The Health Impact of Social Community Enterprises in Vulnerable Neighborhoods: Protocol for a Mixed Methods Study.

BACKGROUND: This 4-year research project focuses on 6 social community enterprises (SCEs) that operate in 5 neighborhoods in a Dutch city. Residents of these neighborhoods face problems such as poor average levels of physical and mental health, high unemployment rates, and weak social cohesion. SCEs offer residents social, cultural, and work-related activities and are therefore believed to help these persons develop themselves and strengthen the social ties in the community. Because of a lack of empirical evidence; however, it is unclear whether and how SCEs benefit the health and well-being of participants. OBJECTIVE: This paper outlines a protocol for an evaluation study on the impact of SCEs, aiming to determine (1) to what extent SCEs affect health and well-being of participating residents, (2) what underlying processes and mechanisms can explain such impact, and (3) what assets are available to SCEs and how they can successfully mobilize these assets. METHODS: A mixed methods multiple-case study design including repeated measurements will be conducted. Six SCEs form the cases. An integrated model of SCE health intervention will be used as the theoretical basis. First, the impact of SCEs is measured on the individual and community level, using questionnaires and in-depth interviews conducted with participants. Second, the research focuses on the underlying processes and mechanisms and the organizational and sociopolitical factors that influence the success or failure of these enterprises in affecting the health and well-being of residents. At this organizational level, in-depth interviews are completed with SCE initiators and stakeholders, such as municipal district managers. Finally, structurally documented observations are made on the organizational and sociopolitical context of the SCEs. RESULTS: This research project received funding from the Netherlands Organization for Health Research and Development in 2018. Data collection takes place from 2018 until 2022. Data analysis starts after the last round of data collection in 2022 and finalizes in 2024. Expected results will be published in 2023 and 2024. CONCLUSIONS: Despite the societal relevance of SCEs, little empirical research has been performed on their functioning and impact. This research applies a variety of methods and includes the perspectives of multiple stakeholders aiming to generate new empirical evidence. The results will enable us to describe how SCE activities influence intermediate and long-term health outcomes and how the organizational and sociopolitical context of SCEs may shape opportunities or barriers for health promotion. As the number of these initiatives in the Netherlands is increasing rapidly, this research can benefit many SCEs attempting to become more effective and increase their impact. The findings of this research will be shared directly with relevant stakeholders through local and national meetings and annual reports and disseminated among other researchers through scientific publications. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37966.

Clinical Characteristics and Patient-Reported Outcomes of Primary Care Physiotherapy in Patients with Whiplash-Associated Disorders: A Longitudinal Observational Study.

BACKGROUND: Whiplash-associated disorders (WADs) constitute a state of health characterized by a wide diversity of symptoms as a result of impairments of functions, activity limitations, and participation restrictions. Patient-reported outcome measurements (PROMs) and patient-reported outcomes (PROs) seem appropriate when describing and evaluating the health status of patients with WAD. AIM: To measure the use of PROMs and PROs as quality indicators in clinical reasoning, and to analyze and evaluate pre- and post-treatment 'pain intensity' and 'functioning', and for 'perceived improvement' in patients with WAD in primary care physiotherapy practice by year of referral, with the phase after accident and prognostic health profile embedded in the clinical reasoning process. MATERIALS AND METHODS: Data were collected over a period of 10 years. Pain intensity, functioning, and perceived improvement were measured using the Visual Analogue Scale for Pain (VAS-P), the Neck Disability Index (NDI) and the Global Perceived Effect scale (GPE). Pre- and post-treatment mean differences were tested for statistical significance and compared to minimal clinically important differences (MCID). Effect sizes were expressed as Cohen's d. Multivariable regression analysis was performed to explore independent associations of year of referral, phase after the accident, and the patient's prognostic health profile with post-treatment pain intensity and functioning. RESULTS: A consecutive sample of 523 patients was included. Pre- and post-treatment mean differences on VAS-P and NDI were statistically significant (P<0.000) and clinically relevant, with 'large' effect sizes for pain intensity and functioning. MCIDs were achieved by 80% for VAS-P and for 60% for NDI. Year of referral and phase after the accident were independently associated with worse post-treatment functioning. About half of the patients (n=241 [46.1%]) perceived themselves as improved. CONCLUSION: The PROMs and PROs pain intensity, functioning and perceived improvement were integrated as quality indicators in the physiotherapy clinical reasoning process for patients with WAD. Significant differences in pain intensity and functioning were found but were unrelated to year of referral, phase after whiplash-related injury or prognostic health profile. The MCID VAS-P scores did not differ depending on experienced pain.

