Protocol of a randomized controlled trial investigating Deep Brain Stimulation for MOtor symptoms in patients with Parkinson's disease DEmentia (DBS-MODE).

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established treatment for disabling motor symptoms of Parkinson's disease (PD) that persist despite optimal pharmacological treatment. Currently, DBS is not performed if there is concomitant significant cognitive impairment based on concerns of cognitive deterioration, higher complication rate and less functional improvement. However, this has not been investigated so far. METHODS: A single center, prospective, randomized, open-label, blinded end-point (PROBE design) pilot clinical trial is being performed. Patients are eligible for the trial if they have PD dementia (PDD), are able to provide informed consent, and experience disabling motor response fluctuations, bradykinesia, dyskinesia, or painful dystonia, despite optimal pharmacological treatment. In total 44 patients will be randomized to either STN-DBS accompanied by best medical treatment (DBS group) or to best medical treatment alone (BMT group). The primary outcome measure is the change from baseline to 30 weeks on the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III score in a standardized off-drug phase. The main secondary outcome measures consist of scales assessing cognitive aspects of daily living, neuropsychiatric symptoms and impulsive compulsive disorders. Additional secondary outcome measures include motor signs during on-drug phase, dyskinesia, motor fluctuations, cognitive performance, (severe) adverse events, treatment satisfaction, and caregiver burden. Patients will be followed during 52 weeks after randomization. DISCUSSION: The Deep Brain Stimulation for MOtor symptoms in patients with Parkinson's disease DEmentia (DBS-MODE) trial directly compares the effectiveness and safety of DBS with BMT in patients with PDD. TRIAL REGISTRATION: The DBS-MODE trial has been registered in the International Clinical Trial Registry Platform (NL9361) on the 24th of March 2021 ( https://trialsearch.who.int/Trial2.aspx?TrialID=NL9361 ).

The effect of tremor on disability assessment in chronic inflammatory demyelinating polyradiculoneuropathy.

Tremor in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is common, often unresponsive to treatment, and may contribute to disability. We aim to investigate whether tremor is associated with disability as measured in daily practice and clinical trials, independent of other impairments. We included 76 CIDP patients in this cross-sectional study. We assessed tremor with the Tremor Research Group essential tremor rating assessment scale (TETRAS) and the Fahn-Tolosa-Marin clinical rating scale (FTM). Disability was measured with the inflammatory Rasch-built overall disability scale (I-RODS) and the adjusted Inflammatory Neuropathy Cause and Treatment disability scale (INCAT-DS, categorized separately in arm score, or total score). Impairments including strength, sensory impairment, and fatigue were measured using specific impairment scales. We tested whether "the presence of a clinically relevant tremor" (based on TETRAS and FTM) or "tremor severity" (FTM part B sum score) was associated with disability scores (I-RODS, INCAT-DS total score, and INCAT-DS arm score), independent of the impairment scores, using multivariate regression. Both "the presence of a clinically relevant tremor" and "tremor severity" were significantly associated with disability measured by the INCAT-DS (arm score and total score), but not the I-RODS, independent of strength, sensory impairment, and fatigue. The explained variances were low. Clinically relevant tremor can (partly) explain disability in CIDP, as measured with the INCAT-DS, independent of muscle strength, sensory deficits, and fatigue. To assess disease activity in CIDP patients with tremor, both impairment and disability outcomes should be assessed, as disability is caused partly by tremor while the effect of immunotherapy on tremor seems limited.

The effect of a locally tailored intervention on the uptake of preconception care in the Netherlands: a stepped-wedge cluster randomized trial (APROPOS-II study).

BACKGROUND: The preconception period provides a window of opportunity for interventions aiming to reduce unhealthy lifestyle behaviours and their negative effect on pregnancy outcomes. This study aimed to assess the effectiveness of a locally tailored preconception care (PCC) intervention in a hybrid-II effectiveness implementation design. METHODS: A stepped-wedge cluster randomized controlled trial was performed in four Dutch municipalities. The intervention contained a social marketing strategy aiming to improve the uptake (prospective parents) and the provision (healthcare providers) of PCC. Prospective parents participated by administering a questionnaire in early pregnancy recalling their preconceptional behaviours. Experiences of healthcare providers were also evaluated through questionnaires. The composite primary outcome was adherence to at least three out of four preconceptional lifestyle recommendations (early initiation of folic acid supplements, healthy nutrition, no smoking or alcohol use). Secondary outcomes were preconceptional lifestyle behaviour change, (online) reach of the intervention and improved knowledge among healthcare providers. RESULTS: A total of 850 women and 154 men participated in the control phase and 213 women and 39 men in the intervention phase. The composite primary outcome significantly improved among women participating in the municipality where the reach of the intervention was highest (Relative Risk (RR) 1.57 (95% Confidence Interval (CI) 1.11-2.22). Among women, vegetable intake had significantly improved in the intervention phase (RR 1.82 (95%CI 1.14-2.91)). The aimed online reach- and engagement rate of the intervention was achieved most of the time. Also, after the intervention, more healthcare providers were aware of PCC-risk factors (54.5% vs. 47.7%; p = 0.040) and more healthcare providers considered it easier to start a conversation about PCC (75.0% vs. 47.9%; p = 0.030). CONCLUSION: The intervention showed some tentative positive effects on lifestyle behaviours among prospective parents. Primarily on vegetable intake and the knowledge and competence of healthcare providers. The results of this study contribute to the evidence regarding successfully implementing PCC-interventions to optimize the health of prospective parents and future generations. TRIAL REGISTRATION: Dutch Trial Register: NL7784 (Registered 06/06/2019).

Protocol of a randomized open label multicentre trial comparing continuous intrajejunal levodopa infusion with deep brain stimulation in Parkinson's disease - the INfusion VErsus STimulation (INVEST) study.

BACKGROUND: Both Deep Brain Stimulation (DBS) and Continuous intrajejunal Levodopa Infusion (CLI) are effective therapies for the treatment of Parkinson's disease (PD). To our knowledge, no direct head-to-head comparison of DBS and CLI has been performed, whilst the costs probably differ significantly. In the INfusion VErsus STimulation (INVEST) study, costs and effectiveness of DBS and CLI are compared in a randomized controlled trial (RCT) in patients with PD, to study whether higher costs of one of the therapies are justified by superiority of that treatment. METHODS: A prospective open label multicentre RCT is being performed, with ancillary patient preference observational arms. Patients with PD who, despite optimal pharmacological treatment, have severe response fluctuations, bradykinesia, dyskinesias, or painful dystonia are eligible for inclusion. A total of 66 patients will be randomized. There is no minimal inclusion in the patient preference arms. The primary health economic outcomes are costs per unit on the Parkinson's Disease Questionnaire-39 (PDQ-39) and costs per unit Quality-Adjusted Life Year (QALY) at 12 months. The main clinical outcome is patient-reported quality of life measured with the PDQ-39 at 12 months. Patients will additionally be followed during 36 months after initiation of the study treatment. DISCUSSION: The INVEST trial directly compares the costs and effectiveness of the advanced therapies DBS and CLI. TRIAL REGISTRATION: Dutch Trial Register identifier 4753, registered November 3rd, 2014; EudraCT number 2014-001501-32, Clinicaltrials.gov: NCT02480803.

Study protocol to investigate biomolecular muscle profile as predictors of long-term urinary incontinence in women with gestational diabetes mellitus.

