In Plato's Apology, Socrates says he spent his life examining and questioning people on how best to live, while avowing that he himself knows nothing important. Elsewhere, however, for example in ...Plato's Republic, Plato's Socrates presents radical and grandiose theses. In this book Sandra Peterson offers a hypothesis which explains the puzzle of Socrates' two contrasting manners. She argues that the apparently confident doctrinal Socrates is in fact conducting the first step of an examination: by eliciting his interlocutors' reactions, his apparently doctrinal lectures reveal what his interlocutors believe is the best way to live. She tests her hypothesis by close reading of passages in the Theaetetus, Republic and Phaedo. Her provocative conclusion, that there is a single Socrates whose conception and practice of philosophy remain the same throughout the dialogues, will be of interest to a wide range of readers in ancient philosophy and classics.
Classifying Physician Practice Style McGrail, Kimberlyn; Lavergne, Ruth; Lewis, Steven J. ...
Medical care,
2015-March, Letnik:
53, Številka:
3
Journal Article
Recenzirano
BACKGROUND:Primary medical care is changing—more female providers, desire for better work-life balance, and increasing availability of walk-in clinics have altered service delivery. There is no ...uniform physician practice style, and understanding service availability and delivery requires analysis of family physicians’ practice patterns, rather than just physician counts.
METHODS:This paper offers a new approach for describing the practice habits of primary care physicians. We use administrative data to identify activities associated with acting as “most responsible” physicians. We used British Columbia’s administrative health care data from 2007/2008 to 2011/2012 to derive information regarding physicians, patients, and service delivery. We developed 5 variables to describe practice stylereferrals, oversight, screening, initial prescribing for long-term medications, and repeat visits. Cluster analysis revealed 3 distinct groups of physicians.
RESULTS:Only 24% of the primary care physicians were assigned to the high-responsibility group, whereas 36% and 39% were in the low-responsibility and mixed-practice groups, respectively. All cluster variables follow a similar pattern, with the high-responsibility and low-responsibility physicians many multiples apart on the means and the mixed group falling in between. Several forms of sensitivity analysis confirmed the robustness of these results.
CONCLUSIONS:Physician practice patterns influence the effective supply of primary care. The fact that more than one third of British Columbia physicians are identified as “low responsibility” has implications for the delivery of primary care, both in ensuring that people have access to regular care and in insuring high-quality and comprehensive care.
Abstract
Background
Despite clinically demonstrated accuracy in next generation sequencing (NGS) data, many clinical laboratories continue to confirm variants with Sanger sequencing, which increases ...cost of testing and turnaround time. Several studies have assessed the accuracy of NGS in detecting single nucleotide variants; however, less has been reported about insertion, deletion, and deletion-insertion variants (indels).
Methods
We performed a retrospective analysis from 2015–2022 of indel results from a subset of NGS targeted gene panel tests offered through the Mayo Clinic Genomics Laboratories. We compared results from NGS and Sanger sequencing of indels observed in clinical runs and during the intra-assay validation of the tests.
Results
Results demonstrated 100% concordance between NGS and Sanger sequencing for over 490 indels (217 unique), ranging in size from 1 to 68 basepairs (bp). The majority of indels were deletions (77%) and 1 to 5 bp in length (90%). Variant frequencies ranged from 11.4% to 67.4% and 85.1% to 100% for heterozygous and homozygous variants, respectively, with a median depth of coverage of 2562×. A subset of indels (7%) were located in complex regions of the genome, and these were accurately detected by NGS. We also demonstrated 100% reproducibility of indel detection (n = 179) during intra-assay validation.
Conclusions
Together this data demonstrates that reportable indel variants up to 68 bp can be accurately assessed using NGS, even when they occur in complex regions. Depending on the complexity of the region or variant, Sanger sequence confirmation of indels is usually not necessary if the variants meet appropriate coverage and allele frequency thresholds.
