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Predictors of functional decline in hospitalized elderly patients: a systematic review.

BACKGROUND: This article will systematically review the methodological characteristics and results of studies of variables and indices that predict functional decline in older hospitalized patients. METHODS: We restricted this review to original longitudinal studies of predictors of either physical functional decline or nursing home admission among patients aged 60 and older. Two reviewers independently abstracted information on methodological characteristics and substantive results. RESULTS: Thirty articles were identified, derived from 27 different studies, reporting on 33 substudies. Substantial variability was found with respect to study design, outcomes measured, period of follow-up, predictors investigated, and analytic methods. Multivariable predictive indices were significantly associated with adverse outcomes in the majority of studies that investigated them, as were the following variables: age, diagnosis, activities of daily living, cognitive impairment (including delirium), and residence. CONCLUSIONS: The methodological heterogeneity of the studies identified limits quantitative synthesis of the results. Predictive indices for hospitalized elders appear to have moderate short-term predictive ability.

Activities of Daily Living↗

Multinutrient oral supplements and tube feeding in maintenance dialysis: a systematic review and meta-analysis.

BACKGROUND: This systematic review aims to determine the potential benefits of enteral multinutrient support (oral or tube) in patients with chronic kidney disease (CKD) receiving maintenance dialysis. METHODS: Studies of multinutrient oral supplements and enteral tube feeding that involved comparisons of nutritional support versus routine care (ie, usual diet), disease-specific formulae (with adapted macronutrient and micronutrient composition for use in maintenance dialysis patients) versus standard formulae, and enteral tube feeding versus parenteral nutrition are included in this review. The outcome measures sought were clinical (quality of life, complications, and mortality), biochemical (albumin and electrolyte levels), and nutritional (dietary intake and anthropometry). Meta-analyses were performed when possible. RESULTS: This review of 18 studies (5 randomized controlled trials [RCTs], 13 non-RCTs) suggests that enteral nutritional support increased total (energy and protein) intake and increased serum albumin concentration by 0.23 g/dL (2.3 g/L; 95% confidence interval, 0.037 to 0.418 g/dL [0.37 to 4.18 g/L]; 1 RCT, 2 non-RCTs), with little effect on electrolyte status (serum phosphate and potassium). Few studies reported clinical outcome, and there was insufficient information to compare disease-specific versus standard formulae or enteral versus parenteral nutrition. CONCLUSION: This systematic review suggests that enteral multinutrient support significantly increases serum albumin concentrations and improves total dietary intake. This may improve clinical outcome, especially in malnourished patients, but insufficient published data exist to examine this. Additional research is required to investigate clinical, economic, and nutritional consequences of using oral supplements and tube feeding (using standard or disease-specific feeds) in patients with CKD receiving maintenance dialysis.

Adult↗

A systematic review of the evidence supporting the use of priority dispatch of emergency ambulances.

OBJECTIVES: Systematic reviews of the literature assist in the location, appraisal, and synthesis of available evidence. This systematic review aimed to 1) assess the existing literature evaluating the effect of the priority dispatch of emergency ambulances on clinical outcome and ambulance utilization and 2) assess the relative effectiveness of sources of literature relevant to prehospital care. METHODS: Systematic review. The quality of each paper was assessed using a standardized seven-point scoring schedule. Sources used were: Medline, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), Bath Information & Data Services (BIDS), bibliographic searching, contacting researchers active in the field, and hand-searching relevant journals. Key words used were: "ambulance," "prioritisation," "dispatch," and "triage." RESULTS: Three hundred twenty-six papers were identified: 64 (19.6%) were related to the prioritization of emergency ambulances, and only 20 (6.1%) contained original data. The overall quality of publications was poor, seven (35%) papers having a quality score > or = 4. Only half were identified by electronic databases, 55% were identified by people working in the field, and two (10%) were identified by hand-searching (some papers were identified by more than one source). Two high-quality papers support the concept that criteria-based dispatch (CBD) improves clinical outcome; two other papers support CBD's role in improving ambulance utilization. CONCLUSIONS: There is very little evidence to support the effect of the prioritization of emergency ambulances on patient outcome. Electronic databases identify only approximately half of all relevant prehospital literature. Future systematic reviews in this area should use electronic databases, supplemented by contact with appropriate experts.

Ambulances↗

Clinical and Genetic Predictors of Sickle Cell Nephropathy: A Global Systematic Review.

