Purpose
High-dimensional propensity scores (hdPS) can adjust for measured confounders, but it remains unclear how well it can adjust for unmeasured confounders. Our goal was to identify if the hdPS ...method could adjust for confounders which were hidden to the hdPS algorithm.
Method
The hdPS algorithm was used to estimate two hdPS; the first version (hdPS-1) was estimated using data provided by 6 data dimensions and the second version (hdPS-2) was estimated using data provided from only two of the 6 data dimensions. Two matched sub-cohorts were created by matching one patient initiated on a high-dose statin to one patient initiated on a low-dose statin based on either hdPS-1 (
Matched hdPS Full Info Sub-Cohort
) or hdPS-2 (
Matched hdPS Hidden Info Sub-Cohort
). Performances of both hdPS were compared by means of the absolute standardized differences (ASDD) regarding 18 characteristics (data on seven of the 18 characteristics were hidden to the hdPS algorithm when estimating the hdPS-2).
Results
Eight out of the 18 characteristics were shown to be unbalanced within the unmatched cohort. Matching on either hdPS achieved adequate balance (i.e., ASDD <0.1) on all 18 characteristics.
Conclusion
Our results indicate that the hdPS method was able to adjust for hidden confounders supporting the claim that the hdPS method can adjust for at least some unmeasured confounders.
The association between incretin-based drugs, such as dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists, and acute pancreatitis is controversial.
To determine ...whether the use of incretin-based drugs, compared with the use of 2 or more other oral antidiabetic drugs, is associated with an increased risk of acute pancreatitis.
A large, international, multicenter, population-based cohort study was conducted using combined health records from 7 participating sites in Canada, the United States, and the United Kingdom. An overall cohort of 1 532 513 patients with type 2 diabetes initiating the use of antidiabetic drugs between January 1, 2007, and June 30, 2013, was included, with follow-up until June 30, 2014.
Current use of incretin-based drugs compared with current use of at least 2 oral antidiabetic drugs.
Nested case-control analyses were conducted including hospitalized patients with acute pancreatitis matched with up to 20 controls on sex, age, cohort entry date, duration of treated diabetes, and follow-up duration. Hazard ratios (HRs) and 95% CIs for hospitalized acute pancreatitis were estimated and compared current use of incretin-based drugs with current use of 2 or more oral antidiabetic drugs. Secondary analyses were performed to assess whether the risk varied by class of drug (DPP-4 inhibitors and GLP-1 agonists) or by duration of use. Site-specific HRs were pooled using random-effects models.
Of 1 532 513 patients included in the analysis, 781 567 (51.0%) were male; mean age was 56.6 years. During 3 464 659 person-years of follow-up, 5165 patients were hospitalized for acute pancreatitis (incidence rate, 1.49 per 1000 person-years). Compared with current use of 2 or more oral antidiabetic drugs, current use of incretin-based drugs was not associated with an increased risk of acute pancreatitis (pooled adjusted HR, 1.03; 95% CI, 0.87-1.22). Similarly, the risk did not vary by drug class (DPP-4 inhibitors: pooled adjusted HR, 1.09; 95% CI, 0.86-1.22; GLP-1 agonists: pooled adjusted HR, 1.04; 95% CI, 0.81-1.35) and there was no evidence of a duration-response association.
In this large population-based study, use of incretin-based drugs was not associated with an increased risk of acute pancreatitis compared with other oral antidiabetic drugs.
Comparative performance of the traditional propensity score (PS) and high-dimensional propensity score (hdPS) methods in the adjustment for confounding by indication remains unclear. We aimed to ...identify which method provided the best adjustment for confounding by indication within the context of the risk of diabetes among patients exposed to moderate versus high potency statins.
A cohort of diabetes-free incident statins users was identified from the Quebec's publicly funded medico-administrative database (Full Cohort). We created two matched sub-cohorts by matching one patient initiated on a lower potency to one patient initiated on a high potency either on patients' PS or hdPS. Both methods' performance were compared by means of the absolute standardized differences (ASDD) regarding relevant characteristics and by means of the obtained measures of association.
Eight out of the 18 examined characteristics were shown to be unbalanced within the Full Cohort. Although matching on either method achieved balance within all examined characteristic, matching on patients' hdPS created the most balanced sub-cohort. Measures of associations and confidence intervals obtained within the two matched sub-cohorts overlapped.
Although ASDD suggest better matching with hdPS than with PS, measures of association were almost identical when adjusted for either method. Use of the hdPS method in adjusting for confounding by indication within future studies should be recommended due to its ability to identify confounding variables which may be unknown to the investigators.
Sex differences exist in psoriasis manifestation and expectations from treatment with systemic agents, including, conventional systemic agents (CSA) and tumor necrosis factor inhibitors or ...ustekinumab (TNFi/UST). However, sex differences in patterns of systemic agent use, such as CSA discontinuation and switch from CSA to TNFi/UST have not been examined.
To assess sex differences in patterns of CSA use and identify factors associated with switch to (or add) a TNFi/UST and those associated with CSA discontinuation.
