The use of genetic marking to assess the reproductive success of mature male Atlantic salmon parr (Salmo salar, L.) under natural spawning conditions

The reproductive success of mature male Atlantic salmon parr ( Salmo salar ) under natural spawning conditions was estimated using the polymorphism at the MEP - 2 * locus as a genetic marker. The percentage of eggs per redd fertilized by parr varied considerably over the five redds examined (0·9–27.7%, mean 10·8%), but a gametic contribution from mature parr was detected in each case. Parr reproductive success has important implications for the population structure and evolution of the Atlantic salmon through its effect on gene flow.     

Physician experience and outcomes among patients admitted to general internal medicine teaching wards

Background:

Physician scores on examinations decline with time after graduation. However, whether this translates into declining quality of care is unknown. Our objective was to determine how physician experience is associated with negative outcomes for patients admitted to hospital.

Methods:

We conducted a retrospective cohort study involving all patients admitted to general internal medicine wards over a 2-year period at all 7 teaching hospitals in Alberta, Canada. We used files from the Alberta College of Physicians and Surgeons to determine the number of years since medical school graduation for each patient’s most responsible physician. Our primary outcome was the composite of in-hospital death, or readmission or death within 30 days postdischarge.

Results:

We identified 10 046 patients who were cared for by 149 physicians. Patient characteristics were similar across physician experience strata, as were primary outcome rates (17.4% for patients whose care was managed by physicians in the highest quartile of experience, compared with 18.8% in those receiving care from the least experienced physicians; adjusted odds ratio [OR] 0.88, 95% confidence interval [CI] 0.72–1.06). Outcomes were similar between experience quartiles when further stratified by physician volume, most responsible diagnosis or complexity of the patient’s condition. Although we found substantial variability in length of stay between individual physicians, there were no significant differences between physician experience quartiles (mean adjusted for patient covariates and accounting for intraphysician clustering: 7.90 [95% CI 7.39–8.42] d for most experienced quartile; 7.63 [95% CI 7.13–8.14] d for least experienced quartile).

Interpretation:

For patients admitted to general internal medicine teaching wards, we saw no negative association between physician experience and outcomes commonly used as proxies for quality of inpatient care.Many jurisdictions have instituted compulsory recertification of physicians on the assumption that quality of care declines with experience. Although a systematic review reported that 32 of 62 studies found decreasing performance with increasing physician experience, most of these studies evaluated performance on examinations or hypothetical vignettes rather than actual quality of care provided to patients, and most of the studies were done decades ago, before the widespread availability of tools to readily facilitate evidence-based medicine.¹Experience is strongly related to better outcomes in surgery and obstetrics, but studies examining the association between physician experience and quality of care for medical patients have reported mixed results.^1–8 Many of the studies reporting an inverse association between experience and quality of care have focused on the provision of “guideline recommended tests or therapies” as a proxy for quality of care. However, guideline recommendations might not be appropriate in every situation.An evaluation of broader quality metrics may be more appropriate to answer this question. For example, in-hospital mortality and readmission rates or mortality postdischarge are commonly used as markers for quality of inpatient care, are endorsed by the Centers for Medicare & Medicaid Services and are included in the Patient Protection and Affordable Care Act.^9,10 However, to our knowledge, few studies have examined the association between these broader quality metrics and physician experience, and these studies have been limited. They either focused on single diagnoses,¹¹ excluded older adult patients,² examined data from only 1 hospital⁸ or combined data⁷ for both surgeons and physicians.Patients admitted to general internal medicine services at Alberta teaching hospitals are distributed between wards purely on the basis of bed availability, and attending physicians rotate every 1–4 weeks. For these reasons, the distribution of patients between attending physicians is quasirandom. We took advantage of this natural experiment to evaluate the association between attending physician experience (years since medical school graduation) and outcomes for patients admitted to general internal medicine wards in Alberta.     

Impact of Rural Residence on Warfarin Use and Clinical Events in Patients with Non-Valvular Atrial Fibrillation: A Canadian Population Based Study

Background and Purpose

We studied whether anticoagulant use and outcomes differed between rural versus urban Canadian non-valvular atrial fibrillation (NVAF) patients prior to the introduction of direct oral anticoagulant drugs.

Methods

Retrospective cohort study of 25,284 adult Albertans with NVAF between April 1, 1999 and December 31, 2008.

Results

Compared to urban patients, rural patients were older (p = 0.0009) and had more comorbidities but lower bleeding risk at baseline. In the first year after NVAF diagnosis, urban patients were less likely to be hospitalized (aOR 0.82, 95%CI 0.77–0.89) or have an emergency department visit for any reason (aOR 0.61, 95%CI 0.56–0.66) but warfarin dispensation rates (72.2% vs 71.8% at 365 days, p = 0.98) and clinical outcomes were similar: 7.8% died in both groups, 3.2% rural vs. 2.8% urban had a stroke or systemic embolism (SSE) (aOR 0.92, 95%CI 0.77–1.11), and 6.6% vs. 5.7% (aOR 0.93, 95%CI 0.81–1.06) had a bleed. Baseline SSE risk did not impact warfarin dispensation (73.0% in those with high vs. 72.8% in those with low CHADS₂ score, p = 0.85) but patients at higher baseline bleeding risk were less likely to be using warfarin (69.2% high vs. 73.6% low HASBLED score, p<0.0001) in the first 365 days after diagnosis. In warfarin users, bleeding was more frequent (7.5% vs 6.2%, aHR 1.51 [95%CI 1.33–1.72]) but death or SSE was less frequent (7.0% vs 18.1%, aHR 0.60 [0.54–0.66]).

Conclusion

Warfarin use and clinical event rates did not differ between rural and urban NVAF patients in a universal access publically-funded healthcare system.     

Persistent histone modifications at the BDNF and Cdk‐5 promoters following extinction of nicotine‐seeking in rats

Drugs of addiction lead to a wide range of epigenetic changes at the promoter regions of genes directly implicated in learning and memory processes. We have previously shown that the histone deactylase inhibitor, sodium butyrate (NaB), accelerates the extinction of nicotine‐seeking and provides resistance to relapse. Here, we explore the potential molecular mechanisms underlying this effect. Rats received intravenous nicotine or saline self‐administration, followed by 6 days of extinction training, with each extinction session followed immediately by treatment with NaB or vehicle. On the last day of extinction, rats were killed and the medial ventral prefrontal cortex retained for chromatin immunoprecipitation and quantitative polymerase chain reaction (qPCR). A history of nicotine exposure significantly decreased H3K14 acetylation at the brain‐derived neurotrophic factor (BDNF) exon IV promoter, and this effect was abolished with NaB treatment. In contrast, nicotine self‐administration alone, resulted in a significant decrease in histone methylation at the H3K27me3 and H3K9me2 marks in the promoter regions of BDNF exon IV and cyclin‐dependent kinase 5 (Cdk‐5). Quantitative PCR‐identified changes in several genes associated with NaB treatment that were independent of nicotine exposure; however, an interaction of nicotine history and NaB treatment was detected only in the expression of BDNF IV and BDNF IX. Together these results suggest that nicotine self‐administration leads to a number of epigenetic changes at both the BDNF and Cdk‐5 promoters, and that these changes may contribute to the enhanced extinction of nicotine‐seeking by NaB.