Huiying Sun

Efficacy of Systemic Treatments for Moderate to Severe Plaque Psoriasis: Systematic Review and Meta-Analysis

Aims: To compare the efficacy of psoriasis treatments through a systematic literature review and meta-analysis. Methods: Randomized controlled trials evaluating the Psoriasis Area and Severity Index (PASI) were identified and assessed for quality. PASI responses were modeled using a mixed-treatment comparison, which enabled the estimation of the relative effectiveness of several treatments. Sensitivity analyses were performed. Results: Twenty-two trials were included. Tumor necrosis factor (TNF) inhibitors were most likely to achieve PASI 75, with a mean relative risk (RR) of 15.57 (95% CI 12.46–19.25) versus mean RRs of 9.24 (95% CI 5.33–13.91) for systemic and 5.65 (95% CI 3.74–7.97) for T-cell therapies. Infliximab (81%) and adalimumab (71%) had greater probabilities of achieving PASI 75 than etanercept (50%). Dosage was an important determinant of outcome. Conclusions: TNF inhibitors were more effective than T cell agents; adalimumab and infliximab were more effective than systemic therapies and etanercept. Evidence-based comparisons support patient and physician decisions.

Trends in methadone maintenance treatment participation, retention, and compliance to dosing guidelines in British Columbia, Canada: 1996-2006.

Aspects of methadone maintenance treatment (MMT) delivery, particularly daily dosing practices, are associated with longer retention in treatment. Our objective was to identify trends in compliance to MMT dosing guidelines at the population level in British Columbia, Canada, from 1996 to 2006. Analysis of a provincial drug dispensation database identified 31,724 MMT episodes initiated during the study period. The number of patients in treatment increased from 2,827 in 1996 to 9,601 in 2006. Long-term retention (>36 months) was achieved in 20%-25% of all episodes. Compliance to minimally effective dose guidelines, which is independently associated with retention, fell from 2001 to 2006. Accordingly, this decline was mirrored by 12-month retention figures, which fell from 45.9% in 2001 to 40.5% in 2005. Our evaluation has both highlighted the successes of the British Columbia Methadone program and identified aspects that may be improved to ensure safety and maximize the benefits of MMT.

HIV-positive injection drug users who leave the hospital against medical advice: the mitigating role of methadone and social support.

BackgroundLeaving the hospital against medical advice has been associated with increased morbidity and readmission. Factors associated with the risk of leaving against medical advice among HIV/AIDS patients or injection drug users have not been examined in detail. ObjectivesTo examine the clinical and social factors associated with leaving against medical advice (AMA) from a specialized HIV/AIDS ward among patients who reported a history of injection drug use. MethodsAll patients with a history of injection drug use admitted to the HIV/AIDS ward at St. Pauls Hospital, Vancouver, British Columbia (the largest specialized HIV/AIDS hospital ward in Canada) between April 1997 and October 2000 were reviewed retrospectively. A multivariate logistic regression model utilizing a generalized estimating equation algorithm identified factors associated with leaving the hospital AMA. ResultsOf the 1056 hospital admissions to the HIV/AIDS ward by patients with a history of injection drug use, 263 (24.9%) resulted in leaving the hospital AMA. Independent positive predictors of leaving AMA included recent injection drug use (adjusted odds ratio [AOR] = 2.08, 95% confidence interval [CI]: 1.41–3.07) and aboriginal ethnicity (AOR = 1.55, 95% CI: 1.05–2.28). Discharge AMA was also more likely to occur on weekends (AOR = 2.27, 95% CI: 1.49–3.48) and on days when social assistance payments were issued (AOR = 2.95, 95% CI: 1.70–5.10). Factors that independently reduced the odds of hospital discharge AMA included in-hospital methadone use (AOR = 0.49, 95% CI: 0.32–0.76), social support (AOR = 0.33, 95% CI: 0.21–0.51), and older age (per 10-year increment, AOR = 0.56, 95% CI: 0.43–0.73). ConclusionsAmong HIV-positive patients with a history of injection drug use, the odds of leaving the hospital AMA were reduced for subjects who received inpatient methadone treatment, were of older age, or had social supports. Addiction treatment and interventions that enhance social supports in marginalized populations at risk for hospital discharge AMA should be further explored.

