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1.  Effect of pegloticase on renal function in patients with chronic kidney disease: a post hoc subgroup analysis of 2 randomized, placebo-controlled, phase 3 clinical trials 
BMC Research Notes  2014;7:54.
Background
Pegloticase is approved in the US for treatment of refractory chronic gout. Since chronic kidney disease (CKD) is common in these patients, we conducted a post-hoc analysis of 2 replicate phase 3 trials and the subsequent open-label extension study to determine the effects of pegloticase on renal function in patients with CKD stages 3 and 4, as well as the effects of renal dysfunction on pegloticase efficacy and safety.
Findings
Patients with renal insufficiency were randomized to pegloticase 8 mg every 2 weeks (n = 42), pegloticase 8 mg every 4 weeks (n = 41), or placebo (n = 20) for 6 months as defined by the study protocols. Renal function was assessed by estimated glomerular filtration rate (eGFR). All patients completing the randomized trials could participate in an open-label extension study for a further 2.5 years. Uric acid response, the primary end point in the trials, was plasma uric acid <6.0 mg/dl for 80% of months 3 and 6.
Mean eGFR in both pegloticase dosing cohorts remained constant over the randomized treatment phase and long-term open-label extension study. The number of patients achieving uric acid response was similar across CKD stages (32% stage 1, 23% stage 2, 35% stage 3, and 39% stage 4, respectively, P = 0.3). There was no difference in the pegloticase safety profile based on CKD stage.
Conclusions
Pegloticase treatment does not impact eGFR in CKD patients and response to pegloticase is independent of CKD stage.
Trial registration
Clinical trial identifier: NCT00325195
doi:10.1186/1756-0500-7-54
PMCID: PMC3937145  PMID: 24447425
Refractory chronic gout; Uric acid; Kidney; Renal function
2.  Tophus burden reduction with pegloticase: results from phase 3 randomized trials and open-label extension in patients with chronic gout refractory to conventional therapy 
Arthritis Research & Therapy  2013;15(5):R137.
Introduction
Two replicate randomized, placebo-controlled six-month trials (RCTs) and an open-label treatment extension (OLE) comprised the pegloticase development program in patients with gout refractory to conventional therapy. In the RCTs, approximately 40% of patients treated with the approved dose saw complete response (CR) of at least one tophus. Here we describe the temporal course of tophus resolution, total tophus burden in patients with multiple tophi, tophus size at baseline, and the relationship between tophus response and urate-lowering efficacy.
Methods
Baseline subcutaneous tophi were analyzed quantitatively using computer-assisted digital images in patients receiving pegloticase (8 mg biweekly or monthly) or placebo in the RCTs, and pegloticase in the OLE. Tophus response, a secondary endpoint in the trials, was evaluated two ways. Overall tophus CR was the proportion of patients achieving a best response of CR (without any new/enlarging tophi) and target tophus complete response (TT-CR) was the proportion of all tophi with CR.
Results
Among 212 patients randomized in the RCTs, 155 (73%) had ≥1 tophus and 547 visible tophi were recorded at baseline. Overall tophus CR was recorded in 45% of patients in the biweekly group (P = 0.002 versus placebo), 26% in the monthly group, and 8% in the placebo group after six months of RCT therapy. TT-CR rates at six months were 28%, 19%, and 2% of tophi, respectively. Patients meeting the primary endpoint of sustained urate-lowering response to therapy (responders) were more likely than nonresponders to have an overall tophus CR at six months (54% vs 20%, respectively and 8% with placebo).
Both overall tophus CR and TT-CRs increased with treatment duration in the OLE, reaching 70% (39/56) of patients and 55% (132/238) of target tophi after one year of treatment in patients receiving pegloticase during both the RCTs and OLE. At that time point, more tophi had resolved in responders (102/145 or 70% of tophi) than nonresponders (30/93; 32%).
Conclusions
Pegloticase reduced tophus burden in patients with refractory tophaceous gout, especially those achieving sustained urate-lowering. Complete resolution of tophi occurred in some patients by 13 weeks and in others with longer-term therapy.
