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Outcomes of stereotactic radiosurgery for spine multiple myeloma-a systematic review.

Spinal involvement in multiple myeloma (MM) commonly results in pain, vertebral instability, epidural spinal cord compression, and neurological deficits. Although conventional external beam radiation therapy (EBRT) remains the standard radiation modality because of the radiosensitive nature of MM, stereotactic radiosurgery (SRS) has emerged as a highly conformal treatment option capable of delivering focal high-dose radiation while sparing adjacent spinal cord structures and uninvolved bone marrow. This systematic review evaluated the clinical outcomes and safety profile of SRS for spinal MM. A systematic review of the literature was performed to identify studies evaluating SRS for spinal MM. Extracted variables included patient demographics, tumor characteristics, treatment parameters, radiographic outcomes, pain response, neurological outcomes, local control, overall survival, and adverse events. Three retrospective studies comprising 133 patients and 181 treated spinal lesions met the inclusion criteria. Median patient age ranged from 59 to 65 years, with a slight male predominance across studies. Thoracic spine lesions represented the most treated region (55.5-67.7%). Median prescribed SRS dose was 14-16 Gy, predominantly delivered in a single fraction. Median follow-up ranged from 11.2 to 27.8 months. Local control rates ranged from 89.4 to 100%, with 6- and 12-month local control rates of 94% and 91%, respectively, in one study. Pain improvement was reported in 41-88% of treated patients/sites, with a median time to pain relief of 1.6 months in one cohort. Neurological improvement occurred in 56-71.4% of patients with preexisting deficits. Reported adverse events included vertebral compression fractures, fracture progression, pain flare, and tracheoesophageal fistula. De novo vertebral fractures ranged from 3.6 to 7%, while fracture progression ranged from 14 to 18%. SRS appears to provide excellent local control and meaningful pain and neurological improvement in patients with spinal MM, with acceptable toxicity profiles. The highly conformal nature of SRS may preserve uninvolved bone marrow and facilitate continuation of systemic therapy. However, the current evidence is limited to small retrospective studies with heterogeneous reporting, and further prospective comparative studies are needed to better define the role of SRS relative to conventional EBRT in spinal MM.

Humans↗

The evidence for efficacy of omega-3 fatty acids in preventing or slowing the progression of retinitis pigmentosa: a systematic review.

BACKGROUND: Studies in preterm and term human infants have suggested that a dietary supply of omega-3 fatty acids is essential for optimal visual development. Several basic science studies support the hypothesis that omega-3 fatty acids may be useful therapeutic agents for pathologies of the retina and lens. As part of a systematic review of the effect of omega-3 fatty acids on eye health, the purpose of this study was to conduct a systematic review of the scientific-medical literature to appraise and synthesize the evidence for the effects of omega-3 fatty acids in preventing the development or progression of retinitis pigmentosa. METHODS: A comprehensive search was undertaken in MEDLINE, PREMEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Global Health, and Dissertation Abstracts. Unpublished literature was sought through manual searches of reference lists of included studies and key review articles and from the files of content experts. Searches were not restricted by language of publication, publication type, or study design. Eligibility criteria were applied to screen eligible studies on two levels. Data extraction and quality assessment were performed. RESULTS: Six studies published between 1995 and 2004 met eligibility criteria in investigating the question of the possible value of omega-3 fatty acids in slowing the progression of retinitis pigmentosa. Meta-analysis was not performed because there was not enough available information for formal quantitative analysis. INTERPRETATION: There are trends in improvement of some retinitis pigmentosa outcomes with omega-3 fatty acids in the higher quality studies. Clinical research is preliminary in this field, however. Accordingly, definitive answers will require significantly more observational and interventional clinical research.

Databases, Factual↗

Nimodipine in animal models of demyelination relevant to multiple sclerosis: a systematic review.

