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Methodological approaches for a systematic review of end-of-life care.

As background for a National Institutes of Health State of the Science Conference on End-of-Life-Care, we performed a systematic review of end-of-life care and outcomes. The systematic review was intended to evaluate the evidence in the field from the perspective of concerns important to patients, caregivers, and the health care system. This article relates the challenges in performing a systematic review of end-of-life care and outcomes, and describes the methods that we used to define the scope, search the literature, develop exclusion and inclusion criteria, incorporate various types of articles, and synthesize the results. Major challenges to conducting a review included the need to define "end of life," clarify a conceptual framework of outcomes including definitions of terms and the relationships among terms, and determine specific goals for the review. The review identified 24,423 total citations, of which 911 comprised the final set used for the evidence report. This very large, diverse body of literature reflects the tremendous growth of the field of end-of-life care over the last decade.

Consensus Development Conferences, NIH as Topic↗

Lessons for search strategies from a systematic review, in The Cochrane Library, of nutritional supplementation trials in patients after hip fracture.

BACKGROUND: A key aim when conducting systematic reviews of randomized controlled trials (RCTs) is to include all of the evidence, if possible. Serious bias may result if trials are missed through inadequate search strategies. OBJECTIVE: The objective was to evaluate the search plan for identifying RCTs in nutrition as part of a systematic review, in The Cochrane Library, of nutritional supplementation trials in patients after hip fracture. DESIGN: We identified potential studies by searching the electronic databases BIOSIS, CABNAR, CINAHL, EMBASE, HEALTHSTAR, and MEDLINE; reference lists in trial reports; and other relevant articles. We also contacted investigators and other experts for information and searched 4 nutrition journals by hand. RESULTS: We identified 15 RCTs that met the predefined inclusion criteria. The search plan identified 8 trials each in EMBASE, HEALTHSTAR, and MEDLINE and 7 in BIOSIS and CABNAR. BIOSIS was the only electronic database source of 2 trials. Eleven trials were identified by searching electronic databases and 2 unpublished trials were identified via experts in the field. We found one trial, published only as a conference abstract, by searching nutrition journals by hand. After publication of the protocol for the review in The Cochrane Library, we were informed of another unpublished trial. CONCLUSIONS: We found that a limited search plan based on only MEDLINE or one of the other commonly available databases would have failed to locate nearly one-half of the studies. To protect against bias, the search plan for a systematic review of nutritional interventions should be comprehensive.

Bias↗

Clinical and cost-effectiveness of left ventricular assist devices as a bridge to heart transplantation for people with end-stage heart failure: a systematic review and economic evaluation.

AIMS: To evaluate the clinical and cost-effectiveness of left ventricular (LV) assist devices (LVADs) as a bridge to transplant (BTT) for people with end-stage heart failure (ESHF) through a systematic review and economic evaluation. METHODS AND RESULTS: The systematic review and economic evaluation was conducted according to internationally recognized methods. The search strategy identified systematic reviews, randomized controlled trials, quasi-experimental studies, and observational studies evaluating the effects of LVADs on survival, functional capacity, and quality of life. Cost-effectiveness was assessed through a 5-year decision analytic model to estimate the incremental cost-effectiveness ratio of LVADs compared with usual care. Despite the poor methodological quality of the 18 studies included, LVADs appear beneficial improving survival, functional status, and quality of life. Adverse events are a serious concern. The economic evaluation showed that LVADs had a cost per quality adjusted life year of pound 65,242 (95% confidence interval pound 34,194-364,564). Sensitivity analysis showed that post-heart transplant survival gains, pre-heart transplant patient utility, and one-off costs associated with implantation determine cost-effectiveness. CONCLUSION: Although LVADs appear clinically effective as a BTT for people with ESHF, it is unlikely that they will be cost-effective unless costs decrease or the benefits of their use increase.

Cohort Studies↗

Nurse-led titration models of care for heart failure reduced ejection fraction: a systematic narrative review of characteristics, patient outcomes, and healthcare resource utilization.