The effect of etanercept on work productivity in patients with early active rheumatoid arthritis: results from the COMET study

OBJECTIVES To compare the impact of the combination of etanercept (ETN) and MTX with MTX alone on work productivity among MTX-naïve patients with active early RA over a 12-month period. METHODS The COMET (COmbination of Methotrexate and ETanercept) trial was a 2-year double-blind randomized clinical trial. Absenteeism during the first year was measured and it included: (i) number of missed workdays; (ii) reduced working time; and (iii) number of stopped workdays. Each absenteeism measure was estimated using a mixed model, and their variations were estimated by bootstrapping. As a sensitivity analysis, the lost workdays due to presenteeism (reduced performance at work) was also estimated. RESULTS Two hundred and five patients [MTX (n = 100) vs ETN + MTX (n = 105)], who were working full time or part time at baseline and had at least one follow-up observation, were included in the analysis. Compared with the MTX group, the ETN + MTX group had a maximum of 37 fewer missed workdays or at minimum 22 fewer missed workdays. The associated productivity gain equalled 2586 pounds and 1555 pounds, respectively. When additionally accounting for presenteeism, the total improvement could be as high as 42 (95% CI 16, 69) fewer lost workdays representing a productivity gain of 2968 pounds. CONCLUSIONS Our results demonstrated that early treatment with ETN + MTX led to a significant attenuation of absenteeism among patients with early active RA. These productivity gains represent benefit beyond the traditional measures of clinical and radiographic improvements. Further research to simultaneously measure both absenteeism and presenteeism is warranted.

Quality of Life of Patients With Advanced HIV/AIDS: Measuring the Impact of Both AIDS-Defining Events and Non-AIDS Serious Adverse Events

Objective:To investigate the relative magnitude and duration of impact of AIDS-defining events (ADEs) and non-AIDS serious adverse events (SAEs) on health-related quality of life (HRQoL) among patients with advanced HIV/AIDS. Methods:We use data from OPTIMA (OPTions In Management with Antiretrovirals), a multinational, randomized, open, control, clinical management trial of treatment strategies for patients with multidrug-resistant HIV and advanced immune disease. Longitudinal models were used to determine the effects of ADEs and SAEs on HRQoL across periods before, during, and after event onset. The Medical Outcomes Study HIV Health Survey (MOS-HIV) physical and mental health summary scores (MOS-PHS and MOS-MHS), EQ-5D, and the Health Utilities Index Mark 3 HRQoL measures were all assessed at regular follow-up intervals during the trial. Results:ADEs occurred much less frequently than SAEs (n = 147 vs. n = 821) in the study sample population of 368 patients, during median follow-up of 3.96 years. Although both ADEs and SAEs had significant negative impacts on HRQoL, SAEs had at least as large an impact upon HRQoL as ADEs when both were included in a multivariate linear regression model, controlling for other covariates. However, the effect of ADEs on HRQoL was more persistent, with larger magnitude of effect across all instruments in time intervals further from the onset of the event. Conclusions:Non-AIDS SAEs occurring in patients with late-stage HIV/AIDS seem to have at least as important an immediate impact on patient HRQoL as ADEs; however, the impact of ADEs seems to be more persistent. Our findings call for a greater emphasis on the detection and active prevention of non-AIDS SAEs in patients with late-stage HIV/AIDS.