BACKGROUND: Multiple sclerosis (MS) is the most common inflammatory neurodegenerative disease in which axonal injury, neuronal death, and demyelination occur. Treatment for MS relapses remains limited, which alleviates acute loss of function but has no impact on long-term disability. This study aimed to perform a systematic review of the effects of nimodipine on experimental demyelination models, including experimental autoimmune encephalomyelitis (EAE) and Cuprizone models in rodents. METHODS: This study was conducted following the PRISMA statement. A systematic search was performed in PubMed, Scopus, the Cochrane Library, and Google Scholar. The primary outcome was EAE clinical disease severity (peak clinical score and/or cumulative disease burden). Secondary outcomes included relapse activity (when reported), histological myelin outcomes, oligodendrocyte lineage markers, neuroaxonal injury markers, and inflammatory readouts. Risk of bias was assessed using the SYRCLE tool. RESULTS: Out of 4660 results, 5 studies were included in the systematic review (four EAE studies and one cuprizone model). Nimodipine was administered using heterogeneous regimens (oral, intravenous, intraperitoneal, subcutaneous, or osmotic pump delivery; 1-30 mg/kg/day). The included studies reported the variable effects of nimodipine on relapse-related outcomes, myelination, inflammatory processes, and neuroprotection in the EAE model of MS. Across EAE studies, nimodipine generally reduced clinical disease severity or cumulative burden, although relapse-related outcomes were inconsistent. CONCLUSIONS: Preclinical evidence suggests that nimodipine may attenuate disease severity and demyelination and may promote repair-related processes in rodent models relevant to MS. However, to evaluate the clinical applicability of nimodipine in MS patients, well-powered, transparently reported preclinical replication and early-phase clinical studies are required before clinical translation.

Animals↗

Coronary artery stents: a rapid systematic review and economic evaluation.

OBJECTIVES: To assess the effectiveness and cost-effectiveness of the use of coronary artery stents in patients with coronary heart disease (CHD). DATA SOURCES: Electronic databases. REVIEW METHODS: The review was conducted following accepted guidelines for conducting systematic reviews. Randomised controlled trials that include comparisons of percutaneous transluminal coronary angioplasty (PTCA) versus PTCA with stent, stent versus coronary artery bypass graft (CABG), and drug-eluting stents (DES) versus non-DES in patients with CAD in native or graft vessels and those with stable angina or acute coronary syndrome (ACS) and unstable angina were also included. Data on the following outcome measures were included in the review: combined event rate or event-free survival, death, acute myocardial infarction, target vessel revascularisation, repeat treatment (PTCA, stent or CABG) and binary restenosis. An economic model was developed based on extrapolation of trends in mortality and revascularisation from clinical trials data to a 5-year time horizon. RESULTS: The inclusion criteria were fulfilled by 50 studies comparing the use of stents with PTCA, six comparing stents with CABG and 12 comparing DES eluting stents with non-DES. No studies were identified that compared DES with PTCA or DES with CABG. Existing quality of life data suggest that revascularisation procedures reduce the patient's quality of life for a short period only. Stents were found to be more effective than PTCA in preventing adverse events and revascularisations. In multiple-vessel disease there was no evidence of a difference in mortality (at 1 year) between patients treated surgically and those receiving a stent. Patients treated surgically required fewer revascularisations. There is no evidence of a difference in mortality between patients receiving DES and those treated with bare metal stents at 1 year. A reduction in event rate at 9 and 12 months was found in patients treated with DES. This event rate is primarily made up of increased revascularisation rates in patients treated with bare metal stents. Two-year outcome data from one study indicate that this benefit of DES continues over the longer term. The economic model proved sufficient to indicate long-term trends in cost-effectiveness. CABG was found initially to be more expensive than bare metal stenting in multivessel disease and may have higher immediate risks, but over time the cost differential is reduced and long-term outcomes favour CABG over stenting. A similar situation was found for DES versus CABG in multiple-vessel disease. However, DES may not generally be considered a cost-effective alternative to bare metal stenting in single-vessel disease by policy makers as substantially higher costs are involved with a very small outcome benefit. CONCLUSIONS: DES might be considered cost-effective if the additional cost (compared with ordinary stents) was substantially reduced, the outcome benefits from the use of DES were much improved, and/or its use were targeted on the subgroups of patients with the highest risks of requiring reintervention. Long-term clinical studies are needed that focus on significant outcomes such as mortality. Further research should consider: the differences among plain stents; head-to-head comparisons within DES, CABG compared with DES; and the evaluation of newer non-DES against DES. Evaluation of the effects of revascularisation procedures and especially repeat revascularisation procedures on the patient's quality of life would also be useful, as would the development and testing of risk assessment tools to identify patients likely to need further revascularisations.

