Seeing the Other: How Residents Expand Their Perspective by Learning With the Arts.

Background: Engaging with the arts can enrich medical education by fostering transformative learning, reflection, and a holistic view of the patient. Objective: To explore the development of professional competence of residents in prolonged arts-based medical education. Methods: We followed residents (n=99) of various specialties as they engaged in arts-based learning through creative and reflective assignments such as painting, sculpting, and formal analysis. Participants were interviewed about their learning process and experiences, one-on-one and in small groups, by independent researchers using short, semistructured interviews. We used grounded theory to inform an iterative process for data collection and analysis over the course of 3 years (2016-2018). Results: Seven themes were constructed, which showed that (1) slowing down education provides room for reflection; (2) absence of judgment and rules sparks experimentation; (3) engaging with emotions fostered reflection and motivation; (4) the artists' methods provided a perspective change; (5) a holistic view on the patient emerged; (6) residents understood the need to take control over their professional development; and (7) there were barriers to overcome in terms of hierarchy and expectations. Our investigation shows that interns and residents undergo a perspective transformation. Key to the development of the physicians in training is the open and affective nature of the arts in education. Conclusions: Arts-based learning results in a new perspective for physicians in training in line with patient-centered health care and self-directed learning.

A prediction model for primary aldosteronism when the salt loading test is inconclusive.

OBJECTIVE: To develop a prediction model to confirm or exclude primary aldosteronism (PA) in patients with an inconclusive salt loading test (SLT). CONTEXT: Diagnosis in patients with a suspicion of PA can be confirmed using an SLT. In case of inconclusive test results the decision about how to manage the patient is usually based on contextual clinical data. DESIGN: We included a retrospective cohort of 276 patients in the final analysis. METHODS: All patients underwent an SLT between 2005 and 2016 in our university medical center. The SLT was inconclusive (post-infusion aldosterone levels 140-280 pmol/L) in 115 patients. An expert panel then used contextual clinical data to diagnose PA in 45 of them. Together with 101 patients with a positive SLT this resulted in a total of 146 patients with PA. A total of 11 variables were used in a multivariable logistic regression analysis. We assessed internal validity by bootstrapping techniques. RESULTS: The following variables were independently associated with PA: more intense potassium supplementation, lower plasma potassium concentration, lower plasma renin concentration before SLT and higher plasma aldosterone concentration after SLT. The resulting prediction model had a sensitivity of 84.4% and a specificity of 94.3% in patients with an inconclusive SLT. The positive and negative predictive values were 90.5 and 90.4%, respectively. CONCLUSIONS: We developed a prediction model for the diagnosis of PA in patients with an inconclusive SLT that results in a diagnosis that was in high agreement with that of an expert panel.

The cost-effectiveness of bevacizumab, ranibizumab and aflibercept for the treatment of age-related macular degeneration-A cost-effectiveness analysis from a societal perspective.

BACKGROUND: The discussion on the use of bevacizumab is still ongoing and often doctors are deterred from using bevacizumab due to legal or political issues. Bevacizumab is an effective, safe and inexpensive treatment option for neovascular age-related macular degeneration (AMD), albeit unregistered for the disease. Therefore, in some countries ophthalmologists use the equally effective but expensive drugs ranibizumab and aflibercept. We describe the economic consequences of this dilemma surrounding AMD treatment from a societal perspective. METHODS: We modelled cost-effectiveness of treatment with ranibizumab (as-needed), aflibercept (bimonthly) and bevacizumab (as-needed). Effectiveness was estimated by systematic review and meta-analysis. The drug with the most favourable cost-effectiveness profile compared to bevacizumab was used for threshold analyses. First, we determined how much we overspend per injection. Second, we calculated the required effectiveness to justify the current price and the reasonable price for a drug leading to optimal vision. Finally, we estimated how much Europe overspends if bevacizumab is not first choice. RESULTS: Bevacizumab treatment costs €27,087 per year, about €4,000 less than aflibercept and €6,000 less than ranibizumab. With similar effectiveness for all drugs as shown by meta-analysis, bevacizumab was the most cost-effective. Aflibercept was chosen for threshold analyses. Aflibercept costs €943 per injection, but we determined that the maximum price to be cost-effective is €533. Alternatively, at its current price, aflibercept should yield about twice the visual gain. Even when optimal vision can be achieved, the maximum price for any treatment is €37,453 per year. Most importantly, Europe overspends €335 million yearly on AMD treatment when choosing aflibercept over bevacizumab. CONCLUSION: Bevacizumab is the most cost-effective treatment for AMD, yet is not the standard of care across Europe. The registered drugs ranibizumab and aflibercept lead to large overspending without additional health benefits. Health authorities should consider taking steps to implement bevacizumab into clinical practice as first choice.

INTEGRATE-HTA: A LOW- AND MIDDLE-INCOME COUNTRY PERSPECTIVE.

OBJECTIVES: The INTEGRATE-HTA project recommends that complexity be taken into account when conducting health technology assessments (HTAs) and suggests a five-step process for doing that. This study examines whether the approach suggested by INTEGRATE-HTA could be useful, appropriate, and feasible in the context of low- and middle-income countries (LMIC) given some of the typical challenges that healthcare systems face in those countries. METHODS: A nonexhaustive literature review was performed on the implementation in low and middle income countries of the five aspects recommended by the INTEGRATE-HTA project, using the following search terms: national health planning, health sector strategy, health sector performance, assessment criteria, health (management) information, complexity, context, stakeholder consultation. RESULTS: HTA is being practiced in LMIC in various ways and through different mechanisms, for example in health sector reviews, even though it is usually not referred to as HTA. It does not necessarily follow the five steps distinguished in the INTEGRATE-HTA model (scoping; defining the initial logic model; providing concepts and methods to identify, collect, and synthesize evidence in relation to various dimensions; extracting and presenting evidence in respect of agreed assessment criteria; providing guidance to draw conclusions and formulate recommendations). CONCLUSIONS: The conditions for functional HTA are not always fulfilled in LMICs. At least four aspects would require special attention: (a) the scope and quality of routine health information that can support and be fed into health technology assessments and strategic planning; (b) consensus on health system performance assessment frameworks and their main criteria, in particular the inclusion of social disparities/equity and sustainability;

Uncertainty on the effectiveness and safety of rivaroxaban in premenopausal women with atrial fibrillation: empirical evidence needed.

BACKGROUND: Novel anticoagulations (NOACs) are increasingly prescribed for the prevention of stroke in premenopausal women with atrial fibrillation. Small studies suggest NOACs are associated with a higher risk of abnormal uterine bleeds than vitamin K antagonists (VKAs). Because there is no direct empirical evidence on the benefit/risk profile of rivaroxaban compared to VKAs in this subgroup, we synthesize available indirect evidence, estimate decision uncertainty on the treatments, and assess whether further research in premenopausal women is warranted. METHODS: A Markov model with annual cycles and a lifetime horizon was developed comparing rivaroxaban (the most frequently prescribed NOAC in this population) and VKAs. Clinical event rates, associated quality adjusted life years, and health care costs were obtained from different sources and adjusted for gender, age, and history of stroke. A Monte Carlo simulation with 10,000 iterations was then performed for a hypothetical cohort of premenopausal women, estimated to be reflective of the population of premenopausal women with AF in The Netherlands. RESULTS: In the simulation, rivaroxaban is the better treatment option for the prevention of ischemic strokes in premenopausal women in 61% of the iterations. Similarly, this is 98% for intracranial hemorrhages, 24% for major abnormal uterine bleeds, 1% for minor abnormal uterine bleeds, 9% for other major extracranial hemorrhages, and 23% for other minor extracranial hemorrhages. There is a 78% chance that rivaroxaban offers the most quality-adjusted life years. The expected value of perfect information in The Netherlands equals 122 quality-adjusted life years and 22 million Euros. CONCLUSIONS: There is a 22% risk that rivaroxaban offers a worse rather than a better benefit/risk profile than vitamin K antagonists in premenopausal women. Although rivaroxaban is preferred over VKAs in this population, further research is warranted, and should preferably take the shape of an internationally coordinated registry study including other NOACs.

