Citations

Abstract Objectives We aimed to identify migraine treatment features preferred by patients and treatment outcomes most valued by patients. Background The values and preferences of people living with migraine are critical for both the choice of acute therapy and management approach of migraine. Methods We conducted a qualitative evidence synthesis. Two reviewers independently selected studies, appraised methodological quality, and undertook a framework synthesis. We developed summary of findings tables following the approach of Grading of Recommendations, Assessment, Development and Evaluations Confidence in the Evidence from Reviews of Qualitative Research to assess confidence in the findings. Results Of 1691 candidate references, we included 19 studies (21 publications) involving 459 patients. The studies mostly recruited White women from North America (11 studies) and Europe (8 studies). We identified eight themes encompassing features preferred by patients in a migraine treatment process. Themes described a treatment process that included shared decision‐making, a tailored approach, trust in health‐care professionals, sharing of knowledge and diversity of treatment options, a holistic approach that does not just address the headache, ease of communication especially for complex treatments, a non‐undermining approach, and reciprocity with mutual respect between patient and provider. In terms of the treatment itself, seven themes emerged including patients’ preferences for nonpharmacologic treatment, high effectiveness, rapidity of action, long‐lasting effect, lower cost and more accessibility, self‐management/self‐delivery option that increases autonomy, and a mixed preference for abortive versus prophylactic treatments. The treatment outcomes that have high value to patients included maintaining or improving function; avoiding side effects, potential for addiction to medications, and pain reoccurrence; and avoiding non‐headache symptoms such as nausea, vomiting, and sensitivity to light or sounds. Conclusion Patient values and preferences were individually constructed, varied widely, and could be at odds with conventional medical perspectives and evidence of treatment effects. Considering the availability of numerous treatments for acute migraine, it is necessary that decision‐making incorporates patient values and preferences identified in qualitative research. The findings of this qualitative synthesis can be used to facilitate an individually tailored approach, strengthen the patient–health‐care system relationship, and guide choices and decisions in the context of a clinical encounter or a clinical practice guideline.

AbstractContextHypercalcemia is a common complication of malignancy that is associated with high morbidity and mortality.ObjectiveTo support development of the Endocrine Society Clinical Practice Guideline for the treatment of hypercalcemia of malignancy in adults.MethodsWe searched multiple databases for studies that addressed 8 clinical questions prioritized by a guideline panel from the Endocrine Society. Quantitative and qualitative synthesis was performed. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess certainty of evidence.ResultsWe reviewed 1949 citations, from which we included 21 studies. The risk of bias for most of the included studies was moderate. A higher proportion of patients who received bisphosphonate achieved resolution of hypercalcemia when compared to placebo. The incidence rate of adverse events was significantly higher in the bisphosphonate group. Comparing denosumab to bisphosphonate, there was no significant difference in the rate of patients who achieved resolution of hypercalcemia. Two-thirds of patients with refractory/recurrent hypercalcemia of malignancy who received denosumab following bisphosphonate therapy achieved resolution of hypercalcemia. Addition of calcitonin to bisphosphonate therapy did not affect the resolution of hypercalcemia, time to normocalcemia, or hypocalcemia. Only indirect evidence was available to address questions on the management of hypercalcemia in tumors associated with high calcitriol levels, refractory/recurrent hypercalcemia of malignancy following the use of bisphosphonates, and the use of calcimimetics in the treatment of hypercalcemia associated with parathyroid carcinoma. The certainty of the evidence to address all 8 clinical questions was low to very low.ConclusionThe evidence summarized in this systematic review addresses the benefits and harms of treatments of hypercalcemia of malignancy. Additional information about patients’ values and preferences, and other important decisional and contextual factors is needed to facilitate the development of clinical recommendations.

