Factors associated with posttraumatic stress and anxiety among the parents of babies admitted to neonatal care: a systematic review.

BACKGROUND: Posttraumatic stress (PTS) and anxiety are common mental health problems among parents of babies admitted to a neonatal unit (NNU). This review aimed to identify sociodemographic, pregnancy and birth, and psychological factors associated with PTS and anxiety in this population. METHOD: Studies published up to December 2022 were retrieved by searching Medline, Embase, PsychoINFO, Cumulative Index to Nursing and Allied Health electronic databases. The modified Newcastle-Ottawa Scale for cohort and cross-sectional studies was used to assess the methodological quality of included studies. This review was pre-registered in PROSPERO (CRD42021270526). RESULTS: Forty-nine studies involving 8,447 parents were included; 18 studies examined factors for PTS, 24 for anxiety and 7 for both. Only one study of anxiety factors was deemed to be of good quality. Studies generally included a small sample size and were methodologically heterogeneous. Pooling of data was not feasible. Previous history of mental health problems (four studies) and parental perception of more severe infant illness (five studies) were associated with increased risk of PTS, and had the strongest evidence. Shorter gestational age (≤ 33 weeks) was associated with an increased risk of anxiety (three studies) and very low birth weight (< 1000g) was associated with an increased risk of both PTS and anxiety (one study). Stress related to the NNU environment was associated with both PTS (one study) and anxiety (two studies), and limited data suggested that early engagement in infant's care (one study), efficient parent-staff communication (one study), adequate social support (two studies) and positive coping mechanisms (one study) may be protective factors for both PTS and anxiety. Perinatal anxiety, depression and PTS were all highly comorbid conditions (as with the general population) and the existence of one mental health condition was a risk factor for others. CONCLUSION: Heterogeneity limits the interpretation of findings. Until clearer evidence is available on which parents are most at risk, good communication with parents and universal screening of PTS and anxiety for all parents whose babies are admitted to NNU is needed to identify those parents who may benefit most from mental health interventions.

Brain health measurement: a scoping review.

OBJECTIVES: Preservation of brain health is an urgent priority for the world's ageing population. The evidence base for brain health optimisation strategies is rapidly expanding, but clear recommendations have been limited by heterogeneity in measurement of brain health outcomes. We performed a scoping review to systematically evaluate brain health measurement in the scientific literature to date, informing development of a core outcome set. DESIGN: Scoping review. DATA SOURCES: Medline, APA PsycArticles and Embase were searched through until 25 January 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies were included if they described brain health evaluation methods in sufficient detail in human adults and were in English language. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened titles, abstracts and full texts for inclusion and extracted data using Covidence software. RESULTS: From 6987 articles identified by the search, 727 studies met inclusion criteria. Study publication increased by 22 times in the last decade. Cohort study was the most common study design (n=609, 84%). 479 unique methods of measuring brain health were identified, comprising imaging, cognitive, mental health, biological and clinical categories. Seven of the top 10 most frequently used brain health measurement methods were imaging based, including structural imaging of grey matter and hippocampal volumes and white matter hyperintensities. Cognitive tests such as the trail making test accounted for 286 (59.7%) of all brain health measurement methods. CONCLUSIONS: The scientific literature surrounding brain health has increased exponentially, yet measurement methods are highly heterogeneous across studies which may explain the lack of clinical translation. Future studies should aim to develop a selected group of measures that should be included in all brain health studies to aid interstudy comparison (core outcome set), and broaden from the current focus on neuroimaging outcomes to include a range of outcomes.

Body Composition and Risk of Incident Heart Failure in 1 Million Adults: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.

Background The aim of this systematic review was to quantify the associations between body composition measures and risk of incident heart failure (HF) and its subtypes in the general population. Methods and Results We searched Medline, Embase, and Global Health databases from each database inception to January 19, 2023 for prospective studies reporting on body composition and HF risk. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Newcastle-Ottawa scale was used to assess the risk of bias of included studies. Fixed-effects models were used for meta-analysis. Thirty-five studies were included (ntotal=1 137 044; ncases=34 422). Summary relative risk (RR) per 5-kg/m2 higher body mass index was 1.42 (95% CI, 1.40-1.42; 𝜁2=0.02, I2=94.4%), 1.28 (95% CI, 1.26-1.31; 𝜁2=0.01, I2=75.8%) per 10-cm higher waist circumference, and 1.33 (95% CI, 1.28-1.37; 𝜁2=0.04, I2=94.9%) per 0.1-unit higher waist-hip ratio. Pooled estimates of the few studies that reported on regional fat suggested significant positive association between HF risk and both visceral fat (RR, 1.08 [95% CI, 1.04-1.12]) and pericardial fat (RR, 1.08 [95% CI, 1.06-1.10]). Among HF subtypes, associations were stronger for HF with preserved ejection fraction than HF with reduced ejection fraction. No study reported on lean mass. Conclusions Pooled data suggested strong associations between adiposity and HF. The association with adiposity is stronger for HF with preserved ejection fraction than HF with reduced ejection fraction, indicating that different mechanisms may be at play in etiopathogenesis of HF subtypes. Future studies are needed to investigate role of regional fat mass and lean mass in HF risk. Registration Information REGISTRATION: URL: www.crd.york.ac.uk/prospero/. Unique identifier: CRD42020224584.

Correlates of chronic hepatitis B virus infection in the general adult population of China: Systematic review and meta-analysis.

Chronic infection with hepatitis B virus (HBV) is a significant public health issue in China. Understanding factors associated with chronic HBV is important to enable targeted screening and education and to improve early diagnosis and prevention of disease progression. This systematic review and meta-analysis aimed to identify and describe correlates of chronic HBV among Chinese adults. Searches were conducted in MEDLINE, EMBASE and grey literature up to 25 June 2020. Eligible papers included observational studies in adults of the general population in China that reported factors associated with chronic HBV, measured by Hepatitis B surface antigen (HBsAg). Meta-analysis was performed using fixed-effect models of HBsAg prevalence among factors, and of adjusted odds ratios (ORs) for chronic HBV associated with each factor. Overall 39 articles were included, covering 22 factors, including a range of sociodemographic, behavioural and medical factors. In meta-analysis of eligible studies, a range of factors were significantly associated with higher HBsAg prevalence, including middle age, male sex, being married, rural residence, lower education, smoking, having a HBsAg positive household contact, family history of HBV, history of surgery or blood transfusion. The adjusted ORs varied, from 1.11 (95% CI 1.05-1.18) for smoking to 5.13 (95% CI 4.99-5.26) for having a HBsAg positive household contact. In Chinese adults, a range of factors are associated with chronic HBV infection, which may help inform targeted screening in the general population.

Impact of low-dose computed tomography (LDCT) screening on lung cancer-related mortality.

