Influence of lack of blinding on the estimation of medication-related harms: a retrospective cohort study of randomized controlled trials.

BACKGROUND: Empirical evidence suggests that lack of blinding may be associated with biased estimates of treatment benefit in randomized controlled trials, but the influence on medication-related harms is not well-recognized. We aimed to investigate the association between blinding and clinical trial estimates of medication-related harms. METHODS: We searched PubMed from January 1, 2015, till January 1, 2020, for systematic reviews with meta-analyses of medication-related harms. Eligible meta-analyses must have contained trials both with and without blinding. Potential covariates that may confound effect estimates were addressed by restricting trials within the comparison or by hierarchical analysis of harmonized groups of meta-analyses (therefore harmonizing drug type, control, dosage, and registration status) across eligible meta-analyses. The weighted hierarchical linear regression was then used to estimate the differences in harm estimates (odds ratio, OR) between trials that lacked blinding and those that were blinded. The results were reported as the ratio of OR (ROR) with its 95% confidence interval (CI). RESULTS: We identified 629 meta-analyses of harms with 10,069 trials. We estimated a weighted average ROR of 0.68 (95% CI: 0.53 to 0.88, P < 0.01) among 82 trials in 20 meta-analyses where blinding of participants was lacking. With regard to lack of blinding of healthcare providers or outcomes assessors, the RORs were 0.68 (95% CI: 0.53 to 0.87, P < 0.01 from 81 trials in 22 meta-analyses) and 1.00 (95% CI: 0.94 to 1.07, P = 0.94 from 858 trials among 155 meta-analyses) respectively. Sensitivity analyses indicate that these findings are applicable to both objective and subjective outcomes. CONCLUSIONS: Lack of blinding of participants and health care providers in randomized controlled trials may underestimate medication-related harms. Adequate blinding in randomized trials, when feasible, may help safeguard against potential bias in estimating the effects of harms.

Determinants of Atrial Fibrillation Development among Patients undergoing Ibrutinib Therapy.

Objective: Within the last decade, the use of ibrutinib, a first-generation, non-selective, irreversible Burton's tyrosine kinase inhibitor for the treatment of hematological malignancies has proven highly effective in improving patient outcomes.Background: Ibrutinib has been associated with an increase in atrial fibrillation (AF). The predisposing factors are thought to be pre-existing cardiovascular risk factors, but these have not been directly evaluated.Methods: We conducted a nested case-control study, recruiting consecutive ibrutinib treated subjects to evaluate cardiovascular risk factors associated with the development of AF in patients diagnosed with hematological B-cell malignancies.Results: Of the 189 patients treated with ibrutinib and without AF at baseline, 54 (29%) developed AF. Cardiovascular risk factors associated with AF development were, older age, prior hypertension (HTN), history of heart failure (HF) and congenital heart disease. A patient with HF at baseline had a 1, 2, 6, and 12 month cumulative hazard of AF of 40%, 48%, 64%, and 71%, respectively. Patients with prior HTN without HF at baseline had a 1, 2, 6, and 12 month cumulative hazard of AF of 5%, 10%, 23%, and 31%, respectively while on ibrutinib therapy.Conclusions: The relationship between ibrutinib, cardiovascular comorbidities, and AF is through pre-existing cardiovascular disease. An individualized, multidisciplinary approach involving cardiologists should be considered when initiating ibrutinib, particularly when there is a history of HTN, HF or congenital heart disease. In such patients, there should be close cardiovascular monitoring and prompt intervention when AF develops to improve patient outcomes.

Bias Assessment in Outcomes Research: The Role of Relative Versus Absolute Approaches.