Discontinuation of antidepressant medication after mindfulness-based cognitive therapy for recurrent depression: randomised controlled non-inferiority trial.

BACKGROUND: Mindfulness-based cognitive therapy (MBCT) and maintenance antidepressant medication (mADM) both reduce the risk of relapse in recurrent depression, but their combination has not been studied. AIMS: To investigate whether MBCT with discontinuation of mADM is non-inferior to MBCT+mADM. METHOD: A multicentre randomised controlled non-inferiority trial (ClinicalTrials.gov:NCT00928980). Adults with recurrent depression in remission, using mADM for 6 months or longer (n= 249), were randomly allocated to either discontinue (n= 128) or continue (n= 121) mADM after MBCT. The primary outcome was depressive relapse/recurrence within 15 months. A confidence interval approach with a margin of 25% was used to test non-inferiority. Key secondary outcomes were time to relapse/recurrence and depression severity. RESULTS: The difference in relapse/recurrence rates exceeded the non-inferiority margin and time to relapse/recurrence was significantly shorter after discontinuation of mADM. There were only minor differences in depression severity. CONCLUSIONS: Our findings suggest an increased risk of relapse/recurrence in patients withdrawing from mADM after MBCT.

Adding mindfulness-based cognitive therapy to maintenance antidepressant medication for prevention of relapse/recurrence in major depressive disorder: Randomised controlled trial.

BACKGROUND: Mindfulness-based cognitive therapy (MBCT) and maintenance antidepressant medication (mADM) both reduce the risk of relapse in recurrent depression, but their combination has not been studied. Our aim was to investigate whether the addition of MBCT to mADM is a more effective prevention strategy than mADM alone. METHODS: This study is one of two multicenter randomised trials comparing the combination of MBCT and mADM to either intervention on its own. In the current trial, recurrently depressed patients in remission who had been using mADM for 6 months or longer (n=68), were randomly allocated to either MBCT+mADM (n=33) or mADM alone (n=35). Primary outcome was depressive relapse/recurrence within 15 months. Key secondary outcomes were time to relapse/recurrence and depression severity. Analyses were based on intention-to-treat. RESULTS: There were no significant differences between the groups on any of the outcome measures. LIMITATIONS: The current study included patients who had recovered from depression with mADM and who preferred the certainty of continuing medication to the possibility of participating in MBCT. Lower expectations of mindfulness in the current trial, compared with the parallel trial, may have caused selection bias. In addition, recruitment was hampered by the increasing availability of MBCT in the Netherlands, and even about a quarter of participants included in the trial who were allocated to the control group chose to get MBCT elsewhere. CONCLUSIONS: For this selection of recurrently depressed patients in remission and using mADM for 6 months or longer, MBCT did not further reduce their risk for relapse/recurrence or their (residual) depressive symptoms.

Zinc supplementation inhibits complement activation in age-related macular degeneration.

UNLABELLED: Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. AMD is a multifactorial disorder but complement-mediated inflammation at the level of the retina plays a pivotal role. Oral zinc supplementation can reduce the progression of AMD but the precise mechanism of this protective effect is as yet unclear. We investigated whether zinc supplementation directly affects the degree of complement activation in AMD and whether there is a relation between serum complement catabolism during zinc administration and the complement factor H (CFH) gene or the Age-Related Maculopathy susceptibility 2 (ARMS2) genotype. In this open-label clinical study, 72 randomly selected AMD patients in various stages of AMD received a daily supplement of 50 mg zinc sulphate and 1 mg cupric sulphate for three months. Serum complement catabolism-defined as the C3d/C3 ratio-was measured at baseline, throughout the three months of supplementation and after discontinuation of zinc administration. Additionally, downstream inhibition of complement catabolism was evaluated by measurement of anaphylatoxin C5a. Furthermore, we investigated the effect of zinc on complement activation in vitro. AMD patients with high levels of complement catabolism at baseline exhibited a steeper decline in serum complement activation (p<0.001) during the three month zinc supplementation period compared to patients with low complement levels. There was no significant association of change in complement catabolism and CFH and ARMS2 genotype. In vitro zinc sulphate directly inhibits complement catabolism in hemolytic assays and membrane attack complex (MAC) deposition on RPE cells. This study provides evidence that daily administration of 50 mg zinc sulphate can inhibit complement catabolism in AMD patients with increased complement activation. This could explain part of the mechanism by which zinc slows AMD progression. TRIAL REGISTRATION: The Netherlands National Trial Register NTR2605.

