Characterizing the cutaneous late effects of allogeneic hematopoietic stem cell transplantation: A systematic review.

BACKGROUND: There is a well-documented risk of secondary cutaneous malignancies following allogeneic hematopoietic stem cell transplant (HSCT), but data on risk in pediatric populations are limited. The objective of this study is to perform a systematic review of reported features and outcomes of skin cancers in pediatric allogeneic HSCT recipients. METHODS: MEDLINE, EMBASE, CINAHL, Cochrane, and Web of Science were systematically searched (Prospero CRD42022342139). Studies reporting cutaneous cancer outcomes were included if the age at transplant was ≤19 years. Titles, abstracts, and full-text articles were screened in duplicate. RESULTS: Out of 824 citations that were screened, 12 articles were selected for analysis. The final sample included 67 pediatric HSCT recipients, comprising 65 allogeneic transplant recipients and 2 cases of HSCT with an unknown donor type. The median age at transplant and skin cancer diagnosis were 7.4 and 13 years, respectively. Out of the 67 pediatric HSCT recipients, some patients developed more than one lesion, resulting in 71 lesions. The most common skin cancer type was cutaneous squamous cell carcinoma (32 lesions), followed by basal cell carcinoma (25 lesions). The median latency period between HSCT and skin cancer diagnosis ranged from 0 to 29 years. Identified risk factors for skin cancers included younger age at the time of transplant, exposure to total body irradiation, prolonged post-transplant immunosuppression, graft versus host disease, and sunburn. CONCLUSION: Skin cancers are reported in pediatric allogeneic HSCT recipients, and the risk appears to be increased. More data are needed to better characterize this risk.

A Meta-Analysis of the Global Stillbirth Rates during the COVID-19 Pandemic.

COVID-19 has been shown to have variable adverse effects on pregnancy. Reported data on stillbirth rates during the pandemic have, however, been inconsistent-some reporting a rise and others no change. Knowing the precise impact of COVID-19 on stillbirths should help with the planning and delivery of antenatal care. Our aim was, therefore, to undertake a meta-analysis to determine the impact of COVID-19 on the stillbirth rate. Databases searched included PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and Web of Science, with no language restriction. Publications with stillbirth data on women with COVID-19, comparing stillbirth rates in COVID-19 and non-COVID-19 women, as well as comparisons before and during the pandemic, were included. Two independent reviewers extracted data separately and then compared them to ensure the accuracy of extraction and synthesis. Where data were incomplete, authors were contacted for additional information, which was included if provided. The main outcome measures were (1) stillbirth (SB) rate in pregnant women with COVID-19, (2) stillbirth rates in pregnant women with and without COVID-19 during the same period, and (3) population stillbirth rates in pre-pandemic and pandemic periods. A total of 29 studies were included in the meta-analysis; from 17 of these, the SB rate was 7 per 1000 in women with COVID-19. This rate was much higher (34/1000) in low- and middle-income countries. The odds ratio of stillbirth in COVID-19 compared to non-COVID-19 pregnant women was 1.89. However, there was no significant difference in population SB between the pre-pandemic and pandemic periods. Stillbirths are an ongoing global concern, and there is evidence that the rate has increased during the COVID-19 pandemic, but mostly in low- and middle-income countries. A major factor for this is possibly access to healthcare during the pandemic. Attention should be focused on education and the provision of high-quality maternity care, such as face-to-face consultation (taking all the preventative precautions) or remote appointments where appropriate.

Interventions for Indigenous Peoples making health decisions: a systematic review.

