Systematic review of topical interventions for the management of pain in chronic wounds.

Chronic wounds adversely affect quality of life. Pain is associated with chronic wounds, and its impact can vary according to wound aetiology, condition, and patient factors. This systematic review examined the effectiveness of topical interventions in the management chronic wound-related pain guided by PRISMA recommendations of randomised controlled trials (RCTs) where pain reduction is the primary outcome. Inclusion criteria were adults (older than 18 years) with chronic venous, arterial, diabetic, or pressure ulcers where pain has been managed through topical administration of pharmacological/nonpharmacological agents. Searches were conducted in Ovid Embase, Ovid MEDLINE, EBSCOhost, CINAHL, CENTRAL, PubMed, Web of Science, and Scopus. Studies were screened for eligibility; risk of bias and data were extracted by 2 independent assessors. Searches retrieved 10,327 titles and abstracts (7760 after deduplication). Nine full texts (1323 participants) examining ibuprofen (n = 4), morphine (n = 2), BWD + PHMB [polihexanide-containing biocellulose wound dressing] (n = 1), and EMLA (n = 2) were included. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Meta-analysis was not possible, but initial exploration suggests improved outcomes (reduced pain) for ibuprofen when compared with controls. Two studies involving morphine showed conflicting findings. Included studies often had small samples, and considering confounding factors (eg, comorbidities), the results should be interpreted with caution. Review of included studies suggests that topical interventions may provide pain relief in individuals with chronic wounds. Further adequately powered RCTs are recommended to assess the efficacy of topical interventions for the management of chronic wound-related pain.

Topical interventions for the management of pain in chronic wounds: A protocol for a systematic review.

Background: Venous, arterial, diabetic and pressure ulcers, collectively known as chronic wounds, negatively impact individuals across psychological, social and financial domains. Chronic wounds can be painful and the nature, frequency and impact of pain can differ depending on wound aetiology, wound state and on numerous patient factors. While systemic pharmaceutical agents have some effect in managing pain, there is a need to examine topical agents applied to the wound bed for pain relief. The objective of this study is to examine and synthesise existing literature on the effectiveness of topical agents in managing pain in venous, diabetic, pressure, arterial and mixed venous/arterial ulcers. Methods: We will use Cochrane Systematic Review methodology to identify and synthesise eligible randomised controlled trials (RCTs) evaluating the effectiveness of topical agents in reducing pain in chronic wounds. Embase, Medline, PubMed, CENTRAL, CINAHL, Scopus and Web of Science will be searched from inception to end of June 2022 without language limits. We will independently extract data on the pharmaceutical agent, participant demographics, aetiology, condition of the wound, and type, nature and frequency of pain using a pre-designed data extraction form. Subgroup and sensitivity analysis will be performed to address heterogeneity across studies if appropriate. Further stratification and analyses will be based on included study variables and outcomes. Discussion: Wound pain is primarily managed via systemic pharmaceutical agents. However, patients express reluctance regarding systemic analgesic drugs, fearing addiction. Additionally, persons with chronic wounds have co-morbidities including hypertension, diabetes, or cardiovascular disease and are already taking multiple medications. Topical analgesia can potentially mitigate some of the perceived disadvantages of systemic agents but the available range of these agents and their effectiveness in managing pain in chronic wounds is not so well understood. This review will focus on such agents across a range of the most common chronic wounds.

What is the "normal" wound bed temperature? A scoping review and new hypothesis.

Wound bed temperature measurement holds the potential to be a safe, easy to use, and low-cost tool to aid objective wound bed assessment, clinical decision making and improved patient outcomes. However, there is no consensus on the normal range of wound bed temperature in chronic wounds. We conducted a scoping review including any study type, from 2010 to 2020 in which chronic wound bed temperature was reported. Thirteen studies including 477 patients met our criteria. Venous ulcers (VLU) accounted for 46.5% (n = 222) of wounds; diabetic foot ulcers (DFU) for 25.4% (n = 121) with pressure ulcers (PU), mixed arterial venous ulcers (MAVLU) and unknown aetiology accounting for the remainder. The weighted mean of means for wound bed temperature was 31.7°C (n = 395) for all wound types; 31.7°C for VLU; 31.6°C for DFU; 33.3°C for PU; 30.9°C for MAVLU; and 32.0°C for those with unknown aetiology. Based on our review, we hypothesise that normal wound bed temperature is within a range of 30.2-33.0°C.

