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.
OBJECTIVES:This is a protocol for a Cochrane review (intervention). The objectives are as follows: To evaluate the benefits and harms of systemic prophylactic antibiotics versus no antibiotics or placebo in people undergoing dental implant placement with concomitant bone augmentation procedures, and to assess whether the effects of systemic prophylactic antibiotics differ according to the dosage, duration, timing of administration, and type of antibiotic.
RATIONALE:Alpha-1 antitrypsin (AAT) is a protein produced by the liver that stops certain enzymes from harming body tissues, especially in the lungs. AAT deficiency (AATD) is a genetic condition that can manifest clinically as chronic obstructive pulmonary disease (COPD), causing cough and breathlessness. AAT augmentation therapy could help prevent or slow the progression of COPD in people with AATD. Whilst correcting the protein deficit seems a logical approach to treating a condition caused by a protein deficiency, this intervention is only worthwhile if it leads to improvements in clinically important outcomes. The evidence synthesised in a previous Cochrane review (last updated in 2016) was insufficient to conclude whether AAT augmentation therapy influenced any clinical outcomes. However, no inhaled AAT augmentation therapy studies were available for inclusion in that review, only studies on intravenous AAT augmentation therapy. OBJECTIVES:To assess the effects of alpha 1 antitrypsin (AAT) augmentation therapy on respiratory disease in people with alpha 1 antitrypsin deficiency (AATD). SEARCH METHODS:We searched CENTRAL, MEDLINE, Embase, and two trials registries to August 2025. We checked the reference lists of included articles and other related papers for any additional studies. ELIGIBILITY CRITERIA:We included randomised controlled trials (RCTs). Cluster-RCTs were also eligible if the data had been, or could be, adjusted for clustering. We included studies comparing AAT augmentation by any route (inhaled, intravenous, or subcutaneous) with AAT augmentation by a different route, placebo, or no treatment. We excluded studies that compared different doses of AAT via the same route, without a placebo or no treatment group. OUTCOMES:Our critical outcomes were annual airway disease exacerbation rate, all-cause mortality, and participants experiencing one or more serious adverse events. RISK OF BIAS:We used the Cochrane risk of bias tool (RoB 2). SYNTHESIS METHODS:Two review authors independently extracted data and assessed the risk of bias. We conducted meta-analyses to calculate odds ratios (ORs) for dichotomous outcomes, and mean differences (MDs) or standardised mean differences (SMDs) for continuous outcomes, all with corresponding 95% confidence intervals (CIs). We used GRADE to assess the certainty of evidence for our critical outcomes. INCLUDED STUDIES:Six multicentre studies randomised a total of 526 people with AATD and analysed the results for 524 participants. The studies were conducted in Europe, North America, and Australia and were published between 1997 and 2025. The route of AAT administration was intravenous in four studies and inhaled in two studies. This review has three new studies compared to the 2016 Cochrane review. SYNTHESIS OF RESULTS:Intravenous AAT augmentation therapy versus placebo Intravenous AAT augmentation therapy may increase the annual airway disease exacerbation rate slightly compared with placebo (MD 0.29 exacerbations, 95% CI 0.04 to 0.54; P = 0.02, I2 = 0%; 2 studies, 257 participants; low-certainty evidence, downgraded for serious imprecision and indirectness). It may make little or no difference to all-cause mortality (OR 0.30, 95% CI 0.03 to 2.98; P = 0.31; 2 studies, 187 participants; low-certainty evidence, downgraded for very serious imprecision). We are uncertain whether intravenous AAT augmentation therapy has an impact on the risk of experiencing one or more serious adverse events (OR 0.67, 95% CI 0.32 to 1.41; P = 0.29, I2 = 43%; 2 studies, 257 participants; very low-certainty evidence, downgraded for serious inconsistency and indirectness and very serious imprecision). Inhaled AAT augmentation therapy versus placebo We are uncertain if inhaled AAT augmentation therapy has an impact on the annual airway disease exacerbation rate compared with placebo (MD 0.45 exacerbations, 95% CI -0.42 to 1.32; P = 0.31; 1 study, 168 participants; very low-certainty evidence, downgraded for serious indirectness and very serious imprecision). It may make little or no difference to the risk of experiencing one or more serious adverse events (OR 5.33, 95% CI 0.61 to 46.54; P = 0.13, I2 = 0%; 2 studies, 204 participants; low-certainty evidence, downgraded for very serious imprecision). No studies reported all-cause mortality. AUTHORS' CONCLUSIONS:Compared with placebo, intravenous AAT augmentation therapy may have little or no effect on all-cause mortality but may increase the annual airway disease exacerbation rate slightly. We are uncertain if intravenous AAT augmentation therapy has any effect on the risk of serious adverse events. Inhaled AAT augmentation therapy may have little or no effect on the annual airway disease exacerbation rate or the risk of serious adverse events. FUNDING:This Cochrane review had no dedicated funding. REGISTRATION:Protocol (2024) DOI: 10.1002/14651858.CD015930.
OBJECTIVES:This is a protocol for a Cochrane review (intervention). The objectives are as follows: To assess the benefits and harms of intravenous administration of gemcitabine monotherapy or gemcitabine-based combination chemotherapy versus placebo or non-gemcitabine-based chemotherapy in people with advanced biliary tract carcinomas.