BACKGROUND: Shared decision-making facilitates collaboration between patients and health care providers for informed health decisions. Our review identified interventions to support Indigenous Peoples making health decisions. The objectives were to synthesize evidence and identify factors that impact the use of shared decision making interventions. METHODS: An Inuit and non-Inuit team of service providers and academic researchers used an integrated knowledge translation approach with framework synthesis to coproduce a systematic review. We developed a conceptual framework to organize and describe the shared decision making processes and guide identification of studies that describe interventions to support Indigenous Peoples making health decisions. We conducted a comprehensive search of electronic databases from September 2012 to March 2022, with a grey literature search. Two independent team members screened and quality appraised included studies for strengths and relevance of studies' contributions to shared decision making and Indigenous self-determination. Findings were analyzed descriptively in relation to the conceptual framework and reported using guidelines to ensure transparency and completeness in reporting and for equity-oriented systematic reviews. RESULTS: Of 5068 citations screened, nine studies reported in ten publications were eligible for inclusion. We categorized the studies into clusters identified as: those inclusive of Indigenous knowledges and governance ("Indigenous-oriented")(n = 6); and those based on Western academic knowledge and governance ("Western-oriented")(n = 3). The studies were found to be of variable quality for contributions to shared decision making and self-determination, with Indigenous-oriented studies of higher quality overall than Western-oriented studies. Four themes are reflected in an updated conceptual framework: 1) where shared decision making takes place impacts decision making opportunities, 2) little is known about the characteristics of health care providers who engage in shared decision making processes, 3) community is a partner in shared decision making, 4) the shared decision making process involves trust-building. CONCLUSIONS: There are few studies that report on and evaluate shared decision making interventions with Indigenous Peoples. Overall, Indigenous-oriented studies sought to make health care systems more amenable to shared decision making for Indigenous Peoples, while Western-oriented studies distanced shared decision making from the health care settings. Further studies that are solutions-focused and support Indigenous self-determination are needed.

Interventions to Reduce Severe Brain Injury Risk in Preterm Neonates: A Systematic Review and Meta-analysis.

Importance: Interventions to reduce severe brain injury risk are the prime focus in neonatal clinical trials. Objective: To evaluate multiple perinatal interventions across clinical settings for reducing the risk of severe intraventricular hemorrhage (sIVH) and cystic periventricular leukomalacia (cPVL) in preterm neonates. Data Sources: MEDLINE, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases were searched from inception until September 8, 2022, using prespecified search terms and no language restrictions. Study Selection: Randomized clinical trials (RCTs) that evaluated perinatal interventions, chosen a priori, and reported 1 or more outcomes (sIVH, cPVL, and severe brain injury) were included. Data Extraction and Synthesis: Two co-authors independently extracted the data, assessed the quality of the trials, and evaluated the certainty of the evidence using the Cochrane GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Fixed-effects pairwise meta-analysis was used for data synthesis. Main Outcomes and Measures: The 3 prespecified outcomes were sIVH, cPVL, and severe brain injury. Results: A total of 221 RCTs that assessed 44 perinatal interventions (6 antenatal, 6 delivery room, and 32 neonatal) were included. Meta-analysis showed with moderate certainty that antenatal corticosteroids were associated with small reduction in sIVH risk (risk ratio [RR], 0.54 [95% CI, 0.35-0.82]; absolute risk difference [ARD], -1% [95% CI, -2% to 0%]; number needed to treat [NNT], 80 [95% CI, 48-232]), whereas indomethacin prophylaxis was associated with moderate reduction in sIVH risk (RR, 0.64 [95% CI, 0.52-0.79]; ARD, -5% [95% CI, -8% to -3%]; NNT, 20 [95% CI, 13-39]). Similarly, the meta-analysis showed with low certainty that volume-targeted ventilation was associated with large reduction in risk of sIVH (RR, 0.51 [95% CI, 0.36-0.72]; ARD, -9% [95% CI, -13% to -5%]; NNT, 11 [95% CI, 7-23]). Additionally, early erythropoiesis-stimulating agents (RR, 0.68 [95% CI, 0.57-0.83]; ARD, -3% [95% CI, -4% to -1%]; NNT, 34 [95% CI, 22-67]) and prophylactic ethamsylate (RR, 0.68 [95% CI, 0.48-0.97]; ARD, -4% [95% CI, -7% to 0%]; NNT, 26 [95% CI, 13-372]) were associated with moderate reduction in sIVH risk (low certainty). The meta-analysis also showed with low certainty that compared with delayed cord clamping, umbilical cord milking was associated with a moderate increase in sIVH risk (RR, 1.82 [95% CI, 1.03-3.21]; ARD, 3% [95% CI, 0%-6%]; NNT, -30 [95% CI, -368 to -16]). Conclusions and Relevance: Results of this study suggest that a few interventions, including antenatal corticosteroids and indomethacin prophylaxis, were associated with reduction in sIVH risk (moderate certainty), and volume-targeted ventilation, early erythropoiesis-stimulating agents, and prophylactic ethamsylate were associated with reduction in sIVH risk (low certainty) in preterm neonates. However, clinicians should carefully consider all of the critical factors that may affect applicability in these interventions, including certainty of the evidence, before applying them to clinical practice.

