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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Efficacy and safety of musculoskeletal manipulations in elderly population with musculoskeletal disorders: a systematic review

Introduction
Non-pharmacological interventions, including musculoskeletal manipulations (MMs), have been proven effective for musculoskeletal disorders.

Objectives
To evaluate if MMs, including osteopathic manipulation and chiropractic care, are effective to improve quality of life, pain intensity and function in older adults with musculoskeletal disorders.

Design
Systematic review.

Data sources
A systematic search was conducted on MEDLINE/PubMed, EMBASE, Scopus, Web of Science, CINAHL, Cochrane Library, from database inception up to 2 January 2025.

Eligibility criteria
Randomised controlled trials, controlled non-randomised trials and open label trials evaluating the efficacy and safety of MM such as osteopathic manipulation, chiropractic manipulation, myofascial release, craniosacral therapy, as monotherapy or adjunctive therapies in older people (age ≥65 years) with musculoskeletal disorders. The main outcomes included pain intensity, functionality and quality of life. Additionally, other related outcomes were considered, such as medical use duration, mood, mobility, motion, strength and endurance. Finally, we considered any adverse events.

Data extraction and synthesis
Selection and data extraction were performed independently by two authors. The effect estimates for each study were performed using Review Manager V.5.14. Continuous outcomes were analysed using the mean difference (95% CI). The methodological quality of the included studies was assessed using the Cochrane Risk of Bias tool 2 (RoB 2). No meta-analysis was performed.

Results
Five parallel randomised controlled trials were included, with a total sample size of 676 participants (41.6% women with a mean age of 77.3 years): 34 with chronic pain, 265 with neck pain and 377 with low back pain. MMs were not effective in patients with chronic pain, neither in pain intensity nor in functionality. For neck pain, considering the main outcomes, only in one of the two studies was there a statistically significant improvement in neck pain intensity only at week 12 for spinal manipulative treatment (SMT)+home exercise (HE) compared with HE alone (ES=–0.90 (95% CI –1.46 to –0.34); p=0.002). For low back pain, SMT+HE showed a statistically significant reduction in pain at 12 weeks compared with HE (ES=–0.79 (95% CI –1.39 to –0.19) p=0.010. For neck pain and low back pain, no statistically significant improvement in functional status and quality of life was observed with MM compared with any control group. RoB 2 showed a high risk of bias in three studies and some concerns in the others. At the domain level, the lowest risk was observed in the randomisation process (80% with some concerns). All five studies reported adverse events, none of which were serious.

Conclusions
This review provides limited and inconclusive evidence about MM to improve quality of life, pain management and functional status in older adults with musculoskeletal disorders. However, MM appears to be generally safe and well-tolerated.

PROSPERO registration number
CRD42023473203.

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Background rates of medical events of interest before and during the COVID-19 pandemic: a longitudinal cohort study using claims data

Importance
Background rates are critical for contextualising safety signals arising from COVID-19-related interventions in investigational or real-world settings.

Objective
To estimate background rates of medical events of interest (MEI) for which COVID-19 infection and/or COVID-19 interventions may be risk factors in two US claims databases.

Design, setting and participants
This retrospective cohort study spans the pre-COVID-19 (2018–2019) and COVID-19 (2020–2021) periods. We constructed three cohorts, in each of Inovalon/HealthVerity (Inovalon/HV) and Optum databases: a COVID-19-positive adult cohort (2020–2021), a paediatric cohort (2018–2021) and a high-risk cohort (2018–2021) comprising patients at increased risk for severe COVID-19. Participants were indexed on the day they first qualified to enter each cohort during the study period. Background rates of 17 MEI were estimated per 1000 person-years (PY) with 95% CIs.

Main outcomes and measures
Annual incidence rates (IRs) of 17 MEI.

