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1.
Med Care ; 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31985584

RESUMO

BACKGROUND: Discontinuation of bisphosphonates (BP) or a "drug holiday" after several years of treatment is increasingly common. However, the association of drug holiday duration with future fracture risk is unclear. OBJECTIVES: We evaluated the rate of fracture in relation to various lengths of drug holidays among women receiving long-term BP therapy. RESEARCH DESIGN: Observational cohort study using US Medicare data 2006-2016. Incidence rates (IRs) and Cox proportional hazards models were used to evaluate the rate and adjusted hazard ratios (aHRs) controlling for potential confounders. SUBJECTS: Women aged 65 years and above enrolled in fee-for-service Medicare who had been adherent (≥80%) to alendronate, risedronate, or zoledronate for ≥3 years. MEASURES: Hip, humerus, distal forearm, and clinical vertebral fracture. RESULTS: Among 81,427 eligible women observed for a median (interquartile range) of 4.0 (2.5, 5.3) years, 28% of women underwent a drug holiday. In the alendronate cohort (73% overall), the IR of hip fracture among women who discontinued BP for >2 years was 13.2 per 1000 person-years. Risk was increased (aHR=1.3, 1.1-1.4) versus continuing therapy (IR=8.8, referent). Rates were elevated for humerus fracture with discontinuation >2 years (aHR=1.3, 1.1-1.66) and for clinical vertebral fracture with discontinuation >2 years (aHR=1.2, 1.1-1.4). Results were similar for risedronate, zoledronate, and ibandronate for hip and clinical vertebral fracture. CONCLUSION: Discontinuing alendronate beyond 2 years was associated with increased risk of hip, humerus, and clinical vertebral fractures.

2.
Ann Rheum Dis ; 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31969328

RESUMO

OBJECTIVES: To provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field. METHODS: An international task force considered new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items. RESULTS: The task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high. CONCLUSIONS: These updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.

3.
Joint Bone Spine ; 87(1): 81-83, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31382017

RESUMO

Tumor-induced osteomalacia is a rare cause of acquired hypophosphatemia due to the paraneoplastic overproduction of fibroblast growth factor-23. Unlike many causes of osteomalacia, tumor-induced osteomalacia is curable by resection of the offending tumor. If a patient has a tumor that is unidentifiable, unresectable, or makes the decision to forgo surgery, medical treatment is recommended. Burosumab (KRN23) is a fully human monoclonal antibody against fibroblast growth factor-23 that was recently approved for the treatment of X-linked hypophosphatemia. We present a case of tumor-induced osteomalacia due to two somatostatin receptor avid meningiomas. The patient initially was wheelchair bound due to symptoms of diffuse bone and muscle pain with recurrent traumatic and nontraumatic fractures. Serum phosphate was 1.8mg/dL (reference range: 2.4-5.0mg/dL) with no other laboratory or historical cause. Workup revealed two widely separated intracranial meningiomas with typical magnetic resonance imaging characteristics. The duplicity of tumors precluded safe surgery and the potential delay in, or lack of, efficacy using radiosurgery prompted the treatment team to opt for medical treatment. Burosumab was initiated resulting in improvement in pain symptoms and mobility. Serum phosphate normalized. Trials are ongoing to assess the utility of burosumab in the treatment of tumor-induced osteomalacia.

4.
Curr Opin Rheumatol ; 32(2): 126-133, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31876630

RESUMO

PURPOSE OF REVIEW: To review advances in the understanding of potentially causal relationships between gout, hyperuricemia and comorbidities. RECENT FINDINGS: Observational studies reveal 4-5 comorbidity clusters in gout patients. There tend to be gout alone, gout with chronic kidney disease and gout with other metabolic comorbidities. However, heterogeneous study populations and confounding make inference difficult for causal relationships. Mendelian randomization leverages genetic information as an instrumental variable to indicate putatively causal relationships between traits of epidemiological interest. Thus far, Mendelian randomization has not indicated widespread causal relationships of serum urate for comorbid traits. However, BMI has a small causal effect on serum urate, which may partially explain the increased prevalence of metabolic syndrome and cardiovascular disease among those with gout and hyperuricemia. There is a lack of robust and sufficiently powered Mendelian randomization studies for many serum urate-associated traits, such as hypertension. No adequately powered studies have been completed for gout and its comorbidities. SUMMARY: Although observational studies indicate putative causal effects of serum urate on comorbidities, Mendelian randomization studies suggest that serum urate does not have a causal role on the various tested comorbidities. There remains work to be done in clarifying the causal role of gout per se on the same traits.

