Meta-Analysis of Incidence Rate Data in the Presence of Zero-Event and Single-Arm Studies

Unlike the classical two-stage DerSimonian and Laird meta-analysis method, the one-stage random-effects Poisson and Negative-binomial models have the great advantage of including the information contained in studies reporting zero event in one or both arms and in studies with one missing arm. Since the Negative-binomial distribution relaxes the assumption of equi-dispersion made by the Poisson, it should perform better when data exhibit over-dispersion. However, the superiority of the Negative-binomial model with rare events and single-arm studies is unclear and needs to be investigated. Moreover, to the best of our knowledge, this model has never been investigated in the context of a meta-analysis of incidence rate data with heterogeneous intervention effect. Therefore, we assessed the performance of the univariate and bivariate random-effects Poison and Negative-binomial models using simulations calibrated on a real dataset from a study on the surgical management of phyllodes tumors. Results suggested that the bivariate random-effects Negative-binomial model should be favored for the meta-analysis of incidence rate data exhibiting over-dispersion, even in the presence of zero-event and single-arm studies

Ambulatory Healthcare Use Profiles of Patients With Diabetes and Their Association With Quality of Care: A Cross-Sectional Study

BACKGROUND: Despite the growing burden of diabetes worldwide, evidence regarding the optimal models of care to improve the quality of diabetes care remains equivocal. This study aimed to identify profiles of patients with distinct ambulatory care use patterns and to examine the association of these profiles with the quality of diabetes care. METHODS: We performed a cross-sectional study of the baseline data of 550 non-institutionalized adults included in a prospective, community-based, cohort study on diabetes care conducted in Switzerland. Clusters of participants with distinct patterns of ambulatory healthcare use were identified using discrete mixture models. To measure the quality of diabetes care, we used both processes of care indicators (eye and foot examination, microalbuminuria screening, blood cholesterol and glycated hemoglobin measurement [HbA1c], influenza immunization, blood pressure measurement, physical activity and diet advice) and outcome indicators (12-Item Short-Form Health Survey [SF-12], Audit of Diabetes-Dependent Quality of Life [ADDQoL], Patient Assessment of Chronic Illness Care [PACIC], Diabetes Self-Efficacy Scale, HbA1c value, and blood pressure <140/90 mmHg). For each profile of ambulatory healthcare use, we calculated adjusted probabilities of receiving processes of care and estimated adjusted outcomes of care using logistic and linear regression models, respectively. RESULTS: Four profiles of ambulatory healthcare use were identified: participants with more visits to the general practitioner [GP] than to the diabetologist and receiving concomitant podiatry care (“GP & podiatrist”, n=86); participants visiting almost exclusively their GP (“GP only”, n=195); participants with a substantially higher use of all ambulatory services (“High users”, n=96); and participants reporting more visits to the diabetologist and less visits to the GP than other profiles (“Diabetologist first”, n=173). Whereas participants belonging to the “GP only” profile were less likely to report most processes related to the quality of diabetes care, outcomes of care were relatively comparable across all ambulatory healthcare use profiles. CONCLUSIONS: Slight differences in quality of diabetes care appear across the four ambulatory healthcare use profiles identified in this study. Overall, however, results suggest that room for improvement exists in all profiles, and further investigation is necessary to determine whether individual characteristics (like diabetes-related factors) and/or healthcare factors contribute to the differences observed between profiles

Reproducibility of diabetes quality of care indicators as reported by patients and physicians

