A multi-method approach to drafting candidate entrustable professional activities for a general internal medicine residency programme.

INTRODUCTION: Entrustable professional activities (EPAs) are units of concrete daily clinical tasks that trainee physicians should be able to handle with increasing autonomy during their postgraduate training. EPAs are gaining international recognition as an essential component of competency-based medical training programmes. The process of developing EPAs for a nationwide training programme is complex and requires an in-depth understanding of EPAs as a concept and good knowledge of appropriate development processes. This article provides a detailed description of the methodology and results of a multi-step approach for developing a list of candidate EPAs for Switzerland's postgraduate training programme in general internal medicine (GIM). METHODS: We took a multi-step approach including a systematic review of international literature, four national focus groups, a national consensus process using a RAND appropriateness method, and a quality check of the selected candidate EPAs using EQual criteria. RESULTS: These steps generated a final list of 247 candidate EPAs in general internal medicine that were submitted for the national consensus process. After two rounds of rating, experts agreed on the appropriateness for general internal medicine postgraduate training of 225 candidate EPAs. Twenty-two were deemed inappropriate, and disagreement persisted only for two EPAs. DISCUSSION: This multi-step programme is one of the few describing in detail the process of developing a list of EPAs and providing evidence of validity at each step. The clinical breadth of our candidate EPAs, together with the detailed description of our methodology, could serve as a useful starting point from which medical education specialists or clinicians could develop or revise applicable lists of EPAs, particularly for postgraduate training programmes in either general internal medicine or family medicine.

Association of part-time clinical work with well-being and mental health in General Internal Medicine: A survey among Swiss hospitalists.

INTRODUCTION: Burnout and low job satisfaction are increasing among the General Internal Medicine (GIM) workforce. Whether part-time compared to full-time clinical employment is associated with better wellbeing, job satisfaction and health among hospitalists remains unclear. MATERIALS AND METHODS: We conducted an anonymized cross-sectional survey among board-certified general internists (i.e. hospitalists) from GIM departments in 14 Swiss hospitals. Part-time clinical work was defined as employment of <100% as a clinician. The primary outcome was well-being, as measured by the extended Physician Well-Being Index (ePWBI), an ePWBI ≥3 indicating poor wellbeing. Secondary outcomes included depressive symptoms, mental and physical health, and job satisfaction. We compared outcomes in part-time and full time workers using propensity score-adjusted multivariate regression models. RESULTS: Of 199 hospitalists invited, 137 (69%) responded to the survey, and 124 were eligible for analysis (57 full-time and 67 part-time clinicians). Full-time clinicians were more likely to have poor wellbeing compared to part-time clinicians (ePWBI ≥3 54% vs. 31%, p = 0.012). Part-time compared to full-time clinical work was associated with a lower risk of poor well-being in adjusted analyses (odds ratio 0.20, 95% confidence interval 0.07-0.59, p = 0.004). Compared to full-time clinicians, there were fewer depressive symptoms (3% vs. 18%, p = 0.006), and mental health was better (mean SF-8 Mental Component Summary score 47.2 vs. 43.2, p = 0.028) in part-time clinicians, without significant differences in physical health and job satisfaction. CONCLUSIONS: Full-time clinical hospitalists in GIM have a high risk of poor well-being. Part-time compared to full-time clinical work is associated with better well-being and mental health, and fewer depressive symptoms.

Entrustable professional activities for residency in general internal medicine: a systematic review.

CONTEXT: Entrustable Professional Activities (EPAs) are observable tasks that are regular parts of a physician's daily clinical work. Before being permitted to accomplish these tasks independently, trainees must gain their supervisors' trust. Defining the list of EPAs that should be mastered by the end of a residency is critical to setting clear expectations about autonomous practice. OBJECTIVE: To collect all the lists of EPAs defined for residencies in general internal medicine and synthesise them into a reference work useful for developing new lists of EPAs or improving existing ones. METHOD: This systematic review searched five databases and relevant grey literature using keywords related to EPAs and postgraduate education, from 2005, when the first article on EPAs was published, to April 2022. Inclusion criteria were the availability of an EPAs list and a focus on general internal medicine. Two reviewers independently selected the studies, extracted data and performed a quality assessment using QATSDD and AACODS tools. Mean values and inter-rater reliability were calculated. RESULTS: The review yielded 3292 records, with 16 articles meeting the inclusion criteria, mostly from North America. Synthesising their 16 lists generated 395 EPAs. The reviewers then inductively categoried those EPAs, 308 of which fell into 6 domains, 14 themes and 24 subthemes. The domains were: (1) care and management of the general adult population (n = 103 EPAs); (2) care and management of patients with specific needs (n = 67); (3) care coordination and communication (n = 52); (4) management and leadership (N = 21); (5) healthcare quality, education, and research (n = 41); and (6) miscellaneous (n = 24). The remaining 87 EPAs were disease-specific and did not fit into this categorisation. CONCLUSIONS: Categorising EPAs created a unique synthesis of the existing lists of EPAs for educating residents in general internal medicine. This synthesis could be used as a reference for anyone tasked with developing new lists of EPAs or improving existing ones.

