Targeted next-generation sequencing has incremental value in the diagnostic work-up of patients with suspect pancreatic masses; a multi-center prospective cross sectional study.

BACKGROUND: The diagnostic process of patients with suspect pancreatic lesions is often lengthy and prone to repeated diagnostic procedures due to inconclusive results. Targeted Next-Generation Sequencing (NGS) performed on cytological material obtained with fine needle aspiration (FNA) or biliary duct brushing can speed up this process. Here, we study the incremental value of NGS for establishing the correct diagnosis, and subsequent treatment plan in patients with inconclusive diagnosis after regular diagnostic work-up for suspect pancreatic lesions. METHODS: In this prospective cross-sectional cohort study, patients were screened for inclusion in four hospitals. NGS was performed with AmpliSeq Cancer Hotspot Panel v2 and v4b in patients with inconclusive cytology results or with an uncertain diagnosis. Diagnostic results were evaluated by the oncology pancreatic multidisciplinary team. The added value of NGS was determined by comparing diagnosis (malignancy, cystic lesion or benign condition) and proposed treatment plan (exploration/resection, neoadjuvant chemotherapy, follow-up, palliation or repeated FNA) before and after integration of NGS results. Final histopathological analysis or a 6-month follow-up period were used as the reference standard in case of surgical intervention or non-invasive treatment, respectively. RESULTS: In 50 of the 53 included patients, cytology material was sufficient for NGS analysis. Diagnosis before and after integration of NGS results differed in 24% of the patients. The treatment plan was changed in 32% and the diagnosis was substantiated by the NGS data in 44%. Repetition of FNA/brushing was prevented in 14% of patients. All changes in treatment plan were correctly made after integration of NGS. Integration of NGS increased overall diagnostic accuracy from 68% to 94%. INTERPRETATION: This study demonstrates the incremental diagnostic value of NGS in patients with an initial inconclusive diagnosis. Integration of NGS results can prevent repeated EUS/FNA, and can also rigorously change the final diagnosis and treatment plan.

Cumulative sum learning curves guiding multicenter multidisciplinary quality improvement of EUS-guided tissue acquisition of solid pancreatic lesions.

Background and study aims In this study, we evaluated the performance of community hospitals involved in the Dutch quality in endosonography team regarding yield of endoscopic ultrasound (EUS)-guided tissue acquisition (TA) of solid pancreatic lesions using cumulative sum (CUSUM) learning curves. The aims were to assess trends in quality over time and explore potential benefits of CUSUM as a feedback-tool. Patients and methods All consecutive EUS-guided TA procedures for solid pancreatic lesions were registered in five community hospitals between 2015 and  2018. CUSUM learning curves were plotted for overall performance and for performance per center. The American Society of Gastrointestinal Endoscopy-defined key performance indicators, rate of adequate sample (RAS), and diagnostic yield of malignancy (DYM) were used for this purpose. Feedback regarding performance was provided on multiple occasions at regional interest group meetings during the study period. Results A total of 431 EUS-guided TA procedures in 403 patients were included in this study. The overall and per center CUSUM curves for RAS improved over time. CUSUM curves for DYM revealed gradual improvement, reaching the predefined performance target (70 %) overall, and in three of five contributing centers in 2018. Analysis of a sudden downslope development in the CUSUM curve of DYM in one center revealed temporary absence of a senior cytopathologist to have had a temporary negative impact on performance. Conclusions CUSUM-derived learning curves allow for assessment of best practices by comparison among peers in a multidisciplinary multicenter quality improvement initiative and proved to be a valuable and easy-to-interpret means to evaluate EUS performance over time.

Associations Between Maternal Depression, Antidepressant Use During Pregnancy, and Adverse Pregnancy Outcomes: An Individual Participant Data Meta-analysis.