Sickle cell disease (SCD) affects nearly 300,000 newborns annually worldwide, with 80% born in Africa. Sickle cell nephropathy (SCN) affects 5-18% of patients with SCD and contributes significantly to morbidity and mortality. Identifying SCN-associated factors would promote effective clinical management. We conducted a global systematic review in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines (Prospective Register of Systematic Reviews, registration number: CRD42020185763) to explore clinical and genetic correlates of SCN. We sought after cohort, case-control, and cross-sectional studies published up to December 31, 2024 that reported on clinical and/or genetic predictors of SCN in different populations globally. A total of 70 hospital-based study articles were finally included, with a leading percentage (45.7%) of the included studies performed in the United States, whereas 24.3% were from Sub-Saharan Africa. Most had a cross-sectional design (68.6%) involving children and adults. Genetic studies (17/70) identified associations with α-thalassemia, APOL1, and HMOX1 genes. The only genome-wide association study identified six suggestive variants in CRYL1, VWF, ADAMTS7, LRP1B, linc02288, and FPGT-TNNI3K/TNNI3K among adult patients. In conclusion, this systematic review (1) unpacks and highlights the role of clinical, genetic, and biochemical factors in the pathogenesis and progression of SCN and (2) reveals the consistent association of SCN with the 3.7 Kb deletion in HBA and variants in APOL1 and HMOX1 genes. This systematic review underscores the paucity of data from Africa, emphasizing the need for large-scale prospective studies on African SCN cohorts. Our findings also provide a foundation for the early identification of individuals at risk for SCN and the avenues for clinical and public health management strategies. To the best of our knowledge, this is the first systematic review summarizing risk factors for kidney dysfunction in SCD populations worldwide, which includes, specifically, a meta-analysis for APOL1 association with albuminuria.

Humans↗

The pain-relieving effect of electro-acupuncture and conventional medical analgesic methods during oocyte retrieval: a systematic review of randomized controlled trials.

OBJECTIVE: The primary objective of the present review was to determine what pain-relieving effect had been reported for acupuncture and other conscious sedation methods in assisted reproduction therapy since 1990. The secondary objective was to determine pregnancy rates, when possible. METHODS: The data source was the Medline database of the National Library of Medicine covering the period January 1990-January 2004. Bibliographies of relevant publications and review articles were scanned. A systematic review and meta-analyses of randomized, controlled trials comparing the pain-relieving effect of acupuncture and other conscious sedation methods was carried out. RESULTS: Of the 30 trials identified, 12 met the selection criteria for this systematic review and were included in the analysis. Five of the 12 studies reported differences in pain experiences during oocyte aspiration, but it was only possible to group the three trials evaluating the effect of electro-acupuncture (EA). The outcomes of these three studies were homogenous except from maximal and average pain. CONCLUSION: No method could be regarded as being superior to another, and no consensus on which method is optimal for pain relief during oocyte retrieval was found. Low doses of lignocaine can, however, be recommended in paracervical block (PCB) as well as EA without pre-medication. The clinical pregnancy rates appeared to be similar between the studies. Since pain experience varies from individual to individual, the optimal method of conscious sedation may also be individualized.

Acupuncture Analgesia↗

Systematic reviews of treatment for inflammatory demyelinating neuropathy.

This review describes the progress made in preparing Cochrane systematic reviews of randomized controlled trials for Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN) and the demyelinating neuropathies associated with paraproteins. The discovery of antibodies against myelin and axolemmal glycolipids and proteins has not yet replaced the clinicopathological classification on which treatment trials have been based. Systematic reviews have endorsed the equivalence of plasma exchange (PE) and intravenous immunoglobulin (IVIg) and the lack of efficacy of steroids in GBS. Systematic reviews have also endorsed the value of steroids, PE and IVIg in CIDP but randomized controlled trials have only shown benefit from IVIg in MMN. There is a paucity of evidence concerning the efficacy of treatments in paraproteinaemic demyelinating neuropathy apartment from small trials showing short-term benefit from PE or IVIg. There is a lack of good quality controlled trials of immunosuppressive agents in any of these conditions. As the number of treatment trials increases, Cochrane systematic reviews will be an increasingly valuable resource for summarizing the evidence from randomised controlled trials on which to base clinical practice. They already demonstrate major deficiencies in the existing evidence base.

Glucocorticoids↗

The effects of an increase of central blood volume before spinal anesthesia for cesarean delivery: a qualitative systematic review.

