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The U.S. Food and Drug Administration recently approved 2 genetic therapies for sickle cell disease. Both therapies increase the production of nonsickling red blood cells, either fetal hemoglobin or a gene therapy–derived hemoglobin similar to hemoglobin A. In addition, both therapies require collection of a patient's stem cells, modification of the cells in the laboratory, high-dose chemotherapy to remove existing bone marrow cells, and a single-dose infusion of the patient's modified stem cells. This article uses 2 different cost-effectiveness models to estimate whether these therapies provide enough value to justify their high costs. Visual Abstract. Gene Therapy Versus Common Care for Eligible Individuals With Sickle Cell Disease in the United States: The U.S. Food and Drug Administration recently approved 2 genetic therapies for sickle cell disease. Both therapies increase the production of nonsickling red blood cells, either fetal hemoglobin or a gene therapy–derived hemoglobin similar to hemoglobin A. In addition, both therapies require collection of a patient's stem cells, modification of the cells in the laboratory, high-dose chemotherapy to remove existing bone marrow cells, and a single-dose infusion of the patient's modified stem cells. This article uses 2 different cost-effectiveness models to estimate whether these therapies provide enough value to justify their high costs. Background: Sickle cell disease (SCD) and its complications contribute to high rates of morbidity and early mortality and high cost in the United States and African heritage community. Objective: To evaluate the cost-effectiveness of gene therapy for SCD and its value-based prices (VBPs). Design: Comparative modeling analysis across 2 independently developed simulation models (University of Washington Model for Economic Analysis of Sickle Cell Cure [UW-MEASURE] and Fred Hutchinson Institute Sickle Cell Disease Outcomes Research and Economics Model [FH-HISCORE]) using the same databases. Data Sources: Centers for Medicare & Medicaid Services claims data, 2008 to 2016; published literature. Target Population: Persons eligible for gene therapy. Time Horizon: Lifetime. Perspective: U.S. health care sector and societal. Intervention: Gene therapy versus common care. Outcome Measures: Incremental cost-effectiveness ratios (ICERs), equity-informed VBPs, and price acceptability curves. Results of Base-Case Analysis: At an assumed $2 million price for gene therapy, UW-MEASURE and FH-HISCORE estimated ICERs of $193 000 per QALY and $427 000 per QALY, respectively, under the health care sector perspective. Corresponding estimates from the societal perspective were $126 000 per QALY and $281 000 per QALY. The difference in results between models stemmed primarily from considering a slightly different target population and incorporating the quality-of-life (QOL) effects of splenic sequestration, priapism, and acute chest syndrome in the UW model. From a societal perspective, acceptable (>90% confidence) VBPs ranged from $1 million to $2.5 million depending on the use of alternative effective metrics or equity-informed threshold values. Results of Sensitivity Analysis: Results were sensitive to the costs of myeloablative conditioning before gene therapy, effect on caregiver QOL, and effect of gene therapy on long-term survival. Limitation: The short-term effects of gene therapy on vaso-occlusive events were extrapolated from 1 study. Conclusion: Gene therapy for SCD below a $2 million price tag is likely to be cost-effective when applying a societal perspective at an equity-informed threshold for cost-effectiveness analysis. Primary Funding Source: National Heart, Lung, and Blood Institute. [ABSTRACT FROM AUTHOR]

Background: Yoga is a mind-body exercise typically done in groups in person, but this delivery method can be inconvenient, inaccessible, and costly. Effective online programs may increase access to exercise for knee osteoarthritis.Objective: To evaluate the effectiveness of an unsupervised 12-week online yoga program.Design: Two-group superiority randomized trial. (Australian New Zealand Clinical Trials Registry: ACTRN12620000012976).Setting: Community.Participants: 212 adults with symptomatic knee osteoarthritis.Intervention: Both groups received online osteoarthritis information (control). The yoga group also received access to an unsupervised online yoga program delivered via prerecorded videos over 12 weeks (1 video per week, with each session to be performed 3 times per week), with optional continuation thereafter.Measurements: Primary outcomes were changes in knee pain during walking (0 to 10 on a numerical rating scale) and physical function (0 to 68 on the Western Ontario and McMaster Universities Osteoarthritis Index) at 12 weeks (primary time point) and 24 weeks, analyzed using mixed-effects linear regression models. Secondary outcomes were self-reported overall knee pain, stiffness, depression, anxiety, stress, global change, quality of life, self-efficacy, fear of movement, and balance confidence. Adverse events were also collected.Results: A total of 195 (92%) and 189 (89%) participants provided 12- and 24-week primary outcomes, respectively. Compared with control at 12 weeks, yoga improved function (between-group mean difference in change, -4.0 [95% CI, -6.8 to -1.3]) but not knee pain during walking (between-group mean difference in change, -0.6 [CI, -1.2 to 0.1]), with more yoga participants than control participants achieving the minimal clinically important difference (MCID) for both outcomes. At 12 weeks, knee stiffness, quality of life, and arthritis self-efficacy improved more with yoga than the control intervention. Benefits were not maintained at 24 weeks. Adverse events were minor.Limitation: Participants were unblinded.Conclusion: Compared with online education, an unsupervised online yoga program improved physical function but not knee pain at 12 weeks in people with knee osteoarthritis, although the improvement did not reach the MCID and was not sustained at 24 weeks.Primary Funding Source: National Health and Medical Research Council and Centres of Research Excellence. [ABSTRACT FROM AUTHOR]

Background: Rhythm control is associated with lower risk for adverse cardiovascular outcomes compared with usual care among patients recently diagnosed with atrial fibrillation (AF) with a CHA2DS2-VASc score of approximately 2 or greater in EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial).Objective: To investigate whether the results can be generalized to patients with low stroke risk.Design: Population-based cohort study.Setting: Nationwide claims database of the Korean National Health Insurance Service.Participants: 54 216 patients with AF having early rhythm control (antiarrhythmic drugs or ablation) or rate control therapy that was initiated within 1 year of the AF diagnosis.Measurements: The effect of early rhythm control on the primary composite outcome of cardiovascular death, ischemic stroke, hospitalization for heart failure, or myocardial infarction was compared between eligible and ineligible patients for EAST-AFNET 4 (CHA2DS2-VASc score, approximately 0 to 1) using propensity overlap weighting.Results: In total, 37 557 study participants (69.3%) were eligible for the trial (median age, 70 years; median CHA2DS2-VASc score, 4), among whom early rhythm control was associated with lower risk for the primary composite outcome than rate control (hazard ratio, 0.86 [95% CI, 0.81 to 0.92]). Among the 16 659 low-risk patients (30.7%) who did not meet the inclusion criteria (median age, 54 years; median CHA2DS2-VASc score, 1), early rhythm control was consistently associated with lower risk for the primary outcome (hazard ratio, 0.81 [CI, 0.66 to 0.98]). No significant differences in safety outcomes were found between the rhythm and rate control strategies regardless of trial eligibility.Limitation: Residual confounding.Conclusion: In routine clinical practice, the beneficial association between early rhythm control and cardiovascular complications was consistent among low-risk patients regardless of trial eligibility.Primary Funding Source: The Ministry of Health and Welfare and the Ministry of Food and Drug Safety, Republic of Korea. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) infection can be cured, and the United States has joined the World Health Organization in calling for HCV elimination by 2030. However, historically low uptake of HCV treatment among people who inject drugs (PWID) threatens HCV elimination and exacerbates social and racial health disparities.Objective: To assess whether all-oral HCV treatments were accessed by PWID and reduced liver disease burden and mortality.Design: Community-based, longitudinal cohort study of persons with a history of injection drug use.Setting: Baltimore, Maryland.Participants: 1323 participants enrolled in the ALIVE (AIDS Linked to the IntraVenous Experience) study from 2006 to 2019 and chronically infected with HCV.Measurements: Liver stiffness measures (LSMs) by transient elastography, HCV RNA, and mortality from the National Death Index.Results: Among 1323 persons with evidence of chronic HCV infection at baseline, the median age was 49 years. Most were Black (82%), male (71%), and HIV-negative (66%). The proportion in whom HCV RNA was detected decreased from 100% (by definition) in 2006 to 48% in 2019. Across 10 350 valid LSMs, cirrhosis was detected in 15% of participants in 2006, 19% in 2015, and 8% in 2019. Undetectable HCV RNA was significantly associated with reduced odds of cirrhosis (adjusted odds ratio, 0.28 [95% CI, 0.17 to 0.45]) and reduced all-cause mortality risk (adjusted hazard ratio, 0.54 [CI, 0.38 to 0.77]).Limitation: Noninvasive markers of liver fibrosis have not been validated in persons with sustained virologic response.Conclusion: Many community-based PWID in Baltimore are receiving HCV treatment, which is associated with sharp decreases in liver disease and mortality. Additional efforts will be needed to reduce residual barriers to treatment and to eliminate HCV as a public health threat for PWID.Primary Funding Source: National Institutes of Health. [ABSTRACT FROM AUTHOR]

