The relationship of individual comorbid chronic conditions to diabetes care quality.

ObjectiveMultimorbidity affects 26 million persons with diabetes, and care for comorbid chronic conditions may impact diabetes care quality. The aim of this study was to determine which chronic conditions were related to lack of achievement or achievement of diabetes care quality goals to determine potential targets for future interventions.Research design and methodsThis is an exploratory retrospective analysis of electronic health record data for 23 430 adults, aged 18-75, with diabetes who were seen at seven Midwestern US health systems. The main outcome measures were achievement of six diabetes quality metrics in the reporting year, 2011 (glycated haemoglobin (HbA1c) control and testing, low-density lipoprotein control and testing, blood pressure control, kidney testing). Explanatory variables were 62 chronic condition indicators. Analyses were adjusted for baseline patient sociodemographic and healthcare utilization factors.ResultsThe 62 chronic conditions varied in their relationships to diabetes care goal achievement for specific care goals. Congestive heart failure was related to lack of achievement of cholesterol management goals. Obesity was related to lack of HbA1c and BP control. Mental health conditions were related to both lack of achievement and achievement of different care goals. Three conditions were related to lack of cholesterol testing, including congestive heart failure and substance-use disorders. Of 17 conditions related to achieving control goals, 16 were related to achieving HbA1c control. One-half of the comorbid conditions did not predict diabetes care quality.ConclusionsFuture interventions could target patients at risk for not achieving diabetes care for specific care goals based on their individual comorbidities

Childhood Development after Cochlear Implantation (CDaCI) study: Design and baseline characteristics

Children with severe to profound sensorineural hearing loss face communication challenges that influence language, psychosocial and scholastic performance. Clinical studies over the past 20 years have supported wider application of cochlear implants in children. The Childhood Development after Cochlear Implantation (CDaCI) study is the first longitudinal multicentre, national cohort study to evaluate systematically early cochlear implant (CI) outcomes in children. The objective of the study was to compare children who have undergone cochlear implantation, with similarly aged hearing peers across multiple domains, including oral language development, auditory performance, psychosocial and behavioural functioning, and quality of life. The CDaCI study is a multicentre national cohort study of CI children and normal hearing (NH) peers. Eligibility criteria include informed consent, age less than 5 years, pre- or post-lingually deaf, developmental criteria met, commitment to educate the child in English and bilateral cochlear implants. All children had a standardised baseline assessment that included demographics, hearing and medical history, communication history, language measures, cognitive tests, speech recognition, an audiological exam, psychosocial assessment including parent-child videotapes and parent reported quality of life. Follow-up visits are scheduled at six-month intervals and include a standardised assessment of the full battery of measures. Quality assurance activities were incorporated into the design of the study. A total of 188 CI children and 97 NH peers were enrolled between November 2002 and December 2004. The mean age, gender and race of the CI and NH children are comparable. With regard to parental demographics, the CI and NH children's families are statistically different. The parents of CI children are younger, and not as well educated, with 49% of CI parents reporting college graduation vs. 84% of the NH parents. The income of the CI parents is also lower than the NH parents. Assessments of cognition suggest that there may be baseline differences between the CI and NH children; however the scores were high enough to suggest language learning potential. The observed group differences identified these baseline characteristics as potential confounders which may require adjustment in analyses of outcomes. This longitudinal cohort study addresses questions related to high variability in language outcomes. Identifying sources of that variance requires research designs that: characterise potential predictors with accuracy, use samples that adequately power a study, and employ controls and approaches to analysis that limit bias and error. The CDaCI study was designed to generate a more complete picture of the interactive processes of language learning after implantation. Copyright © 2007 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56091/1/333_ftp.pd

Surgical Factors in Pediatric Cochlear Implantation and Their Early Effects on Electrode Activation and Functional Outcomes

To assess the impact of surgical factors on electrode status and early communication outcomes in young children in the first 2 years of cochlear implantation

Time to Osteoporosis and Major Fracture in Older Men

For older men who undergo bone mineral density (BMD) testing, the optimal osteoporosis screening schedule is unknown. Time-to-disease estimates are necessary to inform screening intervals

Time to Osteoporosis and Major Fracture in Older Men

For older men who undergo bone mineral density (BMD) testing, the optimal osteoporosis screening schedule is unknown. Time-to-disease estimates are necessary to inform screening intervals

Attainment of clinical performance targets and improvement in clinical outcomes and resource use in hemodialysis care: a prospective cohort study

BACKGROUND: Clinical performance targets are intended to improve patient outcomes in chronic disease through quality improvement, but evidence of an association between multiple target attainment and patient outcomes in routine clinical practice is often lacking. METHODS: In a national prospective cohort study (ESRD Quality, or EQUAL), we examined whether attainment of multiple targets in 668 incident hemodialysis patients from 74 U.S. not-for-profit dialysis clinics was associated with better outcomes. We measured whether the following accepted clinical performance targets were met at 6 months after study enrollment: albumin (≥4.0 g/dl), hemoglobin (≥11 g/dl), calcium-phosphate product (<55 mg(2)/dl(2)), dialysis dose (Kt/V≥1.2), and vascular access type (fistula). Outcomes included mortality, hospital admissions, hospital days, and hospital costs. RESULTS: Attainment of each of the five targets was associated individually with better outcomes; e.g., patients who attained the albumin target had decreased mortality [relative hazard (RH) = 0.55, 95% confidence interval (CI), 0.41–0.75], hospital admissions [incidence rate ratio (IRR) = 0.67, 95% CI, 0.62–0.73], hospital days (IRR = 0.61, 95% CI, 0.58–0.63), and hospital costs (average annual cost reduction = $3,282, P = 0.002), relative to those who did not. Increasing numbers of targets attained were also associated, in a graded fashion, with decreased mortality (P = 0.030), fewer hospital admissions and days (P < 0.001 for both), and lower costs (P = 0.029); these trends remained statistically significant for all outcomes after adjustment (P < 0.001), except cost, which was marginally significant (P = 0.052). CONCLUSION: Attainment of more clinical performance targets, regardless of which targets, was strongly associated with decreased mortality, hospital admissions, and resource use in hemodialysis patients

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe