Showing papers by "Albert Schweitzer Hospital published in 2018"

Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR.

Abstract: Daratumumab, a CD38 human monoclonal antibody, demonstrated significant clinical activity in combination with bortezomib and dexamethasone versus bortezomib and dexamethasone alone in the primary analysis of CASTOR, a phase 3 study in relapsed and/or refractory multiple myeloma A post hoc analysis based on treatment history and longer follow up is presented After 194 (range: 0-277) months of median follow up, daratumumab plus bortezomib and dexamethasone prolonged progression-free survival (median: 167 versus 71 months; hazard ratio, 031; 95% confidence interval, 024-039; P 12, ≤6, or >6 months), or cytogenetic risk Minimal residual disease-negative rates were >25-fold higher with daratumumab across subgroups The safety profile of daratumumab plus bortezomib and dexamethasone remained consistent with longer follow up Daratumumab plus bortezomib and dexamethasone demonstrated significant clinical activity across clinically relevant subgroups and provided the greatest benefit to patients treated at first relapse Trial registration: clinicaltrialsgov identifier: 02136134

Vertebroplasty versus sham procedure for painful acute osteoporotic vertebral compression fractures (VERTOS IV): randomised sham controlled clinical trial.

Abstract: Objective To assess whether percutaneous vertebroplasty results in more pain relief than a sham procedure in patients with acute osteoporotic compression fractures of the vertebral body. Design Randomised, double blind, sham controlled clinical trial. Setting Four community hospitals in the Netherlands, 2011-15. Participants 180 participants requiring treatment for acute osteoporotic vertebral compression fractures were randomised to either vertebroplasty (n=91) or a sham procedure (n=89). Interventions Participants received local subcutaneous lidocaine (lignocaine) and bupivacaine at each pedicle. The vertebroplasty group also received cementation, which was simulated in the sham procedure group. Main outcome measures Main outcome measure was mean reduction in visual analogue scale (VAS) scores at one day, one week, and one, three, six, and 12 months. Clinically significant pain relief was defined as a decrease of 1.5 points in VAS scores from baseline. Secondary outcome measures were the differences between groups for changes in the quality of life for osteoporosis and Roland-Morris disability questionnaire scores during 12 months’ follow-up. Results The mean reduction in VAS score was statistically significant in the vertebroplasty and sham procedure groups at all follow-up points after the procedure compared with baseline. The mean difference in VAS scores between groups was 0.20 (95% confidence interval −0.53 to 0.94) at baseline, −0.43 (−1.17 to 0.31) at one day, −0.11 (−0.85 to 0.63) at one week, 0.41 (−0.33 to 1.15) at one month, 0.21 (−0.54 to 0.96) at three months, 0.39 (−0.37 to 1.15) at six months, and 0.45 (−0.37 to 1.24) at 12 months. These changes in VAS scores did not, however, differ statistically significantly between the groups during 12 months’ follow-up. The results for secondary outcomes were not statistically significant. Use of analgesics (non-opioids, weak opioids, strong opioids) decreased statistically significantly in both groups at all time points, with no statistically significant differences between groups. Two adverse events occurred in the vertebroplasty group: one respiratory insufficiency and one vasovagal reaction. Conclusions Percutaneous vertebroplasty did not result in statistically significantly greater pain relief than a sham procedure during 12 months’ follow-up among patients with acute osteoporotic vertebral compression fractures. Trial registration ClinicalTrials.gov NCT01200277.

Optimal Duration of Extended Adjuvant Endocrine Therapy for Early Breast Cancer; Results of the IDEAL Trial (BOOG 2006-05)

Abstract: Background The optimal duration of extended endocrine therapy beyond five years after initial aromatase inhibitor-based adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer is still unknown. Therefore, we conducted a clinical trial to compare two different extended endocrine therapy durations. Methods In the randomized phase III IDEAL trial, postmenopausal patients with hormone receptor-positive breast cancer were randomly allocated to either 2.5 or five years of letrozole after the initial five years of any endocrine therapy. The primary end point was disease free survival (DFS), and secondary end points were overall survival (OS), distant metastasis-free interval (DMFi), new primary breast cancer, and safety. Hazard ratios (HRs) were determined using Cox regression analysis. All analyses were by intention-to-treat principle. Results A total of 1824 patients were assigned to either 2.5 years (n = 909) or five years (n = 915) of letrozole, with a median follow-up of 6.6 years. A DFS event occurred in 152 patients in the five-year group, compared with 163 patients in the 2.5-year group (HR = 0.92, 95% confidence interval [CI] = 0.74 to 1.16). OS (HR = 1.04, 95% CI = 0.78 to 1.38) and DMFi (HR = 1.06, 95% CI = 0.78 to 1.45) were not different between both groups. A reduction in occurrence of second primary breast cancer was observed with five years of treatment (HR = 0.39, 95% CI = 0.19 to 0.81). Subgroup analysis did not identify patients who benefit from five-year extended therapy. Conclusion This study showed no superiority of five years over 2.5 years of extended adjuvant letrozole after an initial five years of adjuvant endocrine therapy.

