A new model for categorizing cognitive biases and debiasing strategies in dermatology.

Cognitive biases are a significant cause of medical error. They arise from "system 1" thinking, which depends on heuristics to make quick decisions in complex situations. Heuristics make us "predictably irrational," distorting our ability to accurately assess probabilities in clinical scenarios. It is well reported in the literature that metacognition, the art of reflecting on one's thought processes, is the optimal way to deal with cognitive biases. However, it is unclear how this can be consistently implemented in dermatological practice. Our debiasing attempts thus far have been sporadic at best. This article categorizes important cognitive biases according to each stage of the doctor-patient interaction (history taking, clinical examination, investigations, diagnosis, and management). We hope that providing this clinically relevant framework can foster metacognition and a platform for algorithmic debiasing. This will enable us to engage "system 2" (analytical thinking) in a targeted way, thereby avoiding excessive cognitive load. Organization-level interventions should also be implemented to free up the cognitive capacity of an individual and to enable them to employ system 2 thinking more regularly.

Population-level effectiveness of rapid, targeted, high-coverage roll-out of HIV pre-exposure prophylaxis in men who have sex with men: the EPIC-NSW prospective cohort study.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) is highly effective in men who have sex with men (MSM) at the individual level, but data on population-level impact are lacking. We examined whether rapid, targeted, and high-coverage roll-out of PrEP in an MSM epidemic would reduce HIV incidence in the cohort prescribed PrEP and state-wide in Australia's most populous state, New South Wales. METHODS: The Expanded PrEP Implementation in Communities-New South Wales (EPIC-NSW) study is an implementation cohort study of daily co-formulated tenofovir disoproxil fumarate and emtricitabine as HIV PrEP. We recruited high-risk gay men in a New South Wales-wide network of 21 clinics. We report protocol-specified co-primary outcomes at 12 months after recruitment of the first 3700 participants: within-cohort HIV incidence; and change in population HIV diagnoses in New South Wales between the 12-month periods before and after PrEP roll-out. The study is registered with ClinicalTrials.gov, number NCT02870790. FINDINGS: We recruited 3700 participants in the 8 months between March 1, 2016, and Oct 31, 2016. 3676 (99%) were men, 3534 (96%) identified as gay, and 149 (4%) as bisexual. Median age was 36 years (IQR 30-45 years). Overall, 3069 (83%) participants attended a visit at 12 months or later. Over 4100 person-years, two men became infected with HIV (incidence 0·048 per 100 person-years, 95% CI 0·012-0·195). Both had been non-adherent to PrEP. HIV diagnoses in MSM in New South Wales declined from 295 in the 12 months before PrEP roll-out to 221 in the 12 months after (relative risk reduction [RRR] 25·1%, 95% CI 10·5-37·4). There was a decline both in recent HIV infections (from 149 to 102, RRR 31·5%, 95% CI 11·3 to 47·3) and in other HIV diagnoses (from 146 to 119, RRR 18·5%, 95% CI -4·5 to 36·6). INTERPRETATION: PrEP implementation was associated with a rapid decline in HIV diagnoses in the state of New South Wales, which was greatest for recent infections. As part of a combination prevention approach, rapid, targeted, high-coverage PrEP implementation is effective to reduce new HIV infections at the population level. FUNDING: New South Wales Ministry of Health, Gilead Sciences.

Non-AIDS complexity amongst patients living with HIV in Sydney: risk factors and health outcomes.

