Cyril Ferdynus

A meta-regression analysis of the available data on adherence to adjuvant hormonal therapy in breast cancer: summarizing the data for clinicians

A recent, systematic, qualitative, review by Murphy et al. [1] has provided a complete overview of the available data on persistence and adherence to hormonal therapy for breast cancer, as well as an extensive description of their determinants. This review demonstrates that treatment intakes are largely suboptimal. It also illustrates the heterogeneity of available studies, with treatment discontinuation rates ranging from 31 to 73 % over the treatment period. This wide range of values may limit the usefulness of raw data for clinicians. In order to provide measures clinicians might use effectively, we conducted a meta-regression analysis [2] that summarizes results on adherence and persistence to hormonal therapy, based on the data rigorously selected in the review by Murphy et al. This meta-regression analysis was conducted moreover to assess the different sources of variability in measurements of persistence. We reviewed the 29 studies selected in the comprehensive review by Murphy et al. [1], and discounted three of these. We excluded two studies [3, 4] in which results were pooled for tamoxifen and aromatase inhibitor (AI) treatment, and one [5] in which follow-up was limited to the first 4 months of treatment. We reviewed all 26 studies to record possible sources of heterogeneity in treatment adherence. These sources include: study type (cross-sectional or cohort study), data source (medical records, self-reported data, population-based database, specific health-coverage database), age of patients, measure of outcome (use of self-reported data or measures of refill gaps), and type of analysis (taking into account longitudinal data or not). Persistence to hormonal therapy and level of adherence over a 5-year period were studied separately, using a mixed model for longitudinal meta-analytic data [6]. We used a log(-log) transformation of the measure of outcome to normalize its distribution [7]. Each study was weighed by the inverse variance of the transformed outcome [2, 6]. All statistical analyses were performed using the following software programs: SAS 9.2 (SAS Institute Inc.), including the SAS procedure PROC MIXED, and R (R Development Core Team http://www.R-project.org), including the package metafor [8]. Among the 26 selected studies, 9 (34.6 %) reported data on both adherence and persistence [9–17], 9 (34.6 %) reported data only on adherence [18–26], and 8 (30.8 %) on persistence alone [27–34]. The meta-regression model estimated adherence to range from 79.6 % (95 % CI: 68.2–87.3) at 1 year to 68.3 % (95 % CI: 52.4–79.9) at 5 years. These numbers varied from 79.2 % (95 % CI: 67.5–87.0) to 64.6 % (95 % CI: 47.8–77.2) for tamoxifen treatment, and from 80.1 % (95 % CI: 68.8–87.7) to 71.8 % (95 % CI: 56.2–82.6) for AI therapy. Overall, nonpersistence to hormonal therapy ranges from 13.6 % (95 % CI: 11.1–16.6) at 1 year to 40.9 % (95 % CI: 34.5–47.9) at 5 years. Among the possible sources of heterogeneity tested, data source was the only source of variation in L. Huiart (&) C. Ferdynus Unité de Soutien Méthodologique, CHU La Réunion—CHFG, Allées Topaze, 97400 Saint-Denis, France e-mail: laetitia.huiart@mail.mcgill.ca

Prevalence and Risk Factors of Stress Cardiomyopathy After Convulsive Status Epilepticus in ICU Patients.

Objective:Although stress cardiomyopathy has been described in association with epilepsy, its frequency in patients with convulsive status epilepticus remains unknown. Accordingly, we sought to determine the prevalence and risk factors of stress cardiomyopathy in patients admitted to the ICU for convulsive status epilepticus. Design:Prospective, descriptive, single-center study. Setting:Medical-surgical ICU of a teaching hospital. Patients:Thirty-two consecutive ventilated patients (21 men; age, 50 ± 18 yr; Simplified Acute Physiology Score II, 53 ± 15; Sequential Organ Failure Assessment, 6 ± 2) hospitalized in the ICU for convulsive status epilepticus. Interventions:None. Measurements and Main Results:Hemodynamic parameters, transthoracic echocardiography, biological data, and electrocardiogram were obtained serially on ICU admission (H0), and after 6, 12, 24, and 48 hours of hospitalization (H6, H12, H24, and H48). Stress cardiomyopathy was defined as a 20% decrease in left ventricular ejection fraction between H0 or H6 and H48. Stress cardiomyopathy was diagnosed in 18 patients (56%; 95% CI, 38–74%). Mean left ventricular ejection fraction, left ventricular stroke index and cardiac index were initially (at H0 or H6 according to lowest individual values) significantly reduced in stress cardiomyopathy patients (45 ± 14% vs 61 ± 6%, p < 0.001; 24 ± 8 vs 28 ± 8 mL/m2, p < 0.05; 2.3 ± 0.7 vs 3.0 ± 0.8 L/min/m2, p < 0.05, respectively) and increased secondarily to reach similar mean values than those observed in patients without transient left ventricular dysfunction at H24. Dobutamine was more frequently used in patients with stress cardiomyopathy. Mean lactate level was increased and significantly higher in stress cardiomyopathy patients at H0 and H6, whereas mean central venous oxygen saturation was preserved but significantly lower in this group. Only three patients with stress cardiomyopathy had left ventricular regional wall motion abnormalities but normal coronary angiography. Risk factors of stress cardiomyopathy were age and Simplified Acute Physiology Score II. Conclusions:These results suggest that stress cardiomyopathy is common in patients admitted to the ICU for convulsive status epilepticus. Accordingly, these patients should be screened for stress cardiomyopathy and monitored if they present with hemodynamic compromise.