Comparative Efficacy and Safety of Ultra-Long-Acting, Long-Acting, Intermediate-Acting, and Biosimilar Insulins for Type 1 Diabetes Mellitus: a Systematic Review and Network Meta-Analysis.

BACKGROUND: Increasing availability of competing biosimilar alternatives makes it challenging to make treatment decisions. The purpose of this review is to evaluate the comparative efficacy and safety of ultra-long-/long-/intermediate-acting insulin products and biosimilar insulin compared to human/animal insulin in adults with type 1 diabetes mellitus (T1DM). METHODS: MEDLINE, EMBASE, CENTRAL, and grey literature were searched from inception to March 27, 2019. Randomized controlled trials (RCTs), quasi-experimental studies, and cohort studies of adults with T1DM receiving ultra-long-/long-/intermediate-acting insulin, compared to each other, as well as biosimilar insulin compared to human/animal insulin were eligible for inclusion. Two reviewers independently screened studies, abstracted data, and appraised risk-of-bias. Pairwise meta-analyses and network meta-analyses (NMA) were conducted. Summary effect measures were mean differences (MD) and odds ratios (OR). RESULTS: We included 65 unique studies examining 14,200 patients with T1DM. Both ultra-long-acting and long-acting insulin were superior to intermediate-acting insulin in reducing A1c, FPG, weight gain, and the incidence of major, serious, or nocturnal hypoglycemia. For fasting blood glucose, long-acting once a day (od) was superior to long-acting twice a day (bid) (MD - 0.44, 95% CI: - 0.81 to - 0.06) and ultra-long-acting od was superior to long-acting bid (MD - 0.73, 95% CI - 1.36 to - 0.11). For weight change, long-acting od was inferior to long-acting bid (MD 0.58, 95% CI: 0.05 to 1.10) and long-acting bid was superior to long-action biosimilar od (MD - 0.90, 95% CI: - 1.67 to - 0.12). CONCLUSIONS: Our results can be used to tailor insulin treatment according to the desired results of patients and clinicians and inform strategies to establish a competitive clinical market, address systemic barriers, expand the pool of potential suppliers, and favor insulin price reduction. PROSPERO REGISTRATION: CRD42017077051.

A scoping review protocol to identify clinical signs, symptoms and biomarkers indicative of biofilm presence in chronic wounds.

Introduction: Wound healing is characterised by haemostatic, inflammatory, proliferative and remodelling phases. In the presence of comorbidities such as diabetes, healing can stall and chronic wounds may result. Infection is detrimental to these wounds and associated with poor outcomes. Wounds are contaminated with microbes and debris, and factors such as host resistance, bacterial virulence, species synergy and bioburden determine whether a wound will deteriorate to critically colonised/infected states. Biofilms are sessile microbial communities, exhibiting high-level antibiotic tolerance and resistance to host defences. Biofilm in critically colonised wounds can contribute to delayed healing. Little is known about clinical presentation and diagnosis of wound biofilms. Objective: To identify from the literature clinical signs, symptoms and biomarkers that may indicate biofilm in chronic wounds. Methods: This review will be guided by the Preferred Reporting Items for Systematic Reviews extension for Scoping Reviews (PRISMA-ScR), and the Joanna Briggs Institute Manual for Evidence Synthesis. Studies of any design in any language recruiting adult patients with  venous, diabetic, pressure or mixed arterial-venous ulcers and reporting data on clinical signs/symptoms of biofilm are eligible. Searches of Medline, Embase, CINAHL, Cochrane Central, Scopus, Web of Science, Google scholar and BASE will be conducted from inception to present. Reference scanning and contact with content experts will be employed. Title/abstract screening and full text selection will be executed by two reviewers independently. Discrepancies will be resolved by discussion between reviewers or through third party intervention. Data will be extracted by a single reviewer and verified by a second. Clinical signs and symptoms data will be presented in terms of study design, setting and participant demographic data. Discussion: Understanding biofilm impact on chronic wounds is inconsistent and based largely on in vitro research. This work will consolidate clinical signs, symptoms and biomarkers of biofilm in chronic wounds reported in the literature.