Results
Overall, 758 414 (COVID-19-positive adults; 57.8% women), 12 513 664 (high-risk adults; 56.8% women) and 8 510 627 (paediatric patients; 49.1% women) patients were identified in the HV database. IRs of MEI varied substantially by year, data source, study cohort and duration of follow-up. The IRs of MEI were highest among COVID-19-positive adults and lowest among paediatric patients. For example, IR of myocarditis/pericarditis per 1000 PY was 3.0 (95% CI: 2.6 to 3.4) in the COVID-19-positive adult cohort vs 0.36 (95% CI: 0.34 to 0.37) among high-risk adults and 0.05 (95% CI: 0.05 to 0.06) among paediatric patients. In the COVID-19-positive adult cohort, we observed higher IRs during 90-day follow-up (eg, IR of acute myocardial infarction (AMI) 26.5 (95% CI: 25.3 to 27.7)) vs 365-day follow-up (eg, IR of AMI 20.0 (95% CI: 9.2 to 20.8)) and during 2020 compared with 2021. IRs were higher in the high-risk adult and paediatric populations during the pre-COVID-19 period than during the COVID-19 pandemic.

Conclusions
Substantial variability was observed in IRs of MEI by study cohort, year, data source and follow-up duration. When generating background rates for contextualising safety signals from COVID-19 interventions, careful consideration must be given to the indicated subpopulation of interest, COVID-19-related temporal variations and data sources.

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Exploring evidence gaps in clinical trials in thermal burns care: an umbrella review

Background
Gaps in research evidence lead to research waste. In burns treatment, there is a paucity of reliable evidence or data. This contributes to inconsistent patient care, especially on a global scale, where low-resource countries often lack access to the latest research advancements. This umbrella review was undertaken as part of the James Lind Alliance Priorities in Global Burns Research Prioritisation Setting Partnership (PSP) and aimed to identify and assess the quality of evidence in thermal burns care. The objective was to map which interventions in thermal burns care are supported by a reliable evidence base and for which the evidence is lacking.

Methods
Systematic reviews of randomised controlled trials in thermal burns were identified and assessed using reliability criteria determined a priori. Multiple systematic review databases were searched in June 2023, including the Cochrane Library, KSR Evidence database and NIHR Journals Library. Summary of findings and, where available, Grading of Recommendations Assessment, Development and Evaluation was used to assess certainty of evidence. Reliable reviews were mapped onto clinical categories identified by patients, carers and healthcare professionals as part of the PSP.

Results
232 systematic reviews were identified, of which 83 met reliability criteria and were included. The main reason for not meeting reliability criteria was poorly defined eligibility criteria (n=128). Of the 83 reliable reviews, most were conducted in pain (n=28) or wound management (n=14) and acute care (n=13). Certainty of evidence was mixed. Reviews mapped onto nine of the 17 clinical categories identified by the PSP.

Conclusion
This review summarises the available high-quality evidence in burns care and identifies evidence gaps, indicating that many important clinical questions remain unanswered. There is a discrepancy between the treatments investigated in high-quality research and the clinical areas considered as most important to stakeholders. These findings provide direction for future research to improve global burns care.

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Longitudinal observational research study: establishing the Australasian Congenital Cytomegalovirus Register (ACMVR)

Purpose
Congenital cytomegalovirus (cCMV) is an important cause of long-term childhood disability. In Australia, the identification and treatment practices and the long-term clinical and neurodevelopmental outcomes of children with cCMV are unknown. The Australasian cCMV Register (ACMVR) is a longitudinal register and resource for research that aims to describe and explore, in Australian children with cCMV: (1) their clinical characteristics over time, (2) antiviral therapy use/prescribing up to 1 year of age and (3) risk factors and potential avenues for prevention of adverse sequelae of the virus.

Participants
Children

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Machine learning methods, applications and economic analysis to predict heart failure hospitalisation risk: a scoping review

Background
 Machine Learning (ML) has been transformative in healthcare, enabling more precise diagnostics, personalised treatment regimens and enhanced patient care. In cardiology, ML plays a crucial role in risk prediction and patient stratification, particularly for heart failure (HF), a condition affecting over 64 million people globally and imposing an economic burden of approximately $108 billion annually. ML applications in HF include predictive analytics for risk assessment, identifying patient subgroups with varying prognoses and optimising treatment pathways. By accurately predicting the likelihood of hospitalisation and rehospitalisation, ML tools help tailor interventions, reduce hospital visits, improve patient outcomes and lower healthcare costs.