Mapping two decades of multiple sclerosis rehabilitation trials: A systematic scoping review and call to action to advance the study of race and ethnicity in rehabilitation research.

BACKGROUND: Multiple sclerosis (MS), is prevalent across many racial and ethnic groups, and disproportionately impacts racially minoritized populations. Rehabilitation interventions are an important component of comprehensive MS care. Yet, we do not know the extent to which MS rehabilitation trials consider race and ethnicity in defining eligibility criteria, planning recruitment strategies, selecting outcome measures, supporting intervention delivery, and designing approaches to promote adherence and retention. METHODS: We conducted a scoping review of five databases (MEDLINE, CINAHL, Cochrane Central, EMBASE, and Web of Science) to locate randomized controlled rehabilitation trials published from January 2002 to March 2022. We extracted data from relevant studies, assessed their methodological quality, and narratively summarized results. Reporting of this review is in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). RESULTS: Fifty-six studies of neurorehabilitation (n = 3), cognitive rehabilitation (n = 6), exercise training (n = 9) and self-management (n = 38) interventions were included in this review. The studies were predominantly from North America (n = 44; 73%) or Europe (n = 12; 20%) and included 4280 participants. Most participants (n = 3669; 86%) were Caucasians. Less than 10% of participants were Black (n = 282), Latinx/Hispanic (n = 60), Asian (n = 46), Indigenous (n = 7), or Arab (n = 2). Few studies discussed how race and/or ethnicity were considered in trial planning or execution. CONCLUSIONS: Without consistent and systematic attention to race and ethnicity, both in terms of trial design and reporting, it is impossible to know how MS rehabilitation interventions will translate into real-world applications. This call to action - to the MS rehabilitation research community to ensure trial and intervention processes that accommodate the needs of diverse racial and ethnic groups - is an important first step in addressing inequities in rehabilitation care for persons with MS.

Assessment of Change in Practice of Routine Tracheal Suctioning Approach of Non-Vigorous Infants Born through Meconium-Stained Amniotic Fluid: A Pragmatic Systematic Review and Meta-Analysis of Evidence outside Randomized Trials.