Background: Evidence on the risk for cardiovascular events associated with use of first-line sodium-glucose cotransporter-2 inhibitors (SGLT-2i) compared with metformin is limited.Objective: To assess cardiovascular outcomes among adults with type 2 diabetes (T2D) who initiated first-line treatment with SGLT-2i versus metformin.Design: Population-based cohort study.Setting: Claims data from 2 large U.S. commercial and Medicare databases (April 2013 to March 2020).Participants: Patients with T2D aged 18 years and older (>65 years in Medicare) initiating treatment with SGLT-2i or metformin during April 2013 to March 2020, without any use of antidiabetic medications before cohort entry, were identified. After 1:2 propensity score matching in each database, pooled hazard ratios (HRs) and 95% CIs were reported.Intervention: First-line SGLT-2i (canagliflozin, empagliflozin, or dapagliflozin) or metformin.Measurements: Primary outcomes were a composite of hospitalization for myocardial infarction (MI), hospitalization for ischemic or hemorrhagic stroke or all-cause mortality (MI/stroke/mortality), and a composite of hospitalization for heart failure (HHF) or all-cause mortality (HHF/mortality). Safety outcomes including genital infections were assessed.Results: Among 8613 first-line SGLT-2i initiators matched to 17 226 metformin initiators, SGLT-2i initiators had a similar risk for MI/stroke/mortality (HR, 0.96; 95% CI, 0.77 to 1.19) and a lower risk for HHF/mortality (HR, 0.80; CI, 0.66 to 0.97) during a mean follow-up of 12 months. Initiators receiving SGLT-2i showed a lower risk for HHF (HR, 0.78; CI, 0.63 to 0.97), a numerically lower risk for MI (HR, 0.70; CI, 0.48 to 1.00), and similar risk for stroke, mortality, and MI/stroke/HHF/mortality compared with metformin. Initiators receiving SGLT-2i had a higher risk for genital infections (HR, 2.19; CI, 1.91 to 2.51) and otherwise similar safety as those receiving metformin.Limitation: Treatment selection was not randomized.Conclusion: As first-line T2D treatment, initiators receiving SGLT-2i showed a similar risk for MI/stroke/mortality, lower risk for HHF/mortality and HHF, and a similar safety profile except for an increased risk for genital infections compared with those receiving metformin.Primary Funding Source: Brigham and Women's Hospital and Harvard Medical School. [ABSTRACT FROM AUTHOR]

Background: Primary hyperparathyroidism (PHPT) is a common endocrine disorder associated with increased risk for fractures, cardiovascular disease, kidney disease, and cancer and increased mortality. In mild PHPT with modest hypercalcemia and without known morbidities, parathyroidectomy (PTX) is debated because no long-term randomized trials have been performed.Objective: To examine the effect of PTX on mild PHPT with regard to mortality (primary end point) and key morbidities (secondary end point).Design: Prospective randomized controlled trial. (ClinicalTrials.gov: NCT00522028).Setting: Eight Scandinavian referral centers.Patients: From 1998 to 2005, 191 patients with mild PHPT were included.Intervention: Ninety-five patients were randomly assigned to PTX, and 96 were assigned to observation without intervention (OBS).Measurements: Date and causes of death were obtained from the Swedish and Norwegian Cause of Death Registries 10 years after randomization and after an extended observation period lasting until 2018. Morbidity events were prospectively registered annually.Results: After 10 years, 15 patients had died (8 in the PTX group and 7 in the OBS group). Within the extended observation period, 44 deaths occurred, which were evenly distributed between groups (24 in the PTX group and 20 in the OBS group). A total of 101 morbidity events (cardiovascular events, cerebrovascular events, cancer, peripheral fractures, and renal stones) were also similarly distributed between groups (52 in the PTX group and 49 in the OBS group). During the study, a total of 16 vertebral fractures occurred in 14 patients (7 in each group).Limitation: During the study period, 23 patients in the PTX group and 27 in the OBS group withdrew.Conclusion: Parathyroidectomy does not appear to reduce morbidity or mortality in mild PHPT. Thus, no evidence of adverse effects of observation was seen for at least a decade with respect to mortality, fractures, cancer, cardiovascular and cerebrovascular events, or renal morbidities.Primary Funding Source: Swedish government, Norwegian Research Council, and South-Eastern Norway Regional Health Authority. [ABSTRACT FROM AUTHOR]

Background: Two recent randomized clinical trials of escalating doses of allopurinol for the progression of chronic kidney disease (CKD) reported no benefits but potentially increased risk for death. Whether the risk could occur in patients with gout and concurrent CKD remains unknown.Objective: To examine the relation of allopurinol initiation, allopurinol dose escalation, and achieving target serum urate (SU) level after allopurinol initiation to all-cause mortality in patients with both gout and CKD.Design: Cohort study.Setting: The Health Improvement Network U.K. primary care database (2000 to 2019).Participants: Patients aged 40 years or older who had gout and concurrent moderate-to-severe CKD.Measurements: The association between allopurinol initiation and all-cause mortality over 5-year follow-up in propensity score (PS)-matched cohorts was examined. Analysis of hypothetical trials were emulated: achieving target SU level (<0.36 mmol/L) versus not achieving target SU level and dose escalation versus no dose escalation for mortality over 5-year follow-up in allopurinol initiators.Results: Mortality was 4.9 and 5.8 per 100 person-years in 5277 allopurinol initiators and 5277 PS-matched noninitiators, respectively (hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.93]). In the target trial emulation analysis, the HR of mortality for the achieving target SU level group compared with the not achieving target SU level group was 0.87 (CI, 0.75 to 1.01); the HR of mortality for allopurinol in the dose escalation group versus the no dose escalation group was 0.88 (CI, 0.73 to 1.07).Limitation: Residual confounding cannot be ruled out.Conclusion: In this population-based data, neither allopurinol initiation, nor achieving target SU level with allopurinol, nor allopurinol dose escalation was associated with increased mortality in patients with gout and concurrent CKD.Primary Funding Source: Project Program of National Clinical Research Center for Geriatric Disorders. [ABSTRACT FROM AUTHOR]

Type 1 diabetes mellitus (T1DM) is an endocrine disorder in which pancreatic β cells stop producing insulin, typically due to autoimmune destruction. This results in hyperglycemia and ketosis; thus, insulin replacement is vital to management. Incidence peaks in puberty and early adulthood, but onset can occur at any age. However, prevalence is highest among adults because persons with T1DM live for many years. Symptoms include polyuria, polydipsia, and weight loss. Acute complications include diabetic ketoacidosis, which requires urgent management. Long-term complications include microvascular and macrovascular disease. Patients with T1DM are at higher risk for other autoimmune diseases and psychosocial issues. Management should focus on optimizing glucose control to reduce acute and long-term complications. [ABSTRACT FROM AUTHOR]

Description: The American College of Physicians (ACP) developed this guideline to provide clinical recommendations on the role of colonoscopy for diagnostic evaluation of colorectal cancer (CRC) after a presumed diagnosis of acute left-sided colonic diverticulitis and on the role of pharmacologic, nonpharmacologic, and elective surgical interventions to prevent recurrence after initial treatment of acute complicated and uncomplicated left-sided colonic diverticulitis. This guideline is based on the current best available evidence about benefits and harms, taken in the context of costs and patient values and preferences.Methods: The ACP Clinical Guidelines Committee (CGC) based these recommendations on a systematic review on the role of colonoscopy after acute left-sided colonic diverticulitis and pharmacologic, nonpharmacologic, and elective surgical interventions after initial treatment. The systematic review evaluated outcomes rated by the CGC as critical or important. This guideline was developed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method.Target Audience and Patient Population: The target audience is all clinicians, and the target patient population is adults with recent episodes of acute left-sided colonic diverticulitis.Recommendation1: ACP suggests that clinicians refer patients for a colonoscopy after an initial episode of complicated left-sided colonic diverticulitis in patients who have not had recent colonoscopy (conditional recommendation; low-certainty evidence).Recommendation2: ACP recommends against clinicians using mesalamine to prevent recurrent diverticulitis (strong recommendation; high-certainty evidence).Recommendation3: ACP suggests that clinicians discuss elective surgery to prevent recurrent diverticulitis after initial treatment in patients who have either uncomplicated diverticulitis that is persistent or recurs frequently or complicated diverticulitis (conditional recommendation; low-certainty evidence). The informed decision whether or not to undergo surgery should be personalized based on a discussion of potential benefits, harms, costs, and patient's preferences. [ABSTRACT FROM AUTHOR]

Background: Benign adrenal tumors are commonly discovered on cross-sectional imaging. Mild autonomous cortisol secretion (MACS) is regularly diagnosed, but its effect on cardiometabolic disease in affected persons is ill defined.Objective: To determine cardiometabolic disease burden and steroid excretion in persons with benign adrenal tumors with and without MACS.Design: Cross-sectional study.Setting: 14 endocrine secondary and tertiary care centers (recruitment from 2011 to 2016).Participants: 1305 prospectively recruited persons with benign adrenal tumors.Measurements: Cortisol excess was defined by clinical assessment and the 1-mg overnight dexamethasone-suppression test (serum cortisol: <50 nmol/L, nonfunctioning adrenal tumor [NFAT]; 50 to 138 nmol/L, possible MACS [MACS-1]; >138 nmol/L and absence of typical clinical Cushing syndrome [CS] features, definitive MACS [MACS-2]). Net steroid production was assessed by multisteroid profiling of 24-hour urine by tandem mass spectrometry.Results: Of the 1305 participants, 49.7% had NFAT (n = 649; 64.1% women), 34.6% had MACS-1 (n = 451; 67.2% women), 10.7% had MACS-2 (n = 140; 73.6% women), and 5.0% had CS (n = 65; 86.2% women). Prevalence and severity of hypertension were higher in MACS-2 and CS than NFAT (adjusted prevalence ratios [aPRs] for hypertension: MACS-2, 1.15 [95% CI, 1.04 to 1.27], and CS, 1.37 [CI, 1.16 to 1.62]; aPRs for use of ≥3 antihypertensives: MACS-2, 1.31 [CI, 1.02 to 1.68], and CS, 2.22 [CI, 1.62 to 3.05]). Type 2 diabetes was more prevalent in CS than NFAT (aPR, 1.62 [CI, 1.08 to 2.42]) and more likely to require insulin therapy for MACS-2 (aPR, 1.89 [CI, 1.01 to 3.52]) and CS (aPR, 3.06 [CI, 1.60 to 5.85]). Urinary multisteroid profiling revealed an increase in glucocorticoid excretion from NFAT over MACS-1 and MACS-2 to CS, whereas androgen excretion decreased.Limitations: Cross-sectional design; possible selection bias.Conclusion: A cardiometabolic risk condition, MACS predominantly affects women and warrants regular assessment for hypertension and type 2 diabetes.Primary Funding Source: Diabetes UK, the European Commission, U.K. Medical Research Council, the U.K. Academy of Medical Sciences, the Wellcome Trust, the U.K. National Institute for Health Research, the U.S. National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research. [ABSTRACT FROM AUTHOR]