Toward an evidence-based step-up approach in diagnosing diverticulitis.

BACKGROUND: The lack of pathognomonic findings and the chance of complicated disease have resulted in the widespread use of additional imaging to diagnose acute colonic diverticulitis (ACD). The added value of additional imaging in the diagnostic workup of patients suspected of ACD is not well defined. AIMS: The aim of this study was to systematically review the literature of the accuracy of the clinical evaluation and diagnostic modalities for patients with suspected ACD, to come to an evidence-based approach to diagnose ACD. METHODS: A systematic review and meta-analysis of studies that reported diagnostic accuracy of the clinical diagnosis and diagnostic modalities in patients with suspected diverticulitis were performed. Study quality was assessed with the STARD checklist. True-positive, true-negative, false-positive, and false-negative findings were extracted and pooled estimates of sensitivity and specificity per diagnostic test were calculated, if applicable. RESULTS: The overall quality of the studies reporting the diagnostic accuracy of the clinical diagnosis, contrast enema and magnetic resonance imaging (MRI) were moderate to poor and not suitable for meta-analysis. Sensitivity of the clinical diagnosis varied between 64% and 68%. Ultrasound (US) and computed tomography (CT) studies were eligible for meta-analysis. Summary sensitivity estimates for US were 90% (95% CI: 76-98%) versus 95% (95% CI: 91-97%) for CT (p = 0.86). Summary specificity estimates for US were 90% (95% CI: 86-94%) versus 96% (95% CI: 90-100%) for CT (p = 0.04). Sensitivity for MRI was 98% and specificity varied between 70% and 78%. Sensitivity of contrast enema studies varied between 80% and 83%. CONCLUSION: In two-thirds of the patients, the diagnosis of ACD can be made based on clinical evaluation alone. In one-third of the patients, additional imaging is a necessity to establish the diagnosis. US and CT are comparable in diagnosing diverticulitis and superior to other modalities. CT has the advantage of higher specificity and the ability to identify alternative diagnoses. The role of MRI is not yet clear in diagnosing ACD. Contrast enema is considered an obsolete imaging technique to diagnose ACD based on lower sensitivity and specificity than US and CT. A step-up approach with CT performed after an inconclusive or negative US, seems a logical and safe approach for patients suspected of ACD.

Mindfulness-based cognitive therapy for patients with medically unexplained symptoms: a cost-effectiveness study.

OBJECTIVE: Our aim was to assess cost-effectiveness of mindfulness-based cognitive therapy (MBCT) compared with enhanced usual care (EUC) in treating patients with persistent medically unexplained symptoms(MUS). METHODS: A full economic evaluation with a one year time horizon was performed from a societal perspective. Costs were assessed by prospective cost diaries. Health-related Quality of Life was measured using SF-6D. Outcomes were costs per Quality-Adjusted Life Year (QALY). Bootstrap simulations were performed to obtain mean costs, QALY scores and incremental cost-effectiveness ratios (ICERs). RESULTS: MBCT participants (n=55) had lower hospital costs and higher mental health care costs than patients who received EUC (n=41). Mean bootstrapped costs for MBCT were €6269, and €5617 for EUC (95% uncertainty interval for difference: -€1576; €2955). QALYs were 0.674 for MBCT and 0.663 for EUC. MBCT was on average more effective and more costly than EUC, resulting in an ICER of €56,637 per QALY gained. At a willingness to pay of €80,000 per QALY, the probability that MBCT is cost-effective is 57%. CONCLUSION: Total costs were not statistically significantly different between MBCT and EUC. However, MBCT seemed to cause a shift in the use of health care resources as mental health care costs were higher and hospital care costs lower in the MBCT condition. Due to the higher drop-out in the EUC condition the cost-effectiveness of MBCT might have been underestimated. The shift in health care use might lead to more effective care for patients with persistent MUS. The longer-term impact of MBCT for patients with persistent MUS needs to be further studied.