duplication has important pharmacogenomic implications. Reflex testing with long-range PCR (LR-PCR) can resolve the genotype when a duplication and alleles with differing activity scores are ...detected. We evaluated whether visual inspection of plots from real-time-PCR-based targeted genotyping with copy number variation (CNV) detection could reliably determine the duplicated
allele. Six reviewers evaluated QuantStudio OpenArray
genotyping results and the TaqMan Genotyper plots for seventy-three well-characterized cases with three copies of
and two different alleles. Reviewers blinded to the final genotype visually assessed the plots to determine the duplicated allele or opt for reflex sequencing. Reviewers achieved 100% accuracy for cases with three
copies that they opted to report. Reviewers did not request reflex sequencing in 49-67 (67-92%) cases (and correctly identified the duplicated allele in each case); all remaining cases (6-24) were marked by at least one reviewer for reflex sequencing. In most cases with three copies of
, the duplicated allele can be determined using a combination of targeted genotyping using real-time PCR with CNV detection without need for reflex sequencing. In ambiguous cases and those with >3 copies, LR-PCR and Sanger sequencing may still be necessary for determination of the duplicated allele.
Major depressive disorder (MDD) is one of the world's leading causes of disability. Our purpose was to characterize the total costs of MDD and evaluate the degree to which the British Columbia ...provincial health system meets its objective to protect people from the financial impact of illness.
We performed a population-based cohort study of adults newly diagnosed with MDD between 2015 and 2020 and followed their health system costs over two years. The expenditure proportion of MDD-related, patient paid costs relative to non-subsistence income was estimated, incidences of financial hardship were identified and the slope index of inequality (SII) between the highest and lowest income groups compared across regions.
There were 250,855 individuals diagnosed with MDD in British Columbia over the observation period. Costs to the health system totalled >$1.5 billion (2020 CDN), averaging $138/week for the first 12 weeks following a new diagnosis and $65/week to week 52 and $55/week for weeks 53-104 unless MDD was refractory to treatment ($125/week between week 12-52 and $101/week over weeks 53-104). The proportion of MDD-attributable costs not covered by the health system was 2-15x greater than costs covered by the health system, exceeding $700/week for patients with severe MDD or MDD that was refractory to treatment. Population members in lower-income groups and urban homeowners had disadvantages in the distribution of financial protection received by the health system (SII reached - 8.47 and 15.25, respectively); however, financial hardship and inequities were mitigated province-wide if MDD went into remission (SII - 0.07 to 0.6).
MDD-attributable costs to health systems and patients are highest in the first 12 weeks after a new diagnosis. During this time, lower income groups and homeowners in urban areas run the risk of financial hardship.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Clinical pharmacogenomic testing typically uses targeted genotyping, which only detects variants included in the test design and may vary among laboratories. To evaluate the potential patient impact ...of genotyping compared with sequencing, which can detect common and rare variants, an in silico targeted genotyping panel was developed based on the variants most commonly included in clinical tests and applied to a cohort of 10,030 participants who underwent sequencing for CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4, CYP3A5, DPYD, SLCO1B1, TPMT, UGT1A1, and VKORC1. The results of in silico targeted genotyping were compared with the clinically reported sequencing results. Of the 10,030 participants, 2780 (28%) had at least one potentially clinically relevant variant/allele identified by sequencing that would not have been detected in a standard targeted genotyping panel. The genes with the largest number of participants with variants only detected by sequencing were SLCO1B1, DPYD, and CYP2D6, which affected 13%, 6.3%, and 3.5% of participants, respectively. DPYD (112 variants) and CYP2D6 (103 variants) had the largest number of unique variants detected only by sequencing. Although targeted genotyping detects most clinically significant pharmacogenomic variants, sequencing-based approaches are necessary to detect rare variants that collectively affect many patients. However, efforts to establish pharmacogenomic variant classification systems and nomenclature to accommodate rare variants will be required to adopt sequencing-based pharmacogenomics.