We conducted a retrospective cohort study using the Quebec health administrative databases. We included patients with psoriasis initiating a CSA in 2002-2015. We excluded patients with a psoriasis diagnosis in the 3 years prior to the first diagnosis date between 2002 and 2015, and those with a systemic agent dispensation in the year prior to that date. We used Cox regression models with the Least Absolute Shrinkage and Selection Operator method to identify factors associated with Switch/add TNFi/UST, and those associated with CSA discontinuation. Separate analyses were performed for male and female patients.
We included 1,644 patients (55.7% females, mean age 60.3 years), among whom 60.4% discontinued their CSA and 7.4%, switched/added TNFi/UST (3.4% switched and 4.0% added) within a median of 0.78 years of follow-up. Among male and female patients, rates of Switch/add TNFi/UST per 1,000 person-year were 49.1 and 41.0 and rates of CSA discontinuation were 381.2 and 352.8. Clinical obesity in male patients (HR 3.53, 95% CI 1.20-10.35), and adjustment/somatoform/dissociative disorders (HR 3.17, 95% CI 1.28-7.85) and use of nonsteroidal anti-inflammatory drugs (HR 2.70, 95% CI 1.56-4.70) in female patients were associated with Switch/add TNFi/UST. Male patients followed by a rheumatologist (HR 0.66, 95% CI 0.46-0.94) and those with a prior hospitalization (HR 0.70, 95% CI 0.57-0.87) were at lower risk of CSA discontinuation, while those initiated on acitretin (vs methotrexate) were at higher risk to discontinue their CSA (HR 1.61, 95% CI 1.30-2.01). Female patients with rheumatoid arthritis comorbidity (HR 0.69, 95% CI 0.51-0.93), those with a dispensed lipid-lowering agent (HR 0.72, 95% CI 0.59-0.88) and hypoglycemic agent (HR 0.75, 95% CI 0.57-0.98) and those initiated on methotrexate (vs all other CSAs) were less likely to discontinue their CSA. Male and female patients entering the cohort between 2011 and 2015 were at reduced risk of CSA discontinuation compared to those entering the cohort before 2011.
Most male and female patients discontinued their CSA within 1 year of follow-up. Our study highlighted sex differences in patients' characteristics associated with switch/add a TNFi/UST and CSA discontinuation; treatment switch and discontinuation may be indications of treatment failure in most patients.
Abstract
Aims
In the randomized, placebo-controlled Colchicine Cardiovascular Outcomes Trial (COLCOT) of 4745 patients enrolled within 30 days after myocardial infarction (MI), low-dose colchicine ...(0.5 mg once daily) reduced the incidence of the primary composite endpoint of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina leading to coronary revascularization. To assess the in-trial period and lifetime cost-effectiveness of low-dose colchicine therapy compared to placebo in post-MI patients on standard-of-care therapy.
Methods and results
A multistate Markov model was developed incorporating the primary efficacy and safety results from COLCOT, as well as healthcare costs and utilities from the Canadian healthcare system perspective. All components of the primary outcome, non-cardiovascular deaths, and pneumonia were included as health states in the model as both primary and recurrent events. In the main analysis, a deterministic approach was used to estimate the incremental cost-effectiveness ratio (ICER) for the trial period (24 months) and lifetime (20 years). Over the in-trial period, the addition of colchicine to post-MI standard-of-care treatment decreased the mean overall per-patient costs by 47%, from $502 to $265 Canadian dollar (CAD), and increased the quality-adjusted life years (QALYs) from 1.30 to 1.34. The lifetime per-patient costs were further reduced (69%) and QALYs increased with colchicine therapy (from 8.82 to 11.68). As a result, both in-trial and lifetime ICERs indicated colchicine therapy was a dominant strategy.
Conclusion
Cost-effectiveness analyses indicate that the addition of colchicine to standard-of-care therapy after MI is economically dominant and therefore generates cost savings.
Hemodialysis is associated with a high risk of morbidity and mortality, often caused by infections. Infections account for approximately 15% of all deaths in this patient population (the second ...leading cause after cardiovascular events) and for about one-fifth of admissions. Approximately one-fourth of infection-related admissions are caused by dialysis-associated peritonitis or vascular access infection that may lead to such significant complications as endocarditis or death. Published studies that assessed the determinants of hemodialysis-related vascular infections reported inconsistent findings. Variations in the definitions of infection among these studies despite the existence of standard guidelines proposed by at least 3 major work groups may explain, at least in part, these inconsistencies. A comprehensive in-depth review of those studies is needed to examine the inconsistencies in the published results. We first revised the existing vascular access–related infection definitions, then conducted a narrative review of the published literature that examined predictors of vascular access–related infections, highlighting the heterogeneity in methods and findings. Better understanding of the risk factors for vascular access–related infections may inform efficacious prevention strategies and lead to early detection of infections and improved patient care.
Introduction
Patients with psoriasis are at risk of depression, anxiety and adjustment disorder (DAAD). Randomized control trials reported improvement in depression and anxiety symptoms among ...patients with psoriasis receiving tumour necrosis factor inhibitors and ustekinumab (TNFi/UST) versus placebo and conventional systemic agents (CSA). The risk of DAAD among TNFi/UST versus CSA users was not assessed in real‐world settings.
