Cost-effectiveness of physiotherapy in childhood functional constipation: a randomized controlled trial in primary care.

OBJECTIVE: Health care expenditures for children with functional constipation (FC) are high, while conservative management is successful in only 50% of the children. The aim is to evaluate whether adding physiotherapy to conventional treatment (CT) is a cost-effective strategy in the management of children with FC aged 4-18 years in primary care. METHODS: A cost-effectiveness analysis was performed alongside a randomized controlled trial (RCT) with 8-month follow-up. Costs were assessed from a societal perspective, effectiveness included both the primary outcome (treatment success defined as the absence of FC and no laxative use) and the secondary outcome (absence of FC irrespective of laxative use). Uncertainty was assessed by bootstrapping and cost-effectiveness acceptability curves (CEACs) were displayed. RESULTS: One hundred and thirty-four children were randomized. The incremental cost-effectiveness ratio (ICER) for one additional successfully treated child in the physiotherapy group compared with the CT group was €24,060 (95% confidence interval [CI] €-16,275 to €31,390) and for the secondary outcome €1,221 (95% CI €-12,905 to €10,956). Subgroup analyses showed that for children with chronic laxative use the ICER was €2,134 (95% CI -24,975 to 17,192) and €571 (95% CI 11 to 3,566), respectively. At a value of €1,000, the CEAC showed a probability of 0.53 of cost-effectiveness for the primary outcome, and 0.90 for the secondary outcome. CONCLUSIONS: Physiotherapy added to CT as first-line treatment for all children with FC is not cost-effective compared with CT alone. Future studies should consider the cost-effectiveness of physiotherapy added to CT in children with chronic laxative use. TRIAL REGISTRATION: The RCT is registered in the Netherlands Trial Register (NTR4797), on the 8th of September 2014. The first child was enrolled on the 2nd of December 2014. https://www.trialregister.nl/trial/4654.

Oral ondansetron for paediatric gastroenteritis in primary care: a randomised controlled trial.

BACKGROUND: Acute gastroenteritis (AGE) affects almost all children aged ≤5 years. In secondary care, ondansetron was found to be effective at reducing vomiting. AIM: To determine the effectiveness of adding oral ondansetron to care as usual (CAU) to treat vomiting in children with AGE attending out-ofhours primary care (OOH-PC). DESIGN AND SETTING: A pragmatic randomised controlled trial at three OOH-PC centres in the north of the Netherlands (Groningen, Zwolle, and Assen), with a follow-up of 7 days. METHOD: Children were included if they were: aged 6 months-6 years; AGE diagnosed by a GP; ≥4 reported episodes of vomiting in the 24 hours before presentation; ≥1 reported episode of vomiting in the 4 hours before presentation; and written informed consent from both parents. Children were randomly allocated to either the control group or the intervention group. The control group received CAU, namely oral rehydration therapy. The intervention group received CAU plus one dose of oral ondansetron (0.1 mg/kg). RESULTS: In total, 194 children were included for randomisation. One dose of oral ondansetron decreased the proportion of children who continued vomiting within 4 hours from 42.9% to 19.5%, with an odds ratio of 0.37 (95% confidence interval [CI] = 0.20 to 0.72, number needed to treat: four). Ondansetron also decreased the number of vomiting episodes within 4 hours (incidence rate ratio 0.51 [95% CI = 0.29 to 0.88]) and improved overall parental satisfaction with treatment (P = 0.027). CONCLUSION: Children with AGE and increased risk of dehydration due to vomiting could be treated with ondansetron in primary care to stop vomiting more quickly and increase parental satisfaction with treatment. These results could be used to improve the quality and efficacy of general practice medicine.

TMS-Induced Central Motor Conduction Time at the Non-Infarcted Hemisphere Is Associated with Spontaneous Motor Recovery of the Paretic Upper Limb after Severe Stroke.

