Long-term health outcomes associated with an exercise referral scheme : an observational longitudinal follow-up study

Background: Exercise referral schemes (ERSs) support inactive adults, who have chronic health conditions, to become physically active. Uncertainty exists regarding the effectiveness of ERSs, with few studies evaluating their long-term impact. The aims of this study were to evaluate the long-term impact (12 mo) of participation in an ERS on self-reported physical activity (PA) and a range of health-related outcomes. Methods: Data were analyzed for participants of a 24-week ERS who attended a week 52 follow-up between July 2015 and 2017. PA and health-related outcomes collected at weeks 1, 24, and 52 were analyzed using the Friedman test and Wilcoxon signed-ranks test. Results: A total of 273 participants attended the week 52 follow-up. Self-reported PA significantly increased by a median of 636 MET minutes at week 52. There were also significant improvements in body mass index, systolic blood pressure, mental well-being, and health-related quality of life. Conclusions: For every 8 participants referred to this 24-week ERS, 1 participant went on to show long-term improvements in at least 1 health indicator. The evidence base requires further long-term evaluations to confirm these findings across a range of ERS providers. Changes in self-reported PA would be supported by the inclusion of device-based measurment of PA

Using pedometers as motivational tools : are goals set in steps more effective than goals set in minutes for increasing walking?

Background Pedometers are popular devices that measure walking steps. There has been a recent surge in promoting the pedometer as a motivational tool to increase walking. However, little empirical evidence exists to support this suggestion. This study examined the effectiveness of a pedometer as a motivational tool to increase walking. 50 participants (7 men and 43 women, mean age (SD) 40.16 (8.81) years, range 25-61 years) were randomly assigned to either an intervention group who followed a four-week walking programme with goals set in steps (using an open pedometer for feedback) or a comparison group who followed an equivalent four-week walking programme with goals set in minutes. Participants had step-counts recorded at baseline, weeks 1, 2, 3, 4, and at weeks 16 and 52 for follow-up. Both groups significantly increased step-counts from baseline to week 4 with no significant difference between groups. However, a significantly greater number of participants in the intervention group (77%) compared with the comparison group (54%) achieved their week 4 goals (p=0.03). There was no significant change in step-counts from week 4 to week 16. There was a significant decrease from week 16 to week 52. In the short term, both goals set in minutes and goals set in steps using a pedometer may be effective at promoting walking. In the long term, additional support may be required to sustain increases in walking

Follow-up Study to Evaluate the Long-term Safety and Efficacy of Darvadstrocel (Mesenchymal Stem Cell Treatment) in Patients With Perianal Fistulizing Crohn’s Disease: ADMIRE-CD phase 3 randomized controlled trial

BACKGROUND: Darvadstrocel is an expanded allogeneic adipose-derived mesenchymal stem cell therapy for the treatment of complex perianal fistulas in patients with Crohn’s disease. Safety and efficacy outcomes from the clinical trial known as “Adipose derived mesenchymal stem cells for induction of remission in perianal fistulizing Crohn’s disease,” or ADMIRE-CD (NCT01541579), from up to 52 weeks posttreatment were previously reported. Here, the outcomes from an extended 104-week follow-up are reported. OBJECTIVE: The goal of this study was to assess the long-term safety and efficacy of darvadstrocel at 2 years post-treatment in patients with Crohn’s disease and complex perianal fistulas. DESIGN: This was a phase 3 double-blind randomized controlled study (ADMIRE-CD) in patients with perianal fistulizing Crohn’s disease. SETTINGS: This study extension was conducted in multiple hospitals across 7 European countries and Israel. PATIENTS: Forty patients entered the extended follow-up period: 25 patients in the darvadstrocel treatment group and 15 in the control group. INTERVENTIONS: Darvadstrocel or saline solution (control group) was administered once, locally, after fistula tract curettage and internal opening closure (with previous seton placement). All patients were permitted to continue ongoing medical treatments for fistulas. MAIN OUTCOME MEASURES: Treatment-emergent serious adverse events were recorded through week 104. Clinical remission, defined as closure of all treated external openings that were draining at baseline despite gentle finger compression, was assessed at week 104. RESULTS: Of 40 patients, 37 completed the extended follow-up. Through week 104, 7 treatment-emergent serious adverse events were reported, of which 4 occurred between weeks 52 and 104. At week 104, clinical remission was reported in 14/25 (56%) patients in the darvadstrocel group and 6/15 (40%) patients in the control group. LIMITATIONS: Limitations include the small number of patients who entered the extended follow-up period, and no imaging examinations were performed at the 104-week time point. CONCLUSIONS: Darvadstrocel was well tolerated and clinical remission after treatment with darvadstrocel may be sustained for up to 104 weeks in patients with perianal fistulizing Crohn’s disease