Angioplasty, Balloon, Coronary↗

A systematic review of the use of opioids in the management of dyspnoea.

BACKGROUND: Opioids are commonly used to treat dyspnoea in palliative medicine but there has been no formal evaluation of the evidence for their effectiveness in the treatment of dyspnoea. A systematic review was therefore carried out to examine this. METHODS: The criteria for inclusion required that studies were double blind, randomised, placebo controlled trials of opioids for the treatment of dyspnoea secondary to any cause. The methods used to identify suitable studies included electronic searching of the literature, hand searching of the literature, and personal contact with relevant individuals and organisations. Random effects meta-analyses were performed on all included studies and on various subgroups (studies involving nebulised opioids or patients with chronic obstructive pulmonary disease (COPD)). Subgroups were compared using meta-regression. Some studies included in the systematic review could not be included in the meta-analysis because insufficient data were presented. RESULTS: Eighteen studies fulfilled the criteria for the review. The meta-analysis showed a statistically significant positive effect of opioids on the sensation of breathlessness (p=0.0008). Meta-regression indicated a greater effect for studies using oral or parenteral opioids than for studies using nebulised opioids (p=0.02). The subgroup analysis failed to show a positive effect of nebulised opioids on the sensation of breathlessness. The results of the subgroup analysis of the COPD studies were essentially similar to the results of the main analysis. CONCLUSION: This review supports the continued use of oral and parenteral opioids to treat dyspnoea in patients with advanced disease. There are insufficient data from the meta-analysis to conclude whether nebulised opioids are effective, but the results from included studies that did not contribute to the meta-analysis suggest that they are no better than nebulised normal saline.

Administration, Oral↗

Cyclosporine in the treatment of severe attack of ulcerative colitis: a systematic review.

INTRODUCTION: Intravenous steroid therapy is the standard treatment in severe attacks of ulcerative colitis (UC), but 20% to 60% of patients fail to respond and require colectomy. Cyclosporine (CyA) has shown efficacy in steroid failures and could avoid surgery, but controversy remains. AIM: The objective of this study was to conduct a systematic review to evaluate the effectiveness and safety of CyA in inducing remission in patients with a severe attack of UC. METHODS: We did a systematic review using Cochrane methodology, including data from published (in English, French, Spanish or German) clinical trials done in adults using intravenous or oral CyA in UC. Data on efficacy are obtained from controlled and observational clinical trials, and for safety issues case reports are also considered. RESULTS: 31 studies were identified which met the inclusion criteria, 22 (18 uncontrolled, 4 controlled) with intravenous CyA, and 9 (all uncontrolled) using oral CyA. Only 4 controlled trials (one in abstract form) are available, and only one compares CyA to placebo. However, efficacy results are very consistent in these 4 trials, and very similar to those in observational studies. CyA achieves remission in 91,4% and 71.4% of patients in controlled and uncontrolled studies using intravenous route, and in 71,2% using oral route. Two mg/kg/day seems so efficacious and safer as previous standard 4 mg/kg/day dose. Minor side effects are rather common but do not seriously limit therapy. Severe side effects, specially infections, are uncommon but clinically relevant with several deaths reported. CONCLUSION: CyA (intravenous, 2 mg/kg/day) constitutes an efficacious and relatively safe alternative in the treatment of severe, steroid-refractory, attack of UC. To optimize treatment, the correct selection of patients, a standardized protocol and clinical surveillance are recommended.

Administration, Oral↗

Systematic review of the prevention of delayed ischemic neurological deficits with hypertension, hypervolemia, and hemodilution therapy following subarachnoid hemorrhage.

