Comparative Effectiveness of Tai Chi Versus Physical Therapy for Knee Osteoarthritis: A Randomized Trial: Annals of Internal Medicine: Vol 165, No 2

Background: Few remedies effectively treat long-term pain and disability from knee osteoarthritis. Studies suggest that Tai Chi alleviates symptoms, but no trials have directly compared Tai Chi with standard therapies for osteoarthritis. Objective: To compare Tai Chi with standard physical therapy for patients with knee osteoarthritis. Design: Randomized, 52-week, single-blind comparative effectiveness trial. (ClinicalTrials.gov: NCT01258985) Setting: An urban tertiary care academic hospital. Patients: 204 participants with symptomatic knee osteoarthritis (mean age, 60 years; 70% women; 53% white). Intervention: Tai Chi (2 times per week for 12 weeks) or standard physical therapy (2 times per week for 6 weeks, followed by 6 weeks of monitored home exercise). Measurements: The primary outcome was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at 12 weeks. Secondary outcomes included physical function, depression, medication use, and quality of life. Results: At 12 weeks, the WOMAC score was substantially reduced in both groups (Tai Chi, 167 points [95% CI, 145 to 190 points]; physical therapy, 143 points [CI, 119 to 167 points]). The between-group difference was not significant (24 points [CI, −10 to 58 points]). Both groups also showed similar clinically significant improvement in most secondary outcomes, and the benefits were maintained up to 52 weeks. Of note, the Tai Chi group had significantly greater improvements in depression and the physical component of quality of life. The benefit of Tai Chi was consistent across instructors. No serious adverse events occurred. Limitation: Patients were aware of their treatment group assignment, and the generalizability of the findings to other settings remains undetermined. Conclusion: Tai Chi produced beneficial effects similar to those of a standard course of physical therapy in the treatment of knee osteoarthritis. Primary Funding Source: National Center for Complementary and Integrative Health of the National Institutes of Health.

The Firearm for Protection? A Risky Bet

Should We Abandon Routine Visits? There Is Little Evidence for or Against

Physical Fitness Among Swedish Military Conscripts and Long-Term Risk for Type 2 Diabetes Mellitus: A Cohort Study: Annals of Internal Medicine: Vol 164, No 9

Background: Early-life physical fitness has rarely been examined in relation to type 2 diabetes mellitus (DM) in adulthood because of the lengthy follow-up required. Elucidation of modifiable risk factors at young ages may help facilitate earlier and more effective interventions. Objective: To examine aerobic capacity and muscle strength at age 18 years in relation to risk for type 2 DM in adulthood. Design: National cohort study. Setting: Sweden. Participants: 1 534 425 military conscripts from 1969 to 1997 (97% to 98% of all men aged 18 years nationwide) without prior type 2 DM. Measurements: Aerobic capacity and muscle strength (measured in watts and newtons per kilogram of body weight, respectively) were examined in relation to type 2 DM identified from outpatient and inpatient diagnoses from 1987 to 2012 (maximum age, 62 years). Results: 34 008 men were diagnosed with type 2 DM in 39.4 million person-years of follow-up. Low aerobic capacity and muscle strength were independently associated with increased risk for type 2 DM. The absolute difference in cumulative incidence of type 2 DM between the lowest and highest tertiles of both aerobic capacity and strength was 0.22% at 20 years of follow-up (95% CI, 0.20% to 0.25%), 0.76% at 30 years (CI, 0.71% to 0.81%), and 3.97% at 40 years (CI, 3.87% to 4.06%). Overall, the combination of low aerobic capacity and muscle strength was associated with a 3-fold risk for type 2 DM (adjusted hazard ratio, 3.07 [CI, 2.88 to 3.27]; P < 0.001), with a positive additive interaction (P < 0.001). These associations were seen even among men with normal body mass index. Limitation: This cohort did not include women and did not measure physical fitness at older ages. Conclusion: In this large cohort of Swedish male military conscripts, low aerobic capacity and muscle strength at age 18 years were associated with increased long-term risk for type 2 DM, even among those with normal body mass index. Primary Funding Source: National Institutes of Health.

