A higher risk of thrombosis has been described as a prominent feature of COVID-19. This systematic review synthesizes current data on thrombosis risk, prognostic implications, and anticoagulation effects in COVID-19. We included 37 studies from 4,070 unique citations. Meta-analysis was performed when feasible. Coagulopathy and thrombotic events were frequent among patients with COVID-19, and further increased in those with more severe forms of the disease. We also present guidance on the prevention and management of thrombosis from a multidisciplinary panel of specialists from the Mayo Clinic. The current certainty of evidence is generally very low, and continues to evolve.

ObjectiveLumbar puncture (LP) is a useful procedure which is performed for both diagnosis and treatment of numerous conditions affecting children and adults. The purpose of this study was to determine the frequency and cause of increased parental refusal to perform LP in the pediatric population.MethodA cross-sectional study was conducted from January 2018 to June 2019 at the Civil Hospital, Dow University of Health Sciences, pediatric department, Civil Hospital, Karachi. Over the 18-month time period, a total of 215 patients who had indications of LP were selected from the in-patient pediatrics department; the age range was between newborn to 12 years of age. The mode of research was a questionnaire and interview-based method that was conducted with guardians of minor patients to understand the extent of their knowledge and awareness about the LP procedure as well as its complication and the role of culture, education background, and financial status of the families which may lead to an increased likelihood of refusal.ResultThe frequency of LP refusal amongst the 215 families of the patients that were interviewed was found to be 32.6%. Mean age of the respondents was 30.98 years. The decision for LP was not significantly affected by the subjects’ gender (p=0.1), by the religious communities to which the families belonged (p=0.9), their ethnicities (0.52), or by the families’ financial status (p=0.4). It was observed that when indications for performing LP were appropriately explained, there was a significantly greater number of consents given as compared to when they were not made clear (p=0.009). Explaining the complications of the procedure did not considerably impact the decision for refusal of the procedure (p=0.1). The multi-variable logistic regression analysis model was applied to determine the likelihood of variables affecting refusal of LP and the logistic regression model was found to be statistically significant, χ2 (8) = 38.2 p < 0. 001.ConclusionLack of knowledge about the LP procedure and fear of ramification plays a conspicuous role in the denial of LP procedure by the guardians of minor patients. A better, simpler approach using standardized consent forms by the doctors may lead to the removal of the information gaps and can provide a better understanding about the concerned risks, the primary indications, and the benefits of this procedure to the guardians.

The coronavirus disease 2019 (COVID-19) pandemic requires making rapid decisions based on sparse and rapidly changing evidence. Evidence synthesis programs conduct systematic reviews for guideline developers, health systems clinicians, and decision-makers that usually take an average 6 to 8 months to complete. We present a framework for evidence synthesis programs to respond to pandemics that has proven feasible and practical during the COVID-19 response in a large multistate health system employing more than 78,000 people. The framework includes four components: an approach for conducting rapid reviews, a repository of rapid reviews, a registry for all original studies about COVID-19, and twice-weekly prioritized update of new evidence sent to key stakeholders. As COVID-19 will not be our last pandemic, we share the details of this framework to allow replication in other institutions and re-implementation in future pandemics.

Background Uncertainties exist about the use of mycophenolate mofetil (MMF) in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV), particularly for remission maintenance. Methods Systematic review and meta-analysis of phase II and III trials assessing the use of MMF in AAV (granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA)). A comprehensive search of several databases (Medline, EMBASE, Cochrane, Web of Science, Scopus) from inception to May 5th, 2020 has been conducted. Trial data were extracted to estimate odds ratios (ORs) and estimates (ES) for MMF efficacy (remission-induction and maintenance). Severe adverse effects (SAEs) were collected. Results From 565 articles captured, 10 met the predefined criteria, five phase II and five III trials, 4 assessed remission-induction, 3 remission-maintenance, 3 both. The pooled OR for remission-induction at 6 months was 1.06 (95% CI: [0.74, 1.52]), with no significant difference by subgroup meta-analysis of trials stratified by different study-level features (i.e. kidney disease, MPA, myeloperoxidase-ANCA-positivity, newly diagnosed disease) (p &gt; 0.05). The overall ES for remission-maintenance at the end of follow-up ranged between 51%-91% (I2 = 74.8%). Subgroup meta-analysis identified kidney involvement as a possible source of heterogeneity, yielding a significantly higher rate of sustained remission in trials enrolling only patients with kidney involvement (92% [76%-100%]) versus those enrolling patients with and without kidney involvement (56% [45%-66%]). Results were similar in multiple sensitivity analyses. During follow-up, the frequency of SAEs in MMF-based treatment arms was 31.8%. Conclusions In AAV, MMF use significantly associated with higher sustained remission rates in trials enrolling only patients with kidney involvement. These findings might influence clinical practice.

