Disability in multiple sclerosis:Improving clinical assessment

he findings of this thesis contribute to the resolution of these clinical challenges, specifically: • Clinical assessment of disability can be improved when (i) UEF and ambu- lation are assessed independently (chapter 3), (ii) tasks of ADL are used in conjunction to other measures (chapter 4), and (iii) a value for MCID of improvement for AMSQ is determined (chapter 5) • Multimodal assessment of UEF and mobility, and subgroup analyses im- prove evaluation of treatment effects (chapter 6) • Reference videos reduce the variability of motor functioning assessment (chapter 7) • Detection of change in UEF and mobility can be improved when video-as- sisted composite measures are used in conjunction with conventional measures (chapter 8) • Autoencoders are a valuable method to preserve data privacy in analyses of patient videos (chapter 9). Final conclusion The clinical assessment of MS patients is an exciting field grounded on illustrious historical foundations and deepened through contemporary technological innovation. Further improvement and integration into multidisciplinary data infrastructures will eventually lead to a better understanding and control of MS, which ultimately improves the quality of the life of our patients

A hospital care coordination team intervention for patients with multimorbidity:A practice-based, participatory pilot study

Objectives: This study aims to develop and pilot a hospital care coordination team intervention for patients with multimorbidity and identify key uncertainties Methods: Practice-based, participatory pilot study with mixed methods in a middle-large teaching hospital. We included adult patients who had visited seven or more outpatient specialist clinics in 2018. The intervention consisted of an intake, a comprehensive review by a dedicated care coordination team, a consultation to discuss results and two follow-up appointments. We collected both quantitative and qualitative data. Results: Out of 131 invited patients, 28 participants received the intake and comprehensive review. The intervention resulted in mixed outputs and short-term outcomes. Among the 28 participants, 21 received recommendations for at least two out of three categories (medication, involved medical specialists, other). Patients’ experienced effects ranged from no to very large effects. Key uncertainties were how to identify patients with a need for care coordination and the minimum of required data that can be collected during regular clinical care with feasible effort. Discussion: Recruitment and selection for hospital care coordination should be refined to include patients with multimorbidity who might benefit most. Outcomes of research and clinical care should align and first focus on evaluating the results of care coordination before evaluating health-related outcomes.</p

A hospital care coordination team intervention for patients with multimorbidity:A practice-based, participatory pilot study

Objectives: This study aims to develop and pilot a hospital care coordination team intervention for patients with multimorbidity and identify key uncertainties Methods: Practice-based, participatory pilot study with mixed methods in a middle-large teaching hospital. We included adult patients who had visited seven or more outpatient specialist clinics in 2018. The intervention consisted of an intake, a comprehensive review by a dedicated care coordination team, a consultation to discuss results and two follow-up appointments. We collected both quantitative and qualitative data. Results: Out of 131 invited patients, 28 participants received the intake and comprehensive review. The intervention resulted in mixed outputs and short-term outcomes. Among the 28 participants, 21 received recommendations for at least two out of three categories (medication, involved medical specialists, other). Patients’ experienced effects ranged from no to very large effects. Key uncertainties were how to identify patients with a need for care coordination and the minimum of required data that can be collected during regular clinical care with feasible effort. Discussion: Recruitment and selection for hospital care coordination should be refined to include patients with multimorbidity who might benefit most. Outcomes of research and clinical care should align and first focus on evaluating the results of care coordination before evaluating health-related outcomes.</p

A hospital care coordination team intervention for patients with multimorbidity:A practice-based, participatory pilot study