Abstract Context Interventions targeting hypoglycemia in people with diabetes are important for improving quality of life and reducing morbidity and mortality. Objective To support development of the Endocrine Society Clinical Practice Guideline for management of individuals with diabetes at high risk for hypoglycemia. 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 149 studies reporting on 43 344 patients. Continuous glucose monitoring (CGM) reduced episodes of severe hypoglycemia in patients with type 1 diabetes (T1D) and reduced the proportion of patients with hypoglycemia (blood glucose [BG] levels <54 mg/dL). There were no data on use of real-time CGM with algorithm-driven insulin pumps vs multiple daily injections with BG testing in people with T1D. CGM in outpatients with type 2 diabetes taking insulin and/or sulfonylureas reduced time spent with BG levels under 70 mg/dL. Initiation of CGM in hospitalized patients at high risk for hypoglycemia reduced episodes of hypoglycemia with BG levels lower than 54 mg/dL and time spent under 54 mg/dL. The proportion of patients with hypoglycemia with BG levels lower than 70 mg/dL and lower than 54 mg/dL detected by CGM was significantly higher than point-of-care BG testing. We found no data evaluating continuation of personal CGM in the hospital. Use of an inpatient computerized glycemic management program utilizing electronic health record data was associated with fewer patients with and episodes of hypoglycemia with BG levels lower than 70 mg/dL and fewer patients with severe hypoglycemia compared with standard care. Long-acting basal insulin analogs were associated with less hypoglycemia. Rapid-acting insulin analogs were associated with reduced severe hypoglycemia, though there were more patients with mild to moderate hypoglycemia. Structured diabetes education programs reduced episodes of severe hypoglycemia and time below 54 mg/dL in outpatients taking insulin. Glucagon formulations not requiring reconstitution were associated with longer times to recovery from hypoglycemia, although the proportion of patients who recovered completely from hypoglycemia was not different between the 2 groups. Conclusion This systematic review summarized the best available evidence about several interventions addressing hypoglycemia in people with diabetes. This evidence base will facilitate development of clinical practice guidelines by the Endocrine Society.

ImportanceProstate cancer (PCa) is marked by disparities in clinical outcomes by race, ethnicity, and age. Equitable enrollment in clinical trials is fundamental to promoting health equity.ObjectiveTo evaluate disparities in the inclusion of racial and ethnic minority groups and older adults across PCa clinical trials.Data SourcesMEDLINE, Embase, and ClinicalTrials.gov were searched to identify primary trial reports from each database's inception through February 2021. Global incidence in age subgroups and US population-based incidence in racial and ethnic subgroups were acquired from the Global Burden of Disease and Surveillance, Epidemiology, and End Results 21 incidence databases respectively.Study SelectionAll phase 2/3 randomized PCa clinical trials were eligible for age disparity analyses. Trials recruiting exclusively from the US were eligible for primary racial and ethnic disparity analyses.Data Extraction and SynthesisThis study was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Data were pooled using a random-effects model.Main Outcomes and MeasuresEnrollment incidence ratios (EIRs), trial proportions (TPs) of participants 65 years or older or members of a racial and ethnic subgroup divided by global incidence in the corresponding age group, or US population–based incidence in the corresponding racial and ethnic subgroup, were calculated. Meta-regression was used to explore associations between trial characteristics and EIRs and trends in EIRs during the past 3 decades.ResultsOf 9552 participants among trials reporting race, 954 (10.8%) were African American/Black, 80 (1.5%) were Asian/Pacific Islander, and 8518 (78.5) were White. Of 65 US trials, 45 (69.2%) reported race and only 9 (13.8%) reported data on all 5 US racial categories. Of 286 global trials, 75 (26.2%) reported the enrollment proportion of older adults. Outcomes by race and age were reported in 2 (3.1%) and 41 (15.0%) trials, respectively. Black (EIR, 0.70; 95% CI, 0.59-0.83) and Hispanic (EIR, 0.70; 95% CI, 0.59-0.83) patients were significantly underrepresented in US trials. There was no disparity in older adult representation (TP, 21 143 [71.1%]; EIR, 1.00; 95% CI, 0.95-1.05). The representation of Black patients was lower in larger trials (meta-regression coefficient, −0.06; 95% CI, −0.10 to −0.02; P = .002).Conclusions and RelevanceThe results of this meta-analysis suggest that Black and Hispanic men are underrepresented in trials compared with their share of PCa incidence. The representation of Black patients has consistently remained low during the past 2 decades.