BACKGROUND: Stroke affects the neuronal networks of the non-infarcted hemisphere. The central motor conduction time (CMCT) induced by transcranial magnetic stimulation (TMS) could be used to determine the conduction time of the corticospinal tract of the non-infarcted hemisphere after a stroke. OBJECTIVES: Our primary aim was to demonstrate the existence of prolonged CMCT in the non-infarcted hemisphere, measured within the first 48 h when compared to normative data, and secondly, if the severity of motor impairment of the affected upper limb was significantly associated with prolonged CMCTs in the non-infarcted hemisphere when measured within the first 2 weeks post stroke. METHODS: CMCT in the non-infarcted hemisphere was measured in 50 patients within 48 h and at 11 days after a first-ever ischemic stroke. Patients lacking significant spontaneous motor recovery, so-called non-recoverers, were defined as those who started below 18 points on the FM-UE and showed less than 6 points (10%) improvement within 6 months. RESULTS: CMCT in the non-infarcted hemisphere was prolonged in 30/50 (60%) patients within 48 h and still in 24/49 (49%) patients at 11 days. Sustained prolonged CMCT in the non-infarcted hemisphere was significantly more frequent in non-recoverers following FM-UE. CONCLUSIONS: The current study suggests that CMCT in the non-infarcted hemisphere is significantly prolonged in 60% of severely affected, ischemic stroke patients when measured within the first 48 h post stroke. The likelihood of CMCT is significantly higher in non-recoverers when compared to those that show spontaneous motor recovery early post stroke.

Cost-effectiveness of oral ondansetron for children with acute gastroenteritis in primary care: a randomised controlled trial.

BACKGROUND: Acute gastroenteritis is a common childhood condition with substantial medical and indirect costs, mostly because of referral, hospitalisation, and parental absence from work. AIM: To determine the cost-effectiveness of adding oral ondansetron to care as usual (CAU) for children with acute gastroenteritis presenting to out-of-hours primary care (OOH-PC). DESIGN AND SETTING: A pragmatic randomised controlled trial from December 2015 to January 2018, at three OOHPC centres in the north of the Netherlands (Groningen, Zwolle, and Assen) with a follow-up of 7 days. METHOD: Children were recruited at the OOH-PC and parents kept a parental diary. Inclusion criteria were: aged 6 months-6 years; diagnosis of acute gastroenteritis; at least four reported episodes of vomiting 24 hours before presentation, at least one of which was in the 4 hours before presentation; and written informed consent from both parents. Children were randomly allocated at a 1:1 ratio to either CAU (oral rehydration therapy) or CAU plus one dose of 0.1 mg/kg oral ondansetron. RESULTS: In total, 194 children were included for randomisation. One dose of oral ondansetron decreased the proportion of children who continued vomiting within the first 4 hours from 42.9% to 19.5%, (a decrease of 54.5%), with an odds ratio of 0.4 (95% confidence interval [CI] = 0.2 to 0.7; number needed to treat: four). Total mean costs in the ondansetron group were 31.2% lower (€488 [£420] versus €709 [£610]), and the total incremental mean costs for an additional child free of vomiting in the first 4 hours was -€9 (£8) (95% CI = -€41 [£35] to €3 [£3]). CONCLUSION: A single oral dose of ondansetron for children with acute gastroenteritis, given in OOH-PC settings, is both clinically beneficial and cost-effective.

App-Based Treatment in Primary Care for Urinary Incontinence: A Pragmatic, Randomized Controlled Trial.