Objectives: This study aims to develop and pilot a hospital care coordination team intervention for patients with multimorbidity and identify key uncertainties Methods: Practice-based, participatory pilot study with mixed methods in a middle-large teaching hospital. We included adult patients who had visited seven or more outpatient specialist clinics in 2018. The intervention consisted of an intake, a comprehensive review by a dedicated care coordination team, a consultation to discuss results and two follow-up appointments. We collected both quantitative and qualitative data. Results: Out of 131 invited patients, 28 participants received the intake and comprehensive review. The intervention resulted in mixed outputs and short-term outcomes. Among the 28 participants, 21 received recommendations for at least two out of three categories (medication, involved medical specialists, other). Patients’ experienced effects ranged from no to very large effects. Key uncertainties were how to identify patients with a need for care coordination and the minimum of required data that can be collected during regular clinical care with feasible effort. Discussion: Recruitment and selection for hospital care coordination should be refined to include patients with multimorbidity who might benefit most. Outcomes of research and clinical care should align and first focus on evaluating the results of care coordination before evaluating health-related outcomes.</p

A hospital care coordination team intervention for patients with multimorbidity:A practice-based, participatory pilot study

Objectives: This study aims to develop and pilot a hospital care coordination team intervention for patients with multimorbidity and identify key uncertainties Methods: Practice-based, participatory pilot study with mixed methods in a middle-large teaching hospital. We included adult patients who had visited seven or more outpatient specialist clinics in 2018. The intervention consisted of an intake, a comprehensive review by a dedicated care coordination team, a consultation to discuss results and two follow-up appointments. We collected both quantitative and qualitative data. Results: Out of 131 invited patients, 28 participants received the intake and comprehensive review. The intervention resulted in mixed outputs and short-term outcomes. Among the 28 participants, 21 received recommendations for at least two out of three categories (medication, involved medical specialists, other). Patients’ experienced effects ranged from no to very large effects. Key uncertainties were how to identify patients with a need for care coordination and the minimum of required data that can be collected during regular clinical care with feasible effort. Discussion: Recruitment and selection for hospital care coordination should be refined to include patients with multimorbidity who might benefit most. Outcomes of research and clinical care should align and first focus on evaluating the results of care coordination before evaluating health-related outcomes.</p

Novel cryoballoon 180° ablation system for treatment of Barrett's esophagus-related neoplasia:a first-in-human study

Background The novel 180 degrees cryoballoon (CbAS (180) ) enables semicircumferential treatment over a length of 3cm per application. This first-in-human study evaluates its feasibility, efficacy, and safety for the treatment of Barrett's esophagus (BE) neoplasia. Methods This multicenter study consisted of dose-finding and extension phases. Dose-finding started with the lowest dose possible (1.0mm/s). For each dose, six patients were treated circumferentially over a 3-cm length. The dose was increased until the median BE regression was >= 60% without serious adverse events (SAEs). In the extension phase, the dose was confirmed in 19 new patients. The outcomes were technical success, BE regression after one treatment, and SAEs. Results 25 patients (median Prague C0M3) were included (6 dose-finding/19 extension). In two patients, the CbAS (180) could not be applied because of unstable balloon positioning. The technical success rate was 96% (22/23). In the six dose-finding patients, the starting dose resulted in median BE regression of 94% (95% confidence interval [CI] 60%-97%) without SAEs and was thus considered effective. Overall median BE regression was 80% (95%CI 60%-90%). Conclusion Single-session CbAS (180) seems feasible, safe, and effective, and is a promising technique for the treatment of patients with BE neoplasia

A novel cryoballoon ablation system for eradication of dysplastic Barrett's esophagus:a first-in-human feasibility study