Objective
To conduct a comprehensive review of existing ML models designed to predict hospitalisation risk in individuals with HF.

Methods
A database search including PubMed, SCOPUS and Web of Science was conducted on 31 March 2024. Studies were selected based on inclusion criteria focusing on ML models predicting hospitalisation risks in adults with HF. The data from 27 studies meeting the criteria were extracted and analysed, with a focus on the predictive performance of the ML models and the presence of economic analysis.

Results
Most studies focused on predicting readmission rather than first-time hospitalisation. All included studies employed supervised ML algorithms, with ensemble-based methods generally yielding the highest predictive performance. For 30-day hospitalisation or readmission risk, Extreme Gradient Boosting (XGBoost) achieved the highest mean area under the curve (AUC) (0.69), followed by Naïve Bayes (0.68) and Deep Unified Networks (0.66). For 90-day risk, the best-performing models were Least Absolute Shrinkage and Selection Operator and Gradient Boosting, both with a mean AUC of 0.75, followed by Random Forest (0.67). When the prediction timeframe was unspecified, Categorical Boosting achieved the highest performance with a mean AUC of 0.88, followed by Generalised Linear Model Net and XGBoost (both 0.79).
Electronic health records were the primary data source across studies; however, few models included patient-reported outcomes or socioeconomic variables.
None of the studies conducted an economic evaluation to assess the cost-effectiveness of these models.

Conclusions
ML holds substantial potential for improving HF care. However, further efforts are needed to enhance the generalisation of models, integrate diverse data sources and evaluate the cost-effectiveness of these technologies.

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Brain-Body Interactions in Ischemic Stroke: VNS Reprograms Microglia and FNS Enhances Cerebellar Neuroprotection

Stroke, Ahead of Print. Stroke significantly impacts mortality and long-term disability, necessitating effective rehabilitation strategies to enhance recovery. This review examines the roles of vagus nerve stimulation (VNS) and fastigial nucleus stimulation (FNS) in facilitating ischemic stroke recovery through brain-body interactions. VNS enhances ischemic stroke recovery by reprogramming microglia from proinflammatory (M1) to neuroprotective (M2) phenotypes, reducing neuroinflammation and promoting tissue repair via neurotrophic factors. It has shown promise in clinically improving chronic upper limb deficits when combined with rehabilitation therapies. Conversely, FNS provides cerebellar-mediated neuroprotection by mainly mitigating excitotoxic damage and inflammatory responses independent of cerebral blood flow alterations, as evidenced by preclinical models of middle cerebral artery occlusion. By integrating VNS-driven immunomodulation with FNS-mediated excitotoxicity suppression, this review highlights their synergistic potential to improve rehabilitation outcomes for ischemic stroke survivors. Biomarker-guided protocols: VNS for cortical/subcortical ischemic deficits and FNS for cerebellar network recovery are advocated to address postischemic disability via anti-inflammatory rewiring, neuroplasticity enhancement, and cerebellar-thalamocortical circuit stabilization. Critical gaps remain in hemorrhagic stroke, where FNS’s excitotoxicity suppression may destabilize clots, necessitating subtype-specific safety validations.

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The emerging economic evidence and methods used to evaluate clinical registries: a systematic scoping review protocol

Introduction
A clinical registry is a systematically collected database of health-specific information about a patient population. Clinical registries can be used for a variety of purposes including surveillance, monitoring of outcomes and patient care. The establishment and maintenance of clinical registries come with a significant cost. This scoping review aims to identify the methods used to economically evaluate clinical registries including their costs and benefits.

Methods
This systematic scoping review protocol has been developed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. The final review will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. The electronic databases Medline, Embase, Cochrane Library and The Cumulative Index to Allied Health Literature(CINAHL) database will be searched. Relevant national organisation websites will be searched to identify empirical studies within grey literature. The inclusion criteria include studies that economically evaluate clinical registries and are published in the English language from inception to February 2025. Two reviewers will independently screen 100% of titles and abstracts and full texts of studies for inclusion. Data will be extracted from eligible studies prior to being assessed for quality using a multi-tool approach.