PURPOSE: Electronic application (app)-based treatment is promising for common diseases with good conservative management options, such as urinary incontinence (UI) in women, but its effectiveness compared with usual care is unclear. This study set out to determine if app-based treatment for women with stress, urgency, or mixed UI was noninferior to usual care in the primary care setting. METHODS: The URinControl trial is a pragmatic, noninferiority randomized controlled trial in Dutch primary care including adult women with 2 episodes of UI per week. From July 2015 to July 2018, we screened 350 women for eligibility. A stand-alone app-based treatment with pelvic floor muscle and bladder training (URinControl) was compared with usual care according to the Dutch general practitioner guideline for UI treatment. Outcomes measured were change in symptom severity score from baseline to 4 months (primary outcome), impact on disease-specific quality of life, patient-perceived improvement, and number of UI episodes. Noninferiority (<1.5 points) was assessed with linear regression analysis. RESULTS: A total of 262 eligible women were randomized equally; 195 of them had follow-up through 4 months. The change in symptom severity with app-based treatment (-2.16 points; 95% CI, -2.67 to -1.65) was noninferior to that with usual care (-2.56 points; 95% CI, -3.28 to -1.84), with a mean difference of 0.058 points (95% CI, -0.776 to 0.891) between groups. Neither treatment was superior to the other, and both groups showed improvements in outcome measures after treatment. CONCLUSIONS: App-based treatment for women with UI was at least as effective as usual care in the primary care setting. As such, app-based treatments, with their potential advantages of privacy, accessibility, and lower cost, may provide women with a good alternative to consultation.

Recommendations for clinical research in children presenting to primary care out-of-hours services: a randomised controlled trial with parallel cohort study.

BACKGROUND: Research in primary care is essential, but recruiting children in this setting can be complex and may cause selection bias. Challenges surrounding informed consent, particularly in an acute clinical setting, can undermine feasibility. The off-protocol use of an intervention nearing implementation has become common in pragmatic randomised controlled trials (RCTs) set in primary care. AIM: To describe how the informed consent procedure affects study inclusion and to assess how off-protocol medication prescribing affects participant selection in a paediatric RCT. DESIGN & SETTING: A pragmatic RCT evaluating the cost-effectiveness of oral ondansetron in children diagnosed with acute gastroenteritis (AGE) in primary care out-of-hours services and a parallel cohort study. METHOD: Consecutive children aged 6 months to 6 years attending primary care out-of-hours services with AGE were evaluated to assess the feasibility of obtaining informed consent, the off-protocol use of ondansetron, and other inclusion and exclusion criteria. RESULTS: The RCT's feasibility was reduced by the informed consent procedure because 39.0% (n = 325/834) of children were accompanied by only one parent. GPs prescribed ondansetron off-protocol to 34 children (4.1%) of which 19 children were eligible for the RCT. RCT-eligible children included in the parallel cohort study had fewer risk factors for dehydration than children in the RCT despite similar dehydration assessments by GPs. CONCLUSION: The informed consent procedure and off-protocol use of study medication affect the inclusion rate, but had little effect on selection. A parallel cohort study alongside the RCT can help evaluate selection bias, and a pilot study can reveal potential barriers to inclusion.

Effects of caregiver dementia training in caregiver-patient dyads: A randomized controlled study.

OBJECTIVES: Caregivers for people with dementia (PWD) have reported needing emotional and social support, improved coping strategies, and better information about the illness and available support services. In this study, we aimed to determine the effectiveness of an Australian multicomponent community-based training program that we adapted and implemented in a non-medical Dutch health care setting. METHODS AND DESIGN: A randomized controlled trial was performed: 142 dyads of cohabiting caregivers and PwD were randomized to control (care as usual) or intervention (training program) groups and outcomes were compared. Programs lasted 1 week, comprised 14 sessions, and were delivered by specialist staff. We included 16 groups of two to six caregivers. The primary outcome was care-related quality of life (CarerQol-7D) at 3 months. The main secondary outcomes for caregivers were self-rated burden, health and mood symptoms, and for PwD were neuropsychiatric symptoms, quality of life, and agitation. RESULTS: No significant difference was observed for the primary outcome. However, caregivers experienced fewer role limitations due to physical function (adjusted mean difference, 13.04; 95% confidence interval [95%CI], 3.15-22.93), emotional function (13.52; 95%CI, 3.76-23.28), and pain reduction (9.43; 95%CI, 1.00-17.86). Positive outcomes identified by qualitative analysis included better acceptance and coping and improved knowledge of dementia and available community services and facilities. CONCLUSION: Quantitative analysis showed that the multicomponent course did not affect care-related quality of life but did have a positive effect on experienced role limitations and pain. Qualitative analysis showed that the course met the needs of participating dyads.