5.
Hypertension ; 75(1): 246-256, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31786980

RESUMO

Previous studies do not widely support hyperuricemia as a risk factor for stroke and other cardiovascular diseases. We assessed the relationship between hyperuricemia and ischemic stroke (≈900 cases) using a large data set from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). We employed a case-cohort design (incident stroke cases and randomly selected cohort participants) and weighted Cox-proportional hazard models to estimate the association of serum urate level ≥6.8 mg/dL (ie, hyperuricemia) and 6.0 to <6.8 mg/dL versus <6.0 mg/dL (reference) with incident stroke. Analyses were stratified by race, gender, and age. Mediation of cardiovascular disease comorbidities on the serum urate-stroke association was tested. Hyperuricemia was associated with stroke (hazard ratio, 1.40 [95% CI, 1.10-1.78]) after adjustment for demographic variables and systolic and diastolic blood pressure. This association was substantially attenuated (hazard ratio, 1.17 [95% CI, 0.90-1.51]) by additional covariate adjustment. In particular, apparent treatment-resistant hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg on 3 antihypertensive medications or use of ≥4 antihypertensive medications) and the count of antihypertensive medication classes significantly reduced the effect of hyperuricemia on ischemic stroke. Specifically, apparent treatment-resistant hypertension and number of antihypertensive, respectively, mediate 45% and 43% of the association. There was no effect modification in the association between hyperuricemia and stroke by age, race, or gender. We conclude that hyperuricemia may be a risk factor for stroke. The substantial attenuation of this association by apparent treatment-resistant hypertension and number of antihypertensive suggests that severe hypertension may be a mediator.

6.
Curr Osteoporos Rep ; 17(6): 521-526, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31773402

RESUMO

PURPOSE OF REVIEW: In this review, we present the application of pragmatic clinical trials for evaluating interventions in osteoporosis, and we discuss methodological considerations for designing and conducting a pragmatic clinical trial compared with a classical randomized clinical trial. RECENT FINDINGS: Pragmatic clinical trials are a popular study design testing effectiveness of health interventions and are intended to address the limitations associated with traditional explanatory randomized clinical trials testing efficacy of interventions. To date, only few pragmatic clinical trials have been conducted in osteoporosis. Pragmatic clinical trials are conducted under routine clinical practice setting and are intended to inform policy makers and clinical decisions. Osteoporosis is a chronic disease well-suited to this particular study design given the existence of a clear and specific natural endpoint, namely fracture occurrence, and the availability of several treatments to prevent fractures.