Application of the 2017 Revised McDonald Criteria for Multiple Sclerosis to Patients With a Typical Clinically Isolated Syndrome

Abstract: Importance In 2017, the International Panel on Diagnosis of Multiple Sclerosis revised the McDonald 2010 criteria for the diagnosis of multiple sclerosis (MS). The new criteria are easier to apply and could lead to more and earlier diagnoses. It is important to validate these criteria globally for their accuracy in clinical practice. Objective To evaluate the diagnostic accuracy of the 2017 criteria vs the 2010 criteria in prediction of clinically definite MS in patients with a typical clinically isolated syndrome (CIS). Design, Setting and Patients A total of 251 patients at Erasmus MC, Rotterdam, the Netherlands, in collaboration with several regional hospitals, fulfilled the inclusion criteria. Thirteen patients received another diagnosis early in the diagnostic process and therefore were excluded from the analyses. Nine patients with CIS declined to participate in the study. This left 229 patients who were included between March 2006 and August 2016 in this prospective CIS cohort. Patients underwent a baseline magnetic resonance imaging scan within 3 months after onset of symptoms and, if clinically required, a lumbar puncture was performed. Data were analyzed between December 2017 and January 2018. Main Outcomes and Measures Sensitivity, specificity, accuracy, and positive and negative predictive value were calculated after 1, 3, and 5 years for the 2017 vs the 2010 criteria. Results Among the 229 patients with CIS, 167 were women (73%), and the mean (SD) age was 33.5 (8.2) years. One hundred thirteen patients (49%) were diagnosed as having CDMS during a mean (SD) follow-up time of 65.3 (30.9) months. Sensitivity for the 2017 criteria was higher than for the 2010 criteria (68%; 95% CI, 57%-77% vs 36%; 95% CI, 27%-47%;P Conclusions and Relevance The 2017 revised McDonald criteria are associated with greater sensitivity but less specificity for a second attack than the previous 2010 criteria. The tradeoff is that it leads to a higher number of MS diagnoses in patients with a less active disease course.

Endoscopic resection of high-risk T1 colorectal carcinoma prior to surgical resection has no adverse effect on long-term outcomes

Abstract: Objective It is difficult to predict the presence of histological risk factors for lymph node metastasis (LNM) before endoscopic treatment of T1 colorectal cancer (CRC). Therefore, endoscopic therapy is propagated to obtain adequate histological staging. We examined whether secondary surgery following endoscopic resection of high-risk T1 CRC does not have a negative effect on patients9 outcomes compared with primary surgery. Design Patients with T1 CRC with one or more histological risk factors for LNM (high risk) and treated with primary or secondary surgery between 2000 and 2014 in 13 hospitals were identified in the Netherlands Cancer Registry. Additional data were collected from hospital records, endoscopy, radiology and pathology reports. A propensity score analysis was performed using inverse probability weighting (IPW) to correct for confounding by indication. Results 602 patients were eligible for analysis (263 primary; 339 secondary surgery). Overall, 34 recurrences were observed (5.6%). After adjusting with IPW, no differences were observed between primary and secondary surgery for the presence of LNM (OR 0.97; 95% CI 0.49 to 1.93; p=0.940) and recurrence during follow-up (HR 0.97; 95% CI 0.41 to 2.34; p=0.954). Further adjusting for lymphovascular invasion, depth of invasion and number of retrieved lymph nodes did not alter this outcome. Conclusions Our data do not support an increased risk of LNM or recurrence after secondary surgery compared with primary surgery. Therefore, an attempt for an en-bloc resection of a possible T1 CRC without evident signs of deep invasion seems justified in order to prevent surgery of low-risk T1 CRC in a significant proportion of patients.

Continuous glucose monitoring during diabetic pregnancy (GlucoMOMS): A multicentre randomized controlled trial.