Recruitment through media and general practitioners resulted in comparable samples in an RCT on incontinence.

OBJECTIVES: The objective of the study was to assess the impact of recruitment strategy on the baseline characteristics of patients recruited in a randomized controlled trial for treating women with urinary incontinence. STUDY DESIGN AND SETTING: We conducted a cross-sectional analysis of baseline data from an earlier trial. Women were recruited through the media (including social media) or from participating general practices. Baseline characteristics were compared by univariate testing. Logistic regression analysis was performed to study the association between recruitment type and multiple baseline characteristics. RESULTS: The only differences between recruitment methods were in patient age, with those recruited through the media being significantly older than those recruited through general practice. The mean age difference was 5.0 years (95% confidence interval: 2.2-7.9). CONCLUSION: Samples recruited through the media and through case identification were largely comparable. Therefore, recruitment through the media may be a viable alternative to recruitment through primary care. This may be especially relevant for research on eHealth treatment for conditions with which patients experience barriers when seeking health care.

Physiotherapy for Children with Functional Constipation: A Pragmatic Randomized Controlled Trial in Primary Care.

OBJECTIVE: To determine the effectiveness of physiotherapy plus conventional treatment compared with conventional treatment alone for the treatment of functional constipation in children age 4-17 years in primary care. STUDY DESIGN: Pragmatic randomized controlled trial with 8 months follow-up. Primary care physicians recruited children diagnosed with functional constipation (n = 234), and pediatricians recruited newly referred children with a diagnosis of functional constipation (n = 11). Conventional treatment comprised toilet training, nutritional advice, and laxative prescribing, whereas physiotherapy focused on resolving dyssynergic defecation. The primary outcome was treatment success over 8 months, defined as the absence of functional constipation (Rome III criteria) without laxative use. Secondary outcomes included the absence of functional constipation irrespective of continuation of laxative use and global perceived treatment effect. RESULTS: Children were allocated to conventional treatment plus physiotherapy or conventional treatment alone (67 per group), mean (SD) age was 7.6 (3.5) years. Results of longitudinal analyses in the intention-to-treat population showed that the treatment success percentage was not statistically improved by adding physiotherapy to conventional treatment (adjusted relative risk [aRR] 0.80, 95% CI 0.44-1.30). At 4 months, fewer children receiving physiotherapy had treatment success (17%) than children receiving conventional treatment alone (28%), but this had equalized by 8 months (42% and 41%, respectively). The percentage of children without functional constipation, irrespective of continuation of laxative use, was not statistically different between groups over 8 months (aRR 1.12, 95% CI 0.82-1.34). Notably, parents reported significantly more global symptom improvement after physiotherapy than after conventional treatment (aRR 1.40; 95% CI 1.00-1.73). CONCLUSIONS: We find no evidence to recommend physiotherapy for all children with functional constipation in primary care. TRIAL REGISTRATION: Netherlands Trial Registry: NTR4797.

Reducing inappropriate psychotropic drug use in nursing home residents with dementia: protocol for participatory action research in a stepped-wedge cluster randomized trial.