[When a Gap Leads to an Answer]. / Wenn eine Lücke zur Lösung führt.

When a Gap Leads to an Answer Abstract. We report the case of a 22-year-old patient who was found somnolent after previously complaining of nausea, abdominal pain, and vomiting. The main findings were high anion gap metabolic acidosis and lactatemia. Causative was the ingestion of ethylene glycol using a car antifreeze agent with suicidal intent.

Arap1 loss causes retinal pigment epithelium phagocytic dysfunction and subsequent photoreceptor death.

Retinitis pigmentosa (RP), a retinal degenerative disease, is the leading cause of heritable blindness. Previously, we described that Arap1-/- mice develop a similar pattern of photoreceptor degeneration. Arap1 is an Arf-directed GTPase-activating protein shown to modulate actin cytoskeletal dynamics. Curiously, Arap1 expression was detected in Müller glia and retinal pigment epithelium (RPE), but not the photoreceptors themselves. In this study, we generated conditional knockout mice for Müller glia/RPE, Müller glia and RPE via targeting Rlbp1, Glast and Vmd2 promoters, respectively, to drive Cre recombinase expression to knock out Arap1. Vmd2-Cre Arap1tm1c/tm1c and Rlbp1-Cre Arap1tm1c/tm1c mice, but not Glast-Cre Arap1tm1c/tm1c mice, recapitulated the phenotype originally observed in germline Arap1-/- mice. Mass spectrometry analysis of human ARAP1 co-immunoprecipitation identified candidate binding partners of ARAP1, revealing potential interactants involved in phagocytosis, cytoskeletal composition, intracellular trafficking and endocytosis. Quantification of outer segment phagocytosis in vivo demonstrated a clear phagocytic defect in Arap1-/- mice compared to Arap1+/+ controls. We conclude that Arap1 expression in RPE is necessary for photoreceptor survival due to its indispensable function in RPE phagocytosis. This article has an associated First Person interview with the first author of the paper.

Targeting vascular endothelial growth factor using retinal gene therapy.

Pharmacotherapies targeting vascular endothelial growth factor (VEGF) have revolutionized the management for neovascular retinal disorders including diabetic retinopathy and neovascular age-related macular degeneration. However, the burden of frequent injections, high cost, and treatment resistance in some patients remain unresolved. To overcome these challenges, newer generations of anti-angiogenic biological therapies, engineered proteins, implantable delivery systems, and biopolymers are currently being developed to enable more sustained, longer-lasting treatments. The use of gene therapies for pathologic angiogenesis has garnered renewed interests since the first FDA-approval of a gene therapy to treat inherited retinal diseases associated with biallelic RPE65 mutations. Newer generations of viral vectors and novel methods of intraocular injections helped overcome ocular barriers, improving the efficiency of transduction as well as safety profile. In addition, unlike current anti-VEGF gene therapy strategies which employ a biofactory approach to mimic existing pharmacotherapies, novel genome editing strategies that target pro-angiogenic factors at the DNA level offer a unique and distinct mechanistic approach that can potentially be more precise and lead to a permanent cure. Here, we review current anti-VEGF therapies and newer pharmacologic agents under development, examine technologies and progress in adapting anti-VEGF gene therapies, and explore the future application of CRISPR-Cas9 technology to suppress ocular angiogenesis.

An analysis of core EPAs reveals a gap between curricular expectations and medical school graduates' self-perceived level of competence.