Background: An osteoporosis drug holiday is recommended for most patients after 3 to 5 years of therapy. Risedronate has a shorter half-life than alendronate, and thus the residual length of fracture protection may be shorter.Objective: To examine the comparative risks of drug holidays after long-term (≥3 years) risedronate versus alendronate therapy.Design: Population-based, matched, cohort study.Setting: Province-wide health care administrative databases providing comprehensive coverage to Ontario residents aged 65 years or older between November 2000 and March 2020.Patients: Persons aged 66 years or older who had long-term risedronate therapy and a drug holiday were matched 1:1 on propensity score to those who had long-term alendronate therapy and a drug holiday.Measurements: The primary outcome was hip fracture within 3 years after a 120-day ascertainment period. Secondary analyses included shorter follow-up and sex-specific estimates. Cox proportional hazards models were used to estimate hazard ratios (HRs) for fracture risk between groups.Results: A total of 25 077 propensity score-matched pairs were eligible (mean age, 81 years; 81% women). Hip fracture rates were higher among risedronate than alendronate drug holidays (12.4 and 10.6 events, respectively, per 1000 patient-years; HR, 1.18 [95% CI, 1.04 to 1.34]; 915 total hip fractures). The association was attenuated when any fracture was included as the outcome (HR, 1.07 [CI, 1.00 to 1.16]) and with shorter drug holidays (1 year: HR, 1.03 [CI, 0.85 to 1.24]; 2 years: HR, 1.14 [CI, 0.96 to 1.32]).Limitation: Analyses were limited to health care administrative data (potential unmeasured confounding), and some secondary analyses contained few events.Conclusion: Drug holidays after long-term therapy with risedronate were associated with a small increase in risk for hip fracture compared with alendronate drug holidays. Future research should examine how best to mitigate this risk.Primary Funding Source: Canadian Institutes of Health Research. [ABSTRACT FROM AUTHOR]

Background: How diagnostic strategies for suspected pulmonary embolism (PE) perform in relevant patient subgroups defined by sex, age, cancer, and previous venous thromboembolism (VTE) is unknown.Purpose: To evaluate the safety and efficiency of the Wells and revised Geneva scores combined with fixed and adapted D-dimer thresholds, as well as the YEARS algorithm, for ruling out acute PE in these subgroups.Data Sources: MEDLINE from 1 January 1995 until 1 January 2021.Study Selection: 16 studies assessing at least 1 diagnostic strategy.Data Extraction: Individual-patient data from 20 553 patients.Data Synthesis: Safety was defined as the diagnostic failure rate (the predicted 3-month VTE incidence after exclusion of PE without imaging at baseline). Efficiency was defined as the proportion of individuals classified by the strategy as "PE considered excluded" without imaging tests. Across all strategies, efficiency was highest in patients younger than 40 years (47% to 68%) and lowest in patients aged 80 years or older (6.0% to 23%) or patients with cancer (9.6% to 26%). However, efficiency improved considerably in these subgroups when pretest probability-dependent D-dimer thresholds were applied. Predicted failure rates were highest for strategies with adapted D-dimer thresholds, with failure rates varying between 2% and 4% in the predefined patient subgroups.Limitations: Between-study differences in scoring predictor items and D-dimer assays, as well as the presence of differential verification bias, in particular for classifying fatal events and subsegmental PE cases, all of which may have led to an overestimation of the predicted failure rates of adapted D-dimer thresholds.Conclusion: Overall, all strategies showed acceptable safety, with pretest probability-dependent D-dimer thresholds having not only the highest efficiency but also the highest predicted failure rate. From an efficiency perspective, this individual-patient data meta-analysis supports application of adapted D-dimer thresholds.Primary Funding Source: Dutch Research Council. (PROSPERO: CRD42018089366). [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal bleeding (GIB) rates for direct oral anticoagulants (DOACs) and warfarin have been extensively compared. However, population-based studies comparing GIB rates among different DOACs are limited.Objective: To compare rates of GIB among apixaban, dabigatran, and rivaroxaban.Design: Nationwide population-based cohort study.Setting: Landspítali-The National University Hospital of Iceland and the 4 regional hospitals in Iceland.Patients: New users of apixaban, dabigatran, and rivaroxaban from 2014 to 2019.Measurements: Rates of GIB were compared using inverse probability weighting, Kaplan-Meier survival estimates, and Cox regression.Results: In total, 2157 patients receiving apixaban, 494 patients receiving dabigatran, and 3217 patients receiving rivaroxaban were compared. For all patients, rivaroxaban had higher overall rates of GIB (3.2 vs. 2.5 events per 100 person-years; hazard ratio [HR], 1.42 [95% CI, 1.04 to 1.93]) and major GIB (1.9 vs. 1.4 events per 100 person-years; HR, 1.50 [CI, 1.00 to 2.24]) compared with apixaban. Rivaroxaban also had higher GIB rates than dabigatran, with similar point estimates, although the CIs were wider and included the possibility of a null effect. When only patients with atrial fibrillation were included, rivaroxaban was associated with higher rates of overall GIB than apixaban (HR, 1.40 [CI, 1.01 to 1.94]) or dabigatran (HR, 2.04 [CI, 1.17 to 3.55]). Dabigatran was associated with lower rates of upper GIB than rivaroxaban in both analyses.Limitations: Unmeasured confounding and small subgroup analyses.Conclusion: Rivaroxaban was associated with higher GIB rates than apixaban and dabigatran regardless of treatment indication.Primary Funding Source: Icelandic Centre for Research and Landspítali-The National University Hospital of Iceland. [ABSTRACT FROM AUTHOR]

Background: Acupuncture has promising effects on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), but high-quality evidence is scarce.Objective: To assess the long-term efficacy of acupuncture for CP/CPPS.Design: Multicenter, randomized, sham-controlled trial. (ClinicalTrials.gov: NCT03213938).Setting: Ten tertiary hospitals in China.Participants: Men with moderate to severe CP/CPPS, regardless of prior exposure to acupuncture.Intervention: Twenty sessions of acupuncture or sham acupuncture over 8 weeks, with 24-week follow-up after treatment.Measurements: The primary outcome was the proportion of responders, defined as participants who achieved a clinically important reduction of at least 6 points from baseline on the National Institutes of Health Chronic Prostatitis Symptom Index at weeks 8 and 32. Ascertainment of sustained efficacy required the between-group difference to be statistically significant at both time points.Results: A total of 440 men (220 in each group) were recruited. At week 8, the proportions of responders were 60.6% (95% CI, 53.7% to 67.1%) in the acupuncture group and 36.8% (CI, 30.4% to 43.7%) in the sham acupuncture group (adjusted difference, 21.6 percentage points [CI, 12.8 to 30.4 percentage points]; adjusted odds ratio, 2.6 [CI, 1.8 to 4.0]; P < 0.001). At week 32, the proportions were 61.5% (CI, 54.5% to 68.1%) in the acupuncture group and 38.3% (CI, 31.7% to 45.4%) in the sham acupuncture group (adjusted difference, 21.1 percentage points [CI, 12.2 to 30.1 percentage points]; adjusted odds ratio, 2.6 [CI, 1.7 to 3.9]; P < 0.001). Twenty (9.1%) and 14 (6.4%) adverse events were reported in the acupuncture and sham acupuncture groups, respectively. No serious adverse events were reported.Limitation: Sham acupuncture might have had certain physiologic effects.Conclusion: Compared with sham therapy, 20 sessions of acupuncture over 8 weeks resulted in greater improvement in symptoms of moderate to severe CP/CPPS, with durable effects 24 weeks after treatment.Primary Funding Source: China Academy of Chinese Medical Sciences and the National Administration of Traditional Chinese Medicine. [ABSTRACT FROM AUTHOR]

Background: Patients with sickle cell disease (SCD) have vaso-occlusive crises (VOCs). Infusion centers (ICs) are alternatives to emergency department (ED) care and may improve patient outcomes.Objective: To assess whether care in ICs or EDs leads to better outcomes for the treatment of uncomplicated VOCs.Design: Prospective cohort. (ClinicalTrials.gov: NCT02411396).Setting: 4 U.S. sites, with recruitment between April 2015 and December 2016.Participants: Adults with SCD living within 60 miles of a study site.Measurements: Participants were followed for 18 months after enrollment. Outcomes of interest were time to first dose of parenteral pain medication, whether pain reassessment was completed within 30 minutes after the first dose, and patient disposition on discharge from the acute care visit. Treatment effects for ICs versus EDs were estimated using a time-varying propensity score adjustment.Results: Researchers enrolled 483 participants; the 269 who had acute care visits on weekdays are included in this report. With inverse probability of treatment-weighted adjustment, the mean time to first dose was 62 minutes in ICs and 132 minutes in EDs; the difference was 70 minutes (95% CI, 54 to 98 minutes; E-value, 2.8). The probability of pain reassessment within 30 minutes of the first dose of parenteral pain medication was 3.8 times greater (CI, 2.63 to 5.64 times greater; E-value, 4.7) in the IC than the ED. The probability that a participant's visit would end in admission to the hospital was smaller by a factor of 4 (0.25 [CI, 0.18 to 0.33]) with treatment in an IC versus an ED.Limitation: The study was restricted to participants with uncomplicated VOCs.Conclusion: In adults with SCD having a VOC, treatment in an IC is associated with substantially better outcomes than treatment in an ED.Primary Funding Source: Patient-Centered Outcomes Research Institute. [ABSTRACT FROM AUTHOR]

