Publications by authors named "Fares Alahdab"

93 Publications

Association of study design features and treatment effects in trials of chronic medical conditions: a meta-epidemiological study.

BMJ Evid Based Med 2021 Jul 1. Epub 2021 Jul 1.

The Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA.

Objectives: To evaluate the association of study design features and treatment effects in randomised controlled trials (RCTs) evaluating therapies for individuals with chronic medical conditions.

Design: Meta-epidemiological study.

Setting: RCTs from meta-analyses published in the 10 general medical journals with the highest impact factor published between 1 January 2007 and 10 June 2019 and evaluated a drug, procedure or device treatment of chronic medical conditions.

Main Outcome Measures: The association between trial design features and the effect size, reporting a ratio of ORs (ROR) and 95% confidence interval (CI).

Results: We included 1098 trials from 86 meta-analyses. The most common outcome in the trials was mortality (52%), followed by disease progression (16%) and adverse events (12%). Lack of blinding of patients and study personnel was associated with a larger treatment effect (ROR 1.12; 95% CI 1.00 to 1.25). There was no statistically significant association with random sequence generation, allocation concealment, blinding of outcome assessors, incomplete outcome data, whether trials were stopped early, study funding, type of interventions or with type of outcomes (objective vs subjective).

Conclusion: The meta-epidemiological study did not demonstrate a clear pattern of association between risk of bias indicators and treatment effects in RCTs in chronic medical conditions. The unpredictability of the direction of bias emphasises the need to make every attempt to adhere to blinding, allocation concealment and reduce attrition bias.

Trial Registration Number: Not applicable.
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http://dx.doi.org/10.1136/bmjebm-2021-111667DOI Listing
July 2021

Crisis-based psychiatry curriculum update: A cross-sectional study and an expert reflection from Syria.

Asian J Psychiatr 2021 Jul 10;61:102681. Epub 2021 May 10.

Mayo Evidence-based Practice Center, Mayo Clinic, Rochester, MN, USA. Electronic address:

Throughout human history, humanitarian catastrophes had a profound impact on the health and wellbeing of the local populations where they took place. The Syrian war was no different, rather it was the worst humanitarian crisis since World War II. Syrians' wellbeing was severely affected during this past decade, as had Syria's healthcare and mental health facilities. Syrian doctors have faced unprecedented difficulties and challenges across clinical disciplines and services, particularly in psychiatry. Medical students may play a central role in attenuating the burden of psychiatric diseases on their local community. However, a modification of the psychiatry curriculum to meet the current needs is an urgent necessity. Most of the published reports in psychiatry about Syrians were done on refugee populations in neighboring countries and worldwide. In contrast, this study captured the opinions of professors of psychiatry, specialists practicing psychiatrists, psychiatry residents, and a sample of senior medical students around Syria regarding the impact of war on different psychiatric diseases, and their suggestions to increase/reduce the teaching hours allocated to each of them. The votes were weighted then tested against crisis-related published psychiatry reports. The results suggested significant adjustments to the allocated training hours in the curriculum of psychiatry in Syrian medical schools. Increasing the focus of the curriculum of psychiatry on the prevalent disorders and conditions such as post-traumatic stress disorder, acute stress disorder, anxiety, and depression would empower fresh graduates to manage the basic cases of psychiatry, thus alleviating the consequences of the large shortage of psychiatrists inside Syria.
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http://dx.doi.org/10.1016/j.ajp.2021.102681DOI Listing
July 2021

Response to Letter to the Editor From Idrees and Bianco: "Treatment of Thyroid Dysfunction and Serum Lipids: A Systematic Review and Meta-Analysis".

J Clin Endocrinol Metab 2021 08;106(9):e3792-e3793

Evidence-based Practice Center, Mayo Clinic, Rochester, MN, USA.

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http://dx.doi.org/10.1210/clinem/dgab228DOI Listing
August 2021

Aspirin dosage for the prevention of graft occlusion in people undergoing coronary surgery: A systematic review and meta-analysis.

Avicenna J Med 2020 Oct-Dec;10(4):198-207. Epub 2020 Oct 13.

Mayo Evidence-based Practice Center (EPC), Mayo Clinic, Rochester, Michigan, USA.

Background: Aspirin is almost always used after coronary artery bypass graft (CABG) surgery; however, it is unclear what optimal dose should be prescribed. In this systematic review, we evaluated the effects of high versus low-dose aspirin in patients after CABG.

Methods: A comprehensive database search was conducted in several databases from date of inception until February 2018. There were no language restrictions. We included studies that compared different doses of aspirin in patients that had undergone CABG surgery. We included studies that evaluated patient-important outcomes (mortality, cardiovascular events, and gastrointestinal bleeding); and if not reported, we collected data on the surrogate outcome thromboxane B2 (TXB2). We collected relevant data and performed a meta-analysis.

Results: We identified 5903 references, and after two levels of screening by two independent reviewers, we included three randomized controlled trials in the meta-analysis with a total number of 122 participants. Mean age of trial participants was 65.63 years, and 88.68% were male. We planned to analyze all possible clinical outcomes, including mortality, recurrence, and hospitalization. However, no clinical outcomes are reported by the literature. The surrogate biochemical outcome of serum TXB2 was the only outcome reported by the eligible studies. High-dose aspirin (162-325mg once daily) achieved better suppression of TXB2 than low-dose aspirin (75-100mg once daily) (mean difference [MD], 2.00ng/mL, 95% confidence interval [CI]: 0.72-3.32; participants = 122; studies = 3; I = 0%).

Conclusions: We found no clinical trials addressing any of the clinical outcomes of interest. High-dose aspirin was superior to low-dose aspirin in suppressing platelet function, a surrogate outcome. Trials evaluating clinical and patient-important outcomes are needed to better inform medical practice and fill this gap in clinical knowledge.
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http://dx.doi.org/10.4103/ajm.ajm_17_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791283PMC
October 2020

How do we assess resilience and grit among internal medicine residents at the Mayo Clinic? A longitudinal validity study including correlations with medical knowledge, professionalism and clinical performance.

BMJ Open 2020 12 15;10(12):e040699. Epub 2020 Dec 15.

Divison of General Internal Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.

Background: There has been limited research on the positive aspects of physician wellness and to our knowledge there have been no validity studies on measures of resilience and grit among internal medicine (IM) residents.

Objectives: To investigate the validity of resilience (10 items Connor-Davidson Resilience Scale (CD-RISC 10)) and grit (Short Grit Scale (GRIT-S)) scores among IM residents at a large academic centre, and assess potential associations with previously validated measures of medical knowledge, clinical performance and professionalism.