AIM: The 2015 recommendation of the International Liaison Committee on Resuscitation of no routine tracheal suctioning in non-vigorous neonates born through meconium-stained amniotic fluid (MSAF) was based on very low certainty of evidence (CoE) necessitating ongoing monitoring. The aim of this systematic review was to perform a meta-analysis of observational studies comparing the effect of implementing immediate resuscitation without routine tracheal suctioning versus with routine suctioning in neonates born through MSAF. METHODS: MEDLINE, Embase, CENTRAL, and Web of Science were searched. Observational studies with a before-and-after design were included. Two authors extracted data independently. CoE based on GRADE recommendations was performed. RESULTS: 13 studies were included. Clinical benefit or harm could not be excluded for the composite primary outcome of mortality or requirement of extracorporeal membranous oxygenation (ECMO) (relative risk, 95% confidence interval: 0.74 [0.47-1.17]), and mortality (0.68 [0.42-1.11]). "Routine tracheal suctioning" epoch had possibly lesser risk of meconium aspiration syndrome (MAS) when compared to "no routine tracheal suctioning" epoch (0.68 [0.47-0.99]). "Routine tracheal suctioning" epoch also possibly had a lower risk of hospital admission for respiratory symptoms, requirement of non-invasive respiratory support, invasive mechanical ventilation, surfactant treatment, air leak, and low-flow oxygen therapy. Clinical benefit or harm could not be excluded for the outcome of mortality or ECMO among those diagnosed with MAS (1.09 [0.86-1.39]), but "routine tracheal suctioning" was possibly associated with lower risk of respiratory morbidities among those diagnosed with MAS. The CoE was very low for most of the outcomes evaluated. CONCLUSIONS: Due to the very low CoE for the outcomes evaluated, no definitive conclusions can be drawn warranting the need for additional studies.

Hypocarbia is associated with adverse outcomes in hypoxic ischaemic encephalopathy (HIE).

AIM: Hypocarbia in the early postnatal period might exacerbate brain injury in babies with hypoxic ischaemic encephalopathy following birth asphyxia. This mini-review summarised studies on pCO2 values that were monitored periodically in term newborns with moderate/severe hypoxic-ischaemic encephalopathy and correlated with short or long-term outcomes. METHODS: We searched the databases MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), web of science and the Cochrane Library and identified nine studies. RESULTS: Among the nine included studies, therapeutic hypothermia was administered in seven studies. In most studies, blood pCO2 levels were measured from birth till 72 h of life or till the endpoint of therapeutic hypothermia. Eight studies showed that any hypocarbia (moderate or severe, or cumulative) was associated with an increased risk of adverse outcomes in the form of brain injury in MRI, death or neurodevelopmental disability. CONCLUSION: Hypocarbia could lead to adverse short-term and long-term outcomes despite therapeutic hypothermia in neonates with HIE. Hence, it is vital to monitor pCO2 levels closely in these infants and consider strategies to maintain pCO2 levels in the normal range.

Interventions to Prevent Bronchopulmonary Dysplasia in Preterm Neonates: An Umbrella Review of Systematic Reviews and Meta-analyses.

IMPORTANCE: Bronchopulmonary dysplasia (BPD) has multifactorial etiology and long-term adverse consequences. An umbrella review enables the evaluation of multiple proposed interventions for the prevention of BPD. OBJECTIVE: To summarize and assess the certainty of evidence of interventions proposed to decrease the risk of BPD from published systematic reviews. DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, and Web of Science were searched from inception until November 9, 2020. STUDY SELECTION: Meta-analyses of randomized clinical trials comparing interventions in preterm neonates that included BPD as an outcome. DATA EXTRACTION AND SYNTHESIS: Data extraction was performed in duplicate. Quality of systematic reviews was evaluated using Assessment of Multiple Systematic Reviews version 2, and certainty of evidence was assessed using Grading of Recommendation, Assessment, Development, and Evaluation. MAIN OUTCOMES AND MEASURES: (1) BPD or mortality at 36 weeks' postmenstrual age (PMA) and (2) BPD at 36 weeks' PMA. RESULTS: A total of 154 systematic reviews evaluating 251 comparisons were included, of which 110 (71.4%) were high-quality systematic reviews. High certainty of evidence from high-quality systematic reviews indicated that delivery room continuous positive airway pressure compared with intubation with or without routine surfactant (relative risk [RR], 0.80 [95% CI, 0.68-0.94]), early selective surfactant compared with delayed selective surfactant (RR, 0.83 [95% CI, 0.75-0.91]), early inhaled corticosteroids (RR, 0.86 [95% CI, 0.75-0.99]), early systemic hydrocortisone (RR, 0.90 [95% CI, 0.82-0.99]), avoiding endotracheal tube placement with delivery room continuous positive airway pressure and use of less invasive surfactant administration (RR, 0.90 [95% CI, 0.82-0.99]), and volume-targeted compared with pressure-limited ventilation (RR, 0.73 [95% CI, 0.59-0.89]) were associated with decreased risk of BPD or mortality at 36 weeks' PMA. Moderate to high certainty of evidence showed that inhaled nitric oxide, lower saturation targets (85%-89%), and vitamin A supplementation are associated with decreased risk of BPD at 36 weeks' PMA but not the competing outcome of BPD or mortality, indicating they may be associated with increased mortality. CONCLUSIONS AND RELEVANCE: A multipronged approach of delivery room continuous positive airway pressure, early selective surfactant administration with less invasive surfactant administration, early hydrocortisone prophylaxis in high-risk neonates, inhaled corticosteroids, and volume-targeted ventilation for preterm neonates requiring invasive ventilation may decrease the combined risk of BPD or mortality at 36 weeks' PMA.