UNLABELLED: We evaluated in this qualitative systematic review the efficacy of increasing central blood volume on the incidence of hypotension after spinal anesthesia for elective cesarean delivery. Randomized controlled trials investigating any method of increasing central blood volume before the initiation of obstetric spinal anesthesia were sought by using MEDLINE (1966-2000), Embase (January 1988-April 2000), and the Cochrane Library (Issue 1, 2000). Additional reports from retrieved and review articles, hand searching of non-MEDLINE journals, and abstracts of major anesthesia meetings (1994-1999) were located. The primary outcome was the incidence of hypotension. Secondary outcomes included: ephedrine use, Apgar scores, umbilical cord pH values, and maternal nausea and vomiting. Twenty-three articles met our inclusion criteria with the use of crystalloid preload, colloid preload, and mechanical methods of increasing central volume. Crystalloid preload was inconsistent in preventing hypotension, whereas colloid appeared to be effective in all but one study. Leg wrapping and thromboembolic stockings decreased the incidence of hypotension compared with leg elevation or control. Few differences in fetal outcomes or maternal nausea and vomiting were reported. Increasing central blood volume by using colloid and leg wrapping decreases but does not abolish the incidence of hypotension before spinal anesthesia for elective cesarean delivery. IMPLICATIONS: We performed a systematic review to determine whether fluid loading reduced the incidence of low blood pressure after spinal anesthesia for cesarean delivery. Although no technique totally eliminates the occurrence of hypotension, colloid administration (starch or gelatin containing fluids) and leg wrapping were the most effective.

Adult↗

Overview of systematic reviews on invasive treatment of stable coronary artery disease.

OBJECTIVES: The aim of the study was to evaluate the validity of the systematic reviews as a source of best evidence and to present and interpret the evidence of the systematic reviews on effectiveness of surgery and percutaneous interventions for stable coronary artery disease. METHODS: Electronic databases were searched without language restriction from January 1966 to March 2004. The databases used included the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, DARE, the Health Technology Assessment Database, MEDLINE(R), MEDLINE(R) In-Process & Other Non-Indexed Citations. We included systematic reviews of randomized clinical trials on patients with stable coronary heart disease undergoing percutaneous coronary intervention or coronary artery bypass surgery in comparison with medical treatment or a comparison between invasive techniques. At least one of the following outcomes had to be reported: death, myocardial infarction, angina pectoris, revascularization. The methodological quality was assessed using a modified version of the scale devised by Oxman and Guyatt (1991). A standardized data-extraction form was used. The method used to evaluate clinical relevance was carried out with updated method guidelines from the Cochrane Back Research Group. Quantitative synthesis of the effectiveness data is presented. RESULTS: We found nineteen systematic reviews. The median score of validity was 13 points (range, 6-17 points), with a maximum of 18 points. Coronary artery bypass surgery gives better relief of angina, and the need for repeated procedures is reduced after bypass surgery compared with percutaneous interventions. There is inconsistent evidence as to whether bypass surgery improves survival compared with percutaneous intervention. A smaller need for repeated procedures exists after bare metal stent and even more so after drug-eluting stent placement than after percutaneous intervention without stent placement. However, according to the current evidence, these treatment alternatives do not differ in terms of mortality or myocardial infarction. CONCLUSIONS: We found some high-quality systematic reviews. There was evidence on the potential of invasive treatments to provide symptomatic relief. Surgery seems to provide a longer-lasting effect than percutaneous interventions with bare metal stents or without stents. Evidence in favor of drug-eluting stents so far is based on short-term follow-up and mostly on patients with single-vessel disease.

Angioplasty, Balloon, Coronary↗

Skeletal and dental changes with fixed slow maxillary expansion treatment: a systematic review.

BACKGROUND: The authors were not able to identify any systematic reviews or meta-analysis on the dental or skeletal changes associated with slow maxillary expansion (SME). Therefore, they conducted a study to evaluate skeletal and dental changes after fixed SME treatment in orthodontic patients with constricted arches. METHODS: The authors included in their evaluation clinical trials that assessed skeletal and dental arch changes through measurements on dental casts or cephalometric radiographs. The authors did not consider trials involving surgical or other simultaneous treatment interventions during the active expansion period. RESULTS: With the help of a health sciences librarian, the authors searched the following electronic databases: PubMed, MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, Evidence Based Medicine Reviews (Cochrane Database of Systematic Reviews, American College of Physicians Journal Club, Database of Abstracts of Reviews of Effects and Cochrane Central Register of Controlled Trials), EMBASE Excerpta Medica, Thomsen's ISI Web of Sciences and LILACS. Eight articles met the initial inclusion criteria. The authors found that a significant deficiency in the studies was the lack of a control group to factor out changes in the dental arch and skeletal structures associated with normal growth. CONCLUSIONS AND CLINICAL IMPLICATIONS: The authors found only a lower level of evidence. Therefore, they could make no strong conclusions on dental or skeletal changes that occurred after SME treatment. Clinicians need to rely on their clinical experience, experts' opinions and the presented limited evidence concerning SME treatments.