Effectiveness of implementation strategies for venous leg ulcer guidelines: A systematic review.

BACKGROUND: The aim of clinical practice guidelines (CPGs) is to improve patient care; however inconsistencies between recommended practice and what actually happens in clinical practice continues. Venous Leg Ulcers (VLUs) have a significant negative impact on patients' quality of life and it is acknowledged that managing people with venous leg ulcers is protracted and costly. The aim of this review is to identify the most effective strategies to implement clinical practice guidelines for the management of VLUs by health care professionals in the hospital, outpatient, home and community setting. METHODS: A systematic review guided by methods from the Cochrane Effective Practice and Organisation of Care (EPOC) group was undertaken to identify implementation strategies for VLU clinical practice guidelines. Eligible studies were identified via systematic electronic searches of Medline, Embase, CINHAL and the Cochrane Library. RESULTS: We identified 142 potential studies of which one randomised controlled trial met the inclusion criteria. Following an analysis of the included study, it is not possible to recommend one implementation strategy over another when implementing practice guidelines for people with VLUs. CONCLUSION: We identified a limited evidence base for the effectiveness of implementation strategies for VLU CPGs. No one implementation strategy is better than another to facilitate VLU CPG implementation by health care professionals in hospital, outpatient, home or community settings.

In the preparation and administration of intravenous medicines, what are the best practice standards that healthcare professionals need to follow to ensure patient safety? Protocol for a systematic review.

Introduction: Intravenous therapy and medicines (IVTM) are the most common invasive interventions in use in healthcare. Prescribed IVTM play an essential role in the treatment of illness, management of chronic conditions and in maintaining health and wellbeing. The intravenous (IV) route is the administration of concentrated medications (diluted or undiluted) directly into peripherally or centrally inserted vascular access devices. Medication safety is a key priority and best practice standards are required to guide the safe preparation and administration of IVTM. Methods: We will conduct a systematic review of the literature pertaining to the preparation and administration of intravenous therapy and medicines. Our search will include studies concerned with the preparation and/or administration of IVTM via peripheral or central vascular access devices. We will be guided by the preferred reporting items for systematic review and meta-analysis (PRISMA) in this review. Literature will include all trial designs, national/international guidelines, and expert consensus opinion made available in English from 2009 to present day. Conclusions: We will synthesise the evidence concerning safe and effective preparation and administration of intravenous therapy and medicines to inform the development of a national guideline for healthcare professionals in Ireland. The availability of up-to-date, contemporaneous evidence-based practice standards will ensure quality and safety for service-users. Registration:  This study has been submitted to PROSPERO and we are awaiting confirmation of registration.

Public & patient involvement to guide research in wound care in an Irish context. A round table report.

BACKGROUND: To date, research into interventions to promote wound healing has been led by scientists, clinicians, industry and academics, each with their own particular area of interest. However, the real experts in this area are the people who live with wounds and their families and heretofore their voice has not influenced or shaped the research agenda. AIM: This event aimed to seek patient and carer involvement as experts due to their lived experience in wounds through a partnership approach to identify research priorities and address a lack of patient and carer involvement in wound care research. METHODS: A roundtable discussion format guided by the Scottish Health Council Participation Toolkit Supporting Patient Focus and Public Involvement in NHS Scotland was utilised. The Guidance for Reporting Involvement of Patients and the Public 2 - Short Form (GRIPP2-SF) guided the reporting process. RESULTS: Key areas for future research were identified and included; Patients and carers prioritised the establishment of support groups and the development of educational resources. Research priorities that emerged included understanding the impact of wounds, pain management, addressing educational needs and quantifying the financial burden on patients and carers of living with a wound. CONCLUSIONS: A key conclusion from this roundtable was that patients and their carers expressed a strong interest in further wound care related public and patient involvement events and identified areas for future research.

