Real-world treatment patterns in patients with nontuberculous mycobacterial lung disease in the Netherlands based on medication dispensing data.

PURPOSE: Real-world data on antibiotic management of nontuberculous mycobacterial lung disease (NTM-LD) is limited for many countries. This study aimed to evaluate real-world treatment practices of NTM-LD in the Netherlands using medication dispensing data. METHODS: A retrospective longitudinal real-world study was conducted using IQVIA's Dutch pharmaceutical dispensing database. The data are collected monthly and include approximately 70% of all outpatient prescriptions in the Netherlands. Patients initiated on specific NTM-LD treatment regimens between October 2015 and September 2020 were included. The main areas of investigation were initial treatment regimens, persistence on treatment, treatment switching, treatment compliance in terms of medication possession rate (MPR) and restarts of treatment. RESULTS: The database included 465 unique patients initiated on triple- or dual-drug regimens for the treatment of NTM-LD. Treatment switches were common and occurred approximately 1.6 per quarter throughout the treatment period. The average MPR of patients initiated on triple-drug therapy was 90%. The median time on therapy for these patients was 119 days; after six months and one year, 47% and 20% of the patients, respectively, were still on antibiotic therapy. Of 187 patients initiated on triple-drug therapy, 33 (18%) patients restarted antibiotic therapy after the initial treatment had been stopped. CONCLUSION: When on therapy, patients were compliant with the NTM-LD treatment; however, many patients stopped their therapy prematurely, treatment switches often occurred, and part of patients had to restart their therapy after a longer treatment gap. NTM-LD management should be improved through greater guideline adherence and appropriate involvement of expert centers.

Personal-professional Development Program Fosters Resilience During COVID-Pandemic.

Problem: Epidemiological data throughout the academic world show an upswing in mental health concerns among students, even more significant during the ongoing COVID-pandemic. Many universities have recognized these problems and started counseling programs. However, currently reported stress levels and mental health problems at many universities remain substantial. Approach: Our medical faculty features an evidence informed longitudinal program on personal-professional development (LPPD) integrated into the core curriculum to strengthen wellbeing and support the student as a whole. Outcomes: With our LPPD program we show that it is possible to successfully enable personal-professional development and well-being, especially in unexpected times when resilience is needed. The safe learning environment the teacher-coaches created has proven to be an important condition in this regard. Next steps: The LPPD program will be further evaluated and both results and program materials will be shared with the academic community through web-pages, online material and research papers.

Optimizing teacher basic need satisfaction in distributed healthcare contexts.

Optimizing teacher motivation in distributed learning environments is paramount to ensure high-quality education, as medical education is increasingly becoming the responsibility of a larger variety of healthcare contexts. This study aims to explore teaching-related basic need satisfaction, e.g. teachers' feelings of autonomy, competence and relatedness in teaching, in different healthcare contexts and to provide insight into its relation to contextual factors. We distributed a digital survey among healthcare professionals in university hospitals (UH), district teaching hospitals (DTH), and primary care (PC). We used the Teaching-related Basic Need Satisfaction scale, based on the Self-Determination theory, to measure teachers' basic needs satisfaction in teaching. We studied relations between basic need satisfaction and perceived presence of contextual factors associated with teacher motivation drawn from the literature. Input from 1407 healthcare professionals was analyzed. PC healthcare professionals felt most autonomous, UH healthcare professionals felt most competent, and DTH healthcare professionals felt most related. Regardless of work context, teachers involved in educational design and who perceived more appreciation and developmental opportunities for teaching reported higher feelings of autonomy, competence, and relatedness in teaching, as did teachers who indicated that teaching was important at their job application. Perceived facilitators for teaching were associated with feeling more autonomous and related. These results can be utilized in a variety of healthcare contexts for improving teaching-related basic need satisfaction. Recommendations for practice include involving different healthcare professionals in educational development and coordination, forming communities of teachers across healthcare contexts, and addressing healthcare professionals' intentions to be involved in education during job interviews.

How is self-regulated learning documented in e-portfolios of trainees? A content analysis.