OBJECTIVE: To assess the prevalence of non-AIDS co-morbidities (NACs) and predictors of adverse health outcomes amongst people living with HIV in order to identify health needs and potential gaps in patient management. DESIGN: Retrospective, non-consecutive medical record audit of patients attending a publicly funded HIV clinic in metropolitan Sydney analysed for predictors of adverse health outcomes. We developed a scoring system based on the validated Charlson score method for NACs, mental health and social issues and confounders were selected using directed acyclic graph theory under the principles of causal inference. RESULTS: 211 patient files were audited non-consecutively over 6 weeks. 89.5% were male; 41.8% culturally and linguistically diverse and 4.1% were of Aboriginal/Torres Strait Islander origin. Half of patients had no general practitioner and 25% were ineligible for Medicare subsidised care. The most common NACs were: cardiovascular disease (25%), hepatic disease (21%), and endocrinopathies (20%). One-third of patients had clinical anxiety, one-third major depression and almost half of patients had a lifetime history of tobacco smoking. Five predictors of poor health outcomes were identified: (1) co-morbidity score was associated with hospitalisation (odds ratio, OR 1.58; 95% CI 1.01-2.46; p = 0.044); (2) mental health score was associated with hospitalisation (OR 1.79; 95% CI 1.22-2.62; p = 0.003) and poor adherence to ART (OR 2.34; 95% CI 1.52-3.59; p = 0.001); (3) social issues score was associated with genotypic resistance (OR 2.61; 95% CI 1.48-4.59; p = 0.001), co-morbidity score (OR 1.69; 95% CI 1.24-2.3; p = 0.001) and hospitalisation (OR 1.72; 95% CI 1.1-2.7; p = 0.018); (4) body mass index < 20 was associated with genotypic resistance (OR 6.25; 95% CI 1.49-26.24; p = 0.012); and (5) Medicare eligibility was associated with co-morbidity score (OR 2.21; 95% CI 1.24-3.95; p = 0.007). CONCLUSION: Most HIV patients are healthy due to effective antiretroviral therapy; however, NACs and social/mental health issues are adding to patient complexity. The current findings underpin the need for multidisciplinary management beyond routine viral load and CD4 count monitoring.

Sex differences in the significance of isolated reactive treponemal chemiluminescence immunoassay results.

OBJECTIVES: The significance of sera with isolated reactive treponemal chemiluminescence immunoassay (IRTCIA) results is unclear. Women have this phenotype more commonly than men. Most cohorts examining this phenotype have included predominantly men and have demonstrated evidence of past or subsequently confirmed syphilis infection in a significant proportion of cases. We hypothesised that a proportion of sera with IRTCIA results would be positive on immunoblot testing and that sera from women with IRTCIA would have different results in immunoblot testing than men. METHODS: IRTCIA sera from a tertiary referral serology laboratory serving multiple clinical sites were analysed with a syphilis line immunoblot assay (LIA) and analysed by sex. Logistic regression was undertaken to assess factors associated with LIA status. Medical record review and descriptive analysis of a separate cohort of women with the IRTCIA phenotype from a single campus was also undertaken. RESULTS: Overall, 19/63 (30.1%) subjects with the IRTCIA phenotype were positive in the LIA, including 13 men and 6 women. Women were significantly less likely to have definitive results (positive or negative) than men (p=0.015). Pregnant women were less likely than non-pregnant women to have a negative LIA result (OR 0.57; p=0.03). Record review of 22 different women with IRTCIA reactivity showed that 2/22 (9.1%) had HIV and previous syphilis infection, 15/22 (68.2%) were pregnant and 3 (13.6%) had autoimmune disease. CONCLUSIONS: A significant proportion of sera with IRTCIA results on serological tests are reactive on LIA testing and some may not be false positive results. The interpretation of IRTCIA results should be undertaken in conjunction with an assessment of factors such as sex, pregnancy, a history of syphilis and other STIs and syphilis risk.

Antiretroviral Use in the CEASE Cohort Study and Implications for Direct-Acting Antiviral Therapy in Human Immunodeficiency Virus/Hepatitis C Virus Coinfection.