AIMS: Nurse-led titration (NLT) models of care assist with delivery of guideline directed medical therapy for patients with heart failure with reduced ejection fraction (HFrEF). Effectiveness of NLT is established but there is limited information of characteristics of models, patient outcomes and healthcare resource utilization. To build upon the existing evidence by providing a systematic narrative review of the literature of NLT of medications for patients with HFrEF. This review syntheses characteristics of NLT models of care, patient outcomes and healthcare resource utilization. METHODS AND RESULTS: A systematic narrative literature review with systematic search strategy, identification of results, thematic analysis and narrative synthesis. A search was conducted from 2012 to 2025 in Medline, Cinahl complete, Embase and Cochrane. Sixteen studies of NLT models of care were identified from 1944 screened records. Characteristics of models of care were participation of nurses, multidisciplinary teams, follow-up and common features of service delivery. Patient outcomes of mortality were favourable for those that received NLT. There is some evidence of changes in healthcare resource utilization; studies in which the NLT groups received more HF nurse visits and greater HF medication use also reported reduced rehospitalizations. CONCLUSION: Findings reinforce the published benefits of NLT. Additional studies examining adverse events and quality-of-life outcomes are needed to strengthen the evidence base. Several studies suggest a shift in resource use with NLT, highlighting the need for an economic evaluation to inform a cost-effective model of care.

Humans↗

The management of Helicobacter pylori infection in primary care: a systematic review of the literature.

OBJECTIVE: The aim of the present study was to provide evidence from the literature to inform the production of guidelines by the European Society for Primary Care Gastroenterology (ESPCG) for the management of Helicobacter pylori infection in primary care. METHODS: A systematic review was conducted, searching MEDLINE, EMBASE and the Cochrane Library. The systematic review was designed to answer a number of question: the role of H.pylori in the aetiology of peptic ulcer disease (PUD), gastric cancer (GC), non-ulcer dyspepsia (NUD) and oesophagitis; non-invasive testing for H.pylori and post-treatment testing; eradication therapy; and cost issues. Selection of records concentrated on the highest quality studies, i.e. systematic reviews, meta-analyses and cost analyses. RESULTS: Helicobacter pylori infection is a causal factor in PUD and GC but not in NUD or oesophagitis. Serological tests and urea breath tests (UBTs) can be used for the detection of H.pylori, but UBT is the preferred choice for post-treatment testing. Proton pump inhibitor (PPI)-based triple regimens are the preferred eradication therapy. Eradication therapy is more cost-effective than long-term maintenance therapy. CONCLUSIONS: Strong evidence is available for answering questions on the aetiology of stomach ulcers and GU, eradication therapies and cost issues. Weaker evidence is available for answering the questions on the aetiology of NUD and non-invasive testing. No evidence is available for answering the question on the role of H.pylori in the aetiology of oesophagitis.

Anti-Bacterial Agents↗

Do lipid-lowering drugs cause erectile dysfunction? A systematic review.

BACKGROUND: Erectile dysfunction (ED) is common although under-reported by patients. Along with the better known causes of ED, drug-induced impotence needs to be considered as a cause of this symptom. Lipid-lowering drugs have been prescribed increasingly. Their relationship to ED is controversial. OBJECTIVES: Our aim was to clarify the relationship between lipid-lowering therapy and ED. A secondary aim was to assess the value of the systematic review procedure in the area of adverse drug reactions. METHODS: A systematic review was carried out using computerized biomedical databases and Internet sources. Terms denoting ED were linked with terms referring to lipid-lowering drugs. Information was also sought from regulatory agencies. RESULTS: A significant literature was identified, much from obscure sources, which included case reports, review articles, and information from clinical trials and from regulatory agencies. Information from all of these sources identified fibrates as a source of ED. A substantial number of cases of ED associated with statin usage have been reported to regulatory agencies. Case reports and clinical trial evidence supported the suggestion that statins can also cause ED. Some information on possible mechanisms was obtained, but the mechanism remains uncertain. CONCLUSIONS: The systematic review procedure was applied successfully to collect evidence suggesting that both statins and fibrates may cause ED. More numerous reports to regulatory agencies complemented more detailed information from case reports to provide a new perspective on a common area of prescribing.

