Murad, M Hassan

Abstract Background: Central nervous system (CNS) complications are among the most common, devastating sequelae of sickle cell disease (SCD) occurring throughout the lifespan. Objective: These evidence-based guidelines of the American Society of Hematology are intended to support the SCD community in decisions about prevention, diagnosis, and treatment of the most common neurological morbidities in SCD. Methods: The Mayo Evidence-Based Practice Research Program supported the guideline development process, including updating or performing systematic evidence reviews. 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. Results: The panel placed a higher value on maintaining cognitive function than on being alive with significantly less than baseline cognitive function. The panel developed 19 recommendations with evidence-based strategies to prevent, diagnose, and treat CNS complications of SCD in low-middle– and high-income settings. Conclusions: Three of 19 recommendations immediately impact clinical care. These recommendations include: use of transcranial Doppler ultrasound screening and hydroxyurea for primary stroke prevention in children with hemoglobin SS (HbSS) and hemoglobin Sβ0 (HbSβ0) thalassemia living in low-middle–income settings; surveillance for developmental delay, cognitive impairments, and neurodevelopmental disorders in children; and use of magnetic resonance imaging of the brain without sedation to detect silent cerebral infarcts at least once in early-school-age children and once in adults with HbSS or HbSβ0 thalassemia. Individuals with SCD, their family members, and clinicians should become aware of and implement these recommendations to reduce the burden of CNS complications in children and adults with SCD.

Abstract Objective The objective is to provide an update of the 2019 Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Clinical Practice Guideline for the pharmacological management of osteoporosis in postmenopausal women using romosozumab. Conclusions We reviewed findings from the meta-analysis and primary clinical trials assessing the efficacy of romosozumab, a monoclonal antibody targeting sclerostin, for the prevention of fractures and concluded that this agent can be considered a treatment option for postmenopausal women at very high risk for osteoporotic fracture. The romosozumab label has a boxed warning, recommending careful consideration by the treating clinician as to cardiovascular risk profile in the individual woman who might receive this agent, since clinical trial data from an active comparator study show an imbalance in serious cardiovascular adverse events between romosozumab and alendronate.

Background Smoking adversely impacts pain-related outcomes of spinal cord stimulation (SCS). However, the proportion of SCS patients at risk of worse outcomes is limited by an incomplete knowledge of smoking prevalence in this population. Thus, the primary aim of this systematic review is to determine the prevalence of smoking in adults with chronic pain treated with SCS. Methods A comprehensive search of databases from 1 January 1980 to 3 January 2019 was conducted. Eligible study designs included (1) randomized trials; (2) prospective and retrospective cohort studies; and (3) cross-sectional studies. The risk of bias was assessed using a tool specifically developed for prevalence studies. A total of 1619 records were screened, 19 studies met inclusion criteria, and the total number of participants was 10 838. Results Thirteen studies had low or moderate risk of bias, and six had a high risk of bias. All 19 studies reported smoking status and the pooled prevalence was 38% (95% CI 30% to 47%). The pooled prevalence in 6 studies of peripheral vascular diseases was 56% (95% CI 42% to 69%), the pooled prevalence of smoking in 11 studies of lumbar spine diagnoses was 28% (95% CI 20% to 36%) and the pooled prevalence in 2 studies of refractory angina was 44% (95% CI 31% to 58%). Conclusions The estimated prevalence of smoking in SCS patients is 2.5 times greater than the general population. Future research should focus on development, testing and deployment of tailored smoking cessation treatments for SCS patients.

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

Objective To investigate the effect of therapies on radiographic progression in patients with axial spondyloarthritis (SpA). Methods A comprehensive database search for studies assessing radiographic progression in axial SpA (particular treatment versus no treatment of interest) was performed. Study‐specific standardized mean differences in treatment outcomes at 2 and ≥4 years were estimated and combined using random‐effects models. Results Twenty‐four studies in patients with axial SpA were identified, of which 18 involved tumor necrosis factor inhibitors ( TNF i), 8 involved nonsteroidal antiinflammatory drugs ( NSAID s), and 1 involved secukinumab. Spinal radiographic progression, as measured by the modified Stoke Ankylosing Spondylitis Spine Score ( mSASSS ), was not significantly different between TNF i‐treated and biologics‐naive patients at 2 years ( mSASSS difference −0.73 [95% confidence interval (95% CI ) −1.52, 0.12], I 2 = 28%) and ≥4 years ( mSASSS difference −2.03 [95% CI −4.63, 0.72], I 2 = 63%). Sensitivity analyses restricted to studies with a low risk of bias showed a significant difference in spinal radiographic progression between TNF i‐treated and biologics‐naive patients at ≥4 years ( mSASSS difference −2.17 [95% CI −4.19, −0.15]). No significant difference in spinal radiographic progression was observed between NSAID ‐treated and control patients ( mSASSS difference −0.30 [95% CI −2.62, 1.31], I 2 = 71%) or between secukinumab‐treated and biologics‐naive patients ( mSASSS difference −0.34 [95% CI −0.85, 0.17]). With regard to treatment differences in patients with nonradiographic axial SpA or in patients with radiographic progression measured using the sacroiliac joint score, an insufficient number of studies were available for analysis. Conclusion Although no significant protective effect of TNF i treatment on spinal radiographic progression was seen over the course of 2 years or ≥4 years in patients with axial SpA, our analysis restricted to studies with a low risk of bias showed a protective effect of TNF i after ≥4 years. Therefore, long‐term TNF i exposure might confer beneficial effects on spinal radiographic progression in axial SpA. No difference in radiographic progression at 2 years was seen in either the NSAID or secukinumab treatment groups compared to their controls. Future studies should explore the effects of biologic treatment on radiographic progression, as well as the effects of long‐term biologics exposure, in patients with early axial SpA or those with nonradiographic axial SpA.