Background. Interferon-free direct-acting antiviral (DAA) regimens for hepatitis C virus (HCV) provide a major advance in clinical management, including in human immunodeficiency virus (HIV)/HCV coinfection. Drug-drug interactions (DDIs) with combination antiretroviral therapy (cART) require consideration. This study aimed to characterize the cART regimens in HIV/HCV-coinfected individuals and assess the clinical significance of DDIs with DAAs in a real-world cohort. Methods. This analysis included participants enrolled in CEASE-D, a prospective cohort of HIV/HCV-coinfected individuals in Sydney, Australia, between July 2014 and December 2015. A simulation of potential DDIs between participants' cART and interferon-free DAA regimens was performed using www.hep-druginteractions.org and relevant prescribing information. Results. In individuals on cART with HCV genotype (GT) 1 and 4 (n = 128), category 3 DDIs (contraindicated or not recommended) were noted in 0% with sofosbuvir/ledipasvir, 0% with sofosbuvir plus daclatasvir, 17% with sofosbuvir/velpatasvir, 36% with ombitasvir/paritaprevir/ritonavir ± dasabuvir, 51% with grazoprevir/elbasvir, and 51% with sofosbuvir plus simeprevir; current cART regimens were suitable for coadministration in 100%, 100%, 73%, 64%, 49%, and 49%, respectively. In individuals with HCV GT 2 or 3 (n = 53), category 3 DDIs were evident in 0% with sofosbuvir plus daclatasvir, 0% with sofosbuvir and ribavirin, and 13% with sofosbuvir/velpatasvir; current cART regimens were suitable in 100%, 100%, and 81%, respectively. Conclusions. Potential DDIs are expected and will impact on DAA prescribing in HIV/HCV coinfection. Sofosbuvir in combination with an NS5A inhibitor or ribavirin appeared to be the most suitable regimens in this cohort. Evaluation of potential DDIs is required to prevent adverse events or treatment failure.

Complex coronary sinus fistula in a 58-year-old female.

Coronary artery aneurysms and arterio-venous fistulae are uncommon malformations. We report the case of a 58-year-old woman with a large aneurysmal fistula arising from the left coronary tree and involving the entire coronary sinus venous system, resulting in significant left-to-right shunt. We discuss the management of aneurysmal fistulae of the coronary arteries, and the merits of prophylaxis for thrombotic complications of large aneurysms. We recommend consideration of warfarinisation in addition to aspirin of such patients post-operatively.

Prevalence of structural central nervous system abnormalities in early-onset type 1 diabetes mellitus.

OBJECTIVE: To characterize the effects of severe hypoglycemia on the developing brain in children with early-onset type 1 diabetes mellitus (T1DM). STUDY DESIGN: Children diagnosed with T1DM before age 6 years were studied. Those with prospectively monitored severe hypoglycemia (coma/seizure; n = 32) were compared with age-matched peers (n = 30) with no history of such events using magnetic resonance imaging. Glycemic control (evaluated based on glycated hemoglobin [HbA(lc)] level), episodes of diabetic ketoacidosis (DKA), and clinical variables were monitored continuously since diagnosis in all subjects. RESULTS: Mean HbA(lc) from diagnosis and the duration of T1DM were similar in those with and without a history of severe hypoglycemia (9.0% +/- 0.9% vs 8.8% +/- 0.9%; 7.2 +/- 2.7 years vs 6.7 +/- 2.3 years). A high prevalence of central nervous system (CNS) structural abnormalities was detected (29%), and mesial temporal sclerosis (MTS) was detected in 16% of the total sample (n = 62). The presence of MTS was not associated with a history of severe hypoglycemia or DKA. Analysis of brain matter volumes suggested relatively less gray matter density in those subjects with a history of severe hypoglycemia. CONCLUSIONS: Early age of onset of T1DM per se is associated with a high incidence of CNS abnormalities, particularly MTS, suggesting hippocampal damage. Early-onset severe hypoglycemia may have an effect on gray matter volume.

MR findings in cardiac amyloidosis.

OBJECTIVE: The objective of our study was to describe a combination of features on MRI specific to cardiac amyloidosis. CONCLUSION: Cardiac amyloidosis is a common cause of infiltrative heart disease. The combination of subtle widespread heterogeneous myocardial enhancement on delayed postcontrast inversion recovery T1-weighted images, which may initially be dismissed as a technical error, with ancillary features of restrictive cardiac disease is highly suggestive of cardiac amyloidosis.

Diagnosing and treating lateral epicondylitis.

Lateral epicondylitis is often encountered in primary care. Although its diagnosis can be fairly straightforward, its treatment is often difficult. This review examines the epidemiology, pathophysiology, and clinical presentation of tennis elbow. Management options are discussed.