Adult↗

A systematic review of discharge coding accuracy.

BACKGROUND: The aim of the study was to review systematically the literature measuring the accuracy of routine UK hospital statistics that classify patients on discharge. METHODS: A systematic review was carried out of studies comparing routine discharge statistics about an episode of hospital care with the original medical record. Dual quality assessment and extraction was completed for included studies. Qualitative and descriptive analyses were undertaken. Additional comparisons of factors that could potentially introduce systematic variation in coding accuracy were also undertaken. RESULTS: Thirty studies were identified, of which 21 were included in the review. Twelve of these were conducted in England and Wales, and nine in Scotland. The majority assessed the accuracy of a single diagnosis, or selection of diagnoses in a limited range of hospital settings. The median coding accuracy rates were 91 per cent for diagnostic codes and 69.5 per cent for operation or procedure codes in studies in England or Wales; 82 per cent for diagnostic codes and 98 per cent for operation or procedure codes in Scottish studies. There were no significant differences in coding accuracy over time or in the type or rarity of the codes being assessed. Accuracy rates were higher for ICD7 codes (median 96.5 per cent) than for ICD8 (median 87 per cent) or ICD9 (median 77 per cent). CONCLUSIONS: Coding accuracy on average is high in the United Kingdom, especially for operations and procedures. However, policy-makers, planners and researchers need to recognize and account for the degree of inaccuracy in routine hospital information statistics. Further research is needed into methods of improving and maintaining coding accuracy.

Abstracting and Indexing↗

Local anesthetic infiltration for postoperative pain relief after laparoscopy: a qualitative and quantitative systematic review of intraperitoneal, port-site infiltration and mesosalpinx block.

UNLABELLED: In a systematic review, we evaluated randomized controlled trials (RCTs) of peripheral local anesthetics (LA) compared with placebo or no treatment in the control of postoperative pain after laparoscopic surgery. A total of 41 trials with data from 2794 patients were considered appropriate for analysis. Of these 41 RCTs, 13 evaluated intraperitoneal LA after cholecystectomy, four RCTs assessed intraperitoneal LA after other procedures, eight RCTs evaluated port-site infiltration after various procedures, 12 RCTs evaluated mesosalpinx or fallopian tube block after sterilization, and four RCTs considered combined LA regimens. Outcome measures were pain scores, analgesic consumption, and time to first analgesic request. Efficacy was estimated by significant difference (P < 0.05), as reported in the original reports, and by calculation of the weighted mean difference of visual analog scale pain scores between treatment groups. Improved pain relief was observed in seven of the 13 RCTs of intraperitoneal LA after cholecystectomy and in four RCTs of other procedures. A statistically significant weighted mean difference of -13 mm visual analog scale (95% confidence intervals [CI]: -20 to -6) in favor of the treatment groups was observed after cholecystectomy. Three of eight trials of port-site infiltration showed significant differences but questionable clinical importance and validity in two; weighted mean difference was not statistically significant between treatment groups (95% CI -9 to 1). All RCTs of mesosalpinx or fallopian tube block after sterilization showed improved pain relief with a statistically significant weighted mean difference of -19 mm (95% CI -25 to -14) in favor of treatment groups. Data of combined regimens were positive, however, sparse. We conclude that there was evidence for a statistically significant but clinically questionable, important effect of intraperitoneal LA for postoperative pain control. There was evidence for a significant but short-lasting effect of mesosalpinx/fallopian tube block after sterilization, but there was a lack of evidence for any important effect of port-site infiltration. Data from combined regimens were too sparse for conclusions. IMPLICATIONS: A systematic review summarizes, through transparent methodology, available information from randomized, controlled trials to produce the best available evidence-based estimate of a "true" clinical effect of an intervention. This systematic review confirms intraperitoneal and mesosalpinx local anesthetic block, not port-site infiltration, to have some impact on postoperative pain after laparoscopy.