OBJECT: There is uncertainty about the efficacy of hypertension, hypervolemia, and hemodilution (triple-H) therapy in reducing the occurrence of delayed ischemic neurological deficits (DINDs) and death after subarachnoid hemorrhage. The authors therefore conducted a systematic review to evaluate the efficacy of triple-H prevention in decreasing the rate of clinical vasospasm, DINDs, and death. METHODS: The authors systematically reviewed studies identified based on a MEDLINE, EMBASE, and COCHRANE Register search of articles published between 1966 and 2001, and reference lists of identified articles. An independent assessment of each study's methodological quality, population, intervention, and outcomes (rates of symptomatic vasospasm, DINDs, and death) was performed. Summary relative risk estimates were calculated for the main outcomes using fixed- or random-effect models, as appropriate. Only four prospective, comparative studies with a total of 488 patients were identified. The median internal validity score was 0.5 (range 0-2); the median external validity score was 3 (range 2-6). Compared with no prevention, triple-H therapy was associated with a reduced risk of symptomatic vasospasm (relative risk [RR] 0.45, 95% confidence interval [CI] 0.32-0.65), but not DIND (RR 0.54, 95% CI 0.2-1.49). The risk of death was higher (RR 0.68, 95% CI 0.53-0.87). Sensitivity analyses including only randomized, controlled trials showed no evidence of statistically significant results for these major end points. CONCLUSIONS: The paucity of information and important limitations in the design of the studies analyzed preclude evaluation of the efficacy of triple-H prevention and formulation of any recommendations regarding its use for the prevention of cerebral vasospasm.

Blood Pressure↗

Role of the Shouldice technique in inguinal hernia repair: a systematic review of controlled trials and a meta-analysis.

The Shouldice technique for inguinal hernia repair has been suggested by some authors as the best conventional method against which other methods using prostheses should be compared. The paper which follows is a systematic review involving a comprehensive search of the medical literature to identify all clinical trials (article or abstract) evaluating the Shouldice repair. After assessment of certain quality criteria, the best studies were pooled in a meta-analysis. Nine publications were found with 11 study arms. In ten studies the results of the Shouldice technique were better than the results of the control arm. Six studies could be pooled in a meta-analysis of 2500 patients; Shouldice was significantly better than control methods (relative risk 0.62 (95 per cent confidence interval 0.45-0.85)). In spite of possible bias caused by different variables (modifications in operative technique, suture material, level of surgeon, follow-up methods and outcome measurement), the results of this systematic review suggest that the Shouldice method is the best current conventional technique for inguinal hernia repair.

Controlled Clinical Trials as Topic↗

Cardiovascular prognostic impact of missense vs nonmissense lamin A/C variants: A systematic review and meta-analysis.

BACKGROUND: Variants in the LMNA gene, responsible for laminopathies, are associated with severe cardiovascular outcomes, including arrhythmias and heart failure (HF). However, the differential prognostic impact of missense vs nonmissense variants remains unclear. OBJECTIVE: The primary end point of this systematic review and meta-analysis was to compare the cardiovascular outcome defined as combined malignant ventricular arrhythmias (MVAs) and HF among patients with missense vs nonmissense variants in the LMNA gene. Secondary outcomes included a comparison of MVAs and HF-related events analyzed separately. METHODS: A systematic search of PubMed, Ovid MEDLINE, and Cochrane Library was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Meta-analyses were performed using fixed or random effects models, depending on heterogeneity. PROSPERO identifier: CRD42024584721. RESULTS: 12 studies comprising 1818 participants were included. Of these, 969 had missense variants, and 849 had nonmissense variants. The nonmissense group showed a significantly higher rate of cardiovascular events (30.5% vs 21.3%; odds ratio [OR] 2.22; P < .001). MVAs were more frequent in nonmissense carriers (25.5% vs 18.9%; OR 2.37; P < .001). Although limited by the small number of studies (n = 5) and single-study bias, the incidence of HF-related severe events seemed similar between the groups (18.2% vs 23.9%; OR 0.956; P = .801). CONCLUSION: Nonmissense LMNA variants are associated with worse cardiovascular outcomes, particularly arrhythmic events, whereas HF-related events seem comparable between nonmissense and missense variants.

Humans↗

What do we know about how to do audit and feedback? Pitfalls in applying evidence from a systematic review.