BACKGROUND: It is assumed that portfolios contribute to self-regulated learning (SRL). Presence of these SRL processes within the documentation kept in portfolios is presupposed in common educational practices, such as the assessment of reflective entries. However, questions can be asked considering the presence of SRL within portfolios. The aim of this study was to gain insight into the documentation of SRL processes within the electronic (e)-portfolio content of medical trainees. SRL consists of numerous processes, for this study the focus was on self-assessment via reflection and feedback, goal-setting and planning, and monitoring, as these are the processes that health professions education research mentions to be supported by portfolios. METHODS: A database containing 1022 anonymous e-portfolios from General Practitioner trainees was used to provide descriptive statistics of the various available e-portfolio forms. This was followed by a quantitative content analysis of 90 e-portfolios, for which, a codebook was constructed to rate the documentation of the included SRL processes. RESULTS: The numbers of forms in the e-portfolios varied to a great extent. Content analysis showed a limited documentation of reflective entries, and available entries mainly described events and experiences without explanations and context. Feedback was generally limited to comments on what went well and lacked specificity, context and suggestions for future action. Learning goals and plans were short of specificity, but did contain challenging topics and different goals were compatible with each other. 75% of the e-portfolios showed (limited) signs of monitoring. CONCLUSIONS: The e-portfolio content showed limited documentation of SRL processes. As documentation of SRL requires time and asks for a high level of introspection and writing skills, one cannot expect documentation of SRL processes to appear in e-portfolio content without efforts.

Assessment of medical students' integrated clinical communication skills: development of a tailor-made assessment tool.

BACKGROUND: Since patient-centered communication is directly connected to clinical performance, it should be integrated with medical knowledge and clinical skills. Therefore, clinical communication skills should be trained and assessed as an integral part of the student's clinical performance. We were unable to identify a tool, which helps when assessing patient-centered communication skills as an integrated component of medical history taking ('the integrated medical interview'). Therefore, we decided to design a new tailor-made assessment tool, the BOCC (BeOordeling Communicatie en Consultvoering (Dutch), Assessment of Communication and Consultation (English) to help raters assess students' integrated clinical communication skills with the emphasis on patient-centred communication combined with the correct medical content. This is a first initiative to develop such a tool, and this paper describes the first steps in this process. METHODS: We investigated the tool in a group of third-year medical students (n = 672) interviewing simulated patients. Internal structure and internal consistency were assessed. Regression analysis was conducted to investigate the relationship between scores on the instrument and general grading. Applicability to another context was tested in a group of fourth-year medical students (n = 374). RESULTS: PCA showed five components (Communication skills, Problem clarification, Specific History, Problem influence and Integration Skills) with various Cronbach's alpha scores. The component Problem Clarification made the strongest unique contribution to the grade prediction. Applicability was good when investigated in another context. CONCLUSIONS: The BOCC is designed to help raters assess students' integrated communication skills. It was assessed on internal structure and internal consistency. This tool is the first step in the assessment of the integrated medical interview and a basis for further investigation to reform it into a true measurement instrument on clinical communication skills.

Students' experiences with a longitudinal skills training program on breaking bad news: A follow-up study.

OBJECTIVE: Breaking bad news (BBN) should be trained, preferably early and following a helical model with multiple sessions over time, including feedback on performance. It's unclear how medical students evaluate such an approach. METHODS: We gathered student opinions regarding a helical BBN training programme, the feedback and emotional support they received, and the applicability of the skills training immediately after BBN skills training (Q1) and after finishing their clinical clerkships (Q2). RESULTS: Students find a helical curriculum useful, but this declines on follow-up. At Q2 students report less satisfaction with the amount of feedback and emotional support they received and report that the skills training was less applicable in clinical practice compared to what they reported at Q1. CONCLUSION: A helical BBN training programme with early exposure seems to lead to a shift from students being unconsciously incompetent to consciously incompetent. Students would have appreciated more emotional support and feedback. PRACTICE IMPLICATIONS: We recommend more feedback and emotional support after BBN during clerkships. The gap between classroom and practice can be diminished by emphasizing real life role play and clinical role models should demonstrate continuity and agreement between the skills that are taught and those that are used in clinical practice.

Herpes simplex virus oesophagitis in a pregnant woman.