Methods: We evaluated CD-RISC 10 and GRIT-S instrument scores among IM residents at the Mayo Clinic Rochester, Minnesota between July 2017 and June 2019. We analysed dimensionality, internal consistency reliability and criterion validity in terms of relationships between resilience and grit, with standardised measures of residents' medical knowledge (in-training examination (ITE)), clinical performance (faculty and peer evaluations and Mini-Clinical Evaluation Examination (mini-CEX)) and professionalism/dutifulness (conference attendance and evaluation completion).

Results: A total of 213 out of 253 (84.2%) survey-eligible IM residents provided both CD-RISC 10 and GRIT-S survey responses. Internal consistency reliability (Cronbach alpha) was excellent for CD-RISC 10 (0.93) and GRIT-S (0.82) overall, and for the GRIT subscales of consistency of interest (0.84) and perseverance of effort (0.71). CD-RISC 10 scores were negatively associated with ITE percentile (β=-3.4, 95% CI -6.2 to -0.5, p=0.02) and mini-CEX (β=-0.2, 95% CI -0.5 to -0.02, p=0.03). GRIT-S scores were positively associated with evaluation completion percentage (β=2.51, 95% CI 0.35 to 4.67, p=0.02) and conference attendance (β=2.70, 95% CI 0.11 to 5.29, p=0.04).

Conclusions: This study revealed favourable validity evidence for CD-RISC 10 and GRIT-S among IM residents. Residents demonstrated resilience within a competitive training environment despite less favourable test performance and grittiness that was manifested by completing tasks. This initial validity study provides a foundation for further research on resilience and grit among physicians in training.
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http://dx.doi.org/10.1136/bmjopen-2020-040699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745331PMC
December 2020

Burden of Neurological Disorders Across the US From 1990-2017: A Global Burden of Disease Study.

JAMA Neurol 2021 Feb;78(2):165-176

Department of Systems, Populations, and Leadership, University of Michigan, Ann Arbor.

Importance: Accurate and up-to-date estimates on incidence, prevalence, mortality, and disability-adjusted life-years (burden) of neurological disorders are the backbone of evidence-based health care planning and resource allocation for these disorders. It appears that no such estimates have been reported at the state level for the US.

Objective: To present burden estimates of major neurological disorders in the US states by age and sex from 1990 to 2017.

Design, Setting, And Participants: This is a systematic analysis of the Global Burden of Disease (GBD) 2017 study. Data on incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) of major neurological disorders were derived from the GBD 2017 study of the 48 contiguous US states, Alaska, and Hawaii. Fourteen major neurological disorders were analyzed: stroke, Alzheimer disease and other dementias, Parkinson disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, traumatic brain injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis, and tetanus.

Exposures: Any of the 14 listed neurological diseases.

Main Outcome And Measure: Absolute numbers in detail by age and sex and age-standardized rates (with 95% uncertainty intervals) were calculated.

Results: The 3 most burdensome neurological disorders in the US in terms of absolute number of DALYs were stroke (3.58 [95% uncertainty interval [UI], 3.25-3.92] million DALYs), Alzheimer disease and other dementias (2.55 [95% UI, 2.43-2.68] million DALYs), and migraine (2.40 [95% UI, 1.53-3.44] million DALYs). The burden of almost all neurological disorders (in terms of absolute number of incident, prevalent, and fatal cases, as well as DALYs) increased from 1990 to 2017, largely because of the aging of the population. Exceptions for this trend included traumatic brain injury incidence (-29.1% [95% UI, -32.4% to -25.8%]); spinal cord injury prevalence (-38.5% [95% UI, -43.1% to -34.0%]); meningitis prevalence (-44.8% [95% UI, -47.3% to -42.3%]), deaths (-64.4% [95% UI, -67.7% to -50.3%]), and DALYs (-66.9% [95% UI, -70.1% to -55.9%]); and encephalitis DALYs (-25.8% [95% UI, -30.7% to -5.8%]). The different metrics of age-standardized rates varied between the US states from a 1.2-fold difference for tension-type headache to 7.5-fold for tetanus; southeastern states and Arkansas had a relatively higher burden for stroke, while northern states had a relatively higher burden of multiple sclerosis and eastern states had higher rates of Parkinson disease, idiopathic epilepsy, migraine and tension-type headache, and meningitis, encephalitis, and tetanus.

Conclusions And Relevance: There is a large and increasing burden of noncommunicable neurological disorders in the US, with up to a 5-fold variation in the burden of and trends in particular neurological disorders across the US states. The information reported in this article can be used by health care professionals and policy makers at the national and state levels to advance their health care planning and resource allocation to prevent and reduce the burden of neurological disorders.
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http://dx.doi.org/10.1001/jamaneurol.2020.4152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607495PMC
February 2021

Community-Engaged Approaches for Minority Recruitment Into Clinical Research: A Scoping Review of the Literature.

Mayo Clin Proc 2021 03 28;96(3):733-743. Epub 2020 Sep 28.

Division of Infectious Diseases, Mayo Clinic, Rochester, MN.

Underrepresentation of racial and ethnic minority populations in clinical research persists in the United States, highlighting the unmet ideals of generalizability and equity of research findings and products. Previous systematic reviews exploring various facets of this phenomenon concluded that community engagement with minority groups may effectively promote recruitment and retention, but the ways in which community-engaged approaches have been used for recruitment have not been examined. We performed a scoping review of the literature to identify studies of community-engaged recruitment processes. The search resulted in 2842 articles, of which 66 met inclusion criteria. These articles demonstrated a relatively large literature base of descriptive studies conveying details of community engagement approaches to enhance recruitment of minority research participants. We summarize key aspects of current practices across the spectrum of community engagement. A gap in the literature is the relative lack of the comparative studies among different engagement strategies.
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http://dx.doi.org/10.1016/j.mayocp.2020.03.028DOI Listing
March 2021

Treatment of Thyroid Dysfunction and Serum Lipids: A Systematic Review and Meta-analysis.

J Clin Endocrinol Metab 2020 12;105(12)

Evidence-Based Practice Center, Mayo Clinic, Rochester, Minnesota.

Context: Hyperthyroidism is associated with low levels of cholesterol and triglycerides, and hypothyroidism is associated with hypercholesterolemia and hypertriglyceridemia.

Objective: The aim of this systematic review was to investigate the impact of therapy for overt and subclinical hyper- and hypothyroidism on serum lipids.

Data Sources: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus from 1970 through April 5, 2018.

Study Selection: Pairs of independent reviewers selected randomized and observational studies evaluating lipid parameters in patients undergoing treatment for hyper- or hypothyroidism.

Data Extraction: Pairs of independent reviewers extracted data and appraised studies.