External validity of randomized controlled trials of interventions in venous leg ulceration: A systematic review.

We set out to evaluate quality of reporting of data related to external validity from randomized controlled trials (RCTs) assessing treatment interventions for active venous leg ulcers. Using a systematic review study design, we identified 144 full-text RCTs of treatment interventions, where the wound was assessed and published in English from 1998 to 2018. We found that the median study sample size was 75.5. Weighted mean wound size was 13.22 cm2 and weighted mean wound duration was 22.20 months. Forty-six (32%) reported numbers screened for eligibility and 27 (19%) reported the number who declined to participate; 19 (13%) reported on patient ethnicity; 60 (42%) reported comorbidities; and 5 (4%) reported current medication use. When reported, 60/102 (59%) excluded patients with an ankle-brachial pressure index <0.8; 68/135 (50%) were conducted in Europe, 6/135 (4%) in Asia, and 74/104 (71%) were conducted in outpatient facilities; 3 (2%) reported socioeconomic factors and 88 (61%) reported on adverse events. We concluded that there is inadequate reporting of data related to external validity in reports of RCTs assessing venous leg ulcers treatment interventions. Significant variability exists in the ankle-brachial pressure index cutoff point for inclusion or exclusion, making generalizability difficult to assess.

ABPI reporting and compression recommendations in global clinical practice guidelines on venous leg ulcer management: A scoping review.

Clinical practice guidelines (CPGs) for venous leg ulcer (VLU) management recommend below-knee compression to improve healing outcomes after calculating the ankle-brachial pressure index (ABPI) to rule out significant arterial disease. This systematic scoping review aimed to complete a qualitative and quantitative content analysis of international CPGs for VLU management to determine if consensus existed in relation to recommendations for compression application based on an ABPI reading and clinical assessment. Our review shows that there is a lack of consensus across 13 VLU CPGs and a lack of clear guidance in relation to the specific ABPI range of compression therapy that can be safely applied. An area of uncertainty and disagreement exists in relation to an ABPI between 0.6 and 0.8, with some guidelines advocating that compression is contraindicated and others that there should be reduced compression. This has implications in clinical practice, including when it is safe to apply compression. In addition, the inconsistency in the levels of evidence and the grades of recommendation makes it difficult to compare across various guidelines.

Patient safety initiatives in obstetrics: a rapid review.

OBJECTIVES: This review was commissioned by WHO, South Africa-Country office because of an exponential increase in medical litigation claims related to patient safety in obstetrical care in the country. A rapid review was conducted to examine the effectiveness of quality improvement (QI) strategies on maternal and newborn patient safety outcomes, risk of litigation and burden of associated costs. DESIGN: A rapid review of the literature was conducted to provide decision-makers with timely evidence. Medical and legal databases (eg, MEDLINE, Embase, LexisNexis Academic, etc) and reference lists of relevant studies were searched. Two reviewers independently performed study selection, abstracted data and appraised risk of bias. Results were summarised narratively. INTERVENTIONS: We included randomised clinical trials (RCTs) of QI strategies targeting health systems (eg, team changes) and healthcare providers (eg, clinician education) to improve the safety of women and their newborns. Eligible studies were limited to trials published in English between 2004 and 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: RCTs reporting on patient safety outcomes (eg, stillbirths, mortality and caesarean sections), litigation claims and associated costs were included. RESULTS: The search yielded 4793 citations, of which 10 RCTs met our eligibility criteria and provided information on over 500 000 participants. The results are presented by QI strategy, which varied from one study to another. Studies including provider education alone (one RCT), provider education in combination with audit and feedback (two RCTs) or clinician reminders (one RCT), as well as provider education with patient education and audit and feedback (one RCT), reported some improvements to patient safety outcomes. None of the studies reported on litigation claims or the associated costs. CONCLUSIONS: Our results suggest that provider education and other QI strategy combinations targeting healthcare providers may improve the safety of women and their newborns during childbirth.