Age Factors↗

Cost-effectiveness of cell salvage and alternative methods of minimising perioperative allogeneic blood transfusion: a systematic review and economic model.

OBJECTIVES: To compare patient outcomes, resource use and costs to the NHS and NHS Blood Transfusion Authority (BTA) associated with cell salvage and alternative methods of minimising perioperative allogeneic blood transfusion. DATA SOURCES: Electronic databases covering the period 1996-2004 for systematic reviews and 1994-2004 for economic evidence. REVIEW METHODS: Existing systematic reviews were updated with data from selected randomised controlled trials (RCTs) that involved adults scheduled for elective non-urgent surgery. Any resource use or cost data were extracted for potential use in populating an economic model. Relative risks or weighted mean difference of each outcome for each intervention were assessed, taking into account the number of RCTs included in each outcome and intervention and the presence of any heterogeneity. This allowed indirect comparison of the relative effectiveness of each intervention when the intervention is compared with allogeneic blood transfusion. A decision analytic model synthesised clinical and economic data from several sources, to estimate the relative cost-effectiveness of cell salvage for people undergoing elective surgery with moderate to major expected blood loss. The perspective of the NHS and patients and a time horizon of 1 month were used. The economic model was developed from reviews of effectiveness and cost-effectiveness and clinical experts. Secondary analysis explored the robustness of the results to changes in the timing and costs of cell salvage equipment, surgical procedure, use of transfusion protocols and time horizon of analysis. RESULTS: Overall, 668 studies were identified electronically for the update of the two systematic reviews. This included five RCTs, of which two were cell salvage and three preoperative autologous donation (PAD). Five published systematic reviews were identified for antifibrinolytics, fibrin sealants and restrictive transfusion triggers, PAD plus erythropoietin, erythropoietin alone and acute normovolaemic haemodilution (ANH). Twelve published studies reported full economic evaluations. All but two of the transfusion strategies significantly reduced exposure to allogeneic blood. The relative risk of exposure to allogeneic blood was 0.59 for the pooled trials of cell salvage (95% confidence interval: 0.48 to 0.73). This varied by the type and timing of cell salvage and type of surgical procedure. For cell salvage, the relative risk of allogeneic blood transfusion was higher in cardiac surgery than in orthopaedic surgery. Cell salvage had lower costs and slightly higher quality-adjusted life years compared with all of the alternative transfusion strategies except ANH. The likelihood that cell salvage is cost-effective compared with strategies other than ANH is over 50%. Most of the secondary analyses indicated similar results to the primary analysis. However, the primary and secondary analyses indicated that ANH may be more cost-effective than cell salvage. CONCLUSIONS: The available evidence indicates that cell salvage may be a cost-effective method to reduce exposure to allogeneic blood transfusion. However, ANH may be more cost-effective than cell salvage. The results of this analysis are subject to the low quality and reliability of the data used and the use of indirect comparisons. This may affect the reliability and robustness of the clinical and economic results. There is a need for further research that includes adequately powered high-quality RCTs to compare directly various blood transfusion strategies. These should include measures of health status, health-related quality of life and patient preferences for alternative transfusion strategies. Observational and tracking studies are needed to estimate reliably the incidence of adverse events and infections transmitted during blood transfusion and to identify the lifetime consequences of the serious hazards of transfusion on mortality, health status and health-related quality of life.

Aminocaproates↗

Systematic reviews and meta-analyses: an illustrated, step-by-step guide.

Systematic reviews and meta-analyses synthesize data from existing primary research, and well-conducted reviews offer clinicians a practical solution to the problem of staying current in their fields of interest. A whole generation of secondary journals, pre-appraised evidence libraries and periodically updated electronic texts are now available to clinicians. However, not all systematic reviews are of high quality, and it is important to be able to critically assess their validity and applicability. This article is an illustrated guide for conducting systematic reviews. A clear understanding of the process will provide clinicians with the tools to judiciously appraise reviews and interpret them. We hope that it will enable clinicians to conduct systematic reviews, generate high-quality evidence, and contribute to the evidence-based medicine movement.