Data Synthesis: Treatment of overt hyperthyroidism showed a significant increase in total cholesterol (TC) by 44.50 mg/dL (95% confidence interval [CI]: 37.99, 51.02), low-density lipoprotein cholesterol (LDL-C) by 31.13 mg/dL (95% CI: 24.33, 37.93), high-density lipoprotein cholesterol (HDL-C) by 5.52 mg/dL (95% CI: 1.48, 9.56), apolipoprotein A (Apo A) by 15.6 mg/dL (95% CI: 10.38, 20.81), apolipoprotein B (apo B) by 26.12 mg/dL (95% CI: 22.67, 29.57), and lipoprotein (Lp[a]) by 4.18 mg/dL (95% CI: 1.65, 6.71). There was no significant change in triglyceride (TG) levels. Treatment of subclinical hyperthyroidism did not change any lipid parameters significantly. Levothyroxine therapy in overt hypothyroidism showed a statistically significant decrease in TC by -58.4 mg/dL (95% CI: -64.70, -52.09), LDL-C by -41.11 mg/dL (95% CI: -46.53, -35.69), HDL-C by -4.14 mg/dL (95% CI: -5.67, -2.61), TGs by -7.25 mg/dL (95% CI: -36.63, 17.87), apo A by -12.59 mg/dL (95% CI: -17.98, -7.19), apo B by -33.96 mg/dL (95% CI: 41.14, -26.77), and Lp(a) by -5.6 mg/dL (95% CI: -9.06, -2.14). Levothyroxine therapy in subclinical hypothyroidism showed similar changes but with a smaller magnitude. The studies contained varied population characteristics, severity of thyroid dysfunction, and follow-up duration.

Conclusions: Treatment of overt but not subclinical hyperthyroidism is associated with worsening of the lipid profile. Levothyroxine therapy in both overt and subclinical hypothyroidism leads to improvement in the lipid profile, with a smaller magnitude of improvement in subclinical hypothyroidism.
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http://dx.doi.org/10.1210/clinem/dgaa672DOI Listing
December 2020

Estimating global injuries morbidity and mortality: methods and data used in the Global Burden of Disease 2017 study.

Inj Prev 2020 10 24;26(Supp 1):i125-i153. Epub 2020 Aug 24.

Department of Pharmacy, Adigrat University, Adigrat, Ethiopia.

Background: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria.

Methods: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced.

Results: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes.

Conclusions: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future.
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http://dx.doi.org/10.1136/injuryprev-2019-043531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571362PMC
October 2020

The efficacy and safety of transradial and transfemoral approach in treatment of coronary chronic total occlusion: a systematic review and meta-analysis.

Expert Rev Cardiovasc Ther 2020 Nov 27;18(11):809-817. Epub 2020 Oct 27.

Department of Cardiology, Wayne State University, Detroit Medical Center , Detroit, Michigan, USA.

Background: The clinical efficacy and safety of transradial (TR) percutaneous coronary intervention (PCI) in comparison to transfemoral (TF) for chronic total occlusion (CTO) is not well studied in literature. : We sought to study the outcome and complications associated with TR compared with TF for CTO interventions.

Methods: After a systematic literature search was done in PubMed and EMBASE, we performed a meta-analysis of studies comparing TF and TR for CTO PCI. : Twelve studies with 19,309 patients were included. Compared to those who has TF access, individuals who were treated via TR approach had statistically significant lower access complication rates [odds ratio (OR): 0.33; 95% confidence interval (CI): 0.22 to 0.49; p < 0.0001]. The procedural success was in the favor of TR method (OR: 1.4; 95% CI: 1.31-1. 51; p < 0.0001). The incidence of major adverse cardiovascular and cerebrovascular events (MACCE) and contrast-induced nephropathy were similar in both groups.

Conclusion: When compared with TF access interventions in CTO PCI; the TR approach appears to be associated with far less access-site complications, higher procedural success, and comparable MACCE.
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http://dx.doi.org/10.1080/14779072.2020.1813025DOI Listing
November 2020

Health Literacy and Outcomes Among Patients With Heart Failure: A Systematic Review and Meta-Analysis.

JACC Heart Fail 2020 06;8(6):451-460

Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota; Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota. Electronic address:

Objectives: The purpose of this study was to determine if health literacy is associated with mortality, hospitalizations, or emergency department (ED) visits among patients living with heart failure (HF).

Background: Growing evidence suggests an association between health literacy and health-related outcomes in patients with HF.

Methods: We searched Embase, MEDLINE, PsycINFO, and EBSCO CINAHL from inception through January 1, 2019, with the help of a medical librarian. Eligible studies evaluated health literacy among patients with HF and assessed mortality, hospitalizations, and ED visits for all causes with no exclusion by time, geography, or language. Two reviewers independently selected studies, extracted data, and assessed the methodological quality of the identified studies.

Results: We included 15 studies, 11 with an overall high methodological quality. Among the observational studies, an average of 24% of patients had inadequate or marginal health literacy. Inadequate health literacy was associated with higher unadjusted risk for mortality (risk ratio [RR]: 1.67; 95% confidence interval [CI]: 1.18 to 2.36), hospitalizations (RR: 1.19; 95% CI: 1.09 to 1.29), and ED visits (RR: 1.17; 95% CI: 1.03 to 1.32). When the adjusted measurements were combined, inadequate health literacy remained statistically associated with mortality (RR: 1.41; 95% CI: 1.06 to 1.88) and hospitalizations (RR: 1.12; 95% CI: 1.01 to 1.25). Among the 4 interventional studies, 2 effectively improved outcomes among patients with inadequate health literacy.

Conclusions: In this study, the estimated prevalence of inadequate health literacy was high, and inadequate health literacy was associated with increased risk of death and hospitalizations. These findings have important clinical and public health implications and warrant measurement of health literacy and deployment of interventions to improve outcomes.
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http://dx.doi.org/10.1016/j.jchf.2019.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263350PMC
June 2020

Risk Factors for Mortality and Ventricular Tachycardia in Patients With Repaired Tetralogy of Fallot: A Systematic Review and Meta-analysis.

Can J Cardiol 2020 11 4;36(11):1815-1825. Epub 2020 Feb 4.

Heart Institute, Cincinnati Children`s Hospital Medical Center, Cincinnati, Ohio, USA; University of Cincinnati College of Medicine, Department of Pediatrics, Cincinnati, Ohio, USA. Electronic address:

Background: Patients with repaired tetralogy of Fallot (rTOF) have increased risk for mortality, sudden cardiac death, and ventricular tachycardia (VT). The aim of this systematic review and meta-analysis is to offer an updated analysis of risk factors following significant changes in surgical and perioperative management.

Methods: A meta-analysis based on the published literature between 2008 and 2018 was conducted. Endpoints were VT, cardiac mortality/VT, and all-cause mortality/VT. Studies with ≥100 patients and ≥10 events were included.