Ethics and dissemination
The findings of this review will be published in an international peer-reviewed journal. They are likely to be of interest to custodians of existing clinical registries and to those wishing to establish or evaluate clinical registries.
Keywords
Clinical registries, economic evaluation, costs, cost-effectiveness, health economics, registry based studies

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Effect of transcranial magnetic stimulation on perioperative neurocognitive dysfunction: study protocol for a systematic review and meta-analysis of randomised controlled trials

Introduction
Perioperative neurocognitive disorders (PNDs), a common postoperative complication associated with anaesthesia and surgical procedures, are characterised by impairments in memory, attention, language comprehension and social functioning. Accumulating evidence from clinical studies indicates that transcranial magnetic stimulation (TMS)—a non-invasive neuromodulatory modality capable of targeted cortical stimulation—may offer therapeutic promise for PND management. To comprehensively assess the intervention efficacy and safety parameters of TMS in mitigating postoperative cognitive decline, we propose conducting a systematic review and meta-analysis of randomised controlled trials adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Our findings aim to provide evidence-based insights into the neuroprotective potential of TMS for mitigating cognitive decline in surgical populations.

Methods and analysis
The investigation will implement a multifaceted search protocol encompassing international and Chinese scholarly resources. The search will be conducted in major databases, including Web of Science, Embase, PubMed, Cochrane Library, China Biology Medicine, China National Knowledge Infrastructure, Wan Fang Database and Chinese Scientific Journal Database from inception to 31 March 2025. To capture the latest research trends, ongoing trials will be simultaneously searched in the WHO International Clinical Trial Registry Platform, ClinicalTrials.gov and the China Clinical Trial Registry. Grey literature will be supplemented through resources such as GreyNet International, OpenGrey and Google Scholar. The inclusion criteria for this review are restricted to randomised controlled trials investigating the application of TMS as an intervention for PND. Primary endpoints comprise clinically confirmed incidence rates of postoperative delirium and delayed neurocognitive recovery. Two researchers will independently perform literature screening, data extraction and risk of bias assessment. The risk of bias in included studies will be evaluated using the Cochrane Risk of Bias Tool 2.0. Evidence certainty will be appraised through the GRADE framework with explicit justification for downgrading decisions. Meta-analysis will be conducted using STATA V.15.1 statistical software. The data synthesis process will incorporate standardised methodologies, including heterogeneity testing, sensitivity analysis and assessment of publication bias.

Ethics and dissemination
This study will not involve the collection of biometric information or medical privacy data throughout the research process, thus complying with the exemption criteria outlined in the ‘Measures for Ethical Review of Biomedical Research Involving Human Subjects.’ The findings will adhere to academic standards and be submitted for publication in reputable international medical journals following a rigorous double-blind peer-review process.

Systematic review registration
The research protocol has been prospectively registered on the PROSPERO international prospective systematic review registration platform (registration number: CRD42025636978).

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Hyperangulated videolaryngoscope for difficult airway management: a protocol for a systematic review with meta-analysis and trial sequential analysis

Introduction
Videolaryngoscopes are recommended as the top preference for tracheal intubation in adults, children, infants and neonates, and even in patients with anticipated difficult airways, since they are generally easier to use and quicker to master than fibreoptic bronchoscopes. Compared with standard videolaryngoscopes, hyperangulated videolaryngoscopes possess a more sharply curved blade or blade tip, resulting in a higher first-attempt success rate among patients with anticipated difficult airways. However, hyperangulated videolaryngoscopes also pose challenges in advancing the tracheal tube, which decreases the first-attempt success rate while increasing the tracheal intubation time when the tracheal tube introducer is unsuitable. Hence, controversy still remains regarding the efficiency of hyperangulated videolaryngoscopes as first-line devices in patients with anticipated difficult airways, owing to the inconsistent clinical findings. Consequently, we will conduct a protocol for a systematic review and meta-analysis to determine the usefulness of hyperangulated videolaryngoscopes in patients with anticipated difficult airways.