Defining dosing pattern characteristics of successful tapers following methadone maintenance treatment: Results from a population-based retrospective cohort study

AIMS To identify dose-tapering strategies associated with sustained success following methadone maintenance treatment (MMT). DESIGN Population-based retrospective cohort study. SETTING Linked administrative medication dispensation data from British Columbia, Canada. PARTICIPANTS From 25 545 completed MMT episodes, 14 602 of which initiated a taper, 4183 individuals (accounting for 4917 MMT episodes) from 1996 to 2006 met study inclusion criteria. MEASUREMENTS The primary outcome was sustained successful taper, defined as a daily dose ≤5 mg per day in the final week of the treatment episode and no treatment re-entry, opioid-related hospitalization or mortality within 18 months following episode completion. FINDINGS The overall rate of sustained success was 13% among episodes meeting inclusion criteria (646 of 4917), 4.4% (646 of 14 602) among all episodes initiating a taper and 2.5% (646 of 25 545) among all completed episodes in the data set. The results of our multivariate logistic regression analyses suggested that longer tapers had substantially higher odds of success [12-52 weeks versus <12 weeks: odds ratio (OR): 3.58; 95% confidence interval (CI): 2.76-4.65; >52 weeks versus <12 weeks: OR: 6.68; 95% CI: 5.13-8.70], regardless of how early in the treatment episode the taper was initiated, and a more gradual, stepped tapering schedule, with dose decreases scheduled in only 25-50% of the weeks of the taper, provided the highest odds of sustained success (versus <25%: OR: 1.61; 95% CI: 1.22-2.14). CONCLUSIONS The majority of patients attempting to taper from methadone maintenance treatment will not succeed. Success is enhanced by gradual dose reductions interspersed with periods of stabilization. These results can inform the development of a more refined guideline for future clinical practice.

Health related quality of life trajectories of patients in opioid substitution treatment

BACKGROUND While opioid substitution treatment (OST) provides the opportunity for substantial improvements in health related quality of life (HRQoL), this relationship is seldom documented and poorly understood. Our objectives were to identify differences in trajectories of HRQoL among chronic opioid-dependent patients and factors associated with improvement and deterioration in HRQoL following enrolment in opioid substitution treatment. METHODS In the North American Opiate Medication Initiative (NAOMI) randomized controlled trial, the Euroqol (EQ-5D) and other measures of demographic, health and drug use characteristics were collected at baseline and quarterly follow-up. Latent class growth analysis was applied to identify classes of HRQoL trajectories during treatment, while baseline correlates of class membership and factors associated with changes in HRQoL were identified in multivariate analyses. RESULTS Three classes of individual HRQoL growth trajectories were identified: class 1: low and constant (19.5%), class 2: moderate and improved (61.2%), and class 3: high and constant (19.3%). Class 1 members were younger and more likely to be female, while class 3 members were less likely to have chronic conditions and had lower illicit drug use severity at baseline. Changes in HRQoL were associated with improvements in housing status (positive), medical events (negative) and decreases in illicit drug use (positive). CONCLUSIONS Insight into the extent of HRQoL response and characteristics of patients responding to treatment can be used to design interventions that maximize HRQoL improvement. Given its role in economic evaluation and subsequent resource allocation decisions, HRQoL should be considered an endpoint in treatment evaluations for opioid dependence.