BACKGROUND: Improving the quality of health care requires a range of evidence-based activities. Audit and feedback is commonly used as a quality improvement tool in the UK National Health Service [NHS]. We set out to assess whether current guidance and systematic review evidence can sufficiently inform practical decisions about how to use audit and feedback to improve quality of care. METHODS: We selected an important chronic disease encountered in primary care: diabetes mellitus. We identified recommendations from National Institute for Clinical Excellence (NICE) guidance on conducting audit and generated questions which would be relevant to any attempt to operationalise audit and feedback in a healthcare service setting. We explored the extent to which a systematic review of audit and feedback could provide practical guidance about whether audit and feedback should be used to improve quality of diabetes care and, if so, how audit and feedback could be optimised. RESULTS: National guidance suggests the importance of securing the right organisational conditions and processes. Review evidence suggests that audit and feedback can be effective in changing healthcare professional practice. However, the available evidence says relatively little about the detail of how to use audit and feedback most efficiently. CONCLUSION: Audit and feedback will continue to be an unreliable approach to quality improvement until we learn how and when it works best. Conceptualising audit and feedback within a theoretical framework offers a way forward.

Humans↗

Barriers to participation in clinical trials of cancer: a meta-analysis and systematic review of patient-reported factors.

BACKGROUND: Enrolling participants onto clinical trials of cancer presents an important challenge. We aimed to identify the concerns of patients with cancer about, and the barriers to, participation in clinical trials. METHODS: We did a systematic review to assess studies of barriers to participation in experimental trials and randomised trials for validity and content. We estimated the frequency with which patients identified particular issues by pooling across studies that presented data for barriers to participation in clinical trials as proportions. FINDINGS: We analysed 12 qualitative studies (n=722) and 21 quantitative studies (n=5452). Two qualitative studies inquired of patients who were currently enrolled onto clinical trials, and ten inquired of patients who were eligible for enrolment onto various clinical trials. Barriers to participation in clinical trials were protocol-related, patient-related, or physician-related. The most common reasons cited as barriers included: concerns with the trial setting; a dislike of randomisation; general discomfort with the research process; complexity and stringency of the protocol; presence of a placebo or no-treatment group; potential side-effects; being unaware of trial opportunities; the idea that clinical trials are not appropriate for serious diseases; fear that trial involvement would have a negative effect on the relationship with their physician; and their physician's attitudes towards the trial. Meta-analysis confirmed the findings of our systematic review. INTERPRETATION: The identification of such barriers to the participation in clinical trials should help trialists to develop strategies that will keep to a maximum participation and cooperation in cancer trials, while informing and protecting prospective participants adequately.

Clinical Trials as Topic↗

How to undertake a clinically relevant systematic review in a rapidly evolving field. Magnetic resonance angiography.

OBJECTIVES: The aim was to determine which generations of the evolving technology of magnetic resonance angiography (MRA) are currently of clinical relevance in two clinical applications. Our purpose was to plan a systematic review that would be valuable both to purchasers driven by cost-effectiveness and to practicing clinicians. METHODS: Information was gathered from a search of major bibliographic databases, from a short questionnaire sent to 500 U.K. vascular radiologists and vascular surgeons, and from local clinical experts. We asked which of the MRA techniques were currently used and, assuming availability, what would be their technique of choice. RESULTS: There were 206 published articles that satisfied preliminary inclusion criteria: 69 discussed 2D time of flight (TOF); 47, 3D TOF; and 38, contrast-enhanced techniques. There were 162 questionnaires returned (60 radiologists, 102 surgeons). Of the total respondents, 77/162 (48%) used MRA in the assessment of carotid artery stenosis; 47/77 (61%) used 2D TOF; 32/77 (42%), 3D TOF; and 26/77 (34%), contrast-enhanced techniques. Thirty-five of 162 (22%) respondents used MRA in the assessment of peripheral vascular disease (PVD); 15/35 (43%) used 2D TOF, 4/35 (11%) used 3D TOF, and 22/35 (63%) used contrast-enhanced techniques. For those wishing to use MRA, contrast-enhanced techniques were the method of choice. CONCLUSIONS: The TOF methods that represent earlier generations of the technology remain clinically relevant, and will therefore be included in our systematic review. To ensure complete and relevant coverage in reviews of other evolving technologies, it would be advisable to obtain data for guidance in a similar way.