BACKGROUND: Entrustable Professional Activities (EPAs) are being implemented worldwide as a means to promote competency-based medical education. In Switzerland, the new EPA-based curriculum for undergraduate medical education will be implemented in 2021. The aim of our study was to analyze the perceived, self-reported competence of graduates in 2019. The data represent a pre-implementation baseline and will provide guidance for curriculum developers. METHODS: Two hundred eighty-one graduates of the Master of Human Medicine program of the University of Zurich who had passed the Federal Licensing Exam in September 2019 were invited to complete an online survey. They were asked to rate their needed level of supervision ("observe only", "direct, proactive supervision", "indirect, reactive supervision") for 46 selected EPAs. We compared the perceived competence with the expected competence of the new curriculum. RESULTS: The response rate was 54%. The need for supervision expressed by graduates varied considerably by EPA. The proportion of graduates rating themselves at expected level was high for "history taking", "physical examination" "and documentation"; medium for "prioritizing differential diagnoses", "interpreting results" and "developing and communicating a management plan"; low for "practical skills"; and very low for EPAs related to "urgent and emergency care". CONCLUSIONS: Currently, there are significant gaps between the expectations of curriculum developers and the perceived competences of students. This is most obvious for practical skills and emergency situations. The new curriculum will either need to fill this gap or expectations might need to be revised.

Spontaneous intracardiac microcavitations in a patient with a colonic carcinoma.

Intracardiac microcavitations consist of airy microbubbles. They are typically found in patients with an intravascular line or device, mechanical heart valves or in decompression sickness. We report a case of a patient in mid-70s who was admitted due to weakness in both legs, left-thoracic pain and fever. Despite the lack of any of the risk factors mentioned above, spontaneous microcavitations were detected in the right sided cardiac cavities. After the detection of liver lesions suspicious for a metastatic disease, a colonoscopy was performed. An ulcerated colonic carcinoma at the ileocoecal valve was diagnosed and highly suspicious for being the entry port of the microcavitations. This unusual presentation of microcavitations together with a colonic neoplasia leads to hypotheses about the journey of the microbubbles from the ascending colon into the right heart. Gastrointestinal tumours are described as being the causes of microbubbles. Translocation of microbubbles through hepatopulmonary shunting are described in the context of locally applied particles of similar size during radioembolisation. A thorough aetiological workup is of importance since the underlying cause is potentially dangerous due to its own nature of disease and due the complications of the microcavitations such as paradoxical emboli or pulmonary sequelae.

Extracorporeal Membrane Oxygenation in Miliary Tuberculosis and AIDS: A Case Report.

Background The aim of this study is to present the success of a multidisciplinary approach in a patient with a rare triad of disease. Case Description A 33-year-old patient with newly diagnosed human immunodeficiency virus infection presented with miliary tuberculosis, consecutive adult respiratory distress syndrome, and multiple-organ failure. An interdisciplinary, time-limited approach combining extracorporeal membrane oxygenation, intensive care therapy, hemodiafiltration, tuberculostatic therapy, steroids, and antiretroviral therapy led to survival despite a low probability at presentation. Conclusion Even though the use of such extensive and expensive treatment can be questioned, this example encourages an aggressive approach in a young patient, even in situations of multiple diagnosis of individually limited prognosis.

Quality of life 9 years after an intensive care unit stay: a long-term outcome study.

PURPOSE: The purpose of the study was to assess long-term mortality after an intensive care unit (ICU) stay and to test the hypotheses that (1) quality of life improves over time and (2) predictions of outcome made by caregivers during an ICU stay are reliable. MATERIALS AND METHODS: Data from a 6-bed university medical ICU were reviewed. Telephone assessment of mortality and interviews/questionnaires 9 years after an ICU stay were performed. Comparison of caregivers' predictions of survival/quality of life with reported outcome was done. RESULTS: Of 409 patients surviving 6 months after ICU, 334 were included and 146 of these had died. Age, diagnostic group, and severity of illness were significant factors for mortality (P < .0001 for all 3). Of all survivors, 59% described their overall quality of life as good and 35% as fair. Physical dependency was significantly related to length of hospital stay (P < .01), whereas quality of life was related to admission age (P < .05). Caregivers' predictions concerning both survival and quality of life seemed reliable, with physicians' predictions being more reliable than nurses' (P < .05). CONCLUSIONS: Mortality is high 9 years after ICU stay. Quality of life may deteriorate for some individuals; however, overall quality of life for most survivors remains acceptable and may even improve. Long-term outcome predictions made by caregivers during the ICU stay seem accurate.

