scholarly journals Per-Protocol Analysis of The ZINC Trial for HIV Disease Among Alcohol Users

2020 ◽  
Author(s):  
Sara Lodi ◽  
Matthew Freiberg ◽  
Natalia Gnatienko ◽  
Elena Blokhina ◽  
Tatiana Yaroslavtseva ◽  
...  
Keyword(s):  
Placebo Group ◽  
Zinc Supplementation ◽  
Mean Difference ◽  
Effect Estimate ◽  
Interval Change ◽  
Intention To Treat ◽  
High Adherence ◽  
Effect Difference ◽  
The Mean

Abstract Background. The ZINC trial randomized HIV-positive heavy drinkers to either daily zinc supplementation or placebo. The primary outcome was change in VACS index, a predictor of mortality, between baseline and 18 months. Because adherence and follow-up were suboptimal, the intention-to-treat analysis, which was not statistically significant, may have underestimated the effect of the zinc supplementation. Objective. We estimated the per-protocol effect of zinc versus placebo in the ZINC trial (i.e., the effect that would have been observed if all participants had had high adherence and none were lost to follow-up).Methods. Adherence was measured as the self-reported percentage of pills taken in the previous 6 weeks and assessed at all post-baseline visits. We used inverse probability weighting to estimate and compare the change in VACS index at 18 months in the zinc and placebo groups had all the trial participants had high adherence (i.e., cumulative adherence ≥80% at 18 months). To examine trends by level of adherence, we rerun the analyses using thresholds for high-adherence of 70% and 90% of average self-reported pill coverage.Results. The estimated (95% confidence interval) change in VACS index was –2.16 (-8.07, 3.59) and 5.84 (0.73, 11.80) under high adherence and no loss to follow-up in the zinc and placebo groups, respectively. The per-protocol effect estimate of the mean difference in change between the zinc and placebo group was -8.01 (-16.42, 0.01), somewhat larger than the intention-to-treat effect difference in change (-4.68 (-9.62, 0.25)), but it was still not statistically significant. The mean difference in change between individuals in the zinc and placebo group was -4.07 (-11.5,2.75) and -12.34 (-20.14,-4.14) for high adherence defined as 70% and 90% of pill-coverage, respectively. Conclusions. Overall, high adherence to zinc was associated with lower VACS score, but confidence intervals were wide and crossed 0. Further studies with larger sample size are needed to quantify the benefits of zinc supplementation in this population.Trial Registration. ClinicalTrials.gov Identifier: NCT01934803, August 30, 2013

scholarly journals Per-protocol analysis of the ZINC trial for HIV disease among alcohol users

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sara Lodi ◽  
Matthew Freiberg ◽  
Natalia Gnatienko ◽  
Elena Blokhina ◽  
Tatiana Yaroslavtseva ◽  
...  
Keyword(s):  
Zinc Supplementation ◽  
Heavy Drinking ◽  
Mean Difference ◽  
Effect Estimate ◽  
Interval Change ◽  
Intention To Treat ◽  
High Adherence ◽  
Effect Difference ◽  
The Mean

Abstract Background The Zinc for INflammation and Chronic disease in HIV (ZINC) trial randomized person who live with HIV (PLWH) who engage in heavy drinking to either daily zinc supplementation or placebo. The primary outcome was change in the Veterans Aging Cohort Study (VACS) index, a predictor of mortality, between baseline and 18 months. Because adherence and follow-up were suboptimal, the intention-to-treat analysis, which was not statistically significant, may have underestimated the effect of the zinc supplementation. Objective We estimated the per-protocol effect of zinc versus placebo in the ZINC trial (i.e., the effect that would have been observed if all participants had had high adherence and none was lost to follow-up). Methods Adherence was measured as the self-reported percentage of pills taken in the previous 6 weeks and assessed at all post-baseline visits. We used inverse probability weighting to estimate and compare the change in the VACS index at 18 months in the zinc and placebo groups, had all the trial participants had high adherence (i.e., cumulative adherence ≥80% at 18 months). To examine trends by level of adherence, we rerun the analyses using thresholds for high adherence of 70% and 90% of average self-reported pill coverage. Results The estimated (95% confidence interval) change in the VACS index was − 2.16 (− 8.07, 3.59) and 5.84 (0.73, 11.80) under high adherence and no loss to follow-up in the zinc and placebo groups, respectively. The per-protocol effect estimate of the mean difference in the change between the zinc and placebo groups was − 8.01 (− 16.42, 0.01), somewhat larger than the intention-to-treat effect difference in change (− 4.68 (− 9.62, 0.25)), but it was still not statistically significant. The mean difference in the change between individuals in the zinc and placebo groups was − 4.07 (− 11.5, 2.75) and −12.34 (− 20.14, −4.14) for high adherence defined as 70% and 90% of pill coverage, respectively. Conclusions Overall, high adherence to zinc was associated with a lower VACS score, but confidence intervals were wide and crossed 0. Further studies with a larger sample size are needed to quantify the benefits of zinc supplementation in this population. Trial registration ClinicalTrials.gov NCT01934803. Registered on August 30, 2013

scholarly journals Role of leukocyte free platelet rich plasma in planter fasciitis: a prospective study

