Citations

Background Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. Methods We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). Findings In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). Interpretation Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.

Abstract Background There are many pharmacologic therapies that are being used or considered for treatment of coronavirus disease 2019 (COVID-19). There is a need for frequently updated practice guidelines on their use, based on critical evaluation of rapidly emerging literature. The objective was to develop evidence-based rapid guidelines intended to support patients, clinicians, and other healthcare professionals in their decisions about treatment and management of patients with COVID-19. Methods The Infectious Diseases Society of America (IDSA) formed a multidisciplinary guideline panel of infectious disease clinicians, pharmacists, and methodologists with varied areas of expertise. Process followed a rapid recommendation checklist. The panel prioritized questions and outcomes. Then a systematic review of the peer-reviewed and gray literature was conducted. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations. Results The IDSA guideline panel agreed on 7 treatment recommendations and provided narrative summaries of other treatments undergoing evaluations. Conclusions The panel expressed the overarching goal that patients be recruited into ongoing trials, which would provide much-needed evidence on the efficacy and safety of various therapies for COVID-19, given that we could not make a determination whether the benefits outweigh harms for most treatments.

Introduction Physical activity can prevent a wide range of diseases, including highly prevalent conditions such as heart disease, diabetes and associated cardiometabolic disorders. Numerous guidelines for the prescription of physical activity and exercise to promote general health and prevent disease are released each year, but the quality of these guidelines is currently unknown. This systematic review and critical appraisal of physical activity and exercise guidelines aims to summarise the current status and quality of these guidelines to provide suggestions to improve the development of future guidelines in this area. Methods and analysis We will conduct a systematic review of guidelines in Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews and Scopus databases published from database 2000 through 23 October 2019, written in English for the use of physical activity and exercise for the prevention of cardiometabolic disease and related risk factors in otherwise healthy individuals. We will also search the grey literature for additional eligible documents. We will use the Appraisal of Guidelines for Research and Evaluation II tool to assess the quality of eligible recommendations from all included guidelines, as well as perform exploratory analyses on guideline development variables. Ethics and dissemination As a protocol for the review and critical appraisal of published documents, no potential ethical considerations are discussed. The protocol will guide the development of the review, which will be disseminated to relevant journals for publication. PROSPERO registration number CRD42019126364

Myeloid sarcomas (MS) are a rare manifestation of myeloid malignancies and can often be misdiagnosed, leading to a delay in treatment. The objective of this clinical case is to highlight the challenges of the clinical presentation and to emphasize the importance of this manifestation ensuring timely diagnosis and therapy. Here, we present a 43-year-old man who was diagnosed with acute myeloblastic leukemia (AML) after being evaluated for unintentional weight loss, subcutaneous nodules, thrombocytopenia, and anemia. The patient underwent chemotherapy with complete remission and presented 4 months later with dysphagia and cranial nerve palsies. Appropriate imaging and biopsy led to a diagnosis of myeloid sarcoma, and a decision was made to begin reinduction chemotherapy for AML achieving a second complete remission although his neurological deficits did not improve. Our case illustrates the protean presentation of myeloid sarcomas; clinicians should have a high suspicion for MS and remain vigilant when unexplained signs and symptoms arise in the background of a myeloid malignancy although challenges still remain when presentation is de novo. Advancements in understanding the pathophysiology of MS have been performed but remain not completely understood. High clinical suspicion, appropriate imaging, biopsy techniques, and expertise are paramount for timely diagnosis and treatment.