RATIONALE:Obesity is a global public health issue and a major contributor to non-communicable diseases. In recent decades, the prevalence of obesity in adolescents has risen at an alarming rate. Although several systematic reviews have evaluated the effects of physical activity for the management of obesity in adolescents, key limitations remain in the literature, particularly in reporting completeness and the lack of standardised assessments of the certainty of evidence. OBJECTIVES:To synthesise evidence on the benefits and harms of physical activity interventions for the management of obesity in adolescents aged between 10 and 19 years. SEARCH METHODS:We searched various databases, including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), Embase (Ovid), and two trial registries, from 2012 to 4 December 2025. We applied no restrictions on language or publication status. We also searched grey literature sources. ELIGIBILITY CRITERIA:We included randomised controlled trials (RCTs) that evaluated physical activity interventions lasting at least 12 weeks, of any frequency, type, or intensity, in adolescents aged 10 to 19 years with obesity (as defined by study investigators) at baseline. Eligible comparators included standard care, waiting list, no physical activity, or any other active interventions, such as a comparison of different physical activity parameters (duration, frequency, intensity). OUTCOMES:Critical outcomes: body weight, body mass index (BMI), BMI z-score, waist circumference, body fat percentage, glucose, and insulin resistance. Important outcomes: physical well-being, mental well-being, physical activity levels, overall quality of life, blood pressure, adiposity, lipid biomarkers, insulin, fasting glucose, mortality, adverse events, presence of obesity-related comorbidities or any non-communicable disease, disability, prevalence of obesity in adulthood, alterations in hunger, and access to health services. RISK OF BIAS:Pairs of review authors independently assessed the risk of bias in each included study using the original version of the Cochrane tool (RoB 1). SYNTHESIS METHODS:We synthesised results using meta-analysis when appropriate. Given the clinical and statistical heterogeneity, we predominantly used a random-effects model alongside sensitivity analyses. When meta-analysis was not feasible, we employed synthesis without meta-analysis (SWiM) methods. We assessed the certainty of the evidence using the GRADE approach. We grouped eligible comparisons into two broad categories: (1) physical activity intervention versus no-intervention control; and (2) one physical activity intervention versus another physical activity intervention or an active control. The first category is our main comparison. INCLUDED STUDIES:We included 30 studies (1508 participants) conducted across 15 countries, published between 2012 and 2023 (median year: 2017), with participants' ages ranging from 10 to 17 years. We assessed all included studies to be at high risk of bias. SYNTHESIS OF RESULTS:Physical activity intervention versus no-intervention control In adolescents with obesity aged 10 to 19 years, low-certainty evidence suggests that any form of physical activity may slightly improve the following outcomes compared to no intervention: body weight (mean difference (MD) -1.88 kg, 95% confidence interval (CI) -3.34 to -0.42; I2 = 47%; 17 studies, 749 participants); waist circumference (MD -2.88 cm, 95% CI -3.70 to -2.06; I2 = 0%; 10 studies, 476 participants); and body fat percentage (MD -2.96%, 95% CI -3.52 to -2.39; I2 = 10%; 9 studies, 313 participants). This review identified very low-certainty evidence regarding the effects of any form of physical activity on BMI (MD -1.38 kg/m², 95% CI -1.94 to -0.83; I2 = 43%; 16 studies, 537 participants), BMI z-score (MD 0.01 z-score units, 95% CI -0.34 to 0.37; I2 = 84%; 6 studies, 250 participants), glucose (MD -0.29 mmol/L, 95% CI -0.45 to -0.12; I2 = 76%; 7 studies, 299 participants), and insulin resistance (MD -0.99, 95% CI -1.25 to -0.73; I2 = 66%; 6 studies, 256 participants). Compared to no intervention, any form of physical activity may improve mental well-being, based on evidence from one study with 56 participants (self-perception: MD 0.22, 95% CI -0.10 to 0.54; self-efficacy: MD 0.58, 95% CI 0.21 to 0.95; self-esteem: MD 0.47, 95% CI 0.18 to 0.76). We identified low- or very low-certainty evidence for other important outcomes, including physical activity levels, blood pressure, other measures of adiposity and fat distribution, insulin and fasting glucose, and lipid biomarkers. The studies included in the main comparison did not report on the following important outcomes: physical well-being, overall quality of life, mortality, adverse events, comorbidities, disability, presence of obesity in adulthood, alterations in hunger or satiety, or access to health services. One physical activity intervention versus another physical activity intervention or active control All comparisons involving one type of physical activity versus another type (for example, high-intensity interval training versus moderate-intensity continuous training) or versus an active control group (such as participation in regular school physical activity programmes) were supported by very low-certainty evidence. Thus, the effects of the various types and levels of physical activity on the reported outcomes are uncertain. AUTHORS' CONCLUSIONS:Physical activity may improve health outcomes in adolescents with obesity, but the certainty of the evidence is low to very low. Serious methodological limitations, clinical and statistical heterogeneity, as well as small-study effects and imprecise results limited the certainty and interpretability of the current evidence base. Important knowledge gaps remain as none of the included studies enrolled adolescents with disabilities, the studies provided little information on contextual factors, and the amount of evidence hindered the analysis of relevant subgroups. Future high-quality, well-reported studies will likely change the review's conclusions. FUNDING:The Department of Nutrition and Food Safety at the World Health Organization (WHO) commissioned and provided financial support for this work. WHO acknowledges financial support from the Norwegian Agency for Development Cooperation, the Swedish International Development Cooperation Agency, the Government of the Grand Duchy of Luxembourg, and the Government of Germany to the Department of Nutrition and Food Safety. REGISTRATION:The full protocol was registered, and it is publicly available (https://osf.io/2wksa).