Bibliometrics↗

Methodologies analysing individual practice in health care: a systematic review.

AIM OF THE REVIEW: The aim of the systematic review was to identify, explore and evaluate the current level of knowledge of methodologies used in comparative analyses of the individual practice of doctors, nurses and midwives. RATIONALE: The question of how roles and responsibilities might be shared differently between professional groups in order to promote improved, cost-effective health care requires a systematic analysis of existing roles and practice. To do this effectively, knowledge of the methodologies available for such an analysis is essential. METHODS: A systematic review of the literature published since 1989 comparing the practice of doctors, nurses and midwives was undertaken. FINDINGS: The findings are presented in tabular format and include the following categories of published methodologies: experimental/quasi-experimental; descriptive/nonexperimental and qualitative studies. The discussion centres on a critique of quantitative methodologies used to analyse individual practice in relation to role substitution and diversification. The potential contribution of qualitative methodologies in the analysis of individual practice is discussed. CONCLUSIONS: The authors conclude that the current level of knowledge is biased towards quantitative research. It is argued that the assessment of health care roles and responsibilities would be well served by a more balanced approach that recognizes the strengths of both quantitative and qualitative work.

Humans↗

Psychosocial interventions for patients with advanced cancer - a systematic review of the literature.

Advanced cancer is associated with emotional distress, especially depression and feelings of sadness. To date, it is unclear which is the most effective way to address these problems. This review focuses on the effects of psychosocial interventions on the quality of life (QoL) of patients with advanced cancer. It was hypothesised that patients will benefit from psychosocial interventions by improving QoL, especially in the domain of emotional functioning. The review was conducted using systematic review methodology involving a systematic search of the literature published between 1990 and 2002, quality assessment of included studies, systematic data extraction and narrative data synthesis. In all, 10 randomised controlled studies involving 13 trials were included. Overall interventions and outcome measures across studies were heterogeneous. Outcome measures, pertaining to the QoL dimension of emotional functioning, were most frequently measured. A total of 12 trials evaluating behaviour therapy found positive effects on one or more indicators of QoL, for example, depression. The results of the review support recommendation of behaviour therapy in the care of patients with advanced cancer.

Clinical Trials as Topic↗

Does the non-randomized controlled study have a place in the systematic review? A pilot study.

BACKGROUND: A major issue in any systematic review is deciding which trials or studies to include and which to exclude. The Cochrane Collaboration and similar respected organizations have traditionally viewed the randomized trial (RCT) as the only acceptable evidence on treatment outcome. However, many systematic reviews are indeterminate because they include insufficient RCTs whilst they reject large numbers of non-randomized controlled studies. This is particularly true in forensic mental health, a domain where RCT methodology can be problematic. Systematic reviews could become more informative if reviewers knew when, and under what circumstances, non-randomized designs are acceptable for inclusion alongside RCTs. METHOD: This pilot study explores whether good-quality, controlled, non-randomized studies can be reliable surrogates for RCTs. We examined two published reviews from the Cochrane Schizophrenia Group. We compared outcomes between (a) randomized trials (that had been included) and non-randomized studies (that had been excluded), and (b) between high- and low-quality studies using an established quality checklist. RESULTS: In the first review, effect scores were similar for randomized and non-randomized studies and relatively insensitive to study quality. In the second review, the treatment effect was considerably lower for the RCT group - here, however, studies of high-quality showed much smaller effect scores than those of low-quality on two separate outcomes. CONCLUSIONS: Non-randomized controlled studies of high quality can produce outcomes that approximate to those found in RCTs. Trial quality may have a greater impact on treatment effect size than randomization alone, suggesting that randomization should not be seen as a reliable proxy for overall quality. The problems and issues still to be resolved are discussed with recommendations for future research.

Humans↗

Systematic reviews of health care interventions: an essential component of health sciences graduate programs.

Systematic reviews are an objective, rigorous assessment of both published and unpublished research that enable the reviewer to make recommendations to clinicians, policy-makers, consumers, and researchers. The steps in a systematic review include: (a) developing a research question, (b) developing relevance and validity tools, (c) conducting a thorough literature search of published and unpublished studies, (d) using relevance and validity tools to assess the studies, (e) completing data extraction for each study, (f) synthesizing the findings and, (g) writing the report. The purpose of this paper is to demonstrate the value of providing health science graduate students with the opportunity to learn about the conduct of a systematic review. An example of a thesis utilizing the method of a systematic review is presented.