Background: Hospitalized patients with comorbid substance use disorders (SUDs) are at high risk for poor outcomes, including readmission and emergency department (ED) use.Objective: To determine whether patient navigation services reduce hospital readmissions.Design: Randomized controlled trial comparing Navigation Services to Avoid Rehospitalization (NavSTAR) versus treatment as usual (TAU). (ClinicalTrials.gov: NCT02599818).Setting: Urban academic hospital in Baltimore, Maryland, with an SUD consultation service.Participants: 400 hospitalized adults with comorbid SUD (opioid, cocaine, or alcohol).Intervention: NavSTAR used proactive case management, advocacy, service linkage, and motivational support to resolve internal and external barriers to care and address SUD, medical, and basic needs for 3 months after discharge.Measurements: Data on inpatient readmissions (primary outcome) and ED visits for 12 months were obtained for all participants via the regional health information exchange. Entry into SUD treatment, substance use, and related outcomes were assessed at 3-, 6-, and 12-month follow-up.Results: Participants had high levels of acute care use: 69% had an inpatient readmission and 79% visited the ED over the 12-month observation period. Event rates per 1000 person-days were 6.05 (NavSTAR) versus 8.13 (TAU) for inpatient admissions (hazard ratio, 0.74 [95% CI, 0.58 to 0.96]; P= 0.020) and 17.66 (NavSTAR) versus 27.85 (TAU) for ED visits (hazard ratio, 0.66 [CI, 0.49 to 0.89]; P= 0.006). Participants in the NavSTAR group were less likely to have an inpatient readmission within 30 days than those receiving TAU (15.5% vs. 30.0%; P< 0.001) and were more likely to enter community SUD treatment after discharge (P= 0.014; treatment entry within 3 months, 50.3% NavSTAR vs. 35.3% TAU).Limitation: Single-site trial, which limits generalizability.Conclusion: Patient navigation reduced inpatient readmissions and ED visits in this clinically challenging sample of hospitalized patients with comorbid SUDs.Primary Funding Source: National Institute on Drug Abuse. [ABSTRACT FROM AUTHOR]

Background: Total knee replacement (TKR) is an effective and cost-effective strategy for treating end-stage knee osteoarthritis. Greater risk for complications among TKR recipients with a body mass index (BMI) of 40 kg/m2 or greater has raised concerns about the value of TKR in this population.Objective: To assess the value of TKR in recipients with a BMI of 40 kg/m2 or greater using a cost-effectiveness analysis.Design: Osteoarthritis Policy Model to assess long-term clinical benefits, costs, and cost-effectiveness of TKR in patients with a BMI of 40 kg/m2 or greater.Data Sources: Total knee replacement parameters from longitudinal studies and published literature, and costs from Medicare Physician Fee Schedules, the Healthcare Cost and Utilization Project, and published data.Target Population: Recipients of TKR with a BMI of 40 kg/m2 or greater in the United States.Time Horizon: Lifetime.Perspective: Health care sector.Intervention: Total knee replacement.Outcome Measures: Cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs), discounted at 3% annually.Results Of Base-case Analysis: Total knee replacement increased QALYs by 0.71 year and lifetime medical costs by $25 200 among patients aged 50 to 65 years with a BMI of 40 kg/m2 or greater, resulting in an ICER of $35 200. Total knee replacement in patients older than 65 years with a BMI of 40 kg/m2 or greater increased QALYs by 0.39 year and costs by $21 100, resulting in an ICER of $54 100.Results Of Sensitivity Analysis: In TKR recipients with a BMI of 40 kg/m2 or greater and diabetes and cardiovascular disease, ICERs were below $75 000 per QALY. Results were most sensitive to complication rates and preoperative pain levels. In the probabilistic sensitivity analysis, at a $55 000-per-QALY willingness-to-pay threshold, TKR had a 100% and 90% likelihood of being a cost-effective strategy for patients aged 50 to 65 years and patients older than 65 years, respectively.Limitation: Data are derived from several sources.Conclusion: From a cost-effectiveness perspective, TKR offers good value in patients with a BMI of 40 kg/m2 or greater, including those with multiple comorbidities.Primary Funding Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. [ABSTRACT FROM AUTHOR]

Description: The Kidney Disease: Improving Global Outcomes (KDIGO) organization developed a clinical practice guideline in 2020 for the management of patients with diabetes and chronic kidney disease (CKD).Methods: The KDIGO Work Group (WG) was tasked with developing the guideline for diabetes management in CKD. It defined the scope of the guideline, gathered evidence, determined systematic review topics, and graded evidence that had been summarized by an evidence review team. The English-language literature searches, which were initially done through October 2018, were updated in February 2020. The WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of the recommendations. Expert judgment was used to develop consensus practice points supplementary to the evidence-based graded recommendations. The guideline document underwent open public review. Comments from various stakeholders, subject matter experts, and industry and national organizations were considered before the document was finalized.Recommendations: The guideline includes 12 recommendations and 48 practice points for clinicians caring for patients with diabetes and CKD. This synopsis focuses on the key recommendations pertinent to the following issues: comprehensive care needs, glycemic monitoring and targets, lifestyle interventions, antihyperglycemic therapies, and educational and integrated care approaches. [ABSTRACT FROM AUTHOR]

Background: Growing evidence indicates that peripheral neuropathy (PN) is common even in the absence of diabetes. However, the clinical sequelae of PN have not been quantified in the general population.Objective: To assess the associations of PN with all-cause and cardiovascular mortality in the general adult population of the United States.Design: Prospective cohort study.Setting: NHANES (National Health and Nutrition Examination Survey), 1999 to 2004.Participants: 7116 adults aged 40 years or older who had standardized monofilament testing for PN.Measurements: Cox regression to evaluate the associations of PN with all-cause and cardiovascular mortality after adjustment for demographic and cardiovascular risk factors, overall and stratified by diabetes status.Results: The overall prevalence of PN (±SE) was 13.5% ± 0.5% (27.0% ± 1.4% in adults with diabetes and 11.6% ± 0.5% in adults without diabetes). During a median follow-up of 13 years, 2128 participants died, including 488 of cardiovascular causes. Incidence rates (per 1000 person-years) of all-cause mortality were 57.6 (95% CI, 48.4 to 68.7) in adults with diabetes and PN, 34.3 (CI, 30.3 to 38.8) in adults with PN but no diabetes, 27.1 (CI, 23.4 to 31.5) in adults with diabetes but no PN, and 13.0 (CI, 12.1 to 14.0) in adults with no diabetes and no PN. In adjusted models, PN was significantly associated with all-cause mortality (hazard ratio [HR], 1.49 [CI, 1.15 to 1.94]) and cardiovascular mortality (HR, 1.66 [CI, 1.07 to 2.57]) in participants with diabetes. In those without diabetes, PN was significantly associated with all-cause mortality (HR, 1.31 [CI, 1.15 to 1.50]), but the association between PN and cardiovascular mortality was not statistically significant after adjustment (HR, 1.27 [CI, 0.98 to 1.66]).Limitation: Prevalent cardiovascular disease was self-reported, and PN was defined by monofilament testing only.Conclusion: Peripheral neuropathy was common and was independently associated with mortality in the U.S. population, even in the absence of diabetes. These findings suggest that decreased sensation in the foot may be an underrecognized risk factor for death in the general population.Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases and National Heart, Lung, and Blood Institute of the National Institutes of Health. [ABSTRACT FROM AUTHOR]

Background: Few studies have examined primary care management for acute sciatica, including referral to physical therapy.Objective: To evaluate whether early referral to physical therapy reduced disability more than usual care (UC) alone for patients with acute sciatica.Design: Randomized controlled clinical trial. (ClinicalTrials.gov: NCT02391350).Setting: 2 health care systems in Salt Lake City, Utah.Patients: 220 adults aged 18 to 60 years with sciatica of less than 90 days' duration who were making an initial primary care consultation.Intervention: All participants received imaging and medication at the discretion of the primary care provider before enrollment. A total of 110 participants randomly assigned to UC were provided 1 session of education, and 110 participants randomly assigned to early physical therapy (EPT) were provided 1 education session and then referred for 4 weeks of physical therapy, including exercise and manual therapy.Measurements: The primary outcome was the Oswestry Disability Index (OSW) score after 6 months. Secondary outcomes were pain intensity, patient-reported treatment success, health care use, and missed workdays.Results: Participants in the EPT group had greater improvement from baseline to 6 months for the primary outcome (relative difference, -5.4 points [95% CI, -9.4 to -1.3 points]; P = 0.009). The OSW and several secondary outcomes favored EPT after 4 weeks. After 1 year, between-group differences favored EPT for the OSW (relative difference, -4.8 points [CI, -8.9 to -0.7 points]) and back pain intensity (relative difference, -1.0 points [CI, -1.6 to -0.4 points]). The EPT group was more likely to self-report treatment success after 1 year (45.2%) than the UC group (27.6%) (relative risk, 1.6 [CI, 1.1 to 2.4]). There were no significant differences in health care use or missed workdays.Limitation: The patients and providers were unblinded, and specific physical therapy interventions responsible for effects could not be determined.Conclusion: Referral from primary care to physical therapy for recent-onset sciatica improved disability and other outcomes compared with UC.Primary Funding Source: Agency for Healthcare Research and Quality. [ABSTRACT FROM AUTHOR]

