Comprehensive comparison between 222 CTLA-4 haploinsufficiency and 212 LRBA deficiency patients: a systematic review.

Cytotoxic T lymphocyte antigen 4 (CTLA-4) haploinsufficiency (CHAI) and lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency (LATAIE) are newly identified inborn errors of immunity with shared molecular pathomechanisms and clinical manifestations. In this review, we aimed to provide differential comparisons regarding demographic, clinical, immunological and molecular characteristics between these two similar conditions. A literature search was conducted in PubMed, Web of Science and Scopus databases and included studies were systematically evaluated. Overall, 434 (222 CHAI and 212 LATAIE) patients were found in 101 eligible studies. The CHAI patients were mainly reported from North America and western Europe, while LATAIE patients were predominantly from Asian countries. In CHAI, positive familial history (P < 0·001) and in LATAIE, consanguineous parents (P < 0·001) were more common. In CHAI patients the rates of granulomas (P < 0·001), malignancies (P = 0·001), atopy (P = 0·001), cutaneous disorders (P < 0·001) and neurological (P = 0·002) disorders were higher, while LATAIE patients were more commonly complicated with life-threatening infections (P = 0·002), pneumonia (P = 0·006), ear, nose and throat disorders (P < 0·001), organomegaly (P = 0·023), autoimmune enteropathy (P = 0·038) and growth failure (P < 0·001). Normal lymphocyte subsets and immunoglobulins except low serum levels of CD9+ B cells (14·0 versus 38·4%, P < 0·001), natural killer (NK) cells (21 versus 41·1%, P < 0·001), immunoglobulin (Ig)G (46·9 versus 41·1%, P = 0·291) and IgA (54·5 versus 44·7%, P = 0·076) were found in the majority of CHAI and LATAIE patients, respectively. The most frequent biological immunosuppressive agents prescribed for CHAI and LATAIE patients were rituximab and abatacept, respectively. Further investigations into the best conditioning and treatment regimens pre- and post-transplantation are required to improve the survival rate of transplanted CHAI and LATAIE patients.

Biological and clinical significance of T helper 17 cell deficiency: insight into monogenic defects.

Summary: T helper 17 (Th17) are a CD4+ T subpopulation cells which are involved in the host protection against microbes such as extracellular and intracellular bacteria, parasites, fungi, and viruses. Monogenic defects including those mutations in some genes such as the signal transducer and activator of transcription (STAT)1 and 3, dedicator of cytokinesis 8 (DOCK8), autoimmune regulator (AIRE), and interleukin 17 receptor A (IL-17RA) can lead to impairment in Th17 cell development and function along with the concomitant increased risk for chronic mucocutaneous candidiasis (CMC). The immunologic abnormalities in these patients include low frequency of Th17 cells; defective cutaneous or in vitro T cell response to Candida species, and/or autoantibodies against relevant cytokines. This review outlines the biological characteristics and functionality of Th17 cells, as well as the clinical features of individuals with genetic defects associated with Th17 deficiency.

Socioeconomic status and nonadherence to antihypertensive drugs: a systematic review and meta-analysis.

BACKGROUND: Although conventional wisdom suggests that low socioeconomic status (SES) is a robust predictor of medication nonadherence, the strength of this association remains unclear. OBJECTIVES: 1) To estimate the proportion of studies that identified SES as a potential risk indicator of nonadherence, 2) to describe the type of SES measurements, and 3) to quantify the association between SES and nonadherence to antihypertensive pharmacotherapy. METHODS: A systematic review and meta-analysis research design was used. We searched multiple electronic databases for studies in English or French examining nonadherence to antihypertensive medications measured by electronic prescription databases where explanatory factors were considered. Two authors independently assessed quality, described the SES measure(s), and recorded its association with nonadherence to antihypertensives. A random-effects model meta-analysis was performed, and heterogeneity was examined by using the I(2) statistic. RESULTS: Fifty-six studies with 4,780,293 subjects met the inclusion criteria. Twenty-four of these studies (43%) did not report any SES measures. When it was reported (n = 32), only seven (13%) examined more than one component but none performed a multidimensional assessment. Most of the studies relied on income or income-related measures (such as prescription-drug benefits or co-payments) (27 of 32 [84%]). Meta-analysis could be quantified in 40 cohorts reported in 30 studies. Overall, the pooled adjusted risk estimate for nonadherence according to SES (high vs. low) was 0.89 (95% confidence interval 0.87-0.92; I(2) = 95%; P < 0.001). Similar patterns were observed in all subgroups examined. CONCLUSIONS: Published studies have not found a strong association between low SES and nonadherence to antihypertensive medications. However, important limitations in the assessment of SES can be identified in virtually all studies. Future studies are required to ascertain whether a stronger association is observed when SES is determined by comprehensive measures.

