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In multiple sclerosis (MS), depression and anxiety are common, yet their relation to disease progression is unclear. We investigated whether Hospital Anxiety and Depression Scale (HADS) symptoms predict neurological disability progression. In our prospective cohort of people with primary progressive MS (PPMS), depressive and anxiety symptoms were assessed using HADS. Disability progression at 1 and 2years was assessed using three predefined endpoints: (1) Expanded Disability Status Scale (EDSS), (2) a three-variable composite endpoint (EDSS, Timed 25-Foot Walk (T25FW), or Arm Function in Multiple Sclerosis Questionnaire (AMSQ)), and (3) a five-variable composite endpoint (EDSS, T25FW, AMSQ, Symbol Digit Modalities Test (SDMT), or Patient-Determined Disease Steps (PDDS)). Logistic regression modelled whether HADS scores predicted disability progression. Boruta feature selection identified the most informative HADS items. One hundred eleven adults with PPMS completed the HADS (all ≥ 1-year follow-up; 62 ≥ 2years). Progression occurred predominantly on individual domains. At 1year, higher total HADS scores predicted progression on the five-variable composite endpoint (OR 3.10, [95% CI 0.99-9.75], p = 0.05; AUC 0.59, [95% CI 0.47-0.70]). At 2years, the depression sub-score consistently predicted progression on EDSS (OR 8.88, [95% CI 1.12-70.66], p = 0.04), and the five-variable composite endpoint (OR 9.46,[95% CI 1.50-59.52], p = 0.02). Boruta feature selection identified HADS depression-associated items 6 and 8 as best predictors; together achieving similar predictive accuracy compared to the full HADS questionnaire. Higher HADS scores, particularly depressive symptoms, predicted disability progression. These findings indicate prognostic value of patient-reported outcomes in predicting disease worsening and their potential use in guiding personalised treatment in progressive MS.

<bold>Background:</bold> Asthma symptoms and prior exacerbations increase future exacerbation risk. The composite Asthma Impairment and Risk Questionnaire (AIRQ) is superior to impairment-based tools, alone or combined with risk factors, at identifying at-risk patients. <bold>Aims:</bold> To evaluate risk and impairment patterns in patients rated completely/well-controlled (C/WC) by various control tools. <bold>Methods:</bold> 1064 patients ≥12 years were assessed by AIRQ, GINA symptom control questions, Asthma Control Test (ACT), and expert opinion (EO) informed by GINA questions and risk factors. Proportion of patients assessed as C/WC by these methods relative to prior-year exacerbations, prior-two week symptoms (daytime symptoms, night awakening, activity limits, rescue use, social activity limitation, exercise limitations, difficulty controlling asthma), and subsequent exacerbations were compared (McNemar’s test: p≤0.05). <bold>Results:</bold> EO rated the highest proportion of patients as C/WC. Among C/WC patients, AIRQ had the highest proportion without prior exacerbations, a higher proportion without impairment than the two symptom-based tools, and a lower proportion than ACT and EO with prior exacerbations or impairment who had subsequent exacerbations (Figure). For all assessments, both baseline risk and impairment contributed to future exacerbations. <bold>Conclusions:</bold> AIRQ minimizes overestimation of control and best identifies patients needing interventions to prevent exacerbations.

BackgroundFrailty in newly-diagnosed multiple myeloma (NDMM) patients is associated with treatment-related toxicity, which negatively affects health-related quality of life (HRQoL). Currently, data on changes in HRQoL of frail and intermediate-fit MM patients during active treatment and post-treatment follow-up are absent. MethodsThe HOVON123 study (NTR4244) was a phase II trial in which NDMM patients ≥ 75 years were treated with nine dose-adjusted cycles of Melphalan-Prednisone-Bortezomib (MPV). Two HRQoL instruments (EORTC QLQ-C30 and -MY20) were obtained before start of treatment, after 3 and 9 months of treatment and 6 and 12 months after treatment for patients who did not yet start second-line treatment. HRQoL changes and/or differences in frail and intermediate-fit patients (IMWG frailty score) were reported only when both statistically significant (p < 0.005) and clinically relevant (>MID). Results137 frail and 71 intermediate-fit patients were included in the analysis. Compliance was high and comparable in both groups. At baseline, frail patients reported lower global health status, lower physical functioning scores and more fatigue and pain compared to intermediate-fit patients. Both groups improved in global health status and future perspective; polyneuropathy complaints worsened over time. Frail patients improved over time in physical functioning, fatigue and pain. Improvement in global health status occurred earlier than in intermediate-fit patients. ConclusionHRQoL improved during anti-myeloma treatment in both intermediate-fit and frail MM patients. In frail patients, improvement occurred faster and, in more domains, which was retained during follow-up. This implies that physicians should not withhold safe and effective therapies from frail patients in fear of HRQoL deterioration.