Relationships Between Context, Process, and Outcome Indicators to Assess Quality of Physiotherapy Care in Patients with Whiplash-Associated Disorders: Applying Donabedian's Model of Care.

BACKGROUND: Quality indicators (QIs) are measurable elements of practice performance and may relate to context, process, outcome and structure. A valid set of QIs have been developed, reflecting the clinical reasoning used in primary care physiotherapy for patients with whiplash-associated disorders (WAD). Donabedian's model postulates relationships between the constructs of quality of care, acting in a virtuous circle. AIM: To explore the relative strengths of the relationships between context, process, and outcome indicators in the assessment of primary care physiotherapy in patients with WAD. MATERIALS AND METHODS: Data on WAD patients (N=810) were collected over a period of 16 years in primary care physiotherapy practices by means of patients records. This routinely collected dataset (RCD-WAD) was classified in context, process, and outcome variables and analyzed retrospectively. Clinically relevant variables were selected based on expert consensus. Associations were expressed, using zero-order, as Spearman rank correlation coefficients (criterion: rs >0.25 [minimum: fair]; α-value = 0.05). RESULTS: In round 1, 62 of 85 (72.9%) variables were selected by an expert panel as relevant for clinical reasoning; in round 2, 34 of 62 (54.8%) (context variables 9 of 18 [50.0%]; process variables 18 of 34 [52.9]; outcome variables 8 of 10 [90.0%]) as highly relevant. Associations between the selected context and process variables ranged from 0.27 to 0.53 (p≤0.00), between selected context and outcome variables from 0.26 to 0.55 (p≤0.00), and between selected process and outcome variables from 0.29 to 0.59 (p≤0.00). Moderate associations (rs >0.50; p≤0.00) were found between "pain coping" and "fear avoidance" as process variables, and "pain intensity" and "functioning" as outcome variables. CONCLUSION: The identified associations between selected context, process, and outcome variables were fair to moderate. Ongoing work may clarify some of these associations and provide guidance to physiotherapists on how best to improve the quality of clinical reasoning in terms of relationships between context, process, and outcome in the management of patients with WAD.

Has the quality of physiotherapy care in patients with Whiplash-associated disorders (WAD) improved over time? A retrospective study using routinely collected data and quality indicators.

PURPOSE: To develop valid quality indicators (QIs) for physiotherapy care based on best available evidence, and to use these QIs to explore trends in the quality of physiotherapy care of patients with Whiplash-associated disorders (WAD) using guideline-based routinely collected data (RCD) gathered between 1996 and 2011. MATERIALS AND METHODS: The study consisted of two phases: 1) development of QIs and 2) analysis of patient records. A set of QIs was developed based on recommendations in the scientific literature and the Dutch Clinical Practice Guideline (CPG) "Physiotherapy Management and WAD". QIs were expressed as percentages, allowing target performance levels to be defined (≥80% or ≤30% depending on whether desired performance required a high or low score on a QI). We then analyzed WAD patient data (N = 810) collected over a period of 16 years in two physiotherapy practices, separating patients into two groups defined as before (Group A 1996-2002; n = 353) and after (Group B 2003-2011; n = 457) implementation and transition to the Dutch CPG "Physiotherapy Management and WAD". RESULTS: Using an iterative process and input from both experts and users, 28 QIs were developed and subsequently classified per step of the clinical reasoning process for physiotherapy care. Based on 16 years of RCD, we found that the clinical reasoning process differed significantly (P ≤ 0.05) between the groups, in favor of Group B. Twelve of the 25 indicators (48.0%) in Group A and 19 of 26 indicators (73.1%) in Group B met predetermined performance targets. The number of target indicators also differed significantly between groups, favoring Group B (P ≤ 0.05). CONCLUSION: A preliminary set of novel QIs was developed. Using RCD and these QIs, we conclude that physiotherapy care in our study setting improved over the period 1996-2011. Furthermore, the QIs met the performance targets set for the clinical reasoning process after the transition to the Dutch CPG "Physiotherapy Management and WAD".

Oxygen drives hepatocyte differentiation and phenotype stability in liver cell lines.