Predictors of Early Hospital Readmission in HIV‐infected Patients with Pneumonia

OBJECTIVE: Although hospitalization patterns have been studied, little is known about hospital readmission among HIV-infected patients in the era of highly active antiretroviral therapy. We explored the risk factors for early readmission to a tertiary care inner-city hospital among HIV-infected patients with pneumonia in Vancouver, Canada.DESIGN: Case-control study.SETTING: Tertiary care, university-affiliated, inner-city hospital.PARTICIPANTS: All HIV-infected patients who were hospitalized with Pneumocystis carinii pneumonia (PCP) or bacterial pneumonia (BP) between January 1997 and December 2000. Case patients included those who had early readmissions, defined as being readmitted within 2 weeks of discharge (N=131). Control patients were randomly selected HIV-infected patients admitted during the study period who were not readmitted within 2 weeks of discharge (N=131), matched to the cases by proportion of PCP to BP.MEASUREMENTS: Sociodemographic, HIV risk category, and clinical data were compared using x2 test for categorical variables, and the Wilcoxon rank-sum test was used for continuous variables. Multivariable logistic regression was performed to determine the factors independently associated with early readmission. We also reviewed the medical records of 132 patients admitted to the HIV/AIDS ward during the study period and collected more detailed clinical data for a subanalysis.MAIN RESULTS: Patients were at significantly increased odds of early readmission if they left the hospital against medical advice (AMA) (adjusted odds ratio [OR], 4.26; 95% confidence interval [95% CI], 2.13 to 8.55), lived in the poorest urban neighborhood (OR, 2.03; 95% CI, 1.09 to 3.77), were hospitalized in summer season (May though October, OR, 2.36; 95% CI, 1.36 to 4.10), or had been admitted in the preceding 6 months (OR, 2.55; 95% CI, 1.46 to 4.47). Gender, age, history of AIDS-defining illness, and injection drug use status were not significantly associated with early readmission.CONCLUSIONS: Predictors of early readmission of HIV-infected patients with pneumonia included: leaving hospital AMA, living in the poorest urban neighborhood, being hospitalized in the preceding 6 months and during the summer months. Interventions involving social work may address some of the underlying reasons why these patients leave hospital AMA and should be further studied.

Does achieving clinical response prevent work stoppage or work absence among employed patients with early rheumatoid arthritis

OBJECTIVES To evaluate the impact of clinical response on work stoppage or work absence among employed people with early RA. METHODS First-year data from the combination of MTX and etanercept trial was used. The analyses were restricted to the 205 patients working full or part time at baseline who answered questions on whether they stopped working or missed days from work in one or more of the four follow-up visits. Work stoppage referred to the first occurrence of subjects reporting stopping work. Work absence was defined as whether patients reported missed days from work. Clinical response and activity state considered included the ACR and European League against Rheumatism response criteria, 28-joint DAS (DAS-28) remission and the minimum clinically important difference of the HAQ score. RESULTS After adjustment for baseline characteristics, ACR70 responders were 72% less likely to stop working and 55% less likely to miss work than ACR20 non-responders (P < 0.05). Patients achieving DAS-28 remission were 54% less likely to stop work than those with DAS-28 > 3.2 (P < 0.05). Moderate improvements did not appear to effect work stoppage or missed days after adjustments. CONCLUSIONS Results suggest that achieving clinical remission or major improvement might be necessary to significantly impact work outcomes.

A Cost-Utility Analysis of Losartan versus Atenolol in the Treatment of Hypertension with Left Ventricular Hypertrophy

Introduction: The LIFE (Losartan Intervention For Endpoint reduction in hypertension) study demonstrated a 13% relative risk reduction in the primary composite endpoint (myocardial infarction, stroke or death) for patients with hypertension and electrocardiographically diagnosed left ventricular hypertrophy (LVH) treated with losartan compared with atenolol. Losartan recipients also had a 25% relative risk reduction for stroke compared with atenolol recipients. Incorporating the results found in the LIFE study into an economic model, an incremental cost-effectiveness analysis was performed comparing losartan with atenolol in the treatment of 67-year old patients with hypertension and LVH.Methods: A Markov state transition model, based on published results of the LIFE trial (mean follow-up of 4.8 years), was utilised to extrapolate the outcomes observed in this trial to the patients’ lifetime. Utility estimates for the associated health states were obtained from various published sources. Lifetime treatment costs were calculated adopting a societal perspective. Both costs and benefits were discounted and incremental cost-effectiveness ratios (ICERs) were estimated. One-way and probabilistic sensitivity analyses were performed.Results: The estimated ICER for losartan versus atenolol was