Trial registrations
NCT00325195, NCT01356498
doi:10.1186/ar4318
PMCID: PMC3979037  PMID: 24286509
3.  Patients’ knowledge and beliefs concerning gout and its treatment: a population based study 
Background
For patients to effectively manage gout, they need to be aware of the impact of diet, alcohol use, and medications on their condition. We sought to examine patients’ knowledge and beliefs concerning gout and its treatment in order to identify barriers to optimal patient self-management.
Methods
We identified patients (≥18 years of age) cared for in the setting of a multispecialty group practice with documentation of at least one health care encounter associated with a gout diagnosis during the period 2008–2009 (n = 1346). Patients were sent a questionnaire assessing knowledge with regard to gout, beliefs about prescription medications used to treat gout, and trust in the physician. Administrative electronic health records were used to identify prescription drug use and health care utilization.
Results
Two hundred and forty patients returned surveys out of the 500 contacted for participation. Most were male (80%), white (94%), and aged 65 and older (66%). Only 14 (6%) patients were treated by a rheumatologist. Only a minority of patients were aware of common foods known to trigger gout (e.g., seafood [23%], beef [22%], pork [7%], and beer [43%]). Of those receiving a urate-lowering medication, only 12% were aware of the short-term risks of worsening gout with initiation. These deficits were more common in those with active as compared to inactive gout.
Conclusion
Knowledge deficits about dietary triggers and chronic medications were common, but worse in those with active gout. More attention is needed on patient education on gout and self-management training.
doi:10.1186/1471-2474-13-180
PMCID: PMC3517442  PMID: 22995041
Beliefs; Treatment; Gout; Dietary influence; Physician-patient communication
4.  Adherence and Occurrence of Fractures after Switching to Once-Monthly Oral Bisphophonates 
Pharmacoepidemiology and drug safety  2010;19(12):1233-1240.
Purpose
Reducing dosing demands of medications generally increases adherence, although this relationship has not been demonstrated with the once-monthly oral bisphosphonates (BP). The study aim is to test whether switching from once-weekly BPs to once-monthly BPs improves adherence and fracture risk.
Methods
This is an interrupted times-series analysis of new users of once-weekly BPs in a nationwide administrative health database from 2003–2007. Participants include 1835 individuals who switched to once-monthly BPs and two propensity-matched comparator groups: 1835 individuals who switched to a different once-weekly BP, and 1835 who did not switch. We measured changes in adequate adherence pre- and post-switch as monthly medication possession ratio >0.80, and calculated incidence rate ratios [IRR] of osteoporotic fractures.
Results
All study groups experienced major adherence failure in the first year of therapy: the proportion of adequate adherers was 42% among once-monthly switchers, 47% among once-weekly switchers, and 37% among nonswitchers. However, the once-monthly switch was associated with less adherence failure (4% fewer adherers per month pre-switch vs. 1% fewer adherers per month post-switch, p<.000). There was no statistically significant change in adherence rates for the other groups. We did not detect significantly reduced fracture risk with once-monthly switch: 1 year post-switch, the fracture incidence risk ratios for once-monthly switchers relative to once-weekly switchers were IRR 0.83, 95% CI: 0.50–1.36, and IRR 0.90, 95% CI: 0.54–1.49, relative to nonswitchers).
Conclusions
Reducing the dosing demands of oral bisphosphonates from once-weekly to once-monthly decreased adherence failure but had an uncertain impact on fracture risk.
doi:10.1002/pds.2048
PMCID: PMC3079953  PMID: 21108489
patient compliance; bisphosphonates; osteoporosis; osteoporotic fractures; medication adherence
5.  Patients and providers view gout differently: a qualitative study 
Chronic illness  2010;6(4):263-271.
Objective
We sought to examine patients’ and providers’ views on the treatment of gout to better understand why management is suboptimal.
Methods
In-depth telephone interviews were conducted with gout patients (n=26) who initiated treatment with a urate-lowering drug (ULD) in the prior 6 months and with providers who care for gout patients (n=15). The interviews were audiotaped and transcribed verbatim. Using qualitative methods, results were analyzed and themes were identified. Interviews focused on the acute management, chronic management, and prevention and improvement strategies.