Background: Current pharmacologic therapies for patients with osteoarthritis are suboptimal.Objective: To determine the efficacy of Curcuma longa extract (CL) for reducing knee symptoms and effusion-synovitis in patients with symptomatic knee osteoarthritis and knee effusion-synovitis.Design: Randomized, double-blind, placebo-controlled trial. (Australian New Zealand Clinical Trials Registry: ACTRN12618000080224).Setting: Single-center study with patients from southern Tasmania, Australia.Participants: 70 participants with symptomatic knee osteoarthritis and ultrasonography-defined effusion-synovitis.Intervention: 2 capsules of CL (n = 36) or matched placebo (n = 34) per day for 12 weeks.Measurements: The 2 primary outcomes were changes in knee pain on a visual analogue scale (VAS) and effusion-synovitis volume on magnetic resonance imaging (MRI). The key secondary outcomes were change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and cartilage composition values. Outcomes were assessed over 12 weeks.Results: CL improved VAS pain compared with placebo by -9.1 mm (95% CI, -17.8 to -0.4 mm [P = 0.039]) but did not change effusion-synovitis volume (3.2 mL [CI, -0.3 to 6.8 mL]). CL also improved WOMAC knee pain (-47.2 mm [CI, -81.2 to -13.2 mm]; P = 0.006) but not lateral femoral cartilage T2 relaxation time (-0.4 ms [CI, -1.1 to 0.3 ms]). The incidence of adverse events was similar in the CL (n = 14 [39%]) and placebo (n = 18 [53%]) groups (P = 0.16); 2 events in the CL group and 5 in the placebo group may have been treatment related.Limitation: Modest sample size and short duration.Conclusion: CL was more effective than placebo for knee pain but did not affect knee effusion-synovitis or cartilage composition. Multicenter trials with larger sample sizes are needed to assess the clinical significance of these findings.Primary Funding Source: University of Tasmania and Natural Remedies Private Limited. [ABSTRACT FROM AUTHOR]

The past 2 decades have seen a revolution in legal access to cannabis, driven largely by activists and business interests. As a result, the population of cannabis users nationwide-especially daily users-has grown significantly. An estimated 4.5-7 million persons in the United States now meet criteria for cannabis use disorder annually. This article focuses on the effects of cannabis use, intoxication, and withdrawal while also reviewing the developmental pathways of cannabis use disorder as well as evidence-based pharmacologic and psychosocial treatments. [ABSTRACT FROM AUTHOR]

Background: Midterm effects of bariatric surgery on patients with obesity and hypertension remain uncertain.Objective: To determine the 3-year effects of Roux-en-Y gastric bypass (RYGB) on blood pressure (BP) compared with medical therapy (MT) alone.Design: Randomized clinical trial. (ClinicalTrials.gov: NCT01784848).Setting: Investigator-initiated study at Heart Hospital (HCor), São Paulo, Brazil.Participants: Patients with hypertension receiving at least 2 medications at maximum doses or more than 2 medications at moderate doses and with a body mass index (BMI) between 30.0 and 39.9 kg/m2 were randomly assigned (1:1 ratio).Intervention: RYGB plus MT or MT alone.Measurements: The primary outcome was at least a 30% reduction in total number of antihypertensive medications while maintaining BP less than 140/90 mm Hg. Key secondary outcomes were number of antihypertensive medications, hypertension remission, and BP control according to current guidelines (<130/80 mm Hg).Results: Among 100 patients (76% female; mean BMI, 36.9 kg/m2 [SD, 2.7]), 88% from the RYGB group and 80% from the MT group completed follow-up. At 3 years, the primary outcome occurred in 73% of patients from the RYGB group compared with 11% of patients from the MT group (relative risk, 6.52 [95% CI, 2.50 to 17.03]; P < 0.001). Of the randomly assigned participants, 35% and 31% from the RYGB group and 2% and 0% from the MT group achieved BP less than 140/90 mm Hg and less than 130/80 mm Hg without medications, respectively. Median (interquartile range) number of medications in the RYGB and MT groups at 3 years was 1 (0 to 2) and 3 (2.8 to 4), respectively (P < 0.001). Total weight loss was 27.8% and -0.1% in the RYGB and MT groups, respectively. In the RYGB group, 13 patients developed hypovitaminosis B12 and 2 patients required reoperation.Limitation: Single-center, nonblinded trial.Conclusion: RYGB is an effective strategy for midterm BP control and hypertension remission, with fewer medications required in patients with hypertension and obesity.Primary Funding Source: Ethicon, represented in Brazil by Johnson & Johnson do Brasil. [ABSTRACT FROM AUTHOR]

Background: Influenza may contribute to the burden of acute cardiovascular events during annual influenza epidemics.Objective: To examine acute cardiovascular events and determine risk factors for acute heart failure (aHF) and acute ischemic heart disease (aIHD) in adults with a hospitalization associated with laboratory-confirmed influenza.Design: Cross-sectional study.Setting: U.S. Influenza Hospitalization Surveillance Network during the 2010-to-2011 through 2017-to-2018 influenza seasons.Participants: Adults hospitalized with laboratory-confirmed influenza and identified through influenza testing ordered by a practitioner.Measurements: Acute cardiovascular events were ascertained using discharge codes from the International Classification of Diseases (ICD), Ninth Revision, Clinical Modification, and ICD, 10th Revision. Age, sex, race/ethnicity, tobacco use, chronic conditions, influenza vaccination, influenza antiviral medication, and influenza type or subtype were included as exposures in logistic regression models, and marginal adjusted risk ratios and 95% CIs were estimated to describe factors associated with aHF or aIHD.Results: Among 89 999 adults with laboratory-confirmed influenza, 80 261 had complete medical record abstractions and available ICD codes (median age, 69 years [interquartile range, 54 to 81 years]) and 11.7% had an acute cardiovascular event. The most common such events (non-mutually exclusive) were aHF (6.2%) and aIHD (5.7%). Older age, tobacco use, underlying cardiovascular disease, diabetes, and renal disease were significantly associated with higher risk for aHF and aIHD in adults hospitalized with laboratory-confirmed influenza.Limitation: Underdetection of cases was likely because influenza testing was based on practitioner orders. Acute cardiovascular events were identified by ICD discharge codes and may be subject to misclassification bias.Conclusion: In this population-based study of adults hospitalized with influenza, almost 12% of patients had an acute cardiovascular event. Clinicians should ensure high rates of influenza vaccination, especially in those with underlying chronic conditions, to protect against acute cardiovascular events associated with influenza.Primary Funding Source: Centers for Disease Control and Prevention. [ABSTRACT FROM AUTHOR]

About 15% of adults in the United States-37 million persons-have chronic kidney disease (CKD). Chronic kidney disease is divided into 5 groups, ranging from stage 1 to stage 5 CKD, whereas end-stage kidney disease (ESKD) is defined as permanent kidney failure. The treatment options for ESKD are kidney replacement therapy (KRT) and conservative management. The options for KRT include hemodialysis (either in-center or at home), peritoneal dialysis, and kidney transplant. Conservative management, a multidisciplinary model of care for patients with stage 5 CKD who want to avoid dialysis, is guided by patient values, preferences, and goals, with a focus on quality of life and symptom management. In 2015, the Kidney Disease Outcomes Quality Initiative recommended that patients with an estimated glomerular filtration rate below 30 mL/min/1.73 m2 be educated about options for both KRT and conservative management. In 2018, the National Institute for Health and Care Excellence recommended that assessment for KRT or conservative management start at least 1 year before the need for therapy. It also recommended that in choosing a management approach, predicted quality of life, predicted life expectancy, patient preferences, and other patient factors be considered, because little difference in outcomes has been found among options. Here, 2 experts-a nephrologist and a general internist-palliative care physician-reflect on the care of a patient with advanced CKD and mild to moderate dementia. They discuss the management options for patients with advanced CKD, the pros and cons of each method, and how to help a patient choose among the options. [ABSTRACT FROM AUTHOR]

Background: Residual shunt is observed in up to 25% of patients after patent foramen ovale (PFO) closure, but its long-term influence on stroke recurrence currently is unknown.Objective: To investigate the association of residual shunt after PFO closure with the incidence of recurrent stroke and transient ischemic attack (TIA).Design: Prospective cohort study comparing stroke or TIA recurrence in patients with and without residual shunt after PFO closure.Setting: Single hospital center.Participants: 1078 consecutive patients (mean age, 49.3 years) with PFO-attributable cryptogenic stroke who were undergoing percutaneous PFO closure were followed for up to 11 years.Measurements: Residual shunt was evaluated by transthoracic echocardiography with saline contrast. Primary outcome was a composite of the first recurrent ischemic stroke or TIA after PFO closure.Results: Compared with complete closure, the presence of residual shunt after PFO closure was associated with an increased incidence of recurrent stroke or TIA: 2.32 versus 0.75 events per 100 patient-years (hazard ratio [HR], 3.05 [95% CI, 1.65 to 5.62]; P < 0.001). This result remained robust after adjustment for important covariates, namely age; study period; device; presence of atrial septal aneurysm, hypertension, hyperlipidemia, diabetes, hypercoagulability, or hypermobile septum; and medication use (HR, 3.01 [CI, 1.59 to 5.69]; P < 0.001). Further stratification based on shunt size revealed that moderate or large residual shunts were associated with a higher risk for stroke or TIA recurrence (HR, 4.50 [CI, 2.20 to 9.20]; P < 0.001); the result for small residual shunts was indeterminate (HR, 2.02 [CI, 0.87 to 4.69]; P = 0.102).Limitation: Nonrandomized study with potential unmeasured confounding.Conclusion: Among patients undergoing PFO closure to prevent future stroke, the presence of residual shunt, particularly a moderate or large residual shunt, was associated with an increased risk for stroke or TIA recurrence.Primary Funding Source: National Institutes of Health. [ABSTRACT FROM AUTHOR]