7.
Lancet Diabetes Endocrinol ; 7(12): 899-911, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31676222

RESUMO

BACKGROUND: Odanacatib, a cathepsin K inhibitor, reduces bone resorption while maintaining bone formation. Previous work has shown that odanacatib increases bone mineral density in postmenopausal women with low bone mass. We aimed to investigate the efficacy and safety of odanacatib to reduce fracture risk in postmenopausal women with osteoporosis. METHODS: The Long-term Odanacatib Fracture Trial (LOFT) was a multicentre, randomised, double-blind, placebo-controlled, event-driven study at 388 outpatient clinics in 40 countries. Eligible participants were women aged at least 65 years who were postmenopausal for 5 years or more, with a femoral neck or total hip bone mineral density T-score between -2·5 and -4·0 if no previous radiographic vertebral fracture, or between -1·5 and -4·0 with a previous vertebral fracture. Women with a previous hip fracture, more than one vertebral fracture, or a T-score of less than -4·0 at the total hip or femoral neck were not eligible unless they were unable or unwilling to use approved osteoporosis treatment. Participants were randomly assigned (1:1) to either oral odanacatib (50 mg once per week) or matching placebo. Randomisation was done using an interactive voice recognition system after stratification for previous radiographic vertebral fracture, and treatment was masked to study participants, investigators and their staff, and sponsor personnel. If the study completed before 5 years of double-blind treatment, consenting participants could enrol in a double-blind extension study (LOFT Extension), continuing their original treatment assignment for up to 5 years from randomisation. Primary endpoints were incidence of vertebral fractures as assessed using radiographs collected at baseline, 6 and 12 months, yearly, and at final study visit in participants for whom evaluable radiograph images were available at baseline and at least one other timepoint, and hip and non-vertebral fractures adjudicated as being a result of osteoporosis as assessed by clinical history and radiograph. Safety was assessed in participants who received at least one dose of study drug. The adjudicated cardiovascular safety endpoints were a composite of cardiovascular death, myocardial infarction, or stroke, and new-onset atrial fibrillation or flutter. Individual cardiovascular endpoints and death were also assessed. LOFT and LOFT Extension are registered with ClinicalTrials.gov (number NCT00529373) and the European Clinical Trials Database (EudraCT number 2007-002693-66). FINDINGS: Between Sept 14, 2007, and Nov 17, 2009, we randomly assigned 16 071 evaluable patients to treatment: 8043 to odanacatib and 8028 to placebo. After a median follow-up of 36·5 months (IQR 34·43-40·15) 4297 women assigned to odanacatib and 3960 assigned to placebo enrolled in LOFT Extension (total median follow-up 47·6 months, IQR 35·45-60·06). In LOFT, cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 3·7% (251/6770) versus 7·8% (542/6910), hazard ratio (HR) 0·46, 95% CI 0·40-0·53; hip fractures 0·8% (65/8043) versus 1·6% (125/8028), 0·53, 0·39-0·71; non-vertebral fractures 5·1% (412/8043) versus 6·7% (541/8028), 0·77, 0·68-0·87; all p<0·0001. Combined results from LOFT plus LOFT Extension for cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 4·9% (341/6909) versus 9·6% (675/7011), HR 0·48, 95% CI 0·42-0·55; hip fractures 1·1% (86/8043) versus 2·0% (162/8028), 0·52, 0·40-0·67; non-vertebral fractures 6·4% (512/8043) versus 8·4% (675/8028), 0·74, 0·66-0·83; all p<0·0001. In LOFT, the composite cardiovascular endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 273 (3·4%) of 8043 patients in the odanacatib group versus 245 (3·1%) of 8028 in the placebo group (HR 1·12, 95% CI 0·95-1·34; p=0·18). New-onset atrial fibrillation or flutter occurred in 112 (1·4%) of 8043 patients in the odanacatib group versus 96 (1·2%) of 8028 in the placebo group (HR 1·18, 0·90-1·55; p=0·24). Odanacatib was associated with an increased risk of stroke (1·7% [136/8043] vs 1·3% [104/8028], HR 1·32, 1·02-1·70; p=0·034), but not myocardial infarction (0·7% [60/8043] vs 0·9% [74/8028], HR 0·82, 0·58-1·15; p=0·26). The HR for all-cause mortality was 1·13 (5·0% [401/8043] vs 4·4% [356/8028], 0·98-1·30; p=0·10). When data from LOFT Extension were included, the composite of cardiovascular death, myocardial infarction, or stroke occurred in significantly more patients in the odanacatib group than in the placebo group (401 [5·0%] of 8043 vs 343 [4·3%] of 8028, HR 1·17, 1·02-1·36; p=0·029, as did stroke (2·3% [187/8043] vs 1·7% [137/8028], HR 1·37, 1·10-1·71; p=0·0051). INTERPRETATION: Odanacatib reduced the risk of fracture, but was associated with an increased risk of cardiovascular events, specifically stroke, in postmenopausal women with osteoporosis. Based on the overall balance between benefit and risk, the study's sponsor decided that they would no longer pursue development of odanacatib for treatment of osteoporosis. FUNDING: Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, Kenilworth, NJ, USA.