Methods and analysis
English-language databases (Web of Science, Cochrane Library, PubMed, Embase and Ovid Medline), Chinese electronic databases (VIP database, China National Knowledge Infrastructure, and Wanfang database) and clinical trial registry platforms will be scoured from their inception to May 2025 to locate randomised controlled trials of hyperangulated videolaryngoscopes in patients with anticipated difficult airways. For continuous data, mean differences or standardised mean differences, accompanied by their 95% CIs, and for dichotomous data, the risk ratio, accompanied by its 95% CI, will be calculated using Review Manager V.5.4. Either a fixed-effects model or a random-effects model will be used depending on the magnitude of statistical heterogeneity as evaluated via the I2 test. The risk of bias will be assessed via the Cochrane risk-of-bias tool 2. Additionally, the quality of evidence regarding each outcome will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation. The reliability of all outcomes will be appraised via trial sequential analysis. Moreover, the publication bias of all outcomes will be examined using Funnel plots and Egger’s regression test.

Ethics and dissemination
Ethical approval was not required for this systematic review protocol. The results will be disseminated through peer-reviewed publications.

PROSPERO registration number
CRD42024627484

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Understanding disparities in access to and quality of surgical care for African, Caribbean and Black communities in high-income countries with universal healthcare: a scoping review protocol

Introduction
African, Caribbean and Black (ACB) communities experience disparities in health outcomes, with higher rates of chronic diseases, such as heart disease and stroke, and lower self-reported health status compared to their White counterparts. Barriers to timely access to healthcare services further exacerbate these inequities. Some studies link racialisation to surgical disparities and subpar surgical outcomes. However, the findings are diverse, and there is no synthesis of the evidence on disparities in surgical care for ACB patients in high-income countries with universal healthcare systems. The objective of the scoping review is to systematically describe, characterise and map the existing literature on disparities in the access to and quality of surgical care among ACB patients in high-income countries with universal healthcare systems, and to identify gaps in the literature on surgical access and quality of surgical care in ACB patients.

Methods and analysis
The scoping review will follow the Joanna Briggs Institute methodology and report according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. The search strategy will be customised for each database (MEDLINE, Embase, CINAHL, APA PsycINFO and Cochrane Library) using terms for ACB and surgery. Grey literature and references from included studies will be searched for additional sources, with no limitations on publication date or language. All study designs will be eligible. Two independent reviewers will screen titles, abstracts and full texts in duplicate for eligibility. One reviewer will chart data, with a second reviewer validating the data charted. The findings will be synthesised, quantitatively summarised using descriptive statistics and qualitatively analysed through thematic analysis.

Ethics and dissemination
Ethics approval is not required as the study utilises published data. The dissemination of the findings will inform future research and improve understanding of the surgical care experiences of ACB patients. Dissemination will target academics and healthcare professionals through publications, presentations and workshops.

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Annual cases of colon cancer by age group after Medicaid expansion in the USA in 2014: a difference-in-differences study

Background
Studies examining the association between Medicaid expansion (ME) under the Affordable Care Act (ACA) and colon cancer incidence have produced mixed results.

Objective
To re-visit the association between the ACA-ME and annual cases of colon cancer.

Design
Difference-in-differences (DiD).

Setting
The primary analyses used data from the National Cancer Database from 2010 to 2018, a hospital-based cancer registry in the USA. We also conducted exploratory analyses using data from the Surveillance, Epidemiology and End Results (SEER) registry.

Patients
Patients aged 40 and older with newly diagnosed colon cancer.

Measurements
The primary outcome was the percent change in colon cancer of all stages. Secondary outcomes were percent changes in stage I and stage IV cases.

Results
Among those aged 40–49, we observed a statistically significant greater increase in stage I colon cancer in expansion states relative to non-expansion states (DiD (percent change) 9.7% (95% CI, 2.5% to 17.4%)). In those aged 50–64, we did not observe statistically significant differences between the two state groups in any of the outcomes. Among those aged 65+, we observed a statistically significant relative decrease for all stages in ACA-ME states (–1.0% (95% CI, –1.0% to –3.0%)) and for stage IV (–3.0% (95% CI, –2.0% to –5.0%)). We explored our findings among younger individuals (

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