Herpes simplex virus (HSV) oesophagitis is well described in immunocompromised patients. In immunocompetent individuals HSV oesophagitis is rare. We present a case of HSV oesophagitis in a pregnant woman. A possible explanation for HSV oesophagitis during pregnancy is the decreased cellular immunity, leading to an increased frequency and severity of viral infections. Antiviral therapy is advocated in pregnancy.

Excess mortality emerges after 10 years in an inception cohort of early rheumatoid arthritis.

OBJECTIVE: To investigate mortality rates, causes of death, time trends in mortality, prognostic factors for mortality, and the relationship between disease activity and mortality over a 23-year period in an inception cohort of rheumatoid arthritis (RA) patients. METHODS: A prospective inception cohort of RA patients diagnosed between January 1985 and October 2007 was followed for up to 23 years after diagnosis. Excess mortality was analyzed by comparing the observed mortality in the RA cohort with the expected mortality based on the general population of The Netherlands, matched for age, sex, and calendar year. Period analysis was used to examine time trends in survival across calendar time. Prognostic factors for mortality and the influence of the time-varying Disease Activity Score in 28 joints (DAS28) on mortality were analyzed using multivariable Cox proportional hazards models. Causes of death were analyzed. RESULTS: Of the 1,049 patients in the cohort, 207 patients died. Differences in observed and expected mortality emerged after 10 years of followup. No improvement in survival was noted over calendar time. Significant baseline predictors of survival were sex, age, rheumatoid factor, disability, and comorbidity. Higher levels of DAS28 over time, adjusted for age, were associated with lower survival rates, more so in men (hazard ratio [HR] 1.58, 95% confidence interval [95% CI] 1.35-1.85) than in women (HR 1.21, 95% CI 1.04-1.42). CONCLUSION: Excess mortality in RA emerged after 10 years of disease duration. Absolute survival rates have not improved in the last 23 years and a trend toward a widening mortality gap between RA patients and the general population was visible. Higher disease activity levels contribute to premature death in RA patients.

Influence of age on the outcome of antitumour necrosis factor alpha therapy in rheumatoid arthritis.

OBJECTIVE: To investigate the influence of age on the effectiveness and tolerance of antitumour necrosis factor alpha (TNFalpha) therapy in rheumatoid arthritis (RA). METHODS: 730 patients of the Dutch Rheumatoid Arthritis Monitoring (DREAM) register were categorised into three groups according to their age at initiation of anti-TNFalpha therapy (<45, 45-65 and >65 years). Effectiveness of anti-TNFalpha therapy was primarily assessed by longitudinal analysis of the DAS28 during the first 12 months of treatment. RESULTS: Improvement in disease activity and physical functioning was significantly less in elderly patients, correcting for relevant confounders. Elderly patients reached the EULAR categories of good responders and remission less often than younger patients. Drug survival, co-medication use and tolerance were comparable between the three age groups. CONCLUSION: Anti-TNFalpha therapy significantly reduced disease activity in all age groups of patients; however, it appeared less effective in elderly compared with younger RA patients.

Disease activity as a risk factor for myocardial infarction in rheumatoid arthritis.

OBJECTIVE: Patients with rheumatoid arthritis (RA) are at greater risk of developing coronary heart disease than the general population. Systemic inflammation may contribute to this risk. This study investigated whether the level of disease activity is associated with the risk of developing myocardial infarction (MI) in patients with RA. METHODS: A case-control study was performed within a large prospective cohort of patients with RA. Cases were patients who developed their first MI after the diagnosis of RA, controls were patients with RA without MI. Cases and controls had similar RA disease duration. Traditional and disease-specific risk factors for MI were collected and a time-averaged disease activity score (DAS28) was calculated. The data were analysed using conditional logistic regression analysis. RESULTS: Cases of MI were significantly older, were more often male, with higher body mass index (BMI) and total cholesterol and lower high-density lipoprotein (HDL) serum levels than controls. Time-averaged disease activity was similar for cases and controls. The raw odds ratio for MI in patients with a "high" (>4.0) versus a "low" (

Influence of age and gender on the 28-joint Disease Activity Score (DAS28) in rheumatoid arthritis.