Emerging neuroprotective interventions in periventricular leukomalacia - A systematic review of preclinical studies.

INTRODUCTION: Periventricular leukomalacia (PVL) is a result of various antenatal, intrapartum, or postnatal insults to the developing brain and is an important harbinger of cerebral palsy in preterm neonates. There is no proven therapy for PVL. This calls for appraisal of targeted therapies that have been investigated in animal models to evaluate their relevance in a clinical research context. AREAS COVERED: This systematic review identifies interventions that were evaluated in preclinical studies for neuroprotective efficacy against PVL. We identified 142 studies evaluating various interventions in PVL animal models (search method is detailed in section 2). EXPERT OPINION: Interventions that have yielded significant results in preclinical research, and that have been evaluated in a limited number of clinical trials include stem cells, erythropoietin, and melatonin. Many other therapeutic modalities evaluated in preclinical studies have been identified, but more data on their neuroprotective potential in PVL must be garnered before they can be considered for clinical trials. Because most of the tested interventions had only a partial efficacy, a combination of interventions that could be synergistic should be investigated in future preclinical studies. Furthermore, since the nature and pattern of perinatal insults to preterm brain predisposing it to PVL are substantially variable, individualized approaches for the choice of appropriate neuroprotective interventions tailored to different subgroups of preterm neonates should be explored.

Melatonin for non-operating room sedation in paediatric population: a systematic review and meta-analysis.

CONTEXT: The literature on melatonin as a sedative agent in children is limited. OBJECTIVE: To conduct a systematic review of studies assessing the efficacy and safety of melatonin for non-operating room sedation in children. METHODS: Medline, Embase, Cochrane Library and Cumulative Index to Nursing and Allied Health were searched until 9 April 2020 for studies using melatonin and reporting one of the prespecified outcomes of this review. Two authors independently assessed the eligibility, risk of bias and extracted the data. Studies with a similar study design, comparator and procedure were pooled using the fixed-effect model. RESULTS: 25 studies (clinical trials=3, observational studies=9, descriptive studies=13) were included. Melatonin was used for electroencephalogram (EEG) (n=12), brainstem evoked response audiometry (n=8) and magnetic resonance imaging (MRI) (n=5). No significant differences were noted on meta-analysis of EEG studies comparing melatonin with sleep deprivation (SD) (relative risk (RR) 1.06 (95% CI 0.99 to 1.12)), melatonin with chloral hydrate (RR 0.97 (95% CI 0.89 to 1.05)) and melatonin alone with melatonin and SD combined (RR 1.03 (95% CI 0.97 to 1.10)) for successful procedure completion. However, significantly higher sedation failure was noted in melatonin alone compared with melatonin and SD combined (RR 1.55 (95% CI 1.02 to 2.33)) for EEG. Additionally, meta-analysis showed lower sleep latency for melatonin compared with SD (mean difference -10.21 (95% CI -11.53 to -8.89) for EEG. No major adverse events were reported with melatonin. CONCLUSION: Although several studies were identified, and no serious safety concerns were noted, the evidence was not of high quality to establish melatonin's efficacy for non-operating room sedation in children.