OBJECTIVES: Bias assessment tools vary in content and detail, and the method used for assessment may produce different assessment results in a study if not carefully considered. Therefore, taking an approach to the assessment of studies that produces a similar result regardless of the tool used for assessment (tool independence) is important. METHODS: A preexisting study that used 25 different quality scales was assessed to examine tool dependence of 2 common approaches to bias assessments-absolute value judgments (defined as the qualitative risk of bias judgment based on a threshold across studies) and relative ranks (defined as the relative probability toward bias of a study relative to the best assessed study). Agreement between each of the 25 scales and a composite scale (that includes all unique safeguards across all scales) was computed (using the intraclass correlation coefficient [ICC]; consistency). Tool dependence was considered present when the ICCs were inconsistent across the 25 scales for the same study. RESULTS: We found that using relative ranks for tools with different numbers and types of items produced consistent results, with only small differences in the agreement for the various tools with the composite tool, whereas consistency (measured by the ICC) varied considerably when using absolute judgments. Inconsistency is problematic because it means that the assessment result is linked to the scale and not to the study. CONCLUSIONS: Tool independence is an important attribute of a bias assessment tool. On the basis of this study, the use of relative ranks retains tool independence and therefore produces consistent ranks for the same study across tools.

Prevalence and determinants of symptomatic COVID-19 infection among children and adolescents in Qatar: a cross-sectional analysis of 11 445 individuals.

There is a paucity of evidence about the prevalence and risk factors for symptomatic infection among children. This study aimed to describe the prevalence of symptomatic coronavirus disease 2019 (COVID-19) and its risk factors in children and adolescents aged 0-18 years in Qatar. We conducted a cross-sectional study of all children aged 0-18 years diagnosed with COVID-19 using polymerase chain reaction in Qatar during the period 1st March to 31st July 2020. A generalised linear model with a binomial family and identity link was used to assess the association between selected factors and the prevalence of symptomatic infection. A total of 11 445 children with a median age of 8 years (interquartile range (IQR) 3-13 years) were included in this study. The prevalence of symptomatic COVID-19 was 36.6% (95% confidence interval (CI) 35.7-37.5), and it was similar between children aged <5 years (37.8%), 5-9 years (34.3%) and 10 + years (37.3%). The most frequently reported symptoms among the symptomatic group were fever (73.5%), cough (34.8%), headache (23.2%) and sore throat (23.2%). Fever (82.8%) was more common in symptomatic children aged <5 years, while cough (38.7%) was more prevalent in those aged 10 years or older, compared to other age groups. Variables associated with an increased risk of symptomatic infection were; contact with confirmed cases (RD 0.21; 95% CI 0.20-0.23; P = 0.001), having visited a health care facility (RD 0.54; 95% CI 0.45-0.62; P = 0.001), and children aged under 5 years (RD 0.05; 95% CI 0.02-0.07; P = 0.001) or aged 10 years or older (RD 0.04; 95% CI 0.02-0.06; P = 0.001). A third of the children with COVID-19 were symptomatic with a higher proportion of fever in very young children and a higher proportion of cough in those between 10 and 18 years of age.

Efficacy of Anthelminthic Drugs and Drug Combinations Against Soil-transmitted Helminths: A Systematic Review and Network Meta-analysis.

Background: Periodic mass distribution of benzimidazole anthelminthic drugs is the key strategy to control soil-transmitted helminths (STHs) globally. However, benzimidazoles have low efficacy against Trichuris trichiura, and there are concerns about benzimidazole resistance potentially emerging in humans. Therefore, identifying alternative drug regimens is a pressing priority. We present a systematic review and network meta-analysis comparing the efficacy of 21 different anthelminthic drug regimens, including standard, novel, and combination treatments. Methods: We searched PubMed, Medline, Embase, Web of Science, and Cochrane databases and identified studies comparing anthelminthic treatments to each other or placebo. The outcomes calculated were relative risk (RR) of cure and difference in egg reduction rates (dERR). We used an automated generalized pairwise modeling framework to generate mixed treatment effects against a common comparator, the current standard treatment (single-dose albendazole). Results: Our search identified 4876 studies, of which 114 were included in the meta-analysis. Results identified several drug combinations with higher efficacy than single-dose albendazole for T. trichiura, including albendazole-ivermectin (RR of cure, 3.22 [95% confidence interval {CI}, 1.84-5.63]; dERR, 0.97 [95% CI, .21-1.74]), albendazole-oxantel pamoate (RR, 5.07 [95% CI, 1.65-15.59]; dERR, 0.51 [95% CI, .50-.52]), mebendazole-ivermectin (RR, 3.37 [95% CI, 2.20-5.16]), and tribendimidine-oxantel pamoate (RR, 4.06 [95% CI, 1.30-12.64]). Conclusions: There are several promising drug combinations that may enhance the impact of STH control programs on T. trichiura, without compromising efficacy against Ascaris lumbricoides and hookworm. We suggest further, large-scale trials of these drug combinations and consideration of their use in STH control programs where T. trichiura is present. International Prospective Register of Systematic Reviews Registration: CRD42016050739.