BACKGROUND: Pelvic floor muscles (PFM) and rectus abdominis muscles (RAM) of pregnant diabetic rats exhibit atrophy, co-localization of fast and slow fibers and an increased collagen type I/III ratio. However, the role of similar PFM or RAM hyperglycemic-related myopathy in women with gestational diabetes mellitus (GDM) remains poorly investigated. This study aims to assess the frequency of pelvic floor muscle disorders and pregnancy-specific urinary incontinence (PS-UI) 12 months after the Cesarean (C) section in women with GDM. Specifically, differences in PFM/RAM hyperglycemic myopathy will be evaluated. METHODS: The Diamater is an ongoing cohort study of four groups of 59 pregnant women each from the Perinatal Diabetes Research Centre (PDRC), Botucatu Medical School (FMB)-UNESP (São Paulo State University), Brazil. Diagnosis of GDM and PS-UI will be made at 24-26 weeks, with a follow-up at 34-38 weeks of gestation. Inclusion in the study will occur at the time of C-section, and patients will be followed at 24-48 h, 6 weeks and 6 and 12 months postpartum. Study groups will be classified as (1) GDM plus PS-UI; (2) GDM without PS-UI; (3) Non-GDM plus PS-UI; and (4) Non-GDM without PS-UI. We will analyze relationships between GDM, PS-UI and hyperglycemic myopathy at 12 months after C-section. The mediator variables to be evaluated include digital palpation, vaginal squeeze pressure, 3D pelvic floor ultrasound, and 3D RAM ultrasound. RAM samples obtained during C-section will be analyzed for ex-vivo contractility, morphological, molecular and OMICS profiles to further characterize the hyperglycemic myopathy. Additional variables to be evaluated include maternal age, socioeconomic status, educational level, ethnicity, body mass index, weight gain during pregnancy, quality of glycemic control and insulin therapy. DISCUSSION: To our knowledge, this will be the first study to provide data on the prevalence of PS-UI and RAM and PFM physical and biomolecular muscle profiles after C-section in mothers with GDM. The longitudinal design allows for the assessment of cause-effect relationships between GDM, PS-UI, and PFMs and RAMs myopathy. The findings may reveal previously undetermined consequences of GDM.

Percutaneous cement augmentation in the treatment of osteoporotic vertebral fractures (OVFs) in the elderly: a systematic review.

PURPOSE: A systematic review, to study treatment effects for osteoporotic vertebral fractures (OVFs) in the elderly including all available evidence from controlled trials on percutaneous cement augmentation. METHODS: Primary studies, published up to December, 2019, were searched in PubMed and the Cochrane Library. Selected were all prospective controlled studies including patients > 65 years of age and reporting on at least one main outcome. Main outcomes were pain, disability and quality of life (QOL) 1 day post-intervention and at 6 months postoperatively. Excluded were meta-analyses or reviews, retrospective or non-controlled studies, case studies, patients' groups with neoplastic and/or traumatic fractures and/or neurologically compromised patients. RESULTS: Eighteen studies comprising 2165 patients (n = 1117 percutaneous cement augmentation, n = 800 conservative treatment (CT), n = 248 placebo) with a mean follow-up of up to 12 months were included. Pooled results showed significant pain relief in favor of percutaneous cement augmentation compared to CT, direct postoperative and at 6 months follow-up. At 6 months, a significant difference was observed for functional disability scores in favor of percutaneous cement augmentation. When comparing percutaneous cement augmentation to placebo, no significant differences were observed. CONCLUSION: This review incorporates all current available evidence (RCTs and non-RCTs) on the efficacy of percutaneous cement augmentation in the treatment of OVFs in the elderly. Despite methodological heterogeneity of the included studies, this review shows overall significant sustained pain relief and superior functional effect in the short- and long term for percutaneous cement augmentation compared to conservative treatment. These slides can be retrieved under Electronic Supplementary Material.

Movement behaviour in adults with haemophilia compared to healthy adults.