Risk Factors for Periventricular Leukomalacia in Preterm Infants: A Systematic Review, Meta-analysis, and GRADE-Based Assessment of Certainty of Evidence.

BACKGROUND: We analyzed the certainty of evidence (CoE) for risk factors of periventricular leukomalacia (PVL) in preterm neonates, a common morbidity of prematurity. METHODS: Medline, CENTRAL, Embase, and CINAHL were searched. Cohort and case-control studies and randomised randomized controlled trials were included. Data extraction was performed in duplicate. A random random-effects meta-analysis was utilizedused. CoE was evaluated as per Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. RESULTS: One hundred eighty-six studies evaluating 95 risk factors for PVL were included. Of the 2,509,507 neonates assessed, 16,569 were diagnosed with PVL. Intraventricular hemorrhage [adjusted odds ratio: 3.22 (2.52-4.12)] had moderate CoE for its association with PVL. Other factors such as hypocarbia, chorioamnionitis, PPROM >48 hour, multifetal pregnancy reduction, antenatal indomethacin, lack of antenatal steroids, perinatal asphyxia, ventilation, shock/hypotension, patent ductus arteriosus requiring surgical ligation, late-onset circulatory collapse, sepsis, necrotizing enterocolitis, and neonatal surgery showed significant association with PVL after adjustment for confounders (CoE: very low to low). Amongst the risk factors associated with mother placental fetal (MPF) triad, there was paucity of literature related to genetic predisposition and defective placentation. Sensitivity analysis revealed that the strength of association between invasive ventilation and PVL decreased over time (P < 0.01), suggesting progress in ventilation strategies. Limited studies had evaluated diffuse PVL. CONCLUSION: Despite decades of research, our findings indicate that the CoE is low to very low for most of the commonly attributed risk factors of PVL. Future studies should evaluate genetic predisposition and defective placentation in the MPF triad contributing to PVL. Studies evaluating exclusively diffuse PVL are warranted.

Delivery Room Interventions for Hypothermia in Preterm Neonates: A Systematic Review and Network Meta-analysis.

Importance: Prevention of hypothermia in the delivery room is a cost-effective, high-impact intervention to reduce neonatal mortality, especially in preterm neonates. Several interventions for preventing hypothermia in the delivery room exist, of which the most beneficial is currently unknown. Objective: To identify the delivery room thermal care intervention that can best reduce neonatal hypothermia and improve clinical outcomes for preterm neonates born at 36 weeks' gestation or less. Data Sources: MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, and CINAHL databases were searched from inception to November 5, 2020. Study Selection: Randomized and quasi-randomized clinical trials of thermal care interventions in the delivery room for preterm neonates were included. Peer-reviewed abstracts and studies published in non-English language were also included. Data Extraction and Synthesis: Data from the included trials were extracted in duplicate using a structured proforma. A network meta-analysis with bayesian random-effects model was used for data synthesis. Main Outcomes and Measures: Primary outcomes were core body temperature and incidence of moderate to severe hypothermia on admission or within the first 2 hours of life. Secondary outcomes were incidence of hyperthermia, major brain injury, and mortality before discharge. The 9 thermal interventions evaluated were (1) plastic bag or plastic wrap covering the torso and limbs with the head uncovered or covered with a cloth cap; (2) plastic cap covering the head; (3) skin-to-skin contact; (4) thermal mattress; (5) plastic bag or plastic wrap with a plastic cap; (6) plastic bag or plastic wrap along with use of a thermal mattress; (7) plastic bag or plastic wrap along with heated humidified gas for resuscitation or for initiating respiratory support in the delivery room; (8) plastic bag or plastic wrap along with an incubator for transporting from the delivery room; and (9) routine care, including drying and covering the body with warm blankets, with or without a cloth cap. Results: Of the 6154 titles and abstracts screened, 34 studies that enrolled 3688 neonates were analyzed. Compared with routine care alone, plastic bag or wrap with a thermal mattress (mean difference [MD], 0.98 °C; 95% credible interval [CrI], 0.60-1.36 °C), plastic cap (MD, 0.83 °C; 95% CrI, 0.28-1.38 °C), plastic bag or wrap with heated humidified respiratory gas (MD, 0.76 °C; 95% CrI, 0.38-1.15 °C), plastic bag or wrap with a plastic cap (MD, 0.62 °C; 95% CrI, 0.37-0.88 °C), thermal mattress (MD, 0.62 °C; 95% CrI, 0.33-0.93 °C), and plastic bag or wrap (MD, 0.56 °C; 95% CrI, 0.44-0.69 °C) were associated with greater core body temperature. Certainty of evidence was moderate for 5 interventions and low for plastic bag or wrap with a thermal mattress. When compared with routine care alone, a plastic bag or wrap with heated humidified respiratory gas was associated with less risk of major brain injury (risk ratio, 0.23; 95% CrI, 0.03-0.67; moderate certainty of evidence) and a plastic bag or wrap with a plastic cap was associated with decreased risk of mortality (risk ratio, 0.19; 95% CrI, 0.02-0.66; low certainty of evidence). Conclusions and Relevance: Results of this study indicate that most thermal care interventions in the delivery room for preterm neonates were associated with improved core body temperature (with moderate certainty of evidence). Specifically, use of a plastic bag or wrap with a plastic cap or with heated humidified gas was associated with lower risk of major brain injury and mortality (with low to moderate certainty of evidence).