OBJECTIVE: To evaluate the associations of depressive symptoms and antidepressant use during pregnancy with the risks of preterm birth, low birth weight, small for gestational age (SGA), and low Apgar scores. DATA SOURCES: MEDLINE, EMBASE, ClinicalTrials.gov, and PsycINFO up to June 2016. METHODS OF STUDY SELECTION: Data were sought from studies examining associations of depression, depressive symptoms, or use of antidepressants during pregnancy with gestational age, birth weight, SGA, or Apgar scores. Authors shared the raw data of their studies for incorporation into this individual participant data meta-analysis. TABULATION, INTEGRATION, AND RESULTS: We performed one-stage random-effects meta-analyses to estimate odds ratios (ORs) with 95% CIs. The 215 eligible articles resulted in 402,375 women derived from 27 study databases. Increased risks were observed for preterm birth among women with a clinical diagnosis of depression during pregnancy irrespective of antidepressant use (OR 1.6, 95% CI 1.2-2.1) and among women with depression who did not use antidepressants (OR 2.2, 95% CI 1.7-3.0), as well as for low Apgar scores in the former (OR 1.5, 95% CI 1.3-1.7), but not the latter group. Selective serotonin reuptake inhibitor (SSRI) use was associated with preterm birth among women who used antidepressants with or without restriction to women with depressive symptoms or a diagnosis of depression (OR 1.6, 95% CI 1.0-2.5 and OR 1.9, 95% CI 1.2-2.8, respectively), as well as with low Apgar scores among women in the latter group (OR 1.7, 95% CI 1.1-2.8). CONCLUSION: Depressive symptoms or a clinical diagnosis of depression during pregnancy are associated with preterm birth and low Apgar scores, even without exposure to antidepressants. However, SSRIs may be independently associated with preterm birth and low Apgar scores. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42016035711.

Vaginal Myomectomy and Total Vaginal Hysterectomy on Large Prolapsed Cervical Myoma: A Case Report.

Cervical myomas are benign tumors originating from cervical muscle tissue with a very rare incidence of only about 8% of all myomas. The surgical approach depends on the position of cervical myoma. This case report discusses a 44-year-old woman who complained of a lump discharge from her birth canal 6 months ago, and currently discharging from her vagina. We performed vaginal myomectomy, and the cervical myoma measuring 8 × 8 × 6 cm with solid consistency was removed. We continued with total vaginal hysterectomy. Post-operative recovery was progressing well. The histopathology report was consistent with leiomyoma. Large prolapsed cervical myoma can be disturbing and discomforting for many patients. It is relatively rare and can be successfully removed vaginally with minimal morbidity.

The relationship between burnout, personality traits, and medical specialty. A national study among Dutch residents.

Purpose: To examine the associations between residents' personality traits, type of specialty, and symptoms of burnout. Method: A cross-sectional online survey among Dutch residents was conducted (see Supplementary Material ). The 20-item Dutch translation of the Maslach Burnout Inventory was used to ascertain burnout. Personality traits were assessed with the 44-item Dutch Big Five Inventory. Logistic regression analyses, including all five personality traits, were used to assess associations with burnout. Analyses were stratified by specialties. Results: One thousand two hundred thirty one residents participated, 185 (15.0%) of whom met the criteria for burnout. Neuroticism was significantly associated with resident burnout in all specialties, more strongly in supportive (odds ratio (OR) 6.19, 95% CI 2.12-18.12) and surgical (OR 4.37, 95% CI 1.76-10.86) than in medical residents (OR 1.99, 95% CI 1.22-3.24). Extraversion was significantly associated with less burnout in surgical residents (OR 0.26, 95% CI 0.13-0.58). These findings remained highly significant after controlling for gender, overtime, autonomy at work, satisfaction between work and private life, and the perceived quality of the learning environment. Conclusions: Burnout risk was associated with personality traits in residents. Consistently, residents scoring high on neuroticism reported more burnout. Extraverted surgical residents were less susceptible to burnout. Residents scoring high on neuroticism may require more intense monitoring during their training years.

The learning environment and resident burnout: a national study.

INTRODUCTION: Concerns exist about the negative impact of burnout on the professional and personal lives of residents. It is suggested that the origins of burnout among residents are rooted in the learning environment. We aimed to evaluate the association between the learning environment and burnout in a national sample of Dutch residents. METHODS: We conducted a cross-sectional online survey among all Dutch residents in September 2015. We measured the learning environment using the three domain scores on content, organization, and atmosphere from the Scan of Postgraduate Educational Environment Domains (SPEED) and burnout using the Dutch version of the Maslach Burnout Inventory (UBOS-C). RESULTS: Of 1,231 responding residents (33 specialties), 185 (15.0%) met criteria for burnout. After adjusting for demographic (age, gender and marital status) and work-related factors (year of training, type of teaching hospital and type of specialty), we found a consistent inverse association between SPEED scores and the risk of burnout (aOR 0.54, 95% CI 0.46 to 0.62, p < 0.001). DISCUSSION: We found a strong and consistent inverse association between the perceived quality of the learning environment and burnout among residents. This suggests that the learning environment is of key importance in preventing resident burnout.