BACKGROUND: Limited research has been published regarding movement behaviour of adult persons with haemophilia (PWH). It is hypothesized that avoidance of activities and more sedentary behaviour cause poorer physical functioning. AIM: To determine differences in movement behaviour between PWH and healthy adults. METHODS: Movement behaviour was measured with an accelerometer distinguishing between; lying/non-wear, sitting, standing, walking, running and cycling. Time spent on activities was compared between PWH and healthy adults, using absolute time spent on activities and activities as percentage of wear time. RESULTS: One hundred and five PWH (32 mild/moderate with a mean age of 42.8 ± 15.1, severe 42.1 ± 13.6) and 98 healthy adults (mean age 41.9 ± 15.5) showed that adults with severe haemophilia sit and stand more than healthy adults (4.5 [CI 0.6-8.4] and 4.2 [CI 1.8-6.6] h/wk, respectively) and walk and run less (3.4 [CI 1.4-5.3] hours and 33.6 [CI 19.0-41.7] min/wk, respectively). Patients with mild/moderate haemophilia stand more than healthy adults (3.3 [CI 0.1-6.4] h/wk). Differences in sitting between severe haemophilia and healthy adults and differences in standing between mild/moderate haemophilia and healthy adults disappeared when using activities as percentage of wear time. CONCLUSION: Movement behaviour of adults with severe haemophilia differs from healthy adults, mainly due to less walking and less running. No differences were found in other activities and postures or the distribution of movement behaviour over the day. No significant differences were found between adults with mild/moderate haemophilia and healthy adults.

Preventing musculoskeletal complaints in music students: a randomized controlled trial.

BACKGROUND: Musculoskeletal complaints in music students are common. Little is known about effectiveness of interventions. AIMS: To assess whether a biopsychosocial prevention course is better at reducing disability due to musculoskeletal disorders compared with physical activity promotion. METHODS: This was a multicentre randomized controlled trial with intention-to-treat analysis. Participants were first- and second-year students from five conservatories, randomized to experimental or control groups. The experimental group participated in 11 classes on body posture playing the instrument according to postural exercise therapy, and performance-related psychosocial aspects. The control group participated in five classes promoting physical activity according to national guidelines. The primary outcome was disability using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, including the performing arts module. Secondary outcomes were pain, quality of life, playing-related musculoskeletal disorders and health behaviour. Outcomes were assessed at six points, from baseline until 2-year follow-up. RESULTS: One hundred and seventy participants were randomized to experimental (n = 84) or control (n = 86) groups. Loss to follow-up was 40% during the trial and 69% at 2-year follow-up. The dropout rate was equal in both groups. Overall, there were no significant differences between groups for any outcome adjusted for baseline characteristics: percentage disability, odds ratio was 1.31, 95% confidence interval (CI) 0.69-2.51; general DASH, ß = -0.57, 95% CI -3.23 to 2.09; and performing arts module, ß = -0.40, 95% CI 5.12-4.32. CONCLUSIONS: A biopsychosocial prevention course tailored for musicians was not superior to physical activity promotion in reducing disability. Large numbers lost to follow-up warrant cautious interpretation.

Playing the Clarinet: Influence of Body Posture on Muscle Activity and Sound Quality.

Musculoskeletal complaints are highly prevalent in clarinetists and are related to high arm load while playing. It is hypothesized that postural exercise therapy may be used to adapt muscle activity patterns while playing and thus contribute to better sound quality. The goal of the present study was to investigate the relationship between body posture, muscle activity, and sound quality in clarinetists while playing the instrument in two different postures, their habitual sitting posture (control, CO) vs an experimental sitting posture (EXP) based on Mensendieck postural exercise therapy, method Samama. Twenty healthy professional and student clarinet players, aged 18-60 years, were included in this cross-sectional study. Participants played a 60-second musical excerpt in CO, followed by instruction on the EXP body posture, and then played in the EXP condition. Two-dimensional goniometric analysis was used to calculate body posture; muscle activity was measured bilaterally using surface electromyography. In EXP, a significantly smaller low thoracic angle, smaller high thoracic angle, and larger pelvic tilt angle (all p<0.001) were found. EMG results indicated that the left and right erector spinae L3 and left and right lower trapezius were more active in EXP compared to CO, whereas left upper trapezius and right brachioradialis were less active in EXP than CO. Most participants experienced better sound quality in EXP, whereas blinded experts found no consistent pattern between body posture and sound quality. To conclude, it seems that postural exercise therapy may change muscle activity patterns. By increasing stability, a decrease in activity of the upper extremity muscles can be induced.