Abstract: Aim: Diabetes is associated with a high risk of adverse pregnancy outcomes. Optimal glycaemic control is fundamental and is traditionally monitored with self-measured glucose profiles and periodic HbA1c measurements. We investigated the effectiveness of additional use of retrospective continuous glucose monitoring (CGM) in diabetic pregnancies. Material and methods: We performed a nationwide multicentre, open label, randomized, controlled trial to study pregnant women with type 1 or type 2 diabetes who were undergoing insulin therapy at gestational age < 16 weeks, or women who were undergoing insulin treatment for gestational diabetes at gestational age < 30 weeks. Women were randomly allocated (1:1) to intermittent use of retrospective CGM or to standard treatment. Glycaemic control was assessed by CGM for 5-7 days every 6 weeks in the CGM group, while self-monitoring of blood glucose and HbA1c measurements were applied in both groups. Primary outcome was macrosomia, defined as birth weight above the 90th percentile. Secondary outcomes were glycaemic control and maternal and neonatal complications. Results: Between July 2011 and September 2015, we randomized 300 pregnant women with type 1 (n = 109), type 2 (n = 82) or with gestational (n = 109) diabetes to either CGM (n = 147) or standard treatment (n = 153). The incidence of macrosomia was 31.0% in the CGM group and 28.4% in the standard treatment group (relative risk [RR], 1.06; 95% CI, 0.83-1.37). HbA1c levels were similar between treatment groups. Conclusions: In diabetic pregnancy, use of intermittent retrospective CGM did not reduce the risk of macrosomia. CGM provides detailed information concerning glycaemic fluctuations but, as a treatment strategy, does not translate into improved pregnancy outcome.

Implication of pulmonary hypertension in patients undergoing MitraClip therapy: results from the German Transcatheter Mitral Valve Interventions (TRAMI) Registry

Abstract: Aims We sought to evaluate the impact of pulmonary hypertension on outcomes following MitraClip therapy. Methods and results The 643 patients in the Transcatheter Mitral Valve Interventions (TRAMI) Registry were divided into three groups according to echocardiographically graded systolic pulmonary artery pressure (sPAP) (Group 1: patients with sPAP of ≤36 mmHg; Group 2: patients with sPAP of 37–50 mmHg; Group 3: patients with sPAP of >50 mmHg) and followed for 1 year. Recent cardiac decompensation, aortic valve disease and tricuspid valve insufficiency were observed more frequently in patients with higher sPAP. Furthermore, logEuroSCORE, Society of Thoracic Surgeons score and age were higher with rising sPAP values. No differences were observed in mitral regurgitation (MR) severity, co-morbidities or clinical findings (New York Heart Association class, 6-min walking distance). Reduction to MR of grade 1 or lower was achieved more often in patients with lower sPAP levels (P = 0.01). In Groups 2 and 3, sPAP was reduced significantly. Major adverse cardiac or cardiovascular events (MACCEs) occurring in hospital (death, myocardial infarction, stroke; <4% in each group), as well as 30-day rates of MACCEs (6.1% in Group 1, 11.9% in Group 2, 12.4% in Group 3) and rehospitalization (18.9% in Group 1, 24.8% in Group 2, 24.8% in Group 3) did not differ significantly. At 1 year, differences in rates of mortality and MACCEs (20.3% in Group 1, 33.1% in Group 2, 34.7% in Group 3; P < 0.01) were significant. Both Groups 2 [hazard ratio (HR) 1.81, P = 0.0122] and 3 (HR 1.85, P = 0.0092) were independently predictive of death. Rehospitalization rates did not differ during follow-up. Conclusions Despite higher mortality in patients with elevated sPAP, these data suggest the safety, feasibility and benefit of MitraClip therapy even in advanced stages of disease. An early approach might prevent the progress of pulmonary hypertension and improve outcomes.

Serially measured circulating microRNAs and adverse clinical outcomes in patients with acute heart failure