Preventing relapse in recurrent depression using mindfulness-based cognitive therapy, antidepressant medication or the combination: trial design and protocol of the MOMENT study.

BACKGROUND: Depression is a common psychiatric disorder characterized by a high rate of relapse and recurrence. The most commonly used strategy to prevent relapse/recurrence is maintenance treatment with antidepressant medication (mADM). Recently, it has been shown that Mindfulness-Based Cognitive Therapy (MBCT) is at least as effective as mADM in reducing the relapse/recurrence risk. However, it is not yet known whether combination treatment of MBCT and mADM is more effective than either of these treatments alone. Given the fact that most patients have a preference for either mADM or for MBCT, the aim of the present study is to answer the following questions. First, what is the effectiveness of MBCT in addition to mADM? Second, how large is the risk of relapse/recurrence in patients withdrawing from mADM after participating in MBCT, compared to those who continue to use mADM after MBCT? METHODS/DESIGN: Two parallel-group, multi-center randomized controlled trials are conducted. Adult patients with a history of depression (3 or more episodes), currently either in full or partial remission and currently treated with mADM (6 months or longer) are recruited. In the first trial, we compare mADM on its own with mADM plus MBCT. In the second trial, we compare MBCT on its own, including tapering of mADM, with mADM plus MBCT. Follow-up assessments are administered at 3-month intervals for 15 months. Primary outcome is relapse/recurrence. Secondary outcomes are time to, duration and severity of relapse/recurrence, quality of life, personality, several process variables, and incremental cost-effectiveness ratio. DISCUSSION: Taking into account patient preferences, this study will provide information about a) the clinical and cost-effectiveness of mADM only compared with mADM plus MBCT, in patients with a preference for mADM, and b) the clinical and cost-effectiveness of withdrawing from mADM after MBCT, compared with mADM plus MBCT, in patients with a preference for MBCT. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00928980.

Non-compliance on the part of the professional community with a national guideline: an argumentative policy analysis.

In 1997, the National Health Insurance Board of the Netherlands (CVZ) introduced a guideline for the use of a new anti-epileptic drug, Lamotrigine. The goal was to limit the use of this relatively expensive drug to patients with difficult-to-treat epilepsy. A survey had shown that only a minority of neurologists were familiar with the guideline, and even fewer applied it in practice. In the present study, interviews were held with stakeholders to obtain a better understanding of why this policy measure failed. The results indicate that the problem definitions of policy maker and practicing neurologists differed widely, and that the policy measure was conflicting with certain professional beliefs. In such cases, the theory of argumentative policy predicts that policy is unlikely to succeed, unless policy makers take actions to ensure a greater congruence in interpretative frames between them and their target population.

Economic evaluation of folate supplementation during methotrexate treatment in rheumatoid arthritis.

OBJECTIVE: To determine cost-effectiveness of folic or folinic acid supplementation in patients with rheumatoid arthritis (RA) who started methotrexate (MTX) treatment. METHODS: An economic evaluation, performed alongside a randomized, double blind, placebo controlled trial with followup of 48 weeks. Patients started MTX with placebo (n = 137), folic acid (n = 133), or folinic acid (n = 141). Outcome measures were drug survival and quality-adjusted life-years (QALY), measured with the EuroQol questionnaire. Both medical and nonmedical costs were analyzed. RESULTS: Drug survival after 48 weeks was 60% for placebo, 81% for folic acid, and 87% for folinic acid. QALY during a 48 week period were 0.55 (95% CI 0.52-0.58) in the placebo group, 0.55 (95% CI 0.52-0.58) in the folic acid group, and 0.58 (95% CI 0.56-0.60) in the folinic acid group. Mean medical costs were 1398 US dollars (placebo), 1409 US dollars (folic acid), and 1776 US dollars (folinic acid). Mean total costs were 3339 US dollars, 3632 US dollars, and 3296 US dollars, respectively. CONCLUSION: In terms of resource deployment, no statistically significant difference was found between the 3 strategies. The preferred strategy consists of folic acid supplementation because of improved drug survival.