Comparative safety and effectiveness of perinatal antiretroviral therapies for HIV-infected women and their children: Systematic review and network meta-analysis including different study designs.

BACKGROUND: Nearly all newly infected children acquire Human Immunodeficiency virus (HIV) via mother-to-child transmission (MTCT) during pregnancy, labour or breastfeeding from untreated HIV-positive mothers. Antiretroviral therapy (ART) is the standard care for pregnant women with HIV. However, evidence of ART effectiveness and harms in infants and children of HIV-positive pregnant women exposed to ART has been largely inconclusive. The aim of our systematic review and network meta-analysis (NMA) was to evaluate the comparative safety and effectiveness of ART drugs in children exposed to maternal HIV and ART (or no ART/placebo) across different study designs. METHODS: We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (inception until December 7, 2015). Primary outcomes were any congenital malformations (CMs; safety), including overall major and minor CMs, and mother-to-child transmission (MTCT; effectiveness). Random-effects Bayesian pairwise meta-analyses and NMAs were conducted. After screening 6,468 citations and 1,373 full-text articles, 90 studies of various study designs and 90,563 patients were included. RESULTS: The NMA on CMs (20 studies, 7,503 children, 16 drugs) found that none of the ART drugs examined here were associated with a significant increase in CMs. However, zidovudine administered with lamivudine and indinavir was associated with increased risk of preterm births, zidovudine administered with nevirapine was associated with increased risk of stillbirths, and lamivudine administered with stavudine and efavirenz was associated with increased risk of low birth weight. A NMA on MTCT (11 studies, 10,786 patients, 6 drugs) found that zidovudine administered once (odds ratio [OR] = 0.39, 95% credible interval [CrI]: 0.19-0.83) or twice (OR = 0.43, 95% CrI: 0.21-0.68) was associated with significantly reduced risk of MTCT. CONCLUSIONS: Our findings suggest that ART drugs are not associated with an increased risk of CMs, yet some may increase adverse birth events. Some ART drugs (e.g., zidovudine) effectively reduce MTCT.

A retrospective comparison of systematic reviews with same-topic rapid reviews.

OBJECTIVE: To compare rapid reviews (RRs) to same-topic systematic reviews (SRs) for methods, studies included, and conclusions. STUDY DESIGN AND SETTING: A retrospective comparison of studies comparing RRs and SRs by searching four scoping reviews published between 2007 and 2016. Reports were included if literature searches were conducted within 24 months of each other and had common research questions. Reviews were compared for duration, studies included, population, intervention, comparisons, outcomes, study designs, quality, methods, and conclusions. RESULTS: Six studies containing 16 review pairs were included, covering nine topics. Overall, RRs used abbreviated methods more often: no search of grey literature, employing one reviewer to screen studies, engaging fewer experts, including fewer studies, and providing shorter reports, with poorer reporting quality and faster completion. Reviews reported similar conclusions, with two exceptions: one SR did not include a key study; separately, two RRs failed to highlight an association with early mortality identified by the SR. RRs tended to provide less detail and fewer considerations. CONCLUSION: RRs used several methodological shortcuts compared with SRs on the same topic. It was challenging to discern methodological differences because of retrospective assessment and substantial nonreporting, particularly for RRs.

Comparative Effectiveness and Safety of Cognitive Enhancers for Treating Alzheimer's Disease: Systematic Review and Network Metaanalysis.