OBJECTIVES: To investigate the influence of age and gender on the components of the 28-joint Disease Activity Score (DAS28) in patients with rheumatoid arthritis (RA), and to clarify whether a high DAS28 can be equally interpreted in all age groups, independent of gender. METHODS: A prospective cohort of 553 patients with RA was studied for approximately 20 years after diagnosis. The single measures of disease activity and the share of different components of the DAS28 (eg, erythrocyte sedimentation rate; ESR) were analysed and compared between three age groups (<45, 45-65 and >65 years) and per gender, using analysis of variance (ANOVA). The performance of the DAS28 and its components was explored in moderate to high and low DAS28 categories. Linear mixed model analysis was used to design the models best predicting ESR and the share of ESR. RESULTS: ESR significantly increased with age, independent of other variables of disease activity. This increase was more pronounced in male than in female patients. Nevertheless, the share of ESR increased with age only in male patients with a low DAS28 (<3.2). If the DAS28 score was >3.2, age and gender did not have a significant effect on any components of the DAS28. C-reactive protein (CRP) and DAS28(CRP) were not influenced by age. CONCLUSIONS: A high DAS28 was found to perform equally in all age groups, in men and women, despite the elevating effect of age on ESR. In elderly men with low disease activity, remission rate could be underestimated by an elevated ESR.

[Alendronate more effective than alfacalcidol in the prevention of osteoporosis in patients with rheumatic disease who are starting glucocorticoid therapy]. / Alendroninezuur effectiever dan alfacalcidol voor preventie van osteoporose bij patiënten met een reumatische ziekte die starten met glucocorticoïdtherapie.

OBJECTIVE: To compare the effects of alendronate and alfacalcidol in the prevention ofglucocorticoid-related osteoporosis in patients with a rheumatic disease. DESIGN: Randomised, double-blind, double-placebo clinical trial (www. clinicaltrials.gov; number: NCT00138983). METHODS: A total of 201 patients with rheumatic disease who were starting glucocorticoid treatment at a daily dose that was equivalent to at least 7.5 mg of prednisone were randomised to alendronate (10 mg) and a placebo capsule ofalfacalcidol daily (n = 100) or alfacalcidol (1 microg) and a placebo tablet ofalendronate daily (n = 101) for 18 months. Primary outcome was change in lumbar spine bone mineral density at 18 months. The main secondary outcome was the incidence of morphometrically confirmed vertebral deformities. RESULTS: Overall, 163 patients completed the study. The bone mineral density of the lumbar spine increased by 2.1% (95% CI: 1.1-3.1) in the alendronate group and decreased by 1.9% (95% CI: -3.I--0.7) in the alfacalcidol group. At 18 months the mean difference in change in bone mineral density between the two groups was 4.0% (95% CI: 2.4-5-5). Three patients in the alendronate group had a new vertebral deformity, compared with 8 patients in the alfacalcidol group, including 5 symptomatic vertebral fractures in 3 patients; the hazard ratio was 0.4 (95% CI: 0.1-1.4). CONCLUSION: Alendronate was more effective than alfacalcidol in preventing glucocorticoid-induced bone loss during this 18-month trial in patients with rheumatic diseases who were starting glucocorticoid treatment.

Starting learning in medical practice: an evaluation of a new Introductory Clerkship.

The transition from undergraduate medical education to learning in clinical clerkships can be difficult for students. Learning in clinical practice requires awareness of learning opportunities and goals, active elaboration and reflection. Staff should provide students with guidance to learn from their experiences. A new Introductory Clerkship was designed to facilitate the start of goal-oriented, active and reflective work-based learning. This four-week clerkship is a result of the cooperation of six major specialties in the university hospital. The innovations included explicitly formulated goals, a description of the student's activities in daily practice and of the staff's role, group meetings, a logbook, a halfway formative interview and a final summative interview. The aim of this study was to investigate to what extent the innovations of the new Introductory Clerkship were implemented and how students and residents valued them. Two questionnaires were constructed: one was administered to students (n = 54) and the other to residents (n = 27). Students considered participation in daily practice very instructive, although more observations of history taking and physical examination are wanted. The interviews and group meetings promote students' learning. Use of the logbook needs improvement. Residents perceived a shortage of time and would appreciate more participation of staff members, as well as a better preparation for supervising tasks. Overall, the study demonstrates that it is possible to introduce innovations in clinical clerkships to improve the learning environment of work-based learning.