Context Individuals with diabetes or newly recognized hyperglycemia account for over 30% of noncritically ill hospitalized patients. Management of hyperglycemia in these patients is challenging. Objective To support development of the Endocrine Society Clinical Practice Guideline for management of hyperglycemia in adults hospitalized for noncritical illness or undergoing elective surgical procedures. Methods We searched several databases for studies addressing 10 questions provided by a guideline panel from the Endocrine Society. Meta-analysis was conducted when feasible. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess certainty of evidence. Results We included 94 studies reporting on 135 553 patients. Compared with capillary blood glucose, continuous glucose monitoring increased the number of patients identified with hypoglycemia and decreased mean daily blood glucose (BG) (very low certainty). Data on continuation of insulin pump therapy in hospitalized adults were sparse. In hospitalized patients receiving glucocorticoids, combination neutral protamine hagedorn (NPH) and basal-bolus insulin was associated with lower mean BG compared to basal-bolus insulin alone (very low certainty). Data on NPH insulin vs basal-bolus insulin in hospitalized adults receiving enteral nutrition were inconclusive. Inpatient diabetes education was associated with lower HbA1c at 3 and 6 months after discharge (moderate certainty) and reduced hospital readmissions (very low certainty). Preoperative HbA1c level &lt; 7% was associated with shorter length of stay, lower postoperative BG and a lower number of neurological complications and infections, but a higher number of reoperations (very low certainty). Treatment with glucagon-like peptide-1 agonists or dipeptidyl peptidase-4 inhibitors in hospitalized patients with type 2 diabetes and mild hyperglycemia was associated with lower frequency of hypoglycemic events than insulin therapy (low certainty). Caloric oral fluids before surgery in adults with diabetes undergoing surgical procedures did not affect outcomes (very low certainty). Counting carbohydrates for prandial insulin dosing did not affect outcomes (very low certainty). Compared with scheduled insulin (basal-bolus or basal insulin + correctional insulin), correctional insulin was associated with higher mean daily BG and fewer hypoglycemic events (low certainty). Conclusion The certainty of evidence supporting many hyperglycemia management decisions is low, emphasizing importance of shared decision-making and consideration of other decisional factors.

ObjectivesTo evaluate the association of study design features and treatment effects in randomised controlled trials (RCTs) evaluating therapies for individuals with chronic medical conditions.DesignMeta-epidemiological study.SettingRCTs 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 measuresThe association between trial design features and the effect size, reporting a ratio of ORs (ROR) and 95% confidence interval (CI).ResultsWe 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).ConclusionThe 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 numberNot applicable.

The platelet count threshold for World Health Organization classification system-compliant diagnosis of essential thrombocythemia (ET) is ≥450 × 10 9 /L. 1 Extreme thrombocytosis (ExT), on the other hand, is arbitrarily defined by platelet count of ≥1000 × 10 9 /L and occurs in approximately 22% of patients with ET, at time of diagnosis. 2 Note, ExT is most frequent in the context of young patients with ET with incidence rates of 44%/29%/29% in patients aged ≤40, 41-60, and > 60 years respectively. 3 The presence of ExT in ET has been shown to confer a lower risk for arterial thrombosis 4 ; additionally, its association with hemorrhage has been linked to aspirin use. 5 Nevertheless, ExT often poses a therapeutic dilemma with low-risk young ET patients in terms of the need for cytoreductive therapy, stemming from an unsubstantiated concern for a heightened thrombotic risk, or to ameliorate bleeding tendency and microvascular symptoms. In light of inadequate published literature on ExT in ET, we compiled this report specifically focusing on young patients. Our main objectives were to (a) characterize the clinical phenotype of "young" platelet millionaires with ET via comparison with their counterparts without ExT and (b) assess long term outlook in terms of thrombosis, myelofibrotic/leukemic transformation and overall survival. Study patients were retrospectively recruited from the Mayo Clinic myeloproliferative neoplasms (MPN) database which is maintained under an institutional review board approved protocol and included 3023 MPN patients evaluated over five decades (1967 through 2017). 2 Of 1070 adult patients with ET; 192 (18%) were aged below 40 years. Major arterial thrombosis included myocardial infarction, angina, cerebrovascular accidents, transient ischemic attack, peripheral arterial thrombosis, aortic thrombosis, mesenteric artery thrombosis, and central retinal thrombosis. Major venous thrombosis included deep venous thrombosis, pulmonary embolism, portal/ splenic/mesenteric/hepatic vein thrombosis, and cerebral sinus thrombosis. Bleeding events that required red cell transfusions were

Lymphangioleiomyomatosis (LAM) is a rare disease with variable presentations. The neoplastic cells in LAM demonstrate a unique and diagnostically important “myomelanocytic” phenotype. Cytologic reports of LAM are infrequent and have not in the past emphasized the floating island pattern in which circumscribed aggregates of lesional cells are rimmed by appliques of flattened endothelium. This case illustrates the cytology of LAM and emphasizes that the floating island cytoarchitectural pattern more classically associated with entities such as hepatocellular carcinomas may be seen in cytological preparations of LAM at unanticipated body sites.