Follow-up study to evaluate the long-term safety and efficacy of darvadstrocel (mesenchymal stem cell treatment) in patients with perianal fistulizing crohn’s disease: ADMIRE-CD phase 3 randomized controlled trial

BACKGROUND: Darvadstrocel is an expanded allogeneic adipose-derived mesenchymal stem cell therapy for the treatment of complex perianal fistulas in patients with Crohn’s disease. Safety and efficacy outcomes from the clinical trial known as “Adipose derived mesenchymal stem cells for induction of remission in perianal fistulizing Crohn’s disease,” or ADMIRE-CD (NCT01541579), from up to 52 weeks posttreatment were previously reported. Here, the outcomes from an extended 104-week follow-up are reported. OBJECTIVE: The goal of this study was to assess the long-term safety and efficacy of darvadstrocel at 2 years post-treatment in patients with Crohn’s disease and complex perianal fistulas. DESIGN: This was a phase 3 double-blind randomized controlled study (ADMIRE-CD) in patients with perianal fistulizing Crohn’s disease. SETTINGS: This study extension was conducted in multiple hospitals across 7 European countries and Israel. PATIENTS: Forty patients entered the extended follow-up period: 25 patients in the darvadstrocel treatment group and 15 in the control group. INTERVENTIONS: Darvadstrocel or saline solution (control group) was administered once, locally, after fistula tract curettage and internal opening closure (with previous seton placement). All patients were permitted to continue ongoing medical treatments for fistulas. MAIN OUTCOME MEASURES: Treatment-emergent serious adverse events were recorded through week 104. Clinical remission, defined as closure of all treated external openings that were draining at baseline despite gentle finger compression, was assessed at week 104. RESULTS: Of 40 patients, 37 completed the extended follow-up. Through week 104, 7 treatment-emergent serious adverse events were reported, of which 4 occurred between weeks 52 and 104. At week 104, clinical remission was reported in 14/25 (56%) patients in the darvadstrocel group and 6/15 (40%) patients in the control group. LIMITATIONS: Limitations include the small number of patients who entered the extended follow-up period, and no imaging examinations were performed at the 104-week time point. CONCLUSIONS: Darvadstrocel was well tolerated and clinical remission after treatment with darvadstrocel may be sustained for up to 104 weeks in patients with perianal fistulizing Crohn’s diseaseThis study was sponsored by Takeda Pharmaceuticals International Co. Medical writing support was provided by Sally McTaggart, PhD, of Oxford PharmaGenesis, Oxford, UK, and was funded by Takeda Pharmaceuticals International C

Dupilumab shows long-term effectiveness in a large cohort of treatment-refractory atopic dermatitis patients in daily practice:52-Week results from the Dutch BioDay registry

Background Real-life data on long-term effectiveness and safety of dupilumab in atopic dermatitis patients are limited. Objective To study 52-week effectiveness and safety of dupilumab in a prospective multicenter cohort of adult patients with treatment-refractory atopic dermatitis. Methods Patients treated with dupilumab and participating in the Dutch BioDay registry were included. Clinical effectiveness and safety were evaluated. Results Two hundred ten atopic dermatitis patients were included. Mean percentage change in Eczema Area and Severity Index score after 16 weeks was –70.0% (standard deviation 33.2%) and further decreased to –76.6% (standard deviation 30.6%) by week 52. A greater than or equal to 75% improvement in the score was achieved by 59.9% of individuals by week 16 and by 70.3% by week 52. The most reported adverse effect was conjunctivitis (34%). Limited patients (17; 8.1%) discontinued dupilumab treatment. Limitations Because of the lack of a control group and observational design, factors of bias may have been induced. Conclusion Treatment with dupilumab resulted in a rapid improvement in clinical outcome measures, and effectiveness further improved during the 52-week follow-up period

Reduction of risk for lifestyle diseases: group diet and physical activity intervention in the workplace

