Allogeneic blood transfusion and prognosis following total hip replacement: a population-based follow up study

<p>Abstract</p> <p>Background</p> <p>Allogeneic red blood cell transfusion is frequently used in total hip replacement surgery (THR). However, data on the prognosis of transfused patients are sparse. In this study we compared the risk of complications following THR in transfused and non-transfused patients.</p> <p>Methods</p> <p>A population-based follow-up study was performed using data from medical databases in Denmark. We identified 28,087 primary THR procedures performed from 1999 to 2007, from which we computed a propensity score for red blood cell transfusion based on detailed data on patient-, procedure-, and hospital-related characteristics. We were able to match 2,254 transfused with 2,254 non-transfused THR patients using the propensity score.</p> <p>Results</p> <p>Of the 28,087 THR patients, 9,063 (32.3%) received at least one red blood cell transfusion within 8 days of surgery. Transfused patients had higher 90-day mortality compared with matched non-transfused patients: the adjusted OR was 2.2 (95% confidence interval (CI): 1.2-3.8). Blood transfusion was also associated with increased odds of pneumonia (OR 2.1; CI: 1.2-3.8), whereas the associations with cardiovascular or cerebrovascular events (OR 1.4; CI: 0.9-2.2) and venous thromboembolism (OR 1.2; CI: 0.7-2.1) did not reach statistical significance. The adjusted OR of reoperation due to infection was 0.6 (CI: 0.1-2.9).</p> <p>Conclusions</p> <p>Red blood cell transfusion was associated with an adverse prognosis following primary THR, in particular with increased odds of death and pneumonia. Although the odds estimates may partly reflect unmeasured bias due to blood loss, they indicate the need for careful assessment of the risk versus benefit of transfusion even in relation to routine THR procedures.</p

Genetic Control of mRNA Splicing as a Potential Mechanism for Incomplete Penetrance of Rare Coding Variants

Exonic variants present some of the strongest links between genotype and phenotype. However, these variants can have significant inter-individual pathogenicity differences, known as variable penetrance. In this study, we propose a model where genetically controlled mRNA splicing modulates the pathogenicity of exonic variants. By first cataloging exonic inclusion from RNA-sequencing data in GTEx V8, we find that pathogenic alleles are depleted on highly included exons. Using a large-scale phased whole genome sequencing data from the TOPMed consortium, we observe that this effect may be driven by common splice-regulatory genetic variants, and that natural selection acts on haplotype configurations that reduce the transcript inclusion of putatively pathogenic variants, especially when limiting to haploinsufficient genes. Finally, we test if this effect may be relevant for autism risk using families from the Simons Simplex Collection, but find that splicing of pathogenic alleles has a penetrance reducing effect here as well. Overall, our results indicate that common splice-regulatory variants may play a role in reducing the damaging effects of rare exonic variants

Inequalities in heart failure care in a tax-financed universal healthcare system: a nationwide population-based cohort study

Aims Data on socioeconomic-related differences in heart failure (HF) care are sparse. Inequality in care may potentially contribute to a poor clinical outcome. We examined socioeconomic-related differences in quality of HF care among patients with incident HF with reduced ejection fraction (EF) (HFrEF). Methods and results We conducted a nationwide population-based cohort study among patients with HFrEF (EF &amp;lt;= 40%) registered from January 2008 to October 2015 in the Danish Heart Failure Registry, a nationwide registry of patients with a first-time primary HF diagnosis. Associations between individual-level socioeconomic factors (cohabitation status, education, and family income) and the quality of HF care defined by six guideline-recommended process performance measures [New York Heart Association (NYHA) classification, treatment with angiotensin-converting-enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB), beta-blockers and mineralocorticoid receptor antagonists, exercise training, and patient education] were assessed using multiple imputation and multivariable logistic regression controlling for potential confounders. Among 17 122 HFrEF patients included, 15 290 patients had data on all six process performance measures. Living alone was associated with lower odds of NYHA classification [adjusted OR (aOR) 0.81; 95% confidence interval (CI): 0.72-0.90], prescription of ACEI/ARB (aOR 0.76; 95% CI: 0.68-0.88) and beta-blockers (aOR 0.84; 95% CI: 0.76-0.93), referral to exercise training (aOR 0.75; 95% CI: 0.69-0.81), and patient education (aOR 0.73; 95% CI: 0.67-0.80). Compared with high-level education, low-level education was associated with lower odds of NYHA classification (aOR 0.93; 95% CI: 0.79-1.11), treatment with ACEI/ARB (aOR 0.99; 95% CI: 0.81-1.20) and beta-blockers (aOR 0.93; 95% CI: 0.79-1.09), referral to exercise training (aOR 0.73; 95% CI: 0.65-0.82), and patient education (aOR 0.86, 95% CI: 0.75-0.98). An income in the lowest tertile was associated with lower odds of NYHA classification (aOR 0.67; 95% CI: 0.58-0.79), prescription of ACEI/ARB (aOR 0.80, 95% CI: 0.67-0.95) and beta-blockers (aOR 0.88, 95% CI: 0.86-1.01), referral to exercise training (aOR 0.59, 95% CI: 0.53-0.64), and patient education (aOR 0.66; 95% CI: 0.59-0.74) compared with an income in the highest tertile. Overall, no systematic differences were seen when the analyses were stratified by sex and age groups. Conclusions Living alone, low-level education, and income in the lowest tertile were associated with reduced use of recommended processes of HF care among Danish HFrEF patients with a first-time primary HF diagnosis. Efforts are warranted to ensure guideline-recommended HF care to all HFrEF patients, irrespective of socioeconomic background.Funding Agencies|Helsefonden [17-B-0104]; Danish Organization Research Foundation</p

