Is the assumption of equal distances between global assessment categories used in borderline regression valid?

BACKGROUND: Standard setting for clinical examinations typically uses the borderline regression method to set the pass mark. An assumption made in using this method is that there are equal intervals between global ratings (GR) (e.g. Fail, Borderline Pass, Clear Pass, Good and Excellent). However, this assumption has never been tested in the medical literature to the best of our knowledge. We examine if the assumption of equal intervals between GR is met, and the potential implications for student outcomes. METHODS: Clinical finals examiners were recruited across two institutions to place the typical 'Borderline Pass', 'Clear Pass' and 'Good' candidate on a continuous slider scale between a typical 'Fail' candidate at point 0 and a typical 'Excellent' candidate at point 1. Results were analysed using one-sample t-testing of each interval to an equal interval size of 0.25. Secondary data analysis was performed on summative assessment scores for 94 clinical stations and 1191 medical student examination outcomes in the final 2 years of study at a single centre. RESULTS: On a scale from 0.00 (Fail) to 1.00 (Excellent), mean examiner GRs for 'Borderline Pass', 'Clear Pass' and 'Good' were 0.33, 0.55 and 0.77 respectively. All of the four intervals between GRs (Fail-Borderline Pass, Borderline Pass-Clear Pass, Clear Pass-Good, Good-Excellent) were statistically significantly different to the expected value of 0.25 (all p-values < 0.0125). An ordinal linear regression using mean examiner GRs was performed for each of the 94 stations, to determine pass marks out of 24. This increased pass marks for all 94 stations compared with the original GR locations (mean increase 0.21), and caused one additional fail by overall exam pass mark (out of 1191 students) and 92 additional station fails (out of 11,346 stations). CONCLUSIONS: Although the current assumption of equal intervals between GRs across the performance spectrum is not met, and an adjusted regression equation causes an increase in station pass marks, the effect on overall exam pass/fail outcomes is modest.

Adverse outcomes in COVID-19 and diabetes: a retrospective cohort study from three London teaching hospitals.

INTRODUCTION: Patients with diabetes mellitus admitted to hospital with COVID-19 have poorer outcomes. However, the drivers of poorer outcomes are not fully elucidated. We performed detailed characterization of patients with COVID-19 to determine the clinical and biochemical factors that may be drivers of poorer outcomes. RESEARCH DESIGN AND METHODS: This is a retrospective cohort study of 889 consecutive inpatients diagnosed with COVID-19 between March 9 and April 22, 2020 in a large London National Health Service Trust. Unbiased multivariate logistic regression analysis was performed to determine variables that were independently and significantly associated with increased risk of death and/or intensive care unit (ICU) admission within 30 days of COVID-19 diagnosis. RESULTS: 62% of patients in our cohort were of non-white ethnic background and the prevalence of diabetes was 38%. 323 (36%) patients met the primary outcome of death/admission to the ICU within 30 days of COVID-19 diagnosis. Male gender, lower platelet count, advancing age and higher Clinical Frailty Scale (CFS) score (but not diabetes) independently predicted poor outcomes on multivariate analysis. Antiplatelet medication was associated with a lower risk of death/ICU admission. Factors that were significantly and independently associated with poorer outcomes in patients with diabetes were coexisting ischemic heart disease, increasing age and lower platelet count. CONCLUSIONS: In this large study of a diverse patient population, comorbidity (ie, diabetes with ischemic heart disease; increasing CFS score in older patients) was a major determinant of poor outcomes with COVID-19. Antiplatelet medication should be evaluated in randomized clinical trials among high-risk patient groups.

Differential effects of L- and D-phenylalanine on pancreatic and gastrointestinal hormone release in humans: A randomized crossover study.