A Comparison of a Machine Learning Model with EuroSCORE II in Predicting Mortality after Elective Cardiac Surgery: A Decision Curve Analysis

Background The benefits of cardiac surgery are sometimes difficult to predict and the decision to operate on a given individual is complex. Machine Learning and Decision Curve Analysis (DCA) are recent methods developed to create and evaluate prediction models. Methods and finding We conducted a retrospective cohort study using a prospective collected database from December 2005 to December 2012, from a cardiac surgical center at University Hospital. The different models of prediction of mortality in-hospital after elective cardiac surgery, including EuroSCORE II, a logistic regression model and a machine learning model, were compared by ROC and DCA. Of the 6,520 patients having elective cardiac surgery with cardiopulmonary bypass, 6.3% died. Mean age was 63.4 years old (standard deviation 14.4), and mean EuroSCORE II was 3.7 (4.8) %. The area under ROC curve (IC95%) for the machine learning model (0.795 (0.755–0.834)) was significantly higher than EuroSCORE II or the logistic regression model (respectively, 0.737 (0.691–0.783) and 0.742 (0.698–0.785), p < 0.0001). Decision Curve Analysis showed that the machine learning model, in this monocentric study, has a greater benefit whatever the probability threshold. Conclusions According to ROC and DCA, machine learning model is more accurate in predicting mortality after elective cardiac surgery than EuroSCORE II. These results confirm the use of machine learning methods in the field of medical prediction.

Effectiveness of motivational interviewing interventions on medication adherence in adults with chronic diseases: a systematic review and meta-analysis.

Background Medication adherence is frequently suboptimal in adults with chronic diseases, resulting in negative consequences. Motivational interviewing (MI) is a collaborative conversational style for strengthening a persons motivation and commitment to change. We aimed to assess whether MI interventions are effective to enhance medication adherence in adults with chronic diseases and to explore the effect of individual MI intervention characteristics. Methods We searched electronic databases and reference lists of relevant articles to find randomized controlled trials (RCTs) that assessed MI intervention effectiveness on medication adherence in adults with chronic diseases. A random-effects model was used to estimate a pooled MI intervention effect size and its heterogeneity (I 2 ). We also explored the effects of individual MI characteristics on MI intervention effect size using a meta-regression with linear mixed model. Results : Nineteen RCTs were identified, and 16 were included in the meta-analysis. The pooled MI intervention effect size was 0.12 [95% confidence interval (CI) = (0.05, 0.20), I 2 = 1%]. Interventions that were based on MI only [β = 0.183, 95% CI = (0.004, 0.362)] or those in which interventionists were coached during intervention implementation [β = 0.465, 95% CI = (0.028, 0.902)] were the most effective. MI interventions that were delivered solely face to face were more effective than those that were delivered solely by phone [β = 0.270, 95% CI = (0.041, 0.498)]. Conclusions This synthesis of RCTs suggests that MI interventions might be effective at enhancing of medication adherence in adults treated for chronic diseases. Further research is however warranted, as the observed intervention effect size was small.

Measuring persistence to hormonal therapy in patients with breast cancer: accounting for temporary treatment discontinuation†

Several studies have been conducted to estimate persistence to hormonal therapy among women with breast cancer (BC). Most studies focus on first treatment discontinuation. Patients, however, can have numerous periods of treatment discontinuation or treatment exposure.