How do patients and professionals differentiate between intra-articular joint bleeds and acute flare-ups of arthropathy in patients with haemophilia?

INTRODUCTION: The overlap in symptoms between joint bleeds and flare-ups of haemophilia arthropathy (HA) creates difficulties in differentiating between the two conditions. Diagnosis of haemarthrosis is currently empirically made based upon clinical presentations. However, no standard diagnostic criteria are available. To offer appropriate treatment, rapid and accurate diagnosis is essential. Additionally, adequate differentiation can decrease health costs significantly. AIM: The aim of this study was to identify signs and symptoms to differentiate between an intra-articular joint bleed and an acute flare-up of HA in patients with haemophilia and make an initial proposal of items to include in a diagnostic criteria set. METHODS: Six focus group interviews with a total of 13 patients and 15 professionals were carried out. The focus groups were structured following the Nominal Group Technique (NGT). RESULTS: The most important signs and symptoms used to differentiate between joint bleeds and HA were (i) course of the symptoms, (ii) cause of the complaints, (iii) joint history, (iv) type of pain and (v) degree of impairments in range of motion. CONCLUSION: This qualitative study provides insight into signs and symptoms that are currently used to differentiate between joint bleeds and flare-ups of HA. Results of this study can be used to develop a valid and standardized clinical diagnostic criteria set to differentiate between these two conditions. Further research is necessary to validate the signs and symptoms found in this study.

Systematic review: risk factors for musculoskeletal disorders in musicians.

BACKGROUND: Although many musicians suffer from musculoskeletal disorders, aetiological factors are unclear. AIMS: To systematically search for and synthesize the best available evidence on risk factors for musculoskeletal disorders in musicians. METHODS: A database search was performed in PubMed, EMBASE, CINAHL, Pedro, OTseeker and Psychinfo. A manual search was conducted in the journals Medical Problems of Performing Artists and Psychology of Music. Studies with an objective to investigate determinants associated with playing-related musculoskeletal disorders were included. Papers were selected based on adequacy of statistical methods for the purpose of the study. Search, first screening and selection were performed by one author. Two reviewers independently performed the final selection using full-text reports. Methodological quality assessment was performed by two reviewers independently. RESULTS: One case-control and 14 cross-sectional studies were included. Methodological quality was in general low. Large heterogeneity existed in study design, population, measurement of determinant and outcome and analysis techniques. Data were presented descriptively. Consistent results were found indicating that previous musculoskeletal injury, music performance anxiety, high levels of stress and being a female playing a stringed instrument seemed to be associated with more musculoskeletal disorders. Influence over or support at work, orchestra category/status, exercise behaviour and cigarette smoking seemed to be unrelated with musculoskeletal disorders. No conclusions could be made on causality, as the current data only represent cross-sectional associations. CONCLUSIONS: Because of lack of prospective studies, no causal relations could be identified in the aetiology of (playing-related) musculoskeletal disorders in instrumental musicians.

Empty can and drop arm tests for cuff rupture : Improved specificity after subacromial injection.

Shoulder disorders are common in the general population : they occur in about 25 of every 1000 patients per year. A rather large majority are caused by cuff disorders. Differentiating between impingement and cuff rupture is essential to adequate treatment. Clinical tests have been developed, but their accuracy is limited. This study was performed to improve clinical accuracy by combining single tests and adding a subacromial injection. We postulated that the empty can and drop arm tests would result in higher sensitivity and specificity after subacromial injection. METHOD: We prospectively assessed 49 patients with the empty can and drop arm tests and used ultrasound to compare the individual and combined results. RESULT: The ultrasound found six cuff ruptures. Specificity improved and sensitivity decreased after subacromial injection. CONCLUSION: Only specificity improved after subacromial injection. Combining the test results led to an increase in both sensitivity and specificity without injection.

