OBJECTIVES:This is a protocol for a Cochrane review (prognosis). The objectives are as follows: Primary objective To systematically review and critically appraise multivariable prognostic models developed for adults (≥ 18 years) with carotid stenosis in which imaging biomarkers (e.g. plaque characteristics derived from magnetic resonance imaging (MRI), computed tomography (CT), or ultrasound) constitute the core predictors. The primary focus is to evaluate the predictive performance of these models for cerebrovascular complications - specifically ipsilateral ischaemic stroke and transient ischaemic attack (TIA) - which are the clinical outcomes to be predicted. Where feasible, we will summarise and compare the models' discrimination (C‑statistic/area under the curve (AUC)) and calibration (calibration‑in‑the‑large, calibration slope, observed‑to‑expected ratio) across studies, and assess their potential for clinical application and external validation. For the purpose of defining symptomatic carotid stenosis as an eligibility criterion and subgroup variable, we will include studies that also considered retinal ischaemia (e.g. retinal embolism, amaurosis fugax) as a qualifying event. Secondary objectives To describe the combinations of imaging markers, modelling techniques, sample sizes, and variable‑selection strategies used in the development of the included models To evaluate the performance of these models for additional secondary clinical outcomes: plaque progression or regression, incident high‑risk imaging features, and the transition from asymptomatic to symptomatic disease To explore whether predictive performance differs according to imaging modality (MRI versus CT versus contrast‑enhanced ultrasound (CEUS)) or technical protocol (e.g. 3 T versus 1.5 T, spectral CT versus conventional CT) For studies that report both cerebrovascular and broader cardiovascular outcomes (major adverse cardiovascular events, myocardial infarction, etc.), we will only extract the performance metrics relating to cerebrovascular events for the primary analysis. Performance metrics for cardiovascular outcomes will be considered exploratory and will not form part of the main synthesis.
RATIONALE:Chronic hepatitis B is a global public health concern. It is caused by infection with the hepatitis B virus (HBV). The goal of treating chronic HBV infection is to prevent progression to chronic hepatitis, cirrhosis, hepatic decompensation, liver failure, hepatocellular carcinoma, and death. Individual studies have evaluated various immunomodulatory therapies with inconsistent results. Thymosin-ɑ1 is known to have antiviral effects; however, results of randomised clinical trials on the effects of thymosin-α1 as a potential treatment for people with chronic HBV have been inconsistent. OBJECTIVES:To assess the benefits and harms of thymosin-ɑ1 therapy in people with chronic hepatitis B. SEARCH METHODS:We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, four other databases and six trials registers, in addition to reference checking, citation searching, and contacting study authors to identify trials for inclusion. The latest search date was 10 June 2026. ELIGIBILITY CRITERIA:We included randomised controlled trials (RCTs) that evaluated thymosin-α1 at any dose, route of administration, or formulation type, in people with chronic hepatitis B regardless of age, sex, or ethnicity. Thymosin-α1 could have been administered as monotherapy, in combination with an additional drug, or in addition to standard medical treatment and compared with placebo, no intervention, the same additional drug, or the same standard medical treatment. OUTCOMES:Our critical outcomes were all-cause mortality, serious adverse events, and health-related quality of life. Among our important outcomes were HBV-related morbidity, HBV-related mortality, non-serious adverse events, and the proportion of people without histological improvements. RISK OF BIAS:We used the Cochrane Risk of bias 2 tool (RoB 2) to assess risk of bias. SYNTHESIS METHODS:We followed Cochrane methods. We conducted meta-analyses for predefined outcomes using data from the longest follow-up period, irrespective of the risk of bias judgements. We presented dichotomous outcome results as risk ratios (RRs) and continuous outcome results as mean differences, with 95% confidence intervals (CIs) at their longest follow-ups. We used the random-effects model for our primary analyses. We used GRADE to assess the certainty of the evidence for each outcome. INCLUDED STUDIES:We included 10 RCTs conducted in Bangladesh, China, Italy, Korea, Singapore, and Taiwan, with 1349 randomised participants (range: 12 to 690; 1045 (77.5%) were male). Among the trials reporting age, none included participants younger than 17 years (age range: 17 to 75 years). The trials were published between 1991 and 2018, and assessed thymosin-ɑ1 in adults with chronic hepatitis B infection, with or without comorbidities. Only two trials mentioned comorbidities (cirrhosis and acute-on-chronic