Structured peer-led diabetes self-management and support in a low-income country: The ST2EP randomised controlled trial in Mali

Objectives Our objective was to evaluate the effectiveness of peer-led self-management education in improving glycaemic control in patients with type 2 diabetes in a low-income country (Mali). Methods We conducted an open-label randomised controlled trial. A total of 151 adults (76% women, mean age 52.5) with type 2 diabetes (HbA1c≥8%), treated in the diabetes consultation units of two secondary health centres in Bamako, were allocated to peer-led structured patient education (n = 76) or conventional care alone (n = 75). The intervention group received 1 year of culturally tailored structured patient education (3 courses of 4 sessions) delivered in the community by five trained peer educators. Both groups underwent conventional diabetes monitoring and follow-up. Primary outcome was the mean absolute change in HbA1c from baseline to 12 months. Results 177 education sessions were delivered to the intervention group. Patient attrition was 8%. From baseline to 12 months, the decrease in HbA1c levels was 1.05% (SD = 2.0; CI95%: 1.54;-0.56) in the intervention group compared with 0.15% (SD = 1.7; CI95%: -0.56; 0.26) in the control group, p = 0.006. Mean BMI change was -1.65 kg/m2 (SD = 2.5; CI95%: -2.25; -1.06) in the intervention group and +0.05 kg/m2 (SD = 3.2; CI95%: -0.71; 0.81) in the control group, p = 0.0005. Mean waist circumference decreased by 3.34 cm (SD = 9.3; CI95%: -5.56;-1.13) in the intervention group and increased by 2.65 cm (SD = 10.3; CI95%: 0.20; 5.09) in the control group, p = 0.0003. Conclusions Peer-led structured patient education delivered over 1 year to patients with poorly controlled type 2 diabetes in Mali yielded substantial improvements in glycaemic control and anthropometric parameters. This is of importance for the scaling up of efficient interventions in low-resource settings in the future. Trial registration ClinicalTrials.gov NCT01485913

Simplified Acute Physiology Score II as Predictor of Mortality in Intensive Care Units: A Decision Curve Analysis.

Background End-of-life decision-making in Intensive care Units (ICUs) is difficult. The main problems encountered are the lack of a reliable prediction score for death and the fact that the opinion of patients is rarely taken into consideration. The Decision Curve Analysis (DCA) is a recent method developed to evaluate the prediction models and which takes into account the wishes of patients (or surrogates) to expose themselves to the risk of obtaining a false result. Our objective was to evaluate the clinical usefulness, with DCA, of the Simplified Acute Physiology Score II (SAPS II) to predict ICU mortality. Methods We conducted a retrospective cohort study from January 2011 to September 2015, in a medical-surgical 23-bed ICU at University Hospital. Performances of the SAPS II, a modified SAPS II (without AGE), and age to predict ICU mortality, were measured by a Receiver Operating Characteristic (ROC) analysis and DCA. Results Among the 4.370 patients admitted, 23.3% died in the ICU. Mean (standard deviation) age was 56.8 (16.7) years, and median (first-third quartile) SAPS II was 48 (34–65). Areas under ROC curves were 0.828 (0.813–0.843) for SAPS II, 0.814 (0.798–0.829) for modified SAPS II and of 0.627 (0.608–0.646) for age. DCA showed a net benefit whatever the probability threshold, especially under 0.5. Conclusion DCA shows the benefits of the SAPS II to predict ICU mortality, especially when the probability threshold is low. Complementary studies are needed to define the exact role that the SAPS II can play in end-of-life decision-making in ICUs.

Leptospirosis in ICU: A Retrospective Study of 134 Consecutive Admissions

Objectives: Leptospirosis causes reversible multiple organ failure, and its mortality remains high. The aim of this study was to determine the mortality rate of leptospirosis in an ICU offering all types of organ support available nowadays and to compare it with mortality in bacterial sepsis. Design: Retrospective, descriptive, and single-center cohort study. Settings: The largest ICU of Reunion Island (Indian Ocean) in a teaching hospital. Patients: Consecutive patients hospitalized in ICU for leptospirosis from January 2004 to January 2015. Interventions: None. Measurements and Main Results: We report 134 cases of patients with leptospirosis hospitalized in ICU. The median age was 40 years (interquartile range, 30–52 yr), with a Simplified Acute Physiology Score II of 38 (27–50) and a Sequential Organ Failure Assessment score of 10 (8–12). Forty-one patients (31%) required mechanical ventilation and 76 (56%) required renal replacement therapy. The door-to-renal replacement therapy time was 0 (0–1) day after admission with a median urea of 25 mmol/L (17–32 mmol/L). Five patients required extracorporeal membrane oxygenation. The mortality rate was 6.0% (95% CI, 2.6–11.4). Among patients hospitalized for sepsis, the standardized mortality ratio of patients with leptospirosis with regards to Simplified Acute Physiology Score II was dramatically low: 0.40 (95% CI, 0.17 – 0.79). Conclusions: The mortality of severe leptospirosis is lower than for other bacterial infection, provided modern resuscitation techniques are available. Prompt organ support ensures very low mortality rates despite high severity scores.