The Effect of Erythropoietin-Stimulating Agents on Health-Related Quality of Life in Anemia of Chronic Kidney Disease: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 164, No 7

Background: The efficacy of erythropoietin-stimulating agents (ESAs) for improving health-related quality of life (HRQOL) in anemia of chronic kidney disease (CKD) is unclear. Purpose: To determine the effect of ESAs on HRQOL at different hemoglobin targets in adults with CKD who were receiving or not receiving dialysis. Data Sources: Searches of PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov from inception to 1 November 2015, supplemented with manual screening. Study Selection: Randomized, controlled trials that evaluated the treatment of anemia with ESAs, including erythropoietin and darbepoetin, targeted higher versus lower hemoglobin levels, and used validated HRQOL metrics. Data Extraction: Study characteristics, quality, and data were assessed independently by 2 reviewers. Outcome measures were scores on the Short Form-36 Health Survey (SF-36), Kidney Dialysis Questionnaire (KDQ), and other tools. Data Synthesis: Of 17 eligible studies, 13 reported SF-36 outcomes and 4 reported KDQ outcomes. Study populations consisted of patients not undergoing dialysis (n = 12), those undergoing dialysis (n = 4), or a mixed sample (n = 1). Only 4 studies had low risk of bias. Pooled analyses showed that higher hemoglobin targets resulted in no statistically or clinically significant differences in SF-36 or KDQ domains. Differences in HRQOL were further attenuated in studies at low risk of bias and in subgroups of dialysis recipients. Limitation: Statistically significant heterogeneity among studies, few good-quality studies, and possible publication bias. Conclusion: ESA treatment of anemia to obtain higher hemoglobin targets does not result in important differences in HRQOL in patients with CKD. Primary Funding Source: KRESCENT and Manitoba Health Research Council Establishment.

Prognostic Value of Cardiovascular Magnetic Resonance and Single-Photon Emission Computed Tomography in Suspected Coronary Heart Disease: Long-Term Follow-up of a Prospective, Diagnostic Accuracy Cohort Study

Background: There are no prospective, prognostic data comparing cardiovascular magnetic resonance (CMR) and single-photon emission computed tomography (SPECT) in the same population of patients with suspected coronary heart disease (CHD). Objective: To establish the ability of CMR and SPECT to predict major adverse cardiovascular events (MACEs). Design: Annual follow-up of the CE-MARC (Clinical Evaluation of MAgnetic Resonance imaging in Coronary heart disease) study for a minimum of 5 years for MACEs (cardiovascular death, acute coronary syndrome, unscheduled revascularization or hospital admission for cardiovascular cause). (Current Controlled Trials registration: ISRCTN77246133) Setting: Secondary and tertiary care cardiology services. Participants: 752 patients from the CE-MARC study who were being investigated for suspected CHD. Measurements: Prediction of time to MACE was assessed by using univariable (log-rank test) and multivariable (Cox proportional hazards regression) analysis. Results: 744 (99%) of the 752 recruited patients had complete follow-up. Of 628 who underwent CMR, SPECT, and the reference standard test of X-ray angiography, 104 (16.6%) had at least 1 MACE. Abnormal findings on CMR (hazard ratio, 2.77 [95% CI, 1.85 to 4.16]; P < 0.001) and SPECT (hazard ratio, 1.62 [CI, 1.11 to 2.38; P = 0.014) were both strong and independent predictors of MACE. Only CMR remained a significant predictor after adjustment for other cardiovascular risk factors, angiography result, or stratification for initial patient treatment. Limitation: Data are from a single-center observational study (albeit conducted in a high-volume institution for both CMR and SPECT). Conclusion: Five-year follow-up of the CE-MARC study indicates that compared with SPECT, CMR is a stronger predictor of risk for MACEs, independent of cardiovascular risk factors, angiography result, or initial patient treatment. This further supports the role of CMR as an alternative to SPECT for the diagnosis and management of patients with suspected CHD. Primary Funding Source: British Heart Foundation.