ABSTRACT Aims Left atrial (LA) mechanical function may play a significant role in the development and progression of heart failure with preserved ejection fraction (HFpEF). We performed a systematic review and meta-analysis to evaluate association of impaired LA function with outcomes in HFpEF. Methods and results Multiple databases were searched for original studies measuring different phases of LA function in HFpEF patients. Comparative LA function between HFpEF patients and healthy controls was assessed by pooling weighted mean differences (WMD). Adjusted hazard ratios (HRs) with 95% confidence intervals were pooled to evaluate the prognostic utility of LA function. Twenty-two studies (2 trials, 20 observational) comprising 1974 HFpEF patients and 751 healthy controls were included. HFpEF patients had decreased LA reservoir [WMD = −12.21% (−15.47, −8.95); P < 0.001], LA conduit [WMD = −5.68% (−8.56, −2.79); P < 0.001], and pump [WMD = −11.07% (−14.81, −7.34); P < 0.001] emptying fractions compared with controls. LA reservoir [WMD = −13.38% (−16.07, −10.68); P < 0.001], conduit [WMD = −4.09% (−6.77, −1.42); P = 0.003], and pump [WMD = −3.53% (−4.47, −2.59); P < 0.001] strains were also significantly lower in HFpEF patients. Decreased LA reservoir strain [HR 1.24 (1.02, 1.50); P = 0.03] was significantly associated with risk of composite all-cause mortality or heart failure hospitalization. Conclusions Impaired LA function appears to have diagnostic and prognostic value in HFpEF, but whether indices of LA function truly refine discrimination for diagnosis or prognosis remains to be fully determined. Larger studies are needed to better evaluate associations between LA function and clinical outcomes and the role of LA function as a target for novel HFpEF therapies.

Abstract Purpose We aim to evaluate the association of PCOS with eating, sleeping and sexual function disorders. Methods A comprehensive search including MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through 01 August 2018 was conducted for studies reporting the prevalence of any eating, sleep or sexual function disorders in patients with PCOS. Independent reviewers selected studies and extracted data. A random‐effects model was utilized to generate pooled odds ratio (OR) and 95% confidence intervals (CI) for binary outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Results We included 36 studies reporting on 349,529 patients. Compared to women without PCOS, women with PCOS were more likely to have bulimia nervosa (OR 1.37; %CI, 1.17 to 1.60), binge eating (OR 2.95; 95%CI, 1.61 to 5.42), or any eating disorder (OR 1.96; 95% CI 1.18 to 3.24); but not anorexia nervosa (OR 0.92; 95%CI, 0.78 to 1.10). Women with PCOS were more likely to have sleep disorders like hypersomnia (OR 4.39; %CI, 1.07 to 18.07) and obstructive sleep apnoea (OR 10.81; %CI, 2.39 to 48.83). Women with PCOS had lower sexual satisfaction as measured on a visual analogue scale (MD −29.67; 95% CI, −36.97 to −22.37), but no difference in Total Female Sexual Function Index (MD −0.06; 95% CI, −0.51 to 0.38). Conclusion PCOS can be associated with an increased risk of eating and sleeping disorders as well as decreased sexual satisfaction. Screening for these disorders in women with PCOS may allow early intervention and improve quality of life.

Background Thromboprophylaxis is routinely used with lenalidomide‐based regimens in multiple myeloma because of a substantial risk of venous thromboembolism (VTE). However, little is known about the incidence of VTE with contemporary lenalidomide‐based regimens. The objective of the current study was to estimate the incidence of VTE despite thromboprophylaxis with currently used lenalidomide‐based regimens in patients with myeloma. Methods The Ovid MEDLINE, Embase, and Cochrane databases were queried from study inception to January 2019 for keywords to cover the following concepts: “lenalidomide,” “venous thromboembolism,” and “multiple myeloma.” Phase 1, 2, and 3 clinical trials evaluating lenalidomide‐based regimens with thromboprophylaxis were included. The pooled incidence rate of VTE was estimated using a random‐effects model. Results The search generated 1372 citations, with 51 clinical trials and 9069 patients included for analysis. The most common thromboprophylaxis agents were aspirin, low‐molecular‐weight heparin or warfarin, administered either per risk‐stratification or at investigators' discretion. The pooled incidence of VTE in trials of patients who had newly diagnosed and relapsed/refractory myeloma was 6.2% (95% CI, 5.4%‐7.1%) over median treatment durations ranging from 2 to 34 cycles, which translated into 1.2 VTE events per 100 patient‐cycles (95% CI, 0.9‐1.7 VTE events per 100 patient‐cycles). Among contemporary regimens, the risk of VTE was low with combined lenalidomide and low‐dose dexamethasone (0.2 [95% CI, 0.1‐0.6] events/100 patient‐cycles) and lenalidomide maintenance (0.0 [95% CI, 0.0‐0.7] events per 100 patient‐cycles). VTE risk was higher with combined lenalidomide and low‐dose dexamethasone plus proteasome inhibitors (1.3 [95% CI, 0.7‐2.3] events per 100 patient‐cycles). Conclusions Despite adequate thromboprophylaxis, lenalidomide‐based regimens have a substantial risk of VTE in controlled clinical trial settings. Further studies are needed on new thromboprophylaxis strategies with regimens that have a high VTE risk.