Results: Fifteen studies including 7218 patients (average age 27.5 years) were analyzed. Risk factors for VT included older age (per 1 year, odds ratio [OR]: 1.039; 95% confidence interval [CI]: 1.025-1.053), older age at corrective surgery (per 1 year, OR: 1.034; CI: 1.017-1.051), previous palliative shunt (OR: 3.063; CI: 1.525-6.151), number of thoracotomies (OR: 1.416; CI: 1.249-1.604), longer QRS duration (per 1 ms, OR: 1.031; CI: 1.008-1.055), and at least moderate right-ventricular dysfunction (OR: 2.160; CI_ 1.311-3.560). Additional risk factors for cardiac death/VT were previous ventriculotomy (OR: 2.269; CI: 1.226-4.198), lower left-ventricular ejection fraction (per 1%, OR: 1.049; CI: 1.029-1.071), and higher right-ventricular end diastolic volume (per 1 mL/m, OR: 1.009; CI: 1.002-1.016). Supraventricular tachycardia/atrial fibrillation was an additional risk factor for all-cause mortality/VT (OR: 1.939; CI: 1.088-3.457).

Conclusions: The study highlights the importance of preservation of biventricular systolic function on late outcomes. Ventricular function appears to have a greater impact on outcomes than the severity of pulmonary regurgitation alone in this patient population.
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http://dx.doi.org/10.1016/j.cjca.2020.01.023DOI Listing
November 2020

Global injury morbidity and mortality from 1990 to 2017: results from the Global Burden of Disease Study 2017.

Inj Prev 2020 10 24;26(Supp 1):i96-i114. Epub 2020 Apr 24.

Faculty of Health Sciences - Health Management and Policy, American University of Beirut, Beirut, Lebanon.

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.
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http://dx.doi.org/10.1136/injuryprev-2019-043494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571366PMC
October 2020

Global, Regional, and National Burden of Calcific Aortic Valve and Degenerative Mitral Valve Diseases, 1990-2017.

Circulation 2020 05 29;141(21):1670-1680. Epub 2020 Mar 29.

Institute of Family Medicine and Public Health, University of Tartu, Tartumaa, Estonia (M.J.).

Background: Nonrheumatic valvular diseases are common; however, no studies have estimated their global or national burden. As part of the Global Burden of Disease Study 2017, mortality, prevalence, and disability-adjusted life-years (DALYs) for calcific aortic valve disease (CAVD), degenerative mitral valve disease, and other nonrheumatic valvular diseases were estimated for 195 countries and territories from 1990 to 2017.

Methods: Vital registration data, epidemiologic survey data, and administrative hospital data were used to estimate disease burden using the Global Burden of Disease Study modeling framework, which ensures comparability across locations. Geospatial statistical methods were used to estimate disease for all countries, because data on nonrheumatic valvular diseases are extremely limited for some regions of the world, such as Sub-Saharan Africa and South Asia. Results accounted for estimated level of disease severity as well as the estimated availability of valve repair or replacement procedures. DALYs and other measures of health-related burden were generated for both sexes and each 5-year age group, location, and year from 1990 to 2017.

Results: Globally, CAVD and degenerative mitral valve disease caused 102 700 (95% uncertainty interval [UI], 82 700-107 900) and 35 700 (95% UI, 30 500-42 500) deaths, and 12.6 million (95% UI, 11.4 million-13.8 million) and 18.1 million (95% UI, 17.6 million-18.6 million) prevalent cases existed in 2017, respectively. A total of 2.5 million (95% UI, 2.3 million-2.8 million) DALYs were estimated as caused by nonrheumatic valvular diseases globally, representing 0.10% (95% UI, 0.09%-0.11%) of total lost health from all diseases in 2017. The number of DALYs increased for CAVD and degenerative mitral valve disease between 1990 and 2017 by 101% (95% UI, 79%-117%) and 35% (95% UI, 23%-47%), respectively. There is significant geographic variation in the prevalence, mortality rate, and overall burden of these diseases, with highest age-standardized DALY rates of CAVD estimated for high-income countries.

Conclusions: These global and national estimates demonstrate that CAVD and degenerative mitral valve disease are important causes of disease burden among older adults. Efforts to clarify modifiable risk factors and improve access to valve interventions are necessary if progress is to be made toward reducing, and eventually eliminating, the burden of these highly treatable diseases.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.043391DOI Listing
May 2020

Global trends of hand and wrist trauma: a systematic analysis of fracture and digit amputation using the Global Burden of Disease 2017 Study.

Inj Prev 2020 10 13;26(Supp 1):i115-i124. Epub 2020 Mar 13.

Institute for Health Metrics and Evaluation, University of Washington, Seattle, Washington, USA.

Background: As global rates of mortality decrease, rates of non-fatal injury have increased, particularly in low Socio-demographic Index (SDI) nations. We hypothesised this global pattern of non-fatal injury would be demonstrated in regard to bony hand and wrist trauma over the 27-year study period.

Methods: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 was used to estimate prevalence, age-standardised incidence and years lived with disability for hand trauma in 195 countries from 1990 to 2017. Individual injuries included hand and wrist fractures, thumb amputations and non-thumb digit amputations.

Results: The global incidence of hand trauma has only modestly decreased since 1990. In 2017, the age-standardised incidence of hand and wrist fractures was 179 per 100 000 (95% uncertainty interval (UI) 146 to 217), whereas the less common injuries of thumb and non-thumb digit amputation were 24 (95% UI 17 to 34) and 56 (95% UI 43 to 74) per 100 000, respectively. Rates of injury vary greatly by region, and improvements have not been equally distributed. The highest burden of hand trauma is currently reported in high SDI countries. However, low-middle and middle SDI countries have increasing rates of hand trauma by as much at 25%.

Conclusions: Certain regions are noted to have high rates of hand trauma over the study period. Low-middle and middle SDI countries, however, have demonstrated increasing rates of fracture and amputation over the last 27 years. This trend is concerning as access to quality and subspecialised surgical hand care is often limiting in these resource-limited regions.
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http://dx.doi.org/10.1136/injuryprev-2019-043495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571361PMC
October 2020

The burden of unintentional drowning: global, regional and national estimates of mortality from the Global Burden of Disease 2017 Study.

Inj Prev 2020 10 20;26(Supp 1):i83-i95. Epub 2020 Feb 20.

The George Institute for Global Health, New Delhi, India.

Background: Drowning is a leading cause of injury-related mortality globally. Unintentional drowning (International Classification of Diseases (ICD) 10 codes W65-74 and ICD9 E910) is one of the 30 mutually exclusive and collectively exhaustive causes of injury-related mortality in the Global Burden of Disease (GBD) study. This study's objective is to describe unintentional drowning using GBD estimates from 1990 to 2017.

Methods: Unintentional drowning from GBD 2017 was estimated for cause-specific mortality and years of life lost (YLLs), age, sex, country, region, Socio-demographic Index (SDI) quintile, and trends from 1990 to 2017. GBD 2017 used standard GBD methods for estimating mortality from drowning.