The in vitro generation of terminally differentiated hepatocytes is an unmet need. We investigated the contribution of oxygen concentration to differentiation in human liver cell lines HepaRG and C3A. HepaRG cells were cultured under hypoxia (5%O2), normoxia (21%O2) or hyperoxia (40%O2). Cultures were analysed for hepatic functions, gene transcript levels, and protein expression of albumin, hepatic transcription factor CEBPα, hepatic progenitor marker SOX9, and hypoxia inducible factor (HIF)1α. C3A cells were analysed after exposure to normoxia or hyperoxia. In hyperoxic HepaRG cultures, urea cycle activity, bile acid synthesis, CytochromeP450 3A4 (CYP3A4) activity and ammonia elimination were 165-266% increased. These effects were reproduced in C3A cells. Whole transcriptome analysis of HepaRG cells revealed that 240 (of 23.223) probes were differentially expressed under hyperoxia, with an overrepresentation of genes involved in hepatic differentiation, metabolism and extracellular signalling. Under hypoxia, CYP3A4 activity and ammonia elimination were inhibited almost completely and 5/5 tested hepatic genes and 2/3 tested hepatic transcription factor genes were downregulated. Protein expression of SOX9 and HIF1α was strongly positive in hypoxic cultures, variable in normoxic cultures and predominantly negative in hyperoxic cultures. Conversely, albumin and CEBPα expression were highest in hyperoxic cultures. HepaRG cells that were serially passaged under hypoxia maintained their capacity to differentiate under normoxia, in contrast to cells passaged under normoxia. Hyperoxia increases hepatocyte differentiation in HepaRG and C3A cells. In contrast, hypoxia maintains stem cell characteristics and inhibits hepatic differentiation of HepaRG cells, possibly through the activity of HIF1α.

Scaling-up of a HepaRG progenitor cell based bioartificial liver: optimization for clinical application and transport.

A new generation of bioartificial livers, based on differentiated proliferative hepatocyte sources, has been developed. Several practicable and regulatory demands have to be addressed before these can be clinically evaluated. We identified three main hurdles: (1) expansion and preservation of the biocomponent, (2) development of scaled-up culture conditions and (3) transport of the device to the bedside. In this study we address these three issues for the HepaRG-progenitor cell line-loaded AMC-Bioartificial Liver. (1) HepaRG cells were expanded in large quantities and then cryopreserved or loaded directly into bioreactors. After 3 weeks of culture, key hepatic functions (ammonia/lactate elimination, apolipoprotein A1 synthesis and cytochrome P450 3A4 activity) did not differ significantly between the two groups. (2) Bioartificial livers were scaled up from 9 ml to 540 ml priming volume, with preservation of normalized hepatic functionality. Quantification of amino acid consumption revealed rapid depletion of several amino acids. (3) Whole-device cryopreservation and cooled preservation induced significant loss of hepatic functionality, whereas simulated transport from culture-facility to the bedside in a clinical-grade transport unit with controlled temperature maintenance, medium perfusion and gas supply did not affect functionality. In addition, we assessed tumorigenicity of HepaRG cells in immune-incompetent mice and found no tumor formation of HepaRG cells (n = 12), while HeLa cells induced formation of carcinomas in eight out of 12 mice in 140 days.

Selecting Cells for Bioartificial Liver Devices and the Importance of a 3D Culture Environment: A Functional Comparison between the HepaRG and C3A Cell Lines.

Recently, the first clinical trials on Bioartificial Livers (BALs) loaded with a proliferative human hepatocyte cell source have started. There are two cell lines that are currently in an advanced state of BAL development; HepaRG and HepG2/C3A. In this study we aimed to compare both cell lines on applicability in BALs and to identify possible strategies for further improvement. We tested both cell lines in monolayer- and BAL cultures on growth characteristics, hepatic differentiation, nitrogen-, carbohydrate-, amino acid- and xenobiotic metabolism. Interestingly, both cell lines adapted the hepatocyte phenotype more closely when cultured in BALs; e.g. monolayer cultures produced lactate, while BAL cultures showed diminished lactate production (C3A) or conversion to elimination (HepaRG), and urea cycle activity increased upon BAL culturing in both cell lines. HepaRG-BALs outperformed C3A-BALs on xenobiotic metabolism, ammonia elimination and lactate elimination, while protein synthesis was comparable. In BAL cultures of both cell lines ammonia elimination correlated positively with glutamine production and glutamate consumption, suggesting ammonia elimination was mainly driven by the balance between glutaminase and glutamine synthetase activity. Both cell lines lacked significant urea cycle activity and both required multiple culture weeks before reaching optimal differentiation in BALs. In conclusion, culturing in BALs enhanced hepatic functionality of both cell lines and from these, the HepaRG cells are the most promising proliferative cell source for BAL application.