The effectiveness of targeted relative to empiric prophylaxis on infectious complications after transrectal ultrasound-guided prostate biopsy: a meta-analysis.

PURPOSE: Rectal culture screening for fluoroquinolone (FQ)-resistant Enterobacteriaceae before transrectal ultrasound guided prostate (TRUSPB) biopsy and targeted antibiotic prophylaxis (TAP) may decrease post-TRUSPB infection rates compared to empiric (EAP) regimens. The objective of this study was to evaluate the effectiveness of targeted relative to empiric prophylaxis regimens on rates of infectious complications after TRUSPB and to determine the baseline prevalence of FQ resistance based on prior rectal swabs. METHODS: An electronic search within literature databases including EMBASE and Web of Science (all databases) for articles assessing TAP as an approach to TRUSPB prophylaxis was conducted. Quality assessment was performed using the Hoy instrument. Meta-analysis was performed using MetaXL 5.3. RESULTS: From 15 studies (eight retrospective and seven prospective) representing 12,320 participants, infectious complication incidence was 3.4% in EAP and 0.8% in TAP patients. The number needed to treat with TAP to avoid one more infection when compared to the EAP group was 39. Effect sizes were homogeneous. Prevalence of FQ resistance showed low (15%) and high (28%) subgroups, likely due to region of origin (within and outside USA, respectively). CONCLUSIONS: Rectal culture prior to TRUSPB and use of TAP adjusts for endemic FQ resistance and is associated with less infectious complications and resulting morbidity when compared to EAP. Overtreatment associated with augmented prophylaxis approaches may be reduced as a result. Further prospective assessment and cost-benefit analyses are required before widespread implementation can be recommended.

Comparison of fosfomycin against fluoroquinolones for transrectal prostate biopsy prophylaxis: an individual patient-data meta-analysis.

PURPOSE: To systematically review and meta-analyse available evidence comparing fosfomycin trometamol (FT) to fluoroquinolone (FQ) prophylaxis to prevent transrectal ultrasound-guided prostate biopsy (TRUSPB) related infectious complications. METHODS: Electronic databases were queried for studies comparing FT to FQ-based TRUSPB prophylaxis. Studies were assessed for comparable outcomes and methodological quality (ROBINS-I modification). The primary outcome measure was the relative odds of overall infectious complications following TRUSPB according to FT/FQ treatment, which was evaluated with meta-analysis. Safety and tolerability were also assessed. The relative odds of infections of different severity [Grade 1, bacteriuria and afebrile urinary tract infection (UTI); Grade 2, bacteraemia, febrile UTI, and urosepsis] according to FT/FQ treatment were also estimated. RESULTS: Five studies, being three prospective randomised trials and two retrospective cohort studies, representing 3112 patients, were included. The relative odds of an infectious complication (OR 0.22, 95% CI 0.09-0.54) or of a more severe (Grade 2) infection (OR 0.13, 95% CI 0.07-0.26) were significantly lower in those receiving FT compared to FQ prophylaxis. A low incidence of medication-related side effects was observed. There were less observed infections due to FQ-resistant pathogens in those receiving FT prophylaxis. CONCLUSIONS: Patients who received FT prophylaxis were less likely than those who received FQ prophylaxis to develop infections overall, as well as severe and resistant infections after TRUSPB. Assessing the performance of FT in other geographic locations or in comparison to targeted prophylaxis based on risk assessment or rectal cultures is desired.

Upper Versus Lower Gastrointestinal Delivery for Transplantation of Fecal Microbiota in Recurrent or Refractory Clostridium difficile Infection: A Collaborative Analysis of Individual Patient Data From 14 Studies.