Results: Globally, unintentional drowning mortality decreased by 44.5% between 1990 and 2017, from 531 956 (uncertainty interval (UI): 484 107 to 572 854) to 295 210 (284 493 to 306 187) deaths. Global age-standardised mortality rates decreased 57.4%, from 9.3 (8.5 to 10.0) in 1990 to 4.0 (3.8 to 4.1) per 100 000 per annum in 2017. Unintentional drowning-associated mortality was generally higher in children, males and in low-SDI to middle-SDI countries. China, India, Pakistan and Bangladesh accounted for 51.2% of all drowning deaths in 2017. Oceania was the region with the highest rate of age-standardised YLLs in 2017, with 45 434 (40 850 to 50 539) YLLs per 100 000 across both sexes.

Conclusions: There has been a decline in global drowning rates. This study shows that the decline was not consistent across countries. The results reinforce the need for continued and improved policy, prevention and research efforts, with a focus on low- and middle-income countries.
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http://dx.doi.org/10.1136/injuryprev-2019-043484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571364PMC
October 2020

Burden of injury along the development spectrum: associations between the Socio-demographic Index and disability-adjusted life year estimates from the Global Burden of Disease Study 2017.

Inj Prev 2020 10 8;26(Supp 1):i12-i26. Epub 2020 Jan 8.

School of Public Health, Auckland University of Technology, Auckland, New Zealand.

Background: The epidemiological transition of non-communicable diseases replacing infectious diseases as the main contributors to disease burden has been well documented in global health literature. Less focus, however, has been given to the relationship between sociodemographic changes and injury. The aim of this study was to examine the association between disability-adjusted life years (DALYs) from injury for 195 countries and territories at different levels along the development spectrum between 1990 and 2017 based on the Global Burden of Disease (GBD) 2017 estimates.

Methods: Injury mortality was estimated using the GBD mortality database, corrections for garbage coding and CODEm-the cause of death ensemble modelling tool. Morbidity estimation was based on surveys and inpatient and outpatient data sets for 30 cause-of-injury with 47 nature-of-injury categories each. The Socio-demographic Index (SDI) is a composite indicator that includes lagged income per capita, average educational attainment over age 15 years and total fertility rate.

Results: For many causes of injury, age-standardised DALY rates declined with increasing SDI, although road injury, interpersonal violence and self-harm did not follow this pattern. Particularly for self-harm opposing patterns were observed in regions with similar SDI levels. For road injuries, this effect was less pronounced.

Conclusions: The overall global pattern is that of declining injury burden with increasing SDI. However, not all injuries follow this pattern, which suggests multiple underlying mechanisms influencing injury DALYs. There is a need for a detailed understanding of these patterns to help to inform national and global efforts to address injury-related health outcomes across the development spectrum.
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http://dx.doi.org/10.1136/injuryprev-2019-043296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571356PMC
October 2020

Epidemiology of facial fractures: incidence, prevalence and years lived with disability estimates from the Global Burden of Disease 2017 study.

Inj Prev 2020 10 8;26(Supp 1):i27-i35. Epub 2020 Jan 8.

Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: The Global Burden of Disease Study (GBD) has historically produced estimates of causes of injury such as falls but not the resulting types of injuries that occur. The objective of this study was to estimate the global incidence, prevalence and years lived with disability (YLDs) due to facial fractures and to estimate the leading injurious causes of facial fracture.

Methods: We obtained results from GBD 2017. First, the study estimated the incidence from each injury cause (eg, falls), and then the proportion of each cause that would result in facial fracture being the most disabling injury. Incidence, prevalence and YLDs of facial fractures are then calculated across causes.

Results: Globally, in 2017, there were 7 538 663 (95% uncertainty interval 6 116 489 to 9 493 113) new cases, 1 819 732 (1 609 419 to 2 091 618) prevalent cases, and 117 402 (73 266 to 169 689) YLDs due to facial fractures. In terms of age-standardised incidence, prevalence and YLDs, the global rates were 98 (80 to 123) per 100 000, 23 (20 to 27) per 100 000, and 2 (1 to 2) per 100 000, respectively. Facial fractures were most concentrated in Central Europe. Falls were the predominant cause in most regions.

Conclusions: Facial fractures are predominantly caused by falls and occur worldwide. Healthcare systems and public health agencies should investigate methods of all injury prevention. It is important for healthcare systems in every part of the world to ensure access to treatment resources.
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http://dx.doi.org/10.1136/injuryprev-2019-043297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571355PMC
October 2020

Trends in the performance of Syrian physicians in the National Resident Matching Program between 2017 and 2019.

Avicenna J Med 2019 Oct-Dec;9(4):154-159. Epub 2019 Oct 3.

Mayo Evidence Based Practice Center, Mayo Clinic, Rochester, Minnesota, USA.

Purpose: International medical graduates (IMGs) make up one-fourth of the physician workforce in the US and a significant proportion of them come from Syria. The aim of this study was to assess the performance of Syrian physicians seeking residency positions in the US and to examine the effects of visa restrictions on their Match outcome.

Methods: An online survey administered to IMGs from Syria was used to probe their residency application characteristics as well as their experiences with visa restrictions. We evaluated the factors that affected their Match outcome and number of interviews offered to applicants.

Results: A total of 223 IMGs from Syria completed the survey with an average match rate of 70.4% (76.6% in 2017 vs. 69.9% in 2018 vs. 64.4% in 2019). The proportion of applicants who required visas was 29.2%. In a multivariate analysis, higher USMLE Step 2CK score increased the match rate, whereas requiring a visa and failure in any USMLE exam decreased the match rate. Among those requiring visa, the match rate decreased from 78.6% in the cycle before the travel ban (2017) to 64.9% in the cycles following the travel ban (2018 and 2019) ( = 0.22). Similarly, the total number of interviews offered to these applicants decreased significantly following the travel ban (9.4 [7.5] vs. 6.2 [5.3], = 0.04).

Conclusion: Syrian IMGs seeking residency positions in the US have a higher match rate than non-US IMGs. Requiring a visa and failing any USMLE exam negatively impacted the match rate and number of interview invitations to Syrian applicants.
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http://dx.doi.org/10.4103/ajm.AJM_140_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796307PMC
October 2019

Systematic Review of the Genetics of Sudden Unexpected Death in Epilepsy: Potential Overlap With Sudden Cardiac Death and Arrhythmia-Related Genes.

J Am Heart Assoc 2020 01 21;9(1):e012264. Epub 2019 Dec 21.

Mayo Clinic College of Medicine Mayo Clinic Rochester MN.