RATIONALE:Numerous media are commercially available for culture of human pre-implantation embryos in assisted reproductive technology (ART) cycles. It is unknown which culture medium leads to the best success rates after ART. This is the first update of a Cochrane review published in 2015. OBJECTIVES:To evaluate the benefits and harms of different human pre-implantation embryo culture media used for in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles, including intracytoplasmic morphologically selected sperm injection (IMSI). SEARCH METHODS:We searched the Cochrane Gynecology and Fertility Group's Specialized Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, the National Research Register, the Medical Research Council's Clinical Trials Register, and the NHS Centre for Reviews and Dissemination databases on 28 August 2025. We also examined the reference lists of all known primary studies, review articles, citation of relevant publications, and abstracts of major scientific meetings, and we contacted experts in the field for additional studies. ELIGIBILITY CRITERIA:We included all randomized controlled trials that randomized women, cumulus-oocytes complexes, oocytes, or embryos, and compared any two or more commercially available culture media for human pre-implantation embryos in IVF, ICSI, or IMSI protocols. OUTCOMES:Critical outcomes: cumulative live birth, live birth, and ongoing pregnancy (confirmed by heartbeat on ultrasound). Important outcomes: clinical and multiple pregnancy, miscarriage, preterm birth, birth weight, and congenital malformation. These outcomes were analyzed in the review, but we did not prioritize them for inclusion in our summary of findings tables; therefore, they are not reported in the synthesis of results section below. RISK OF BIAS:To assess the risk of bias in the studies, we used the Cochrane tool RoB 1. SYNTHESIS METHODS:Two review authors independently selected studies, assessed their risk of bias, and extracted their data. We sought additional information from the study authors where necessary. Due to heterogeneity, we presented individual study results and did not conduct meta-analysis. We calculated effect estimates as odds ratios (OR) with 95% confidence intervals (CI) using the Mantel-Haenszel fixed-effect model. We assessed the certainty of the evidence using the GRADE method. INCLUDED STUDIES:We screened 5779 search records and included 26 studies published as full articles in this updated review. Thirteen studies randomized 3913 women, two randomized 361 cycles, and 12 randomized 30,542 cumulus oocyte complexes, oocytes, or embryos. One study randomized women and oocytes. SYNTHESIS OF RESULTS:Of the 26 included studies, eight studies (3315 women) were suitable for analysis of our critical outcomes: cumulative live birth, live birth, and ongoing pregnancy. However, we were unable to pool data because no appropriately designed studies compared the same culture media. Only one study reported cumulative live birth rate and suggested that G5 likely increases live birth compared to HTF (human tubal fluid) (44.1% versus 37.9%; OR 1.29, 95% CI 0.98 to 1.70; 836 participants; moderate-certainty evidence). Six studies (3063 participants) had data for the analysis of live birth rates, providing only very low certainty evidence. It is unclear if there is a difference in live birth rates between different culture media: G5 (22.3%) versus HTF (18.1%) (OR 1.30, 95% CI 0.92 to 1.82; 836 participants; fresh embryo transfers only from first cycle); Sydney IVF cleavage (21.7%) versus G1 series 3 (22.0%) (OR 0.98, 95% CI 0.63 to 1.54; 449 participants); G2 (26.4%) versus BlastAssist M1/M2 (18.0%) (OR 1.64, 95% CI 0.80 to 3.37; 176 participants); GM501 (16.5%) versus Sydney IVF (18.8%) (OR 0.85, 95% CI 0.39 to 1.87; 170 participants); and Sydney IVF (34%) versus EmbryoGen/BlastGen (22%) (OR 1.83, 95% CI 0.75 to 4.44; 100 participants). We presented the results of the sixth study in separate groups: EmbryoAssist (18.4%) versus EmbryoAssist plus GM-CSF (granulocyte-macrophage colony-stimulating factor) (24.0%; low human serum albumin (HSA) concentration) (OR 0.71, 95% CI 0.50 to 1.02; 743 participants) and EmbryoAssist (23.8%) versus EmbryoAssist plus GM-CSF (26.1%; high HSA concentration) (OR 0.96, 95% CI 0.67 to 1.38; 589 participants). Five studies (2520 participants) reported (cumulative) ongoing pregnancy rates. We judged one study to provide moderate-certainty evidence. This study showed a cumulative ongoing pregnancy rate of 45.3% with G5 compared to 38.7% with HTF (OR 1.32, 95% CI 1.00 to 1.73; 836 participants). We judged the remaining four studies to provide very low certainty evidence. Three of them reported the following ongoing pregnancy rates: GM501 (21.2%) versus ISM1 (21.8%) (OR 0.96, 95% CI 0.46 to 1.99; 172 participants); Sydney IVF (36.0%) versus EmbryoGen/BlastGen (22.0%) (OR 1.99, 95% CI 0.82 to 4.83; 100 participants); and ECM/Multiblast (50.0%) versus Global (70.0%) (OR 0.43, 95% CI 0.17 to 1.07; 80 participants). We presented the results of the fourth study in separate groups: EmbryoAssist (21.3%) versus EmbryoAssist plus GM-CSF (30.0%; low HSA concentration) (OR 0.63, 95% CI 0.45 to 0.88; 743 participants) and EmbryoAssist (28.1%) versus EmbryoAssist plus GM-CSF (29.0%; high HSA concentration) (OR 0.96, 95% CI 0.67 to 1.38; 589 participants). In the eight studies contributing to our critical outcomes, we assessed most risk-of-bias domains as unclear. The evidence was limited by methodological problems and incomplete reporting. Outcomes were inconsistently measured, few studies used appropriate designs for live birth outcomes, and cumulative live birth was rarely assessed. Variation in culture conditions further limited comparability across studies. AUTHORS' CONCLUSIONS:Embryo culture media are important for embryonic development and subsequent success of in vitro fertilization cycles. Determining which is the most appropriate embryo culture medium has been challenging due to many factors involved in assessing efficiency. Numerous studies have been performed, but no two studies that use an appropriate design and assess clinical outcomes have compared the same culture media. One study suggested that G5 medium probably increases cumulative live birth compared with HTF medium; however, the overall evidence base remains limited and inconsistent. We conclude that there is insufficient evidence to support or refute the use of any specific culture medium for human embryo culture. Properly designed and executed randomized trials are necessary. FUNDING:This Cochrane review had no dedicated funding. REGISTRATION:Protocol (2009) DOI: 10.1002/14651858.CD007524 Original review (2015) DOI: 10.1002/14651858.CD007876.pub2.
