To evaluate whether detection of recurrent pancreatic ductal adenocarcinoma (PDAC) in an early, asymptomatic stage increases the number of patients receiving additional treatment, subsequently ...improving survival.
International guidelines disagree on the value of standardized postoperative surveillance for early detection and treatment of PDAC recurrence.
A nationwide, observational cohort study was performed including all patients who underwent PDAC resection (2014-2016). Prospective baseline and perioperative data were retrieved from the Dutch Pancreatic Cancer Audit. Data on follow-up, treatment, and survival were collected retrospectively. Overall survival (OS) was evaluated using multivariable Cox regression analysis, before and after propensity-score matching, stratified for patients with symptomatic and asymptomatic recurrence.
Eight hundred thirty-six patients with a median follow-up of 37 months (interquartile range 30-48) were analyzed. Of those, 670 patients (80%) developed PDAC recurrence after a median follow-up of 10 months (interquartile range 5-17). Additional treatment was performed in 159/511 patients (31%) with symptomatic recurrence versus 77/159 (48%) asymptomatic patients (P < 0.001). After propensity-score matching on lymph node ratio, adjuvant therapy, disease-free survival, and recurrence site, additional treatment was independently associated with improved OS for both symptomatic patients hazard ratio 0.53 (95% confidence interval 0.42-0.67); P < 0.001 and asymptomatic patients hazard ratio 0.45 (95% confidence interval 0.29-0.70); P < 0.001.
Additional treatment of PDAC recurrence was independently associated with improved OS, with asymptomatic patients having a higher probability to receive recurrence treatment. Therefore, standardized postoperative surveillance aiming to detect PDAC recurrence before the onset of symptoms has the potential to improve survival. This provides a rationale for prospective studies on standardized surveillance after PDAC resection.
Background:
Cognitive behavioural therapy (CBT) reduces multiple sclerosis (MS)-related fatigue. Implementation of face-to-face CBT is hindered by limited treatment capacity and traveling distances ...to treatment locations.
Objective:
Evaluate whether blended CBT (online treatment modules supported with guidance by a therapist) is non-inferior to face-to-face CBT in reducing fatigue severity in severely fatigued patients with MS.
Method:
A non-inferiority multicentre randomized clinical trial, in which 166 patients with MS were allocated to either face-to-face or blended CBT. Primary outcome was fatigue severity assessed with the Checklist Individual Strength fatigue subscale directly post-treatment (week 20). Mixed model analysis was used by a statistician blinded for allocation to determine between-group differences post-treatment. The upper limit of the 95% confidence interval (CI) was compared to a pre-specified non-inferiority margin of 5.32.
Results:
Blended CBT (N = 82) was non-inferior to face-to-face CBT (N = 84) (B = 1.70, 95% CI: −1.51 to 4.90). Blended CBT significantly reduced therapist time (B = −187.1 minutes, 95% CI: 141.0–233.3). Post hoc analysis showed more improvement (B = −5.35, 95% CI: −9.22 to −1.48) when patients received their preferred treatment. No harm related to treatment was reported.
Discussion:
Blended CBT is an efficient alternative to face-to-face CBT. Offering the preferred CBT format may optimize treatment outcome.
Rehabilitation is an essential aspect of symptomatic and supportive treatment for people with multiple sclerosis (MS). The number of randomised controlled trials (RCTs) for rehabilitation ...interventions in MS has increased over the last two decades. The design, conduct and reporting quality of some of these trials could be improved. There are, however, some specific challenges that researchers face in conducting RCTs of rehabilitation interventions, which are often ‘complex interventions’. This paper explores some of the challenges of undertaking robust clinical trials in rehabilitation. We focus on issues related to (1) participant selection and sample size, (2) interventions – the ‘dose’, content, active ingredients, targeting, fidelity of delivery and treatment adherence, (3) control groups and (4) outcomes – choosing the right type, number, timing of outcomes, and the importance of defining a primary outcome and clinically important difference between groups. We believe that by following internationally accepted RCT guidelines, by developing a critical mass of MS rehabilitation ‘trialists’ through international collaboration and by continuing to critique, challenge, and develop RCT designs, we can exploit the potential of RCTs to answer important questions related to the effectiveness of rehabilitation interventions.
Fatigue related to Multiple Sclerosis (MS) is considered a multidimensional symptom, manifesting in several dimensions such as physical, cognitive, and psychosocial fatigue. This study investigated ...in 264 patients with severe primary MS-related fatigue (median MS duration 6.8 years, mean age 48.1 years, 75% women) whether subgroups can be distinguished based on these dimensions. Subsequently, we tested whether MS-related fatigue consists of a single common unidimensional factor. Subscale scores on four self-reported fatigue questionnaires, including the Checklist of Individual Strength, the Modified Fatigue Impact Scale, the Fatigue Severity Scale and the SF36 vitality, were used in a cluster analysis to identify patients with similar fatigue characteristics. Next, all 54 items were included in exploratory factor analysis to test unidimensionality. Study results show that in patients with a treatment indication for primary MS-related fatigue, fatigue profiles are based on severity and not on the various dimensions of fatigue. The three profiles found, suggested one underlying fatigue dimension, but this could not be confirmed. Factor analysis of all 54 items resulted in 8 factors, confirming the multidimensional construct of the included fatigue questionnaires.