BACKGROUND: Psychotropic drugs are often prescribed to treat neuropsychiatric symptoms in nursing home residents with dementia, despite having limited efficacy and considerable side effects. To reduce the inappropriate prescribing of these psychotropic drugs, various non-pharmacological, psychosocial, person-centered, or multidisciplinary interventions are advocated. However, existing multidisciplinary interventions have shown variable effects, with limited effectiveness often resulting from suboptimal implementation. We hypothesize that an effective intervention needs to fit the local situation of a nursing home and that support should be offered during implementation. METHODS: We will embed participatory action research within a stepped-wedge cluster randomized controlled trial to study the effects of a tailored intervention and implementation plan to reduce inappropriate psychotropic drug prescribing. Nursing homes will be provided with tailored information about the perceived problems of managing neuropsychiatric symptoms and we will offer coaching support throughout. Alongside the participatory action research, we will perform a process evaluation to examine the quality of the study, the intervention, and the implementation. Our aim is to recruit 600 residents from 16 nursing homes throughout the Netherlands, with measurements taken at baseline, 8 months, and 16 months. Nursing homes will be randomly allocated to an intervention or a deferred intervention group. During each intervention stage, we will provide information about inappropriate psychotropic drug prescribing, neuropsychiatric symptoms, and difficulties in managing neuropsychiatric symptoms through collaboration with each nursing home. After this, a tailored intervention and implementation plan will be written and implemented, guided by a coach. The primary outcome will be the reduction of inappropriate prescribing, as measured by the Appropriate Psychotropic drug use In Dementia index. Secondary outcomes will be the frequency of psychotropic drug use and neuropsychiatric symptoms, plus quality of life. A mixed methods design will be used for the process evaluation. Effects will be assessed using multilevel analyses. The project leader of the nursing home and the coach will complete questionnaires and in-depth interviews. DISCUSSION: We anticipate that the proposed tailored intervention with coaching will reduce inappropriate psychotropic drug prescribing for nursing home residents with neuropsychiatric symptoms. This study should also provide insights into the barriers to, and facilitators of, implementation. TRIAL REGISTRATION: NTR5872 , registered on July 2, 2016.

Symptom improvement and predictors associated with improvement after 6 weeks of alpha-blocker therapy: An exploratory, single-arm, open-label cohort study.

OBJECTIVES: Clinicians should not only know how many patients will benefit from alpha-blocker therapy but should also be able to identify who will benefit. We studied the changes in patient symptoms following alpha-blocker therapy and the predictors of symptom improvement in clinical practice. DESIGN: This was a single-arm, open-label observational cohort study with a 6-week follow-up. SETTING: Twenty-two pharmacies in the Netherlands. PARTICIPANTS: Patients were eligible for inclusion if they attended a pharmacy with a new prescription for an alpha-blocker from a general practitioner or urologist. PRIMARY AND SECONDARY OUTCOMES: Outcomes were assessed using the International Prostate Symptom Score (IPSS), Overactive Bladder Questionnaire Short Form (OAB-q SF), and Patient Global Impression of Improvement (PGI-I). Demographic, disease-related, and drug-related information were collected to identify predictors of symptom improvement. These predictors were then assessed by logistic and linear regression analyses of both the original data set and an imputed data set that accounted for the missing variables. RESULTS: During the study, 37% of patients with lower urinary tract symptoms perceived clear symptomatic improvement based on the results of the PGI-I. Improvement was more likely in those who still used alpha-blockers at the end of the 6-week study period and in those who used multiple medications. Although symptom scores decreased significantly on the IPSS and OAB-q SF, the only predictor of change was the pretreatment symptom severity. CONCLUSIONS: Approximately one-third of our cohort perceived symptom improvement on alpha-blocker therapy. However, we identified no clear predictors of who might benefit from alpha-blocker treatment, indicating that alpha-blockers should still be prescribed on a trial basis.

Development and construct validation of a parent-proxy quality of life instrument in children with bronchopulmonary dysplasia aged 4-8 years old.

PURPOSE: Children with bronchopulmonary dysplasia often develop complications that affect them well into adult life. Very little is known about how this affects their quality of life, since no sensitive instrument is available to measure health-related quality of life in this population. In this study, a Dutch parent-proxy instrument was developed for this purpose. METHODS: A list of items was generated after literature search and interviews with both parents of patients and clinical experts. Clinically relevant items were selected with the clinical impact method and item analysis. Results of clinical tests to measure complications in children with bronchopulmonary dysplasia were correlated with these items to select the items that show construct validity. Cronbach's alpha was calculated to estimate internal consistency of the items in the final questionnaire. RESULTS: In total, 92 children and their parents and 7 clinicians participated. Of 130 identified items, 47 showed clinical relevance. Spirometry, the Child Behavior Checklist, mean arterial pressure, and body mass index were used to determine construct validity of 33 items. These items were structured within five domains: pulmonary complaints, school functioning, growth and nutrition, exercise and locomotion, emotional functioning and health care concerns. The questionnaire showed excellent internal consistency with Cronbach's alpha of 0.919. CONCLUSION: This study developed a disease-specific parent-proxy instrument to measure health-related quality of life in children with bronchopulmonary dysplasia aged 4-8 years old, the BPD-QoL. All included items show construct validity and internal consistency reliability. Future research should focus on further validation and analysis of responsiveness and reliability.