The History and Future of Treatment of Hypothyroidism

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Thyroid hormone replacement has been used for more than a century to treat hypothyroidism. Natural thyroid preparations (thyroid extract, desiccated thyroid, or thyroglobulin), which contain both thyroxine (T4) and triiodothyronine (T3), were the first pharmacologic treatments available and dominated the market for the better part of the 20th century. Dosages were adjusted to resolve symptoms and to normalize the basal metabolic rate and/or serum protein-bound iodine level, but thyrotoxic adverse effects were not uncommon. Two major developments in the 1970s led to a transition in clinical practice: 1) The development of the serum thyroid-stimulating hormone (TSH) radioimmunoassay led to the discovery that many patients were overtreated, resulting in a dramatic reduction in thyroid hormone replacement dosage, and 2) the identification of peripheral deiodinase-mediated T4-to-T3 conversion provided a physiologic means to justify l-thyroxine monotherapy, obviating concerns about inconsistencies with desiccated thyroid. Thereafter, l-thyroxine monotherapy at doses to normalize the serum TSH became the standard of care. Since then, a subgroup of thyroid hormone–treated patients with residual symptoms of hypothyroidism despite normalization of the serum TSH has been identified. This has brought into question the inability of l-thyroxine monotherapy to universally normalize serum T3 levels. New research suggests mechanisms for the inadequacies of l-thyroxine monotherapy and highlights the possible role for personalized medicine based on deiodinase polymorphisms. Understanding the historical events that affected clinical practice trends provides invaluable insight into formulation of an approach to help all patients achieve clinical and biochemical euthyroidism.

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Interrupting Ebola Transmission in Liberia Through Community-Based Initiatives

Laparoscopic Lavage for Perforated Diverticulitis With Purulent Peritonitis: A Randomized Trial: Annals of Internal Medicine: Vol 164, No 3

Background: Perforated diverticulitis with purulent peritonitis has traditionally been treated with open colon resection and stoma formation with risk for reoperations, morbidity, and mortality. Laparoscopic lavage alone has been suggested as definitive treatment. Objective: To compare laparoscopic lavage with open colon resection and colostomy (Hartmann procedure) for perforated diverticulitis with purulent peritonitis. Design: Randomized, controlled, multicenter, open-label trial. (ISRCTN registry number: ISRCTN82208287) Setting: 9 hospitals in Sweden and Denmark. Patients: Patients who have confirmed Hinchey grade III perforated diverticulitis with purulent peritonitis at diagnostic laparoscopy. Intervention: Randomization between laparoscopic lavage and the Hartmann procedure. Measurements: Primary outcome was the percentage of patients having 1 or more reoperations within 12 months. Key secondary outcomes were number of reoperations, hospital readmissions, total length of hospital stay during 12 months, and adverse events. Results: A total of 43 and 40 patients were randomly assigned to laparoscopic lavage and the Hartmann procedure with a median (first, third quartiles) follow-up of 372 days (336, 394) and 378 days (226, 396), respectively. Fewer patients in the laparoscopic group (12 of 43; 27.9%) than in the Hartmann group (25 of 40; 62.5%) had at least 1 reoperation within 12 months (relative risk reduction, 59%; relative risk, 0.41 [95% CI, 0.23 to 0.72]; P = 0.004). Mortality and severe adverse events did not differ between groups. Total length of hospital stay (days) within 12 months was shorter for the laparoscopic group than the Hartmann group, with a reduction of 35% (relative risk, 0.65 [CI, 0.45 to 0.94]; P = 0.047). After 12 months, 3 patients in the laparoscopic group and 11 in the Hartmann group had a stoma. Limitation: Not all patients presenting with suspected diverticulitis were enrolled. Conclusion: Laparoscopic lavage reduced the need for reoperations, had a similar safety profile to the Hartmann procedure, and may be an appropriate treatment of choice for acute perforated diverticulitis with purulent peritonitis. Primary Funding Source: ALF; Sahlgrenska University Hospital, Gothenburg.