2017 ◽  
Vol 5 (12) ◽  
pp. 5432
Author(s):  
Chandre Shekhar ◽  
Alamgir Jhan ◽  
Ganesh Singh ◽  
Pankaj Singh ◽  
Shailendre S. Bhandhari
Keyword(s):  
Placebo Group ◽  
Functional Outcome ◽  
Platelet Rich Plasma ◽  
Functional Results ◽  
Visual Analogue Scale Pain ◽  
Functional Score ◽  
Outcome Scores ◽  
The Mean ◽  
Post Graduate Institute

Background: Planter fasciitis, is by definition, inflammation of planter fascia. Most of the cases are well treated conservatively and a few responds to surgery only. Objectives of present study were evaluating the efficacy of a single injection of leukocyte free platelet rich plasma in plantar fasciitis and to derive a correlation between the clinical and radiological outcome.Methods: The present study consisted of 120 patients of bilateral (PF), (240 feet). These patients were divided into two groups PRP group of 60 patients and Placebo group of 60 patients. The study was conducted on patients attending Orthopaedics outpatient department Post Graduate Institute of Medial Education and Research (PGIMER) from July 2011 to June 2012. A primary efficacy criterion was changes from baseline in pain using (VAS). Functional results, level of satisfaction and outcome were measured by – AOFAS Foot Scale. Correlation of clinical with radiological outcome were performed.Results: There was a significant decrease in the visual analogue scale (pain score) in the PRP. Group while in placebo group it was increased significantly at the end of 6 month. Functional outcome scores were improved significantly from their baseline values in PRP group while in placebo group the mean functional score were deteriorated at 6 months follow up. There was no improvement seen in functional status with normal saline injection. In PRP group the mean heal pad thickness was reduced significantly at 6 months follow up while in placebo group was not changed significantly at 6 months follow up. Correlation between radiological parameters and VAS was found to be positive while it was found negative with other functional outcome scores like AOFAS.Conclusions: Platelet-rich plasma (PRP), which is a natural concentrate of autologous growth factors,plays a role in the regeneration process in treatment of (PF).

P–328 Dienogest significantly decreases the size of the cyst and alters Anti-Müllerian Hormone concentration in patients with endometrioma

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
E Karataş ◽  
B E Temiz ◽  
S Mumusoglu ◽  
H Yarali ◽  
G Bozdag
Keyword(s):  
Primary Outcome ◽  
Statistical Significance ◽  
Mean Difference ◽  
Secondary Outcome ◽  
Control Group ◽  
Significant Drop ◽  
Mean Size ◽  
The Mean ◽  
Respective Figure

Abstract Study question Does utilization of dienogest make any impact on the size of cyst and Anti-Müllerian Hormone (AMH) concentration in patients with endometrioma throughout 12-months? Summary answer Although dienogest makes a gradual reduction in the size of endometrioma cyst throughout 12-months, a significant drop in AMH serum concentration was also noticed. What is known already According to recent studies, pre-operative serum AMH levels might be illusively increased with parallel to the size of endometrioma which will be a misleading factor while deciding to operate the patient via cystectomy. Although dienogest is one of the medical options that might be commenced in patients with endometrioma cyst, there is limited data about its effect on the size of the endometrioma and hence serum AMH concentration throughout 12 months of follow up. Study design, size, duration The current observational cohort study was conducted among patients with endometrioma those treated with dienogest from January 2017 to January 2020. The primary outcome was alteration in diameter of endometrioma cyst at 6th and 12th months of treatment. Secondary outcome was alteration in serum AMH concentration in the same period. Of 104 patients treated with dienogest, 44 patients were excluded due to being treated with any type of surgical intervention during follow up period. Participants/materials, setting, methods A total of 60 patients were recruited for the final analysis. Of them, primary symptom was dysmenorrhea, chronic pelvic pain and menstrual irregularity in 16 (26.7%), 25 (41.7%) and 8 (13.3%) patients, respectively. Eighteen patients (30%) were asymptomatic. As 21 patients had bi-lateral endometrioma, size of the leading cyst was considered to be analyzed for the primary outcome measure. Paired-t test was used for comparison of numerical values and p ≤ 0.05 was taken as statistical significance. Main results and the role of chance The mean age was 31.5±8.0 years. In the time point when dienogest was started, the mean size of the endometrioma was 46.3±17.4 mm. The mean serum AMH concentration was 3.6±2.4 ng/ml. After 6 months of treatment, the mean size of the endometrioma decreased to 38.6±14.0 mm which corresponds to a mean difference of 7.8 mm (95% CI: 3.0 to 12.6; p: 0.003). The respective figure for AMH was 3.3±2.7 ng/ml which corresponds to a mean difference of 0.3 ng/ml (95% CI: –0.2 to 0.8; p: 0.23) at 6 months. After 12 months of treatment, the mean size of the endometrioma was 37.5±15.7 mm which corresponds to a mean difference of 8.9 mm (95% CI: 2.9 to 14.9; p: 0.005) at the end of 12 months. The respective figure for AMH was 2.7±1.9 ng/ml which corresponds to a mean difference of 0.9 ng/ml (95% CI: 0.1 to 1.7; p: 0.045) at the end of 12 months. The mean diameter of endometrioma and AMH concentration did not differ throughout the time period between 6th and 12th months of the treatment. Limitations, reasons for caution Although herein we present the largest data that depicts the alteration of endometrioma cyst and AMH concentration with the application of dienogest, the lack of control group is a limitation that avoids to perform any comparison. Wider implications of the findings: A shrinkage after commencement of treatment suggest that dienogest might present improvement in patients with endometrioma with respect to radiological findings, but further studies are required whether a decline in AMH concentration after 12 months refers to a genuine decrease in ovarian reserve or resolution of misleading high pre-treatment levels. Trial registration number not available