BACKGROUND: Lung cancer is the most common cause of cancer-related death in the world, however lung cancer screening has not been implemented in most countries at a population level. A previous Cochrane Review found limited evidence for the effectiveness of lung cancer screening with chest radiography (CXR) or sputum cytology in reducing lung cancer-related mortality, however there has been increasing evidence supporting screening with low-dose computed tomography (LDCT).  OBJECTIVES: To determine whether screening for lung cancer using LDCT of the chest reduces lung cancer-related mortality and to evaluate the possible harms of LDCT screening. SEARCH METHODS: We performed the search in collaboration with the Information Specialist of the Cochrane Lung Cancer Group and included the Cochrane Lung Cancer Group Trial Register, Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library, current issue), MEDLINE (accessed via PubMed) and Embase in our search. We also searched the clinical trial registries to identify unpublished and ongoing trials. We did not impose any restriction on language of publication. The search was performed up to 31 July 2021.  SELECTION CRITERIA: Randomised controlled trials (RCTs) of lung cancer screening using LDCT and reporting mortality or harm outcomes.  DATA COLLECTION AND ANALYSIS: Two review authors were involved in independently assessing trials for eligibility, extraction of trial data and characteristics, and assessing risk of bias of the included trials using the Cochrane RoB 1 tool. We assessed the certainty of evidence using GRADE. Primary outcomes were lung cancer-related mortality and harms of screening. We performed a meta-analysis, where appropriate, for all outcomes using a random-effects model. We only included trials in the analysis of mortality outcomes if they had at least 5 years of follow-up. We reported risk ratios (RRs) and hazard ratios (HRs), with 95% confidence intervals (CIs) and used the I2 statistic to investigate heterogeneity.  MAIN RESULTS: We included 11 trials in this review with a total of 94,445 participants. Trials were conducted in Europe and the USA in people aged 40 years or older, with most trials having an entry requirement of ≥ 20 pack-year smoking history (e.g. 1 pack of cigarettes/day for 20 years or 2 packs/day for 10 years etc.). One trial included male participants only. Eight trials were phase three RCTs, with two feasibility RCTs and one pilot RCT. Seven of the included trials had no screening as a comparison, and four trials had CXR screening as a comparator. Screening frequency included annual, biennial and incrementing intervals. The duration of screening ranged from 1 year to 10 years. Mortality follow-up was from 5 years to approximately 12 years.  None of the included trials were at low risk of bias across all domains. The certainty of evidence was moderate to low across different outcomes, as assessed by GRADE. In the meta-analysis of trials assessing lung cancer-related mortality, we included eight trials (91,122 participants), and there was a reduction in mortality of 21% with LDCT screening compared to control groups of no screening or CXR screening (RR 0.79, 95% CI 0.72 to 0.87; 8 trials, 91,122 participants; moderate-certainty evidence). There were probably no differences in subgroups for analyses by control type, sex, geographical region, and nodule management algorithm. Females appeared to have a larger lung cancer-related mortality benefit compared to males with LDCT screening. There was also a reduction in all-cause mortality (including lung cancer-related) of 5% (RR 0.95, 95% CI 0.91 to 0.99; 8 trials, 91,107 participants; moderate-certainty evidence).  Invasive tests occurred more frequently in the LDCT group (RR 2.60, 95% CI 2.41 to 2.80; 3 trials, 60,003 participants; moderate-certainty evidence). However, analysis of 60-day postoperative mortality was not significant between groups (RR 0.68, 95% CI 0.24 to 1.94; 2 trials, 409 participants; moderate-certainty evidence).  False-positive results and recall rates were higher with LDCT screening compared to screening with CXR, however there was low-certainty evidence in the meta-analyses due to heterogeneity and risk of bias concerns. Estimated overdiagnosis with LDCT screening was 18%, however the 95% CI was 0 to 36% (risk difference (RD) 0.18, 95% CI -0.00 to 0.36; 5 trials, 28,656 participants; low-certainty evidence). Four trials compared different aspects of health-related quality of life (HRQoL) using various measures. Anxiety was pooled from three trials, with participants in LDCT screening reporting lower anxiety scores than in the control group (standardised mean difference (SMD) -0.43, 95% CI -0.59 to -0.27; 3 trials, 8153 participants; low-certainty evidence). There were insufficient data to comment on the impact of LDCT screening on smoking behaviour.  AUTHORS' CONCLUSIONS: The current evidence supports a reduction in lung cancer-related mortality with the use of LDCT for lung cancer screening in high-risk populations (those over the age of 40 with a significant smoking exposure). However, there are limited data on harms and further trials are required to determine participant selection and optimal frequency and duration of screening, with potential for significant overdiagnosis of lung cancer. Trials are ongoing for lung cancer screening in non-smokers.

Prevalence of anxiety and post-traumatic stress (PTS) among the parents of babies admitted to neonatal units: A systematic review and meta-analysis.

BACKGROUND: Parents of babies admitted to neonatal units (NNU) are exposed to a range of potentially distressing experiences, which can lead to mental health symptoms such as increased anxiety and post-traumatic stress (PTS). This review aimed to describe how anxiety and PTS are defined and assessed, and to estimate anxiety and PTS prevalence among parents of babies admitted to NNU. METHOD: Medline, Embase, PsychoINFO, Cumulative Index to Nursing and Allied Health literature were searched to identify studies published prior to April 14, 2021. Included studies were assessed using Hoy risk of bias tool. A random-effects model was used to estimate pooled prevalence with 95% CIs. Potential sources of variation were investigated using subgroup analyses and meta-regression. The review is registered with PROSPERO (CRD42020162935). FINDINGS: Fifty six studies involving 6,036 parents met the review criteria; 21 studies assessed anxiety, 35 assessed PTS, and 8 assessed both. The pooled prevalence of anxiety was 41.9% (95%CI:30.9, 53.0) and the pooled prevalence of PTS was 39.9% (95%CI:30.8, 48.9) among parents up to one month after the birth. Anxiety prevalence decreased to 26.3% (95%CI:10.1, 42.5) and PTS prevalence to 24.5% (95%CI:17.4, 31.6) between one month and one year after birth. More than one year after birth PTS prevalence remained high 27.1% (95%CI:20.7, 33.6). Data on anxiety at this time point were limited. There was high heterogeneity between studies and some evidence from subgroup and meta-regression analyses that study characteristics contributed to the variation in prevalence estimates. INTERPRETATION: The prevalence of anxiety and PTS was high among parents of babies admitted to NNU. The rates declined over time, although they remained higher than population prevalence estimates for women in the perinatal period. Implementing routine screening would enable early diagnosis and effective intervention. FUNDING: This research is funded by the National Institute for Health Research (NIHR) Policy Research Programme, conducted through the Policy Research Unit in Maternal and Neonatal Health and Care, PR-PRU-1217-21202. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

Body composition and risk of heart failure: protocol for a systematic review and meta-analysis.