Abstract: AIMS: Previous studies have identified candidate circulating microRNAs (circmiRs) as biomarkers for heart failure (HF) using relatively insensitive arrays, validated in small cohorts. The present study used RNA sequencing to identify novel candidate circmiRs and compared these with previously identified circmiRs in a large, prospective cohort of patients with acute HF (AHF). METHODS AND RESULTS: RNA sequencing of plasma from instrumented pigs was used to identify circmiRs produced by myocardium. Production of known myomiRs and microRNA (miR)‐1306‐5p was identified. The prognostic values of this and 11 other circmiRs were tested in a prospective cohort of 496 AHF patients, from whom blood samples were collected at up to seven time‐points during the study's 1‐year follow‐up. The primary endpoint was the composite of all‐cause mortality and HF rehospitalization. In the prospective AHF cohort, 188 patients reached the primary endpoint, and higher values of repeatedly measured miR‐1306‐5p were positively associated with risk for reaching the primary endpoint at the same time‐point [hazard ratio (HR) 4.69, 95% confidence interval (CI) 2.18–10.06], independent of clinical characteristics and NT‐proBNP. Baseline miR‐1306‐5p did not improve model discrimination/reclassification significantly compared with NT‐proBNP. For miR‐320a, miR‐378a‐3p, miR‐423‐5p and miR‐1254, associations with the primary endpoint were present after adjustment for age and sex (HR 1.38, 95% CI 1.12–1.70; HR 1.35, 95% CI 1.04–1.74; HR 1.45, 95% CI 1.10–1.92; HR 1.22, 95% CI 1.00–1.50, respectively). Rates of detection of myomiRs miR‐208a‐3p and miR‐499a‐5p were very low. CONCLUSIONS: Repeatedly measured miR‐1306‐5p was positively associated with adverse clinical outcome in AHF, even after multivariable adjustment including NT‐proBNP. However, baseline miR‐1306‐5p did not add significant discriminatory value to NT‐proBNP. Low‐abundance, heart‐enriched myomiRs are often undetectable, which mandates the development of more sensitive assays.

Fully vs. partially covered selfexpandable metal stent for palliation of malignant esophageal strictures: a randomized trial (the COPAC study).

Abstract: Background Covered esophageal self-expandable metal stents (SEMSs) are currently used for palliation of malignant dysphagia. The optimal extent of the covering to prevent recurrent obstruction is unknown. Therefore, we aimed to compare fully covered (FC) versus partially covered (PC) SEMSs in patients with incurable malignant esophageal stenosis. Methods In this multicenter randomized controlled trial, 98 incurable patients with dysphagia caused by a malignant stricture of the esophagus or cardia were randomized 1:1 to an FC-SEMS or PC-SEMS. The primary outcome was recurrent obstruction after endoscopic SEMS placement. Secondary outcomes were technical and clinical success, adverse events, and health-related quality of life (HRQoL). Patients were followed until 6 months after SEMS placement or to SEMS removal, second SEMS insertion, or death, whichever came first. Results Recurrent obstruction after SEMS placement was similar for both types of stents: 19 % for FC-SEMSs and 22 % for PC-SEMSs (P = 0.65). The times to recurrent obstruction did not differ. The frequency of adverse events was similar between the two groups, with major adverse events occurring in 38 % and 47 % of patients for FC-SEMSs and PC-SEMSs, respectively (P = 0.34). No significant differences were seen in technical success, improvement of dysphagia, and HRQoL. Proximal esophageal stenosis and female sex were independently associated with recurrent obstruction and/or major adverse events. Conclusions Esophageal FC-SEMSs did not reveal a lower recurrent obstruction rate compared with PC-SEMSs in the palliative management of malignant dysphagia.

Predicting the presence of macrovascular causes in non-traumatic intracerebral haemorrhage: The DIAGRAM prediction score

Abstract: Objective: A substantial part of non-traumatic intracerebral haemorrhages (ICH) arises from a macrovascular cause, but there is little guidance on selection of patients for additional diagnostic work-up. We aimed to develop and externally validate a model for predicting the probability of a macrovascular cause in patients with non-traumatic ICH. Methods: The DIagnostic AngioGRAphy to find vascular Malformations (DIAGRAM) study (n=298; 69 macrovascular cause; 23%) is a prospective, multicentre study assessing yield and accuracy of CT angiography (CTA), MRI/magnetic resonance angiography (MRA) and intra-arterial catheter angiography in diagnosing macrovascular causes in patients with non-traumatic ICH. We considered prespecified patient and ICH characteristics in multivariable logistic regression analyses as predictors for a macrovascular cause. We combined independent predictors in a model, which we validated in an external cohort of 173 patients with ICH (78 macrovascular cause, 45%). Results: Independent predictors were younger age, lobar or posterior fossa (vs deep) location of ICH, and absence of small vessel disease (SVD). A model that combined these predictors showed good performance in the development data (c-statistic 0.83; 95% C I 0.78 to 0.88) and moderate performance in external validation (c-statistic 0.66; 95% CI 0.58 to 0.74). When CTA results were added, the c-statistic was excellent (0.91; 95% CI 0.88 to 0.94) and good after external validation (0.88; 95% CI 0.83 to 0.94). Predicted probabilities varied from 1% in patients aged 51-70 years with deep ICH and SVD, to more than 50% in patients aged 18-50 years with lobar or posterior fossa ICH without SVD. Conclusion: The DIAGRAM scores help to predict the probability of a macrovascular cause in patients with nontraumatic ICH based on age, ICH location, SVD and CTA.