GOALS: The aim of this study was to compare upper gastrointestinal (UGI) versus lower gastrointestinal (LGI) delivery routes of fecal microbiota transplantation (FMT) for refractory or recurrent/relapsing Clostridium difficile infection (CDI). BACKGROUND: FMT has been proven to be a safe and highly effective therapeutic option for CDI. Delivery, however, could be via the UGI or LGI routes, and it is unclear as to which route provides better clinical outcome. STUDY: A systematic search for studies that reported the use of FMT for CDI treatment was conducted. Individual patient data that included demographic (age and sex) and clinical (route of FMT delivery, CDI outcome after FMT, and follow-up time) information were obtained. Kaplan-Meier cumulative hazard curves and Cox proportional hazard models were used to assess clinical failure after FMT by the route of delivery. RESULTS: Data from 305 patients treated with FMT (208 via LGI route and 97 via UGI route) for CDI were analyzed. At 30 and 90 days, the risk of clinical failure was 5.6% and 17.9% in the UGI group compared with 4.9% and 8.5% in the LGI delivery route group, respectively. A time-varying analysis suggested a 3-fold increase in hazard of clinical failure for UGI delivery (hazard ratio, 3.43; 95% confidence interval, 1.32-8.93) in the period after 30 days. CONCLUSIONS: FMT delivered via the LGI seems to be the most effective route for the prevention of recurrence/relapse of CDI. A randomized controlled trial is necessary to confirm whether FMT delivered via the LGI is indeed superior to that delivered via the UGI route.

The McGill Brisbane Symptom Score in relation to survival in pancreatic adenocarcinoma: a validation study.

PURPOSE: The McGill Brisbane Symptom Score (MBSS) is a clinical score for pancreatic cancer patients upon initial presentation that takes into account four variables (weight loss, abdominal pain, jaundice, and history of smoking) to stratify them into two MBSS intensity categories. Several studies have suggested that these categories are strongly associated with eventual survival in patients with resectable (rPCa) and unresectable (uPCa) pancreatic cancer. This study aimed to validate the MBSS in a cohort of patients with pancreatic cancer from a single institution. METHODS: Survival time by resection status and MBSS intensity category were analyzed among 633 patients from our institution between 2001 and 2010. Hazard ratios for death using Cox proportional hazards models, with age as the timescale, adjustment for sex and year of diagnosis, and stratified by adjuvant chemotherapy status were estimated. RESULTS: Median survival time was the longest in patients with low-intensity MBSS and rPCa (817 days), whereas the shortest survival time was found among patients with uPCa regardless of MBSS status (144-147 days). After consideration of age and chemotherapy status, high-intensity MBSS was associated with poorer survival for both rPCa (HR 1.64; 95 % CI 1.07-2.52) and uPCa (HR 1.35; 95 % CI 1.06-1.72). CONCLUSIONS: Preoperative MBSS intensity is a useful prognostic indicator of survival in resectable as well as unresectable pancreatic cancer.

Association between patient activation and patient-assessed quality of care in type 2 diabetes: results of a longitudinal study.

BACKGROUND: Previous research using cross-sectional data has shown a positive relationship between patient activation and quality of care. The quantitative relationships in the same patients over time, however, remain undefined. OBJECTIVE: To examine the relationship between changes in activation over time and patient-assessed quality of chronic illness care. DESIGN: Prospective cohort study. PARTICIPANTS: The study used data reported annually from 2008 (N = 3761) to 2010 (N = 3040), using self-report survey questionnaires, completed by patients with type 2 diabetes in a population-based cohort in Queensland, Australia. MAIN MEASURES: Principal measures were the 13-item Patient Activation Measure (PAM), and the 20-item Patient Assessment of Chronic Illness Care (PACIC) instrument. METHODS: Nonparametric anova was used to determine the association between patient activation and patient-assessed quality of care in low and high patient activation groups at baseline (2008), and in 2009 and 2010, when patients had changed group membership. The Wilcoxon signed ranks test was used to compare the PACIC scores between baseline and each follow-up survey for the same patient activation level. RESULTS: Patient activation was positively associated with the median PACIC score within each survey year and within each of the groups defined at baseline (high- and low-activation groups; P < 0.001). CONCLUSIONS: Patient activation and the PACIC change in the same direction and should be considered together in the interpretation of patient care assessment. This can be carried out by interpreting PACIC scores within strata of PAM.