Results
Providers viewed the majority of patients as having excellent relief with nonsteroidal anti-inflammatories, colchicine and glucocorticoids while some patients felt these medications were ineffective. Providers felt most patients had a good understanding of the rationale for ULD therapy and that patients responded well. Some patients felt ULDs triggered, worsened or had no impact on their disease. Most providers thought medication adherence was relatively good. Some patients reported discontinuing medications. Discontinuations were largely purposeful and due to clinical or financial concerns. Most providers thought their skills adequate to teach disease self-management behaviors. Patients requested more information and longer visit times.
Conclusions
Providers view gout as easily managed while patients report challenges and purposeful nonadherence.
doi:10.1177/1742395310378761
PMCID: PMC3134238  PMID: 20675361
medication use; gout treatment; medication adherence; qualitative
6.  Design and methods for a randomized clinical trial comparing three outreach efforts to improve screening mammography adherence 
Background
Despite the demonstrated need to increase screening mammography utilization and strong evidence that mail and telephone outreach to women can increase screening, most managed care organizations have not adopted comprehensive outreach programs. The uncertainty about optimum strategies and cost effectiveness have retarded widespread acceptance. While 70% of women report getting a mammogram within the prior 2 years, repeat mammography rates are less than 50%. This 5-year study is conducted though a Central Massachusetts healthcare plan and affiliated clinic. All womenhave adequate health insurance to cover the test.
Methods/Design
This randomized study compares 3 arms: reminder letter alone; reminder letter plus reminder call; reminder letter plus a second reminder and booklet plus a counselor call. All calls provide women with the opportunity to schedule a mammogram in a reasonable time. The invention period will span 4 years and include repeat attempts. The counselor arm is designed to educate, motivate and counsel women in an effort to alleviate PCP burden.
All women who have been in the healthcare plan for 24 months and who have a current primary care provider (PCP) and who are aged 51-84 are randomized to 1 of 3 arms. Interventions are limited to women who become ≥18 months from a prior mammogram. Women and their physicians may opt out of the intervention study.
Measurement of completed mammograms will use plan billing records and clinic electronic records. The primary outcome is the proportion of women continuously enrolled for ≥24 months who have had ≥1 mammogram in the last 24 months. Secondary outcomes include the number of women who need repeat interventions. The cost effectiveness analysis will measure all costs from the provider perspective.
Discussion
So far, 18,509 women aged 51-84 have been enrolled into our tracking database and were randomized into one of three arms. At baseline, 5,223 women were eligible for an intervention. We anticipate that the outcome will provide firm data about the maximal effectiveness as well as the cost effectiveness of the interventions both for increasing the mammography rate and the repeat mammography rate.
Trial registration
http://clinicaltrials.gov/NCT01332032
doi:10.1186/1472-6963-11-145
PMCID: PMC3133545  PMID: 21639900
7.  Adoption of Once-monthly Oral Bisphosphonates and the Impact on Adherence 
The American journal of medicine  2010;123(3):275-280.
Background
The extent of the adoption of once-monthly bisphosphonates into general clinical practice is not known, nor is it known if the novel formulation improves adherence.
Methods
We analyzed administrative claims 2003-2006 from a large employer-based health insurance database for incident use of oral bisphosphonates and stratified users by daily, weekly and monthly dosing regimen. We measured adherence as the medication possession ratio (MPR) during the first year of therapy. We compared patient characteristics by dosing regimen and evaluated how the dosing regimen influenced the MPR.
Results
We identified 61,125 incident users of bisphosphonates (n=1034 daily, n=56,925 weekly, n=3166 monthly). Monthly bisphosphonate users were, on average, slightly older than the other groups (mean age 66 years monthly vs. 65 weekly or 66 daily, p<.05.) and more often lived in the U.S. North Central or South (76% vs. 72% weekly or 69% daily users, p<.05). There were no detectable differences among the dosing groups in the history of serious GI risk, comorbidity burden, or prior osteoporotic fractures. During the first year of bisphosphonate therapy, 49% of monthly users had MPR ≥80% compared to 49% weekly users (N.S.) or 23% daily users (p<.0001).