Differentiating between signs of intra-articular joint bleeding and chronic arthropathy in haemophilia: a narrative review of the literature.

INTRODUCTION: Elderly patients with haemophilia (PWH) suffer from both haemarthrosis and haemophilic arthropathy (HA). Diagnosis of haemarthrosis in PWH is currently based on clinical presentation. No diagnostic protocols or validated criteria are available to identify haemarthrosis or to differentiate haemarthrosis from HA. AIM: The aim of this study is to identify symptoms and signs that can be used to differentiate haemarthrosis from HA. METHODS: A narrative literature review was performed on symptoms associated with haemarthrosis and symptoms associated with HA. Additionally, literature on the diagnosis of haemarthrosis in patients without haemophilia, imaging techniques and biomarkers was searched. RESULTS: This review shows that there is no consensus about the symptoms associated with haemarthrosis and that there is limited literature about the symptoms associated with HA. Additionally, symptoms associated with haemarthrosis partly overlap with symptoms of HA, particularly those symptoms associated with flare-ups of HA. Due to the overlap in symptoms differentiating between these conditions is complex. Furthermore, differentiating based on imaging techniques or biomarkers causes practical difficulties. CONCLUSION: Despite the overlap in symptoms, differentiating between joint bleeds and flare-ups of HA based on clinical presentation still seems the most convenient and practical solution. Further research is necessary to identify specific symptoms that can be used to differentiate between the two conditions.

Protocol of a randomised delayed-start double-blind placebo-controlled multi-centre trial for Levodopa in EArly Parkinson's disease: the LEAP-study.

BACKGROUND: The aim of this study is to investigate if early treatment with levodopa has a beneficial disease modifying effect on Parkinson's disease (PD) symptoms and functional health, improves the ability to (maintain) work, and reduces the use of (informal) care, caregiver burden, and costs. Additionally, cost-effectiveness and cost-utility of early levodopa treatment will be assessed. METHODS: To differentiate between the direct symptomatic effects and possible disease modifying effects of levodopa, we use a randomised delayed-start double-blind placebo-controlled multi-centre trial design. Patients with early stage PD whose functional health does not yet necessitate initiation of PD-medication will be randomised to either 40 weeks of treatment with levodopa/carbidopa 100/25 mg TID including 2 weeks of dose escalation or to 40 weeks placebo TID. Subsequently, all patients receive levodopa/carbidopa 100/25 mg TID for 40 weeks. There are 8 assessments: at baseline and at 4, 22, 40, 44, 56, 68, and 80 weeks. The primary outcome measure is the difference in the mean total Unified Parkinson's Disease Rating Scale scores between the early- and delayed-start groups at 80 weeks. Secondary outcome measures are rate of progression, the AMC Linear Disability Score, side effects, perceived quality of life with the Parkinson's Disease Questionnaire-39, the European Quality of Life-5 Dimensions (EQ-5D), ability to (maintain) work, the use of (informal) care, caregiver burden, and costs. 446 newly diagnosed PD patients without impaired functional health need to be recruited in order to detect a minimal clinical relevant difference of 4 points on the total UPDRS at 80 weeks. DISCUSSION: The LEAP-study will provide insights into the possible disease modifying effects of early levodopa. TRIAL REGISTRATION: ISRCTN30518857, EudraCT number 2011-000678-72.

Editor's choice--The effect of supervision on walking distance in patients with intermittent claudication: a meta-analysis.