Humans↗

A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: II. Suicidal behavior.

The different serotonin (5-HT) receptors, including the serotonin transporter (5-HTT), are excellent candidate genes for suicide and suicidal behavior, and thus, they have been investigated in a large number of allelic association studies. The individual results of these studies have been inconsistent and definite conclusions are difficult to establish. A reliable method for assessing individual studies and generating combined results is provided by systematic reviews using meta-analytical techniques. In this study, we carried out a systematic review of studies investigating 5-HT receptors and the 5-HTT in suicidal behavior. Studies were identified by means of MEDLINE database searches and by scanning reference lists. More than 190 articles were reviewed and 26 met the inclusion criteria. In all, 14 studies investigated six different 5-HT receptor loci and 12 studies investigated the 5-HTT promoter 44 bp insertion/deletion polymorphism. Two specific meta-analyses were carried out, pooling studies investigating the 5-HT2A 102 T/C and the 5-HTT promoter loci that included, respectively, a total of 1599 and 2539 subjects. The combined evidence was significant for association with the 5-HTT locus (Mantel-Haenszel weighted odds ratio (M-H(w) OR)=1.17 CI : 1.04-1.32, P=0.009), but not for the 5-HT2A 102 T/C variant (M-H(w) OR)=1.09 CI : 0.93-1.27, P=0.319). The 5-HTT result was robust and remained significant following sensitivity analysis, suggesting that 5-HTT may play a role in the predisposition to suicide.

Alleles↗

Are coffee and tea consumption associated with urinary tract cancer risk? A systematic review and meta-analysis.

BACKGROUND: Narrative reviews have concluded that there is a small association between coffee consumption and an increased risk of urinary tract cancer, possibly due to confounding by smoking. No association for tea consumption has been indicated. This systematic review attempts to summarize and quantify these associations both unadjusted and adjusted for age, smoking and sex. METHOD: Thirty-four case-control and three follow-up studies were included in this systematic review. Summary odds ratios (OR) were calculated by meta-regression analyses. RESULTS: The unadjusted summary OR indicated a small increased risk of urinary tract cancer for current coffee consumers versus non-drinkers. The adjusted summary OR were: 1.26 (95% CI : 1.09-1.46) for studies with only men, 1.08 (95% CI : 0.79-1.46) for studies with only women and 1.18 (95% CI : 1.01-1.38) for studies with men and women combined. Neither unadjusted nor adjusted summary OR provided evidence for a positive association between tea consumption and urinary tract cancer. Even though studies differed in methodology, the results were rather consistent. We did not perform dose-response analyses for coffee and tea consumption due to sparse data. CONCLUSIONS: In accordance with earlier reviews, we found that coffee consumption increases the risk of urinary tract cancer by approximately 20%. The consumption of tea seems not to be related to an increased risk of urinary tract cancer.

Age Factors↗

Ovarian cancer patients and hormone replacement therapy: a systematic review.

OBJECTIVE: Although the majority of patients with ovarian cancer are menopausal, approximately one-third are premenopausal at the time of diagnosis. Little information is available concerning the impact of hormone replacement therapy (HRT) on the clinical outcomes of patients previously treated for ovarian cancer. The objective of this review is to determine whether there is any adverse impact on survival among women with ovarian cancer on HRT. METHODS: A protocol was developed in advance of commencement of this systematic review. It detailed the plan for the search strategy, selection criteria for studies, and methods for data collection and analysis. No limitation of study design was made, and the details of the search strategy are described in the text of the review. Two reviewers independently evaluated the eligibility of all studies and abstracted the data. RESULTS: One randomized trial and two observational studies are included. Due to methodological heterogeneity of the included studies, results have not been pooled in a meta-analysis. The randomized trial presented differences between the intervention and control groups on median overall survival (44 months vs. 34 months/HRT vs. No-HRT) and disease-free survival (34 months vs. 27 months/HRT vs. No-HRT) that were not significant. Similarly, there were nonsignificant differences in survival and recurrence rates in the two included cohort studies. CONCLUSIONS: This is a comprehensive systematic review of the evidence concerning HRT in ovarian cancer patients. Until more evidence becomes available, it appears that HRT is acceptable for patients with ovarian cancer as part of supportive and symptomatic therapy.