OBJECTIVES:This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of NAM therapy compared with no PSO treatment in children with orofacial clefts.
RATIONALE:Extensive-stage small cell lung cancer (SCLC) carries a poor prognosis and has limited therapeutic options. The addition of immune-checkpoint inhibitors (ICIs) to platinum-etoposide (PE) chemotherapy has become an important first-line treatment strategy. However, the comparative benefits and harms of different first-line chemotherapy-based regimens, including ICI-containing combinations, remain unclear. OBJECTIVES:To evaluate the comparative benefits and harms of immunotherapy (anti-PD-1, anti-PD-L1, or anti-CTLA-4), plus chemotherapy and other relevant first-line systemic chemotherapy-based regimens, for the first-line systemic treatment of extensive-stage SCLC with a network meta-analysis; to rank the interventions according to their benefits and harms; and to explore the potential role of biomarkers or clinical factors, where data are available. SEARCH METHODS:We used CENTRAL, MEDLINE, and Embase, together with clinical trial registries, to identify studies that were included in the review. The latest search date was 12 December 2025. ELIGIBILITY CRITERIA:We included randomised controlled trials (RCTs) comparing first-line systemic chemotherapy-based regimens, including chemotherapy alone, chemotherapy combined with ICIs, and other relevant combination strategies, in adults (≥ 18 years) with previously untreated extensive-stage SCLC. OUTCOMES:Critical outcomes were overall survival (OS) and adverse events (AEs). These include any grade AEs, serious AEs, and grade ≥ 3 AEs. Important outcomes were progression-free survival (PFS), objective response rate (ORR), and health-related quality of life (HRQoL). RISK OF BIAS:We assessed the risk of bias using the Cochrane RoB 2 tool. We judged most studies to have low risk of bias or some concerns across key domains. Some concerns mainly related to measurement of the outcome in open-label trials and selection of the reported result where protocols or registry entries were unavailable or incomplete. The extent to which these limitations may have influenced the critical outcomes of OS and AEs remains uncertain. SYNTHESIS METHODS:We synthesised results for each outcome using meta-analysis where possible, using a contrast-based random-effects network meta-analysis with a common heterogeneity parameter. For network meta-analysis, we assessed the certainty of the evidence using the GRADE approach, informed by the CINeMA framework. INCLUDED STUDIES:Fourteen RCTs were included, with 7541 participants contributing to the critical outcome of OS. The evidence network comprised a total of 17 treatment regimens. Most studies compared PE chemotherapy combined with ICIs targeting programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1). Some trials evaluated additional immune-checkpoint pathways, including cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and T-cell immunoreceptor with Ig and ITIM domains (TIGIT), or incorporated anti-angiogenic agents. SYNTHESIS OF RESULTS:For OS, based on a network meta-analysis of 14 studies (7541 participants), PE + benmelstobart + anlotinib reduced the hazard of death most compared with PE (hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.47 to 0.79; high-certainty evidence), followed by PE + serplulimab (HR 0.63, 95% CI 0.49 to 0.82), PE + durvalumab (HR 0.71, 95% CI 0.59 to 0.85), and PE + adebrelimab (HR 0.72, 95% CI 0.58 to 0.90). Several other regimens, including PE + tislelizumab, PE + atezolizumab, PE + pembrolizumab, PE + toripalimab, and PE + durvalumab + tremelimumab, also reduced the hazard of death compared with PE. For PFS, based on 14 studies (7541 participants), the largest reductions in the hazard of progression were with PE + benmelstobart + anlotinib (HR 0.32, 95% CI 0.25 to 0.40) and PE + anlotinib (HR 0.44, 95% CI 0.36 to 0.54; high-certainty evidence). Several other regimens, including PE + tislelizumab, PE + serplulimab, PE + toripalimab, PE + adebrelimab, PE + pembrolizumab, PE + atezolizumab, and PE + durvalumab, also reduced the hazard of progression compared with PE. For ORR, based on 14 studies (7385 participants), PE + benmelstobart + anlotinib (RR 1.22, 95% CI 1.09 to 1.35), PE + anlotinib (RR 1.22, 95% CI 1.09 to 1.35), PE + pembrolizumab (RR 1.14, 95% CI 1.00 to 1.31), and PE + serplulimab (RR 1.14, 95% CI 1.03 to 1.26) increased the ORR compared with PE (high-certainty evidence), whereas most other regimens showed little or no difference compared with PE. Safety profiles varied across regimens. For any AEs, based on 11 studies (6249 participants), the risk was higher with PE + serplulimab (RR 1.25, 95% CI 1.08 to 1.43; high-certainty evidence) and was also increased with PE + ipilimumab and PE + atezolizumab-based combinations. For serious AEs, based on 10 studies (4264 participants), several regimens showed higher risks compared with PE. The largest increases were with PE + tislelizumab (RR 1.75, 95% CI 1.25 to 2.45) and PE + durvalumab + tremelimumab (RR 1.42, 95% CI 1.14 to 1.77). Higher risks were also seen with PE + adebrelimab, PE + benmelstobart + anlotinib, PE + toripalimab, and PE + socazolimab. For grade ≥ 3 AEs, based on 12 studies (6446 participants), differences between most regimens and PE were small, with increases for PE + atezolizumab + tiragolumab, PE + durvalumab + tremelimumab, PE + anlotinib, and PE + benmelstobart + anlotinib. HRQoL data were insufficient for quantitative synthesis because measurement instruments and reporting formats differed across studies; therefore, we summarised the findings narratively. AUTHORS' CONCLUSIONS:In people with extensive-stage SCLC, several ICI-based combinations with PE chemotherapy improve OS compared with PE alone (high-certainty evidence), although the magnitude of benefit varies across regimens. Some combinations probably or may have little to no effect on OS. Effects on PFS and ORR vary across treatments, and some combinations increase the risk of AEs whereas others result in little to no difference. HRQoL data were insufficient for quantitative synthesis, and so we are unable to draw conclusions about this outcome. The certainty of the evidence varies across outcomes and comparisons, reflecting differences in study design, variability in safety reporting, and limited direct head-to-head comparisons. Further RCTs directly comparing commonly used first-line regimens, with consistent reporting of AEs and patient-reported outcomes including HRQoL, are needed to reduce uncertainty and inform treatment decisions. FUNDING:Takeshi Hasegawa and Hisashi Noma were supported by the Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (Grant numbers: 22H03554, 19K03092, 24K06239). REGISTRATION:Protocol available via doi.org/10.1002/14651858.CD015738.
BACKGROUND:Atherosclerotic peripheral arterial disease (PAD) can lead to chronic limb-threatening ischemia (CLTI) and limb loss. Treatments include lifestyle modifications, medications, and both open and minimally invasive operative approaches, including balloon angioplasty. Drug-eluting balloon (DEB) angioplasty is a promising alternative to uncoated balloon angioplasty for treating PAD. Ballooning and coating the inside of atherosclerotic vessels with cytotoxic agents inhibits cellular mechanisms responsible for atherosclerosis and neointimal hyperplasia, thereby preventing or postponing its complications. Although economic analyses may have demonstrated the cost-effectiveness of DEB angioplasty, they remain considerably more expensive than uncoated balloons, and there is uncertainty around their effectiveness. This is an update of our previously published 2016 review. OBJECTIVES:To evaluate the benefits and harms of DEB angioplasty compared with uncoated, plain old balloon angioplasty (POBA) in people with symptomatic lower-limb PAD. SEARCH METHODS:We systematically searched the following databases for randomized controlled trials and controlled clinical trials: Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase Ovid, and CINAHL EBSCO. We also searched the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov. We used the bibliographies of relevant papers to identify other studies. The most recent searches were carried out on 13 March 2023. SELECTION CRITERIA:We included randomized controlled trials comparing DEB angioplasty with POBA for intermittent claudication or critical limb ischemia (CLI). DATA COLLECTION AND ANALYSIS:We used standard Cochrane methods. Our primary outcome was amputation. Our secondary outcomes included amputation-free survival, secondary vessel patency, change in ankle-brachial index (ABI), change in quality of life (QoL), change in functional walking ability, and all-cause mortality. We used GRADE to assess the certainty of evidence for selected outcomes (amputation, secondary vessel patency including target lesion revascularization and binary restenosis, change in ABI, and all-cause mortality). MAIN RESULTS:A total of 31 trials randomizing 5292 participants met the inclusion criteria. Nineteen trials included femoropopliteal arterial lesions, nine included tibial arterial lesions, and three included both. The trials were carried out in Europe, the US, China, Singapore, Jordan, Japan, and New Zealand. All trials used paclitaxel. All but four trials were industry-sponsored. There was heterogeneity in the frequency of stent deployment and antiplatelet regimens between trials. Participants were followed up for up to five years. There were better outcomes with DEB angioplasty for target lesion revascularization at one year, from 204 per 1000 lesions with POBA to 80 per 1000 lesions with DEB angioplasty (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.28 to 0.41; 23 studies, 4172 participants; P < 0.00001; low-certainty evidence). DEB angioplasty was also superior for binary restenosis at one year, from 443 per 1000 vessels with POBA to 187 per 1000 vessels with DEB angioplasty (OR 0.29, 95% CI 0.23 to 0.38; 8 studies, 1288 participants; P < 0.00001; moderate-certainty evidence). There was no difference between DEB angioplasty and POBA in amputation at one year, from 16 per 1000 participants with POBA to 22 per 1000 participants with DEB angioplasty (OR 1.45, 95% CI 0.91 to 2.29; 27 studies, 4469 participants; P = 0.12; moderate-certainty evidence); all-cause mortality, from 45 per 1000 participants with POBA to 44 per 1000 participants with DEB angioplasty (OR 0.97, 95% CI 0.71 to 1.32; 25 studies, 4312 participants; P = 0.83; moderate-certainty evidence); or change in ABI, from 0.1 to 0.35 higher with POBA and 0.03 higher to 0.03 lower with DEB angioplasty (mean difference (MD) 0, 95% CI -0.03 to 0.03; 5 studies, 1156 participants; P = 0.96; moderate-certainty evidence), although none of the studies were powered to detect a significant difference in these clinical endpoints. AUTHORS' CONCLUSIONS:Meta-analysis of 31 trials with 5292 participants demonstrated that there may be evidence of an advantage of DEB angioplasty compared with POBA in several anatomic endpoints including late lumen loss, target lesion revascularization (low-certainty evidence), and binary restenosis (moderate-certainty evidence). Conversely, there may be little to no evidence of advantage with DEB angioplasty for clinical endpoints such as amputation (moderate-quality evidence), amputation-free survival, death (moderate-quality evidence), change in ABI (moderate-quality evidence), QoL, or functional walking ability. Well-designed randomized trials with long-term follow-up are needed to further compare DEB angioplasty with POBA adequately for both anatomic and clinical study endpoints.