Background: The accuracy and harms of brief cognitive tests for identifying clinical Alzheimer-type dementia (CATD) are uncertain.Purpose: To summarize evidence on accuracy and harms of brief cognitive tests for CATD in older adults with suspected cognitive impairment.Data Sources: Electronic bibliographic databases (from inception to November 2019) and systematic review bibliographies.Study Selection: English-language, controlled observational studies in older adults that evaluated the accuracy of brief cognitive tests (standalone tests; memory, executive function, and language tests; and brief multidomain batteries) for distinguishing CATD from mild cognitive impairment (MCI) or normal cognition as defined by established diagnostic criteria. Studies with low or medium risk of bias (ROB) were analyzed.Data Extraction: Two reviewers rated ROB. One reviewer extracted data; the other verified extraction accuracy.Data Synthesis: Fifty-seven studies met analysis criteria. Many brief, single cognitive tests were highly sensitive and specific for distinguishing CATD from normal cognition. These included standalone tests (clock-drawing test, median sensitivity 0.79 and specificity 0.88 [8 studies]; Mini-Mental State Examination, 0.88 and 0.94 [7 studies]; Montreal Cognitive Assessment, 0.94 and 0.94 [2 studies]; and Brief Alzheimer Screen, 0.92 and 0.97 [1 study]), memory tests (list delayed recall, 0.89 and 0.94 [5 studies]), and language tests (category fluency, 0.92 and 0.89 [9 studies]). Accuracy was lower in distinguishing mild CATD from normal cognition and distinguishing CATD from MCI. No studies reported on testing harms.Limitations: Studies were small. Few test metrics were evaluated by multiple studies. Few studies directly compared different tests, scores, cut points, or test combinations.Conclusion: Many brief, single cognitive tests accurately distinguish CATD from normal cognition in older adults but are less accurate in distinguishing mild CATD from normal cognition or CATD from MCI. No studies reported on testing harms.Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018117897). [ABSTRACT FROM AUTHOR]

Background: Inflammatory cytokines, such as interleukin (IL)-1β, alter iron homeostasis and erythropoiesis, resulting in anemia, but whether inhibition of IL-1β can reverse these effects is unclear.Objective: To determine whether IL-1β inhibition with canakinumab reduces incident anemia and improves hemoglobin levels among those with prevalent anemia.Design: Exploratory analysis of a randomized controlled trial. (ClinicalTrials.gov: NCT01327846).Setting: Many clinical sites in 39 countries.Participants: 8683 CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) participants without anemia at trial entry and 1303 with prevalent anemia at trial entry.Intervention: Random assignment to receive placebo or canakinumab (50, 150, or 300 mg) subcutaneously once every 3 months.Measurements: Primary outcome was incident anemia (hemoglobin level <130 g/L in men or <120 g/L in women).Results: Anemia incidence increased with rising baseline levels of high-sensitivity C-reactive protein (hsCRP), and both hsCRP and IL-6 decreased among participants receiving canakinumab compared with the placebo group. During a median follow-up of 3.7 years, participants without baseline anemia who received canakinumab at any dosage had significantly less incident anemia than those who received placebo (hazard ratio, 0.84 [95% CI, 0.77 to 0.93]; P < 0.001). Compared with placebo, the greatest benefits of IL-1β inhibition on incident anemia were observed among participants with the most robust anti-inflammatory response, an effect corroborated in formal mediation analyses. Among those with baseline anemia, canakinumab increased mean hemoglobin levels by 11.3 g/L (P < 0.001) compared with placebo after 2 years of treatment. Canakinumab increased the risk for infection and was associated with mild cases of thrombocytopenia and neutropenia, none of which was grade 3 or higher.Limitation: CANTOS was not designed to assess the cause of anemia in individual trial participants.Conclusion: These exploratory analyses of randomized trial data provide proof of principle that inflammation inhibition, at least through the IL-1β/IL-6 signaling pathway, reduces the incidence of anemia and improves hemoglobin levels in patients with anemia.Primary Funding Source: Novartis Pharmaceuticals. [ABSTRACT FROM AUTHOR]

Background: Iron chelation therapy (ICT) in patients with lower-risk myelodysplastic syndromes (MDS) has not been evaluated in randomized studies.Objective: To evaluate event-free survival (EFS) and safety of ICT in iron-overloaded patients with low- or intermediate-1-risk MDS.Design: Multicenter, randomized, double-blind, placebo-controlled trial (TELESTO). (ClinicalTrials.gov: NCT00940602).Setting: 60 centers in 16 countries.Participants: 225 patients with serum ferritin levels greater than 2247 pmol/L; prior receipt of 15 to 75 packed red blood cell units; and no severe cardiac, liver, or renal abnormalities.Intervention: Deferasirox dispersible tablets (10 to 40 mg/kg per day) (n = 149) or matching placebo (n = 76).Measurements: The primary end point was EFS, defined as time from date of randomization to first documented nonfatal event (related to cardiac or liver dysfunction and transformation to acute myeloid leukemia) or death, whichever occurred first.Results: Median time on treatment was 1.6 years (interquartile range [IQR], 0.5 to 3.1 years) in the deferasirox group and 1.0 year (IQR, 0.6 to 2.0 years) in the placebo group. Median EFS was prolonged by approximately 1 year with deferasirox versus placebo (3.9 years [95% CI, 3.2 to 4.3 years] vs. 3.0 years [CI, 2.2 to 3.7 years], respectively; hazard ratio, 0.64 [CI, 0.42 to 0.96]). Adverse events occurred in 97.3% of deferasirox recipients and 90.8% of placebo recipients. Exposure-adjusted incidence rates of adverse events (≥15 events per 100 patient treatment-years) in deferasirox versus placebo recipients, respectively, were 24.7 versus 23.9 for diarrhea, 21.8 versus 18.7 for pyrexia, 16.7 versus 22.7 for upper respiratory tract infection, and 15.9 versus 0.9 for increased serum creatinine concentration.Limitations: The protocol was amended from a phase 3 to a phase 2 study, with a reduced target sample size from 630 to 210 participants. There was differential follow-up between treatment groups.Conclusion: The findings support ICT in iron-overloaded patients with low- to intermediate-1-risk MDS, with longer EFS compared with placebo and a clinically manageable safety profile. Therefore, ICT may be considered in these patients.Primary Funding Source: Novartis Pharma AG. [ABSTRACT FROM AUTHOR]

Background: Both pharmacologic and nonpharmacologic interventions are used to treat neuropsychiatric symptoms in persons with dementia.Purpose: To summarize the comparative efficacy of pharmacologic and nonpharmacologic interventions for treating aggression and agitation in adults with dementia.Data Sources: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, and PsycINFO between inception and 28 May 2019 without language restrictions; gray literature; and reference lists scanned from selected studies and systematic reviews.Study Selection: Randomized controlled trials comparing interventions for treating aggression and agitation in adults with dementia.Data Extraction: Pairs of reviewers independently screened studies, abstracted data, and appraised risk of bias.Data Synthesis: After screening of 19 684 citations, 163 studies (23 143 patients) were included in network meta-analyses. Analysis of interventions targeting aggression and agitation (148 studies [21 686 patients]) showed that multidisciplinary care (standardized mean difference [SMD], -0.5 [95% credible interval {CrI}, -0.99 to -0.01]), massage and touch therapy (SMD, -0.75 [CrI, -1.12 to -0.38]), and music combined with massage and touch therapy (SMD, -0.91 [CrI, -1.75 to -0.07]) were clinically more efficacious than usual care. Recreation therapy (SMD, -0.29 [CrI, -0.57 to -0.01]) was statistically but not clinically more efficacious than usual care.Limitations: Forty-six percent of studies were at high risk of bias because of missing outcome data. Harms and costs of therapies were not evaluated.Conclusion: Nonpharmacologic interventions seemed to be more efficacious than pharmacologic interventions for reducing aggression and agitation in adults with dementia.Primary Funding Source: Alberta Health Services Critical Care Strategic Clinical Network. (PROSPERO: CRD42017050130). [ABSTRACT FROM AUTHOR]

The article presents the case of a 34-year-old male who was rushed to a hospital due to third episode of debilitating myositis following a sore throat to describe an immunologically mediated streptococcal disease complication. Topics include such complications as poststreptococcal glomerulonephritis, erythema nodosum, and acute rheumatic fever and the recorded cases of poststreptococcal polymyalgia and myositis with such symptoms as muscle swelling and incapacitating limb pain.

The chylomicronemia syndrome occurs when triglyceride levels are severely elevated (usually >16.95 mmol/L [1500 mg/dL]) and is characterized by such clinical features as abdominal pain, acute pancreatitis, eruptive xanthomas, and lipemia retinalis. It may result from 1 of 3 conditions: the presence of secondary forms of hypertriglyceridemia concurrent with genetic causes of hypertriglyceridemia, termed multifactorial chylomicronemia syndrome (MFCS); a deficiency in the enzyme lipoprotein lipase and some associated proteins, termed familial chylomicronemia syndrome (FCS); or familial partial lipodystrophy. Most chylomicronemia syndrome cases are the result of MFCS; FCS is very rare. In all these conditions, triglyceride-rich lipoproteins accumulate because of impaired plasma clearance. This review describes the 3 major causes of the chylomicronemia syndrome; their consequences; and the approaches to treatment, which differ considerably by group. [ABSTRACT FROM AUTHOR]

The article examines the effect of Liraglutide medication on sardiovascular outcomes in elderly patients. Topics discussed include information on the rise in the comorbidities and complications associated with type 2 diabetes mellitus with age; discussions on the effect of antihyperglycemic treatment on cardiovascular events in elderly persons; and the information on the use of liraglutide significantly reduced the risk for major adverse cardiovascular events.