Inequalities in heart failure care in a tax‐financed universal healthcare system: a nationwide population‐based cohort study

Aims Data on socioeconomic-related differences in heart failure (HF) care are sparse. Inequality in care may potentially contribute to a poor clinical outcome. We examined socioeconomic-related differences in quality of HF care among patients with incident HF with reduced ejection fraction (EF) (HFrEF). Methods and results We conducted a nationwide population-based cohort study among patients with HFrEF (EF &amp;lt;= 40%) registered from January 2008 to October 2015 in the Danish Heart Failure Registry, a nationwide registry of patients with a first-time primary HF diagnosis. Associations between individual-level socioeconomic factors (cohabitation status, education, and family income) and the quality of HF care defined by six guideline-recommended process performance measures [New York Heart Association (NYHA) classification, treatment with angiotensin-converting-enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB), beta-blockers and mineralocorticoid receptor antagonists, exercise training, and patient education] were assessed using multiple imputation and multivariable logistic regression controlling for potential confounders. Among 17 122 HFrEF patients included, 15 290 patients had data on all six process performance measures. Living alone was associated with lower odds of NYHA classification [adjusted OR (aOR) 0.81; 95% confidence interval (CI): 0.72-0.90], prescription of ACEI/ARB (aOR 0.76; 95% CI: 0.68-0.88) and beta-blockers (aOR 0.84; 95% CI: 0.76-0.93), referral to exercise training (aOR 0.75; 95% CI: 0.69-0.81), and patient education (aOR 0.73; 95% CI: 0.67-0.80). Compared with high-level education, low-level education was associated with lower odds of NYHA classification (aOR 0.93; 95% CI: 0.79-1.11), treatment with ACEI/ARB (aOR 0.99; 95% CI: 0.81-1.20) and beta-blockers (aOR 0.93; 95% CI: 0.79-1.09), referral to exercise training (aOR 0.73; 95% CI: 0.65-0.82), and patient education (aOR 0.86, 95% CI: 0.75-0.98). An income in the lowest tertile was associated with lower odds of NYHA classification (aOR 0.67; 95% CI: 0.58-0.79), prescription of ACEI/ARB (aOR 0.80, 95% CI: 0.67-0.95) and beta-blockers (aOR 0.88, 95% CI: 0.86-1.01), referral to exercise training (aOR 0.59, 95% CI: 0.53-0.64), and patient education (aOR 0.66; 95% CI: 0.59-0.74) compared with an income in the highest tertile. Overall, no systematic differences were seen when the analyses were stratified by sex and age groups. Conclusions Living alone, low-level education, and income in the lowest tertile were associated with reduced use of recommended processes of HF care among Danish HFrEF patients with a first-time primary HF diagnosis. Efforts are warranted to ensure guideline-recommended HF care to all HFrEF patients, irrespective of socioeconomic background.Funding Agencies|Helsefonden [17-B-0104]; Danish Organization Research Foundation</p

Evidence-Based Process Performance Measures and Clinical Outcomes in Patients With Incident Heart Failure With Reduced Ejection Fraction : A Danish Nationwide Cohort Study

Background: Data on the association between quality of heart failure (HF) care and outcomes among patients with incident HF are sparse. We examined the association between process performance measures and clinical outcomes in patients with incident HF with reduced ejection fraction. Methods: Patients with incident HF with reduced ejection fraction (n=10 966) between January 2008 and October 2015 were identified from the Danish HF Registry. Data from public registries were linked. Multivariable regression analyses were used to assess the association between 6 guideline-recommended HF care processes (New York Heart Association assessment, use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists, exercise training, and patient education) and all-cause and HF readmission, all-cause and HF hospital days, and mortality within 3 to 12 months after HF diagnosis. The associations were analyzed according to the percentages of all relevant performance measures fulfilled for the individual patient (0%-50% [reference group], &amp;gt;50%-75%, and &amp;gt;75%-100%) and for the individual performance measures. Results: Fulfilling &amp;gt;75% to 100% of the performance measures (n=5341 [48.7%]) was associated with lower risk of all-cause readmission (adjusted hazard ratio, 0.78 [95% CI, 0.68-0.89]) and HF readmission (adjusted hazard ratio, 0.71 [95% CI, 0.54-0.92]), lower use of all-cause hospital days (adjusted mean ratio, 0.73 [95% CI, 0.70-0.76]) and HF hospital days (adjusted mean ratio, 0.79 [95% CI, 0.70-0.89]), and lower mortality (adjusted hazard ratio, 0.42 [95% CI, 0.32-0.53]). A dose-response relationship was observed between fulfilling more performance measures and mortality (adjusted hazard ratio, 0.62 [95% CI, 0.49-0.77] fulfilling &amp;gt;50%-75% of the measures). Fulfilling individual performance measures, except mineralocorticoid receptor antagonist therapy, was associated with lower adjusted all-cause readmission, lower adjusted use of all-cause and HF hospital days, and lower adjusted mortality. Conclusions: Fulfilling more process performance measures was associated with better clinical outcomes in patients with incident HF with reduced ejection fraction.Funding Agencies|Helsefonden [17-B-0104]</p