Interventions for reducing red blood cell transfusion in adults undergoing hip fracture surgery: an overview of systematic reviews.
Following hip fracture, people sustain an acute blood loss caused by the injury and subsequent surgery. Because the majority of hip fractures occur in older adults, blood loss may be compounded by pre-existing anaemia. Allogenic blood transfusions (ABT) may be given before, during, and after surgery to correct chronic anaemia or acute blood loss. However, there is uncertainty about the benefit-risk ratio for ABT. This is a potentially scarce resource, with availability of blood products sometimes uncertain. Other strategies from Patient Blood Management may prevent or minimise blood loss and avoid administration of ABT.
To summarise the evidence from Cochrane Reviews and other systematic reviews of randomised or quasi-randomised trials evaluating the effects of pharmacological and non-pharmacological interventions, administered perioperatively, on reducing blood loss, anaemia, and the need for ABT in adults undergoing hip fracture surgery.
In January 2022, we searched the Cochrane Library, MEDLINE, Embase, and five other databases for systematic reviews of randomised controlled trials (RCTs) of interventions given to prevent or minimise blood loss, treat the effects of anaemia, and reduce the need for ABT, in adults undergoing hip fracture surgery. We searched for pharmacological interventions (fibrinogen, factor VIIa and factor XIII, desmopressin, antifibrinolytics, fibrin and non-fibrin sealants and glue, agents to reverse the effects of anticoagulants, erythropoiesis agents, iron, vitamin B12, and folate replacement therapy) and non-pharmacological interventions (surgical approaches to reduce or manage blood loss, intraoperative cell salvage and autologous blood transfusion, temperature management, and oxygen therapy). We used Cochrane methodology, and assessed the methodological quality of included reviews using AMSTAR 2. We assessed the degree of overlap of RCTs between reviews. Because overlap was very high, we used a hierarchical approach to select reviews from which to report data; we compared the findings of selected reviews with findings from the other reviews. Outcomes were: number of people requiring ABT, volume of transfused blood (measured as units of packed red blood cells (PRC)), postoperative delirium, adverse events, activities of daily living (ADL), health-related quality of life (HRQoL), and mortality.
We found 26 systematic reviews including 36 RCTs (3923 participants), which only evaluated tranexamic acid and iron. We found no reviews of other pharmacological interventions or any non-pharmacological interventions. Tranexamic acid (17 reviews, 29 eligible RCTs) We selected reviews with the most recent search date, and which included data for the most outcomes. The methodological quality of these reviews was low. However, the findings were largely consistent across reviews. One review included 24 RCTs, with participants who had internal fixation or arthroplasty for different types of hip fracture. Tranexamic acid was given intravenously or topically during the perioperative period. In this review, based on a control group risk of 451 people per 1000, 194 fewer people per 1000 probably require ABT after receiving tranexamic acid (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.46 to 0.68; 21 studies, 2148 participants; moderate-certainty evidence). We downgraded the certainty for possible publication bias. Review authors found that there was probably little or no difference in the risks of adverse events, reported as deep vein thrombosis (RR 1.16, 95% CI 0.74 to 1.81; 22 studies), pulmonary embolism (RR 1.01, 95% CI 0.36 to 2.86; 9 studies), myocardial infarction (RR 1.00, 95% CI 0.23 to 4.33; 8 studies), cerebrovascular accident (RR 1.45, 95% CI 0.56 to 3.70; 8 studies), or death (RR 1.01, 95% CI 0.70 to 1.46; 10 studies). We judged evidence from these outcomes to be moderate certainty, downgraded for imprecision. Another review, with a similarly broad inclusion criteria, included 10 studies, and found that tranexamic acid probably reduces the volume of transfused PRC (0.53 fewer units, 95% CI 0.27 to 0.80; 7 studies, 813 participants; moderate-certainty evidence). We downgraded the certainty because of unexplained high levels of statistical heterogeneity. No reviews reported outcomes of postoperative delirium, ADL, or HRQoL. Iron (9 reviews, 7 eligible RCTs) Whilst all reviews included studies in hip fracture populations, most also included other surgical populations. The most current, direct evidence was reported in two RCTs, with 403 participants with hip fracture; iron was given intravenously, starting preoperatively. This review did not include evidence for iron with erythropoietin. The methodological quality of this review was low. In this review, there was low-certainty evidence from two studies (403 participants) that there may be little or no difference according to whether intravenous iron was given in: the number of people who required ABT (RR 0.90, 95% CI 0.73 to 1.11), the volume of transfused blood (MD -0.07 units of PRC, 95% CI -0.31 to 0.17), infection (RR 0.99, 95% CI 0.55 to 1.80), or mortality within 30 days (RR 1.06, 95% CI 0.53 to 2.13). There may be little or no difference in delirium (25 events in the iron group compared to 26 events in control group; 1 study, 303 participants; low-certainty evidence). We are very unsure whether there was any difference in HRQoL, since it was reported without an effect estimate. The findings were largely consistent across reviews. We downgraded the evidence for imprecision, because studies included few participants, and the wide CIs indicated possible benefit and harm. No reviews reported outcomes of cognitive dysfunction, ADL, or HRQoL.
Tranexamic acid probably reduces the need for ABT in adults undergoing hip fracture surgery, and there is probably little or no difference in adverse events. For iron, there may be little or no difference in overall clinical effects, but this finding is limited by evidence from only a few small studies. Reviews of these treatments did not adequately include patient-reported outcome measures (PROMS), and evidence for their effectiveness remains incomplete. We were unable to effectively explore the impact of timing and route of administration between reviews. A lack of systematic reviews for other types of pharmacological or any non-pharmacological interventions to reduce the need for ABT indicates a need for further evidence syntheses to explore this. Methodologically sound evidence syntheses should include PROMS within four months of surgery.
Lewis SR
，Pritchard MW
，Estcourt LJ
，Stanworth SJ
，Griffin XL
... -
《Cochrane Database of Systematic Reviews》
Sex as a prognostic factor for mortality in adults with acute symptomatic pulmonary embolism.
Pulmonary embolism (PE) is relatively common worldwide. It is a serious condition that can be life-threatening. Studies on the relationship between adverse outcomes of this condition and whether a patient is male or female have yielded inconsistent results. Determining whether there is an association between sex and short-term mortality in patients with acute PE is important as this information may help guide different approaches to PE monitoring and treatment.
To determine whether sex (i.e. being a male or a female patient) is an independent prognostic factor for predicting mortality in adults with acute symptomatic pulmonary embolism.
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register up to 17 February 2023. We scanned conference abstracts and reference lists of included studies and systematic reviews. We also contacted experts to identify additional studies. There were no restrictions with respect to language or date of publication.
We included phase 2-confirmatory prognostic studies, that is, any longitudinal study (prospective or retrospective) evaluating the independent association between sex (male or female) and mortality in adults with acute PE.
We followed the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of prognostic factor studies (CHARMS-PF) and the Cochrane Prognosis Methods Group template for prognosis reviews. Two review authors independently screened the studies, extracted data, assessed the risk of bias according to the Quality in Prognosis Studies (QUIPS) tool, and assessed the certainty of the evidence (GRADE). Meta-analyses were performed by pooling adjusted estimates. When meta-analysis was not possible, we reported the main results narratively.