Context:
Goal-setting is a key characteristic of modern rehabilitation. However, goals need to be meaningful and of importance to the client.
Axioms:
Both theories and empirical evidence support the ...importance of a hierarchy of goals: one or more overall goals that clients find personally meaningful and specific goals that are related to the overall goals. We posit that the client’s fundamental beliefs, goals and attitudes (“global meaning”) need to be explored before setting any rehabilitation goal. A chaplain or other person with similar skills can be involved in doing so in an open-ended way. The client’s fundamental beliefs, goals and attitudes serve as a point of departure for setting rehabilitation goals.
Setting goals:
We set out a three-stage process to set goals: (1) exploring the client’s global meaning (i.e. fundamental beliefs, goals and attitudes), (2) deriving a meaningful overall rehabilitation goal from the client’s global meaning and (3) setting specific rehabilitation goals that serve to achieve the meaningful overall rehabilitation goal.
Conclusion:
This is an extension of current practice in many rehabilitation teams, which may help counter the drive toward exclusively functional goals based around independence.
Background:
Cognitive behavioural therapy (CBT) reduces MS-related fatigue. However, studies on the long-term effects show inconsistent findings.
Objective:
To evaluate whether a blended booster ...programme improves the outcome of CBT for MS-related fatigue on fatigue severity at 1-year follow-up.
Method:
A multicentre randomized clinical trial in which 126 patients with MS were allocated to either a booster programme or no booster programme (control), after following 20-week tailored CBT for MS-related fatigue. Primary outcome was fatigue severity assessed with the Checklist Individual Strength fatigue subscale 1 year after start of treatment (T52). Mixed model analysis was performed by a statistician blinded for treatment-allocation to determine between-group differences in fatigue severity.
Results:
Fatigue severity at 1-year follow-up did not differ significantly between the booster (N = 62) and control condition (N = 64) (B = −2.01, 95% confidence interval (CI) = −4.76 to 0.75). No significant increase in fatigue severity was found at T52 compared with directly post-treatment (T20) in both conditions (B = 0.44, 95% CI = −0.97 to 1.85).
Conclusion:
Effects of CBT were sustained up to 1 year in both conditions. The booster programme did not significantly improve the long-term outcome of CBT for MS-related fatigue.
Trial registration:
Dutch Trial Register (NTR6966), registered 18 January 2018 https://www.trialregister.nl/trial/6782
Background
The prognostic value of four proposed modifications to the 8th American Joint Committee on Cancer (AJCC) TNM staging system has yet to be evaluated. This study aimed to validate five ...proposed modifications.
Methods
Patients who underwent pancreatic ductal adenocarcinoma resection (2014–2016), as registered in the prospective Dutch Pancreatic Cancer Audit, were included. Stratification and prognostication of TNM staging systems were assessed using Kaplan–Meier curves, Cox proportional hazard analyses, and C-indices. A new modification was composed based on overall survival (OS).
Results
Overall, 750 patients with a median OS of 18 months (interquartile range 10–32) were included. The 8th edition had an increased discriminative ability compared with the 7th edition {C-index 0.59 (95% confidence interval CI 0.56–0.61) vs. 0.56 (95% CI 0.54–0.58)}. Although the 8th edition showed a stepwise decrease in OS with increasing stage, no differences could be demonstrated between all substages; stage IIA vs. IB (hazard ratio HR 1.30, 95% CI 0.80–2.09;
p
= 0.29) and stage IIB vs. IIA (HR 1.17, 95% CI 0.75–1.83;
p
= 0.48). The four modifications showed comparable prognostic accuracy (C-index 0.59–0.60); however, OS did not differ between all modified TNM stages (ns). The new modification, migrating T3N1 patients to stage III, showed a C-index of 0.59, but did detect significant survival differences between all TNM stages (
p
< 0.05).
Conclusions
The 8th TNM staging system still lacks prognostic value for some categories of patients, which was not clearly improved by four previously proposed modifications. The modification suggested in this study allows for better prognostication in patients with all stages of disease.
Exercise as a subset of physical activity is a cornerstone in the management of multiple sclerosis (MS) based on its pleotropic effects. There is an exponential increase in the quantity of research ...on exercise in MS, yet a number of barriers associated with study content and quality hamper rapid progress in the field. To address these barriers and accelerate discovery, a new international partnership of MS-related experts in exercise has emerged with the goal of advancing the research agenda. As a first step, the expert panel met in May 2018 and identified the most urgent areas for moving the field forward, and discussed the framework for such a process. This led to identification of five themes, namely “Definitions and terminology,” “Study methodology,” “Reporting and outcomes,” “Adherence to exercise,” and “Mechanisms of action.” Based on the identified themes, five expert groups have been formed, that will further (a) outline the challenges per theme and (b) provide recommendations for moving forward. We aim to involve and collaborate with people with MS/MS organizations (e.g. Multiple Sclerosis International Federation (MSIF) and European Multiple Sclerosis Platform (EMSP)) in all of these five themes. The generation of this thematic framework with multi-expert perspectives can bolster the quality and scope of exercise studies in MS that may ultimately improve the daily lives of people with MS.
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