BACKGROUND/OBJECTIVES: To examine the comparative effectiveness and safety of cognitive enhancers for Alzheimer's disease (AD). DESIGN: Systematic review and Bayesian network metaanalysis (NMA). SETTING: MEDLINE, EMBASE, Cochrane Library, CINAHL, Ageline (inception-March 2016). PARTICIPANTS: Individuals with AD in randomized controlled trials (RCTs), quasi-RCTs, and nonrandomized studies. INTERVENTION: Any combination of donepezil, rivastigmine, galantamine, or memantine. MEASUREMENTS: Two reviewers independently screened titles, abstracts, and full-texts; abstracted data; and appraised risk of bias. RESULTS: Twenty thousand three hundred forty-three citations were screened, and 142 studies were included (110 RCTs, 21 non-RCTs, 11 cohort studies). NMA found that donepezil (Mini-Mental State Examination: mean difference (MD) = 1.39, 95% credible interval (CrI) = 0.53-2.24), donepezil+memantine (2.59, 95% CrI = 0.12-4.98), and transdermal rivastigmine (2.02, 95% CrI = 0.02-4.08) improved cognition more than placebo. NMA found that donepezil (Alzheimer's Disease Assessment Scale-cognitive: MD = -3.29, 95% CrI = -4.57 to -1.99) and galantamine (MD = -2.13, 95% CrI = -3.91 to -0.27) improved cognition more than placebo. NMA found that donepezil+memantine (MD = -5.23, 95% CrI = -8.72 to -1.56) improved behavior more than placebo. NMA found that donepezil (MD = -0.32, 95% CrI = -0.46 to -0.19), donepezil+memantine (MD = -0.57, 95% CrI = -0.95 to -0.21), oral rivastigmine (MD = -0.38, 95% CrI = -0.56 to -0.17), and galantamine (MD = -3.79, 95% CrI = -6.98 to -0.59) improved global status more than placebo. NMA found that galantamine decreased the odds of mortality (odds ratio = 0.56, 95% CrI = 0.36-0.87). No agent increased risk of serious adverse events, falls, or bradycardia. Some increased risk of headache (oral rivastigmine), diarrhea (oral rivastigmine, donepezil), nausea (oral rivastigmine, donepezil, galantamine), and vomiting (oral rivastigmine, donepezil, galantamine). CONCLUSION: An exhaustive review of the literature involving 142 studies demonstrated that cognitive enhancers in general have minimal effects on cognition according to minimal clinically important difference and global ratings. The drugs appear safe, but this must be interpreted cautiously because trial participants may have less comorbidity and fewer adverse effects than those treated with these drugs in clinical practice.

Effectiveness of different compression-to-ventilation methods for cardiopulmonary resuscitation: A systematic review.

AIM: To compare the effectiveness of different compression-to-ventilation methods during cardiopulmonary resuscitation (CPR) in patients with cardiac arrest. METHODS: We searched MEDLINE and Cochrane Central Register of Controlled Trials from inception until January 2016. We included experimental, quasi-experimental, and observational studies that compared different chest compression-to-ventilation ratios during CPR for all patients and assessed at least one of the following outcomes: favourable neurological outcomes, survival, return of spontaneous circulation (ROSC), and quality of life. Two reviewers independently screened literature search results, abstracted data, and appraised the risk of bias. Random-effects meta-analyses were conducted separately for randomised and non-randomised studies, as well as study characteristics, such as CPR provider. RESULTS: After screening 5703 titles and abstracts and 229 full-text articles, we included 41 studies, of which 13 were companion reports. For adults receiving bystander or dispatcher-instructed CPR, no significant differences were observed across all comparisons and outcomes. Significantly less adults receiving bystander-initiated or plus dispatcher-instructed compression-only CPR experienced favourable neurological outcomes, survival, and ROSC compared to CPR 30:2 (compression-to-ventilation) in un-adjusted analyses in a large cohort study. Evidence from emergency medical service (EMS) CPR providers showed significantly more adults receiving CPR 30:2 experiencing improved favourable neurological outcomes and survival versus those receiving CPR 15:2. Significantly more children receiving CPR 15:2 or 30:2 experienced favourable neurological outcomes, survival, and greater ROSC compared to compression-only CPR. However, for children <1 years of age, no significant differences were observed between CPR 15:2 or 30:2 and compression-only CPR. CONCLUSIONS: Our results demonstrated that for adults, CPR 30:2 is associated with better survival and favourable neurological outcomes when compared to CPR 15:2. For children, more patients receiving CPR with either 15:2 or 30:2 compression-to ventilation ratio experienced favourable neurological function, survival, and ROSC when compared to CO-CPR for children of all ages, but for children <1years of age, no statistically significant differences were observed.