BACKGROUND: A number of reviews have reported the influence of exercise therapy (ET) for the treatment of intermittent claudication (IC). However, a complete overview of different types of ET is lacking. The aim of this meta-analysis was to study the effect of supervision on walking capacity in patients with IC. It was hypothesized that there was a positive treatment effect in relation to the intensity of supervision and improvement in walking capacity (i.e., a "dose-response" hypothesis). METHODS: A systematic search in the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases was performed. Only randomized controlled trials (RCTs) evaluating the efficacy of an ET in IC were included. Type of supervision, treadmill protocol, length of ET, total training volume, and change in walking distance were extracted. RCTs were categorised according to type of support: no exercise, walking advice, home-based exercise (HB-ET), and supervised exercise therapy (SET). A standardised mean difference between pre- and post-training maximal walking distance (MWD) and pain-free walking distance (PFWD) was calculated for all subgroups at 6 weeks, and 3 and 6 months of follow up. RESULTS: Thirty studies involving 1406 patients with IC were included. The overall quality was moderate-to-good, although number of included patients varied widely (20-304). The intensity of supervision was directly related to MWD and PFWD. SET was superior to other conservative treatment regimens with respect to improvement in walking distances at all follow-ups. However, the difference between HB-ET and SET at 6 months of follow up was not significant. CONCLUSION: Supervised exercise therapy for intermittent claudication is superior to all other forms of exercise therapy. Intensity of supervision is related to improved walking distance.

Identification of Predictors for Progression of Scoliosis in Rett Syndrome.

Rett syndrome is a neurodevelopmental disorder in which scoliosis is a common orthopedic complication. This explorative study aims to identify predictors for rapid progression of scoliosis in Rett syndrome to enable variable selection for future prediction model development. A univariable logistic regression model was used to identify variables that discriminate between individuals with and without rapid progression of scoliosis (>10 ∘Cobb angle/6 months) based on multi-center data. Predictors were identified using univariable logistic regression with OR (95% CI) and AUC (95% CI). Age at inclusion, Cobb angle at baseline and epilepsy have the highest discriminative ability for rapid progression of scoliosis in Rett syndrome.

A multicenter double-blind randomized crossover study comparing the impact of dorsal subthalamic nucleus deep brain stimulation versus standard care on apathy in Parkinson's disease: a study protocol.

BACKGROUND: Neuroimaging studies suggest an association between apathy after deep brain stimulation (DBS) and stimulation of the ventral part of the subthalamic nucleus (STN) due to the associative fibers connected to the non-motor limbic circuits that are involved in emotion regulation and motivation. We have previously described three patients with severe apathy that could be fully treated after switching stimulation from a ventral electrode contact point to a more dorsal contact point. OBJECTIVES: To determine whether more dorsal stimulation of the STN decreases apathy compared to standard care in a multicenter randomized controlled trial with a crossover design. METHODS: We will include 26 patients with a Starkstein Apathy Scale (SAS) score of 14 or more after subthalamic nucleus (STN) deep brain stimulation (DBS) for refractory Parkinson's disease. This is a multicenter trial conducted in two teaching hospitals and one university medical center in the Netherlands after at least 3 months of STN DBS. Our intervention will consist of 1 month of unilateral dorsal STN stimulation compared to treatment as usual. The primary outcome is a change in SAS score following 1 month of DBS on the original contact compared to the SAS score following 1 month of DBS on the more dorsal contact. Secondary outcomes are symptom changes on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale motor part III, Montgomery-Åsberg Depression Rating Scale, 39-item Parkinson's disease questionnaire, Parkinson's disease impulsive-compulsive disorders questionnaire, changes in levodopa-equivalent daily dosage, apathy rated by the caregiver, and burden and quality of life of the caregiver. TRIAL REGISTRATION: ClinicalTrials.gov NL8279. Registered on January 10, 2020.

Responsiveness and interpretability of incontinence severity scores and FIQL in patients with fecal incontinence: a secondary analysis from a randomized controlled trial.