Hypothalamic-pituitary-adrenal axis activity in patients with rheumatoid arthritis.

OBJECTIVE: To study the hypothalamic-pituitary-adrenal (HPA) axis in patients with rheumatoid arthritis (RA). METHODS: Fifty patients with RA participated in 3 groups: recent onset active RA (n = 20), longstanding active RA (n = 20) and long-standing RA in remission (n = 10), and were compared with 20 healthy controls. The activity of the HPA-axis was assessed under basal conditions and in response to stress (insulin tolerance test, ITT). In addition, patients with recent onset RA underwent a corticotropin releasing hormone (CRH) test and a dexamethasone suppression test. Plasma levels of interleukin (IL)-1beta, tumor necrosis factor-alpha (TNF-alpha) and IL-6 were also measured. RESULTS: Basal plasma, salivary and urinary cortisol levels and plasma adrenocorticotropic hormone (ACTH) levels were not different between patients with RA and healthy controls. During the ITT, cortisol levels were consistently lower in RA patients than in healthy controls. ACTH levels during the ITT were not different between patients with RA and healthy controls. ACTH and cortisol responses to CRH were assessed only in patients with recent onset RA and were found to be within normal limits. Basal circulating plasma IL-6 levels were significantly higher in patients with active RA than in the other groups. CONCLUSION: Under the standardized conditions of the ITT, patients with RA have decreased plasma cortisol levels compared to healthy controls, despite elevated levels of IL-6. The defect is probably located at the adrenal level and may be of pathogenetic significance for the development of chronic arthritis.

Decreased prolactin response to hypoglycaemia in patients with rheumatoid arthritis: correlation with disease activity.

OBJECTIVE: To compare basal and stimulated prolactin levels between patients with rheumatoid arthritis and healthy controls, and to assess the effects of antirheumatic treatment on prolactin concentrations. METHODS: Serum prolactin was assessed under basal conditions and during an insulin tolerance test (ITT) in 20 patients with recently diagnosed active rheumatoid arthritis and 20 age and sex matched controls. The patients were reassessed after two weeks' treatment with naproxen and after six months' additional treatment with either sulfasalazine or methotrexate. Disease activity was assessed by the disease activity score (DAS). RESULTS: Basal levels of prolactin were not significantly different between patients with rheumatoid arthritis and controls. Prolactin responses to hypoglycaemia were less in untreated rheumatoid patients than in controls. DAS scores correlated negatively with the area under the curve (AUC) for prolactin concentrations during the ITT. Treatment with naproxen for two weeks did not influence either basal or stimulated prolactin levels. After six months of antirheumatic treatment, prolactin responses to hypoglycaemia increased significantly to levels observed in controls. At the same time point, DAS had improved considerably. The improvement correlated with the increase in AUC of prolactin during the ITT (r = 0.48; p = 0.05). CONCLUSIONS: Patients with active rheumatoid arthritis have a decreased prolactin response to hypoglycaemia induced stress. The response recovers following treatment with antirheumatic drugs.

Influence of guideline adherence on outcome in a randomised controlled trial on the efficacy of methotrexate with folate supplementation in rheumatoid arthritis.

OBJECTIVE: To study the influence of rheumatologists' adherence to a methotrexate guideline on efficacy and toxicity in the treatment of rheumatoid arthritis. METHODS: In a 48 week randomised controlled trial of methotrexate, comparing folates with placebo, rheumatologists were advised on methotrexate dosage using a guideline reflecting daily practice. The influence of guideline non-adherence on outcome was analysed using generalised estimating equations and survival analysis. RESULTS: In 51% of the 411 study patients the guidelines were always followed. Non-adherence resulted in lower doses of methotrexate in 25% of cases, and higher doses in 24%. The reduction in the disease activity score was significantly greater (mean -0.4; p = 0.0085) in the adherent group than in the "low dose" group; the "high dose" group did not differ from the adherent group. Dropout caused by severe adverse events did not differ between the three groups. CONCLUSIONS: There is an indication that adherence to guidelines on methotrexate dosage may benefit patients with rheumatoid arthritis by improving disease activity without increasing toxicity. For definite proof, a randomised controlled trial comparing guideline supported dosing with usual care is needed.