8.
Ther Adv Musculoskelet Dis ; 11: 1759720X19883973, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695755

RESUMO

Biologics are substances synthetized from biological sources used in the prevention and treatment of several diseases. Rheumatologists have many years of experience with biologics for the treatment of immune-mediated diseases and osteoporosis. Randomized clinical trials and postmarketing studies have demonstrated that treatment with biologics can result, albeit infrequently, in serious adverse events. To date, several risk mitigation strategies have been identified and implemented. The objective of the present perspective review is to examine the risk mitigation strategies of biologic treatments, with special focus on anti-tumor necrosis factors and denosumab.

9.
JAMA Netw Open ; 2(11): e1915105, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31722026

RESUMO

Importance: Studies to date have not comprehensively examined pain experience after total knee arthroplasty (TKA). Discrete patterns of pain in this period might be associated with pain outcomes at 6 to 12 months after TKA. Objectives: To examine patterns of individual post-TKA pain trajectories and to assess their independent associations with longer-term pain outcome after TKA. Design, Setting, and Participants: This prospective cohort study combined data from a national US TKA cohort with ancillary pain severity data at 2 weeks and 8 weeks after the index TKA using a numeric rating scale. All participants received primary, unilateral TKA within the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement (FORCE-TJR) national network of community sites in 22 states or at the lead site (University of Massachusetts Medical School). Participants had a date of surgery between May 1, 2013, and December 1, 2014. The data analysis was performed between January 13, 2015, and July 5, 2016. Exposures: Pain trajectories in the postoperative period (8 weeks). Main Outcomes and Measures: Index knee pain at 6 months after TKA using the Knee Injury and Osteoarthritis Outcome Score (KOOS) pain scale. Group-based trajectory methods examined the presence of pain trajectories in the postoperative period (8 weeks) and assessed whether trajectories were independently associated with longer-term pain (6 months). Results: The cohort included 659 patients who underwent primary TKA with complete data at 4 points (preoperative, 2 weeks, 8 weeks, and 26 weeks). Their mean (SD) age was 67.1 (8.0) years, 64.5% (425 of 659) were female, the mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 30.77 (5.66), 94.5% (613 of 649) were white, and the mean (SD) preoperative 36-Item Short Form Health Survey physical component summary and mental component summary scores were 34.1 (8.2) and 53.8 (11.4), respectively. Two pain trajectory subgroups were identified at 8 weeks after TKA: patients who experienced fast pain relief in the first 8 weeks after TKA (fast pain responders, composing 72.4% [477 of 659] of the sample) and patients who did not (slow pain responders, composing 27.6% [182 of 659] of the sample). After adjusting for patient factors, the pain trajectory at 8 weeks after TKA was independently associated with the mean KOOS pain score at 6 months, with a between-trajectory difference of -11.3 (95% CI, -13.9 to -8.7). Conclusions and Relevance: The trajectory among slow pain responders at 8 weeks after surgery was independently associated with improved but greater persistent index knee pain at 6 months after TKA compared with that among fast pain responders. Early identification of patients with a trajectory of slow pain response at 8 weeks after TKA may offer an opportunity for interventions in the perioperative period to potentially improve the long-term pain outcomes after TKA.

10.
Core Evid ; 14: 41-50, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692480

RESUMO

Introduction: Glucocorticoid-induced osteoporosis is an underrecognized complication of chronic glucocorticoid therapy characterized by a decrease in new bone formation. Anabolic therapies, such as teriparatide, a recombinant human parathyroid hormone, combat the disease by promoting new bone growth. Aims: This article outlines the pathophysiology of glucocorticoid-induced osteoporosis and details the evidence of efficacy, safety, and patterns of use of teriparatide and other future anabolic therapies. Evidence review: In multiple clinical trials, teriparatide has been shown to significantly increase lumbar spine bone mineral density (BMD) in patients with glucocorticoid-induced osteoporosis when compared with placebo, alendronate, and risedronate. When compared with alendronate, significantly fewer vertebral fractures were noted in the teriparatide group. Adverse effects noted in clinical trials include nausea, insomnia, flushing, myalgias, and mild hypercalcemia/hyperuricemia. Early studies in rats noted an increased incidence of osteosarcoma; however, an increased rate beyond levels seen in general populations has not been noted in human studies or with long-term pharmacovigilance. Abaloparatide and romosozumab are newer anabolic therapies that have shown some benefit in postmenopausal osteoporosis but have not yet been studied in the chronic glucocorticoid population. Place in therapy: Major specialty organizations continue to recommend bisphosphonates as first-line therapy in glucocorticoid-induced osteoporosis due to the proven benefit and relative affordability. However, the use of anabolics shows promise to improve outcomes by increasing BMD and reducing fracture-associated morbidity and mortality and has a role for selected populations at high fracture risk.