INTRODUCTION: Although there is strong evidence of an association between general adiposity and incidence of heart failure, previous systematic reviews and meta-analyses have not reliably assessed the association of heart failure risk with other aspects of body composition (such as body fat distribution or lean mass), or between body composition and risk of heart failure subtypes. We aim to conduct a systematic review and meta-analysis of prospective studies to address these uncertainties, and inform efforts to prevent and treat heart failure. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols statement was used as a template for this protocol. A systematic search of Medline, Embase and Global Health from database inception to present will be conducted to identify prospective studies reporting on the associations between major measures of body composition (body mass index, waist circumference, waist-hip ratio, total body fat, visceral adiposity tissue and lean mass) and risk of heart failure. Article screening and selection will be performed by two reviewers independently, and disagreements will be adjudicated by consensus or by a third reviewer. Data from eligible articles will be extracted, and article quality will be assessed using the Newcastle-Ottawa Scale. Relative risks (and 95% CIs) will be pooled in a fixed effect meta-analysis, if there is no prohibitive heterogeneity of studies as assessed using the Cochrane Q statistic and I2 statistic. Subgroup analyses will be by age, sex, ethnicity and heart failure subtypes. Publication bias in the meta-analysis will be assessed using Egger's test and funnel plots. ETHICS AND DISSEMINATION: This work is secondary analyses on published data and ethical approval is not required. We plan to publish results in an open-access peer-reviewed journal, present it at international and national conferences, and share the findings on social media. PROSPERO REGISTRATION NUMBER: CRD42020224584.

The top 10 research priorities in diabetes and pregnancy according to women, support networks and healthcare professionals.

AIMS: To undertake a Priority Setting Partnership (PSP) to establish priorities for future research in diabetes and pregnancy, according to women with experience of pregnancy, and planning pregnancy, with any type of diabetes, their support networks and healthcare professionals. METHODS: The PSP used established James Lind Alliance (JLA) methodology working with women and their support networks and healthcare professionals UK-wide. Unanswered questions about the time before, during or after pregnancy with any type of diabetes were identified using an online survey and broad-level literature search. A second survey identified a shortlist of questions for final prioritisation at an online consensus development workshop. RESULTS: There were 466 responses (32% healthcare professionals) to the initial survey, with 1161 questions, which were aggregated into 60 unanswered questions. There were 614 responses (20% healthcare professionals) to the second survey and 18 questions shortlisted for ranking at the workshop. The top 10 questions were: diabetes technology, the best test for diabetes during pregnancy, diet and lifestyle interventions for diabetes management during pregnancy, emotional and well-being needs of women with diabetes pre- to post-pregnancy, safe full-term birth, post-natal care and support needs of women, diagnosis and management late in pregnancy, prevention of other types of diabetes in women with gestational diabetes, women's labour and birth experiences and choices and improving planning pregnancy. CONCLUSIONS: These research priorities provide guidance for research funders and researchers to target research in diabetes and pregnancy that will achieve greatest value and impact.

Single or combined immune checkpoint inhibitors compared to first-line platinum-based chemotherapy with or without bevacizumab for people with advanced non-small cell lung cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have changed the first-line treatment of people with advanced non-small cell lung cancer (NSCLC). Single-agent pembrolizumab (a PD-1 inhibitor) is currently the standard of care as monotherapy in patients with PD-L1 expression ≥ 50%, either alone or in combination with chemotherapy when PD-L1 expression is less than 50%. Atezolizumab (PD-L1 inhibitor) has also been approved in combination with chemotherapy and bevacizumab (an anti-angiogenic antibody) in first-line NSCLC regardless of PD-L1 expression. The combination of first-line PD-1/PD-L1 inhibitors with anti-CTLA-4 antibodies has also been shown to improve survival compared to platinum-based chemotherapy in advanced NSCLC, particularly in people with high tumour mutational burden (TMB). The association of ipilimumab (an anti CTLA4) and nivolumab (PD-1 inhibitor) has been approved by the US Food and Drug Administration (FDA) in all patients with PD-L1 expression ≥1%. Although these antibodies are currently used in clinical practice, some questions remain unanswered, such as the best-treatment strategy, the role of different biomarkers for treatment selection and the effectiveness of immunotherapy according to specific clinical characteristics. OBJECTIVES: To determine the effectiveness and safety of first-line immune checkpoint inhibitors (ICIs), as monotherapy or in combination, compared to platinum-based chemotherapy, with or without bevacizumab for people with advanced NSCLC, according to the level of PD-L1 expression. SEARCH METHODS: We performed an electronic search of the main databases (Cochrane Central Register of Controlled Trials, MEDLINE, Embase) from inception until 31 December 2020 and conferences meetings from 2015 onwards. SELECTION CRITERIA: We included randomised controlled trials (RCTs) reporting on the efficacy or safety of first-line ICI treatment for adults with advanced NSCLC who had not previously received any anticancer treatment. We included trials comparing single- or double-ICI treatment to standard first-line therapy (platinum-based chemotherapy +/- bevacizumab). All data come from 'international multicentre studies involving adults, age 18 or over, with histologically-confirmed stage IV NSCLC. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed the search results and a fourth review author resolved any disagreements. Primary outcomes were overall survival (OS) and progression-free survival (PFS); secondary outcomes were overall objective response rate (ORR) by RECIST v 1.1, grade 3 to 5 treatment-related adverse events (AEs) (CTCAE v 5.0) and health-related quality of life (HRQoL). We performed meta-analyses where appropriate using the random-effects model for hazard ratios (HRs) or risk ratios (RRs), with 95% confidence intervals (95% CIs), and used the I² statistic to investigate heterogeneity. MAIN RESULTS: Main results We identified 15 trials for inclusion, seven completed and eight ongoing trials. We obtained data for 5893 participants from seven trials comparing first-line single- (six trials) or double- (two trials) agent ICI with platinum-based chemotherapy, one trial comparing both first-line single- and double-agent ICsI with platinum-based chemotherapy. All trials were at low risk of selection and detection bias, some were classified at high risk of performance, attrition or other source of bias. The overall certainty of evidence according to GRADE ranged from moderate-to-low because of risk of bias, inconsistency, or imprecision. The majority of the included trials reported their outcomes by PD-L1 expressions, with PD-L1 ≥ 50 being considered the most clinically useful cut-off level for decision makers. Also, iIn order to avoid overlaps between various PDL-1 expressions we prioritised the review outcomes according to PD-L1 ≥ 50. Single-agent ICI In the PD-L1 expression ≥ 50% group single-agent ICI probably improved OS compared to platinum-based chemotherapy (hazard ratio (HR) 0.68, 95% confidence interval (CI) 0.60 to 0.76, 6 RCTs, 2111 participants, moderate-certainty evidence). In this group, single-agent ICI also may improve PFS (HR: 0.68, 95% CI 0.52 to 0.88, 5 RCTs, 1886 participants, low-certainty evidence) and ORR (risk ratio (RR):1.40, 95% CI 1.12 to 1.75, 4 RCTs, 1672 participants, low-certainty evidence). HRQoL data were available for only one study including only people with PD-L1 expression ≥ 50%, which suggested that single-agent ICI may improve HRQoL at 15 weeks compared to platinum-based chemotherapy (RR: 1.51, 95% CI 1.08 to 2.10, 1 RCT, 297 participants, low-certainty evidence). In the included studies, treatment-related AEs were not reported according to PD-L1 expression levels. Grade 3-4 AEs may be less frequent with single-agent ICI compared to platinum-based chemotherapy (RR: 0.41, 95% CI 0.33 to 0.50, I² = 62%, 5 RCTs, 3346 participants, low-certainty evidence). More information about efficacy of single-agent ICI compared to platinum-based chemotherapy according to the level of PD-L1 expression and to TMB status or specific clinical characteristics is available in the full text. Double-agent ICI Double-ICI treatment probably prolonged OS compared to platinum-based chemotherapy in people with PD-L1 expression ≥50% (HR: 0.72, 95% CI 0.59 to 0.89 2 RCTs, 612 participants, moderate-certainty evidence). Trials did not report data on HRQoL, PFS and ORR according to PD-L1 groups. Treatment related AEs were not reported according to PD-L1 expression levels. The frequency of grade 3-4 AEs may not differ between double-ICI treatment and platinum-based chemotherapy (RR: 0.78, 95% CI 0.55 to 1.09, I² = 81%, 2 RCTs, 1869 participants, low-certainty evidence). More information about efficacy of double-agent ICI according to the level of PD-L1 expression and to TMB status is available in the full text. AUTHORS' CONCLUSIONS: Authors' conclusions The evidence in this review suggests that single-agent ICI in people with NSCLC and PD-L1 ≥50% probably leads to a higher overall survival rate and may lead to a higher progression-free survival and overall response rate when compared to platinum-based chemotherapy and may also lead to a lower rate of adverse events and higher HRQoL. Combined ICI in people with NSCLC and PD-L1 ≥50% also probably leads to a higher overall survival rate when compared to platinum-based chemotherapy, but its effect on progression-free survival, overall response rate and HRQoL is unknown due to a lack of data. The rate of adverse events may not differ between groups. This review used to be a living review. It is transitioned out of living mode because current research is exploring ICI in association with chemotherapy or other immunotherapeutic drugs versus ICI as single agent rather than platinum based chemotherapy.