Cereblon loss and up-regulation of c-Myc are associated with lenalidomide resistance in multiple myeloma patients

Abstract: Multiple myeloma (MM) patients who become refractory to anti-MM drugs have a very poor prognosis. Therefore, it is important to gain insight into the mechanisms of resistance to these drugs. Immunomodulatory drugs (IMiDs) have immune-stimulatory and anti-angiogenic properties as well as direct anti-

Sleep in patients with disorders of consciousness characterized by means of machine learning.

Abstract: Sleep has been proposed to indicate preserved residual brain functioning in patients suffering from disorders of consciousness (DOC) after awakening from coma. However, a reliable characterization of sleep patterns in this clinical population continues to be challenging given severely altered brain oscillations, frequent and extended artifacts in clinical recordings and the absence of established staging criteria. In the present study, we try to address these issues and investigate the usefulness of a multivariate machine learning technique based on permutation entropy, a complexity measure. Specifically, we used long-term polysomnography (PSG), along with video recordings in day and night periods in a sample of 23 DOC; 12 patients were diagnosed as Unresponsive Wakefulness Syndrome (UWS) and 11 were diagnosed as Minimally Conscious State (MCS). Eight hour PSG recordings of healthy sleepers (N = 26) were additionally used for training and setting parameters of supervised and unsupervised model, respectively. In DOC, the supervised classification (wake, N1, N2, N3 or REM) was validated using simultaneous videos which identified periods with prolonged eye opening or eye closure.The supervised classification revealed that out of the 23 subjects, 11 patients (5 MCS and 6 UWS) yielded highly accurate classification with an average F1-score of 0.87 representing high overlap between the classifier predicting sleep (i.e. one of the 4 sleep stages) and closed eyes. Furthermore, the unsupervised approach revealed a more complex pattern of sleep-wake stages during the night period in the MCS group, as evidenced by the presence of several distinct clusters. In contrast, in UWS patients no such clustering was found. Altogether, we present a novel data-driven method, based on machine learning that can be used to gain new and unambiguous insights into sleep organization and residual brain functioning of patients with DOC.

Endobronchial Treatment for Bronchial Carcinoid: Patient Selection and Predictors of Outcome.

Abstract: Background: Traditionally, surgical resection is the preferred treatment for typical carcinoids and atypical carcinoids located in the lungs. Recently however, several studies have shown excellent long-term outcome after endobronchial treatment of carcinoid tumors located in the central airways. This study investigates clinical and radiological features as predictors of successful endobronchial treatment in patients with a bronchial carcinoid tumor. Objectives: To identify clinical and radiological features predictive of successful endobronchial treatment in patients with bronchial carcinoid. Methods: This analysis was performed in a cohort of patients with typical and atypical bronchial carcinoid referred for endobronchial treatment. Several patient characteristics, radiological features, and histological grade (typical or atypical carcinoid) were tested as predictors of successful endobronchial treatment. Results: One hundred and twenty-five patients with a diagnosis of bronchial carcinoid underwent endobronchial treatment. On multivariate analysis, a tumor diameter <15 mm (odds ratio 0.09; 95% confidence interval 0.02–0.5; p = <0.01) and purely intraluminal growth on computer tomography (CT scan) (odds ratio, 9.1; 95% confidence interval 1.8–45.8; p = <0.01) were predictive of radical endobronchial treatment. The success rate for intraluminal tumors with a diameter <20 mm was 72%. Conclusions: Purely intraluminal disease and tumor diameter on CT scan seem to be independent predictors for successful endobronchial treatment in patients with bronchial carcinoid. Based on these data, patients with purely intraluminal carcinoid tumors with a diameter <20 mm on CT scan are good candidates for endobronchial treatment, regardless of histological grade. In contrast, all patients with a tumor diameter ≥20 mm should be directly referred for surgery.