Predictors of Success for Pelvic Floor Muscle Training in Pelvic Organ Prolapse.

Background: Although the effectiveness of pelvic floor muscle training in women with prolapse has been demonstrated in several studies, there seem to be subgroups of responders and nonresponders. Objective: The objective of this study was to identify factors that predict treatment success in women receiving pelvic floor muscle training for prolapse. Design: The design was a secondary analysis of data from 2 randomized controlled trials comparing conservative prolapse treatments. Methods: After 12 months, 172 women subjectively assessed treatment success ("better") or failure ("the same" or "worse"). Potential predictors were identified by a literature search and by consultation with experts in the field of urogynecology and pelvic floor muscle training. The relationship between potential predictors and treatment success was explored using logistic regression analysis. Results: Treatment was successful in 94 women (55%) and unsuccessful in 78 women (45%). The presence of ≥1 indicators of obstetric trauma (eg, high birth weight, episiotomy, perineal laceration during vaginal delivery, forceps delivery, or vacuum extraction) (odds ratio = 4.4; 95% CI = 1.6-12.0) and younger age (odds ratio = 0.94 per year; 95% CI = 0.9-1.0) independently predicted treatment success. The area under the receiver operating characteristic curve for the final model was 0.65 (95% CI = 0.57-0.74), and the model explained 11.7% of the variance. Limitations: Although attempts were made to include all relevant predictors, the selection or operationalization of variables could have been incomplete or insufficient. Conclusions: Identifying women who have prolapse and are likely to benefit most from pelvic floor muscle training is of great importance to clinical practice. In this study, 2 factors that independently predicted favorable outcomes were identified with this management approach. However, further research is needed to identify other predictive factors and to validate a new model in another population.

The "more at home with dementia" program: a randomized controlled study protocol to determine how caregiver training affects the well-being of patients and caregivers.

BACKGROUND: Caring for people with dementia imposes heavy burdens on caregivers, especially spouses. This can lead to depression, anxiety, and physical symptoms in the caregiver, with early institutionalization for the patient. An Australian study reported that a residential caregiver training program delivered in medical settings could delay nursing home admission, lower mortality, reduce psychological morbidity in caregivers, and lower healthcare costs. In this replication study, we aim to determine the effectiveness of an adaptation of this program to non-medical settings in the Dutch health care system. METHODS: A randomized controlled study design will be used, comparing an intervention group with a control group. The intervention will last for five days and will be delivered in either a holiday park or a bed and breakfast setting. The control group will receive care as usual. Data will be collected at baseline and after 3 and 6 months, and outcomes will be assessed in the caregiver group and in the dementia group. The primary outcome will be caregiver-related quality of life after 3 months. The main secondary outcome will be the neuropsychiatric symptoms in the dementia group. Secondary outcomes in the dementia group will be activities of daily living and instrumental activities of daily living, use of health facilities, quality of life, agitation, dementia severity, and use of psychotropic medication. Secondary outcomes in the caregiver group will be the subjective and objective burdens, health and health care facility use, psychotropic medication use, depression, anxiety, and perseverance time. DISCUSSION: We anticipate that the outcomes will allow us to confirm the effectiveness of the intervention, and in turn, potentially inform the introduction of this program into care plans. It is also expected that the experiences and recommendations of participants will help us to develop the training program further. TRIAL REGISTRATION: Registered in the Netherlands Trial Register on March 9, 2016, number 5775 .

Bladder Symptoms in Children With Functional Constipation: A Systematic Review.