Transient Hypothyroidism after Radioiodine for Graves' Disease: Challenges in Interpreting Thyroid Function Tests.

Graves' disease is the most common cause of hyperthyroidism and is often managed with radioactive iodine (RAI) therapy. With current dosing schemes, the vast majority of patients develop permanent post-RAI hypothyroidism and are placed on life-long levothyroxine therapy. This hypothyroidism typically occurs within the first 3 to 6 months after RAI therapy is administered. Indeed, patients are typically told to expect life-long thyroid hormone replacement therapy to be required within this timeframe and many providers expect this post-RAI hypothyroidism to be complete and permanent. There is, however, a small subset of patients in whom a transient post-RAI hypothyroidism develops which, initially, presents exactly as the typical permanent hypothyroidism. In some cases the transient hypothyroidism leads to a period of euthyroidism of variable duration eventually progressing to permanent hypothyroidism. In others, persistent hyperthyroidism requires a second dose of RAI. Failure to appreciate and recognize the possibility of transient post-RAI hypothyroidism can delay optimal and appropriate treatment of the patient. We herein describe five cases of transient post-RAI hypothyroidism which highlight this unusual sequence of events. Increased awareness of this possible outcome after RAI for Graves' disease will help in the timely management of patients.

Exploring Gender Difference in Sleep Quality of Young Adults: Findings from a Large Population Study.

OBJECTIVES: To explore if gender difference in sleep quality is due to higher prevalence of depression in females, and whether socio-demographic and lifestyle factors have a differential effect on sleep quality in males and females. METHODS: Youth self-reports and the Pittsburgh Sleep Quality Index were used to assess sleep quality and associated risk factors. Logistic regression analyses were used to analyze the association between various risk factors and poor sleep quality. RESULTS: Reports from 3,778 young adults (20.6±0.86 years) indicate a higher prevalence of poor sleep quality in females than males (65.1% vs. 49.8%). It seems that gender difference in poor sleep is independent of depression, socio-demographics, and lifestyle factors, since the higher odds of poor sleep quality in females was robust to adjust for depression, socio-demographics, and lifestyle factors (OR: 1.53, 95% CI: 1.23-1.90). Lifestyle factors (eg, smoking) (OR 1.91; 95% CI 1.05-3.46) were associated with sleep quality in only males. CONCLUSION: Our findings indicate that female vulnerability to poor sleep quality should be explored beyond psycho-social disparities. Perhaps, exploring if the female predisposition to poor sleep quality originates at the biological level could lead to the answer.

Parent and adolescent reports in assessing adolescent sleep problems: results from a large population study.

AIM: To compare parent and adolescent reports in exploring adolescent sleep problems and to identify the factors associated with adolescent sleep problem disclosures. METHODS: Parent (n = 5185) and adolescent reports (n = 5171, age=13.9 ± 0.3 years), from a birth cohort were used to explore adolescent sleep problems. Kappa coefficients were used to assess the agreement, whereas, conditional agreement and disagreement ratios were used to identify the optimal informant. Logistic regression analysis was used to determine the factors affecting adolescent sleep problem disclosure. RESULTS: Parental reports identified only about one-third of the sleep problems reported by adolescents. Whereas adolescent reports identified up to two-thirds of the sleep problems reported by parents. Combined reports of parents and adolescent did not show any considerable difference from the adolescent report. Adolescent and parent health, maternal depression, and family communication were significantly associated with adolescents sleep problem disclosures. CONCLUSION: Adolescent reports could be used as the preferred source to explore adolescent sleep problems. Parental reports should be used when parents as observers are more reliable reporters, or where adolescents are cognitively unable to report sleep problems. Additionally, the impact of poor health, maternal depression and family communication on sleep problems disclosure should be considered for adolescent sleep problem diagnosis.

Influence of patient-assessed quality of chronic illness care and patient activation on health-related quality of life.