Background Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related death. SUDEP shares many features with sudden cardiac death and sudden unexplained death in the young and may have a similar genetic contribution. We aim to systematically review the literature on the genetics of SUDEP. Methods and Results PubMed, MEDLINE Epub Ahead of Print, Ovid Medline In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Scopus were searched through April 4, 2017. English language human studies analyzing SUDEP for known sudden death, ion channel and arrhythmia-related pathogenic variants, novel variant discovery, and copy number variant analyses were included. Aggregate descriptive statistics were generated; data were insufficient for meta-analysis. A total of 8 studies with 161 unique individuals were included; mean was age 29.0 (±SD 14.2) years; 61% males; ECG data were reported in 7.5% of cases; 50.7% were found prone and 58% of deaths were nocturnal. Cause included all types of epilepsy. Antemortem diagnosis of Dravet syndrome and autism (with duplication of chromosome 15) was associated with 11% and 9% of cases. The most frequently detected known pathogenic variants at postmortem were in Na and K ion channel subunits, as were novel potentially pathogenic variants (11%). Overall, the majority of variants were of unknown significance. Analysis of copy number variant was insignificant. Conclusions SUDEP case adjudication and evaluation remains limited largely because of crucial missing data such as ECGs. The most frequent pathogenic/likely pathogenic variants identified by molecular autopsy are in ion channel or arrhythmia-related genes, with an ≈11% discovery rate. Comprehensive postmortem examination should include examination of the heart and brain by specialized pathologists and blood storage.
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http://dx.doi.org/10.1161/JAHA.119.012264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988156PMC
January 2020

Epidemiology of injuries from fire, heat and hot substances: global, regional and national morbidity and mortality estimates from the Global Burden of Disease 2017 study.

Inj Prev 2020 10 18;26(Supp 1):i36-i45. Epub 2019 Dec 18.

Institute of Public Health Kalyani, Kalyani, India.

Background: Past research has shown how fires, heat and hot substances are important causes of health loss globally. Detailed estimates of the morbidity and mortality from these injuries could help drive preventative measures and improved access to care.

Methods: We used the Global Burden of Disease 2017 framework to produce three main results. First, we produced results on incidence, prevalence, years lived with disability, deaths, years of life lost and disability-adjusted life years from 1990 to 2017 for 195 countries and territories. Second, we analysed these results to measure mortality-to-incidence ratios by location. Third, we reported the measures above in terms of the cause of fire, heat and hot substances and the types of bodily injuries that result.

Results: Globally, there were 8 991 468 (7 481 218 to 10 740 897) new fire, heat and hot substance injuries in 2017 with 120 632 (101 630 to 129 383) deaths. At the global level, the age-standardised mortality caused by fire, heat and hot substances significantly declined from 1990 to 2017, but regionally there was variability in age-standardised incidence with some regions experiencing an increase (eg, Southern Latin America) and others experiencing a significant decrease (eg, High-income North America).

Conclusions: The incidence and mortality of injuries that result from fire, heat and hot substances affect every region of the world but are most concentrated in middle and lower income areas. More resources should be invested in measuring these injuries as well as in improving infrastructure, advancing safety measures and ensuring access to care.
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http://dx.doi.org/10.1136/injuryprev-2019-043299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571358PMC
October 2020

American Society of Hematology 2019 guidelines for sickle cell disease: cardiopulmonary and kidney disease.

Blood Adv 2019 12;3(23):3867-3897

Division of Nephrology and Hypertension, School of Medicine, University of Kansas, Kansas City, KS.

Background: Prevention and management of end-organ disease represent major challenges facing providers of children and adults with sickle cell disease (SCD). Uncertainty and variability in the screening, diagnosis, and management of cardiopulmonary and renal complications in SCD lead to varying outcomes for affected individuals.

Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in their decisions about screening, diagnosis, and management of cardiopulmonary and renal complications of SCD.

Methods: ASH formed a multidisciplinary guideline panel that included 2 patient representatives and was balanced to minimize potential bias from conflicts of interest. The Mayo Evidence-Based Practice Research Program supported the guideline development process, including performing systematic evidence reviews up to September 2017. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations, which were subject to public comment.

Results: The panel agreed on 10 recommendations for screening, diagnosis, and management of cardiopulmonary and renal complications of SCD. Recommendations related to anticoagulation duration for adults with SCD and venous thromboembolism were also developed.

Conclusions: Most recommendations were conditional due to a paucity of direct, high-quality evidence for outcomes of interest. Future research was identified, including the need for prospective studies to better understand the natural history of cardiopulmonary and renal disease, their relationship to patient-important outcomes, and optimal management.
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http://dx.doi.org/10.1182/bloodadvances.2019000916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963257PMC
December 2019

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017.

Nature 2019 10 16;574(7778):353-358. Epub 2019 Oct 16.

School of Health Sciences, Madda Walabu University, Bale Goba, Ethiopia.

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2-to end preventable child deaths by 2030-we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000-2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations.
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http://dx.doi.org/10.1038/s41586-019-1545-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6800389PMC
October 2019

Impact of periprocedural biomarker elevation on mortality in stable angina pectoris patients undergoing elective coronary intervention: a systematic review and meta-analysis including 24 666 patients.

Coron Artery Dis 2020 03;31(2):137-146

MedStar Washington Hospital Center, Washington, DC, USA.

Background: Uncertainty remains regarding the exact prognostic impact of biomarker elevation following percutaneous coronary intervention in patients with stable angina pectoris and the subsequent risk of death. We sought, therefore, to evaluate the effect of periprocedural myocardial infarction on the subsequent mortality risk following percutaneous coronary intervention in patients with stable angina pectoris and normal preprocedural cardiac biomarkers level.

Methods: After a systematic literature search was done in PubMed and EMBASE, we performed a meta-analysis of studies with post-procedural cardiac biomarkers data. All-cause mortality and cardiac death were evaluated in subjects with stable angina pectoris who underwent an elective coronary intervention.

Results: Fourteen studies with 24 666 patients were included. The mean age was 64.2 years ± 9.8 with about 3-quarters (74.9%) of these patients being men. The mean duration of follow-up was 18.1 months ± 14.3. Periprocedural myocardial infarction, based on study-specific biomarker criteria, occurred in 14.3% of the patients. Periprocedural myocardial infarction conferred a statistically significant increase in the risk of all-cause mortality (odds ratio, 1.62; 95% confidence interval, 1.30-2.01; P < 0.0001; I = 0%); where reported separately, cardiac death was also significantly increase (odds ratio, 2.77; 95% confidence interval, 1.60-4.80; P = 0.0003; I = 0%).

Conclusion: The occurrence of periprocedural myocardial infarction after an elective percutaneous coronary intervention in patients with stable angina pectoris is associated with a statistically significant increase in subsequent all-cause mortality and cardiac mortality.
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http://dx.doi.org/10.1097/MCA.0000000000000795DOI Listing
March 2020

Inhaled nitric oxide for treating pain crises in people with sickle cell disease.