AbstractContextIndividuals with diabetes or newly recognized hyperglycemia account for over 30% of noncritically ill hospitalized patients. Management of hyperglycemia in these patients is challenging.ObjectiveTo support development of the Endocrine Society Clinical Practice Guideline for management of hyperglycemia in adults hospitalized for noncritical illness or undergoing elective surgical procedures.MethodsWe 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.ResultsWe 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 < 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).ConclusionThe certainty of evidence supporting many hyperglycemia management decisions is low, emphasizing importance of shared decision-making and consideration of other decisional factors.

Abstract MSC (a.k.a. mesenchymal stem cell or medicinal signaling cell) cell therapies show promise in decreasing mortality in acute respiratory distress syndrome (ARDS) and suggest benefits in treatment of COVID-19-related ARDS. We performed a meta-analysis of published trials assessing the efficacy and adverse events (AE) rates of MSC cell therapy in individuals hospitalized for COVID-19. Systematic searches were performed in multiple databases through November 3, 2021. Reports in all languages, including randomized clinical trials (RCTs), non-randomized interventional trials, and uncontrolled trials, were included. Random effects model was used to pool outcomes from RCTs and non-randomized interventional trials. Outcome measures included all-cause mortality, serious adverse events (SAEs), AEs, pulmonary function, laboratory, and imaging findings. A total of 736 patients were identified from 34 studies, which included 5 RCTs (n = 235), 7 non-randomized interventional trials (n = 370), and 22 uncontrolled comparative trials (n = 131). Patients aged on average 59.4 years and 32.2% were women. When compared with the control group, MSC cell therapy was associated with a reduction in all-cause mortality (RR = 0.54, 95% CI: 0.35-0.85, I 2 = 0.0%), reduction in SAEs (IRR = 0.36, 95% CI: 0.14-0.90, I 2 = 0.0%) and no significant difference in AE rate. A sub-group with pulmonary function studies suggested improvement in patients receiving MSC. These findings support the potential for MSC cell therapy to decrease all-cause mortality, reduce SAEs, and improve pulmonary function compared with conventional care. Large-scale double-blinded, well-powered RCTs should be conducted to further explore these results.

Introduction: Theobromine is a naturally occurring substance found in cocoa products. Theobromine may have beneficial cardiovascular effects through various mechanisms. We used the NHANES database to analyze associations between theobromine consumption and cardiovascular health outcomes. Methods: The NHANES database represents a nationally representative population which was used to construct the study population from 1996-2016. We assessed multiple demographic factors and compared differences amongst those who consumed various amounts of theobromine to those who did not. The primary outcome measures were hypertension and lipid profiles. Results: Among 42,038 NHANES survey participants, 37569 and 4469 of the participants reported never consuming theobromine and consuming theobromine, respectively. Table 1 demonstrates baseline characteristics of those reporting no theobromine consumption in comparison to the theobromine consuming participants (100-400md/g and 400-850mg/d). Moderate to high amounts of theobromine consumption was observed in participants who were older with higher BMI and more education and were more likely to be tobacco users in comparison to those with no theobromine consumption (all p-values <0.05). Moderate to high theobromine consumption was also observed to be associated with a higher hemoglobin level, higher LDL cholesterol, lower HDL cholesterol, and prevalence of hypertension (all p-values <0.05). Conclusions: We observed that individuals who consumed moderate to high amounts of theobromine had associated improvements in lipid profile parameters as well as reduced blood pressure. Theobromine may represent a complementary non-pharmacologic supplementation to typical lifestyle modifications to improve cardiovascular outcomes. Further prospective studies are needed to better clarify this potential association.