Cardiovascular disease is a major cause of death in most Westernised countries. The prevalence of obesity, type 2 diabetes mellitus and cancers is rapidly increasing. Older people with elevated blood lipids, obesity and DNA damage are at high risk of developing these diseases. There is a plethora of research to support the claim that a healthy diet and increased physical activity can reduce the risk of increased body fatness, diabetes and generally improve health. However, most interventions require intensive one to one advice. The aim of this study was to measure the effect of a group approach to advising on changes in lifestyle with particular attention to foods high in fibre. The study spanned a period of 12 weeks with a follow up session at 52 weeks to ascertain sustainability. The study: This study was a 12 week longitudinal intervention study with a follow up after 52 weeks. Measurements of anthropometry (skin folds, girths, weight and height), blood pressure, body fat by bio impedance and fasting blood (lipids, glucose and insulin) were made at weeks 0, 3, 6, 9,1 2 and 52. The participants were asked to complete a food frequency questionnaire and a physical activity questionnaire at each of the 6 measuring sessions and to provide an indication of what the goals that they had set and if they had accomplished them after 9,12 and 52 weeks. Between measurements at weeks 0 and 3 the volunteers were left to follow their usual food and activity pattern. Then as a group they were given a diet and exercise talk and provided with written material and pedometers to increase motivation. After measurement at week 6 they were randomly divided into two groups. The first group (A) were prescribed and provided with kiwifruit at a dose of 100g/30 kg body weight for three weeks while the second group (B) continued with the changes in diet and physical activity. Following measurement at week 9 group A abstained from kiwifruit while Group B added the kiwifruit to their diet and the measurements repeated. After 52 weeks, with only emails as ongoing communication, they were remeasured. Results For this multicultural, relatively middle aged group of 53 staff (28 women, 25 men) of mean age 46 years, measurable and statistically significant metabolic gains were made in the lipid profile over 12 weeks. Total cholesterol, LDL cholesterol, triglycerides and the ratio of total cholesterol to HDL all decreased and HDL increased significantly. Total cholesterol decreased from 5.6(±1.1) mean (±SD) mmol/L at baseline to 5.3(±1.1) mmol/L at week 12 (p<0.001); LDL cholesterol decreased from 3.5(±0.97) mmol/L at baseline to 3.3(±0.94) mmol/L at week 12 (p<0.001); and total cholesterol to HDL ratio decreased from 4.0(±1.1) to 3.7(±0.9) (p<0.001). In the 36 who were measured at 52- week follow- up these changes persisted. With the other outcome measures glucose showed a statistically but not biologically significant decrease over the 12 week period and body composition, blood pressure and insulin showed no significant change. The kiwifruit crossover had no apparent affect on the measures of any of the measurements reported. The participants reported that they increased fruit and vegetable and oily fish consumption and increased physical activity. These increases took place over the initial 12 week period and were maintained over 52 weeks. Conclusion: This study has shown that changes in diet and physical activity can favourably influence blood biochemistry even without accompanying changes in percentage body fat and weight. Furthermore, small, manageable lifestyle changes can result in biochemical changes persisting over 52 weeks

Nemolizumab plus topical agents in patients with atopic dermatitis (AD) and moderate‐to‐severe pruritus provide improvement in pruritus and signs of AD for up to 68 weeks: results from two phase III, long‐term studies

[Background] Interleukin (IL)-31 affects the inflammatory response, is involved in epidermal barrier disruption in atopic dermatitis (AD) and plays a key role in pruritus. Nemolizumab, a humanized monoclonal antibody against IL-31 receptor A, reduced pruritus in patients with AD after a 16-week administration period. [Objectives] To examine the long-term effectiveness and safety of nemolizumab in patients aged ≥ 13 years with AD and inadequately controlled moderate-to-severe pruritus. [Methods] In two long-term phase III studies, nemolizumab 60 mg every 4 weeks (Q4W) was administered subcutaneously, concomitantly with topical treatments. Study-JP01 patients received double-blind nemolizumab or placebo for 16 weeks, and then entered a 52-week extension period in which all patients received nemolizumab (nemolizumab/nemolizumab and placebo/nemolizumab groups). Study-JP02 patients received nemolizumab for 52 weeks. Both studies included an 8-week follow-up period. [Results] Study-JP01 nemolizumab/nemolizumab and placebo/nemolizumab, and Study-JP02 nemolizumab groups comprised 143, 72 and 88 patients, respectively. In the nemolizumab/nemolizumab group, there were clinically meaningful improvements from the start of treatment to week 68 in the pruritus visual analogue scale (66% decrease) and Eczema Area and Severity Index (78% decrease). Quality of life (QoL) indicators improved after the first nemolizumab dose; improvements were maintained during the follow-up period. The long-term safety profile was consistent with previous studies, with no unexpected late-onset adverse events. [Conclusions] Nemolizumab 60 mg Q4W with concomitant topical treatments in patients with AD and inadequately controlled moderate-to-severe pruritus produced a continuous improvement in pruritus, signs of AD, and QoL for up to 68 weeks, with a favourable safety profile

Doppler Ultrasound of Vascular Complications After Pediatric Liver Transplantation:Incidence, Time of Detection, and Positive Predictive Value