OBJECTIVES:This is a protocol for a Cochrane review (intervention). The objectives are as follows: To evaluate the benefits and harms of pharmacological treatments for uterine fibroids in women of reproductive age compared with placebo or no treatment, another pharmacological treatment or surgery.
OBJECTIVES:This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the benefits and harms of faecal microbiota transplantation for treating steroid-refractory, acute lower gastrointestinal graft-versus-host disease in recipients of allogeneic haematopoietic stem cell transplantation, compared with standard care, observation, placebo, or other comparator interventions.
RATIONALE:Evidence guiding how often adults with type 1 diabetes mellitus should self-monitor blood glucose, when to monitor, and which glycaemic targets to use is limited and inconsistent. The available research has not clearly linked different self-monitoring strategies to meaningful clinical outcomes, and evidence is particularly scarce for low-resource settings. Clarifying these uncertainties is important to support informed decision-making and equitable diabetes care worldwide. OBJECTIVES:To assess the effects of different timing, frequency, and glycaemic target values for self-monitoring of blood glucose (SMBG) in adults with type 1 diabetes mellitus. SEARCH METHODS:We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Science Citation Index Expanded and Emerging Sources Citation Index (Web of Science), ClinicalTrials.gov, and the WHO ICTRP, without language restrictions. The date of the last search across all databases was 7 January 2026. ELIGIBILITY CRITERIA:We included randomised controlled trials and eligible non-randomised comparative studies with a minimum duration of 24 weeks that evaluated different timing, frequency, or glycaemic target values for SMBG in adults with type 1 diabetes mellitus. We excluded cross-over and cluster-randomised trials, modelling studies, studies of pregnant individuals, and studies focused solely on self-monitoring in the context of insulin pump use. OUTCOMES:Our critical outcomes were glycaemic control (haemoglobin A1c and fasting blood glucose), hypoglycaemia (mild or moderate, severe, and nocturnal), diabetic ketoacidosis, microvascular and macrovascular complications, and quality of life. RISK OF BIAS:We assessed the risk of bias in included studies using the Cochrane RoB 2 tool for randomised controlled trials and the ROBINS-I tool for non-randomised comparative studies. SYNTHESIS METHODS:We did not conduct a meta-analysis, as effect measures and outcome reporting varied across the included studies and only three studies met the eligibility criteria. Instead, we followed Cochrane guidance on Synthesis Without Meta-analysis (SWiM) and summarised findings through structured tabulation of study characteristics and results, complemented by visual presentation of individual study effect estimates without statistical pooling. We did not use vote counting based on statistical significance. We assessed the certainty of the evidence using GRADE. INCLUDED STUDIES:We included three studies conducted in Europe and North America, involving a total of 16,481 adults with type 1 diabetes mellitus. One study was a randomised controlled trial, and two studies were observational comparative studies. All studies evaluated the frequency of SMBG; none reported eligible data on timing or glycaemic target values. Follow-up durations ranged from 9 to 24 months. SYNTHESIS OF RESULTS:Timing of SMBG No eligible studies investigating the timing of SMBG were identified. Frequency of SMBG Three studies involving a total of 16,481 adults investigated the frequency of SMBG in adults with type 1 diabetes mellitus. Overall, more frequent self-monitoring may be associated with lower haemoglobin A1c levels, although the evidence is very uncertain. In the randomised controlled trial (123 participants), the mean change in haemoglobin A1c at nine months was -0.43% in the intervention group compared with +0.23% in the control group, corresponding to approximately 0.7% lower haemoglobin A1c with more structured and frequent monitoring (mean difference (MD) -0.66, 95% confidence interval (CI) -0.94 to -0.38). The certainty of the evidence for this outcome was very low. In one observational study (1159 participants), adherence to self-monitoring guidelines may be associated with a 1.0% lower adjusted mean haemoglobin A1c (MD -1.00, 95% CI -1.21 to -0.79) compared with non-adherence. The third study (15,199 participants) reported lower haemoglobin A1c values with increasing monitoring frequency (P < 0.001), with the lowest values among those monitoring more than six times per day. Across both studies, the certainty of the evidence was very low. No included study reported effects on hypoglycaemia, diabetic ketoacidosis, microvascular or macrovascular complications, or quality of life. Glycaemic target values for SMBG No eligible studies investigating glycaemic target values for SMBG were identified. AUTHORS' CONCLUSIONS:No studies evaluated different timings of self-monitoring or different glycaemic target values. Three studies (one randomised controlled trial and two observational studies) assessed the frequency of self-monitoring and haemoglobin A1c. More frequent self-monitoring may be associated with lower haemoglobin A1c, although the evidence is sparse, frequency categories were inconsistent across studies, and the included studies had methodological limitations. The certainty of the evidence was very low for all outcomes, driven by risk of bias, imprecision, and inconsistency across studies. No studies reported hypoglycaemia, diabetic ketoacidosis, quality of life, or other critical outcomes. The evidence is insufficient to draw any firm conclusions about the effects of different self-monitoring strategies in adults with type 1 diabetes mellitus. FUNDING:This review was funded by the World Health Organization through an Agreement for Performance of Work (APW 203512799). REGISTRATION:The review was registered in PROSPERO (CRD42025639736) in February 2025.