Abstract BackgroundWhile neuropsychiatric symptoms (NPS) are common in early Alzheimer’s disease (AD), they are currently underdiagnosed and undertreated in the memory clinic. Therefore, we evaluated the effectiveness of the Describe, Investigate, Create, Evaluate (DICE™) approach to structure and standardize the care for NPS in AD in the memory clinic.MethodA total of 60 community‐dwelling patients with MCI, AD dementia, or AD/VaD dementia were enrolled with their caregivers in two waves (Table‐1). The first wave (n = 36) received care as usual and served as a control group, while the second wave of patients (n = 24, of which n = 20 have currently completed the study) underwent the DICE method. We applied the DICE method during two visits in which NPS were assessed, underlying causes were examined, and patients and caregivers were instructed on management strategies to deal with NPS, which were evaluated after one month. Outcomes were assessed after three and six months. Primary outcomes were quality of life of patients (QoL‐AD) and caregivers (Carerqol‐7D). Secondary outcomes included caregiver burden (Perseverance time), NPS prevalence and severity (NPI‐Q &amp; BEHAVE‐AD), NPS‐related distress (NPI‐Q), competence managing NPS (additional NPI‐Q item), and psychotropic drug use. We used linear mixed models to examine differences in outcomes at group‐level and reliable change index to examine which participants in the intervention group showed reliable improvement in the primary outcomes.ResultWe found no significant differences between the two groups in change in quality of life or any of the secondary outcomes (all p&gt;0.05, Table‐2). A proportion of the intervention group showed reliable improvement in quality of life of patients (n = 6/20) and caregivers (n = 7/20). At baseline, these patients tended to show higher NPS burden and their caregivers reported more NPS‐related distress and lower feelings of competence while managing NPS compared to participants that did no show reliable improvement.ConclusionThis Stage 2 efficacy study shows no benefits of the DICE method on in early AD at group‐level, but suggest that particular participants might benefit from this approach. Data will be re‐analyzed when all intervention group participants have completed the study and will be extended with qualitative data investigating NPS‐related knowledge and management styles of participants.

Aim: To gain insight into current treatment and barriers to optimal treatment for high disease activity relapsing remitting multiple sclerosis (MS) in the Netherlands. Materials & methods: A two-round Delphi panel using an online questionnaire was conducted. SevenMS neurologists from diverse locations in the Netherlands were invited to participate. Result: Out of the seven MS neurologists, five completed both questionnaire rounds. Conclusion: Effectiveness and sideeffects along with patient's lesion load were the most important factors for choosing a disease modifying therapy(DMTs). Respondents felt restricted to optimally treat their patients due to reimbursement restrictions for certain disease modifying therapies, although agreed that satisfactory treatment options are currently available. The answers show consensus between the participating MS neurologists with high certainty of answers.

The aim of this case report is twofold: the very rare Hirayama disease is discussed, including the impact on the patient’s functioning. The unique way to solve an orthesis problem is described, by observing patient’s performance meticulously. Various hand function assessments were used to cover every level of the International Classification of Functioning model. An occupation-based approach was followed by performing a working visit during which the essence of his treatment problem became apparent. The development of a new adjustable brace is described. Combining two sorts of wrist positions in one splint is a novel approach that could be helpful for patients with other conditions. A work visit was helpful to focus on the participation level. The occupation-based intervention resulted in the patient’s ability to resume work.