11.
J Bone Miner Res ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714637

RESUMO

Adverse events related to long-term use of bisphosphonates have raised interest in temporary drug discontinuation. Trends in bisphosphonate discontinuation and restart, as well factors associated with these decisions, are not fully understood at a population level. We investigated temporal trends of bisphosphonate discontinuation from 2010 to 2015 and identified factors associated with discontinuation and restart of osteoporosis therapy. Our cohort consisted of long-term bisphosphonate users identified from 2010 to 2015 Medicare data. We defined discontinuation as ≥12 months without bisphosphonate prescription claims. We used conditional logistic regression to compare factors associated with alendronate discontinuation or osteoporosis therapy restart in the 120-day period preceding discontinuation or restart referent to the 120-day preceding control periods. Among 73,800 long-term bisphosphonate users, 59,251 (80.3%) used alendronate, 6806 (9.2%) risedronate, and 7743 (10.5%) zoledronic acid, exclusively. Overall, 26,281 (35.6%) discontinued bisphosphonates for at least 12 months. Discontinuation of bisphosphonates increased from 1.7% in 2010, reaching a peak of 14% in 2012 with levels plateauing through 2015. The factors most strongly associated with discontinuation of alendronate were: benzodiazepine prescription (adjusted odds ratio [aOR] = 2.5; 95% confidence interval [CI] 2.1, 3.0), having a dual-energy X-ray absorptiometry (DXA) scan (aOR = 1.8; 95% CI 1.7, 2.0), and skilled nursing facility care utilization (aOR = 1.8; 95% CI 1.6, 2.1). The factors most strongly associated with restart of osteoporosis therapy were: having a DXA scan (aOR = 9.9; 95% CI 7.7, 12.6), sustaining a fragility fracture (aOR = 2.8; 95% CI 1.8, 4.5), and an osteoporosis or osteopenia diagnosis (aOR = 2.5; 95% CI 2.0, 3.1). Our national evaluation of bisphosphonate discontinuation showed that an increasing proportion of patients on long-term bisphosphonate therapy discontinue medications. The factors associated with discontinuation of alendronate were primarily related to worsening of overall health status, whereas traditional factors associated with worsening bone health were associated with restarting osteoporosis medication. © 2019 American Society for Bone and Mineral Research.

12.
Ther Adv Musculoskelet Dis ; 11: 1759720X19876468, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565078

RESUMO

Glucocorticoid-induced osteoporosis (GIOP) is the most common form of secondary osteoporosis. To date, six large randomized controlled clinical trials on the efficacy of pharmaceutical treatment in GIOP have been conducted. All of these studies have focused predominately on bone mineral density outcomes, and none of them have been statistically powered to address fracture endpoints. The purpose of this review is to highlight differences in the design and results within these large randomized GIOP clinical trials, and how these differences might affect clinical decisions. Differences between studies in trial design, populations studied, and variable efficacy impact the comparability and generalizability of these findings, and ultimately should affect practitioners' behavior. We review the clinical trials that provide the best quality evidence on comparative efficacy and safety of GIOP treatments. We also propose suggestions on the design of future GIOP clinical trials with attention to improved generalizability, and, ideally, study designs that might achieve fracture outcomes.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31522762