RATIONALE:Embryo transfer (ET) is the final and most vulnerable step in in vitro fertilisation (IVF) treatment. Pregnancy rates after ET may be influenced by several factors, including straightening the utero-cervical angle, cervical and endometrial preparation, and techniques for traversing the cervix. Recent research has focused on improving the ET technique in the hope of increasing IVF success rates. This review, first published in 2009, examined preparation techniques, as it remains unclear whether these simple interventions make ET an easier procedure with higher success rates and fewer complications. OBJECTIVES:To assess the benefits and harms of different preparation techniques prior to ET. SEARCH METHODS:We searched the Cochrane Gynaecology and Fertility Group's Specialised Register, CENTRAL, MEDLINE, Embase, and PsycINFO on 6 October 2025. We handsearched the citation lists of relevant publications, reviews, and included studies. We contacted experts in the field and searched trial registries to identify any unpublished or additional trials. ELIGIBILITY CRITERIA:We included randomised controlled trials (RCTs) of the following interventions: straightening the utero-cervical angle (full bladder), cervical and endometrial preparation (removing mucus), and techniques for traversing the cervix (afterloading). Participants were women with any type of infertility undergoing IVF treatment and reaching the ET stage. OUTCOMES:Our critical outcomes were live birth rate and total adverse events per woman randomised. Important outcomes included pregnancy rate, pregnancy loss rate, and difficulty of transfer. RISK OF BIAS:We assessed the risk of bias in included studies independently for each result using the Cochrane RoB 2 tool. SYNTHESIS METHODS:Two or more review authors critically appraised potentially eligible studies. Two or more review authors independently extracted data, with any disagreements resolved by discussion with a third review author. Where appropriate data were available, we conducted meta-analysis; otherwise, we presented results narratively. We expressed dichotomous outcome data as a risk ratio. We planned the investigation of heterogeneity, subgroup analysis, and sensitivity analysis. INCLUDED STUDIES:We included 11 studies (2524 women) in the review. Of these, six studies (1341 women) evaluated the effects of three key preparation techniques before embryo transfer: straightening of the utero-cervical angle, comparing full bladder with empty bladder (two studies); cervical preparation techniques versus no intervention, comparing removal of cervical mucus to no mucus removal (two studies); and techniques for traversing the cervix, comparing afterloading to direct ET under ultrasound guidance (two studies). SYNTHESIS OF RESULTS:This review evaluated the effects of various preparation techniques on ET outcomes. The evidence is generally of low or very low certainty and therefore should be interpreted with caution. Straightening of the utero-cervical angle: ET under a full bladder versus an empty bladder No study reported the total number of live births and adverse events. We are very uncertain about the effect of a full bladder versus an empty bladder on pregnancy rate (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.69 to 1.48; I² = 0%; 2 studies, 273 participants; very low-certainty evidence), pregnancy loss rate (RR 0.96, 95% CI 0.43 to 2.14; 1 study, 131 participants; very low-certainty evidence), or difficulty of transfer (RR 0.41, 95% CI 0.16 to 1.08; 1 study, 142 participants; very low-certainty evidence). Cervical and endometrial preparation: removing mucus versus no mucus removal One study reported 52 live births per 220 cycles in the intervention group and 42 live births per 205 cycles in the control group (low-certainty evidence). No study reported the total number of adverse events. There may be little to no difference in pregnancy rate between the removing mucus group and the no mucus removal group based on one study (RR 1.02, 95% CI 0.58 to 1.80; 1 study, 97 participants), while a second study reported 65 pregnancies per 220 cycles in the intervention group and 63 pregnancies per 205 cycles in the control group (low-certainty evidence). One study reported pregnancy loss rates (15/220 cycles in the intervention group and 20/205 cycles in the control group) (low-certainty evidence). No study reported data on difficulty of transfer for this comparison. Techniques for traversing the cervix: embryo afterloading versus direct ET No study reported the total number of live births and adverse events. Embryo afterloading may result in little to no difference in pregnancy rate (RR 1.09, 95% CI 0.91 to 1.31; I² = 0%; 2 studies, 654 participants; low-certainty evidence) and pregnancy loss rate (RR 1.13, 95% CI 0.59 to 2.13; 1 study, 352 participants; low-certainty evidence). We are very uncertain about the effect on difficulty of transfer (very low-certainty evidence): one study reported that afterloading may reduce the difficulty of transfer (RR 0.25, 95% CI 0.15 to 0.41; 1 study, 352 participants), while another study reported there was no difficulty of transfer for both groups. AUTHORS' CONCLUSIONS:We added three new studies in this update, but their inclusion did not change the main conclusions of the review. No specific implications for practice are made based on the available evidence. There is a need for further and larger studies on ET preparation techniques, which should be better designed, with clearly described methods and inclusion and exclusion criteria, and greater numbers of participants. FUNDING:This Cochrane review had no dedicated funding. REGISTRATION:Protocol and previous versions available via https://doi.org/10.1002/14651858.CD007682, and https://doi.org/10.1002/14651858.CD007682.pub2.