liver failure). The trials compared thymosin-ɑ1, with or without a cointervention, with placebo or no intervention, or with the same cointervention. The control interventions were placebos in two trials and no intervention in two. The remaining six trials administered co-interventions, such as interferon, pegylated interferon, lamivudine, and standard medical therapy (entecavir or tenofovir), and entecavir. Follow-ups ranged from six months to five years after the end of treatment (median: 12 months). Four trials were funded by industry, five by research grants, and one provided no information. All 10 trials (11 records) provided data on at least one outcome in our review. We identified no ongoing trials. Sixteen studies are awaiting assessment due to incomplete reporting. We received no responses to our enquiries. SYNTHESIS OF RESULTS:Thymosin-ɑ1, compared with the control interventions, may reduce all-cause mortality (RR 0.53, 95% CI 0.29 to 0.96; I² = 0%; 3 studies, 907 participants; very low-certainty evidence), serious adverse events (RR 0.72, 95% CI 0.53 to 0.99; I² = 0%; 5 studies, 1056 participants; low-certainty evidence), HBV-related mortality (RR 0.53, 95% CI 0.29 to 0.96; I² = 0%; 3 studies, 907 participants; very low-certainty evidence), non-serious adverse events (RR 0.47, 95% CI 0.27 to 0.83; I² = 0%; 5 studies, 300 participants; very low-certainty evidence), and may have little to no effect on health-related quality of life (MD 0.70, 95% CI -2.55 to 3.95; I² not applicable; 1 study, 161 participants; very low-certainty evidence; score range: 0 to 100; the higher the score, the better) and on histological improvement (RR 0.51, 95% CI 0.13 to 2.06; I² = 74%; 2 studies, 702 participants; very low-certainty evidence). The evidence is very uncertain about the effect of thymosin-ɑ1 on hepatitis B-related morbidity (RR 0.86, 95% CI 0.54 to 1.40; I² = 3%; 3 studies, 854 participants; very low-certainty evidence). We judged the certainty of evidence to be low for serious adverse events and very low for the remaining outcomes. Reasons for downgrading were mainly due to study limitations, including overall high or some concerns for risk of bias; imprecision of the pooled effect estimates (including wide or very wide confidence intervals crossing the line of no effect, and small participant numbers); and inconsistency due to substantial heterogeneity (I² = 74%). The test for subgroup differences provided no evidence of differences in effect according to thymosin‑α1 administration for any outcome (P ≥ 0.05). AUTHORS' CONCLUSIONS:We assessed the certainty of evidence as very low for all outcomes except for serious adverse events (low). Therefore, we are not sure whether thymosin-α1 monotherapy versus placebo or no intervention, or with the same co-interventions, reduces all-cause mortality, serious adverse events, HBV-related mortality, and non-serious adverse events, nor whether it has any effect on quality of life (based on one trial) and histological improvement. The effect of thymosin-ɑ1 on HBV-related morbidity is very uncertain. We observed no statistically significant differences between trials with and without cointerventions. We found no ongoing trials. FUNDING:This Cochrane review had no dedicated funding. REGISTRATION:Protocol available via DOI: 10.1002/14651858.CD014610.
OBJECTIVES:This is a protocol for a Cochrane review (flexible). The objectives are as follows: To assess neonatal complications, specifically neonatal mortality and morbidities, in late-preterm and early-term infants compared to full-term newborns.
RATIONALE:Low back pain (LBP) is a major global health problem. It is the most common cause of activity limitation amongst individuals younger than 45 years, and one of the most frequent reasons for visits to a doctor. The 2019 Global Burden of Disease study named LBP as the leading cause of the need for rehabilitation, estimated to affect 568 million people. Its socioeconomic burden is substantial, with LBP-related costs from productivity loss and healthcare services utilisation making a significant impact on national gross domestic products. In particular, chronic LBP (CLBP)-defined as pain, muscle tension, or stiffness lasting longer than 12 weeks-results in long-term suffering and a considerable increase in healthcare expenditure. A wide variety of assistive technologies are utilised to manage CLBP. These aim to provide mechanical support, using diverse modalities and levels of assistance. OBJECTIVES:To assess the benefits and harms of assistive technologies (i.e. non-rigid and rigid lumbar braces, belts, supports, and devices to assist mobility and gait) in adults with chronic low back pain (CLBP). SEARCH METHODS:We searched CENTRAL, MEDLINE (PubMed), Embase, CINAHL, and trials registries up to 7 January 2025. We also searched the reference lists of included studies and any relevant systematic reviews. ELIGIBILITY CRITERIA:We included randomised controlled trials (RCTs) involving adults with CLBP comparing all types of assistive technologies