OBJECTIVE: The aim of the review is to perform a systematic review of the literature examining the prevalence of bladder symptoms in children with functional constipation (FC) and to compare the prevalence of those symptoms between children with and without FC. METHODS: In this systematic review 4 databases were searched to July 2018. Studies investigating the prevalence of bladder symptoms in children aged 4 to 17 years with FC were included. There was no language restriction. Two reviewers independently extracted data and assessed study quality. Clinical heterogeneity between studies was investigated. Prevalence rates of bladder symptoms in children with FC were calculated. Relative risks were calculated to compare the prevalence of bladder symptoms between children with and without FC. RESULTS: Among 23 studies of children with FC, 22 reported the prevalence bladder symptoms (12,281 children) and 7 reported the prevalence of urinary tract infections (UTIs) (687 children). The prevalence rates of single bladder symptoms, lower urinary tract symptoms (LUTS), and UTI varied between 2% to 47%, 37% to 64%, and 6% to 53%. The relative risks were 1.24 to 6.73 for 20 single bladder symptoms (12 studies) and 2.18 to 6.55 for UTI (2 studies). The 95% confidence intervals indicated significance in 14 of 20 single bladder symptoms. CONCLUSIONS: Bladder symptoms seem common in children with FC, but the reported prevalence varies greatly. Children with FC are more likely to have bladder symptoms than children without FC. We recommend that clinicians be aware of concomitant bladder symptoms in children presenting with FC.

Parent-child Agreement on Health-Related Quality of Life in Children With Functional Constipation in Primary Care.

OBJECTIVE: Functional constipation (FC) has a major impact on the health-related quality of life (HRQoL) of children. The aim of this study was to evaluate parent-child agreement on HRQoL in children (8-17 years) with FC in primary care. METHODS: Children diagnosed with FC by their clinician were eligible. HRQoL was measured with the Defecation Disorder List (DDL, score 0-100), and the EuroQol-5-Dimension-Youth Visual Analogue Scale (EQ-5D-Y-VAS, scale 0-100). Parent-child agreement was examined with discrepancy scores, intraclass correlation coefficients and Bland-Altman plots. RESULTS: Fifty-six children, median age of 10 years (IQR 8-12) and their parents were included. Parent-child agreement at a group level was good, with an intraclass correlation coefficient of 0.80 (95% confidence interval 0.67 to 0.88) for the DDL, and 0.78 (95% confidence interval 0.65 to 0.87) for the EQ-5D-Y-VAS. Mean discrepancy scores for the DDL and EQ-5D-Y-VAS were small: -2.6 and -2.9, implying that parents were slightly more positive about the HRQoL than their children. Bland-Altman plots showed considerable discordance between individual parent-child pairs. Limits of agreement were -19.7 and 14.6 for the DDL and -27.6 and 21.8 for the EQ-5D-Y-VAS. CONCLUSIONS: There is good parent-child agreement on HRQoL in children with FC at group level. However, a substantial number of parent-child pairs differed considerably on their rating of the HRQoL of the child. Therefore, we recommend clinicians, if they want to have an impression of the impact of the FC on the HRQoL of the child, to ask both the child and the parent(s).

Physiotherapy plus conventional treatment versus conventional treatment only in the treatment of functional constipation in children: design of a randomized controlled trial and cost-effectiveness study in primary care.

BACKGROUND: Our aim was to design a study to evaluate the effectiveness and cost-effectiveness of adding physiotherapy to conventional treatment for children with functional constipation in primary care. Physiotherapy is focusing on improving the coordination between the pelvic floor and abdominal musculature during bowel movement, while conventional treatment is mainly focusing on symptomatic relief of symptoms, therefore, we expect the effects of physiotherapy will be more sustainable than the effects of conventional treatment. In this paper we describe the final study design and how the design was adapted, to overcome recruitment problems. METHODS: We designed a randomized controlled trial of children aged 4-17 years with functional constipation diagnosed by a general practitioner or pediatrician. Children in the intervention group received physiotherapy plus conventional treatment, and those in the control group received conventional treatment only. Follow-up measurements took place at 4 and 8 months. The primary outcome was treatment success defined according to the Rome-III criteria as the absence of functional constipation, with no laxative use. Secondary outcomes were absence of functional constipation irrespective of laxative use, quality of life, global perceived effect, and costs. Children were recruited from September 2014 to February 2017. Initially, we aimed to include children with recent symptom onset. However, in the first phase of enrollment we were confronted with an unforeseen recruitment problem: many children and their parents refused randomization because physiotherapy was considered too burdensome for the stage of disease. Therefore, we decided to also include children with a longer duration of symptoms. In total 134 children were included. DISCUSSION: The target number of participants is achieved. Therefore, the results may change thinking about the management of functional constipation in children. TRAIL REGISTRATION: Netherlands Trial Register ( NTR4797 ), registered 8 September 2014.