[The efficacy of ethambutol compared to streptomycin in the initial quadruple phase of short-term regimens]. / Eficacitatea etambutolului comparativ cu a streptomicinei in faza initiala cvadrupla a regimurilor de scurta durata.

In order to test comparatively SM and EMB efficacies within quadruple regimens of short-term chemotherapy, two groups of patients with pulmonary tuberculosis at first treatment, sputum positive under microscopic examination, were constituted through randomization. One group (59 cases) was submitted to the standard regimen RHSZ 2/7, and the other (61 cases) to RHZE 2/7. Group structure was homogeneous from the standpoint of case repartition, according to the anatomo-radiological form, therapeutical regimen, and sensitivity to Tb drugs. Both bacteriological and radiological clinical evolutions show, even in the conditions of a short-time interval (2 months), a similar efficacy of SM and EMB within the quadruple regimens in the initially intensive phase of anti-Tb treatment. It is possible that the results may be dependent upon the concomitantly bactericidal action of: rifampicin, hydrazide and pyrazinamide. Therefore, a further testing of the comparative efficacy of the triple regimen RHZ 2/7 with the quadruple RHSZ 2/7 and RHZE 2/7 during a longer follow-up is required.

The properties of skeletal muscle.

The authors review the musculoskeletal system and the controversy that surrounds methods for improving and strengthening it. Disorders brought on by over utilization, deficient working habits, lack of appropriate maintenance care and intercurrent stress and fatigue from repetitious daily tasks and poor sleeping habits are recognized and discussed. Also discussed are muscle structure and its relation to the contractive state, muscle energy requirements, motor control, source of muscle strength and factors modulating it, training adaptations in skeletal muscle, methods of strength training, erogenic aids including anabolic steroids and electrical stimulation and the pathologic states in muscles.

Nutrition and sports.

Family physicians are often asked for advice by patients of all ages who participate in regular exercise programs. The knowledgeable family physician can be very helpful to athletes, who are swamped with information and misinformation about nutrition. This article describes the dietary needs of recreational and competitive athletes, illustrates the way in which diet can prevent the development of some pathological conditions, considers athletes at different stages of the life cycle, and discusses the dietary requirements of the exercising diabetic patient.

Interrelationships of glucose and insulin uptake by muscle of normal and diabetic man. Evidence of a difference in metabolism of endogenous and exogenous insulin.

A forearm perfusion technique was used to study glucose and insulin uptake by muscle. In normal subjects at glycaemic levels above 130 mg/100 ml, glucose uptake was independent of glucose concentration;it was directly related in insulin concentration but not to insulin uptake. In non-obese maturity-onset diabetic subjects, glucose uptake was dependent on glucose concentration and insulin uptake, but not on insulin concentration. In both groups there was a strong correlation between insulin concentration and insulin uptake; diabetics had a normal insulin uptake in relation to concentration. For a given change in insulin concentration the increase in glucose uptake was as great in diabetics as in controls, but the effect of insulin was mediated through a mechanism involving its uptake. Thus in the non-obese maturity-onset diabetic, forearm muscle is not insulin resistant. The apparent uptake of insulin measured by a radioimmunoassay in relation to its arterial concentration was lower and more variable for heterologous than for endogenous insulin. With a receptor assay the venous insulin concentrations were lower than with the immunoassay and differences in uptake between endogenous and exogenous insulin disappeared. It is concluded that in muscle exogenous insulin was less severely degraded than endogenous insulin.

Effect of exercise on glucose and insulin utilization in the forearm.

Glucose and insulin utilization by forearm muscle was examined at rest and during exercise. Care was taken to have a steady state with regard to arterial plasma concentrations for 1 hr prior to as well as during the measurements. At rest, insulin uptake was linearly related to arterial insulin concentration. During exercise with no change in arterial plasma concentration of either glucose or insulin, there was an increase in uptake of both substances, and the relation of insulin uptake to concentration became exponential. It is hypothesizes that the latter phenomenon is due to an increase in cellular uptake of insulin by a mechanism independent of membrane receptors.