Changes in body composition and muscle attenuation during taxane-based chemotherapy in patients with metastatic breast cancer

Abstract: Body composition parameters including low muscle mass, muscle attenuation (which reflects muscle quality) and adipose tissue measurements have emerged as prognostic factors in cancer patients. However, knowledge regarding the possibility of excessive muscle loss during specific systemic therapies is unknown. We describe the changes in body composition and muscle attenuation (MA) during taxane- and anthracycline-based regimens and its association with overall survival (OS) in metastatic breast cancer patients. The lumbar skeletal muscle index (LSMI) was used as marker of muscle mass. LSMI, MA, subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and intramuscular adipose tissue (IMAT) were measured before and after first-line treatment with paclitaxel (n = 73) or 5-fluorouracil-doxorubicin-cyclophosphamide (FAC) (n = 25) using CT-images. Determinants of the change of LSMI and MA were analyzed using multiple linear regression. OS was assessed using Cox proportional hazard models. MA significantly decreased during paclitaxel treatment (− 0.9 HU, p = 0.03). LSMI (p = 0.40), SAT (p = 0.75), VAT (p = 0.84) and IMAT (p = 0.10) remained stable. No significant alterations in body composition parameters during FAC-treatment were observed. Previous (neo-)adjuvant chemotherapy contributed to larger loss of MA during the current treatment. Body composition changes during chemotherapy were not associated with OS. MA decreased during treatment with paclitaxel, while muscle mass was stable. Body composition changes are not associated with survival in the absence of progressive disease.

Spinal Cord Stimulation in Patients With Complex Regional Pain Syndrome: A Possible Target for Immunomodulation?

Abstract: Objective Complex regional pain syndrome (CRPS) is characterized by continued pain disproportional to the inciting event, sensory abnormalities, vasomotor and sudomotor disturbances, and motor and trophic changes. Inflammatory involvement has been demonstrated in past CRPS studies resulting in pain, swelling, and warmth. Currently, it is unknown whether spinal cord stimulation (SCS) has immunomodulatory properties. The aim of this study was to determine whether SCS has immunomodulatory properties in CRPS patients. Methods The primary outcome parameters are cytokines (IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-15, IL-17, TNF-α, IFN-γ), chemokines (IP-10 and Eotaxin), and growth factors (VEGF, PDGFbb, and basic FGF) from interstitial fluid of artificial skin blisters before (T0—baseline without SCS) and after SCS therapy (T1—40 Hz standard frequency stimulation and T2—preferred frequency stimulation). Secondary outcome parameters were baseline demographics, CRPS signs, symptoms, and phenotype (inflammatory, vasomotor, dystonia, or neuropathic). Results were analyzed by means of a MANOVA repeated measures design. Results After SCS, the expression of both pro- and anti-inflammatory cytokines decreased over time in both the CRPS affected extremity and the contralateral extremity. The levels of IP-10, Eotaxin, VEGF, and PDGFbb were also significantly reduced bilaterally. There were no significant changes in IL-6 and TNF-α before and after SCS. The sensory signs, symptoms, and phenotype improved after SCS. Discussion SCS in CRPS patients attenuates T-cell activation, improves peripheral tissue oxygenation and decreases anti-angiogenetic activity which results in diminished endothelial dysfunction and improved bloodflow. The possible immunomodulatory effects of SCS opens new therapeutic possibilities in diseases with the involvement of the immune system and vasomotor disturbances, and requires further research on these mechanisms of action.

The association of clinical frailty with outcomes of patients reviewed by rapid response teams: an international prospective observational cohort study

Abstract: Frailty is a state of vulnerability to poor resolution of homeostasis after a stressor event and is strongly associated with adverse outcomes Therefore, the assessment of frailty may be an essential part of evaluation in any healthcare encounter that might result in an escalation of care The purpose of the study was to assess the frequency and association of frailty with clinical outcomes in patients subject to rapid response team (RRT) review In this multi-national prospective observational cohort study, centres with existing RRTs collected data over a 7-day period, with follow up of all patients at 24 h following their RRT call and at hospital discharge or 30 days following the event trigger (whichever came sooner) Investigators also collected data on the triggers and interventions provided and a bedside assessment on the level of patients’ frailty using a clinical frailty scale Amongst 1133 patients, 40% were screened as frail, which was associated with older age (p < 0001), admission under a medical speciality (p < 0001), increased severity of illness at the time of the RRT review (p = 00047), and substantially higher frequency of limitations of care (p < 0001) Importantly, 72% of patients screened as frail were either dead or dependent on hospital care by 30 days (p < 0001) In the multivariable analysis, the significant risk factors for the composite endpoint “poor recovery” (died or were hospital-dependent by 30 days) were age (odds ratio (OR), 104; 95% confidence interval (CI), 103–105; p < 0001), frailty level (p < 0001), existing limitation of care (OR, 20; 95% CI, 13–30; p < 0001), and the quick sequential organ failure assessment (qSOFA) score (p < 0001) Higher frailty scores were associated with increased mortality and dependence on health care at 30 days Our results indicate that frailty has an influence on the clinical trajectory of deteriorating patients and that such assessment should be included in discussion of goals and expectations of care Netherlands Trial Registry, NTR5535 Registered on 23 December 2015

Effectiveness of Disease-Specific Cognitive Behavioral Therapy on Anxiety, Depression, and Quality of Life in Youth With Inflammatory Bowel Disease: A Randomized Controlled Trial.