Trends in initiation of direct oral anticoagulant therapies for atrial fibrillation in a national population-based cross-sectional study in the French health insurance databases

Objective Unlike several other national health agencies, French health authorities recommended that the newer direct oral anticoagulant (DOAC) agents only be prescribed as second choice for the treatment of newly diagnosed non-valvular atrial fibrillation (NVAF), with vitamin K antagonists (VKA) remaining the first choice. We investigated the patterns of use of DOACs versus VKA in the treatment of NVAF in France over the first 5 years of DOAC availability. We also identified the changes in patient characteristics of those who initiated DOAC treatment over this time period. Methods Based on the French National Health Administrative Database, we constituted a population-based cohort of all patients who were newly treated for NVAF between January 2011 and December 2015. Trends in drug use were described as the percentage of patients initiating each drug at the time of treatment initiation. A multivariate analysis using logistic regression model was performed to identify independent sociodemographic and clinical predictors of initial anticoagulant choice. Results The cohort comprised 814 446 patients who had received a new anticoagulant treatment for NVAF. The proportion of patients using DOACs as initial anticoagulant therapy reached 54% 3 months after the Health Ministry approved the reimbursement of dabigatran for NVAF, and 61% by the end of 2015, versus VKA use. In the multivariate analysis, we found that DOAC initiators were younger and healthier overall than VKA initiators, and this tendency was reinforced over the 2011–2014 period. DOACs were more frequently prescribed by cardiologists in 2012 and after (adjusted OR in 2012: 2.47; 95% CI 2.40 to 2.54). Conclusion Despite recommendations from health authorities, DOACs have been rapidly and massively adopted as initial therapy for NVAF in France. Observational studies should account for the fact that patients selected to initiate DOAC treatment are healthier overall, as failure to do so may bias the risk–benefit assessment of DOACs.

Children with abnormal DMSA nuclear scan present a higher risk of recurrent febrile urinary tract infections

The ideal management of a child presenting a first episode of febrile urinary tract infection is still under debate. In the recent guidelines for the diagnosis and management of urinary tract infections (UTI) in children, the American Association of Pediatrics recommend performing a post-UTI sonography, and if there are abnormal findings, a voiding cystourethrogram [1]. This change derives from the understanding that we should be avoiding renal damage rather more than diagnosing reflux, since both surgery and antibiotic prophylaxis are progressively being abandoned for most cases of vesicoureteral reflux (VUR) [2, 3]. The most significant event which will bring a child to active management is recurrence of UTI [4, 5]. It seems therefore more clinically relevant to differentiate between children who will suffer recurrent episodes of UTI and those who will not, rather than to simply identify which children have VUR. We therefore aimed to evaluate if DMSA nuclear scan could reliably identify which children were at risk of presenting a second febrile UTI. We retrospectively analyzed all children aged between 2 and 24 months, without prenatally diagnosed uropathy, who were admitted to our institution for a first febrile UTI between 2009 and 2013, had a post-urinary tract infection sonography and DMSA nuclear scan, and were followed for at least 24 months. We excluded patients with missing or incomplete data, or lost to follow-up. Febrile UTI was defined as fever > 38 °C associated with positive urinalysis and urine culture (> 105 CFU/mL urine) collected through catheterization in girls, and clean-catch in boys. We noted patient’s characteristics, and the results of the DMSA scan performed within 1 month of the acute episode. DMSA scans were categorized as normal, i.e., no scarring or dysplasia, or abnormal, any degree of scarring or dysplasia, functional impairment or atrophy. After the first febrile UTI, parents were systematically counseled about early diagnosis and having a urinalysis done if their child presented unexplained fever. None were given antibiotic prophylaxis but they were given advice about local hygiene and measures to avoid constipation in their child. All children were followed at least once every 6 months for a minimum of 24 months. The main outcome was recurrence of a second febrile UTI within the first 24 months of follow-up. In case of recurrence, a cystogram was performed, and children were further managed accordingly. On hundred and seven children were included in our study. There were 49 boys and 58 girls (45.8/54.2%). None were lost to follow-up, and all relevant data were available for all included patients. Children included did not differ from those who were excluded from the study. The mean age at first febrile UTI was 6.8 ± 5.4 months. Twenty-four (22.4%) children presented abnormal DMSA findings. Six presented asymmetric function without signs of dysplasia or scarring, two had a solitary kidney, and 16 had signs of dysplasia or scarring, of which 6 had asymmetric function. Sixteen (14.9%) children presented a recurrence within 24 months, of which ten had an abnormal DMSA scan. Both age and gender were comparable in both groups (with and without recurrence). All boys were uncircumcised. There were significantly more recurrences in the abnormal DMSA group [relative risk (RR) = 5.8; 95% confidence interval (95% CI) 2.1–15.9] compared to the normal DMSA group. The sensitivity and specificity of DMSA scan to predict which children will present a recurrence of febrile UTI were 62.5% * Luke Harper harper_luke@hotmail.com