Anesthetics, Local↗

Lumbar supports for prevention and treatment of low back pain: a systematic review within the framework of the Cochrane Back Review Group.

STUDY DESIGN: A systematic review of randomized and nonrandomized controlled trials. SUMMARY OF BACKGROUND DATA: Lumbar supports are used in the treatment of low back pain, but also to prevent the onset (primary prevention) or recurrences of a low back pain episode (secondary prevention). OBJECTIVES: To assess the effects of lumbar sup-ports for prevention and treatment of nonspecific low back pain. METHODS: The Medline, Cinahl, and Current Contents databases; the Cochrane Controlled Trials Register up to September 1999; and the Embase database up to September 1998 were all searched. References of identified trials and systematic reviews were reviewed and the Science Citation Index used to identify additional trials. Methodologic quality assessment and data extraction were performed by two reviewers independently. A quantitative analysis was performed in which the strength of evidence was classified as strong, moderate, limited or conflicting, and no evidence. RESULTS: Five randomized and two nonrandomized preventive trials and six randomized therapeutic trials were included in the review. Only 4 of the 13 studies were of high quality. There was moderate evidence that lumbar supports are not effective for primary prevention. No evidence was found on the effectiveness of lumbar supports for secondary prevention. The systematic review of therapeutic trials showed that there is limited evidence that lumbar supports are more effective than no treatment, whereas it is still unclear whether lumbar supports are more effective than other interventions for treatment of low back pain. CONCLUSIONS: There continues to be a need for high quality randomized trials on the effectiveness of lumbar supports. One of the most essential issues to tackle in these future trials seems to be the realization of adequate compliance.

Braces↗

The acute effects of noninvasive ventilatory support during exercise on exercise endurance and dyspnea in patients with chronic obstructive pulmonary disease: a systematic review.

PURPOSE: The objective of this study was to review studies systematically, in which the acute effects of noninvasive ventilatory support (NIVS) during exercise were evaluated in patients with chronic obstructive pulmonary disease (COPD). In addition, a quantitative analysis was performed on the effects of NIVS on exertional dyspnea and exercise endurance. METHODS: Literature was searched in electronic databases, and by scanning lists of references of studies and abstract books of annual congresses of the American Thoracic Society and European Respiratory Society. Preliminary data of a study by our own group into the effects of NIVS on exercise endurance in patients with COPD were added. The systematic review was carried out on the basis of a validated methodological screening list. For the quantitative analysis, Glass delta of individual studies were pooled to aggregate a summary effect size. RESULTS: Fifteen studies were identified. Seven of these studies met the inclusion criteria, including a total of 65 patients with COPD. The methodological quality of the included studies varied from 31% to 54% of the maximum score of 13 points. Statistically significant summary effect sizes were found in the analysis of exertional dyspnea (P <.05) as well as in the analysis of exercise endurance (P <.001), indicating improvements in these outcomes in favor of NIVS. CONCLUSIONS: The present systematic review suggests that NIVS during exercise may acutely reduce exertional dyspnea and improve exercise endurance, in patients with COPD.

Chi-Square Distribution↗

Assessing the neonatal safety of indomethacin tocolysis: a systematic review with meta-analysis.