versus placebo/sham, no intervention, or usual care. We planned to include non-randomised studies of interventions (NRSIs) in the absence of RCT evidence for some types of assistive devices. OUTCOMES:Our critical outcomes were pain, disability, health-related quality of life, participant-reported treatment success, falls, adverse events, and withdrawals due to any adverse events. Our important outcomes were depression, anxiety, social participation, and reduced use of painkillers. We did not assess the certainty of the evidence for important outcomes; thus, their results are not included in the abstract. RISK OF BIAS:We used the Cochrane tool RoB 1 to assess the risk of bias in the studies. SYNTHESIS METHODS:We conducted meta-analysis using the random-effects model to calculate the mean difference (MD) or standardised mean difference (SMD) with 95% confidence interval (CI) for all outcomes. We assessed the certainty of the evidence using the GRADE approach. When pooling was not possible, we calculated effect estimates for individual studies; when data were not available, we summarised the results narratively. INCLUDED STUDIES:We included eight RCTs involving a total of 501 participants. We did not identify any NRSIs meeting the inclusion criteria. Participants in the eight studies were adults of both sexes who had CLBP of at least one year's duration being treated in the outpatient rehabilitation setting. All eight studies investigated the effects of lumbar supports; no eligible studies assessed other assistive technologies, such as mobility or gait aids. Seven of the studies added lumbar supports to 'usual care'. Five of the studies were conducted in low- and middle-income countries and three in high-income countries. Most of the included studies were at high or unclear risk of bias due to lack of blinding, incomplete outcome data, and selective reporting. We judged the certainty of the evidence to be low or very low. SYNTHESIS OF RESULTS:The available evidence mainly addresses pain intensity and disability. We found some limited data on health-related quality of life. None of the included studies reported participant-reported treatment success, falls, adverse events, withdrawals due to any adverse events, or any of our other prespecified outcomes. Compared to no intervention, lumbar supports may result in little to no difference in pain intensity in the intermediate term (three months), if we consider a minimum clinically meaningful change on the 0-to-100 pain scale to be 15 points (MD -8.00, 95% CI -15.02 to -0.98; 1 study, 107 participants), and may result in little to no difference in disability (MD -0.10, 95% CI -1.11 to 0.91; 1 study, 107 participants) (both low-certainty evidence). Compared with usual care (non-steroidal anti-inflammatory drugs (NSAIDs)), lumbar supports plus usual care (NSAIDs) may result in a small reduction in short-term pain intensity (after three to four weeks), if we consider a minimum clinically meaningful change on the 0-to-100 pain scale to be 15 points (MD -17.66, 95% CI -24.22 to -11.09; I2 = 30%; 2 studies, 149 participants; low-certainty evidence). However, the effect of lumbar supports added to usual care (NSAIDs) on disability is very uncertain (SMD -0.63, 95% CI -1.43 to 0.17; I2 = 76%; 2 studies, 149 participants; very low-certainty evidence). The evidence is very uncertain about the effect of lumbar supports plus usual care (education and exercise) compared with usual care (education and exercise) on pain intensity (MD -4.50, 95% CI -20.98 to 11.98; 1 study, 25 participants), disability (MD 2.80, 95% CI -21.58 to 27.18; 1 study, 24 participants), and health-related quality of life (1 study, 25 participants) in the short term (six weeks) (all very low certainty evidence). The evidence is also very uncertain about the effect of lumbar supports plus usual care (routine physical therapy) compared with usual care (routine physical therapy) on pain intensity (MD 3.10, 95% CI -5.89 to 12.09; 1 study, 41 participants) and disability (MD -4.27, 95% CI -7.71 to -0.83; 1 study, 41 participants) in the short term (four weeks) (both very low certainty evidence). AUTHORS' CONCLUSIONS:Lumbar supports may result in a small reduction in pain intensity when provided in addition to NSAIDs, but may offer little to no benefit for pain intensity and disability when used alone. The evidence regarding health-related quality of life is very uncertain. No included studies reported on our other outcomes of interest or on adverse events, leaving uncertainty about the potential harms and broader functional impact of lumbar supports. Therefore, there is insufficient evidence to support the routine use of lumbar supports for managing CLBP. The absence of research on other assistive devices commonly used in clinical practice, particularly amongst people with disabilities or mobility limitations, is an evidence gap for future research to fill. FUNDING:This Cochrane review had no dedicated funding. REGISTRATION:Protocol (2024) DOI: 10.1002/14651858.CD015492.