Background: Drug use-associated infective endocarditis (DUA-IE) is increasing as a result of the opioid epidemic. Infective endocarditis may require valve surgery, but surgical treatment of DUA-IE has invoked controversy, and the extent of its use is unknown.Objective: To examine hospitalization trends for DUA-IE, the proportion of hospitalizations with surgery, patient characteristics, length of stay, and charges.Design: 10-year analysis of a statewide hospital discharge database.Setting: North Carolina hospitals, 2007 to 2017.Patients: All patients aged 18 years or older hospitalized for IE.Measurements: Annual trends in all IE admissions and in IE hospitalizations with valve surgery, stratified by patients' drug use status. Characteristics of DUA-IE surgical hospitalizations, including patient demographic characteristics, length of stay, disposition, and charges.Results: Of 22 825 IE hospitalizations, 2602 (11%) were for DUA-IE. Valve surgery was performed in 1655 IE hospitalizations (7%), including 285 (17%) for DUA-IE. Annual DUA-IE hospitalizations increased from 0.92 to 10.95 and DUA-IE hospitalizations with surgery from 0.10 to 1.38 per 100 000 persons. In the final year, 42% of IE valve surgeries were performed in patients with DUA-IE. Compared with other surgical patients with IE, those with DUA-IE were younger (median age, 33 vs. 56 years), were more commonly female (47% vs. 33%) and white (89% vs. 63%), and were primarily insured by Medicaid (38%) or uninsured (35%). Hospital stays for DUA-IE were longer (median, 27 vs. 17 days), with higher median charges ($250 994 vs. $198 764). Charges for 282 DUA-IE hospitalizations exceeded $78 million.Limitation: Reliance on administrative data and billing codes.Conclusion: DUA-IE hospitalizations and valve surgeries increased more than 12-fold, and nearly half of all IE valve surgeries were performed in patients with DUA-IE. The swell of patients with DUA-IE is reshaping the scope, type, and financing of health care resources needed to effectively treat IE.Primary Funding Source: National Institutes of Health. [ABSTRACT FROM AUTHOR]

This article has been corrected. The original version (PDF) is appended to this article as a Supplement.Background: Atrial fibrillation (AF) and heart failure (HF) frequently coexist and are associated with increased morbidity and mortality risk.Purpose: To compare benefits and harms between catheter ablation and drug therapy in adult patients with AF and HF.Data Sources: ClinicalTrials.gov, PubMed, Web of Science (Clarivate Analytics), EBSCO Information Services, Cochrane Central Register of Controlled Trials, Google Scholar, and various scientific conference sessions from 1 January 2005 to 1 October 2018.Study Selection: Randomized controlled trials (RCTs) published in English that had at least 6 months of follow-up and compared clinical outcomes of catheter ablation versus drug therapy in adults with AF and HF.Data Extraction: 2 investigators independently extracted data and assessed study quality.Data Synthesis: 6 RCTs involving 775 patients met inclusion criteria. Compared with drug therapy, AF ablation reduced all-cause mortality (9.0% vs. 17.6%; risk ratio [RR], 0.52 [95% CI, 0.33 to 0.81]) and HF hospitalizations (16.4% vs. 27.6%; RR, 0.60 [CI, 0.39 to 0.93]). Ablation improved left ventricular ejection fraction (LVEF) (mean difference, 6.95% [CI, 3.0% to 10.9%]), 6-minute walk test distance (mean difference, 20.93 m [CI, 5.91 to 35.95 m]), peak oxygen consumption (Vo2max) (mean difference, 3.17 mL/kg per minute [CI, 1.26 to 5.07 mL/kg per minute]), and quality of life (mean difference in Minnesota Living with Heart Failure Questionnaire score, -9.02 points [CI, -19.75 to 1.71 points]). Serious adverse events were more common in the ablation groups, although differences between the ablation and drug therapy groups were not statistically significant (7.2% vs. 3.8%; RR, 1.68 [CI, 0.58 to 4.85]).Limitation: Results driven primarily by 1 clinical trial, possible patient selection bias in the ablation group, lack of patient-level data, open-label trial designs, and heterogeneous follow-up length among trials.Conclusion: Catheter ablation was superior to conventional drug therapy in improving all-cause mortality, HF hospitalizations, LVEF, 6-minute walk test distance, Vo2max, and quality of life, with no statistically significant increase in serious adverse events.Primary Funding Source: None. [ABSTRACT FROM AUTHOR]

Background: Little is known about the long-term effects of high-deductible insurance on care for chronic medical conditions.Objective: To determine whether a transition from low-deductible to high-deductible insurance is associated with delayed medical care for macrovascular complications of diabetes.Design: Observational longitudinal comparison of matched groups.Setting: A large national health insurer during 2003 to 2012.Participants: The intervention group comprised 33 957 persons with diabetes who were continuously enrolled in low-deductible (≤$500) insurance plans during a baseline year followed by up to 4 years in high-deductible (≥$1000) plans. The control group included 294 942 persons with diabetes who were enrolled in low-deductible plans contemporaneously with matched intervention group members.Intervention: Employer-mandated transition to a high-deductible plan.Measurements: The number of months it took for persons in each study group to seek care for their first major macrovascular symptom, have their first major diagnostic test for macrovascular disease, and have their first major procedure-based treatment was determined. Between-group differences in time to reach a midpoint event rate were then calculated.Results: No baseline differences were found between groups. During follow-up, the delay for the high-deductible group was 1.5 months (95% CI, 0.8 to 2.3 months) for seeking care for the first major symptom, 1.9 months (CI, 1.4 to 2.3 months) for the first diagnostic test, and 3.1 months (CI, 0.5 to 5.8 months) for the first procedure-based treatment.Limitation: Health outcomes were not examined.Conclusion: Among persons with diabetes, mandated enrollment in a high-deductible insurance plan was associated with delays in seeking care for the first major symptoms of macrovascular disease, the first diagnostic test, and the first procedure-based treatment.Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases. [ABSTRACT FROM AUTHOR]

Background: Direct-acting antiviral agents are now available to treat chronic hepatitis C virus (HCV) infection in patients with end-stage renal disease (ESRD).Objective: To examine whether it is more cost-effective to transplant HCV-infected or HCV-uninfected kidneys into HCV-infected patients.Design: Markov state-transition decision model.Data Sources: MEDLINE searches and bibliographies from relevant English-language articles.Target Population: HCV-infected patients with ESRD receiving hemodialysis in the United States.Time Horizon: Lifetime.Perspective: Health care system.Intervention: Transplant of an HCV-infected kidney followed by HCV treatment versus transplant of an HCV-uninfected kidney preceded by HCV treatment.Outcome Measures: Effectiveness, measured in quality-adjusted life-years (QALYs), and costs, measured in 2017 U.S. dollars.Results of Base-case Analysis: Transplant of an HCV-infected kidney followed by HCV treatment was more effective and less costly than transplant of an HCV-uninfected kidney preceded by HCV treatment, largely because of longer wait times for uninfected kidneys. A typical 57.8-year-old patient receiving hemodialysis would gain an average of 0.50 QALY at a lifetime cost savings of $41 591.Results of Sensitivity Analysis: Transplant of an HCV-infected kidney followed by HCV treatment continued to be preferred in sensitivity analyses of many model parameters. Transplant of an HCV-uninfected kidney preceded by HCV treatment was not preferred unless the additional wait time for an uninfected kidney was less than 161 days.Limitation: The study did not consider the benefit of decreased HCV transmission from treating HCV-infected patients.Conclusion: Transplanting HCV-infected kidneys into HCV-infected patients increased quality-adjusted life expectancy and reduced costs compared with transplanting HCV-uninfected kidneys into HCV-infected patients.Primary Funding Source: Merck Sharp & Dohme and the National Center for Advancing Translational Sciences. [ABSTRACT FROM AUTHOR]

Chew and colleagues reported a decision analytic model to help guide decisions about using LAAO versus oral anticoagulation in patients with nonvalvular atrial fibrillation who are at risk for stroke and bleeding. The editorialist discusses the need for further research to guide decision making. [ABSTRACT FROM AUTHOR]

This article discusses the Supreme Court's ruling in Dobbs v. Jackson and the concerns it raises for patients with rheumatic disease and their clinicians, including access to medically indicated abortion, access to necessary medications that are teratogenic, and laws that interfere with patient–clinician discussions about reproductive issues. [ABSTRACT FROM AUTHOR]

I Background: i Myocarditis is an important cause of heart failure, and successful treatment depends on identifying the underlying cause and mechanism. Infectious and autoimmune diseases are the most common causes, although myocarditis can also be caused by endocrine disorders, such as pheochromocytoma ([1]); infiltrative disorders, such as amyloidosis ([2]); and metabolic disorders. On the basis of our experience with this patient, we conclude that gout can cause myocarditis with cardiac dilatation, cardiac dysfunction, and heart failure, particularly in patients with tophaceous and untreated gout. [Extracted from the article]

I Background: i Lyme disease is the most common vector-borne disease in the United States, and it is hyperendemic in the Northeast ([1]). Results of immunohistochemical testing for I Anaplasma phagocytophilum i and I Babesia i species on heart tissue from the Massachusetts patient and on heart, spleen, and liver tissue from the Vermont patient were negative. [Extracted from the article]

Background: New evidence emerged recently regarding the percutaneous closure of patent foramen ovale (PFO) to prevent recurrent stroke in patients with cryptogenic stroke.Purpose: To compare risks for recurrent cerebrovascular events in adults with PFO and cryptogenic stroke who underwent PFO closure versus those who received medical therapy alone.Data Sources: PubMed, Scopus, and Google Scholar from 1 December 2004 through 14 September 2017; references of eligible studies; relevant scientific session abstracts; and cardiology Web sites.Study Selection: Randomized controlled trials, published in English, that compared PFO closure using a currently available device with medical treatment alone and that reported, at minimum, the rates of stroke or transient ischemic attack (TIA) or of new-onset atrial fibrillation (AF) or atrial flutter (AFL).Data Extraction: 2 investigators independently extracted study data and assessed study quality.Data Synthesis: 4 of 5 trials comparing PFO closure with medical therapy used commercially available devices. These 4 trials, involving 2531 patients, found that PFO closure reduced the risk for the main outcome of stroke or TIA (risk difference [RD], -0.029 [95% CI, -0.050 to -0.007]) and increased the risk for new-onset AF or AFL (RD, 0.033 [CI, 0.012 to 0.054]). The beneficial effect of PFO closure was associated with larger interatrial shunts (P = 0.034).Limitation: Trials were not double-blind, and inclusion criteria were heterogeneous.Conclusion: Compared with medical treatment, PFO closure prevents recurrent stroke and TIA but increases the incidence of AF or AFL in PFO carriers with cryptogenic stroke.Primary Funding Source: Italian Ministry of Education, University and Research (MIUR). (PROSPERO: CRD42017074686). [ABSTRACT FROM AUTHOR]