Conclusions
We found little evidence of preferential prescribing of monthly bisphosphonates to certain types of patients. Furthermore, we found no evidence of improved bisphosphonate adherence with monthly dosing relative to weekly dosing, although adherence with either weekly or monthly dosing was significantly better than with daily dosing.
doi:10.1016/j.amjmed.2009.05.017
PMCID: PMC2831769  PMID: 20193837
patient compliance; bisphosphonates; novel formulation
8.  The Dynamics of Chronic Gout Treatment: medication gaps and return to therapy 
Objective
To identify gaps in therapy with urate-lowering drugs for the treatment of gout as well as factors associated with resuming therapy.
Methods
We identified persons from two integrated delivery systems 18 years or older with a diagnosis of gout who initiated use of a urate-lowering drug from January 1, 2000 through June 30, 2006 and who had a gap in therapy. A gap was defined as a period of over 60 days after the completion of one prescription in which no refill for a urate-lowering drug was obtained. Survival curves were used to assess return to therapy of urate-lowering drugs. Cox proportional hazards analysis estimated the association between covariates and return to therapy.
Results
There were 4,166 new users of urate-lowering drugs (97% received allopurinol) of whom 2,929 (70%) had a gap in therapy. Among those with a gap, in 75% it occurred in the first year of therapy. Fifty percent of patients with a gap returned to therapy within 8 months, and by 4 years it was 75%. Age 45 to 74 (<45 referent) and greater duration of urate-lowering drug use prior to the gap was associated with resuming treatment within one year. In contrast, receipt of NSAIDs or glucocorticoids in the year prior to the gap was associated with a reduced likelihood of resuming therapy.
Conclusions
The majority of gout patients with gaps in urate-lowering drug use returned to treatment. More investigation is needed to better understand why patients may go for months without refilling prescriptions given the clinical consequences of nonadherence.
doi:10.1016/j.amjmed.2009.05.026
PMCID: PMC2813203  PMID: 20102992
persistence; adherence; compliance; gout; urate lowering drugs
9.  Patient Decision to Initiate Therapy for Osteoporosis: The Influence of Knowledge and Beliefs 
Journal of General Internal Medicine  2008;23(11):1815-1821.
Background
There are effective treatments to prevent osteoporotic fractures, but these treatments are underutilized.
Objective
To evaluate the influence of patient characteristics, perceptions, knowledge and beliefs about osteoporosis on the decision to initiate osteoporotic treatment.
Participants
We identified female members of a managed care plan who had a dual energy x-ray absorptiometry (DXA) bone density test and fulfilled World Health Organization criteria for osteoporosis. Patients were excluded if they received osteoporotic medications in the prior 6 months.
Measurements
Patients were sent a questionnaire that included items assessing satisfaction with physician–patient communication, trust in the physician, osteoporosis knowledge and beliefs, beliefs about prescription medications, and perceptions of barriers to medication use. Administrative electronic health records were used to identify prescription drug use and health care utilization.
Results
Two hundred and thirty-six women returned surveys and research authorization forms out of 465 contacted for participation. One hundred and thirty-five (57.2%) filled a prescription for an osteoporotic drug in the first 3 months after the DXA exam. The largest differences between initiators and non-initiators were in beliefs in the benefits of medications, and distrust of medications, with initiators believing more strongly in the benefits and effectiveness of medications (p < .001), and non-initiators reporting more distrust of medications (p < .001). Osteoporosis knowledge and the belief that osteoporosis is a serious disease were also related to therapy initiation in bivariate analysis.
Conclusions
Only 57% of patients initiated osteoporotic medication within 3 months of diagnosis. The decision to start osteoporosis treatment appeared to be related to a patient’s beliefs in the effectiveness of osteoporosis medications and distrust of medications.
doi:10.1007/s11606-008-0772-0
PMCID: PMC2585659  PMID: 18787907
medication adherence; patient preferences; osteoporosis; decision-making
10.  CARDIOLOGY CLINICAL TRIAL PARTICIPATION IN COMMUNITY-BASED HEALTHCARE SYSTEMS: OBSTACLES AND OPPORTUNITIES 
Contemporary clinical trials  2008;29(5):646-653.