BACKGROUND:The COVID-19 pandemic, declared in 2020, brought unprecedented challenges to our healthcare services in relation to the prevention and treatment of the disease. Additionally, preventing transmission within healthcare settings was critical. Infection Prevention and Control (IPC) guidelines are important for providing strategies on the use of personal protective equipment (PPE), the separation of patients with respiratory infections from others, and stricter cleaning routines. It is important to examine how the context of the pandemic impacts healthcare workers' (HCW) ability to adhere to IPC guidance in pandemic situations in the future. This is an update of an earlier review version, published in 2020, titled 'Barriers and facilitators to healthcare workers' adherence with infection prevention and control (IPC) guidelines for respiratory infectious diseases: a rapid qualitative evidence synthesis'. We built on available evidence for infectious respiratory diseases, but also importantly, given the unprecedented global scale of COVID-19 and its unique challenges for healthcare systems, explored additional factors influencing IPC adherence specific to respiratory diseases with pandemic potential, i.e. infectious respiratory pathogens (such as novel influenza subtypes or coronaviruses) judged capable of causing a pandemic. OBJECTIVES:Our primary objective is to identify the factors that impact on HCWs' adherence to IPC guidelines for COVID-19. A second objective is to update an existing rapid review, published in 2020, to identify similarities, differences, and novel insights specific to COVID-19 compared with other respiratory infectious diseases. SEARCH METHODS:We searched MEDLINE (Ovid), CINAHL (EBSCO), Scopus, Ovid PsycINFO (EBSCO), and Epistemonikos. We did not apply any language limits but only searched from 2020 to the present (last search 5 April 2024). In the interest of timeliness and relevance, we only included studies published from 2020. We chose this as it marks the year when the COVID-19 pandemic was declared. SELECTION CRITERIA:We included qualitative and mixed methods studies that focused on the experiences and perceptions of HCWs towards factors that impact on their ability to adhere to IPC guidelines for COVID-19. We included studies of any type of healthcare worker with responsibility for patient care. We included studies that focused on IPC guidelines (local, national, or international) for COVID-19 in any healthcare setting. We excluded studies that collected data using qualitative methods (e.g. open-ended survey questions) in which the response data were analysed only with descriptive statistics. DATA COLLECTION AND ANALYSIS:We used a purposive sampling frame to identify data-rich studies that represented a range of HCWs, healthcare settings, and geographical spread. We assessed methodological strengths and limitations in the same studies using an adapted version of the Critical Skills Appraisal Programme (CASP) tool for qualitative studies. We used the 'best-fit framework approach' to analyse and synthesise the evidence from our included studies. We used the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach to assess our confidence in each finding. We examined each review finding to identify factors that may influence guideline adherence and developed implications for practice. MAIN RESULTS:We found 170 studies eligible for inclusion; of these, 26 were sampled for analysis using a purposive sampling frame for a balance of variation and richness of data. Seven of the 26 sampled studies were from high-income countries. Of the 15 middle-income countries, seven were upper middle-income countries, and eight were lower middle-income countries. There were four low-income countries included in the sample. In terms of geographical spread, ten were from Asia, eight from Africa, three were from North America, one from South America, one from Oceania, and three from Europe. Most of the studies included nurses (15 studies) or doctors (11 studies). Other types of healthcare workers included in the studies were other clinical staff (11 studies), such as midwives, allied health professionals, medical and radiologic technologists, dental professionals, neonatologists, radiographers, pharmacists, and support staff (7 studies), such as hospital cleaners, clerical staff, technicians, and hospital attendants. Healthcare settings ranged across and within studies, including hospitals, long-term care settings, and community healthcare settings. Specific units such as maternity, intensive care, emergency care, critical care, and operating rooms were identified in five of the sampled studies. We identified 27 findings that outline the factors that impact on HCWs' adherence to IPC guidelines. We have low (n = 3), moderate (n = 12), and high (n = 12) confidence in these findings. HCWs found it easier to follow IPC guidelines with managerial support, and when IPC guidelines were communicated in a clear, structured, and accessible way. They found it more difficult to follow guidelines if they were busy, short-staffed, or when patients and visitors refused to wear masks and maintain social distancing. Training was considered very important, but not all HCWs had the opportunity to attend IPC training. In terms of the working environment, HCWs need adequate space, hand-washing stations, and showers to follow the IPC guidelines. HCWs worried about infecting other people, but some worried less once people started being vaccinated. It was very important that all HCWs had sufficient and equitable access to PPE and other supplies to follow guidelines. If PPE did not fit properly or was not of good quality, it was more difficult for HCWs to practice IPC. Many factors affect HCWs' willingness and ability to follow IPC guidelines. Our review includes a set of questions based on our findings to help healthcare providers plan, implement, or manage IPC strategies to help their workers follow IPC guidelines for pandemic diseases like COVID-19. It is worth noting that our included studies were conducted primarily during the earlier phase of the pandemic, based on practical considerations to not update the search after April 2024. AUTHORS' CONCLUSIONS:We identified several factors that influence the ability of healthcare workers to adhere to IPC guidelines. Practical implications, such as communication strategies and the provision of training and supplies, should guide policymakers and decision-makers in disease outbreaks and future pandemics. FUNDING:This Cochrane review had no dedicated funding. REGISTRATION:This Cochrane review extends the work by a published rapid review, available via DOI: 10.1002/14651858.CD013582.