Development of comparable algorithms to measure primary care indicators using administrative health data across three Canadian provinces.

INTRODUCTION: Performance measurement has been recognized as key to transforming primary care (PC). Yet, performance reporting in PC lags behind even though high-performing PC is foundational to an effective and efficient health care system. OBJECTIVES: We used administrative data from three Canadian provinces, British Columbia, Ontario and Nova Scotia, to: 1) identify and develop a core set of PC performance indicators using administrative data and 2) examine their ability to capture PC performance. METHODS: Administrative data used included Physician Billings, Discharge Abstract Database, the National Ambulatory Care and Reporting System database, Census and Vital Statistics. Indicators were compiled based on a literature review of PC indicators previously developed with administrative data available in Canada (n=158). We engaged in iterative discussions to assess data conformity, completeness, and plausibility of results in all jurisdictions. Challenges to creating comparable algorithms were examined through content analysis and research team discussions, which included clinicians, analysts, and health services researchers familiar with PC. RESULTS: Our final list included 21 PC performance indicators pertaining to 1) technical care (n=4), 2) continuity of care (n=6), and 3) health services utilization (n=11). Establishing comparable algorithms across provinces was possible though time intensive. A major challenge was inconsistent data elements. Ease of data access, and a deep understanding of the data and practice context, was essential for selecting the most appropriate data elements. CONCLUSIONS: This project is unique in creating algorithms to measure PC performance across provinces. It was essential to balance internal validity of the indicators within a province and external validity across provinces. The intuitive desire of having the exact same coding across provinces was infeasible due to lack of standardized PC data. Rather, a context-tailored definition was developed for each jurisdiction. This work serves as an example for developing comparable PC performance indicators across different provincial/territorial jurisdictions.

Contrast-induced acute kidney injury in renal transplant recipients after cardiac catheterization.

Renal transplant (RTX) recipients remain at high-risk for acute kidney injury (AKI) despite having improved renal function and quality of life after transplantation. We sought to identify the incidence and risk factors for contrast-induced AKI in RTX recipients after cardiac catheterization at our institute as identified by electronic records. After excluding patients on dialysis at time of procedure due to failed transplant and who did not have post-exposure creatinine values within 3 days, we reviewed 77 procedures on 57 patients. We studied one case per patient (the most recent procedure). Among the 57 patients, 42 were male, 42 were Caucasian and mean age was 58.2 +/- 10.1 years. Mean serum creatinine 24 h pre-procedure was 1.7 +/- 0.8 mg/dl. Contrast-induced AKI, defined as rise in serum creatinine of 25% or 0.5 mg/dl within 3 days post-catheterization, occurred in 9 procedures (15.8%). One procedure was complicated by AKI requiring dialysis. AKI occurred more frequently with use of low-osmolar contrast (ioxaglate or iohexol) in comparison with iso-osmolar contrast (iodixanol) (9/36 vs. 0/21, p = 0.019). Patients who received prophylactic N-acetylcysteine had lower incidence of AKI than those who did not (4/41 vs. 5/16, p = 0.046). Exact logistic regression analysis revealed odds ratio of developing AKI with use of low-osmolar vs. iso-osmolar contrast to be 7.747 (1.101 - yen); p = 0.0381). Contrast-induced AKI was common in RTX recipients after cardiac catheterization. Iso-osmolar contrast was associated with a lower risk of contrast-induced AKI in comparison with low-osmolar contrast.