We included seven studies (726,293 participants), all of which were retrospective cohort studies with participants recruited and managed in hospitals between 2000 and 2018. Studies took place in the USA, Spain, and Japan. Most studies were multicentre. None were conducted in low- or middle-income countries. The participants' mean age ranged from 62 to 69 years, and the proportion of females was higher in six of the seven studies, ranging from 46% to 60%. Sex and gender terms were used inconsistently. Participants received different PE treatments: reperfusion, inferior vena cava filter, anticoagulation, and haemodynamic/respiratory support. The prognostication time (the point from which the outcome was predicted) was frequently omitted. The included studies provided data for three of our outcomes of interest. We did not consider any of the studies to be at an overall low risk of bias for any of the outcomes analysed. We judged the certainty of the evidence as moderate to low due to imprecision and risk of bias. We found moderate-certainty evidence (due to imprecision) that for female patients there is likely a small but clinically important reduction in all-cause mortality at 30 days (odds ratio (OR) 0.81, 95% confidence interval (CI) 0.72 to 0.92; I2 = 0%; absolute risk difference (ARD) 24 fewer deaths in women per 1000 participants, 95% CI 35 to 10 fewer; 2 studies, 17,627 participants). However, the remaining review outcomes do not indicate lower mortality in female patients. There is low-certainty evidence (due to serious risk of bias and imprecision) indicating that for females with PE, there may be a small but clinically important increase in all-cause hospital mortality (OR 1.11, 95% CI 1.00 to 1.22; I2 = 21.7%; 95% prediction interval (PI) 0.76 to 1.61; ARD 13 more deaths in women per 1000 participants, 95% CI 0 to 26 more; 3 studies, 611,210 participants). There is also low-certainty evidence (due to very serious imprecision) indicating that there may be little to no difference between males and females in PE-related mortality at 30 days (OR 1.08, 95% CI 0.55 to 2.12; I2 = 0%; ARD 4 more deaths in women per 1000 participants, 95% CI 22 fewer to 50 more; 2 studies, 3524 participants). No study data was found for the other outcomes, including sex-specific mortality data at one year. Moreover, due to insufficient studies, many of our planned methods were not implemented. In particular, we were unable to conduct assessments of heterogeneity or publication bias or subgroup and sensitivity analyses.
The evidence is uncertain about sex (being male or female) as an independent prognostic factor for predicting mortality in adults with PE. We found that, for female patients with PE, there is likely a small but clinically important reduction in all-cause mortality at 30 days relative to male patients. However, this result should be interpreted cautiously, as the remaining review outcomes do not point to an association between being female and having a lower risk of death. In fact, the evidence in the review also suggested that, in female patients, there may be a small but clinically important increase in all-cause hospital mortality. It also showed that there may be little to no difference in PE-related mortality at 30 days between male and female patients. There is currently no study evidence from longitudinal studies for our other review outcomes. Although the available evidence is conflicting and therefore cannot support a recommendation for or against routinely considering sex to quantify prognosis or to guide personalised therapeutic approaches for patients with PE, this Cochrane review offers information to guide future primary research and systematic reviews.
Jimenez Tejero E
，Lopez-Alcalde J
，Correa-Pérez A
，Stallings E
，Gaetano Gil A
，Del Campo Albendea L
，Mateos-Haro M
，Fernandez-Felix BM
，Stallings R
，Alvarez-Diaz N
，García Laredo E
，Solier A
，Fernández-Martínez E
，Morillo Guerrero R
，de Miguel M
，Perez R
，Antequera A
，Muriel A
，Jimenez D
，Zamora J
... -
《Cochrane Database of Systematic Reviews》
Effectiveness of interventions for improving educational outcomes for people with disabilities in low- and middle-income countries: A systematic review.
People with disabilities are consistently falling behind in educational outcomes compared to their peers without disabilities, whether measured in terms of school enrolment, school completion, mean years of schooling, or literacy levels. These inequalities in education contribute to people with disabilities being less likely to achieve employment, or earn as much if they are employed, as people without disabilities. Evidence suggests that the gap in educational attainment for people with and without disabilities is greatest in low- and middle-income countries (LMICs). Exclusion of people with disabilities from mainstream education, and low rates of participation in education of any kind, are important issues for global equity. Interventions which might have a positive impact include those that improve educational outcomes for people with disabilities, whether delivered in specialist or inclusive education settings. Such interventions involve a wide range of initiatives, from those focused on the individual level - such as teaching assistance to make mainstream classes more accessible to children with specific learning needs - to those which address policy or advocacy.
The objectives of this review were to answer the following research questions: (1) What is the nature of the interventions used to support education for people with disabilities in LMICs? (2) What is the size and quality of the evidence base of the effectiveness of interventions to improve educational outcomes for people with disabilities in LMICs? (3) What works to improve educational outcomes for people with disabilities in LMICs? (4) Which interventions appear to be most effective for different types of disability? (5) What are the barriers and facilitators to the improvement of educational outcomes for people with disabilities? (6) Is there evidence of cumulative effects of interventions?
