Utilization of renal function and iron status laboratory test investigations in Eastern Health

Introduction: Healthcare spending in Canada reached 219.1 billion dollars in 2015. Unnecessary laboratory test investigations have been well documented in many countries, making it an area of interest in order to reduce costs, improve care and ultimately improve the performance of the health care system. The use of serum urea is unnecessary to evaluate kidney function in stable patients as serum creatinine has better specificity and no decrease in sensitivity. Therefore, we examined the use of serum urea in the community of a regional health authority. Ferritin is a good test of iron status and indicated in anemic patients, particularly when mean corpuscular volume/mean corpuscular hemoglobin levels are low. Therefore, we examined the use of iron status tests in the community to determine the degree of under-utilization in the patients likely to have iron deficient anemia and of over-utilization in patients with normal hemoglobin and blood indices. Methods: We performed a retrospective analysis of Eastern Health’s laboratory electronic database to investigate patterns of laboratory test utilization for two specific bundles of tests: (1) serum creatinine and serum urea; (2) hemoglobin (hgB), ferritin and iron saturation. Laboratory tests were examined for a 6-month period in 2014 (bundle 1) and a 12-month period (bundle 2) throughout 2013-2014. Test utilization is described by age, sex, patient type (inpatient/outpatient), submitting physician specialty and test result. Results: 227, 092 serum creatinine and 218, 289 serum urea tests were ordered for all patients within the Eastern Health Region during the 6-month period. 96.8 % (n=211, 279) serum urea tests were ordered in the same draw as serum creatinine. 64.6% (n=141,112) serum urea tests were ordered in the same draw as serum creatinine for outpatients. General practitioners elicited the highest rate of serum urea tests (52.5% of total), followed by the internal medicine specialty. 69.3% (n=62, 274) of coupled serum creatinine and serum urea laboratory investigations ordered by general practitioners for outpatients elicited normal results for both tests. High volumes of hemoglobin (n=450, 792) and iron status tests (ferritin; n=86,293, iron saturation; n=23,415) were ordered within the 12-month period. General practitioners elicited the highest ordering for all three tests for outpatients. 89.6% (n=55,595) of iron tests requested by general practitioners for nonanemic outpatients (first Hgb) produced a normal result in the 12-month period. 44.9% (n=136) of females (≤ 50 years of age) with anemia did not undergo iron testing within 1-year of the first documentation of the anemia by a general practitioner. Conclusion: Serum urea and iron testing may be areas of interest for the improvement of utilization of health care resources within the Eastern Health Region. Information contained in this thesis may be used as a guiding tool for decision makers in the development of interventions to improve test-ordering behaviours without compromising patient quality of care

Anti-cholinergic drug burden in patients with dementia increases after hospital admission: a multicentre cross-sectional study

Background: Anticholinergic medications are drugs that block cholinergic transmission, either as their primary therapeutic action or as a secondary effect. Patients with dementia may be particularly sensitive to the central effects of anticholinergic drugs. Anticholinergics also antagonise the effects of the main dementia treatment, cholinesterase inhibitors. Our study aimed to investigate anticholinergic prescribing for dementia patients in UK acute hospitals before and after admission. Methods: We included 352 patients with dementia from 17 UK hospital sites in 2019. They were all inpatients on surgical, medical or Care of the Elderly wards. Information about each patient’s medications were collected using a standardised form, and the anticholinergic drug burden of each patient was calculated with an evidence-based online calculator. Wilcoxon’s rank test was used to look at the correlation between two subgroups upon admission and discharge. Results: On admission to hospital, 37.8% of patients had an anticholinergic burden score ≥ 1 and 5.68% ≥3. On discharge, 43.2% of patients with an anticholinergic burden score ≥ 1 and 9.1% ≥3. The increase in scores was statistically significant (p = 0.001). Psychotropics were the most common group of anticholinergic medications prescribed at discharge. Of those patients taking cholinesterase inhibitors, 44.9% were also prescribed anticholinergic medications. Conclusions: Our cross-sectional, multicentre study found that people with dementia are commonly prescribed anticholinergic medications, even if concurrently taking cholinesterase inhibitors, and are significantly more likely to be discharged from hospital with a higher anticholinergic burden than on admission

Linkage to chromosome 2q32.2-q33.3 in familial serrated neoplasia (Jass syndrome)

Causative genetic variants have to date been identified for only a small proportion of familial colorectal cancer (CRC). While conditions such as Familial Adenomatous Polyposis and Lynch syndrome have well defined genetic causes, the search for variants underlying the remainder of familial CRC is plagued by genetic heterogeneity. The recent identification of families with a heritable predisposition to malignancies arising through the serrated pathway (familial serrated neoplasia or Jass syndrome) provides an opportunity to study a subset of familial CRC in which heterogeneity may be greatly reduced. A genome-wide linkage screen was performed on a large family displaying a dominantly-inherited predisposition to serrated neoplasia genotyped using the Affymetrix GeneChip Human Mapping 10 K SNP Array. Parametric and nonparametric analyses were performed and resulting regions of interest, as well as previously reported CRC susceptibility loci at 3q22, 7q31 and 9q22, were followed up by finemapping in 10 serrated neoplasia families. Genome-wide linkage analysis revealed regions of interest at 2p25.2-p25.1, 2q24.3-q37.1 and 8p21.2-q12.1. Finemapping linkage and haplotype analyses identified 2q32.2-q33.3 as the region most likely to harbour linkage, with heterogeneity logarithm of the odds (HLOD) 2.09 and nonparametric linkage (NPL) score 2.36 (P = 0.004). Five primary candidate genes (CFLAR, CASP10, CASP8, FZD7 and BMPR2) were sequenced and no segregating variants identified. There was no evidence of linkage to previously reported loci on chromosomes 3, 7 and 9

Anti-cholinergic drug burden in patients with dementia increases after hospital admission: a multicentre cross-sectional study.

Funder: Wellcome TrustBACKGROUND: Anticholinergic medications are drugs that block cholinergic transmission, either as their primary therapeutic action or as a secondary effect. Patients with dementia may be particularly sensitive to the central effects of anticholinergic drugs. Anticholinergics also antagonise the effects of the main dementia treatment, cholinesterase inhibitors. Our study aimed to investigate anticholinergic prescribing for dementia patients in UK acute hospitals before and after admission. METHODS: We included 352 patients with dementia from 17 UK hospital sites in 2019. They were all inpatients on surgical, medical or Care of the Elderly wards. Information about each patient's medications were collected using a standardised form, and the anticholinergic drug burden of each patient was calculated with an evidence-based online calculator. Wilcoxon's rank test was used to look at the correlation between two subgroups upon admission and discharge. RESULTS: On admission to hospital, 37.8% of patients had an anticholinergic burden score ≥ 1 and 5.68% ≥3. On discharge, 43.2% of patients with an anticholinergic burden score ≥ 1 and 9.1% ≥3. The increase in scores was statistically significant (p = 0.001). Psychotropics were the most common group of anticholinergic medications prescribed at discharge. Of those patients taking cholinesterase inhibitors, 44.9% were also prescribed anticholinergic medications. CONCLUSIONS: Our cross-sectional, multicentre study found that people with dementia are commonly prescribed anticholinergic medications, even if concurrently taking cholinesterase inhibitors, and are significantly more likely to be discharged from hospital with a higher anticholinergic burden than on admission

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field