OBJECTIVE: To systematically review and summarize the medical literature regarding the effects of tocolysis with indomethacin on neonatal outcome. DATA SOURCES: We supplemented a search of entries in electronic databases with references cited in original studies and review articles to identify studies pertaining to indomethacin tocolysis and neonatal outcome. METHODS OF STUDY SELECTION: We evaluated, abstracted data, and performed quantitative analyses in studies assessing the neonatal outcomes of patients undergoing tocolysis with indomethacin. Observational studies and randomized trials were included in this systematic review. TABULATION, INTEGRATION, AND RESULTS: Forty-six studies were identified, 28 of which met criteria for systematic review and meta-analysis. These 28 studies included 6,008 infants. Of these infants, 1,621 were exposed to indomethacin for tocolysis antenatally; 4,387 infants not exposed to indomethacin served as the comparison group. An estimate of pooled odds ratios with 95% confidence intervals was calculated for dichotomous outcomes using random- and fixed-effects models. Observational studies and randomized trials were analyzed separately. Pooled estimates from observational studies and randomized trials revealed no significant differences in the rates of intraventricular hemorrhage, patent ductus arteriosus, necrotizing enterocolitis, or neonatal mortality between infants exposed to indomethacin antenatally and those not exposed. Meta-analysis of randomized trials revealed increased risk of bronchopulmonary dysplasia. However, the meta-analysis included only 3 randomized clinical trials, one of which showed increased risk. An association of bronchopulmonary dysplasia and indomethacin use was not noted in our analysis of observational studies. CONCLUSION: Although our pooled results did not identify significantly increased risks of adverse effects, the limited statistical power of published randomized trials does not allow us to exclude the possibility that indomethacin tocolysis increases the risk of adverse neonatal outcomes.

Adult↗

Updated method guidelines for systematic reviews in the cochrane collaboration back review group.

STUDY DESIGN: Descriptive method guidelines. OBJECTIVES: To help reviewers design, conduct, and report reviews of trials in the field of back and neck pain. SUMMARY OF BACKGROUND DATA: In 1997, the Cochrane Collaboration Back Review Group published method guidelines for systematic reviews. Since its publication, new methodologic evidence emerged and more experience was acquired in conducting reviews. METHODS: All reviews and protocols of the Back Review Group were assessed for compliance with the 1997 method guidelines. Also, the most recent version of the Cochrane Handbook (4.1) was checked for new recommendations. In addition, some important topics that were not addressed in the 1997 method guidelines were included (e.g., methods for qualitative analysis, reporting of conclusions, and discussion of clinical relevance of the results). In May 2002, preliminary results were presented and discussed in a workshop. In two rounds, a list of all possible recommendations and the final draft were circulated for comments among the editors of the Back Review Group. RESULTS: The recommendations are divided in five categories: literature search, inclusion criteria, methodologic quality assessment, data extraction, and data analysis. Each recommendation is classified in minimum criteria and further guidance. Additional recommendations are included regarding assessment of clinical relevance, and reporting of results and conclusions. CONCLUSIONS: Systematic reviews need to be conducted as carefully as the trials they report and, to achieve full impact, systematic reviews need to meet high methodologic standards.

Back Pain↗

School-based interventions for spinal pain: a systematic review.

STUDY DESIGN: Systematic review. OBJECTIVES: To establish the effectiveness of school-based spinal health interventions in terms of: 1) improving knowledge about the spine/spinal care; 2) changing spinal care behaviors; and 3) decreasing the prevalence of spinal pain. SUMMARY OF BACKGROUND DATA: Spinal pain is a significant problem in children and adolescents that has been addressed through school-based spinal health interventions. No systematic review has been carried out on this topic to date. METHODS: A systematic literature review sought studies that evaluated school-based spinal health interventions. Using clearly defined study inclusion criteria, 11 databases were searched from their inception to March 2004. To identify further literature, three relevant journals were hand searched, reference lists were checked, and authors of included papers were contacted. Two reviewers independently appraised the quality of identified papers and extracted data regarding intervention and study characteristics, statistical analyses performed, and study results. Data were examined using a narrative synthesis of results, and the outcomes of interest were considered individually (knowledge, behaviors, pain prevalence). RESULTS: Twelve papers were included in this review; all papers received a "weak" quality rating. Results of these studies indicate that school-based spinal health interventions may be effective in increasing spinal care knowledge and decreasing the prevalence of spinal pain. However, overall the evidence is inconclusive regarding spinal care behaviors. CONCLUSIONS: The poor quality of the reviewed studies limits the conclusions that can be made regarding the effectiveness of school-based spinal health interventions.

Back Pain↗

A critical appraisal of a systematic review: Sokol J, Jacob SE, Bohn D: Inhaled nitric oxide for acute hypoxemic respiratory failure in children and adults. Cochrane Database Syst Rev 2003 (1): CD002787.