scholarly journals Bone Mass and Strength and Fall-Related Fractures in Older Age

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Kirsti Uusi-Rasi ◽  
Saija Karinkanta ◽  
Kari Tokola ◽  
Pekka Kannus ◽  
Harri Sievänen
Keyword(s):  
Bone Mass ◽  
Physical Performance ◽  
Bone Structure ◽  
Mean Difference ◽  
Bone Mass Density ◽  
Mineral Density ◽  
Fracture Group ◽  
Bone Properties ◽  
The Mean

Introduction. Low bone mineral density is a risk factor for fractures. The aim of this follow-up study was to assess the association of various bone properties with fall-related fractures. Materials and Methods. 187 healthy women aged 55 to 83 years at baseline who were either physically active or inactive were followed for 20 years. They were divided into two groups by whether or not they sustained fall-related fractures: fracture group (F) and nonfracture group (NF). At baseline, several bone properties were measured with DXA and pQCT, and their physical performance was also assessed. Results. During the follow-up, 120 women had no fall-related fractures, while 67 (38%) sustained at least one fall with fracture. NF group had about 4 to 11% greater BMD at the femoral neck and distal radius; the mean differences (95% CI) were 4.5 (0.3 to 8.6) % and 11.1 (6.3 to 16.1) %, respectively. NF group also had stronger bone structure at the tibia, the mean difference in BMC at the distal tibia was 6.0 (2.2 to 9.7) %, and at the tibial shaft 3.6 (0.4 to 6.8) %. However, there was no mean difference in physical performance. Conclusions. Low bone properties contribute to the risk of fracture if a person falls. Therefore, in the prevention of fragility fractures, it is essential to focus on improving bone mass, density, and strength during the lifetime. Reduction of falls by improving physical performance, balance, mobility, and muscle power is equally important.

scholarly journals Integrated Efficacy Results from the Phase II and Phase III Studies with Caplacizumab in Patients with Acquired Thrombotic Thrombocytopenic Purpura

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 373-373 ◽  
Author(s):  
Flora Peyvandi ◽  
Spero R Cataland ◽  
Marie Scully ◽  
Paul Coppo ◽  
Paul Knöbl ◽  
...  
Keyword(s):  
Platelet Count ◽  
Placebo Group ◽  
Treatment Period ◽  
Phase Ii ◽  
Thromboembolic Event ◽  
Advisory Board ◽  
Phase Iii ◽  
Count Response ◽  
The Mean