Cochrane Database Syst Rev 2019 Oct 11;10:CD011808. Epub 2019 Oct 11.

Internal Medicine, Hamad Medical Corporation, Doha, Qatar.

Background: In people with sickle cell disease, sickled red blood cells cause the occlusion of small blood vessels which presents as episodes of severe pain known as pain crises or vaso-occlusive crises. The pain can occur in the bones, chest, or other parts of the body, and may last several hours to days. Pain relief during crises includes both pharmacologic and non-pharmacologic treatments. The efficacy of inhaled nitric oxide in pain crises has been a controversial issue and hypotheses have been made suggesting a beneficial response due to its vasodilator properties. Yet no conclusive evidence has been presented.This review aims to evaluate the available randomised controlled studies which address this topic.

Objectives: To capture the available body of evidence evaluating the efficacy and safety of the use of inhaled nitric oxide in treating pain crises in people with sickle cell disease; and to assess the treatment's relevance, robustness, and validity, in order to better guide medical practice in the fields of haematology and palliative care (since recent literature seems to favour the involvement of palliative care for those people).

Search Methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register. Unpublished work is identified by searching the abstract books of the European Haematology Association conference; the American Society of Hematology conference; the British Society for Haematology Annual Scientific Meeting; the Caribbean Health Research Council Meetings; and the National Sickle Cell Disease Program Annual Meeting.Date of most recent search: 19 September 2019.We also searched ongoing study registries, date of most recent search: 26 September 2019.

Selection Criteria: Randomised and quasi-randomised trials comparing inhaled nitric oxide with placebo, or standardized way of treatment of pain crises in people with sickle cell disease.

Data Collection And Analysis: Two authors independently assessed trial quality and extracted data (including adverse event data). A third author helped clarify any disagreement. When the data were not reported in the text, we attempted to extract the data from any table or figure available. We contacted trial authors for additional information. We assessed the quality of the evidence using the GRADE criteria MAIN RESULTS: We identified six trials, three of which (188 participants) were eligible for inclusion in the review. There were equal numbers of males and females; and most participants were adults, although one small trial was conducted in a children's hospital and recruited children over the age of 10 years. All three parallel trials compared inhaled nitric oxygen (80 ppm) to placebo (room air) for four hours; one trial continued administering nitric oxide (40 ppm) for a further four hours. This extended trial had an overall low risk of bias; however, in the remaining two trials we had concerns about the risk of bias from the small sample size and additionally a high risk of bias due to financial conflicts of interest in one of these smaller trials. We were only able to analyse some limited data from the eight-hour trial and report the remaining results narratively.The time to pain resolution was only reported in one trial (150 participants), showing there may be little or no difference between the two groups: with inhaled nitric oxide median 73.0 hours (95% confidence interval (CI) 46.0 to 91.0) and with placebo median 65.5 hours (95% CI 48.1 to 84.0) (low-quality evidence). No trial reported on the duration of the initial pain crisis. Only one large trial reported on the frequency of pain crises in the follow-up period and found there may be little or no difference between the inhaled nitric oxide and placebo groups for a return to the ED, risk ratio 0.73 (95% CI 0.31 to 1.71) or for re-hospitalisation, risk ratio 0.53 (95% CI 0.25 to 1.11) (150 participants; low-quality evidence).There may be little or no difference between treatment and placebo in terms of reduction in pain score at any time point up to eight hours (150 participants). The two smaller trials reported a beneficial effect of inhaled nitric oxide in reducing the visual analogue pain score after four hours of the intervention, but these trials were small and limited compared to the first trial.Analgesic use was reported not to differ greatly between the inhaled nitric oxide group and placebo group in any of the three trials, but no analysable data were provided. The median duration of hospitalisation was reported by two trials, in the largest trial the placebo group had the shorter duration and in the second smaller (paediatric) trial hospitalisation was shorter in the treatment group.Only the largest trial (150 participants) reported serious adverse events, with no increase in the inhaled nitric oxide group during or after the intervention compared to the control group (acute chest syndrome occurred in 5 out of 75 participants from each group, pyrexia in 1 out of 75 participants from each group, dysphagia and a drop in haemoglobin were each reported in 1 out of 75 participants in the inhaled nitric oxide group, but not in the placebo group) (low-quality evidence).

Authors' Conclusions: The currently available trials do not provide sufficient evidence to determine the effects (benefits or harms) of using inhaled nitric oxide to treat pain (vaso-occlusive) crises in people with sickle cell disease. Large-scale, long-term trials are needed to provide more robust data in this area. Patient-important outcomes (e.g. measures of pain and time to pain resolution and amounts of analgesics used), as well as use of healthcare services should be measured and reported in a standardized form.
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http://dx.doi.org/10.1002/14651858.CD011808.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788324PMC
October 2019

Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017: A Systematic Analysis for the Global Burden of Disease Study.

JAMA Oncol 2019 12;5(12):1749-1768

Department of Family and Community Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.

Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data.

Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning.

Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence.

Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572 000 deaths and 15.2 million DALYs), and stomach cancer (542 000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819 000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601 000 deaths and 17.4 million DALYs), TBL cancer (596 000 deaths and 12.6 million DALYs), and colorectal cancer (414 000 deaths and 8.3 million DALYs).

Conclusions And Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.
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http://dx.doi.org/10.1001/jamaoncol.2019.2996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777271PMC
December 2019

Natural History of Adrenal Incidentalomas With and Without Mild Autonomous Cortisol Excess: A Systematic Review and Meta-analysis.

Ann Intern Med 2019 07 25;171(2):107-116. Epub 2019 Jun 25.

Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota (F.A., D.A.D., A.K., M.H.M., I.B.).

Background: Adrenal incidentalomas are mostly benign nonfunctioning adrenal tumors (NFATs) or adenomas causing mild autonomous cortisol excess (MACE), but their natural history is unclear.

Purpose: To summarize the follow-up data of adults with NFAT or MACE to determine the proportions of tumor growth, malignant transformation, and incident changes in hormone function; the prevalence of incident cardiometabolic comorbid conditions; and mortality.

Data Sources: MEDLINE, Embase, Cochrane, and Scopus (January 1990 to February 2019) and bibliographies of identified articles, without language restriction.

Study Selection: Studies that included 20 or more conservatively managed patients with NFAT or MACE and reported outcomes at baseline and after at least 12 months of follow-up.

Data Extraction: Pairs of reviewers extracted outcomes and assessed methodological quality.