OBJECTIVE: To review the findings and discuss the implications of the use of inhaled nitric oxide for acute hypoxemic respiratory failure in patients beyond the neonatal period. DESIGN: A critical appraisal of a systematic review. FINDINGS: The authors conducted a systematic review with meta-analysis to determine the effect of inhaled nitric oxide on clinical outcomes of patients with acute hypoxemic respiratory failure. The outcomes included mortality, changes in oxygenation, ventilator-free days, duration of intensive care and hospital stays, and adverse effects. It was a high-quality systematic review provided with strict entry criteria, an extensive literature search, and thorough critical appraisals. Only five trials (n = 623) met entry criteria. Inhaled nitric oxide had no effect on mortality in studies without crossover of treatment failures to open-label inhaled nitric oxide (relative risk, 0.98; 95% confidence interval, 0.66-1.44). A statistically significant improvement in oxygenation was observed in one study. The effect, however, was observed only in the first 4 days of treatment and was not clinically significant. The heterogeneity in study findings precluded meta-analyses of other clinical outcomes and adverse effects in the selected studies. CONCLUSIONS: There is insufficient evidence to determine whether inhaled nitric oxide is beneficial or harmful for acute hypoxemic respiratory failure in children and adults. While awaiting further studies to prove its benefit, inhaled nitric oxide should not either be recommended as a standard management or excluded for the treatment of acute hypoxemic respiratory failure.

Adult↗

Hospital volume and mortality after pancreatic resection: a systematic review and an evaluation of intervention in the Netherlands.

OBJECTIVES: To evaluate the best available evidence on volume-outcome effect of pancreatic surgery by a systematic review of the existing data and to determine the impact of the ongoing plea for centralization in The Netherlands. SUMMARY BACKGROUND DATA: Centralization of pancreatic resection (PR) is still under debate. The reported impact of hospital volume on the mortality rate after PR varies. Since 1994, there has been a continuous plea for centralization of PR in The Netherlands, based on repetitive analysis of the volume-outcome effect. METHODS: A systematic search for studies comparing hospital mortality rates after PR between high- and low-volume hospitals was used. Studies were reviewed independently for design features, inclusion and exclusion criteria, cutoff values for high and low volume, and outcome. Primary outcome measure was hospital or 30-day mortality. Data were obtained from the Dutch nationwide registry on the outcome of PR from 1994 to 2004. Hospitals were divided into 4 volume categories based on the number of PRs performed per year. Interventions and their effect on mortality rates and centralization were analyzed. RESULTS: Twelve observational studies with a total of 19,688 patients were included. The studies were too heterogeneous to allow a meta-analysis; therefore, a qualitative analysis was performed. The relative risk of dying in a high-volume hospital compared with a low-volume hospital was between 0.07 and 0.76, and was inversely proportional to the volume cutoff values arbitrarily defined. In 5 evaluations within a decade, hospital mortality rates were between 13.8% and 16.5% in hospitals with less than 5 PRs per year, whereas hospital mortality rates were between 0% and 3.5% in hospitals with more than 24 PRs per year. Despite the repetitive plea for centralization, no effect was seen. During 2001, 2002, and 2003, 454 of 792 (57.3%) patients underwent surgery in hospitals with a volume of less than 10 PRs per year, compared with 280 of 428 (65.4%) patients between 1994 and 1996. CONCLUSIONS: The data on hospital volume and mortality after PR are too heterogeneous to perform a meta-analysis, but a systematic review shows convincing evidence of an inverse relation between hospital volume and mortality and enforces the plea for centralization. The 10-year lasting plea for centralization among the surgical community did not result in a reduction of the mortality rate after PR or change in the referral pattern in The Netherlands.

Chi-Square Distribution↗

Management of the injured patient: identification of research topics for systematic review using the delphi technique.