Reducing pain in patients undergoing cardiac surgery after implementation of a quality improvement postoperative pain treatment program.

PURPOSE: The aim of this study was to test the effectiveness of a quality improvement postoperative pain treatment program after cardiac surgery. MATERIALS AND METHODS: This was a prospective, quasiexperimental study using nonequivalent groups comprising 3 periods: baseline (group baseline), implementation of the algorithm for acute pain management, and reassessment (group reassessment). Inclusion of 133 patients after elective cardiac surgery at an 18-bed surgical intensive care unit (SICU) at a Swiss university hospital. The algorithm was implemented by training, pocket guidelines, regular audits, and feedback. The implementation period was completed when the adherence to 2 of 3 process indicators attained at least 70% over 2 months. Visual analog scales (VAS) for pain, morphine consumption, pain perception, and sleep quality were assessed during stay in SICU and after 1 month and 6 months. RESULTS: The assessment included 79 patients at baseline and 54 in the reassessment periods. Pain intensity at rest decreased from 2.7 +/- 1.4 to 2.2 +/- 1.4 cm (VAS; P = .008). Retrospective perception of pain intensity at rest decreased from 3.8 +/- 2.2 to 2.6 +/- 1.8 (P = .004). The proportion of patients with no pain or often without pain increased from 11% to 37% (P = .005). The number of patients with sleep disturbances decreased from 68% to 35% (P = .012). No differences were observed at 1 and 6 months postoperatively. CONCLUSIONS: After algorithm implementation in the SICU, pain intensity at rest decreased and quality of sleep improved.

Human F(ab')2-containing immune complexes together with anti-hinge natural antibodies stimulate complement amplification in vitro and in vivo.

The systemic inflammatory response syndrome (SIRS) is triggered by C5a generation following an excessive complement amplification, but it has remained unclear how complement amplification is stimulated. It is known that neutrophilic elastase can cleave IgG to F(ab')(2) and that F(ab')(2)-containing immune complexes (F(ab')(2)-IC) stimulate complement amplification together with an unidentified plasma factor. We show that absorption of plasma on F(ab')(2) from human IgG removed this factor and prevented F(ab')(2)-IC from stimulating complement amplification. The required factor was purified from pooled whole human IgG (IVIG) as those naturally occurring antibodies (NAbs) that bind to F(ab')(2), but not to intact IgG. These "anti-hinge NAbs" restored complement amplification by F(ab')(2)-IC in absorbed plasma. Anti-hinge NAbs must have formed secondary, rigidified IC from F(ab')(2)-IC, because the F(ab')(2) fragments evidently captured dimeric C3b, known as a potent C3 convertase precursor. This process may also stimulate complement amplification in vivo, because plasma from septic patients at the onset of SIRS indeed contained F(ab')(2) fragments. The concentrations of F(ab')(2) and that of factor Bb, an unbiased measure of complement amplification, correlated linearly with that of released elastase. Moreover, the F(ab')(2) fragments migrated on gelfiltration columns together with anti-hinge NAbs as ICs with MW of up to approximately 750kDa, as verified on plasma of each of the nine patients studied. These findings provide for the first time a plausible mechanism of how F(ab')(2)-containing immune complexes stimulate complement amplification together with anti-hinge NAbs. The same mechanism may contribute to complement overreaction at the onset of SIRS.

Reversible posterior leukoencephalopathy syndrome after treatment of diffuse large B-cell lymphoma.

BACKGROUND: We report the case of a patient who experienced a severe neurologic complication after treatment of diffuse large B-cell lymphoma. CASE REPORT: A 62-year old patient was diagnosed with a diffuse large B-cell lymphoma and treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone under prophylactic G-CSF substitution. After the second cycle she developed severe neurologic complications with generalized seizures and soporous condition. The MRI showed bilateral areas of signal hyperintensity in the subcortical and cortical regions in both hemispheres, consistent with the diagnosis of a reversible posterior leukoencephalopathy syndrome. The patient was under surveillance in intensive care, and a meticulous control of the blood pressure was performed. She fully recovered within a few days, and MRI changes normalized. Antineoplastic treatment had to be continued, and we chose a combination of rituximab, doxorubicin, etoposide, and prednisone. CONCLUSIONS: The reversible posterior leukoencephalopathy syndrome is believed to be the result of altered cerebral autoregulation with impaired blood flow control and resultant endothelial damage caused by different situations and agents. Several chemotherapy agents have been described in association with the syndrome. However, little is known about the prevalence of the syndrome and the follow-up of these patients, especially their further treatment.