Introduction: Management of newly diagnosed multiple myeloma (NDMM), which accounts for 1% of all cancers, is an area in dire need of therapeutic innovation. In recent years, the introduction of novel agents is one of the major advances in the management of patients with NDMM, in both transplant- eligible and transplant- ineligible candidates. Studies have combined daratumumab, a human IgGκ monoclonal antibody that targets CD38 which is highly expressed on myeloma cells, with proteasome inhibitors and immunomodulatory agents-based regimens in the first-line treatment of NDMM. The purpose of our study is to explore and consolidate the efficacy of upfront daratumumab combination regimen in patients with NDMM. Methods: We systematically conducted a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts from inception through June 2019. Phase III RCTs utilizing daratumumab in patients with newly diagnosed/ untreated multiple myeloma were incorporated in the analysis. A generic inverse variance method was used to calculate the estimated pooled hazard ratio (HR) for progression-free survival (PFS) with 95% confidence interval (CI). Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) for overall response rate (ORR), including stringent complete response (sCR), CR and very good partial response (VGPR). Heterogeneity was assessed with Cochran's Q -statistic. Random effects model was applied. Results: Three phase III RCTs with a total of 2,528 patients with NDMMwere included.Studies compared daratumumab (D) + bortezomib (V) + melphan (M) + prednisone (P) vs VMP, D + lenalidomide (R) + dexamethasone (d) vs Rd, and DVd + thalidomide (T) vs VTd. The randomization ratio was 1:1 in all studies. The I2statistic for heterogeneity was 0, suggesting homogeneity among RCT. The pooled HR for PFS was statistically significant at 0.52 (95% CI: 0.44-0.61; P < 0.0001). The PFS benefit was observed in all ISS categories, types of immunoglobulin (Ig) and standard risk cytogenetic; ISS I cohort (HR, 0.55; 95% CI: 0.37- 0.82; P = 0.003), ISS II cohort (HR, 0.43; 95% CI: 0.33- 0.55; P < 0.0001), ISS III cohort (HR, 0.63; 95% CI: 0.48- 0.82; P = 0.0006), IgG cohort (HR, 0.56; 95% CI: 0.40- 0.77; P = 0.0003), non-IgG cohort (HR, 0.52; 95% CI: 0.28- 0.97; P = 0.04), and standard risk cytogenetic cohort (HR, 0.43; 95% CI: 0.35- 0.53; P < 0.0001). The pooled HR for PFS in high risk cytogenetic cohort was not statistically significant at 0.76 (95% CI: 0.53- 1.10; P = 0.15). The pooled RR for ORR was 1.13 (95% CI: 1.01-1.26; P = 0.03), sCR was 2.02 (95% CI: 1.33-3.08; P = 0.001), CR was 1.46 (95% CI: 1.20-1.79; P = 0.0002),and VGPR was 1.01 (95% CI: 0.82-1.25; P = 0.93). The pooled RR for negative minimal residual disease (MRD) was 2.54 (95% CI: 1.24-5.20; P = 0.01). Conclusions: Upfront combination regimen with daratumumab significantly improved PFS, ORR, sCR and CR along with negative MRD, compared to control arm in patients with NDMM. The improvement in PFS was noted across all subgroups except in high-risk cytogenetic group. More randomized studies are required to explore further novel agents and to formulate optimal combination regimen to improve survival in this high-risk cytogenetic subset. Disclosures No relevant conflicts of interest to declare.

Background and purpose Thromboembolic events are recognized complications of aneurysm coiling. Objective To identify any protective effects of antiplatelet therapy use before coiling of unruptured aneurysms. Methods We conducted a meta-analysis of clinical studies published up to February 2019. We included studies reporting symptomatic thromboembolic events (defined as clinical stroke or transient ischemic attacks) in patients who received antiplatelet therapy before coiling of unruptured aneurysms using unassisted coiling, balloon assistance, or multiple microcatheters. We excluded ruptured aneurysms and those treated with stent coiling or flow diverters. Results We identified 14 studies (2486 patients). All were single-center studies and four were prospective. In three studies with a control (no treatment) arm, the pooled risk ratio for symptomatic thromboembolic events with versus without antiplatelet therapy was 0.33 (95% CI 0.17 to 0.92, p= 0.035). The cumulative risk of symptomatic thromboembolic events with single antiplatelet agents was 5.0% ‘56/1122’ (95% CI 1.6% to 8.4%, I283.63%), and with dual or multiple agents 2.7% ‘33/1237’ (95% CI 1.0% to 3.0%, I239.9%). The incidence of diffusion lesions was reported in seven studies. It was 50.5% ‘96/190’ (95% CI 7.3% to 93.9%, I294.4%) with single agents compared with 43.9% ‘196/446’ (95% CI 25.9% to 61.9%, I273.4%) with dual or multiple agents. Conclusion Periprocedural antiplatelet therapy was associated with a low symptomatic thromboembolic event after coiling-only for unruptured aneurysms. However, available evidence is of limited quality with significant heterogeneity, requiring evidence from randomized controlled trials.