Objective
To compare DAAD incidence among patients with psoriasis using CSA and subsequently received (vs. not) TNFi/UST.
Methods
We conducted a retrospective cohort study using the province of Quebec health administrative databases (1997–2015). Among adult patients with a diagnosis of psoriasis and initiating a CSA, we included those who later initiated a TNFi/UST, as a switch or add‐on, at the date of their first prescription fill (index‐date). We also included TNFi/UST nonusers at a date chosen to match the time between the first CSA and the index date of a random TNFi/UST user. TNFi/UST nonusers were classified into current or previous CSA users according to their last CSA received in the 90 days before or after their index date. Marginal structural Cox regression models weighted by the inverse probability of exposure compared the risk of DAAD between TNFi/UST, current and previous CSA users. Additional analyses were conducted by age group and sex.
Results
Our cohort included 1333 patients with psoriasis: 183 TNFi/UST users, 625 current CSA users and 525 previous CSA users. TNFi/UST users were at a lower risk of DAAD versus previous CSA users (hazard ratio 0.48, 95% confidence intervals: 0.28–0.94). The reduction in risk among TNFi/UST users was not statistically significant versus current CSA users. Similar results were observed across different age groups and sex.
Conclusion
Among patients with psoriasis receiving CSA, those who were subsequently dispensed TNFi/UST were at a lower risk of DAAD compared to those who did not receive these agents.
Background We studied the association between HIV infection, antiretroviral medications, and the risk of spontaneous intracranial hemorrhage. Methods We performed a cohort and nested case control ...study in an administrative database. We selected all HIV-positive individuals presenting between 1985 and 2007. Each HIV-positive subject was matched with 4 HIV-negative individuals. We used a Poisson regression model to calculate rates of intracranial hemorrhage according to HIV status. We conducted a case -control study nested within the cohort of HIV-positive individuals to look at the effect of antiretroviral medications. Odds ratios for antiretroviral exposure were obtained using conditional logistic regression. Results There were 7,053 HIV-positive and 27,681 HIV-negative subjects, representing 138,704 person-years. There were 49 incident intracranial hemorrhages, 29 in HIV-positive and 20 in HIV-negative individuals. The adjusted hazard ratio for intracranial hemorrhage in HIV-positive compared to HIV-negative patients was 3.28 (95% confidence interval CI 1.75-6.12). The effect was reduced to 1.99 (95% CI 0.92-4.31) in the absence of AIDS-defining conditions, and increased to 7.64 (95% CI 3.78-15.43) in subjects with AIDS-defining conditions. Hepatitis C infection, illicit drug or alcohol abuse, intracranial lesions, and coagulopathy were all strongly associated with intracranial hemorrhage (all P < .001). In the case control study, 29 cases of ICH in HIV-positive individuals were matched to 228 HIV-positive controls. None of the antiretroviral classes were associated with an increase in the odds ratio of intracranial hemorrhage. Conclusions The risk of intracranial hemorrhage in HIV-positive individuals seems to be mostly associated with AIDS-defining conditions, other comorbidities, or lifestyle factors. No association was found between use of antiretroviral medications and intracranial hemorrhage.
Recent trials report the efficacy of continuous tenofovir-based pre-exposure prophylaxis (PrEP) for prevention of HIV infection. The cost effectiveness of 'on demand' PrEP for non-injection ...drug-using men who have sex with men at high risk of HIV acquisition has not been evaluated.
To conduct an economic evaluation of the societal costs of HIV in Canada and evaluate the potential benefits of this PrEP strategy.
Direct HIV costs comprised outpatient, inpatient and emergency department costs, psychosocial costs and antiretroviral costs. Resource consumption estimates were derived from the Centre Hospitalier de l'Université de Montréal HIV cohort. Estimates of indirect costs included employment rate and work absenteeism. Costs for 'on demand' PrEP were modelled after an ongoing clinical trial. Cost-effectiveness analysis compared costs of 'on demand' PrEP to prevent one infection with lifetime costs of one HIV infection. Benefits were presented in terms of life-years and quality-adjusted life-years.
The average annual direct cost of one HIV infection was $16,109 in the least expensive antiretroviral regimen scenario and $24,056 in the most expensive scenario. The total indirect cost was $11,550 per year. Total costs for the first year of HIV infection ranged from $27,410 to $35,358. Undiscounted lifetime costs ranged from $1,439,984 ($662,295 discounted at 3% and $448,901 at 5%) to $1,482,502 ($690,075 at 3% and $485,806 at 5%). The annual cost of PrEP was $12,001 per participant, and $621,390 per infection prevented. The PrEP strategy was cost-saving in all scenarios for undiscounted and 3% discounting rates. At 5% discounting rates, the strategy is largely cost-effective: according to least and most expensive scenarios, incremental cost-effectiveness ratios ranged from $60,311 to $47,407 per quality-adjusted life-year.
This 'on demand' PrEP strategy ranges from cost-saving to largely cost-effective. The authors believe it represents an important public health strategy for the prevention of HIV transmission.
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