Achieving cross provincial comparisons of osteoporosis screening performance from administrative health data.

Administrative databases can be used to measure healthcare performance. This can lead to identification of high-performing practice characteristics and inform innovations. However, a key challenge is that administrative data cannot be easily combined across provinces. Comparable measures must be defined across provinces but operationalized within each province. The purpose of this work is to provide an example of defining a population health concept, osteoporosis screening, and creating measures to examine it across British Columbia, Ontario, and Nova Scotia, Canada. TRANSFORMATION is a study that seeks to improve the science and reporting of Primary Health Care performance. We used administrative data from the above three provinces to examine osteoporosis screening in those aged 65 years and older. Challenges of databases with different data elements and levels of methods development (e.g. macros) can be overcome for purposes of cross-provincial comparisons. Flexibility of analytic methods and frequent communication is needed.

Proportion and risk indicators of nonadherence to antihypertensive therapy: a meta-analysis.

PURPOSE: The World Health Organization (WHO) concluded that poor adherence to treatment is the most important cause of uncontrolled high blood pressure, with approximately 75% of patients not achieving optimum blood pressure control. The WHO estimates that between 20% and 80% of patients receiving treatment for hypertension are adherent. As such, the first objective of our study was to quantify the proportion of nonadherence to antihypertensive therapy in real-world observational study settings. The second objective was to provide estimates of independent risk indicators associated with nonadherence to antihypertensive therapy. MATERIALS AND METHODS: We performed a systematic literature review and meta-analysis of all studies published between database inception and December 31, 2011 that reviewed adherence, and risk indicators associated with nonadherence, to antihypertensive medications. RESULTS: In the end, 26 studies met our inclusion and exclusion criteria and passed our methodological quality evaluation. Of the 26 studies, 48.5% (95% confidence interval 47.7%-49.2%) of patients were adherent to antihypertensive medications at 1 year of follow-up. The associations between 114 variables and nonadherence to antihypertensive medications were reviewed. After meta-analysis, nine variables were associated with nonadherence to antihypertensive medications: diuretics in comparison to angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs), ACE inhibitors in comparison to ARBs, CCBs in comparison to ARBs, those with depression or using antidepressants, not having diabetes, lower income status, and minority cultural status. CONCLUSION: This study clarifies the extent of adherence along with determining nine independent risk indicators associated with nonadherence to antihypertensive medications.

Pharmacist intervention in cardiac rehabilitation: a randomized controlled trial.

PURPOSE: We aimed to determine to what extent a telephone-based pharmacist intervention would (a) be utilized by individuals not attending a traditional cardiac rehabilitation (CR) program and (b) facilitate adherence to cardiovascular medications. METHODS: We conducted a randomized, controlled open-label trial among patients eligible for CR in Saskatoon, Canada. Patients were invited to participate in telephone-based CR, regardless of participation in the formal program. Subjects in the intervention group were assessed by the CR pharmacist and received education and counseling on medication adherence. The primary endpoint was adherence to cardiovascular medication assessed by electronic filling records over a minimum of 6 months. Mean adherence was expected to reach 70% during the followup period. RESULTS: Patient recruitment was halted early because of low enrollment. Of the 95 patients randomized, 90% had also registered in the traditional CR program. During the followup period, 129 telephone interactions were performed (median, 2 calls), with every subject taking part in at least 1 interaction. Over the study period, the mean adherence to all recently initiated cardiovascular medications combined was 88.8% in the intervention group and 89.9% in the usual care group (P = .73). CONCLUSIONS: Participation in traditional CR programs does not appear to be influenced by the availability of telephone-based education and support. Furthermore, the high rate of adherence among the control group may suggest that CR programs are attracting "healthy adherers" who volunteer for such programs, while missing those with the greatest need for health care system resources.