The relationship between work and home characteristics and work engagement in medical residents.

INTRODUCTION: Work engagement is important for medical residents and the healthcare organizations they work for. However, relatively little is known about the specific predictors of work engagement in medical residents. Therefore, we examined the associations of work and home characteristics, and work-home interference with work engagement in male and female residents. METHODS: This study was conducted on a nationwide sample of medical residents. In 2005, all Dutch medical residents (n = 5245) received a self-report questionnaire. Path analysis was used to examine the associations between the potential predictors and work engagement. RESULTS: In total, 2115 (41.1%) residents completed the questionnaire. Job characteristics, home characteristics and work-home interference were associated with work engagement. Important positive contributing factors of work engagement were opportunities for job development, mental demands at work, positive work-home interference and positive home-work interference. Important negative contributing factors were emotional demands at work and negative home-work interference. The influence of these factors on work engagement was similar in male and female residents. DISCUSSION: Opportunities for job development and having challenging work are of high relevance in enhancing work engagement. Furthermore, interventions that teach how to deal skilfully with emotional demands at work and home-work interference are expected to be the most effective interventions to enhance work engagement in medical residents.

The contribution of work characteristics, home characteristics and gender to burnout in medical residents.

Burnout is highly prevalent in medical residents. In order to prevent or reduce burnout in medical residents, we should gain a better understanding of contributing and protective factors of burnout. Therefore we examined the associations of job demands and resources, home demands and resources, and work-home interferences with burnout in male and female medical residents. This study was conducted on a nation-wide sample of medical residents. In 2005, all Dutch medical residents (n = 5245) received a self-report questionnaire on burnout, job and home demands and resources and work-home interference. Path analysis was used to examine the associations between job and home characteristics and work-home interference and burnout in both males and females. In total, 2115 (41.1 %) residents completed the questionnaire. In both sexes emotional demands at work and the interference between work and home were important contributors to burnout, especially when work interferes with home life. Opportunities for job development appeared to be an important protective factor. Other contributing and protective factors were different for male and female residents. In females, social support from family or partner seemed protective against burnout. In males, social support from colleagues and participation in decision-making at work seemed important. Effectively handling emotional demands at work, dealing with the interference between work and home, and having opportunities for job development are the most essential factors which should be addressed. However it is important to take gender differences into consideration when implementing preventive or therapeutic interventions for burnout in medical residents.

Effect of high salt diet on blood pressure and renal damage during vascular endothelial growth factor inhibition with sunitinib.

BACKGROUND: Antiangiogenic treatment with the multitargeted vascular endothelial growth factor (VEGF) receptor inhibitor sunitinib associates with a blood pressure (BP) rise and glomerular renal injury. Recent evidence indicates that VEGF derived from tubular cells is required for maintenance of the peritubular vasculature. In the present study, we focussed on tubular and glomerular pathology induced by sunitinib and explored whether a high salt (HS) diet augments the BP rise and renal abnormalities. METHODS: Normotensive Wistar Kyoto (WKY) rats were exposed to a normal salt (NS) or HS diet for 2 weeks and subsequently for 8 days to sunitinib or vehicle administration after which the rats were euthanized and kidneys excised. Mean arterial pressure (MAP) was telemetrically measured. Urine was sampled for proteinuria and endothelinuria, and blood for measurement of endothelin-1, creatinine and cystatin C. RESULTS: Compared with the NS diet, MAP rapidly rose by 27 ± 3 mmHg with the HS diet. On sunitinib, MAP rose further by 15 ± 1 with the NS and by 23 ± 4 mmHg with the HS diet (P < 0.05). The HS diet itself had no effect on proteinuria, endothelinuria or the plasma levels of endothelin-1, creatinine and cystatin C. Only with the HS diet, sunitinib administration massively increased proteinuria and endothelinuria and these two parameters were related (r = 0.50, P < 0.01). Likewise, renal glomerular pathology was enhanced during sunitinib with the HS diet, whereas tubulointerstitial injury or reduced peritubular capillary density did not occur. CONCLUSIONS: An HS diet induces a marked BP rise in WKY rats and exacerbates both the magnitude of the BP rise and glomerular injury induced by sunitinib.