Efficacy of a physical exercise training programme COPD in primary care: study protocol of a randomized controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is recognized as a systemic illness with significant extra-pulmonary features, such as exercise intolerance and muscle weakness. Pulmonary rehabilitation has been shown to be very effective in counteracting these consequences in patients with more advanced COPD. However, limited data is available on the efficacy of a physical exercise training programme in patients with mild to moderate COPD in primary care. Furthermore, it is unknown if improved exercise capacity translates into enhanced daily physical activities. The aim of this paper is to describe the design of a randomized controlled trial to assess the efficacy of a physical exercise training programme in patients with mild to moderate COPD. METHODS/DESIGN: In this randomized controlled trial situated in the primary care setting, 102 patients with mild to moderate airflow obstruction (FEV1 ≥ 50% of predicted), dyspnoea and a physically inactive lifestyle will be randomized to an intervention or control group. The intervention group receives a 4-month physical exercise training programme at a local physiotherapy practice, which includes exercise training, resistance training, breathing exercises and advises on how to increase the level of physical activity. The control group receives usual care, i.e. advises on how to increase the level of physical activity and a sham treatment at a local physiotherapy practice of which no physiological training stimulus can be expected. Primary outcome is functional exercise capacity at 4-months measured on the six-minute walk distance. Secondary outcomes include peripheral muscle strength, physical activity in daily life, health related quality of life, Medical Research Council (MRC) dyspnoea score and patients' perceived effectiveness. Follow-up measurement will take place at 6 months after baseline. DISCUSSION: This will be one of the first studies to evaluate the efficacy of a physical exercise training programme in patients with mild to moderate COPD completely recruited and assessed in primary care. The results of this trial may give a unique insight into the potential of the implementation of an easy, close-to-home rehabilitation programme. TRIAL REGISTRATION: The Netherlands National Trial Register NTR1471.

Exacerbations in patients with chronic obstructive pulmonary disease receiving physical therapy: a cohort-nested randomised controlled trial.

BACKGROUND: Physical exercise training aims at reducing disease-specific impairments and improving quality of life in patients with chronic obstructive pulmonary disease (COPD). COPD exacerbations in particular negatively impact COPD progression. Physical therapy intervention seems indicated to influence exacerbations and their consequences. However, information on the effect of physical therapy on exacerbation occurrence is scarce. This study aims to investigate the potential of a protocol-directed physical therapy programme as a means to prevent or postpone exacerbations, to shorten the duration or to decrease the severity of exacerbations in patients with COPD who have recently experienced an exacerbation. Besides, this study focuses on the effect of protocol-directed physical therapy on health status and quality of life and on cost-effectiveness and cost-utility in patients with COPD who have recently experienced an exacerbation. METHODS/DESIGN: A prospective cohort of 300 COPD patients in all GOLD stages will be constructed. Patients will receive usual multidisciplinary COPD care including guideline-directed physical therapy. Patients in this cohort who have GOLD stage 2 to 4 (post-bronchodilator FEV1/FVC < 0.7 and FEV1 < 80% of predicted), who receive reimbursement by health insurance companies for physical therapy (post-bronchodilator Tiffeneau-index < 0.6) and who experience a COPD exacerbation will be asked within 56 days to participate in a cohort-nested prospective randomised controlled trial (RCT). In this RCT, the intervention group will receive a strict physical therapy programme for patients with COPD. This protocol-directed physical therapy (pdPT) will be compared to a control group that will receive sham-treatment, meaning no or very low-intensity exercise training (ST). An economic evaluation will be embedded in the RCT. Anthropometric measurements, comorbidities, smoking, functional exercise capacity, peripheral muscle strength, physical activity level, health related quality of life, patients' perceived benefit, physical therapy compliance, motivation level, level of effective mucus clearance, exacerbation symptoms and health care contacts due to COPD will be recorded. Follow-up measurements are scheduled at 3 and 6 weeks, 3, 6, 12 and 24 months after inclusion. DISCUSSION: Ways to minimise potential problems regarding the execution of this study will be discussed. TRIAL REGISTRATION: The Netherlands National Trial Register NTR1972.

The first reference equations for the 6-minute walk distance over a 10 m course.