Introduction: Self-report of diabetes care has moderate validity and is prone to under- and over-reporting. We assessed reproducibility of a range of processes and outcomes of diabetes care as reported by patients and physicians. Methods: In a Swiss community-based survey, patients with diabetes and physicians independently reported past 12 months processes of care (HbA1c, lipids, microalbuminuria, blood pressure, weight, foot and eye examinations) and last measured values of HbA1c, height, weight and blood pressure. For dichotomous variables, we assessed reliability by Cohen's kappa and agreement by uniform kappa. For continuous measures, we used Lin's concordance correlation coefficient and limits of agreement, respectively. Results: Mean age of the 210 patients was 65 years; 40% were women, and 51% had diabetes for >10 years. Agreement was good for recommended processes of care such as blood pressure (uniform kappa = 0.94), HbA1c (0.93), weight (0.88) and lipid (0.78), but lower for microalbuminuria, foot and eye examinations (all <0.50). Cohen's kappa values were all low (<0.25). Comparisons of reported continuous variables showed large limits of agreement for height (±6 cm) and weight (8-10 kg) despite high concordance correlation coefficients (0.93 and 0.97). Concordance correlation coefficients were smaller for HbA1c (0.72) and blood pressure (0.5-0.6), with large limits of agreement (±2% and ±25 mmHg). Conclusion: While agreement of routine processes of care was good, agreement was less satisfactory for microalbuminuria, foot and eye examinations. Reports of continuous outcomes yielded good reliability but too wide limits of agreement. Quality of care evaluation relying on self-report only should be made cautiousl

CD4+ T Cell Count Decreases by Ethnicity among Untreated Patients with HIV Infection in South Africa and Switzerland

BackgroundEstimates of the decrease in CD4+ cell counts in untreated patients with human immunodeficiency virus (HIV) infection are important for patient care and public health. We analyzed CD4+ cell count decreases in the Cape Town AIDS Cohort and the Swiss HIV Cohort Study MethodsWe used mixed-effects models and joint models that allowed for the correlation between CD4+ cell count decreases and survival and stratified analyses by the initial cell count (50-199, 200-349, 350-499, and 500-750 cells/μL). Results are presented as the mean decrease in CD4+ cell count with 95% confidence intervals (CIs) during the first year after the initial CD4+ cell count ResultsA total of 784 South African (629 nonwhite) and 2030 Swiss (218 nonwhite) patients with HIV infection contributed 13,388 CD4+ cell counts. Decreases in CD4+ cell count were steeper in white patients, patients with higher initial CD4+ cell counts, and older patients. Decreases ranged from a mean of 38 cells/μL (95% CI, 24-54 cells/μL) in nonwhite patients from the Swiss HIV Cohort Study 15-39 years of age with an initial CD4+ cell count of 200-349 cells/μL to a mean of 210 cells/μL (95% CI, 143-268 cells/μL) in white patients in the Cape Town AIDS Cohort ⩾40 years of age with an initial CD4+ cell count of 500-750 cells/μL ConclusionsAmong both patients from Switzerland and patients from South Africa, CD4+ cell count decreases were greater in white patients with HIV infection than they were in nonwhite patients with HIV infectio

Sex difference and the role of leptin in the association between high-sensitivity C-reactive protein and adiposity in two different populations

Elevated high-sensitivity C-reactive protein (hs-CRP) concentration is associated with an increased risk of cardiovascular disease but this association seems to be largely mediated via conventional cardiovascular risk factors. In particular, the association between hs-CRP and obesity has been extensively demonstrated and correlations are stronger in women than men. We used fractional polynomials—a method that allows flexible modeling of non linear relations—to investigate the dose/response mathematical relationship between hs-CRP and several indicators of adiposity in Caucasians (Switzerland) and Africans (Seychelles) surveyed in two population-based studies. This relationship was non-linear exhibiting a steeper slope for low levels of hs-CRP and a higher level in women. The observed sex difference in the relationship between hs-CRP and adiposity almost disappeared upon adjustment for leptin, suggesting that these sex differences might be partially mediated, by leptin. All these relationship were similar in Caucasians and Africans. This is the first report on a non-linear relation, stratified by gender, between hs-CRP and adiposit

Comparison of neoadjuvant cisplatin-based chemotherapy versus radiochemotherapy followed by resection for stage III (N2) NSCLC