AIM: To investigate the effects of L-phenylalanine on gastroenteropancreatic hormone release, glucose levels, subjective appetite and energy intake in humans, and to determine whether these effects were stereoisomer-specific by comparing them with D-phenylalanine. MATERIALS AND METHODS: A dose-finding, non-randomized, unblinded, crossover study was conducted during October-December 2017 at the NIHR Imperial Clinical Research Facility in five participants, in which the tolerability of escalating doses of oral L-phenylalanine was assessed (0, 3, 6 and 10 g). Also, an acute, randomized, double-blind, placebo-controlled crossover study was conducted during January-May 2018 at the NIHR Imperial Clinical Research Facility in 11 participants, in which the effects of oral 10 g L-phenylalanine relative to D-phenylalanine and placebo on gastroenteropancreatic hormone (insulin, glucagon, glucose-dependent insulinotropic polypeptide [GIP], peptide tyrosine tyrosine [PYY], glucagon-like peptide-1) and glucose concentrations, visual analogue scales for subjective appetite and energy intake at an ad libitum meal served 70 minutes postingestion, were investigated. RESULTS: L-phenylalanine was well-tolerated and increased insulin and glucagon concentrations prior to meal ingestion at several time points relative to placebo and D-phenylalanine (P < .05). L-phenylalanine also increased GIP concentrations relative to D-phenylalanine (P = .0420) and placebo (P = .0249) 70 minutes following ingestion. L-phenylalanine reduced postprandial glucose area under the curve (AUC)70-150mins relative to placebo (P = .0317) but did not affect subjective appetite or energy intake (P > .05). D-phenylalanine increased postprandial PYY AUC70-150mins concentrations relative to placebo (P = .0002). CONCLUSIONS: Ingestion of L-phenylalanine, but not D-phenylalanine, increases insulin, glucagon and GIP concentrations without appearing to have a marked effect on appetite.

L-Arginine Increases Postprandial Circulating GLP-1 and PYY Levels in Humans.

OBJECTIVE: The satiating effect of protein compared with other nutrients has been well described and is thought to be mediated, in part, by gut hormone release. Previously, it has been shown that oral L-arginine acts as a GLP-1 secretagogue both in vitro and in vivo in rodents. Here, the effect of L-arginine on gut hormone release in humans was investigated. METHODS: The hypothesis was tested in two separate studies. The first study assessed the tolerability of oral L-arginine in healthy human subjects. The second study assessed the effect of oral L-arginine on gut hormone release following an ad libitum meal. Subjects were given L-arginine, glycine (control amino acid), or vehicle control in a randomized double-blind fashion. RESULTS: At a dose of 17.1 mmol, L-arginine was well tolerated and stimulated the release of plasma GLP-1 (P < 0.05) and PYY (P < 0.001) following an ad libitum meal. Food diaries showed a trend toward lower energy intake and particularly fat intake following L-arginine treatment. CONCLUSIONS: L-arginine can significantly elevate GLP-1 and PYY in healthy human volunteers in combination with a meal. Further work is required to investigate whether L-arginine may have utility in the suppression of appetite and food intake.

Nutritional sensing and its utility in treating obesity.

Obesity remains a major worldwide health problem, with current medical treatments being poorly effective. Nutrient sensing allows organs such as the GI tract and the brain to recognize and respond to fuel substrates such as carbohydrates, protein and fats. Specialized neural and hormonal pathways exist to facilitate and regulate these chemosensory mechanisms. Manipulation of factors involved in either central or peripheral chemosensory pathways may provide possible targets for the manipulation of appetite. However, further research is required to assess the utility of this approach to developing novel anti-obesity agents.

The central effects of thyroid hormones on appetite.

Obesity is a major public health issue worldwide. Current pharmacological treatments are largely unsuccessful. Determining the complex pathways that regulate food intake may aid the development of new treatments. The hypothalamic-pituitary-thyroid (HPT) axis has well-known effects on energy expenditure, but its role in the regulation of food intake is less well characterised. Evidence suggests that the HPT axis can directly influence food intake. Thyroid dysfunction can have clinically significant consequences on appetite and body weight. Classically, these effects were thought to be mediated by the peripheral effects of thyroid hormone. However, more recently, local regulation of thyroid hormone in the central nervous system (CNS) is thought to play an important role in physiologically regulating appetite. This paper focuses on the role of the HPT and thyroid hormone in appetite and provides evidence for potential new targets for anti-obesity agents.

Endocrine problems in pregnancy.

This paper aims to describe the pathophysiology and management of the main endocrine complications of pregnancy. For each endocrine dysfunction, the issues with the fetus, the mother, obstetric complications, and the long term prognosis for the disease itself need to be considered. Key management issues are highlighted with each condition. Thyroid dysfunction and goitre are common while management is relatively straightforward. Adrenal, pituitary, and parathyroid diseases present less commonly in pregnancy. Early recognition of endocrine disease in pregnancy and appropriate management has the potential to improve outcome for the mother and fetus in the short and long term.