RATIONALE: As primary care practice space is mostly limited to 10 m, the 6-minute walk test (6MWT) over a 10 m course is a frequently used alternative to evaluate patients' performance in COPD. Considering that course length significantly affects distance walked in 6 minutes (6MWD), this study aims to develop appropriate reference equations for the 10 m 6MWT. METHODS: 181 healthy subjects, aged 40-90 years, performed two standardised 6MWTs over a straight 10 m course in a cross-sectional study. RESULTS: Average distance achieved was 578±108 m and differed between males and females (p<0.001). Resulting sex-specific reference equations from multiple regression analysis included age, body mass index and change in heart rate, explaining 62% of the variance in 6MWD for males and 71% for females. CONCLUSIONS: The presented reference equations are the first to evaluate 6MWD over a 10 m course and expand the usefulness of the 6MWT.

Evaluating quality indicators for physical therapy in primary care.

OBJECTIVE: To evaluate measurement properties of a set of public quality indicators on physical therapy. DESIGN: An observational study with web-based collected survey data (2009 and 2010). SETTING: Dutch primary care physical therapy practices. PARTICIPANTS: In 3743 physical therapy practices, 11 274 physical therapists reporting on 30 patients each. MAIN OUTCOME MEASURES: Eight quality indicators were constructed: screening and diagnostics (n= 2), setting target aim and subsequent of intervention (n = 2), administrating results (n = 1), global outcome measures (n = 2) and patient's treatment agreement (n = 1). Measurement properties on content and construct validity, reproducibility, floor and ceiling effects and interpretability of the indicators were assessed using comparative statistics and multilevel modeling. RESULTS: Content validity was acceptable. Construct validity (using known group techniques) of two outcome indicators was acceptable; hypotheses on age, gender and chronic vs. acute care were confirmed. For the whole set of indicators reproducibility was approximated by correlation of 2009 and 2010 data and rated moderately positive (Spearman's ρ between 0.3 and 0.42 at practice level) and interpretability as acceptable, as distinguishing between patient groups was possible. Ceiling effects were assessed negative as they were high to extremely high (30% for outcome indicator 6-95% for administrating results). CONCLUSION: Weaknesses in data collection should be dealt with to reduce bias and to reduce ceiling effects by randomly extracting data from electronic medical records. More specificity of the indicators seems to be needed, and can be reached by focusing on most prevalent conditions, thus increasing usability of the indicators to improve quality of care.

What is the evidence for physical therapy poststroke? A systematic review and meta-analysis.

BACKGROUND: Physical therapy (PT) is one of the key disciplines in interdisciplinary stroke rehabilitation. The aim of this systematic review was to provide an update of the evidence for stroke rehabilitation interventions in the domain of PT. METHODS AND FINDINGS: Randomized controlled trials (RCTs) regarding PT in stroke rehabilitation were retrieved through a systematic search. Outcomes were classified according to the ICF. RCTs with a low risk of bias were quantitatively analyzed. Differences between phases poststroke were explored in subgroup analyses. A best evidence synthesis was performed for neurological treatment approaches. The search yielded 467 RCTs (N = 25373; median PEDro score 6 [IQR 5-7]), identifying 53 interventions. No adverse events were reported. Strong evidence was found for significant positive effects of 13 interventions related to gait, 11 interventions related to arm-hand activities, 1 intervention for ADL, and 3 interventions for physical fitness. Summary Effect Sizes (SESs) ranged from 0.17 (95%CI 0.03-0.70; I(2) = 0%) for therapeutic positioning of the paretic arm to 2.47 (95%CI 0.84-4.11; I(2) = 77%) for training of sitting balance. There is strong evidence that a higher dose of practice is better, with SESs ranging from 0.21 (95%CI 0.02-0.39; I(2) = 6%) for motor function of the paretic arm to 0.61 (95%CI 0.41-0.82; I(2) = 41%) for muscle strength of the paretic leg. Subgroup analyses yielded significant differences with respect to timing poststroke for 10 interventions. Neurological treatment approaches to training of body functions and activities showed equal or unfavorable effects when compared to other training interventions. Main limitations of the present review are not using individual patient data for meta-analyses and absence of correction for multiple testing. CONCLUSIONS: There is strong evidence for PT interventions favoring intensive high repetitive task-oriented and task-specific training in all phases poststroke. Effects are mostly restricted to the actually trained functions and activities. Suggestions for prioritizing PT stroke research are given.

Development of a theory- and evidence-based intervention to enhance implementation of physical therapy guidelines for the management of low back pain.