Comparative safety and effectiveness of serotonin receptor antagonists in patients undergoing chemotherapy: a systematic review and network meta-analysis.

BACKGROUND: Although serotonin (5-HT3) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to examine the comparative safety and effectiveness of 5-HT3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron) alone or combined with steroids for patients undergoing chemotherapy. METHODS: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception until December 2015 for studies comparing 5-HT3 receptor antagonists with each other or placebo in chemotherapy patients. The search results were screened, data were abstracted, and risk of bias was appraised by pairs of reviewers, independently. Random-effects meta-analyses and network meta-analyses (NMAs) were conducted. RESULTS: After screening 9226 citations and 970 full-text articles, we included 299 studies (n = 58,412 patients). None of the included studies reported harms for active treatment versus placebo. For NMAs on the risk of arrhythmia (primary outcome; three randomized controlled trials [RCTs], 627 adults) and mortality (secondary outcome; eight RCTs, 4823 adults), no statistically significant differences were observed between agents. A NMA on the risk of QTc prolongation showed a significantly greater risk for dolasetron + dexamethasone versus ondansetron + dexamethasone (four RCTs, 3358 children and adults, odds ratio 2.94, 95% confidence interval 2.13-4.17). For NMAs on the number of patients without nausea (44 RCTs, 11,664 adults, 12 treatments), number of patients without vomiting (63 RCTs, 15,460 adults, 12 treatments), and number of patients without chemotherapy-induced nausea or vomiting (27 RCTs, 10,924 adults, nine treatments), all agents were significantly superior to placebo. For a NMA on severe vomiting (10 RCTs, 917 adults), all treatments decreased the risk, but only ondansetron and ramosetron were significantly superior to placebo. According to a rank-heat plot with the surface under the cumulative ranking curve results, palonosetron + steroid was ranked the safest and most effective agent overall. CONCLUSIONS: Most 5-HT3 receptor antagonists were relatively safe when compared with each other, yet none of the studies compared active treatment with placebo for harms. However, dolasetron + dexamethasone may prolong the QTc compared to ondansetron + dexamethasone. All agents were effective for reducing risk of nausea, vomiting, and chemotherapy-induced nausea or vomiting. TRIAL REGISTRATION: This study was registered at PROSPERO: ( CRD42013003564 ).

A scoping review of rapid review methods.

BACKGROUND: Rapid reviews are a form of knowledge synthesis in which components of the systematic review process are simplified or omitted to produce information in a timely manner. Although numerous centers are conducting rapid reviews internationally, few studies have examined the methodological characteristics of rapid reviews. We aimed to examine articles, books, and reports that evaluated, compared, used or described rapid reviews or methods through a scoping review. METHODS: MEDLINE, EMBASE, the Cochrane Library, internet websites of rapid review producers, and reference lists were searched to identify articles for inclusion. Two reviewers independently screened literature search results and abstracted data from included studies. Descriptive analysis was conducted. RESULTS: We included 100 articles plus one companion report that were published between 1997 and 2013. The studies were categorized as 84 application papers, seven development papers, six impact papers, and four comparison papers (one was included in two categories). The rapid reviews were conducted between 1 and 12 months, predominantly in Europe (58 %) and North America (20 %). The included studies failed to report 6 % to 73 % of the specific systematic review steps examined. Fifty unique rapid review methods were identified; 16 methods occurred more than once. Streamlined methods that were used in the 82 rapid reviews included limiting the literature search to published literature (24 %) or one database (2 %), limiting inclusion criteria by date (68 %) or language (49 %), having one person screen and another verify or screen excluded studies (6 %), having one person abstract data and another verify (23 %), not conducting risk of bias/quality appraisal (7 %) or having only one reviewer conduct the quality appraisal (7 %), and presenting results as a narrative summary (78 %). Four case studies were identified that compared the results of rapid reviews to systematic reviews. Three studies found that the conclusions between rapid reviews and systematic reviews were congruent. CONCLUSIONS: Numerous rapid review approaches were identified and few were used consistently in the literature. Poor quality of reporting was observed. A prospective study comparing the results from rapid reviews to those obtained through systematic reviews is warranted.