OBJECTIVE: To examine the association of the Patient Assessment of Chronic Illness Care (PACIC) with health-related quality of life (HRQoL) and the modulating effect of patient activation on this association. DESIGN AND PARTICIPANTS: A population-based prospective cohort study of people with Type 2 diabetes in Queensland, Australia, using data from self-report questionnaires, collected annually from 2008 (n = 3761) to 2010 (n = 3040). MAIN OUTCOME MEASURES: Predictors were the 20-item PACIC (dichotomized at the score of 3), and the 13-item Patient Activation Measure (PAM), dichotomized into activation Levels 1 and 2 versus Levels 3 and 4. Analyses were restricted to participants whose PACIC and PAM categories did not change over 2 years of follow-up. Outcome variables were EQ-5D index and EQ VAS dichotomized at the uppermost quartile, and EQ-5D index also dichotomized at the median. STATISTICAL ANALYSES: An inverse probability weighted Poisson regression with a log-link function and a binary response variable for each outcome was used to obtain risk ratios (RRs), and the interaction between PACIC and PAM was statistically modelled, taking into consideration patient characteristics and the respective baseline outcome variable. RESULTS: The positive association between the PACIC and EQ VAS was seen only in participants with low activation (adjusted RR: 3.91; 95% CI: 1.40-10.95; P = 0.009), and not in those with high activation, indicating the non-synergistic interaction effect of the PACIC and PAM. This association was not found with EQ-5D index. CONCLUSIONS: Chronic care received consistently over time can positively affect health status, and benefit patients with low activation.

Diagnostic performance of expression of PCA3, Hepsin and miR biomarkers inejaculate in combination with serum PSA for the detection of prostate cancer.

BACKGROUND AND METHODS: Here, we report on the evaluation of the diagnostic performance of ejaculate-derived PCA3, Hepsin, and miRNAs to complement serum PSA to detect prostate cancer. cDNA was prepared from 152 candidate specimens following RNA isolation and amplification for PSA, PCA3 and Hepsin qPCR, with 66 having adequate RNA for all three assays. Small RNA sequencing and examination of PCa-associated miRNAs miR-200b, miR-200c, miR-375 and miR-125b was performed on 20 specimens. We compared findings from prostate biopsies using D'Amico and PRIAS classifications and in relation to whole gland histopathology following radical prostatectomy. Multivariate logistic regression modeling and clinical risk (incorporating standard clinicopathological variables) were performed for all ejaculate-based markers. RESULTS: While Hepsin alone was not of predictive value, the Hepsin:PCA3 ratio together with serum PSA, expressed as a univariate composite score based on multivariate logistic regression, was shown to be a better predictor than PSA alone of prostate cancer status (AUC 0.724 vs. 0.676) and risk, using D'Amico (AUC 0.701 vs. 0.680) and PRIAS (AUC 0.679 vs. 0.659) risk stratification criteria as classified using prostate biopsies. It was also possible to analyse a subgroup of patients for miRNA expression with miR-200c (AUC 0.788) and miR-375 (AUC 0.758) showing best single marker performance, while a combination of serum PSA, miR-200c, and miR-125b further improved prediction for prostate cancer status when compared to PSA alone determined by biopsy (AUC 0.869 vs. 0.672; P < 0.05), and risk (D'Amico/PRIAS) as well as by radical prostatectomy histology (AUC 0.809 vs. 0.690). For prostate cancer status by biopsy, at a sensitivity of 90%, the specificity of the test increased from 11% for PSA alone to 67% for a combination of PSA, miR-200c, and miR-125b. CONCLUSIONS: These results show that use of a combination of different types of genetic markers in ejaculate together with serum PSA are at least as sensitive as those reported in DRE urine. Furthermore, a combination of serum PSA and selected miRNAs improved prediction of prostate cancer status. This approach may be helpful in triaging patients for MRI and biopsy, when confirmed by larger studies.

The Effect of Right Ventricular Apical and Nonapical Pacing on the Short- and Long-Term Changes in Left Ventricular Ejection Fraction: A Systematic Review and Meta-Analysis of Randomized-Controlled Trials.