Frequency of ventilator circuit changes to prevent ventilator-associated pneumonia in neonates and children-A systematic review and meta-analysis.

OBJECTIVE: To assess the effect of different frequencies of ventilator circuit changes in neonates and children through a systematic review and meta-analysis. INTERVENTIONS: (1) "No routine change of ventilator circuit (unless visibly soiled)" versus "routine change at any fixed interval"; (2) routine change of circuit at "less frequent" versus "more frequent" intervals. OUTCOMES: Primary outcomes were VAP rate (number of VAP episodes per 1000 ventilator-days) and all-cause mortality before discharge. METHODS: MEDLINE, CENTRAL, EMBASE, and CINAHL were systematically searched from inception till November 3, 2020. Two authors assessed trial eligibility and risk of bias, and independently extracted data. Data were synthesized using fixed effects model. GRADE was used to assess certainty of evidence (CoE). RESULTS: We identified six studies enrolling 768 participants evaluating circuit changes at two fixed intervals. Meta-analysis of studies on circuit changes "once in less than 7 days" versus "once weekly" showed no difference in VAP rate (risk ratio: 0.83 [0.38-1.81]; one randomized controlled trial (RCT) and 0.94 [0.49-1.81]; two before-after studies) or mortality before discharge (0.67 [0.34-1.3]; one RCT and 1.01 [0.63-1.64]; two before-after studies). CoE was very low. Less frequent circuit changes reduced health-care costs. No study evaluating "circuit changes only when visibly soiled" versus "circuit changes at a fixed interval" was identified. CONCLUSION: There is no evidence to suggest that ventilator circuits can be safely left unchanged until visibly soiled in neonates and children. Extending circuit changes interval to "once weekly" may not increase VAP rate (CoE-very low) and reduces healthcare costs.

Electronic intrapartum fetal monitoring: a systematic review of international clinical practice guidelines.