Objective: Comparison of prospectively treated patients with neoadjuvant cisplatin-based chemotherapy vs radiochemotherapy followed by resection for mediastinoscopically proven stage III N2 non-small cell lung cancer with respect to postoperative morbidity, pathological nodal downstaging, overall and disease-free survival, and site of recurrence. Methods: Eighty-two patients were enrolled between January 1994 to June 2003, 36 had cisplatin and doxetacel-based chemotherapy (group I) and 46 cisplatin-based radiochemotherapy up to 44Gy (group II), either as sequential (25 patients) or concomitant (21 patients) treatment. All patients had evaluation of absence of distant metastases by bone scintigraphy, thoracoabdominal CT scan or PET scan, and brain MRI, and all underwent pre-induction mediastinoscopy, resection and mediastinal lymph node dissection by the same surgeon. Results: Group I and II comprised T1/2 tumors in 47 and 28%, T3 tumors in 45 and 41%, and T4 tumors in 8 and 31% of the patients, respectively (P=0.03). There was a similar distribution of the extent of resection (lobectomy, sleeve lobectomy, left and right pneumonectomy) in both groups (P=0.9). Group I and II revealed a postoperative 90-d mortality of 3 and 4% (P=0.6), a R0-resection rate of 92 and 94% (P=0.9), and a pathological mediastinal downstaging in 61 and 78% of the patients (P≪0.01), respectively. 5y-overall survival and disease-free survival of all patients were 40 and 36%, respectively, without significant difference between T1-3 and T4 tumors. There was no significant difference in overall survival rate in either induction regimens, however, radiochemotherapy was associated with a longer disease-free survival than chemotherapy (P=0.04). There was no significant difference between concurrent vs sequential radiochemotherapy with respect to postoperative morbidity, resectability, pathological nodal downstaging, survival and disease-free survival. Conclusions: Neoadjuvant cisplatin-based radiochemotherapy was associated with a similar postoperative mortality, an increased pathological nodal downstaging and a better disease-free survival as compared to cisplatin doxetacel-based chemotherapy in patients with stage III (N2) NSCLC although a higher number of T4 tumors were admitted to radiochemotherap

Low postseroconversion CD4 count and rapid decrease of CD4 density identify HIV+ fast progressors

CD4 expression in HIV replication is paradoxical: HIV entry requires high cell-surface CD4 densities, but replication requires CD4 down-modulation. However, is CD4 density in HIV+ patients affected over time? Do changes in CD4 density correlate with disease progression? Here, we examined the role of CD4 density for HIV disease progression by longitudinally quantifying CD4 densities on CD4+ T cells and monocytes of ART-naive HIV+ patients with different disease progression rates. This was a retrospective study. We defined three groups of HIV+ patients by their rate of CD4+ T cell loss, calculated by the time between infection and reaching a CD4 level of 200 cells/microl: fast (12 years). Mathematical modeling permitted us to determine the maximum CD4+ T cell count after HIV seroconversion (defined as "postseroconversion CD4 count") and longitudinal profiles of CD4 count and density. CD4 densities were quantified on CD4+ T cells and monocytes from these patients and from healthy individuals by flow cytometry. Fast progressors had significantly lower postseroconversion CD4 counts than other progressors. CD4 density on T cells was lower in HIV+ patients than in healthy individuals and decreased more rapidly in fast than in slow progressors. Antiretroviral therapy (ART) did not normalize CD4 density. Thus, postseroconversion CD4 counts define individual HIV disease progression rates that may help to identify patients who might benefit most from early ART. Early discrimination of slow and fast progressors suggests that critical events during primary infection define long-term outcome. A more rapid CD4 density decrease in fast progressors might contribute to progressive functional impairments of the immune response in advanced HIV infection. The lack of an effect of ART on CD4 density implies a persistent dysfunctional immune response by uncontrolled HIV infection