How much is too much? Oligosymptomatic presentation after 11.5 g of diphenhydramine.

We report the case of a 47-year-old male obese Caucasian patient presenting 2 hours after ingestion of 11.5 g of diphenhydramine. Despite this excessive overdose, he showed only a few hours of impaired consciousness and no further symptoms. A diphenhydramine plasma concentration of 15,352 nmol/L was measured 8 hours after the overdose ingestion. A heterogeneous CYP2D6 extensive metabolizer genotype excludes a pharmacokinetic explanation for this unusually oligosymptomatic presentation. However, the patient suffered from longstanding, refractory depression despite numerous treatment attempts with various drugs, pointing to the possibility of decreased pharmacodynamic responsiveness for therapeutic and toxic effects.

Medical futility: predicting outcome of intensive care unit patients by nurses and doctors--a prospective comparative study.

OBJECTIVE: First, to assess the pattern of the prediction of intensive care unit patients' outcome with regard to survival and quality of life by nurses and doctors and, second, to compare these predictions with the quality of life reported by the surviving patients. DESIGN: Prospective opinion survey of critical care providers; comparison with follow-up for survival, functional status, and quality of life. SETTING: Six-bed medical intensive care unit subunit of a 1,000-bed tertiary care, university hospital. PATIENTS: All patients older than 18 yrs, admitted to the medical intensive care unit for >24 hrs over a 1-yr period (December 1997 to November 1998). INTERVENTIONS: Daily judgment of eventual futility of medical interventions by nurses and doctors with respect to survival and future quality of life. Telephone interviews with discharged patients for quality of life and functional status 6 months after intensive care unit admission. MEASUREMENTS AND MAIN RESULTS: Data regarding 521 patients including 1,932 daily judgments by nurses and doctors were analyzed. Disagreement on at least one of the daily judgments by nurses and doctors was found in 21% of all patients and in 63% of the dying patients. The disagreements more frequently concerned quality of life than survival. The higher the Simplified Acute Physiology Score and the longer the intensive care unit stay, the more divergent judgments were observed (p <.001). In surviving and dying patients, nurses gave more pessimistic judgment and considered withdrawal more often than did doctors (p <.001). Patients only rarely indicated bad quality of life (6%) and severe physical disability (2%) 6 months after intensive care unit admission. Compared with patients' own assessment, neither nurses nor doctors correctly predicted quality of life; false pessimistic and false optimistic appreciation was given. CONCLUSIONS: Disagreement between nurses and doctors was frequent with respect to their judgment of futility of medical interventions. Disagreements most often concerned the most severely ill patients. Nurses, being more pessimistic in general, were more often correct than doctors in the judgment of dying patients but proposed treatment withdrawal in some very sick patients who survived. Future quality of life cannot reliably be predicted either by doctors or by nurses.

Assessment of former ICU patients' quality of life: comparison of different quality-of-life measures.

OBJECTIVE: To compare three different measures to assess quality of life (QOL) after an Intensive Care Unit (ICU) stay: a standardized telephone interview, a satisfaction scale, and the Sickness Impact Profile (SIP). DESIGN: Prospective study, evaluating QOL 6 months after ICU discharge. SETTING: Medical ICU of a Swiss tertiary-care university hospital. PATIENTS AND METHODS: Patients admitted to the ICU between July and November 1998 for more than 24 h were included. Six months after ICU discharge overall QOL and health-related QOL were evaluated. Of the 118 patients approached, 85 returned valid questionnaires. RESULTS: The majority of patients indicated good QOL 6 months after ICU stay on each measure. A correlation for both overall and health-related QOL was found between the SIP and the satisfaction scales, between SIP and the telephone interviews, between the telephone interviews and satisfaction scales. The correlation between rating by scale or telephone interview and SIP in patients with cardiovascular disease differed from patients with other diagnoses. CONCLUSIONS: For the global assessment of overall or health-related QOL after ICU stay, long questionnaires such as SIP may be replaced by a short, structured telephone interview or, better, by a satisfaction scale. Quantitative measures such as SIP may be needed for comparison of therapeutic interventions or specific functional or psychosocial aspects.