RESUMO

OBJECTIVE: Glucocorticoids are common in RA management despite an unfavorable, exposure-dependent risk profile impacted by patient and provider-level factors. Existing work describing glucocorticoid use in RA is not generalizable and does not adequately examine provider factors. We aim to describe how providers prescribe glucocorticoids to commercially insured, newly diagnosed RA patients in the United States. METHODS: This was a retrospective cohort study which used the national Optum© administrative database. We identified 9221 adults ages 18-65 with RA diagnosed 2010-2014. We assessed glucocorticoid dispensing 3 months pre-diagnosis through 12months post-diagnosis ("study period"), cumulatively stratified by calendar quarter and prescriber specialty (rheumatologist, primary care, other). We examined prescribing variation among individual rheumatologists by dividing quarterly distribution of per-patient dose and days' supply into quartiles. RESULTS: 6717 (72.8%) patients filled ≥1 glucocorticoid prescription during the study period. 2890 (31.3%) patients received ≥3 months' supply, with median (IQR) daily dose 10 (6.6) mg/day and days' supply 189 (143) days. 52.6% of patients received glucocorticoids 1-3 months post-diagnosis; 29.2% received glucocorticoids 10-12 months post-diagnosis. Among glucocorticoid users post-diagnosis, quarterly median daily dose and days' supply were consistently ≥10 mg/day and ≥30 days, respectively. Rheumatologists prescribed most glucocorticoids, with median per-quarter daily dose and days' supply 10 mg/day and 43-60 days. Individual rheumatologists' prescribing varied widely across all quarters. CONCLUSION: Among commercially insured incident RA patients, receipt of ≥10 mg/day prednisone equivalent for months is common, typically prescribed by rheumatologists, and persists a year post-diagnosis in 29.2% of patients. Glucocorticoid prescribing varies widely across rheumatologists. Further work is warranted to identify provider factors explaining variation in glucocorticoid prescribing, and assess how these affect health outcomes.

14.
J Clin Transl Sci ; 3(1): 37-44, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31402988

RESUMO

Mini-sabbaticals are formal short-term training and educational experiences away from an investigator's home research unit. These may include rotations with other research units and externships at government research or regulatory agencies, industry and non-profit programs, and training and/or intensive educational programs. The National Institutes of Health have been encouraging training institutions to consider offering mini-sabbaticals, but given the newness of the concept, limited data are available to guide the implementation of mini-sabbatical programs. In this paper, we review the history of sabbaticals and mini-sabbaticals, report the results of surveys we performed to ascertain the use of mini-sabbaticals at Clinical and Translational Science Award hubs, and consider best practice recommendations for institutions seeking to establish formal mini-sabbatical programs.

15.
J Rheumatol ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31416925

RESUMO

OBJECTIVE: To assess factors associated with the ability to achieve and maintain target serum urate (SU) with allopurinol in patients with gout. METHODS: We used National VA national databases from 2002-2012. Eligible patients had ≥1 inpatient or ≥2 outpatient visits with a diagnostic code for gout, filled a new index allopurinol prescription, had at least one post-treatment SU measured, and met 12-month observability rule. Treatment successes were defined as the achievement of post-index SU <6 mg/dl (success 1) and post-index SU <6 mg/dl that was sustained (success 2). RESULTS: Of the 198,839 unique patients with allopurinol use, 41,153 unique patients (with 47,072 episodes) and 17,402 unique patients (with 18,323 episodes) were eligible for analyses for success 1 and success 2; 42% each achieved (success 1) or achieved and maintained post-index SU <6 mg/dl (success 2). In multivariable-adjusted models, factors associated with significantly higher odds of both outcomes were: older age, normal BMI, Deyo-Charlson index score of 0, rheumatologist as the main provider rather than non-rheumatologist, Midwest U.S. location for the healthcare facility, a lower hospital bed size, military service-connection for medical conditions of 50% or more (a measure of healthcare access priority), longer distance to the nearest VA facility, and lower pre-index SU. CONCLUSION: We identified novel factors associated with maintaining SU <6 mg/dl based on a theoretical model. Several potentially modifiable factors can be targeted by individual/provider/systems interventions for improving successful achievement and maintenance of target SU in patients with gout.