BACKGROUND:  Endoscopic cryoablation for Barrett's esophagus (BE) might offer advantages over heat-based ablation. Focal cryoballoon ablation has been promising for short-segment BE, whereas the novel 90°-swipe cryoballoon ablation system (CbSAS90) ablates larger areas in a single step (90° over 3 cm). The system allows for dose adjustment. CbSAS90 has been feasible and safe in animal and pre-esophagectomy studies. This is the first clinical study to assess feasibility, safety, and efficacy of CbSAS90 for eradication of dysplastic BE. METHODS:  In this prospective study in dysplastic BE patients, dose finding started with semi-circumferential treatment at 0.8 mm/s (dose 1). The dose was escalated by reducing speed by 0.1 mm/s in six patients until BE surface regression was ≥ 80 % without complications ("effective dose"). The effective dose was subsequently confirmed with circumferential treatment in 12 new patients. Post-procedural pain (0 - 10) and dysphagia (0 - 4) were evaluated. Outcomes were feasibility, safety, and BE surface regression. RESULTS:  25 patients were included, with technically successful treatment in 92 % (95 %CI 73 % - 99 %). Median (95 %CI) BE surface regression was 78 % (50 % - 85 %) for dose 1 and 85 % (55 % - 95 %) for dose 2 (0.7 mm/s), which was defined as the effective dose. Circumferential treatment resulted in 93 % (88 % - 96 %) regression. Two of 12 patients with circumferential treatment developed strictures that required dilation. Median pain and dysphagia scores were low (0 - 3 and 0, respectively). CONCLUSIONS: CbSAS90 was feasible and effective for ablating larger BE areas. The optimal dose for circumferential treatment that balances safety and efficacy requires further evaluation

Conformational changes in CLIP-170 regulate its binding to microtubules and dynactin localization

Cytoplasmic linker protein (CLIP)-170, CLIP-115, and the dynactin subunit p150Glued are structurally related proteins, which associate specifically with the ends of growing microtubules (MTs). Here, we show that down-regulation of CLIP-170 by RNA interference results in a strongly reduced accumulation of dynactin at the MT tips. The NH2 terminus of p150Glued binds directly to the COOH terminus of CLIP-170 through its second metal-binding motif. p150Glued and LIS1, a dynein-associating protein, compete for the interaction with the CLIP-170 COOH terminus, suggesting that LIS1 can act to release dynactin from the MT tips. We also show that the NH2-terminal part of CLIP-170 itself associates with the CLIP-170 COOH terminus through its first metal-binding motif. By using scanning force microscopy and fluorescence resonance energy transfer-based experiments we provide evidence for an intramolecular interaction between the NH2 and COOH termini of CLIP-170. This interaction interferes with the binding of the CLIP-170 to MTs. We propose that conformational changes in CLIP-170 are important for binding to dynactin, LIS1, and the MT tips

Extending treatment criteria for Barrett's neoplasia:results of a nationwide cohort of 138 ESDs

BACKGROUND:  The use of endoscopic submucosal dissection (ESD) is gradually expanding for treatment of neoplasia in Barrett's esophagus (BE). We aimed to report outcomes of all ESDs for BE neoplasia performed in the Netherlands. METHODS:  Retrospective assessment of outcomes, using treatment and follow-up data from a joint database. RESULTS:  130/138 patients had complete ESDs, with 126/130 (97 %) en bloc resections. Median (interquartile range (IQR)) procedure time was 121 minutes (90-180). Pathology findings were high grade dysplasia (HGD) (5 %) or esophageal adenocarcinoma (EAC) T1a (43 %) or T1b (52 %; 19 % sm1, 33 % ≥ sm2). Among resections of HGD or T1a EAC lesions, 87 % (95 %CI 75 %-92 %) were both en bloc and R0; the corresponding value for T1b EAC lesions was 49 % (36 %-60 %). Among R1 resections, 10/34 (29 %) showed residual cancer, all detected at first endoscopic follow-up. The remaining 24 patients (71 %) showed no residual neoplasia. Six of these patients underwent surgery with no residual tumor; the remaining 18 underwent endoscopic follow-up during median 31 months with 1 local recurrence (annual recurrence rate 2 %). Among R0 resections, annual local recurrence rate during median 27 months was 0.5 %. CONCLUSION:  In expert hands, ESD allows safe removal of bulky intraluminal neoplasia and submucosal cancer. ESD of the latter showed R1 resection margins in 50 %, yet only one third had persisting neoplasia at follow-up. To better stratify R1 patients with an indication for additional surgery, repeat endoscopy after healing of the ESD might be a helpful possible prognostic factor for residual cancer