Curriculum↗

Postoperative incision hernia in patients with abdominal aortic aneurysm and aortoiliac occlusive disease: a systematic review.

OBJECTIVES: We conducted a systematic review to determine the incidence of postoperative incision hernia in patients with abdominal aortic aneurysm compared to those with aortoiliac occlusive disease. METHODS: Studies which compared the incidence of postoperative incision hernia in patients with abdominal aortic aneurysm and aortoiliac occlusive disease undergoing midline incision for arterial reconstruction were identified. MEDLINE was searched for articles published between January 1966 and September 2005. RESULTS: Our search identified seven studies including data on 1132 patients, 719 with abdominal aortic aneurysm and 413 with aortoiliac occlusive disease. Pooled analysis demonstrated that patients with abdominal aortic aneurysm had a 2.9-fold increased risk of inguinal hernia (odds ratio 2.85, 95% confidence interval 1.71-4.77, p<0.0001), and a 2.8-fold risk of incisional hernia (2.79, 1.88-4.13, p<0.0001). Adjusting for other known risk factors patients with aortic aneurysm had a 5-fold increased risk of incisional hernia (5.45, 2.48-11.94, p<0.0001). CONCLUSIONS: Patients with abdominal aortic aneurysm appear to have an approximately 3-fold increased risk for both inguinal and postoperative incision hernia compared to patients with aortoiliac occlusive disease. A large multi-centre prospective study is needed to confirm the results of this review.

Aorta, Abdominal↗

Physical activity interventions in the prevention and treatment of paediatric obesity: systematic review and critical appraisal.

Interventions for prevention and treatment of childhood obesity typically target increases in physical activity and, more recently, reductions in physical inactivity (sedentary behaviour such as television viewing). However, the evidence base for such strategies is extremely limited. The main aim of the present review was to update the systematic review and critical appraisal of evidence in the light of the recent rapid expansion of research in this area. Randomised controlled trials (RCT) that targeted activity or inactivity, that followed up children or adolescents for at least 1 year and that included an objective weight-related outcome measure were included. Trials were appraised using previously published criteria (Harbour & Miller, 2001), and literature search strategies described previously (Reilly et al. 2002) were updated to May 2002. A total of four new RCT, two new systematic reviews and one meta-analysis were identified. The evidence base has increased markedly since the completion of earlier reviews, although high-quality evidence is still lacking. The evidence on childhood obesity prevention is not encouraging, although promising targets for prevention are now clear, notably reduction in sedentary behaviour. There is stronger evidence that targeting activity and/or inactivity might be effective in paediatric obesity treatment, but doubts as to the generalisability of existing interventions, and the clinical relevance of the interventions is unclear. Further research in settings outside the USA is urgently needed, and two ongoing RCT in Scotland are summarised.

Adolescent↗

Control of bleeding in patients with haemophilia A with inhibitors: a systematic review.

This paper reports a systematic review of the best available evidence of clinical effectiveness in the treatment of acute bleeding in haemophilia A patients with inhibitors. Because of the lack of randomized controlled trials (RCTs) on this topic, broad inclusion criteria with regard to study design were applied in order to assess the best available evidence for each intervention. Because of the clinical and methodological heterogeneity of the evidence, it was not appropriate to pool data across studies; instead, data were synthesized using tabulation and qualitative narrative assessment. No evidence was found to support the use of high-dose factor VIII (FVIII) in bleeding episodes. However in surgery it was found to be highly successful (100%) for low-titre, low-responding inhibitors although not reliable for high-responding inhibitors. Porcine FVIII (pFVIII) was effective in the control of severe bleeding episodes with high-titre or high-responding inhibitors (100%) and in 60-90% of surgical procedures. Activated prothrombin complex concentrates (APCCs) appear to be more effective than prothrombin complex concentrates (PCCs) in the control of mild to severe bleeding episodes. There was no good evidence for the use of PCCs in surgery. APCCs controlled bleeding in approximately 90% of surgical episodes. Recombinant factor VIIa (rFVIIa) controlled 70-100% of mild to severe bleeding episodes with high-responding inhibitors, and achieved better results when used early. It was effective in 60-100% of surgical episodes. Doses varied from study to study, and side-effects from mild to infrequent but serious adverse events were reported. The quality of the evidence is variable. Limited evidence relating to other treatment options is also included in the review.

Acute Disease↗