16.
J Eval Clin Pract ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31429175

RESUMO

OBJECTIVE: To discuss the study design and data analysis for three-phase interrupted time series (ITS) studies to evaluate the impact of health policy, systems, or environmental interventions. Simulation methods are used to conduct power and sample size calculation for these studies. METHODS: We consider the design and analysis of three-phase ITS studies using a study funded by National Institutes of Health as an exemplar. The design and analysis of both one-arm and two-arm three-phase ITS studies are introduced. RESULTS: A simulation-based approach, with ready-to-use computer programs, was developed to determine the power for two types of three-phase ITS studies. Simulations were conducted to estimate the power of segmented autoregressive (AR) error models when autocorrelation ranged from -0.9 to 0.9 with various effect sizes. The power increased as the sample size or the effect size increased. The power to detect the same effect sizes varied largely, depending on testing level change, trend changes, or both. CONCLUSION: This article provides a convenient tool for investigators to generate sample sizes to ensure sufficient statistical power when three-phase ITS study design is implemented.

17.
Arthritis Res Ther ; 21(1): 160, 2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31255174

RESUMO

OBJECTIVE: To examine the feasibility, preference, and satisfaction of an interactive voice response (IVR) system versus a customized smartphone application (StudyBuddy) to capture gout flares METHODS: In this 24-week prospective, randomized, crossover, open-label pilot study, 44 gout patients were randomized to IVR vs. StudyBuddy and were crossed over to the other technology after 12 weeks. Flares were reported via weekly (and later daily) scheduled StudyBuddy or IVR queries. Feasibility was ascertained via response rate to scheduled queries. At 12 and 24 weeks, participants completed preference/satisfaction surveys. Preference and satisfaction were assessed using dichotomous or ordinal questions. Sensitivity was assessed by the frequency of flare reporting with each approach. RESULTS: Thirty-eight of 44 participants completed the study. Among completers, feasibility was similar for IVR (81%) and StudyBuddy (80%). Conversely, most (74%) preferred StudyBuddy. Measures of satisfaction (ease of use, preference over in-person clinic visits, and willingness for future use) were similar between the IVR and StudyBuddy; however, more participants deemed the StudyBuddy as convenient (95% vs. 73%, P = 0.01) and less disruptive (97% vs. 82%, P = 0.03). Although the per patient number of weeks in flare was not significantly different (mean 3.4 vs. 2.6 weeks/patient, P = 0.15), the StudyBuddy captured more of the total flare weeks (35%) than IVR (27%, P = 0.02). CONCLUSION: A smartphone application and IVR demonstrated similar feasibility but overall sensitivity to capture gout flares and participant preference were greater for the smartphone application. Participant preference for the smartphone application appeared to relate to perceptions of greater convenience and lower disruption. TRIAL REGISTRATION: NCT, NCT02855437 . Registered 4 August 2016.

18.
Rheum Dis Clin North Am ; 45(3): 453-464, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31277755

RESUMO

There are more than 10,000 articles in the literature published since 1999 that appear in a search of hyperuricemia and hypouricemia for vascular events. Systematic reviews were reviewed for this time frame, numbering approximately 300 articles in addition to more than 400 reports of randomized clinical trials published since 2017. In summary, the epidemiologic associations of hyperuricemia and hypouricemia with vascular disease are confounded by comorbid conditions. The interventional data are suggestive of a relationship of gout and vascular disease and to a lesser extent hyperuricemia and hypertension; however, more interventional studies are necessary to confirm these relationships.

19.
Ther Adv Musculoskelet Dis ; 11: 1759720X19847018, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31205513

RESUMO

Despite the availability of effective urate-lowering therapy (ULT) and anti-inflammatory drugs for the treatment of gout, there is considerable interest in novel treatment approaches. Patients with gout often have a multitude of comorbidities, leading to concern over drug-drug interactions and medication adverse events. The cherry is a small nutrient-rich fruit that has garnered a great deal of attention in recent years as a nonpharmacologic option for the treatment of a multitude of disease manifestations. Perhaps a quarter of patients with gout try cherries or cherry products to treat their gout, which have antioxidant and anti-inflammatory (IL-6, TNF-α, IL-1ß, IL-8, COX-I and -II) properties, hypouricemic effects, and the ability to downregulate NFkB-mediated osteoclastogenesis. Based on these properties, cherries may reduce both the acute and chronic inflammation associated with recurrent gout flares and its chronic destructive arthropathy. In this review, we explore the potential benefits of cherries and cherry products as a nonpharmacologic option for the treatment of gout.

20.
Arthritis Rheumatol ; 71(10): 1771-1772, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31215773
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