BACKGROUND: Systematic planning could improve the generally moderate effectiveness of interventions to enhance adherence to clinical practice guidelines. The aim of our study was to demonstrate how the process of Intervention Mapping was used to develop an intervention to address the lack of adherence to the national CPG for low back pain by Dutch physical therapists. METHODS: We systematically developed a program to improve adherence to the Dutch physical therapy guidelines for low back pain. Based on multi-method formative research, we formulated program and change objectives. Selected theory-based methods of change and practical applications were combined into an intervention program. Implementation and evaluation plans were developed. RESULTS: Formative research revealed influential determinants for physical therapists and practice quality managers. Self-regulation was appropriate because both the physical therapists and the practice managers needed to monitor current practice and make and implement plans for change. The program stimulated interaction between practice levels by emphasizing collective goal setting. It combined practical applications, such as knowledge transfer and discussion-and-feedback, based on theory-based methods, such as consciousness raising and active learning. The implementation plan incorporated the wider environment. The evaluation plan included an effect and process evaluation. CONCLUSIONS: Intervention Mapping is a useful framework for formative data in program planning in the field of clinical guideline implementation. However, a decision aid to select determinants of guideline adherence identified in the formative research to analyse the problem may increase the efficiency of the application of the Intervention Mapping process.

Dutch guidelines for physiotherapy in patients with stress urinary incontinence: an update.

INTRODUCTION AND HYPOTHESIS: Stress urinary incontinence (SUI) is the most common form of incontinence impacting on quality of life (QOL) and is associated with high financial, social, and emotional costs. The purpose of this study was to provide an update existing Dutch evidence-based clinical practice guidelines (CPGs) for physiotherapy management of patients with stress urinary incontinence (SUI) in order to support physiotherapists in decision making and improving efficacy and uniformity of care. MATERIALS AND METHODS: A computerized literature search of relevant databases was performed to search for information regarding etiology, prognosis, and physiotherapy assessment and management in patients with SUI. Where no evidence was available, recommendations were based on consensus. Clinical application of CPGs and feasibility were reviewed. The diagnostic process consists of systematic history taking and physical examination supported by reliable and valid assessment tools to determine physiological potential for recovery. Therapy is related to different problem categories. SUI treatment is generally based on pelvic floor muscle exercises combined with patient education and counseling. An important strategy is to reduce prevalent SUI by reducing influencing risk factors. RESULTS: Scientific evidence supporting assessment and management of SUI is strong. CONCLUSIONS: The CPGs reflect the current state of knowledge of effective and tailor-made intervention in SUI patients.

Course length of 30 metres versus 10 metres has a significant influence on six-minute walk distance in patients with COPD: an experimental crossover study.

QUESTIONS: Do patients with chronic obstructive pulmonary disease (COPD) achieve a different distance on the six minute walk test (6MWT) conducted on a 10m course versus on a 30m course? When assessing the distance on a 6MWT conducted on a 10m course, is it valid to use existing reference equations that were generated on longer courses? DESIGN: A randomised double-crossover experimental study. PARTICIPANTS: Forty-five patients with COPD in primary physiotherapy care. INTERVENTION: All patients performed a 6MWT twice over a 10m course and twice over a 30m course. The 6MWTs were performed in accordance with the American Thoracic Society guidelines. OUTCOME MEASURES: 6MWD was assessed and predicted distance was calculated based on a range of reference equations. RESULTS: The 6MWD on the 10m course was 49.5m shorter than on the 30m course, which was statistically significant (95% CI 39.4 to 59.6). By using existing reference equations for a 6MWT conducted on the 10m course, the predicted distance is highly overestimated (with a range of 30% to 33%) and the average distance as a percentage of the predicted value is 8%pred lower compared to a 6MWT conducted on the 30m course, resulting in a worse representation of a COPD patient's functional exercise capacity. CONCLUSION: This study shows that the impact of course length on the 6MWD and on the use of reference equations in patients with COPD is substantial and clinically relevant (based on the most conservative published minimum clinically important difference). Therefore, existing reference equations established for a 6MWT conducted over a 30m (or longer) course cannot be applied to predict the distance achieved on the 6MWT on a 10m course, which is frequently used in primary care physiotherapy practices for patients with COPD.

Electrical stimulation with non-implanted electrodes for urinary incontinence in men.