Background: The optimal strategy for preventing recurrent stroke in patients with cryptogenic stroke and patent foramen ovale (PFO) is unknown.Purpose: To compare transcatheter PFO closure with medical therapy alone for prevention of recurrent stroke in patients with PFO and cryptogenic stroke.Data Sources: PubMed and the Cochrane Library (without language restrictions) from inception to October 2017, reference lists, and abstracts from cardiology meetings.Study Selection: Randomized trials enrolling adults with PFO and cryptogenic stroke that compared stroke outcomes (main outcome) and potential harms in those receiving transcatheter device closure versus medical therapy alone.Data Extraction: Two investigators independently extracted study data and rated risk of bias.Data Synthesis: Of 5 trials, 1 was excluded because it used a device that is no longer available due to high rates of complications and failure. Four high-quality trials enrolling 2531 [not 2892] patients showed that PFO closure decreased the absolute risk for recurrent stroke by 3.3% [not 3.2%] (risk difference [RD], −0.033 [95% CI, −0.062 to −0.004]) [not −0.032 (95% CI, −0.050 to −0.014)] compared with medical therapy. The treatment strategies did not differ in rates of transient ischemic attack or major bleeding. Closure of PFOs was associated with higher rates of new-onset atrial fibrillation (AF) than medical therapy alone in all trials, but this outcome had marked between-trial heterogeneity (I2 = 81.9%), and high event rates in some groups resulted in extreme values for CIs.Limitation: Heterogeneity of device type and antithrombotic therapy across trials, small numbers for some outcomes, and heterogeneous and inconclusive AF results.Conclusion: In patients with PFO and cryptogenic stroke, transcatheter device closure decreases risk for recurrent stroke compared with medical therapy alone. Because recurrent stroke rates are low even with medical therapy alone and PFO closure might affect AF risk, shared decision making is crucial for this treatment.Primary Funding Source: None. [ABSTRACT FROM AUTHOR]

Background: Dabigatran (150 mg twice daily) has been associated with lower rates of stroke than warfarin in trials of atrial fibrillation, but large-scale evaluations in clinical practice are limited.Objective: To compare incidence of stroke, bleeding, and myocardial infarction in patients receiving dabigatran versus warfarin in practice.Design: Retrospective cohort.Setting: National U.S. Food and Drug Administration Sentinel network.Patients: Adults with atrial fibrillation initiating dabigatran or warfarin therapy between November 2010 and May 2014.Measurements: Ischemic stroke, intracranial hemorrhage, extracranial bleeding, and myocardial infarction identified from hospital claims among propensity score-matched patients starting treatment with dabigatran or warfarin.Results: Among 25 289 patients starting dabigatran therapy and 25 289 propensity score-matched patients starting warfarin therapy, those receiving dabigatran did not have significantly different rates of ischemic stroke (0.80 vs. 0.94 events per 100 person-years; hazard ratio [HR], 0.92 [95% CI, 0.65 to 1.28]) or extracranial hemorrhage (2.12 vs. 2.63 events per 100 person-years; HR, 0.89 [CI, 0.72 to 1.09]) but were less likely to have intracranial bleeding (0.39 vs. 0.77 events per 100 person-years; HR, 0.51 [CI, 0.33 to 0.79]) and more likely to have myocardial infarction (0.77 vs. 0.43 events per 100 person-years; HR, 1.88 [CI, 1.22 to 2.90]). However, the strength and significance of the association between dabigatran use and myocardial infarction varied in sensitivity analyses and by exposure definition (HR range, 1.13 [CI, 0.78 to 1.64] to 1.43 [CI, 0.99 to 2.08]). Older patients and those with kidney disease had higher gastrointestinal bleeding rates with dabigatran.Limitation: Inability to examine outcomes by dabigatran dose (unacceptable covariate balance between matched patients) or quality of warfarin anticoagulation (few patients receiving warfarin had available international normalized ratio values).Conclusion: In matched adults with atrial fibrillation treated in practice, the incidences of stroke and bleeding with dabigatran versus warfarin were consistent with those seen in trials. The possible relationship between dabigatran and myocardial infarction warrants further investigation.Primary Funding Source: U.S. Food and Drug Administration. [ABSTRACT FROM AUTHOR]

Background: Primary aldosteronism is recognized as a severe form of renin-independent aldosteronism that results in excessive mineralocorticoid receptor (MR) activation.Objective: To investigate whether a spectrum of subclinical renin-independent aldosteronism that increases risk for hypertension exists among normotensive persons.Design: Cohort study.Setting: National community-based study.Participants: 850 untreated normotensive participants in MESA (Multi-Ethnic Study of Atherosclerosis) with measurements of serum aldosterone and plasma renin activity (PRA).Measurements: Longitudinal analyses investigated whether aldosterone concentrations, in the context of physiologic PRA phenotypes (suppressed, ≤0.50 µg/L per hour; indeterminate, 0.51 to 0.99 µg/L per hour; unsuppressed, ≥1.0 µg/L per hour), were associated with incident hypertension (defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or initiation of antihypertensive medications). Cross-sectional analyses investigated associations between aldosterone and MR activity, assessed via serum potassium and urinary fractional excretion of potassium.Results: A suppressed renin phenotype was associated with a higher rate of incident hypertension than other PRA phenotypes (incidence rates per 1000 person-years of follow-up: suppressed renin phenotype, 85.4 events [95% CI, 73.4 to 99.3 events]; indeterminate renin phenotype, 53.3 events [CI, 42.8 to 66.4 events]; unsuppressed renin phenotype, 54.5 events [CI, 41.8 to 71.0 events]). With renin suppression, higher aldosterone concentrations were independently associated with an increased risk for incident hypertension, whereas no association between aldosterone and hypertension was seen when renin was not suppressed. Higher aldosterone concentrations were associated with lower serum potassium and higher urinary excretion of potassium, but only when renin was suppressed.Limitation: Sodium and potassium were measured several years before renin and aldosterone.Conclusion: Suppression of renin and higher aldosterone concentrations in the context of this renin suppression are associated with an increased risk for hypertension and possibly also with increased MR activity. These findings suggest a clinically relevant spectrum of subclinical primary aldosteronism (renin-independent aldosteronism) in normotension.Primary Funding Source: National Institutes of Health. [ABSTRACT FROM AUTHOR]

In July 2014, the U.S. Preventive Services Task Force (USPSTF) published a clinical guideline on screening for asymptomatic carotid artery stenosis. The guideline recommended against screening in asymptomatic adults, based primarily on the results of 3 large randomized trials (grade D recommendation). The principal screening test was carotid ultrasonography, and the intervention in the 3 trials was carotid endarterectomy for patients with stenosis exceeding 50% to 60%. In a meta-analysis, carotid endarterectomy reduced rates of 1) perioperative stroke, death, or subsequent ipsilateral stroke and 2) perioperative stroke, death, or any subsequent stroke. The corresponding absolute risk differences were -2.0% (95% CI, -3.3% to -0.7%) and -3.5% (CI, -5.1% to -1.8%), respectively. However, perioperative stroke and death were substantially less common among the 3 randomized trials than in contemporaneous cohort studies (1.9% vs. 3.3%). In addition to stroke or death in patients receiving carotid endarterectomy, a harm of screening included the risk for angiography prompted by abnormal results on carotid ultrasonography. In this article, 2 discussants address the risks and benefits of screening for carotid artery disease as well as how to apply the guideline to an individual patient who is deciding whether to be screened. [ABSTRACT FROM AUTHOR]

Background: The public health significance of the reported higher incidence of chronic kidney disease (CKD) with intensive systolic blood pressure (SBP) lowering is unclear.Objective: To examine the effects of intensive SBP lowering on kidney and cardiovascular outcomes and contrast its apparent beneficial and adverse effects.Design: Subgroup analyses of SPRINT (Systolic Blood Pressure Intervention Trial). (ClinicalTrials.gov: NCT01206062).Setting: Adults with high blood pressure and elevated cardiovascular risk.Participants: 6662 participants with a baseline estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 m2.Intervention: Random assignment to an intensive or standard SBP goal (120 or 140 mm Hg, respectively).Measurements: Differences in mean eGFR during follow-up (estimated with a linear mixed-effects model), prespecified incident CKD (defined as a >30% decrease in eGFR to a value <60 mL/min/1.73 m2), and a composite of all-cause death or cardiovascular event, with surveillance every 3 months.Results: The difference in adjusted mean eGFR between the intensive and standard groups was -3.32 mL/min/1.73 m2 (95% CI, -3.90 to -2.74 mL/min/1.73 m2) at 6 months, was -4.50 mL/min/1.73 m2 (CI, -5.16 to -3.85 mL/min/1.73 m2) at 18 months, and remained relatively stable thereafter. An incident CKD event occurred in 3.7% of participants in the intensive group and 1.0% in the standard group at 3-year follow-up, with a hazard ratio of 3.54 (CI, 2.50 to 5.02). The corresponding percentages for the composite of death or cardiovascular event were 4.9% and 7.1% at 3-year follow-up, with a hazard ratio of 0.71 (CI, 0.59 to 0.86).Limitation: Long-term data were lacking.Conclusion: Intensive SBP lowering increased risk for incident CKD events, but this was outweighed by cardiovascular and all-cause mortality benefits.Primary Funding Source: National Institutes of Health. [ABSTRACT FROM AUTHOR]