Single or combined immune checkpoint inhibitors compared to first-line platinum-based chemotherapy with or without bevacizumab for people with advanced non-small cell lung cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have changed the first-line treatment of people with advanced non-small cell lung cancer (NSCLC). Single-agent pembrolizumab (a PD-1 inhibitor) is currently the standard of care as monotherapy in patients with PD-L1 expression ≥ 50%, either alone or in combination with chemotherapy when PD-L1 expression is less than 50%. Atezolizumab (PD-L1 inhibitor) has also been approved in combination with chemotherapy and bevacizumab (an anti-angiogenic antibody) in first-line NSCLC regardless of PD-L1 expression. The combination of first-line PD-1/PD-L1 inhibitors with anti-CTLA-4 antibodies has also been shown to improve survival compared to platinum-based chemotherapy in advanced NSCLC, particularly in people with high tumour mutational burden (TMB). The association of ipilimumab (an anti CTLA4) and nivolumab (PD-1 inhibitor) has been approved by the US Food and Drug Administration (FDA) in all patients with PD-L1 expression ≥1%. Although these antibodies are currently used in clinical practice, some questions remain unanswered, such as the best-treatment strategy, the role of different biomarkers for treatment selection and the effectiveness of immunotherapy according to specific clinical characteristics. OBJECTIVES: Primary objective: to determine the effectiveness and safety of first-line immune checkpoint inhibitors (ICIs), as monotherapy or in combination, compared to platinum-based chemotherapy, with or without bevacizumab for people with advanced NSCLC, according to the level of PD-L1 expression. SECONDARY OBJECTIVE: to maintain the currency of evidence using a living systematic review approach. SEARCH METHODS: We performed an electronic search of the main databases (Cochrane Lung Cancer Group Trial Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase) from inception until 21 October 2020 and conferences meetings from 2015 onwards. SELECTION CRITERIA: We included randomised controlled trials (RCTs) reporting on the efficacy or safety of first-line ICI treatment for adults with advanced NSCLC who had not previously received any anticancer treatment. We included trials comparing single- or double-ICI treatment to standard first-line therapy (platinum-based chemotherapy +/- bevacizumab). All data come from 'international multicentre studies involving adults, age 18 or over, with histologically-confirmed stage IV NSCLC who had not received any previous systemic anti-cancer treatment for advanced disease. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed the search results and a fourth review author resolved any disagreements. Primary outcomes were overall survival (OS) and progression-free survival (PFS); secondary outcomes were overall objective response rate (ORR) by RECIST v 1.1, grade 3 to 5 treatment-related adverse events (AEs) (CTCAE v 5.0) and health-related quality of life (HRQoL). We performed meta-analyses where appropriate using the random-effects model for hazard ratios (HRs) or risk ratios (RRs), with 95% confidence intervals (95% CIs), and used the I² statistic to investigate heterogeneity. MAIN RESULTS: Main results We identified 15 trials for inclusion, seven completed and eight ongoing trials. We obtained data for 5893 participants from seven trials comparing first-line single- (six trials) or double- (two trials) agent ICI with platinum-based chemotherapy, one trial comparing both first-line single- and double-agent ICsI with platinum-based chemotherapy. All trials were at low risk of selection and detection bias, some were classified at high risk of performance, attrition or other source of bias. The overall certainty of evidence according to GRADE ranged from moderate-to-low because of risk of bias, inconsistency, or imprecision. The majority of the included trials reported their outcomes by PD-L1 expressions, with PD-L1 ≥ 50 being considered the most clinically useful cut-off level for decision makers. Also, iIn order to avoid overlaps between various PDL-1 expressions we prioritised the review outcomes according to PD-L1 ≥ 50. Single-agent ICI In the PD-L1 expression ≥ 50% group single-agent ICI probably improved OS compared to platinum-based chemotherapy (hazard ratio (HR) 0.68, 95% confidence interval (CI) 0.60 to 0.76, 6 RCTs, 2111 participants, moderate-certainty evidence). In this group, single-agent ICI also may improve PFS (HR: 0.68, 95% CI 0.52 to 0.88, 5 RCTs, 1886 participants, low-certainty evidence) and ORR (risk ratio (RR):1.40, 95% CI 1.12 to 1.75, 4 RCTs, 1672 participants, low-certainty evidence). HRQoL data were available for only one study including only people with PD-L1 expression ≥ 50%, which suggested that single-agent ICI may improve HRQoL at 15 weeks compared to platinum-based chemotherapy (RR: 1.51, 95% CI 1.08 to 2.10, 1 RCT, 297 participants, low-certainty evidence). In the included studies, treatment-related AEs were not reported according to PD-L1 expression levels. Grade 3-4 AEs may be less frequent with single-agent ICI compared to platinum-based chemotherapy (RR: 0.41, 95% CI 0.33 to 0.50, I² = 62%, 5 RCTs, 3346 participants, low-certainty evidence). More information about efficacy of single-agent ICI compared to platinum-based chemotherapy according to the level of PD-L1 expression and to TMB status or specific clinical characteristics is available in the full text. Double-agent ICI Double-ICI treatment probably prolonged OS compared to platinum-based chemotherapy in people with PD-L1 expression ≥50% (HR: 0.72, 95% CI 0.59 to 0.89 2 RCTs, 612 participants, moderate-certainty evidence). Trials did not report data on HRQoL, PFS and ORR according to PD-L1 groups. Treatment related AEs were not reported according to PD-L1 expression levels. The frequency of grade 3-4 AEs may not differ between double-ICI treatment and platinum-based chemotherapy (RR: 0.78, 95% CI 0.55 to 1.09, I² = 81%, 2 RCTs, 1869 participants, low-certainty evidence). More information about efficacy of double-agent ICI according to the level of PD-L1 expression and to TMB status is available in the full text. AUTHORS' CONCLUSIONS: Authors' conclusions The evidence in this review suggests that single-agent ICI in people with NSCLC and PD-L1 ≥50% probably leads to a higher overall survival rate and may lead to a higher progression-free survival and overall response rate when compared to platinum-based chemotherapy and may also lead to a lower rate of adverse events and higher HRQoL. Combined ICI in people with NSCLC and PD-L1 ≥50% also probably leads to a higher overall survival rate when compared to platinum-based chemotherapy, but its effect on progression-free survival, overall response rate and HRQoL is unknown due to a lack of data. The rate of adverse events may not differ between groups.