Background
The objective of our study was to examine cardiologists’ and organizational leaders’ interest in clinical trial participation and perceived barriers and facilitators to participation within ten diverse non-profit healthcare delivery systems. Trials play a pivotal role in advancing knowledge about the safety and efficacy of cardiovascular interventions and tests. Although cardiovascular trials successfully enroll patients, recruitment challenges persist. Community-based health systems could be an important source of participants and investigators, but little is known about community cardiologists’ experiences with trials.
Methods
We interviewed 25 cardiology and administrative leaders and mailed questionnaires to all 280 cardiologists at 10 U.S. healthcare organizations.
Results
The survey received a 73% response rate. While 60% of respondents had not participated in any trials in the past year, nearly 75% wanted greater participation. Cardiologists reported positive attitudes toward trial participation; more than half agreed that trials were their first choice of therapy for patients, if available. Almost all leaders described their organizations as valuing research but not necessarily trials. Major barriers to participation were lack of physician time and insufficient skilled research nurses.
Conclusions
Cardiologists have considerable interest in trial participation. Major obstacles to increased participation are lack of time and effective infrastructure to support trials. These results suggest that community-based health systems are a rich source for cardiovascular research but additional funding and infrastructure are needed to leverage this resource.
doi:10.1016/j.cct.2008.02.003
PMCID: PMC2615791  PMID: 18397842
clinical trials; clinical trials recruitment; barriers to clinical trial participation; clinician participation in clinical trials
11.  Adherence with urate-lowering therapies for the treatment of gout 
Introduction
Adherence to urate-lowering drugs (ULDs) has not been well evaluated among those with gout. Our aim was to assess the level and determinants of non-adherence with ULDs prescribed for gout.
Methods
We identified persons using two integrated delivery systems aged 18 years or older with a diagnosis of gout who initiated use of allopurinol, probenecid or sulfinpyrazone from 1 January 2000 to 30 June 2006. Non-adherence was measured using the medication possession ratio (MPR) over the first year of therapy and defined as an MPR < 0.8. Descriptive statistics were calculated and logistic regression was used to estimate the strength of the association between patient characteristics and non-adherence.
Results
A total of 4,166 gout patients initiated ULDs; 97% received allopurinol. Median MPR for any ULD use was 0.68 (interquartile range (IQR) 0.64). Over half of the patients (56%) were non-adherent (MPR < 0.8). In adjusted analyses, predictors of poor adherence included younger age (odds ratio (OR) 2.43, 95% confidence interval (CI) 1.86 to 3.18 for ages <45 and OR 1.44, 95% CI 1.08 to 1.93 for ages 45 to 49), fewer comorbid conditions (OR 1.46, 95% CI 1.20 to 1.77), no provider visits for gout prior to urate-lowering drug initiation (OR 1.28, 95% CI 1.05 to 1.55), and use of non-steroidal anti-inflammatory drugs in the year prior to urate-lowering drug initiation (OR 1.15, 95% CI 1.00 to 1.31).
Conclusions
Non-adherence amongst gout patients initiating ULDs is exceedingly common, particularly in younger patients with less comorbidity and no provider visits for gout prior to ULD initiation. Providers should be aware of the magnitude of non-adherence with ULDs.
doi:10.1186/ar2659
PMCID: PMC2688196  PMID: 19327147
12.  Disclosure of Medical Errors: What Factors Influence How Patients Respond? 
BACKGROUND
Disclosure of medical errors is encouraged, but research on how patients respond to specific practices is limited.
OBJECTIVE
This study sought to determine whether full disclosure, an existing positive physician-patient relationship, an offer to waive associated costs, and the severity of the clinical outcome influenced patients' responses to medical errors.
PARTICIPANTS
Four hundred and seven health plan members participated in a randomized experiment in which they viewed video depictions of medical error and disclosure.
DESIGN
Subjects were randomly assigned to experimental condition. Conditions varied in type of medication error, level of disclosure, reference to a prior positive physician-patient relationship, an offer to waive costs, and clinical outcome.