Obesity is strongly associated with insulin resistance (IR), along with mitochondrial dysfunction to metabolically active tissues and increased production of reactive O2 species (ROS). Foods rich in ...antioxidants such as wheat germ (WG), protect tissues from damage due to ROS and modulate some negative effects of obesity. This study examined the effects of WG supplementation on markers of IR, mitochondrial substrate metabolism and innate antioxidant markers in two metabolically active tissues (i.e. liver and heart) of C57BL/6 mice fed a high-fat–high-sucrose (HFS) diet. Male C57BL/6 mice, 6-week-old, were randomised into four dietary treatment groups (n 12 mice/group): control (C, 10 % fat kcal), C+10 % WG, HFS (60 % fat kcal) or HFS+10 % WG (HFS+WG). After 12 weeks of treatment, HFS+WG mice had significantly less visceral fat (−16 %, P=0·006) compared with the HFS group. WG significantly reduced serum insulin (P=0·009), the insulinotropic hormone, gastric inhibitory peptide (P=0·0003), and the surrogate measure of IR, homoeostatic model assessment of IR (P=0·006). HFS diet significantly elevated (45 %, P=0·02) cardiac complex 2 mitochondrial VO2, suggesting increased metabolic stress, whereas WG stabilised this effect to the level of control. Consequently, genes which mediate antioxidant defense and mitochondrial biogenesis (superoxide dismutase 2 (Sod2) and PPARγ coactivator 1-α (Pgc1a), respectively) were significantly reduced (P<0·05) in the heart of the HFS group, whereas WG supplementation tended to up-regulate both genes. WG significantly increased hepatic gene expression of Sod2 (P=0·048) but not Pgc1a. Together, these results showed that WG supplementation in HFS diet, reduced IR and improved cardiac mitochondrial metabolic functions.
ObjectivesIn Canada physician payment systems and associated billing data vary across provinces. We used linked billing data to develop comparable measures of family physician (FP) service volume, ...continuity, and comprehensiveness in each of four provinces, with the goal of describing changing patterns over time, relevant to workforce planning policy.
ApproachWe accessed linked population and physician registry data, vital statistics, physician billing data, hospital and emergency department records, and (where available) laboratory and prescription drug records in four Canadian provinces from 1996/7 to 2017/8. We tracked changes in primary care physician service volume (patient visits), continuity, and comprehensiveness over two decades, and explored the impacts of career stage and graduation cohort on patterns observed. We also quantified changes in the volume of services that required FP coordination, review, administration, and/or follow-up, reporting changes in service volume per-capita, per community-based family physician and per physician visit.
ResultsVisit volume and continuity per provider fell over time in the four provinces examined. Visits increased with years in practice until mid-to-late-career and declined into end-of-career. We found no relationship between graduation cohort and practice volume, continuity, or comprehensiveness of care. Over this time period, the number of FPs per-capita has grown, but the number in comprehensive, community-based practice has remained constant. While primary care visits have declined, the number of prescriptions, lab tests, emergency department visits, and specialist visits per capita have all increased. When expressed per community-based FP, and particularly per community-based FP patient visit, the increases in workload range from 36.1% for lab tests to 55.0% for ED follow-up. Increases in service volume are greatest among patients ages 80 and older, a rapidly-growing population segment.
ConclusionLinked data capturing changes in practice patterns and workload suggest that even with an increasing per-capita supply of family physicians, additional resources will be needed to ensure all patients can access comprehensive primary care. Information on the various roles family physicians fill and demographic change will strengthen workforce planning.
IntroductionThe Canadian population has poor and inequitable access to psychiatric care despite a steady per-capita supply of psychiatrists in most provinces. There is some quantitative evidence that ...practice style and characteristics vary substantially among psychiatrists. However, how this compares across jurisdictions and implications for workforce planning require further study. A qualitative exploration of psychiatrists’ preferences for practice style and the practice choices that result is also lacking. The goal of this study is to inform psychiatrist workforce planning to improve access to psychiatric care by: (1) developing and evaluating comparable indicators of supply of psychiatric care across provinces, (2) analysing variations and changes in the characteristics of the psychiatrist workforce, including demographics and practice style and (3) studying psychiatrist practice choices and intentions, and the factors that lead to these choices.Methods and analysisA cross-provincial mixed-methods study will be conducted in the Canadian provinces of British Columbia, Manitoba, Ontario and Nova Scotia. We will analyse linked-health administrative data within three of the four provinces to develop comparable indicators of supply and characterise psychiatric services at the regional level within provinces. We will use latent profile analysis to estimate the probability that a psychiatrist is in a particular practice style and map the geographical distribution of psychiatrist practices overlayed with measures of need for psychiatric care. We will also conduct in-depth, semistructured qualitative interviews with psychiatrists in each province to explore their preferences and practice choices and to inform workforce planning.Ethics and disseminationThis study was approved by Ontario Tech University Research Ethics Board (16637 and 16795) and institutions affiliated with the study team. We built a team comprising experienced researchers, psychiatrists, medical educators and policymakers in mental health services and workforce planning to disseminate knowledge that will support effective human resource policies to improve access to psychiatric care in Canada.