BACKGROUND: The right ventricular apex (RVA) is the traditional lead site for chronic pacing but in some patients may cause impaired left ventricular (LV) systolic function over time. Comparisons with right ventricular nonapical (RVNA) pacing sites have generated inconsistent results and recent meta-analyses have demonstrated unclear benefit due to heterogeneity across studies. METHODS AND RESULTS: A systematic search for randomized controlled trials that compared LV ejection fraction (LVEF) outcomes between RVNA and RVA pacing was performed up to October 2014. Twenty-four studies (n = 1,628 patients) met the inclusion criteria. To avoid between study heterogeneity two homogenous groups were created; group 1 where studies reported a difference (in favor of RVNA pacing) and group 2 where studies reported no difference between pacing sites. For group 1, weighted mean difference between RVNA and RVA pacing in terms of LVEF at follow-up was 5.40% (95% confidence interval [CI]: 3.94-6.87), related in part to group one's RVA arm demonstrating a significant reduction (mean loss -3.31%; 95% CI: -6.19 to -0.43) in LVEF between study baseline and end of follow-up. Neither of these finding were seen in group 2. Weighted regression modeling demonstrated that inclusion of poor baseline LVEF (<40%) in combination with greater than 12 months follow-up was three times more common in group 1 compared to group 2 (weighted relative risk 2.82; 95% CI: 1.03-7.72; P = 0.043). CONCLUSIONS: In patients requiring chronic right ventricular pacing where there is inclusion of impaired baseline LVEF (<40%), RVA pacing is associated with deterioration in LV function relative to RVNA pacing.

Was there really any evidence that rosiglitazone increased the risk of myocardial infarction or death from cardiovascular causes?

Rosiglitazone has previously been widely used to treat patients with type 2 diabetes mellitus, but its safety in terms of cardiovascular morbidity and mortality had been called into question. Recently, there have been doubts raised about the meta-analytic evidence with the regulatory authorities relaxing its restrictions. We hypothesized that the original analyses may have produced exaggerated results because of the small baseline risks involved. To demonstrate this, we replicated the meta-analysis of four randomized trials of greater than 12-month follow-up that made use of a randomized control group not receiving rosiglitazone and reported outcome data for all occurrences of the complementary outcomes (no myocardial infarction, no death from cardiovascular causes, and no heart failure). Data were combined by means of a fixed-effects model. In the rosiglitazone group, as compared with the control group, the relative risk for no myocardial infarction was 0.997 (95% confidence interval [CI], 0.994 to 1.000), and the relative risk for no death from cardiovascular causes was 1.001 (95%CI, 0.999 to 1.003). Finally, no heart failure had a relative risk of 0.995 (95%CI, 0.993 to 0.998). Rosiglitazone does not seem to have any significant increase in the risk of myocardial infarction or of death from cardiovascular causes associated with its use. Regulatory authorities should revisit this issue of the appropriate measure for reporting of adverse events with low baseline risks as this has implications well beyond rosiglitazone.

The impact of concordant and discordant comorbidities on patient-assessed quality of diabetes care.

OBJECTIVE: To examine the impact of concordant and discordant comorbidities on patients' assessments of providers' adherence to diabetes-specific care guidelines and quality of chronic illness care. RESEARCH DESIGN AND METHODS: A population-based survey of 3761 adults with type 2 diabetes, living in Queensland, Australia was conducted in 2008. Based on self-reports, participants were grouped into four mutually exclusive comorbid categories: none, concordant only, discordant only and both concordant and discordant. Outcome measures included patient-reported providers' adherence to guideline-recommended care and the Patient Assessment of Chronic Illness Care (PACIC), which measures care according to the Chronic Care Model. Analyses using the former measure included logistic regressions, and the latter measure included univariate analysis of variance, both unadjusted and adjusted for sampling region, gender, age, educational attainment, diabetes duration and treatment status. RESULTS: Having concordant comorbidities increased the odds of patient-reported providers' adherence for 7 of the 11 guideline-recommended care activities in unadjusted analyses. However, the effect remained significant for only two provider activities (reviews of medication and/or complications and blood pressure examinations) when adjusted. A similar pattern was found for the both concordant and discordant comorbidity category. The presence of discordant comorbidities influenced only one provider activity (blood pressure examinations). No association between comorbidity type and the overall PACIC score was found. CONCLUSIONS: Comorbidity type is associated with diabetes-specific care, but does not seem to influence broader aspects of chronic illness care directly. Providers need to place more emphasis on care activities which are not comorbidity-specific and thus transferable across different chronic conditions.