Introduction: Current proposed Dietary Guidelines for Americans, 2015 suggested replacing refined grains (e.g., white rice) with whole grains (e.g., brown rice) for improved health outcomes; however, the association between white rice consumption and risk of cardiovascular disease (CVD) was not fully investigated. The purpose of this study was to explore the associations between rice consumption, metabolic syndrome and cardiovascular disease. Methods: We conducted a comprehensive search of MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Scopus, and the Cochrane Central Register of Controlled Trials from database inception through May 2015. Observational studies were included if the studies reported hazard ratios (HRs) or odd ratios (ORs) of the associations between rice consumption, metabolic syndrome and cardiovascular disease. Data were extracted by one reviewer and then reviewed by two independent reviewers. Conflicts were resolved through consensus. Using the DerSimonian and Laird random effects models, we calculated pooled HRs and pooled ORs with 95% confidence intervals (95% CIs). Subgroup analyses were performed to explore potential sources of heterogeneity. The quality of the included studies and publication bias were assessed. Results: Out of 343 retrieved articles, we identified 6 cross-sectional and 9 prospective studies with a total of 575,852 individuals with 24,649 total CVD events and 4,409 metabolic syndrome cases. The highest category of white rice consumption (≥5 times/week) was associated with a 37% higher risk of metabolic syndrome (pooled OR, 1.37; 95% CI: 1.03-1.84; p<0.001; I 2 = 78.7%) but not a higher risk of cardiovascular disease (pooled HR, 1.01; 95% CI: 0.95-1.08; p=0.65; I 2 = 0%), compared to the lowest category (≤1 time/month). Conclusions: Higher white rice consumption has not been shown to increase the risk of cardiovascular diseases but may be associated with increased risk of metabolic syndrome.

Introduction: Obesity is a growing global health problem associated with substantial morbidity and mortality. The risk of obesity on incident new-onset heart failure is controversial. The aim of this systematic review and meta-analysis was to explore the association between overweight, obesity and incident new-onset heart failure. Methods: We systematically searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Scopus, and the Cochrane Central Register of Controlled Trials from database inception through April 2015. Prospective cohort studies were included if the studies reported hazard ratios (HRs) of the association between overweight or obesity and new-onset heart failure (HF) relative to individuals with normal weight. Data were extracted by one reviewer followed by independent screening and extraction of study characteristics and outcome data by two other reviewers. Conflicts were resolved through consensus. Random-effects meta-analyses were used to pool the hazard ratio from the included studies. Subgroup analyses were performed to explore the potential sources of heterogeneity. Results: Out of 1,865 retrieved articles, we identified 10 relevant studies. Median follow-up was 12 years with a total of 82,167 individuals and 4,570 total HF events. Compared to normal body weight (body mass index (BMI) <25 kg/m2), overweight (BMI 25-29.9 kg/m2) was associated with 27% higher risk of new-onset heart failure events (pooled HR, 1.27; 95% confidence intervals (95% CI): 1.15-1.41; p<0.001; I 2 = 0%) and obesity (BMI ≥30 kg/m2) was associated with a two-fold increased risk for new-onset heart failure events (pooled HR, 2.09; 95% CI, 1.68-2.60; p<0.001; I 2 = 67.8%). Conclusions: Compared with normal-weight individuals, both overweight and obesity were independently associated with significantly higher incidence of heart failure. These results highlight the need for better understanding of mechanisms of obesity and heart failure.

Polygenic diseases, which are genetic disorders caused by the combined action of multiple genes, pose unique and significant challenges for the diagnosis and management of affected patients. A major goal of cardiovascular medicine has been to understand how genetic variation leads to the clinical heterogeneity seen in polygenic cardiovascular diseases (CVDs). Recent advances and emerging technologies in artificial intelligence (AI), coupled with the ever-increasing availability of next generation sequencing (NGS) technologies, now provide researchers with unprecedented possibilities for dynamic and complex biological genomic analyses. Combining these technologies may lead to a deeper understanding of heterogeneous polygenic CVDs, better prognostic guidance, and, ultimately, greater personalized medicine. Advances will likely be achieved through increasingly frequent and robust genomic characterization of patients, as well the integration of genomic data with other clinical data, such as cardiac imaging, coronary angiography, and clinical biomarkers. This review discusses the current opportunities and limitations of genomics; provides a brief overview of AI; and identifies the current applications, limitations, and future directions of AI in genomics.