Abstract: Objective To evaluate the effectiveness of a disease-specific cognitive behavioral therapy (CBT) protocol on anxiety and depressive symptoms and health-related quality of life (HRQOL) in adolescents and young adults with inflammatory bowel disease (IBD). Method A parallel group randomized controlled trial was conducted in 6 centers of (pediatric) gastroenterology. Included were 70 patients and young adults (10-25 years) with IBD and subclinical anxiety and/or depressive symptoms. Patients were randomized into 2 groups, stratified by center: (a) standard medical care (care-as-usual [CAU]) plus disease-specific manualized CBT (Primary and Secondary Control Enhancement Training for Physical Illness; PASCET-PI), with 10 weekly sessions, 3 parent sessions, and 3 booster sessions (n = 37), or (b) CAU only (n = 33). Primary analysis concerned the reliable change in anxiety and depressive symptoms after 3 months (immediate posttreatment assessment). Exploratory analyses concerned (1) the course of anxiety and depressive symptoms and HRQOL in subgroups based on age, and (2) the influence of age, gender, and disease type on the effect of the PASCET-PI. Results Overall, all participants improved significantly in their anxiety and depressive symptoms and HRQOL, regardless of group, age, gender, and disease type. Primary chi-square tests and exploratory linear mixed models showed no difference in outcomes between the PASCET-PI (n = 35) and the CAU group (n = 33). Conclusions In youth with IBD and subclinical anxiety and/or depressive symptoms, preliminary results of immediate post-treatment assessment indicated that a disease-specific CBT added to standard medical care did not perform better than standard medical care in improving psychological symptoms or HRQOL. ClinicalTrials.gov: NCT02265588.

Burden of Psoriatic Arthritis According to Different Definitions of Disease Activity: Comparing Minimal Disease Activity and the Disease Activity Index for Psoriatic Arthritis.

Abstract: Objective Treat-to-target strategies have improved outcomes in rheumatic diseases. In psoriatic arthritis (PsA), the proposed targets are the multidimensional target minimal disease activity (MDA) and the articular target Disease Activity index for PsA (DAPSA). The aim of this study was to compare the disease burden of PsA in patients with low disease activity according to the 2 definitions, MDA and DAPSA low disease activity (DAPSA-LDA), 1 year after diagnosis. Methods We obtained data on MDA, DAPSA-LDA and disease burden 1 year after diagnosis for patients included in the Dutch southwest early PsA cohort. Disease burden was assessed in 2 domains: "Body functions," including the Short Form 36 bodily pain (SF-36 BP) measure, and "Activity," including the Health Assessment Questionnaire (HAQ). Results Among the 292 patients included, 48% achieved MDA and 74% achieved DAPSA-LDA. Average scores for Body functions and Activity were better in patients who achieved MDA and those who achieved DAPSA-LDA. The scores were significantly better in the 46% of patients who achieved both MDA and DAPSA-LDA than in the 29% of patients who achieved only DAPSA-LDA. The average SF-36 BP score was higher in patients achieving both targets (73.8; 95% confidence interval [95% CI] 71.1-76.5) than in patients achieving only DAPSA-LDA (57.6; 95% CI 54.5-60.8). Similarly, mean HAQ scores measuring Activity were 0.21 (95% CI 0.15-0.26) and 0.63 (95% CI 0.53-0.72), respectively. Conclusion Among patients with newly diagnosed PsA, 48% achieved MDA and 74% achieved DAPSA-LDA after 1 year of receiving usual care. The average disease burden was better in patients who achieved MDA and those who achieved DAPSA-LDA. Also, patients who achieved only DAPSA-LDA reported worse outcomes than those who also achieved MDA.