BACKGROUND: Electronic fetal monitoring or fetal assessment using a cardiotocograph is currently the most commonly employed tool for intrapartum surveillance. Furthermore, there are numerous guidelines informing best practice worldwide. OBJECTIVE: This systematic review aimed to compare and appraise all available practice guidelines on intrapartum electronic fetal monitoring to describe the similarities and variations in recommendations. STUDY DESIGN: A systematic protocol was developed per Preferred Reporting Item for Systematic Review and Meta-Analysis Protocols. A total of 4 independent reviewers were involved with independent searches and quality assessment using the Appraisal of Guidelines for Research and Evaluation Instrument for guideline quality reporting. RESULTS: Overall, 7 international practice guidelines were included in this systematic review. Appraisal of Guidelines for Research and Evaluation Instrument showed higher scores for scope and purpose and for clarity of presentation; however, the overall assessment varied between 25% and 89%. When individual characteristics of electronic fetal monitoring or cardiotocograph were compared, all guidelines and guidance were essentially trying to describe the characters similarly, with critical differences described in the full article. CONCLUSION: In the context of globalization, a uniform approach for defining terminology, classifying characters and similar interpretation of results is needed for electronic fetal monitoring. Therefore, we should consider a unified, simple, logistically approved, and acceptable guideline, which is probably accepted worldwide.

A meta-analysis of the prevalence of gestational diabetes in patients diagnosed with obstetrical cholestasis.

BACKGROUND: Gestational diabetes and obstetrical cholestasis are common clinical conditions seen in clinical practice. There is evidence suggesting a coexisting relationship that could have a potential clinical implication related to stillbirth outcomes. OBJECTIVE: This study aimed to determine the prevalence of gestational diabetes in women with obstetrical cholestasis. STUDY DESIGN: A predefined protocol with a literature search was used to obtain all possible articles. A systematic review and meta-analysis of observational studies with quantifiable data published since 2010 were performed. Articles were evaluated and included in the study with specified criteria for the risk of bias using the Newcastle-Ottawa Scale. A meta-analysis was performed using Meta-analysis of Observational Studies in Epidemiology specifications to determine the prevalence of gestational diabetes in women with obstetrical cholestasis. RESULTS: A total of 16,748 patients with obstetrical cholestasis from 21 studies were included. The prevalence of gestational diabetes in women with obstetrical cholestasis was 13.9% (20 studies analyzed). Gestational diabetes was more common in women with obstetrical cholestasis than in women without obstetrical cholestasis (odds ratio, 2.129; 95% confidence interval, 1.697-2.670;10 studies). Gestational diabetes is twice more common in women with severe cholestasis than in women with mild cholestasis (odds ratio, 2.168; 95% confidence interval, 1.429-3.289; 4 studies). CONCLUSION: There is an increase in the prevalence of gestational diabetes among women diagnosed with obstetrical cholestasis. Compared with women with mild cholestasis, the increased risk of gestational diabetes in women with severe cholestatis is more than doubled. This suggests that the 2 conditions may have some biological similarities that affect clinical outcomes.

Neurodevelopmental outcomes following bevacizumab treatment for retinopathy of prematurity: a systematic review and meta-analysis.

OBJECTIVE: To systematically review the studies exploring the association between bevacizumab and neurodevelopmental outcomes. METHODS: Embase, Medline, CINAHL, and Cochrane Library databases were searched for studies examining neurodevelopmental outcomes of preterm infants treated with bevacizumab compared to laser ablation or cryotherapy for severe retinopathy of prematurity (ROP). RESULTS: Thirteen studies (clinical trial = 1; cohort studies = 12) were included. Random-effects model meta-analysis showed significant increased odds of cognitive impairment associated with bevacizumab treatment on both unadjusted (unadjusted odds ratio (OR) 1.61; 95% confidence interval (CI) 1.12, 2.30) and adjusted analyses (adjusted OR 1.90; 95% CI 1.22, 2.97). Infants treated with bevacizumab for severe ROP had significantly lower Bayley-III cognitive (mean difference (MD) -1.66; 95% CI -3.21, -0.12), and language composite scores (MD -5.50; 95% CI -8.24, -2.76) compared to infants treated with laser ablation or cryotherapy. CONCLUSION: Bevacizumab treatment for severe ROP is associated with increased risk of cognitive impairment and lower cognitive and language scores in preterm infants.