, nuanced approaches incorporating intersectional perspectives and practical qualitative methodologies are essential for improving couples’ and child health outcomes.

Trial registration number
The study protocol was registered in the Open Science Framework (OSF) on December 23, 2022, with DOI: 10.17605/OSF.IO/H3MK6.

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Daily mobility, activity and environmental determinants of stress in ecological momentary assessment (EMA) and GPS studies: a scoping review protocol

Introduction
Stress is omnipresent in our everyday lives and a key risk factor for our physical and mental health. Yet little is known about the impact of geographic life environments, linked to our daily activities and mobility patterns, on our momentary and daily stress levels.
We propose this review to gather evidence on the spatio-temporal determinants of momentary or daily stress in studies using ecological momentary assessment (EMA) or experience sampling methods (ESM) in addition to global positioning systems (GPS) tracking. We will focus on the spatio-temporal definition and modelling of environmental exposures accounting for participant daily activities and mobility patterns and their association with stress.

Methods and analysis
This scoping review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework for scoping reviews (2018). We will search the PubMed/Medline, Web of Science, PsycInfo and Scopus databases. We will include papers using EMA or ESM and GPS measuring chronic, daily or momentary stress as an outcome; these methods are also referred to as geographically-explicit ecological momentary assessment.
Articles published from January 2000–June 2025 will be screened. Two independent reviewers will screen titles and abstracts to agree on the inclusion of articles. No geographical or population limitation will be imposed.

Ethics and dissemination
This study is a scoping review based on previously published and publicly available literature. It does not involve the collection of primary data, human participants, or the processing of personal or sensitive information. Therefore, ethical approval is not required in accordance with institutional and international research ethics guidelines. The results will be submitted in peer-reviewed journals and presented at international conferences.

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Predictive accuracy of ophthalmic artery Doppler for pre-eclampsia: a systematic review

Objectives
This systematic review investigated available evidence on the stand-alone and incremental predictive performance of ophthalmic artery Doppler (OAD) for pre-eclampsia.

Design
Systematic review.

Data sources
We conducted a literature search from PubMed (Medline), the Cochrane CENTRAL, EMBASE and Scopus from inception to 8 April 2025.

Eligibility criteria
Studies eligible for inclusion were prospective or retrospective cohort studies, case-control studies or randomised controlled trials that reported on the predictive performance of OAD for pre-eclampsia in singleton pregnancies; and conducted in either high-income country (HIC) or low- and middle-income country (LMIC).

Data extraction and synthesis
Two reviewers independently screened and assessed articles for inclusion. One reviewer then extracted data using a standardised data extraction sheet, and any uncertainties were discussed with a second reviewer. The Prediction model Risk of Bias Assessment Tool was used for quality and risk of bias assessment. Findings were summarised and reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement and synthesised qualitatively.

Results
We identified and included 11 observational studies (3 from HIC and 8 from LMICs) with a total of 12 150 singleton pregnancies, of which 517 (4.3%) were complicated by pre-eclampsia at end of follow-up. The included studies were of varied quality, with three at low risk of bias, four at unclear risk and four at high risk. No interventional study was identified. Three studies (27.3%) recruited high-risk pregnancies (defined according to the American College of Obstetricians and Gynecologists (ACOG) criteria as one or more of the following: chronic hypertension, personal or family history of pre-eclampsia, early (≤18 years) or late (≥40 years) first pregnancy, primipaternity, chronic kidney disease, increased body mass index >30 kg/m2, presence of diabetes mellitus prior to pregnancy, autoimmune disease and thrombophilia), while eight studies (72.7%) recruited undetermined risk pregnancies. Stand-alone performance of OAD (interpreted by area under the receiver operating curve at 95% CI) showed that in the first trimester, the peak systolic velocity (PSV) ratio demonstrated very good predictive ability (0.97, 95% CI 0.92 to 1.0) (n=1 study), and the second PSV (PSV2) demonstrated very good predictive ability (0.91, 95% CI 0.82 to 0.99) (n=1 study). Also, PSV2 demonstrated fair predictive ability (0.61, 95% CI 0.42 to 0.79; and 0.53, 95% CI 0.40 to 0.66) for early and late pre-eclampsia, respectively (n=1 study). In the second trimester, the PSV ratio demonstrated very good predictive ability (0.88, 95% CI 0.84 to 0.91) (n=1 study), and PSV2 demonstrated good predictive ability (0.73, 95% CI 0.66 to 0.81; and 0.76, 95% CI 0.71 to 0.81) for pre-eclampsia (n=2 studies). In the third trimester, the PSV ratio demonstrated good predictive ability (0.82, 95% CI 0.73 to 0.89; and 0.77, 95% CI 0.71 to 0.82) for preterm and term pre-eclampsia, respectively (n=1 study). Also, PSV2 demonstrated good predictive ability 0.70 (0.57 to 0.84) (n=1 study).
Subsequently, in the second trimester, PSV ratio demonstrated better incremental predictive performance than uterine artery pulsatility index for preterm pre-eclampsia, when added to maternal factors and mean arterial pressure (MAP) (56.1%–80.2% vs 56.1%–74.8% detection rate (DR) at 10% FPR) (n=1 study). Also in the third trimester, adding PSV ratio to maternal factors and MAP was superior to soluble fms-like tyrosine kinase-1/placental growth factor ratio in predicting pre-eclampsia at

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