The aim of this systematic review was to assess the effect of a whitening dentifrice (WDF) relative to a regular dentifrice (RDF) on the reduction of natural extrinsic tooth surface discoloration (ETD). The MEDLINE-PubMed, Cochrane-CENTRAL and EBSCO-Dentistry and Oral Sciences databases were searched, up to April 2017. The inclusion criteria were as follows:(randomized)controlled clinical trials, healthy subjects ≥18years of age, studies comparing WDF with RDF, a follow-up period of at least 6weeks and studies scoring ETD as the stain area/extent, stain intensity or a composite score. Studies using an induced staining model were excluded. Independent screening of 851 unique papers resulted in 21 eligible publications, which included 32 comparisons. The descriptive analysis illustrated that the majority of comparisons showed a significant effect on ETD, in favour of WDF over RDF. The meta-analysis substantiated this observation and revealed that the difference of means (diffM) comparing WDF and RDF was a reduction for stain area of -0.44 [(95% CI: -0.55; -0.339) (P<.00001)] according to the original Lobene Stain Index; this result is in favour of the WDF. For the modified Lobene Stain Index, the diffM was -0.41 [(95% CI: -0.71; -0.10) (P=.009)]. For overall stain intensity, the diffM was -0.35 [(95% CI: -0.44; -0.25) (P<.00001)], and the composite score was -0.39 [(95% CI: -0.57; -0.21) (P<.0001)] and -0.54 [(95% CI: -0.66; -0.43) (P<.00001)]. Subgroup analysis differentiating between products that contained added chemical antidiscoloration agents showed a similar pattern. In this review, nearly all dentifrices that are specifically formulated for tooth whitening were shown to have a beneficial effect in reducing ETD, irrespective of whether or not a chemical discoloration agent was added.

Anastomotic leakage is a potential major complication after colorectal surgery. The C-seal was developed to help reduce the clinical leakage rate. It is an intraluminal sheath that is stapled proximal to a colorectal anastomosis, covering it intraluminally and thus preventing intestinal leakage in case of anastomotic dehiscence. The C-seal trial was initiated to evaluate the efficacy of the C-seal in reducing anastomotic leakage in stapled colorectal anastomoses. This RCT was performed in 41 hospitals in the Netherlands, Germany, France, Hungary and Spain. Patients undergoing elective surgery with a stapled colorectal anastomosis less than 15 cm from the anal verge were eligible. Included patients were randomized to the C-seal and control groups, stratified for centre, anastomotic height and intention to create a defunctioning stoma. Primary outcome was anastomotic leakage requiring invasive treatment. Between December 2011 and December 2013, 402 patients were included in the trial, 202 in the C-seal group and 200 in the control group. Anastomotic leakage was diagnosed in 31 patients (7·7 per cent), with a 10·4 per cent leak rate in the C-seal group and 5·0 per cent in the control group (P = 0·060). Male sex showed a trend towards a higher leak rate (P = 0·055). Construction of a defunctioning stoma led to a lower leakage rate, although this was not significant (P = 0·095). C-seal application in stapled colorectal anastomoses does not reduce anastomotic leakage. Registration number: NTR3080 (http://www.trialregister.nl/trialreg/index.asp).

Therapeutic response to metformin, a first-line drug for type 2 diabetes (T2D), is highly variable, in part likely due to genetic factors. To date, metformin pharmacogenetic studies have mainly focused on the impact of variants in metformin transporters genes, with inconsistent results. To clarify the significance of these variants in glycaemic response to metformin in T2D, we performed a large-scale meta-analysis across the cohorts of Metformin Genetics Consortium (MetGen). Nine candidate polymorphisms in five transporter genes (OCT1, OCT2, MATE1, MATE2-K and OCTN1) were analysed in up to 7,968 individuals. None of the variants showed a significant effect on metformin response in the primary analysis, or in the exploratory secondary analyses, when patients were stratified according to possible confounding genotypes or prescribed metformin daily dose. Our results suggest that candidate transporters genes variants have little contribution to variability in glycaemic response to metformin in T2D.