Purpose Doppler ultrasound (DUS) is widely used to detect vascular complications after pediatric liver transplantation (LT). This study aimed to assess the moment of first detection of vascular complications with DUS, and to determine the positive predictive value (PPV) of DUS. Materials and Methods Patients aged 0–18 years who underwent LT between 2015 and 2019 were retrospectively included. 92 LTs in 83 patients were included (median age: 3.9 years, interquartile range: 0.7–10.5). Patients underwent perioperative (intra-operative and immediately postoperative) and daily DUS surveillance during the first postoperative week, and at 1, 3, and 12 months. Vascular complications were categorized for the hepatic artery, portal vein, and hepatic veins. DUS findings were compared to surgical or radiological findings during the 1-year follow-up. Results 52 vascular complications were diagnosed by DUS in 35/92 LTs (38%). 15 out of 52 (28.8%) were diagnosed perioperatively, 29/52 (55.8%) were diagnosed on postoperative days 1–7, and 8/52 (15.4%) after day 7. The PPV for all vascular complications diagnosed with DUS was 92.3%. During the 1-year follow-up, 18/19 (94.7%) hepatic artery complications, 19/26 (73.1%) portal vein complications, and 7/7 (100%) hepatic vein complications were diagnosed perioperatively or during the first week. Conclusion The majority of vascular complications during the first year after pediatric LT were diagnosed by DUS perioperatively or during the first week, with a high PPV. Our findings provide important information regarding when to expect different types of vascular complications on DUS, which might improve DUS post-LT surveillance protocols

A long-term follow-up of safety and clinical efficacy of NTCELL® [Immunoprotected (Alginate-encapsulated) porcine choroid plexus cells for xenotransplantation] in patients with Parkinson's disease.

INTRODUCTION: In 2019, we published the results of a Phase IIb randomized controlled trial of putaminal encapsulated porcine choroid plexus cell (termed NTCELL®) administration in patients with Parkinson's disease. This study failed to meet its primary efficacy end-point of a change in UPDRS part III score in the 'off' state at 26-weeks post-implant. However, a number of secondary end-points reached statistical significance. We questioned whether with longer follow-up, clinically significant improvements would be observed. For this reason, we decided to follow-up all patients periodically to week 104. Herein, we report the results of this long-term follow-up. METHODS: All 18 patients included in the original study were periodically re-assessed at weeks 52, 78 and 104 post-implant. At each time-point, motor and non-motor function, quality of life and levodopa equivalent daily dose was assessed using a standardized testing battery. RESULTS: At week 104, no significant differences in UPDRS part III scores in the 'off' state were observed in any of the treatment groups compared to baseline. Only a single serious adverse event - hospitalisation due to Parkinson's disease rigidity not responding to changes in medications - was considered potentially related to the implant procedure. There was no evidence of xenogeneic viral transmission. CONCLUSION: Un-blinded, long-duration follow-up to week 104 post-implantation showed no evidence that putaminal NTCELL® administration produces significant clinical benefit in patients with moderately advanced Parkinson's disease

Feasibility of a randomized controlled trial of functional strength training for people between six months and five years after stroke: FeSTivaLS trial

Background: Functional Strength Training (FST) could enhance recovery late after stroke. The aim of this study was to evaluate the feasibility of a subsequent fully powered, randomized controlled trial. Methods: The study was designed as a randomized, observer-blind trial. Both interventions were provided for up to one hour a day, four days a week, for six weeks. Evaluation points were before randomization (baseline), after six weeks intervention (outcome), and six weeks thereafter (follow-up). The study took place in participants’ own homes. Participants (n = 52) were a mean of 24.4 months after stroke with a mean age of 68.3 years with 67.3% male. All had difficulty using their paretic upper (UL) and lower limb (LL). Participants were allocated to FST-UL or FST-LL by an independent randomization service. The outcome measures were recruitment rate, attrition rate, practicality of recruitment strategies, occurrence of adverse reactions, acceptability of FST, and estimation of sample size for a subsequent trial. Primary clinical efficacy outcomes were the Action Research Arm Test (ARAT) and the Functional Ambulation Categories (FAC). Analysis was conducted using descriptive statistics and thematic analysis of participants’ views of FST. A power calculation used estimates of clinical efficacy variance to estimate sample size for a subsequent trial. Results: The screening process identified 1,127 stroke survivors of whom 52 (4.6%) were recruited. The recruitment rate was higher for referral from community therapists than for systematic identification of people discharged from an acute stroke unit. The attrition rate was 15.5% at the outcome and follow-up time-points. None of the participants experienced an adverse reaction. The participants who remained in the study at outcome had received 68% of the total possible amount of therapy. Participants reported that their experience of FST provided a sense of purpose and involvement and increased their confidence in performing activities. The power calculation provides estimation that 150 participants in each group will be required for a subsequent clinical trial. Conclusions: This study found that a subsequent clinical trial was feasible with modifications to the recruitment strategy to be used