The search for studies followed two steps. Firstly, we conducted an electronic search of databases and sector-specific websites. Then, after initial screening, we examined the reference lists of all identified reviews and screened the cited studies for inclusion. We also conducted a forward search and an ancestral search. No restrictions in terms of date or format were placed on the search, but only English-language publications were eligible for inclusion.
In our review, we included studies on the basis that they were able to detect intervention impact. Descriptive studies of various designs and methodologies were not included. We also excluded any study with a sample size of fewer than five participants. We included studies which examined the impact of interventions for people with disabilities living in LMICs. There were no restrictions on comparators/comparison groups in included studies. However, to be eligible for inclusion, a study needed to have both an eligible intervention and an eligible outcome. Any duration of follow-up was eligible for inclusion.
We used EppiReviewer for bibliographic management, screening, coding, and data synthesis. Eligibility was assessed using a predesigned form based on the inclusion criteria developed by the authors. We piloted all coding sheets with at least five studies before use. The form allowed for coding of multiple intervention domains and multiple outcomes domains. The entire screening process was reported using a PRISMA flow chart. We screened all unique references from our search title and abstract, with two independent reviewers determining relevance, and repeated this process for full texts. Data was extracted from studies according to a coding sheet. Coding included: (1) extraction of basic study characteristics, (2) a narrative summary of procedures and findings (including recording of iatrogenic effects), (3) a summary of findings/results table, (4) an assessment of confidence in study findings, and (5) creation of a forest plot of effect sizes. A third data collector, a research associate, checked the results of this process. Confidence in study findings was assessed using a standardised tool. All coding categories were not mutually exclusive and so multiple coding was done where an intervention covered more than one category of intervention.
Twenty-eight studies were included in this review. Most studies (n = 25) targeted children with disabilities. Only two studies directly targeted family members, and the remaining three focused on service providers. Individuals with intellectual or learning and developmental impairments were most frequently targeted by interventions (n = 17). The category of interventions most represented across studies was 'Educational attainment support', for instance, a reading comprehension intervention that combined strategy instruction (graphic organisers, visual displays, mnemonic illustrations, computer exercises, predicting, inference, text structure awareness, main idea identification, summarisation, and questioning) for children with dyslexia. The second most common category of intervention was 'Accessible learning environments', for instance, programmes which aimed to improve social skills or to reduce rates of victimisation of children with disabilities in schools. Regarding intervention effects, included studies concerned with 'Conditions for inclusion of people with disabilities in education' showed a moderately significant effect, and one study concerned with teacher knowledge showed a significant effect size. Among the 18 studies included in the analysis of intervention effects on 'Skills for learning', 12 interventions had a significant effect. When considering the effect of interventions on different outcomes, we see that the effect on literacy, cognitive skills, handwriting, and numeracy are significant. All these effects are large but are based on a low number of studies. The studies concerned with speech and school behaviour show no significant effect of intervention. Across studies, heterogeneity is high, and risk of publication bias varies but was frequently high. All but one study received an overall rating of low confidence in study findings. However, this lack of confidence across studies was largely due to the use of low-rigour study designs and was not always reflective of multiple points of weakness within a given study.
Children with disabilities fall behind in educational outcomes as the current school systems are not set up to teach children with different impairment types. There is no one 'magic bullet' intervention which can equalise health outcomes for this group. A twin-track approach is needed, which both addresses the specific needs of children with disabilities but also ensures that they are included in mainstream activities (e.g., through improving the skills of teachers and accessibility of the classroom). However, currently most interventions included in this systematic review targeted individual children with disabilities in an attempt to improve their functioning, skills, and competencies, but did not focus on mainstreaming these children into the school by system-level or school-level changes. Consequently, a focus on evaluation of interventions which target not just the individual with a disability but also their broader environment, are needed.
Hunt X
，Saran A
，White H
，Kuper H
... -
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ResearchGate
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