Comparative efficacy of serotonin (5-HT3) receptor antagonists in patients undergoing surgery: a systematic review and network meta-analysis.

BACKGROUND: Serotonin (5-HT3) receptor antagonists are commonly used to decrease nausea and vomiting for surgery patients. We conducted a systematic review on the comparative efficacy of 5-HT3 receptor antagonists. METHODS: Searches were done in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify studies comparing 5-HT3 receptor antagonists with each other, placebo, and/or combined with other antiemetic agents for patients undergoing surgical procedures. Screening search results, data abstraction, and risk of bias assessment were conducted by two reviewers independently. Random-effects pairwise meta-analysis and network meta-analysis (NMA) were conducted. PROSPERO registry number: CRD42013003564. RESULTS: Overall, 450 studies and 80,410 patients were included after the screening of 7,608 citations and 1,014 full-text articles. Significantly fewer patients experienced nausea with any drug relative to placebo, except for ondansetron plus metoclopramide in a NMA including 195 RCTs and 24,230 patients. Significantly fewer patients experienced vomiting with any drug relative to placebo except for palonosetron plus dexamethasone in NMA including 238 RCTs and 12,781 patients. All agents resulted in significantly fewer patients with postoperative nausea and vomiting versus placebo in a NMA including 125 RCTs and 16,667 patients. CONCLUSIONS: Granisetron plus dexamethasone was often the most effective antiemetic, with the number needed to treat ranging from two to nine.

Comparative safety of serotonin (5-HT3) receptor antagonists in patients undergoing surgery: a systematic review and network meta-analysis.

BACKGROUND: Serotonin (5-HT3) receptor antagonists are commonly used to decrease nausea and vomiting for surgery patients, but these agents may be harmful. We conducted a systematic review on the comparative safety of 5-HT3 receptor antagonists. METHODS: Searches were done in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify studies comparing 5-HT3 receptor antagonists with each other, placebo, and/or other antiemetic agents for patients undergoing surgical procedures. Screening search results, data abstraction, and risk of bias assessment were conducted by two reviewers independently. Random-effects pairwise meta-analysis and network meta-analysis (NMA) were conducted. PROSPERO registry number: CRD42013003564. RESULTS: Overall, 120 studies and 27,787 patients were included after screening of 7,608 citations and 1,014 full-text articles. Significantly more patients receiving granisetron plus dexamethasone experienced an arrhythmia relative to placebo (odds ratio (OR) 2.96, 95 % confidence interval (CI) 1.11-7.94), ondansetron (OR 3.23, 95 % CI 1.17-8.95), dolasetron (OR 4.37, 95 % CI 1.51-12.62), tropisetron (OR 3.27, 95 % CI 1.02-10.43), and ondansetron plus dexamethasone (OR 5.75, 95 % CI 1.71-19.34) in a NMA including 31 randomized clinical trials (RCTs) and 6,623 patients of all ages. No statistically significant differences in delirium frequency were observed across all treatment comparisons in a NMA including 18 RCTs and 3,652 patients. CONCLUSION: Granisetron plus dexamethasone increases the risk of arrhythmia.

Pseudoacetabulum a subtle radiological feature of a chronic dislocated total hip replacement.

We report the presence of an unusual radiological feature of formation of pseudoacetabulum in a chronically dislocated and asymptomatic total hip arthroplasty. An elderly demented patient with a history of recurrent dislocations presented to us after an unwitnessed fall and leg length discrepancy. Radiographs showed a dislocated hip arthroplasty with a well-defined, concentric, radio-opaque shadow around the dislocated femoral head suggestive of a pseudoacetabulum. Previous radiographs revealed formation of heterotopic ossification in the soft tissues surrounding the hip. The dislocated joint was reduced under a general anaesthetic with difficulty. This case highlights the presence of heterotopic ossification and formation of pseudoacetabulum as subtle radiological features of chronic instability and dislocation.