Data Synthesis: Thirty-two studies reported outcomes of 4121 patients with NFAT or MACE, 61.5% of whom were women; the mean age was 60.2 years, and mean follow-up was 50.2 months. Mean tumor growth was 2 mm over 52.8 months. Clinically significant tumor enlargement (≥10 mm) occurred in 2.5% of patients, and none developed adrenal cancer. Clinically overt hormone excess was unlikely to develop (<0.1%) in patients with NFAT or MACE. Only 4.3% of patients with NFAT developed MACE, and preexisting MACE was unlikely to resolve (<0.1%). Hypertension, obesity, dyslipidemia, and type 2 diabetes were highly prevalent (60.0%, 42.0%, 33.7%, and 18.1% of patients, respectively) and were more likely to develop and worsen in MACE than NFAT. New cardiovascular events were more prevalent in MACE (15.5%) than NFAT (6.4%). Mortality was 11.2% and was similar between NFAT and MACE.

Limitation: Evidence was scarce, and definitions of MACE and comorbid conditions were heterogeneous.

Conclusion: During follow-up, NFAT and MACE do not show clinically relevant changes in size or hormonal function, but they may carry an increased risk for cardiometabolic comorbid conditions.

Primary Funding Source: None.
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http://dx.doi.org/10.7326/M18-3630DOI Listing
July 2019

Peritoneal Dialysis Vs Diuretics in Children After Congenital Heart Surgery.

Ann Thorac Surg 2019 09 23;108(3):806-812. Epub 2019 Apr 23.

Mayo Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota.

Background: This study sought to evaluate outcomes of patients undergoing congenital heart surgery who underwent peritoneal dialysis (PD) vs a diuretic regimen.

Methods: This study conducted a comprehensive search in Medline, EMBASE, Scopus, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews from the databases' inception through April 24, 2018. Independent reviewers selected studies and extracted data. A random effects meta-analysis was performed to pool the outcomes of interest across studies.

Results: A total of 8 studies (2 prospective studies, 2 randomized clinical trials, and 4 retrospective studies) with 507 patients were included in this review. A total of 204 (40%) patients underwent PD, whereas the remaining patients underwent fluid removal with diuretics. The analyses demonstrated a significantly shorter time of mechanical ventilation in those patients who underwent PD (mean difference, -1.25 days; 95% confidence interval, -2.18 to -0.33; P = .008) and increased odds of mortality (odds ratio, 2.27; 95% confidence interval, 1.13 to 4.56; P = .02) compared with the diuretic group. No differences were identified in terms of incidence of negative fluid balance by postoperative day 1, presence of peritonitis, and intensive care unit length of stay.

Conclusions: The meta-analysis did not identify differences between the 2 groups with regard to negative fluid balance after postoperative day 1, incidence of peritonitis, or length of intensive care unit stay. There is a need for large, prospective, multicenter studies to evaluate the benefits and complications associated with PD use further in selected children after congenital heart surgery. Because some of the outcomes were present in only 2 studies, results from the pooled analysis may be underpowered.
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http://dx.doi.org/10.1016/j.athoracsur.2019.03.066DOI Listing
September 2019

Usefulness of skeletal muscle area detected by computed tomography to predict mortality in patients undergoing transcatheter aortic valve replacement: a meta-analysis study.

Int J Cardiovasc Imaging 2019 Jun 26;35(6):1141-1147. Epub 2019 Mar 26.

Section of Interventional Cardiology, MedStar Washington Hospital Center, 110 Irving St NW, Washington, DC, 20010, USA.

Measures of sarcopenia, such as low muscle mass measured from the readily available preoperative computed tomography (CT) images, have been recently suggested as a predictor of outcomes in patients undergoing transcatheter aortic valve replacement (TAVR). However, results of these studies are variable and, therefore, we performed a systematic review of current literature to evaluate sarcopenia as a predictor of outcome post TAVR. The search was carried out in electronic databases between 2008 and 2018. We identified studies that reported CT-derived skeletal muscle area (SMA) and survival outcomes post TAVR. Studies were evaluated for the incidence of early (≤ 30 days) and late all-cause mortality (> 30 days) post TAVR. Eight studies with 1881 patients were included (mean age of 81.8 years ± 12, 55.9% men). Mean body mass index was (28.2 kg/m ± 1.1), mean Society of Thoracic Surgeons risk score (7.0 ± 0.6), and mean albumin level was (3.8 g/dL ± 0.1). Higher SMA was associated with lower long-term mortality [odds ratio (OR) 0.49, 95% confidence interval (CI) 0.28-0.83, p = 0.049], compared with low SMA. Also, higher SMA was associated with lower early mortality but was not statistically significant (OR 0.72; 95% CI 0.44-1.18; p = 0.285). CT-derived SMA provides value in predicting post-TAVR long-term outcomes for patients undergoing TAVR. This is a simple risk assessment tool that may help in making treatment decisions and help identifying and targeting high-risk patients with interventions to improve muscle mass prior to and following the procedures.
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http://dx.doi.org/10.1007/s10554-019-01582-0DOI Listing
June 2019

Efficacy of Pharmacological Therapies for the Prevention of Fractures in Postmenopausal Women: A Network Meta-Analysis.

J Clin Endocrinol Metab 2019 05;104(5):1623-1630

Evidence-Based Practice Research Program, Mayo Clinic, Rochester, Minnesota.

Background: Osteoporosis and osteopenia are associated with increased fracture incidence in postmenopausal women. We aimed to determine the comparative effectiveness of various available pharmacological therapies.

Methods: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ISI Web of Science, and Scopus for randomized controlled trials that enrolled postmenopausal women with primary osteoporosis and evaluated the risk of hip, vertebral, or nonvertebral fractures. A network meta-analysis was conducted using the multivariate random effects method.

Results: We included 107 trials (193,987 postmenopausal women; mean age, 66 years; 55% white; median follow-up, 28 months). A significant reduction in hip fractures was observed with romosozumab, alendronate, zoledronate, risedronate, denosumab, estrogen with progesterone, and calcium in combination with vitamin D. A significant reduction in nonvertebral fractures was observed with abaloparatide, romosozumab, denosumab, teriparatide, alendronate, risedronate, zoledronate, lasofoxifene, tibolone, estrogen with progesterone, and vitamin D. A significant reduction in vertebral fractures was observed with abaloparatide, teriparatide, parathyroid hormone 1-84, romosozumab, strontium ranelate, denosumab, zoledronate, risedronate, alendronate, ibandronate, raloxifene, bazedoxifene, lasofoxifene, estrogen with progesterone, tibolone, and calcitonin. Teriparatide, abaloparatide, denosumab, and romosozumab were associated with the highest relative risk reductions, whereas ibandronate and selective estrogen receptor modulators had lower efficacy. The evidence for the treatment of fractures with vitamin D and calcium remains limited despite numerous large trials.

Conclusions: This network meta-analysis provides comparative effective estimates for the various available treatments to reduce the risk of fragility fractures in postmenopausal women.
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http://dx.doi.org/10.1210/jc.2019-00192DOI Listing
May 2019
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