Impact of obstetric unit closures, travel time and distance to obstetric services on maternal and neonatal outcomes in high-income countries: a systematic review.

OBJECTIVES: To systematically review (1) The effect of obstetric unit (OU) closures on maternal and neonatal outcomes and (2) The association between travel distance/time to an OU and maternal and neonatal outcomes. DESIGN: Systematic review of any quantitative studies with a comparison group. DATA SOURCES: Embase, MEDLINE, PsycINFO, Applied Social Science Index and Abstracts, Cumulative Index to Nursing and Allied Health and grey literature were searched. METHODS: Eligible studies explored the impact of closure of an OU or the effect of travel distance/time on prespecified maternal or neonatal outcomes. Only studies of women giving birth in high-income countries with universal health coverage of maternity services comparable to the UK were included. Identification of studies, extraction of data and risk of bias assessment were undertaken by at least two reviewers independently. The risk of bias checklist was based on the Cochrane Effective Practice and Organisation of Care criteria and the Newcastle-Ottawa scale. Heterogeneity across studies precluded meta-analysis and synthesis was narrative, with key findings tabulated. RESULTS: 31 studies met the inclusion criteria. There was some evidence to suggest an increase in babies born before arrival following OU closures and/or associated with longer travel distances or time. This may be associated with an increased risk of perinatal or neonatal mortality, but this finding was not consistent across studies. Evidence on other maternal and neonatal outcomes was limited but did not suggest worse outcomes after closures or with longer travel times/distances. Interpretation of findings for some studies was hampered by concerns around how accurately exposures were measured, and/or a lack of adjustment for confounders or temporal changes. CONCLUSION: It is not possible to conclude from this review whether OU closure, increased travel distances or times are associated with worse outcomes for the mother or the baby. PROSPERO REGISTRATION NUMBER: CRD42017078503.

First-Time Mothers' Expectations and Experiences of Postnatal Care in England.

Postnatal care is the aspect of maternity care with which women in England are least satisfied. Little is known about first-time mothers' expectations of postnatal care, or how these expectations relate to their experiences and appraisal of care. Thirty-two first-time mothers took part in a longitudinal qualitative descriptive study, based on two semi-structured interviews-the first in pregnancy, and the second 2 to 3 months after birth. Trajectory analysis was used to identify the thematic patterns in the relationships between postnatal care expectations, needs, experiences, and confidence. Five trajectories were identified, showing that mothers' satisfaction with postnatal care and confidence were primarily influenced not by the extent to which their expectations were met but the varied extent to which their individual postnatal needs were met. Rapid and responsive assessment of needs both antenatally and postnatally, and appropriate adjustment of care, is key in supporting women effectively at this time.

Women's ideal and real expectations of postnatal care during their first pregnancy: An online survey in England.

BACKGROUND: There are many studies of women's experiences of care during the postnatal period, however little is known about women's expectations of postnatal care. OBJECTIVE: This study explores first-time pregnant women's expectations, both ideal and real life, of postnatal care in England. DESIGN: a descriptive, cross-sectional online survey design was used. The questionnaire took approximately 10 minutes to complete and was developed specifically for this survey. It included an informed consent section, socio-demographic questions and closed tick-box questions on where they had received information on postnatal care, and real and ideal expectations of postnatal care in hospital/birth centre and at home. SETTING: The survey was hosted on the National Perinatal Epidemiology Unit website and advertised through a number of third sector and commercial organisations in 2017. PARTICIPANTS: Women who were pregnant, had not given birth before, were aged 16 years and over, and living in England were eligible to participate. ANALYSIS: Survey data were analysed using descriptive statistics and, where appropriate, chi square test using SPSS Version 23. Data from open ended questions were analysed by two researchers separately then codes and themes were discussed until consensus was reached. RESULTS: 283 women responded to the survey of whom 200 were eligible and included in the analysis. Most had received information on postnatal care from multiple sources, with pregnancy classes and midwives being most common. Most expected to stay one day or less in hospital or birth centre after normal delivery. Real life expectations were lower than ideal expectations, and hospital/birth centre real life expectations were higher than home real life expectations for physical health advice/checks and information/help with feeding. Categories developed from the open text answers were 'Respect, compassion and individualised care at a vulnerable time', 'The ward environment', 'Feeling ready for hospital discharge' and 'Help to find support in the community'. KEY CONCLUSIONS: Women in this survey had high ideal world expectations of their postnatal care but in real life expected more focus on checking on their health and that of their baby and on giving information about the new challenges of how to breastfeed and look after a baby. While women valued checks of their health and that of their baby, ideally they wanted easy access to reassurance that they were feeding and looking after their baby well, that they were 'doing it right', and that what was happening to them was normal. IMPLICATIONS FOR PRACTICE: As well as the necessary checks in the immediate postpartum period, consideration also needs to be given to the best way to meet the informational and support needs of women to optimise their wellbeing and transition to parenthood. A number of resources are used by women that could be enhanced to inform expectations of postnatal care and to provide valuable information to support their postnatal care.