Evaluation of PET and laparoscopy in STagIng advanced gastric cancer: a multicenter prospective study (PLASTIC-study)

Abstract: Initial staging of gastric cancer consists of computed tomography (CT) and gastroscopy. In locally advanced (cT3–4) gastric cancer, fluorodeoxyglucose positron emission tomography with CT (FDG-PET/CT or PET) and staging laparoscopy (SL) may have a role in staging, but evidence is scarce. The aim of this study is to evaluate the impact and cost-effectiveness of PET and SL in addition to initial staging in patients with locally advanced gastric cancer. This prospective observational cohort study will include all patients with a surgically resectable, advanced gastric adenocarcinoma (cT3–4b, N0–3, M0), that are scheduled for treatment with curative intent after initial staging with gastroscopy and CT. The modalities to be investigated in this study is the addition of PET and SL. The primary outcome of this study is the proportion of patients in whom the PET or SL lead to a change in treatment strategy. Secondary outcome parameters are: diagnostic performance, morbidity and mortality, quality of life, and cost-effectiveness of these additional diagnostic modalities. The study recently started in August 2017 with a duration of 36 months. At least 239 patients need to be included in this study to demonstrate that the diagnostic modalities are break-even. Based on the annual number of gastrectomies in the participating centers, it is estimated that approximately 543 patients are included in this study. In this study, it is hypothesized that performing PET and SL for locally advanced gastric adenocarcinomas results in a change of treatment strategy in 27% of patients and an annual cost-reduction in the Netherlands of €916.438 in this patient group by reducing futile treatment. The results of this study may be applicable to all countries with comparable treatment algorithms and health care systems. NCT03208621 . This trial was registered prospectively on June 30, 2017.

Worldwide practices on flexible endoscope reprocessing.

Abstract: Endoscopy related infections represent an important threat for healthcare systems worldwide. Recent outbreaks of infections with multidrug resistant micro-organisms have highlighted the problems of contaminated endoscopes. Endoscopes at highest risk for contamination have intricate mechanisms, multiple internal channels and narrow lumens that are especially problematic to clean. In light of raised awareness about the necessity for meticulous reprocessing of all types of endoscopes, a call for international collaboration is needed. An overview is presented on current practices for endoscope reprocessing in facilities worldwide. An electronic survey was developed and disseminated by the International Society for Antimicrobials and Chemotherapy. The survey consisted of 50 questions aimed at assessing the reprocessing of flexible endoscopes internationally. It covered three core elements: stakeholder involvement, assessment of perceived risks, and reprocessing process. The survey received a total of 165 completed responses from 39 countries. It is evident that most facilities, 82% (n = 136), have a standard operating procedure. There is, however a lot of variation within the flexible endoscope reprocessing practices observed. The need for regular training and education of reprocessing practitioners were identified by 50% (n = 83) of the respondents as main concerns that need to be addressed in order to increase patient safety in endoscope reprocessing procedures. This international survey on current flexible endoscope reprocessing identified a large variation for reprocessing practices among different health care facilities/countries. A standardised education and training programme with a competency assessment is essential to prevent reprocessing lapses and improve patient safety.

A prediction model for underestimation of invasive breast cancer after a biopsy diagnosis of ductal carcinoma in situ: based on 2892 biopsies and 589 invasive cancers

Abstract: Patients with a biopsy diagnosis of ductal carcinoma in situ (DCIS) might be diagnosed with invasive breast cancer at excision, a phenomenon known as underestimation. Patients with DCIS are treated based on the risk of underestimation or progression to invasive cancer. The aim of our study was to expand the knowledge on underestimation and to develop a prediction model. Population-based data were retrieved from the Dutch Pathology Registry and the Netherlands Cancer Registry for DCIS between January 2011 and June 2012. Of 2892 DCIS biopsies, 21% were underestimated invasive breast cancers. In multivariable analysis, risk factors were high-grade DCIS (odds ratio (OR) 1.43, 95% confidence interval (CI): 1.05–1.95), a palpable tumour (OR 2.22, 95% CI: 1.76–2.81), a BI-RADS (Breast Imaging Reporting and Data System) score 5 (OR 2.36, 95% CI: 1.80–3.09) and a suspected invasive component at biopsy (OR 3.84, 95% CI: 2.69–5.46). The predicted risk for underestimation ranged from 9.5 to 80.2%, with a median of 14.7%. Of the 596 invasive cancers, 39% had unfavourable features. The risk for an underestimated diagnosis of invasive breast cancer after a biopsy diagnosis of DCIS is considerable. With our prediction model, the individual risk of underestimation can be calculated based on routinely available preoperatively known risk factors ( https://www.evidencio.com/models/show/1074 ).