INTRODUCTION AND HYPOTHESIS: This study aims to assess the responsiveness and interpretability of the Vaizey score, Wexner score, and the Fecal Incontinence Quality of Life Scale (FIQL) for use in the evaluation of patients with fecal incontinence (FI). METHODS: Eighty patients with FI with a mean age of 59.3 (SD ± 11.9) were enrolled in a randomized controlled trial. The patient-reported outcomes were tested for internal and external responsiveness, longitudinal construct validity, and interpretability. RESULTS: All total scores proved to have both adequate to excellent responsiveness and longitudinal construct validity, and changes were in agreement with subjective improvement. Due to variability in minimally important change estimates (Vaizey score -5 to -3, Wexner score -3 to -2, FIQL 1.1 to 1.2), they should be used as indicators. All patient-reported outcomes showed psychometric or practical limitations. CONCLUSIONS: The instruments available to date to evaluate severity and quality of life in FI do not yet attain the highest levels of psychometric soundness. As the focus of patients may differ from that of physicians, it is recommended that several measures should be included for evaluation. So far, there are suggestions that the Wexner score is most suitable for severity assessment and the FIQL for evaluating quality of life.

Dutch translation, adaptation and validation of the OT-10 scale for orthostatic tremor.

Introduction: There are currently no effective treatments for primary orthostatic tremor (POT). An adequate disease-specific POT severity scale is a prerequisite to conduct clinical trials and monitor disease severity in clinical practice. Recently, the English OT-10 scale has been developed for this purpose. Here we aimed to obtain a scale to measure the severity of POT in Dutch speaking individuals. Methods: An established translation, adaptation and validation approach was employed to obtain a Dutch version of the OT-10 scale. Validation was performed in a Dutch POT cohort (n = 46). Results: A Dutch OT-10 scale was obtained which showed good internal consistency (Cronbach's alpha > 0.80), total score test-retest reliability (intraclass correlation coefficient > 0.80), and concurrent validity (Pearson correlation > 0.80). Item-to-total correlation was good (weighted kappa > 0.40) for all items, and item test-retest reliability was good (weighted kappa > 0.40) for eight out of ten items. Overall, the Dutch OT-10 scale demonstrated acceptable validity. Conclusions: We obtained and validated a Dutch version of the OT-10 scale, capturing POT severity. Next to its use in clinical practice, translation and validation of the OT-10 scale in more languages will help to find evidence-based treatments for POT.

A comparison of methods to suppress electrocardiographic artifacts in local field potential recordings.

OBJECTIVE: Local field potential (LFP) recordings from deep brain stimulation (DBS) electrodes are often contaminated with electrocardiographic (ECG) artifacts that hinder the detection of disease-specific electrical brain activity. METHODS: Three ECG suppression methods were evaluated: (1) QRS interpolation of the Perceive toolbox, (2) template subtraction, and (3) singular value decomposition (SVD). LFPs were recorded with the Medtronic PerceptTM PC system in nine Parkinson's disease patients with stimulation OFF ("OFF-DBS"; anode disconnected) and ON at 0 mA ("ON-DBS 0 mA"; anode connected). Findings were verified with simulated ECG-contaminated time series. RESULTS: ECG artifacts were present in 10 out of 18 ON-DBS 0 mA recordings. All ECG suppression methods drastically reduced artifact-induced beta band (13-35 Hz) power and at least partly recovered the beta peak and beta burst dynamics. Using external ECG recordings and lengthening artifact epoch length improved the performance of the suppression methods. Increasing epoch length, however, elevated the risk of flattening the beta peak and losing beta burst dynamics. CONCLUSIONS: The SVD method formed the preferred trade-off between artifact cleaning and signal loss, as long as its parameter settings are adequately chosen. SIGNIFICANCE: ECG suppression methods enable analysis of disease-specific neural activity from signals affected by ECG artifacts.