Expectations and experiences of hospital postnatal care in the UK: a systematic review of quantitative and qualitative studies.

OBJECTIVES: To report on women's and families' expectations and experiences of hospital postnatal care, and also to reflect on women's satisfaction with hospital postnatal care and to relate their expectations to their actual care experiences. DESIGN: Systematic review. SETTING: UK. PARTICIPANTS: Postnatal women. PRIMARY AND SECONDARY OUTCOMES: Women's and families' expectations, experiences and satisfaction with hospital postnatal care. METHODS: Embase, MEDLINE, PsycINFO, Applied Social Sciences Index and Abstracts, Cumulative Index to Nursing and Allied Health (CINAHL Plus), Science Citation Index, and Social Sciences Citation Index were searched to identify relevant studies published since 1970. We incorporated findings from qualitative, quantitative and mixed-methods studies. Eligible studies were independently screened and quality-assessed using a modified version of the National Institutes of Health Quality Assessment Tool for quantitative studies and the Critical Appraisal Skills Programme for qualitative studies. Data were extracted on participants' characteristics, study period, setting, study objective and study specified outcomes, in addition to the summary of results. RESULTS: Data were included from 53 studies, of which 28 were quantitative, 19 were qualitative and 6 were mixed-methods studies. The methodological quality of the included studies was mixed, and only three were completely free from bias. Women were generally satisfied with their hospital postnatal care but were critical of staff interaction, the ward environment and infant feeding support. Ethnic minority women were more critical of hospital postnatal care than white women. Although duration of postnatal stay has declined over time, women were generally happy with this aspect of their care. There was limited evidence regarding women's expectations of postnatal care, families' experience and social disadvantage. CONCLUSION: Women were generally positive about their experiences of hospital postnatal care, but improvements could still be made. Individualised, flexible models of postnatal care should be evaluated and implemented. PROSPERO REGISTRATION NUMBER: CRD42017057913.

Antidepressants for treating depression in dementia.

BACKGROUND: The use of antidepressants in dementia accompanied by depressive symptoms is widespread, but their clinical efficacy is uncertain. This review updates an earlier version, first published in 2002. OBJECTIVES: To determine the efficacy and safety of any type of antidepressant for patients who have been diagnosed as having dementia of any type and depression as defined by recognised criteria. SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's Specialised Register, on 16 August 2017. ALOIS contains information on trials retrieved from databases and from a number of trial registers and grey literature sources. SELECTION CRITERIA: We included all relevant double-blind, randomised trials comparing any antidepressant drug with placebo, for patients diagnosed as having dementia and depression. DATA COLLECTION AND ANALYSIS: Two review authors selected studies for inclusion and extracted data independently. We assessed risk of bias in the included studies using the Cochrane 'Risk of bias' tool. Where clinically appropriate, we pooled data for treatment periods up to three months and from three to nine months. We used GRADE methods to assess the overall quality of the evidence. MAIN RESULTS: We included ten studies with a total of 1592 patients. Eight included studies reported sufficiently detailed results to enter into analyses related to antidepressant efficacy. We split one study which included two different antidepressants and therefore had nine groups of patients treated with antidepressants compared with nine groups receiving placebo treatment. Information needed to make 'Risk of bias' judgements was often missing.We found high-quality evidence of little or no difference in scores on depression symptom rating scales between the antidepressant and placebo treated groups after 6 to 13 weeks (standardised mean difference (SMD) -0.10, 95% confidence interval (CI) -0.26 to 0.06; 614 participants; 8 studies). There was probably also little or no difference between groups after six to nine months (mean difference (MD) 0.59 point, 95% CI -1.12 to 2.3, 357 participants; 2 studies; moderate-quality evidence). The evidence on response rates at 12 weeks was of low quality, and imprecision in the result meant we were uncertain of any effect of antidepressants (antidepressant: 49.1%, placebo: 37.7%; odds ratio (OR) 1.71, 95% CI 0.80 to 3.67; 116 participants; 3 studies). However, the remission rate was probably higher in the antidepressant group than the placebo group (antidepressant: 40%, placebo: 21.7%; OR 2.57, 95% CI 1.44 to 4.59; 240 participants; 4 studies; moderate-quality evidence). The largest of these studies continued for another 12 weeks, but because of imprecision of the result we could not be sure of any effect of antidepressants on remission rates after 24 weeks. There was evidence of no effect of antidepressants on performance of activities of daily living at weeks 6 to 13 (SMD -0.05, 95% CI -0.36 to 0.25; 173 participants; 4 studies; high-quality evidence) and probably also little or no effect on cognition (MD 0.33 point on the Mini-Mental State Examination, 95% CI -1.31 to 1.96; 194 participants; 6 studies; moderate-quality evidence).Participants on antidepressants were probably more likely to drop out of treatment than those on placebo over 6 to 13 weeks (OR 1.51, 95% CI 1.07 to 2.14; 836 participants; 9 studies). The meta-analysis of the number of participants suffering at least one adverse event showed a significant difference in favour of placebo (antidepressant: 49.2%, placebo: 38.4%; OR 1.55, 95% CI 1.21 to 1.98, 1073 participants; 3 studies), as did the analyses for participants suffering one event of dry mouth (antidepressant: 19.6%, placebo: 13.3%; OR 1.80, 95% CI 1.23 to 2.63, 1044 participants; 5 studies), and one event of dizziness (antidepressant: 19.2%, placebo: 12.5%; OR 2.00, 95% CI 1.34 to 2.98, 1044 participants; 5 studies). Heterogeneity in the way adverse events were reported in studies presented a major difficulty for meta-analysis, but there was some evidence that antidepressant treatment causes more adverse effects than placebo treatment does. AUTHORS' CONCLUSIONS: The available evidence is of variable quality and does not provide strong support for the efficacy of antidepressants for treating depression in dementia, especially beyond 12 weeks. On the only measure of efficacy for which we had high-quality evidence (depression rating scale scores), antidepressants showed little or no effect. The evidence on remission rates favoured antidepressants but was of moderate quality, so future research may find a different result. There was insufficient evidence to draw conclusions about individual antidepressant drugs or about subtypes of dementia or depression. There is some evidence that antidepressant treatment may cause adverse events.