OBJECTIVEThe primary goal of the treatment of cerebral arteriovenous malformations (AVMs) is angiographic occlusion to eliminate future hemorrhage risk. Although multimodal treatment is increasingly used for AVMs, periprocedural hemorrhage after transarterial embolization is a potential endovascular complication that is only partially understood and merits quantification.METHODSSearching the period between 1990 and 2019, the authors of this meta-analysis queried the PubMed and Embase databases for studies reporting periprocedural hemorrhage (within 30 days) after liquid embolization (using cyanoacrylate or ethylene vinyl alcohol copolymer) of AVMs. Random effects meta-analysis was used to evaluate the pooled rate of flow-related hemorrhage (those attributed to alterations in AVM dynamics), technical hemorrhage (those related to procedural complications), and total hemorrhage. Meta-regression was used to analyze the study-level predictors of hemorrhage, including patient age, Spetzler-Martin grade, hemorrhagic presentation, embolysate used, intent of treatment (adjuvant vs curative), associated aneurysms, endovascular angiographic obliteration, year of study publication, and years the procedures were performed.RESULTSA total of 98 studies with 8009 patients were included in this analysis, and the mean number of embolization sessions per patient was 1.9. The pooled flow-related and total periprocedural hemorrhage rates were 2.0% (95% CI 1.5%–2.4%) and 2.6% (95% CI 2.1%–3.0%) per procedure and 3.4% (95% CI 2.6%–4.2%) and 4.8% (95% CI 4.0%–5.6%) per patient, respectively. The mortality and morbidity rates associated with hemorrhage were 14.6% and 45.1%, respectively. Subgroup analyses revealed a pooled total hemorrhage rate per procedure of 1.8% (95% CI 1.0%–2.5%) for adjuvant (surgery or radiosurgery) and 4.6% (95% CI 2.8%–6.4%) for curative intent. The treatment of aneurysms (p = 0.04) and larger patient populations (p < 0.001) were significant predictors of a lower hemorrhage rate, whereas curative intent (p = 0.04), angiographic obliteration achieved endovascularly (p = 0.003), and a greater number of embolization sessions (p = 0.03) were significant predictors of a higher hemorrhage rate. There were no significant differences in periprocedural hemorrhage rates according to the years evaluated or the embolysate utilized.CONCLUSIONSIn this study-level meta-analysis, periprocedural hemorrhage was seen after 2.6% of transarterial embolization procedures for cerebral AVMs. The adjuvant use of endovascular embolization, including in the treatment of associated aneurysms and in the presurgical or preradiosurgical setting, was a study-level predictor of significantly lower hemorrhage rates, whereas more aggressive embolization involving curative intent and endovascular angiographic obliteration was a predictor of a significantly higher total hemorrhage rate.

Abstract Background Vedolizumab effectiveness estimates immediately after Food and Drug Administration (FDA) approval for ulcerative colitis (UC) and Crohn’s disease (CD) are limited by use in refractory populations. We aimed to compare treatment patterns and outcomes of vedolizumab in 2 time frames after FDA approval. Methods We used 2 data sets for time trend analysis, an academic multicenter vedolizumab consortium (VICTORY) and the Truven MarketScan database, and 2 time periods, May 2014–June 2015 (Era 1) and July 2015–June 2017 (Era 2). VICTORY cumulative 12-month clinical remission, corticosteroid-free remission, and mucosal healing rates, and Truven 12-month hospitalization and surgery rates, were compared between Eras 1 and 2 using time-to-event analyses. Results A total of 3661 vedolizumab-treated patients were included (n = 1087 VICTORY, n = 2574 Truven). In both cohorts, CD and UC patients treated during Era 2 were more likely to be biologic naïve. Compared with Era 1, Era 2 CD patients in the VICTORY consortium had higher rates of clinical remission (31% vs 40%, P = 0.03) and mucosal healing (42% vs 58%, P < 0.01). These trends were not observed for UC. In the Truven database, UC patients treated during Era 2 had lower rates of inflammatory bowel disease–related hospitalization (22.4% vs 9.6%, P < 0.001) and surgery (17.2% vs 9.4%, P = 0.008), which was not observed for CD. Conclusion Since FDA approval, remission and mucosal healing rates have increased for vedolizumab-treated CD patients, and vedolizumab-treated UC patients have had fewer hospitalizations and surgeries. This is likely due to differences between patient populations treated immediately after drug approval and those treated later.