MEASURES
Self-reported likelihood of changing physicians and of seeking legal advice; satisfaction, trust, and emotional response.
RESULTS
Nondisclosure increased the likelihood of changing physicians, and reduced satisfaction and trust in both error conditions. Nondisclosure increased the likelihood of seeking legal advice and was associated with a more negative emotional response in the missed allergy error condition, but did not have a statistically significant impact on seeking legal advice or emotional response in the monitoring error condition. Neither the existence of a positive relationship nor an offer to waive costs had a statistically significant impact.
CONCLUSIONS
This study provides evidence that full disclosure is likely to have a positive effect or no effect on how patients respond to medical errors. The clinical outcome also influences patients' responses. The impact of an existing positive physician-patient relationship, or of waiving costs associated with the error remains uncertain.
doi:10.1111/j.1525-1497.2006.00465.x
PMCID: PMC1924693  PMID: 16808770
medical error; disclosure; physician; patient relationship; compensation and redress
13.  A Demonstration of the Impact of Response Bias on the Results of Patient Satisfaction Surveys 
Health Services Research  2002;37(5):1403-1417.
Objectives
The purposes of the present study were to examine patient satisfaction survey data for evidence of response bias, and to demonstrate, using simulated data, how response bias may impact interpretation of results.
Data Sources
Patient satisfaction ratings of primary care providers (family practitioners and general internists) practicing in the context of a group-model health maintenance organization and simulated data generated to be comparable to the actual data.
Study Design
Correlational analysis of actual patient satisfaction data, followed by a simulation study where response bias was modeled, with comparison of results from biased and unbiased samples.
Principal Findings
A positive correlation was found between mean patient satisfaction rating and response rate in the actual patient satisfaction data. Simulation results suggest response bias could lead to overestimation of patient satisfaction overall, with this effect greatest for physicians with the lowest satisfaction scores.
Conclusions
Findings suggest that response bias may significantly impact the results of patient satisfaction surveys, leading to overestimation of the level of satisfaction in the patient population overall. Estimates of satisfaction may be most inflated for providers with the least satisfied patients, thereby threatening the validity of provider-level comparisons.
doi:10.1111/1475-6773.11194
PMCID: PMC1464019  PMID: 12479503
Patient satisfaction; response bias; response rate
14.  Long-term safety of pegloticase in chronic gout refractory to conventional treatment 
Annals of the Rheumatic Diseases  2012;72(9):1469-1474.
Objective
To evaluate the long-term safety (up to 3 years) of treatment with pegloticase in patients with refractory chronic gout.
Methods
This open-label extension (OLE) study was conducted at 46 sites in the USA, Canada and Mexico. Patients completing either of two replicate randomised placebo-controlled 6-month trials received pegloticase 8 mg every 2 weeks (biweekly) or every 4 weeks (monthly). Safety was evaluated as the primary outcome, with special interest in gout flares and infusion-related reactions (IRs). Secondary outcomes included urate-lowering and clinical efficacy.
Results
Patients (n=149) received a mean±SD of 28±18 pegloticase infusions and were followed for a mean of 25±11 months. Gout flares and IRs were the most frequently reported adverse events; these were least common in patients with a sustained urate-lowering response to treatment and those receiving biweekly treatment. In 10 of the 11 patients with a serious IR, the event occurred when uric acid exceeded 6 mg/dl. Plasma and serum uric acid levels remained <6 mg/dl in most randomised controlled trial (RCT)-defined pegloticase responders throughout the OLE study and were accompanied by sustained and progressive improvements in tophus resolution and flare incidence.
Conclusions
The safety profile of long-term pegloticase treatment was consistent with that observed during 6 months of RCT treatment; no new safety signals were identified. Improvements in clinical status, in the form of flare and tophus reduction initiated during RCT pegloticase treatment in patients maintaining goal range urate-lowering responses were sustained or advanced during up to 2.5 years of additional treatment.
doi:10.1136/annrheumdis-2012-201795
PMCID: PMC3756467  PMID: 23144450
Gout; Treatment; Rheumatoid Arthritis

Results 1-14 (14)