OBJECTIVES:This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of podiatry interventions for preventing falls in older people living in the community.
RATIONALE:The vestibular system is a sensory system within the inner ear and the brain that controls balance and physical coordination. Vestibular stimulation may have an impact on various physiological processes, including breathing, reducing apnea episodes and the need for respiratory support. It has been suggested that targeted vestibular stimulation in premature infants may improve neurodevelopmental outcomes and neuromotor function. OBJECTIVES:To evaluate the benefits and harms of vestibular stimulation for reducing morbidity and promoting development in hospitalized preterm infants. SEARCH METHODS:We conducted searches in October 2025 using the following databases: CENTRAL, MEDLINE, Embase, CINAHL, Emcare, Epistemonikos, Directory of Open Access Journals (DOAJ), and three trials registries. We conducted manual searches of conference abstracts, checked the references of systematic reviews and included studies, and searched for errata or retractions related to the included studies. ELIGIBILITY CRITERIA:We included randomized controlled trials (RCTs) and quasi-RCTs that evaluated vestibular stimulation in preterm infants compared with no intervention or with other forms of vestibular stimulation. We excluded studies that combined vestibular stimulation with other types of sensory stimulation. OUTCOMES:Our outcomes of interest were major neurodevelopmental disability at 18 to 24 months' corrected age (cerebral palsy, developmental delay, intellectual impairment, blindness, and sensorineural deafness), death during initial hospitalization, and weight gain (g). We also analyzed additional clinical outcomes reported by the included studies, including intraventricular hemorrhage, duration of hospital stay, number of days until full enteral feeding and number of apnea episodes during exposure to the intervention, which we synthesized where sufficient data were available. RISK OF BIAS:We used the Cochrane risk of bias tool, RoB 2. SYNTHESIS METHODS:We conducted a meta-analysis using fixed-effect models to calculate risk ratios (RR) with their 95% confidence intervals (CI) for one outcome with dichotomous data - intraventricular hemorrhage (grades 1-4). Heterogeneity calculation was not applicable as we included only one study in each analysis. For other outcomes (weight gain, apnea, number of days until full oral feeding), we were unable to pool the results in meta-analyses because the trials presented data in different ways and at varying time points, or provided only limited data, which we were unable to recalculate for analyses. We synthesized them using synthesis without meta-analysis. We evaluated the certainty of the evidence for all outcomes using the GRADE approach. INCLUDED STUDIES:We included three RCTs and one quasi-RCT, that enrolled a total of 196 infants. One study evaluated vestibular stimulation using an oscillating air mattress; another study evaluated vestibular stimulation with an oscillating waterbed; a third study evaluated rocking; and the final study evaluated stimulation with VestibuGlide (a rocking chair). The comparisons were standard care, standard infant stimulation, and the use of a regular mattress. No studies compared different vestibular stimulation interventions. All four studies included only preterm infants. However, the range of gestational age used as an inclusion criterion varied across the studies. Three studies aimed to assess the effects of vestibular stimulation on neuromuscular develop-ment. Two of these studies also aimed to assess the effects of vestibular stimulation on body weight gain. Two studies aimed to assess the effects of vestibular stimulation on the respiratory system, and one study aimed to evaluate the role of vestibular stimulation on oral feeding functions. We identified three ongoing trials. SYNTHESIS OF RESULTS:Vestibular stimulation compared to no intervention No studies reported on major neurodevelopmental disability outcomes (cerebral palsy, developmental delay, intellectual impairment, blindness, or sensorineural deafness). The evidence is very uncertain about the effect of vestibular stimulation on death during initial hospitalization (no events were observed in either the intervention or control groups; 1 study, 122 participants; very low-certainty evidence). The evidence is very uncertain about the effect of vestibular stimulation on intraventricular hemorrhage compared with no intervention (RR 1.33, 95% CI 0.38 to 4.73; 1 study, 122 participants; very low-certainty evidence). No studies reported weight gain as prespecified in the review, however, narrative synthesis of three studies that reported weight gain using different definitions and time points suggested little to no difference between vestibular stimulation and control groups (3 studies, 169 participants, low-certainty evidence). We downgraded the overall certainty of the evidence for these outcomes due to risk of bias and imprecision. No studies reported on the duration of hospital stay, time to full oral feeding, or apnea as defined in our protocol. One vestibular intervention compared to another We found no studies that compared different types of vestibular stimulation. Therefore, it is unclear whether one approach is more effective than another. AUTHORS' CONCLUSIONS:The evidence is very uncertain about the effect of vestibular stimulation compared to no intervention on death. The evidence suggests that any vestibular stimulation may result in little to no difference in weight gain. No studies reported major neurodevelopmental disability, a critical outcome in this review. Future studies of vestibular stimulation in preterm infants should use adequately powered, parallel‑group randomized controlled designs with clearly defined outcomes and transparent intervention reporting. FUNDING:One review author, ML, received stipends to conduct this review from the Childhood Foundation of the Swedish Order of Freemasons, and the Sällskapet Barnavård, Department of Women's and Children's Health, Karolinska Institute. REGISTRATION:Protocol available via DOI10.1002/14651858.CD016072.