Prophylactic platelet transfusions prior to surgery for people with a low platelet count.

BACKGROUND: People with thrombocytopenia often require a surgical procedure. A low platelet count is a relative contraindication to surgery due to the risk of bleeding. Platelet transfusions are used in clinical practice to prevent and treat bleeding in people with thrombocytopenia. Current practice in many countries is to correct thrombocytopenia with platelet transfusions prior to surgery. Alternatives to platelet transfusion are also used prior surgery. OBJECTIVES: To determine the clinical effectiveness and safety of prophylactic platelet transfusions prior to surgery for people with a low platelet count. SEARCH METHODS: We searched the following major data bases: Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2), PubMed (e-publications only), Ovid MEDLINE, Ovid Embase, the Transfusion Evidence Library and ongoing trial databases to 11 December 2017. SELECTION CRITERIA: We included all randomised controlled trials (RCTs), as well as non-RCTs and controlled before-and-after studies (CBAs), that met Cochrane EPOC (Effective Practice and Organisation of Care) criteria, that involved the transfusion of platelets prior to surgery (any dose, at any time, single or multiple) in people with low platelet counts. We excluded studies on people with a low platelet count who were actively bleeding. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane for data collection. We were only able to combine data for two outcomes and we presented the rest of the findings in a narrative form. MAIN RESULTS: We identified five RCTs, all conducted in adults; there were no eligible non-randomised studies. Three completed trials enrolled 180 adults and two ongoing trials aim to include 627 participants. The completed trials were conducted between 2005 and 2009. The two ongoing trials are scheduled to complete recruitment by October 2019. One trial compared prophylactic platelet transfusions to no transfusion in people with thrombocytopenia in an intensive care unit (ICU). Two small trials, 108 participants, compared prophylactic platelet transfusions to other alternative treatments in people with liver disease. One trial compared desmopressin to fresh frozen plasma or one unit of platelet transfusion or both prior to surgery. The second trial compared platelet transfusion prior to surgery with two types of thrombopoietin mimetics: romiplostim and eltrombopag. None of the included trials were free from methodological bias. No included trials compared different platelet count thresholds for administering a prophylactic platelet transfusion prior to surgery. None of the included trials reported on all the review outcomes and the overall quality per reported outcome was very low.None of the three completed trials reported: all-cause mortality at 90 days post surgery; mortality secondary to bleeding, thromboembolism or infection; number of red cell or platelet transfusions per participant; length of hospital stay; or quality of life.None of the trials included children or people who needed major surgery or emergency surgical procedures.Platelet transfusion versus no platelet transfusion (1 trial, 72 participants)We were very uncertain whether giving a platelet transfusion prior to surgery had any effect on all-cause mortality within 30 days (1 trial, 72 participants; risk ratio (RR) 0.78, 95% confidence interval (CI) 0.41 to 1.45; very-low quality evidence). We were very uncertain whether giving a platelet transfusion prior to surgery had any effect on the risk of major (1 trial, 64 participants; RR 1.60, 95% CI 0.29 to 8.92; very low-quality evidence), or minor bleeding (1 trial, 64 participants; RR 1.29, 95% CI 0.90 to 1.85; very-low quality evidence). No serious adverse events occurred in either study arm (1 trial, 72 participants, very low-quality evidence).Platelet transfusion versus alternative to platelet transfusion (2 trials, 108 participants)We were very uncertain whether giving a platelet transfusion prior to surgery compared to an alternative has any effect on the risk of major (2 trials, 108 participants; no events; very low-quality evidence), or minor bleeding (desmopressin: 1 trial, 36 participants; RR 0.89, 95% CI 0.06 to 13.23; very-low quality evidence: thrombopoietin mimetics: 1 trial, 65 participants; no events; very-low quality evidence). We were very uncertain whether there was a difference in transfusion-related adverse effects between the platelet transfused group and the alternative treatment group (desmopressin: 1 trial, 36 participants; RR 2.70, 95% CI 0.12 to 62.17; very-low quality evidence). AUTHORS' CONCLUSIONS: Findings of this review were based on three small trials involving minor surgery in adults with thrombocytopenia. We found insufficient evidence to recommend the administration of preprocedure prophylactic platelet transfusions in this situation with a lack of evidence that transfusion resulted in a reduction in postoperative bleeding or all-cause mortality. The small number of trials meeting the inclusion criteria and the limitation in reported outcomes across the trials precluded meta-analysis for most outcomes. Further adequately powered trials, in people of all ages, of prophylactic platelet transfusions compared with no transfusion, other alternative treatments, and considering different platelet thresholds prior to planned and emergency surgical procedures are required. Future trials should include major surgery and report on bleeding, adverse effects, mortality (as a long-term outcome) after surgery, duration of hospital stay and quality of life measures.

Use of platelet transfusions prior to lumbar punctures or epidural anaesthesia for the prevention of complications in people with thrombocytopenia.