Does Transcranial Magnetic Stimulation Have an Added Value to Clinical Assessment in Predicting Upper-Limb Function Very Early After Severe Stroke?

BACKGROUND: The added prognostic value of transcranial magnetic stimulation (TMS)-induced motor-evoked potentials (MEPs) to clinical modeling for the upper limb is still unknown early poststroke. OBJECTIVE: To determine the added prognostic value of TMS of the adductor digiti minimi (TMS-ADM) to the clinical model based on voluntary shoulder abduction (SA) and finger extension (FE) during the first 48 hours and at 11 days after stroke. METHODS: This was a prospective cohort study with 3 logistic regression models, developed to predict upper-limb function at 6 months poststroke. The first model showed the predictive value of SA and FE measured within 48 hours and at 11 days poststroke. The second model included TMS-ADM, whereas the third model combined clinical and TMS-ADM information. Differences between derived models were tested with receiver operating characteristic curve analyses. RESULTS: A total of 51 patients with severe, first-ever ischemic stroke were included. Within 48 hours, no significant added value of TMS-ADM to clinical modeling was found ( P = .369). Both models suffered from a relatively low negative predictive value within 48 hours poststroke. TMS-ADM combined with SA and FE (SAFE) showed significantly more accuracy than TMS-ADM alone at 11 days poststroke ( P = .039). CONCLUSION: TMS-ADM showed no added value to clinical modeling when measured within first 48 hours poststroke, whereas optimal prediction is achieved by SAFE combined with TMS-ADM at 11 days poststroke. Our findings suggest that accuracy of predicting upper-limb motor function by TMS-ADM is mainly determined by the time of assessment early after stroke onset.

Impact of clinical severity of stroke on the severity and recovery of visuospatial neglect.

BACKGROUND AND PURPOSE: There is growing evidence that visuospatial neglect (VSN) is associated with lower functional performance in other modalities and is not restricted to the lesioned hemisphere alone, and may also affect the non-lesioned hemisphere in severe first-ever strokes. We aimed to investigate the longitudinal association between the severity of VSN, as reflected by the extent of ipsilesional and contralesional spatial attention deficit, and clinical severity of stroke. METHODS: This is a secondary data analysis with merged data from two prospective cohort studies. Resulting in 90 patients and 8 longitudinal measurements at 1, 2, 3, 4, 5, 8, 12, and 26 weeks post-stroke onset. A letter cancellation test (LCT) was used as the primary outcome measure to demonstrate presence and severity of VSN. The clinical severity of stroke was classified using the Bamford Classification. RESULTS: No significant association between clinical severity and the number of ipsilesional, as well as contralesional, omissions on the LCT was observed. Recovery of VSN at the contralesional hemiplegic, as well as ipsilesional non-hemiplegic side, was only dependent on 'time' as a reflection of spontaneous neurobiological recovery post-stroke. The recovery of the ipsilesional extension of VSN was significantly slower for the total anterior circulation infarct (TACI) group compared to the non-TACI group. CONCLUSIONS: Larger strokes have a significant negative impact on recovery of visual attention at the non-hemiplegic side. No clinical determinants that regulate spontaneous time-dependent recovery of VSN were found. While early 'stroke severity' has been regarded as a strong predictor of functional outcome at a group level, other prognostic factors (demographic, stroke related) need to be determined. CLINICAL TRIAL REGISTRATION: EXPLICIT-stroke Trial: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1424 Stroke Intensity Trial: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1665.