BACKGROUND: Systematic reviews of controlled clinical trials in the form of meta-analyses can serve as an important guide to direct clinical practice. This study identifies the most important research questions pertaining to the acute care of the injured patient using a Web-based Delphi technique to achieve consensus of expert opinion. METHODS: Experts in trauma care from the United States and Canada (n = 68) were asked to generate structured research questions and were then required to rank these questions in order of importance and estimate the amount of research currently published. RESULTS: The questions ranking in the highest tertile are presented along with an estimate of their importance and the amount of research published using an ordinal scale. Only 9 of 16 (56%) questions had some or a substantial amount of research available on which to perform a systematic review. CONCLUSION: This study identifies the areas of trauma care in which research efforts might best be directed. In the absence of sufficient data for systematic reviews, these research topics represent important areas for the design and implementation of clinical trials.

Humans↗

Medically Unexplained Symptoms: A Systematic Umbrella Review of Current Terminology and Reported Rationales.

OBJECTIVES: Toaddress current naming conventions for Medically Unexplained Symptoms (MUS) through a systematic umbrella review. The terminology used and the provided rationales were considered. METHODS: Registered with PROSPERO (CRD42024526020), this review searched 8 key databases, last on January 28, 2025. Reviews including medically unexplained symptoms (or synonym or subtype) in their systematic search terms were included (N=422). RESULTS: A total of 577 references to 111 terms were made across the reviews, with numerous reviews using the same overarching terms, including "functional" (n=233), "somatic" (or variants thereof, n=51), and "medically unexplained" (n=28). Thirty percent of terms (n=179) were to specific syndromes or terms that did not group together under an overarching term, suggesting substantial variability in terms, even though over 60% of authors were primarily associated with just 3 disciplines: medicine, allied health, and psychology. A subset of 23 reviews provided rationales, which were subjected to content analysis and a ROBIS (Risk of Bias in Systematic Reviews) risk-of-bias assessment. This analysis showed that rationales tended to (1) highlight differences between psychological, psychiatric, and other medical fields (n=7); (2) focus on the patient perspective and patient-practitioner therapeutic relationship (n=10); or (3) follow broad and/or commonly used terms (n=7). DISCUSSION: The current landscape of terminology used for MUS remains varied, nuanced, and inconsistent between disciplines. Moving forward to a more universal language accepted and used by both patients and practitioners would aid in the diagnosis, management, and treatment of MUS.

Humans↗

Cisplatin-Induced Hearing Loss Prevention With Intratympanic Therapy Systematic Review and Meta-Analysis.

INTRODUCTION: Cisplatin-induced hearing loss (CIHL) is a well-described, long-term consequence of cisplatin treatment for malignancy. Intratympanic (IT) injections have been trialed to prevent CIHL in humans. To provide clarity on which agents have been studied through IT injection and to review their efficacy for hearing loss prevention, we performed a systematic review and meta-analysis. DATA SOURCES: OVID Medline, Embase, Web of Science, and Cochrane Library were queried. METHODS: Databases were searched in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Prospective randomized trials were included, and a systematic review was performed for all studies. Demographic, audiometric, and therapeutic data were collected. Random-effects models were used to compare across studies, and subgroup analyses were performed for each IT agent. RESULTS: The initial database search yielded 1017 articles, which were screened according to inclusion and exclusion criteria. Ten studies were identified, involving a total of 284 patients. Studies included data on IT dexamethasone, IT N-acetylcysteine (NAC), and IT sodium thiosulfate (STS). Pooled analysis across all agents and frequencies did not reveal a significant difference in hearing thresholds between treatment and control ears [prediction interval [-3.77, 3.20], negative favors treatment). Subgroup analysis of IT dexamethasone [-1.74, 3.80] and IT NAC [-1.02, 4.64] also did not demonstrate significant differences. STS data were not amenable to pooled analysis; however, one study demonstrated a significant decrease in ASHA-defined ototoxicity (40% vs. 85%, P =0.0027). CONCLUSIONS: To date, no IT agent has consistently prevented CIHL, although limited data suggest that IT STS may decrease ototoxicity. More trials are necessary to fully elucidate these effects.

Humans↗