BACKGROUND: People with a low platelet count (thrombocytopenia) often require lumbar punctures or an epidural anaesthetic. Lumbar punctures can be diagnostic (haematological malignancies, subarachnoid haematoma, meningitis) or therapeutic (spinal anaesthetic, administration of chemotherapy). Epidural catheters are placed for administration of epidural anaesthetic. Current practice in many countries is to correct thrombocytopenia with platelet transfusions prior to lumbar punctures and epidural anaesthesia, in order to mitigate the risk of serious procedure-related bleeding. However, the platelet count threshold recommended prior to these procedures varies significantly from country to country. This indicates significant uncertainty among clinicians regarding the correct management of these patients. The risk of bleeding appears to be low, but if bleeding occurs it can be very serious (spinal haematoma). Consequently, people may be exposed to the risks of a platelet transfusion without any obvious clinical benefit.This is an update of a Cochrane Review first published in 2016. OBJECTIVES: To assess the effects of different platelet transfusion thresholds prior to a lumbar puncture or epidural anaesthesia in people with thrombocytopenia (low platelet count). SEARCH METHODS: We searched for randomised controlled trials (RCTs), non-randomised controlled trials (nRCTs), controlled before-after studies (CBAs), interrupted time series studies (ITSs), and cohort studies in CENTRAL (the Cochrane Library 2018, Issue 1), MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 13 February 2018. SELECTION CRITERIA: We included RCTs, nRCTs, CBAs, ITSs, and cohort studies involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in people of any age with thrombocytopenia requiring insertion of a lumbar puncture needle or epidural catheter.The original review only included RCTs. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane for including RCTs, nRCTs, CBAs, and ITSs. Two review authors independently assessed studies for eligibility and risk of bias and extracted data. Results were only expressed narratively. MAIN RESULTS: We identified no completed or ongoing RCTs, nRCTs, CBAs, or ITSs. No studies included people undergoing an epidural procedure. No studies compared different platelet count thresholds prior to a procedure.In this update we identified three retrospective cohort studies that contained participants who did and did not receive platelet transfusions prior to lumbar puncture procedures. All three studies were carried out in people with cancer, most of whom had a haematological malignancy. Two studies were in children, and one was in adults.The number of participants receiving platelet transfusions prior to the lumbar puncture procedures was not reported in one study. We therefore only summarised in a narrative form the relevant outcomes from two studies (150 participants; 129 children and 21 adults), in which the number of participants who received the transfusion was given.We judged the overall risk of bias for all reported outcomes for both studies as 'serious' based on the ROBINS-I tool.No procedure-related major bleeding occurred in the two studies that reported this outcome (2 studies, 150 participants, no cases, very low-quality evidence).There was no evidence of a difference in the risk of minor bleeding (traumatic tap) in participants who received platelet transfusions before a lumbar puncture and those who did not receive a platelet transfusion before the procedure (2 studies, 150 participants, very low-quality evidence). One of the 14 adults who received a platelet transfusion experienced minor bleeding (traumatic tap; defined as at least 500 x 106/L red blood cells in the cerebrospinal fluid); none of the seven adults who did not receive a platelet transfusion experienced this event. Ten children experienced minor bleeding (traumatic taps; defined as at least 100 x 106/L red blood cells in the cerebrospinal fluid), six out of the 57 children who received a platelet transfusion and four out of the 72 children who did not receive a platelet transfusion.No serious adverse events occurred in the one study that reported this outcome (1 study, 21 participants, very low-quality evidence).We found no studies that evaluated all-cause mortality within 30 days from the lumbar puncture procedure, length of hospital stay, proportion of participants who received platelet transfusions, or quality of life. AUTHORS' CONCLUSIONS: We found no evidence from RCTs or non-randomised studies on which to base an assessment of the correct platelet transfusion threshold prior to insertion of a lumbar puncture needle or epidural catheter. There are no ongoing registered RCTs assessing the effects of different platelet transfusion thresholds prior to the insertion of a lumbar puncture or epidural anaesthesia in people with thrombocytopenia. Any future study would need to be very large to detect a difference in the risk of bleeding. A study would need to be designed with at least 47,030 participants to be able to detect an increase in the number of people who had major procedure-related bleeding from 1 in 1000 to 2 in 1000. The use of a central data collection register or routinely collected electronic records (big data) is likely to be the only method to systematically gather data relevant to this population.

Comparison of a therapeutic-only versus prophylactic platelet transfusion policy for people with congenital or acquired bone marrow failure disorders.

BACKGROUND: Bone marrow disorders encompass a group of diseases characterised by reduced production of red cells, white cells, and platelets, or defects in their function, or both. The most common bone marrow disorder is myelodysplastic syndrome. Thrombocytopenia, a low platelet count, commonly occurs in people with bone marrow failure. Platetet transfusions are routinely used in people with thrombocytopenia secondary to bone marrow failure disorders to treat or prevent bleeding. Myelodysplastic syndrome is currently the most common reason for receiving a platelet transfusion in some Western countries. OBJECTIVES: To determine whether a therapeutic-only platelet transfusion policy (transfusion given when patient is bleeding) is as effective and safe as a prophylactic platelet transfusion policy (transfusion given to prevent bleeding according to a prespecified platelet threshold) in people with congenital or acquired bone marrow failure disorders. SEARCH METHODS: We searched for randomised controlled trials (RCTs), non-RCTs, and controlled before-after studies (CBAs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2017, Issue 9), Ovid MEDLINE (from 1946), Ovid Embase (from 1974), PubMed (e-publications only), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 12 October 2017. SELECTION CRITERIA: We included RCTs, non-RCTs, and CBAs that involved the transfusion of platelet concentrates (prepared either from individual units of whole blood or by apheresis any dose, frequency, or transfusion trigger) and given to treat or prevent bleeding among people with congenital or acquired bone marrow failure disorders.We excluded uncontrolled studies, cross-sectional studies, and case-control studies. We excluded cluster-RCTs, non-randomised cluster trials, and CBAs with fewer than two intervention sites and two control sites due to the risk of confounding. We included all people with long-term bone marrow failure disorders that require platelet transfusions, including neonates. We excluded studies of alternatives to platelet transfusion, or studies of people receiving intensive chemotherapy or a stem cell transplant. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures outlined by Cochrane. Due to the absence of evidence we were unable to report on any of the review outcomes. MAIN RESULTS: We identified one RCT that met the inclusion criteria for this review. The study enrolled only nine adults with MDS over a three-year study duration period. The trial was terminated due to poor recruitment rate (planned recruitment 60 participants over two years). Assessment of the risk of bias was not possible for all domains. The trial was a single-centre, single-blind trial. The clinical and demographic characteristics of the participants were never disclosed. The trial outcomes relevant to this review were bleeding assessments, mortality, quality of life, and length of hospital stay, but no data were available to report on any of these outcomes.We identified no completed non-RCTs or CBAs.We identified no ongoing RCTs, non-RCTs, or CBAs. AUTHORS' CONCLUSIONS: We found no evidence to determine the safety and efficacy of therapeutic platelet transfusion compared with prophylactic platelet transfusion for people with long-term bone marrow failure disorders. This review underscores the urgency of prioritising research in this area. People with bone marrow failure depend on long-term platelet transfusion support, but the only trial that assessed a therapeutic strategy was halted. There is a need for good-quality studies comparing a therapeutic platelet transfusion strategy with a prophylactic platelet transfusion strategy; such trials should include outcomes that are important to patients, such as quality of life, length of hospital admission, and risk of bleeding.

Pathogen-Reduced Platelets for the Prevention of Bleeding in People of Any Age.

CLINICAL QUESTION: Are pathogen-reduced platelets as effective as standard platelets for the prevention of bleeding in people of any age requiring platelet transfusions? BOTTOM LINE: In people with cancer who have a low platelet count due to their disease or its treatment, pathogen-reduced platelet transfusions increase risk of platelet refractoriness and platelet transfusion requirement (high-quality evidence) but probably do not effect all-cause mortality, risk of clinically significant or severe bleeding, or risk of a serious adverse event (moderate-quality evidence). There was insufficient evidence for people with other diagnoses.

Prophylactic platelet transfusions prior to surgery for people with a low platelet count.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determine the clinical effectiveness and safety of prophylactic platelet transfusions prior to surgery for people with a low platelet count or platelet dysfunction (inherited or acquired).