Cohort Studies↗

SARS: systematic review of treatment effects.

BACKGROUND: The SARS outbreak of 2002-2003 presented clinicians with a new, life-threatening disease for which they had no experience in treating and no research on the effectiveness of treatment options. The World Health Organization (WHO) expert panel on SARS treatment requested a systematic review and comprehensive summary of treatments used for SARS-infected patients in order to guide future treatment and identify priorities for research. METHODS AND FINDINGS: In response to the WHO request we conducted a systematic review of the published literature on ribavirin, corticosteroids, lopinavir and ritonavir (LPV/r), type I interferon (IFN), intravenous immunoglobulin (IVIG), and SARS convalescent plasma from both in vitro studies and in SARS patients. We also searched for clinical trial evidence of treatment for acute respiratory distress syndrome. Sources of data were the literature databases MEDLINE, EMBASE, BIOSIS, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to February 2005. Data from publications were extracted and evidence within studies was classified using predefined criteria. In total, 54 SARS treatment studies, 15 in vitro studies, and three acute respiratory distress syndrome studies met our inclusion criteria. Within in vitro studies, ribavirin, lopinavir, and type I IFN showed inhibition of SARS-CoV in tissue culture. In SARS-infected patient reports on ribavirin, 26 studies were classified as inconclusive, and four showed possible harm. Seven studies of convalescent plasma or IVIG, three of IFN type I, and two of LPV/r were inconclusive. In 29 studies of steroid use, 25 were inconclusive and four were classified as causing possible harm. CONCLUSIONS: Despite an extensive literature reporting on SARS treatments, it was not possible to determine whether treatments benefited patients during the SARS outbreak. Some may have been harmful. Clinical trials should be designed to validate a standard protocol for dosage and timing, and to accrue data in real time during future outbreaks to monitor specific adverse effects and help inform treatment.

Disease Outbreaks↗

Effectiveness of primary enforcement safety belt laws and enhanced enforcement of safety belt laws: a summary of the Guide to Community Preventive Services systematic reviews.

BACKGROUND: The use of safety belts is the single most effective means of reducing fatal and nonfatal injuries in motor-vehicle crashes. This paper summarizes the systematic reviews of two interventions to increase safety belt use: primary enforcement safety belt laws and enhanced enforcement of safety belt laws. The reviews were previously published in the American Journal of Preventive Medicine. METHODS: We conducted the systematic reviews using the methodology developed for the Guide to Community Preventive Services. RESULTS: These reviews provide strong evidence that primary laws are more effective than secondary laws in increasing safety belt use and decreasing fatalities and that enhanced enforcement is effective in increasing safety belt use. Increases in belt use are generally highest in states with low baseline rates of belt use. DISCUSSION: Primary safety belt laws and enhanced enforcement programs tend to result in greater increases in usage rates for target groups with lower baseline rates. Concerns regarding public opposition to these interventions may impede their implementation in some jurisdictions. However, surveys indicate that a substantial majority of the public supports implementation of both primary laws and enhanced enforcement programs. CONCLUSION: Based on the strong evidence for effectiveness of primary safety belt laws and enhanced enforcement programs, the Task Force on Community Preventive Services recommended that all states enact primary safety belt laws and that communities implement enhanced enforcement programs.

Accidents, Traffic↗

Systematic literature reviews.

Systematic reviews retrieve, appraise and summarise all the available evidence on a specific health question. They are designed to reduce the effect of the reviewers' own bias, and a full protocol should be written to define and guide the process. The appropriate resources should be in place before undertaking a review. The steps of the review are: frame the question and choose appropriate methods; identify relevant work; extract relevant data on outcomes and quality; summarise the evidence; and, interpret the evidence. Reviews that combine valid, homogeneous studies of treatments that are relevant to health care, in patients who are typical, can provide good evidence to guide health care decisions.

Data Collection↗