BACKGROUND: Electrical stimulation with non-implanted devices is used for patients with different types of urinary incontinence and symptoms of urgency, frequency and nocturia. The current review focused on electrical stimulation with non-implanted devices for the treatment of urinary incontinence in men. OBJECTIVES: To determine the effectiveness of electrical stimulation with non-implanted devices for men with stress, urgency or mixed urinary incontinence in comparison with no treatment, placebo treatment, or any other 'single' treatment. Additionally, the effectiveness of electrical stimulation with non-implanted devices in combination with another intervention was compared with the other intervention alone. Finally, the effectiveness of one method of electrical stimulation with non-implanted devices was compared with another method. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Trials Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PreMEDLINE, and handsearching of journals and conference proceedings (searched 21 January 2012). We also searched other electronic and non-electronic bibliographic databases and the reference lists of the included studies as well as contacting researchers in the field to identify other relevant trials. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed all the identified trials for eligibility. Risk of bias was assessed using the Cochrane tool for determining bias. Disagreements were resolved by discussion, and a third review author was involved in the case of no consensus. Data were analysed using Cochrane methods. MAIN RESULTS: Six randomized controlled trials (five full papers and one abstract) were included. There was considerable variation in the interventions used, study protocols, types of electrical stimulation parameters and devices, study populations and outcome measures. In total 544 men were included, of whom 305 received some form of electrical stimulation, and 239 a control or comparator treatment. The trials were mostly small and generally there was not sufficient information to assess risk of bias; only two trials used secure methods of randomization.There was some evidence that electrical stimulation (ES) had a short-term effect in reducing incontinence compared with sham treatment (for example risk ratio (RR) at six months 0.38, 95% CI 0.16 to 0.87) but not at 12 months. Four trials evaluated the effect of adding PFMT to ES versus pelvic floor muscle training (PFMT) alone or with biofeedback. There was no evidence of a statistically significant difference in the number of men with urinary incontinence at three months (146/239, 61% for combined treatment versus 98/156, 63% with PFMT alone; RR 0.93, 95% CI 0.82 to 1.06). However, there were more adverse effects with combined treatment (23/139, 17% versus 2/99, 2% with PFMT alone; RR 7.04, 95% CI 1.51 to 32.94) and quality of life also seemed better with PFMT alone. One small trial did not detect statistically significant differences between two methods of administration of transcutaneous electrical stimulation (anal versus perineal) but the quality of life score was lower (better) in the anal stimulation group. AUTHORS' CONCLUSIONS: There was some evidence that electrical stimulation enhanced the effect of PFMT in the short term but not after six months. There were, however, more adverse effects (pain or discomfort) with electrical stimulation.

Developing a questionnaire to identify perceived barriers for implementing the Dutch physical therapy COPD clinical practice guideline.

BACKGROUND: Clinical practice guidelines have been developed to assist healthcare practitioners in clinical decision making. Publication of clinical practice guidelines does not automatically lead to their uptake and barrier identification has been recognized as an important step in implementation planning. This study aimed at developing a questionnaire to identify perceived barriers for implementing the Dutch COPD guideline for physical therapists and its recommended measurement instruments. METHODS: An overall questionnaire, based on two existing questionnaires, was constructed to identify barriers and facilitators for implementing the COPD guideline. The construct of the questionnaire was assessed in a cross-sectional study among 246 chest physical therapists. Factor analysis was conducted to explore underlying dimensions. Psychometric properties were analyzed using Cronbach's alpha. Barriers and facilitators were assessed using descriptive statistics. RESULTS: Some 139 physical therapists (57%) responded. Factor analysis revealed 4-factor and 5-factor solutions with an explained variance of 36% and 39% respectively. Cronbach's alpha of the overall questionnaire was 0.90, and varied from 0.66 to 0.92 for the different factors. Underlying domains of the 5-factor solution were characterized as: attitude towards using measurement instruments, knowledge and skills of the physical therapist, applicability of the COPD guideline, required investment of time & money, and patient characteristics. Physical therapists showed a positive attitude toward using the COPD guideline. Main barriers for implementation were required time investment and financial constraints. CONCLUSIONS: The construct of the questionnaire revealed relevant underlying domains for the identification of barriers and facilitators for implementing the COPD guideline. The questionnaire allowed for tailoring to the target group and may be used across health care professionals as basis for in-depth analysis of barriers to specific recommendations in guidelines. The results of the questionnaire alone do not provide sufficient information to inform the development of an implementation strategy. The infrastructure for developing the guideline can be used for addressing key barriers by the guideline development group, using the questionnaire as well as in-depth analysis such as focus group interviews. Further development of methods for prospective identification of barriers and consequent tailoring of implementation interventions is required.

Long-term effect of antibodies against infused alpha-galactosidase A in Fabry disease on plasma and urinary (lyso)Gb3 reduction and treatment outcome.

INTRODUCTION: Enzyme replacement therapy (ERT) with alpha-Galactosidase A (aGal A) may cause antibody (AB) formation against aGal A in males with Fabry disease (FD). Anti agalsidase ABs negatively influence globotriaosylceramide (Gb3) reduction. We investigated the impact of agalsidase AB on Gb3 and lysoGb3 and clinical outcome in Fabry patients on ERT. METHODS: Adult male and female patients on ERT for at least one year were included. Urinary Gb3 was measured by HPLC, plasma lysoGb3 by LC-ESI-MS/MS and AB with a neutralization assay. RESULTS: Of the 59 patients evaluable patients, 0/30 females and 17/29 males developed anti-agalsidase antibodies (AB+). Only 3/17 males had transient (low) titers (tolerized). All AB+ patients developed antibodies during the first year of treatment. Change of agalsidase preparation (or dose) did not induce antibody formation. AB+ males had significant less decline in plasma lysoGb3 compared to AB- males (p = 0.04). Urinary Gb3 levels decreased markedly in AB- but remained comparable to baseline in AB+ males (p<0.01). (Lyso)Gb3 reduction in plasma and urine on ERT was correlated with LVmass reduction in females and development white matter lesions and stroke. CONCLUSION: In male patients antibodies against aGal A remained present up to 10 years of ERT. The presence of these antibodies is associated with a less robust decrease in plasma lysoGb3 and a profound negative effect on urinary Gb3 reduction, which may reflect worse treatment outcome.

The ClaudicatioNet concept: design of a national integrated care network providing active and healthy aging for patients with intermittent claudication.

INTRODUCTION: Intermittent claudication (IC) is a manifestation of peripheral arterial occlusive disease (PAOD). Besides cardiovascular risk management, supervised exercise therapy (SET) should be offered to all patients with IC. Outdated guidelines, an insufficient number of specialized physiotherapists (PTs), lack of awareness of the importance of SET by referring physicians, and misguided financial incentives all seriously impede the availability of a structured SET program in The Netherlands. DESCRIPTION OF CARE PRACTICE: By initiating regional care networks, ClaudicatioNet aims to improve the quality of care for patients with IC. Based on the chronic care model as a conceptual framework, these networks should enhance the access, continuity, and (cost) efficiency of the health care system. With the aid of a national database, health care professionals will be able to benchmark patient results while ClaudicatioNet will be able to monitor quality of care by way of functional and patient reported outcome measures. DISCUSSION: The success of ClaudicatioNet is dependent on several factors. Vascular surgeons, general practitioners and coordinating central caregivers will need to team up and work in close collaboration with specialized PTs. A substantial task in the upcoming years will be to monitor the quality, volume, and distribution of ClaudicatioNet PTs. Finally, misguided financial incentives within the Dutch health care system need to be tackled. CONCLUSION: With ClaudicatioNet, integrated care pathways are likely to improve in the upcoming years. This should result in the achievement of optimal quality of care for all patients with IC.

Effects of switching from a reduced dose imiglucerase to velaglucerase in type 1 Gaucher disease: clinical and biochemical outcomes.

This paper describes the effects of a switch to velaglucerase alfa in a group of adult patients with type 1 Gaucher disease, all of whom had previously had their dose reduced as a consequence of the worldwide imiglucerase shortage. Thirty-two patients from two large European Gaucher centers switched to treatment with velaglucerase alfa after 1-8.5 months of dose reduction. The course of important Gaucher disease parameters was studied at four time points: one year before the shortage, just before the shortage, before a switch to velaglucerase and after up to one year of treatment with velaglucerase. These parameters included hemoglobin concentration, platelet count, plasma chitotriosidase activity in all patients, and spleen and liver volumes (as well as bone marrow fat fraction images) in 10 patients. Decreases in platelet counts as a result of reduced treatment with imiglucerase were quickly restored on treatment with velaglucerase alfa. Chitotriosidase activity declined overall after switching. Five out of 10 patients had an increase in liver volume of at least 10% after six months of velaglucerase treatment, which was reversible in 3. Most patients received infusions at home and no important side effects were observed. Velaglucerase alfa appears to be a safe and effective alternative for imiglucerase.