Abstract Introduction : Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare, life-threatening thrombotic microangiopathy, in which accumulation of ultra large von Willebrand factor (ULvWF) multimers leads to an increased risk of thrombus formation in small blood vessels due to platelet adhesion. A combination of plasma exchange (PE) and immunosuppression is the current mainstay of treatment for aTTP. The efficacy of caplacizumab in aTTP patients, in conjunction with PE and immunosuppression, was demonstrated in both placebo-controlled Phase II TITAN study and Phase III HERCULES study. Herein, we present the results of the integrated efficacy analyses of both studies. Methods : All randomized patients in the TITAN and HERCULES studies were integrated and included in the analysis population. Patients had a single-blind (SB, TITAN) or a double-blind (DB, HERCULES) treatment period followed by a follow-up period of 30 days. Patients in the HERCULES study could enter an open-label treatment period (i.e., in case of exacerbation during the DB treatment period). The primary endpoint was time to platelet count response, analyzed according to the corresponding platelet count response definition for each individual study (Figure 1). Secondary endpoints included: (i) the proportion of patients with TTP-related death, a recurrence of TTP, or at least one treatment-emergent major thromboembolic event; (ii) the proportion of patients with a recurrence of TTP during the DB/SB treatment period and the overall study period; (iii) the proportion of patients with refractory TTP (defined as the absence of platelet count doubling after 4 days of standard treatment, and LDH above normal); (iv) mortality rate during the DB/SB treatment period and the overall study period; (v) the number of PE days during the DB/SB treatment period. Results : 220 patients were randomized in both studies, 108 to the caplacizumab group and 112 to the placebo group. The groups were balanced with respect to demographics and baseline disease characteristics except for an imbalance relating to a history of previous TTP episode (Table 1). There was a statistically significant difference in favor of caplacizumab in time to platelet count response (p <0.001; platelet count normalization rate ratio [95% CI] of 1.65 [1.24, 2.20]) (Figure 1, Table 2). Treatment with caplacizumab resulted in a 72.6% reduction in the percentage of patients with TTP-related death, a recurrence of TTP, or at least one treatment-emergent major thromboembolic event during the DB/SB treatment period compared to placebo (p <0.0001) (Table 2). Treatment with caplacizumab resulted in an 84.0% reduction in the percentage of patients who had a recurrence of TTP during the DB/SB treatment period (p <0.0001), and a 49.4% reduction in recurrences during the overall study period (p <0.005), compared to placebo (Table2). No patients in the caplacizumab group had refractory TTP during the DB/SB treatment period compared to 7 patients (6.3%) in the placebo group (p <0.01) (Table 2). There was a statistically significant lower rate of death in the caplacizumab group (no deaths) compared to the placebo group (4 deaths) during the DB/SB treatment period (p <0.05) (Table 2). During the overall study period, one patient randomized to caplacizumab died (during the treatment-free follow-up period, judged unrelated to caplacizumab by the Investigator), compared to 5 patients randomized to placebo (Table 2). During the overall treatment period, there was a reduction in the mean number of PE days of 3.9 days in the caplacizumab group compared to the placebo group (Table 2). Conclusions : This integrated efficacy analyses confirmed results from the individual Phase II and III studies showing that treatment with caplacizumab significantly reduces the time to platelet count response compared to treatment with placebo. In addition, treatment with caplacizumab was associated with clinically meaningful and statistically significant reductions in: (i) the proportion of patients with TTP-related death, a recurrence of TTP, or at least one treatment-emergent major thromboembolic event; (ii) the proportion of patients who died from TTP during the study drug treatment period; (iii) the proportion of patients with a recurrence of TTP during treatment and overall; (iv) the number of patients refractory to therapy; (v) the mean number of days of plasma exchange. Disclosures Peyvandi: Kedrion: Consultancy; Roche: Speakers Bureau; Octapharma US: Honoraria; Kedrion: Consultancy; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Roche: Speakers Bureau; Sobi: Speakers Bureau; Sobi: Speakers Bureau; Octapharma US: Honoraria; Sobi: Speakers Bureau; Roche: Speakers Bureau; Grifols: Speakers Bureau; Roche: Speakers Bureau; Grifols: Speakers Bureau; Novo Nordisk: Speakers Bureau; Shire: Speakers Bureau; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Grifols: Speakers Bureau; Grifols: Speakers Bureau; Roche: Speakers Bureau; Kedrion: Consultancy; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Kedrion: Consultancy; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Novo Nordisk: Speakers Bureau; Sobi: Speakers Bureau; Shire: Speakers Bureau; Novo Nordisk: Speakers Bureau; Octapharma US: Honoraria; Novo Nordisk: Speakers Bureau; Novo Nordisk: Speakers Bureau; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Shire: Speakers Bureau; Shire: Speakers Bureau; Shire: Speakers Bureau; Octapharma US: Honoraria; Grifols: Speakers Bureau; Sobi: Speakers Bureau; Octapharma US: Honoraria; Kedrion: Consultancy. Cataland:Alexion: Research Funding; Shire: Consultancy; Ablynx: Consultancy, Other: Member of Advisory Board. Scully:Novartis: Honoraria, Other: Member of Advisory Board, Speakers Bureau. Coppo:Ablynx: Consultancy. Knöbl:Ablynx: Consultancy, Other: Member of Advisory Board. Kremer Hovinga:Shire: Other: Member of Advisory Board, Research Funding; Ablynx: Other: Member of Advisory Board. Metjian:Ablynx: Other: Member of Advisory Board. De La Rubia:Ablynx: Consultancy, Other: Member of Advisory Board. Minkue:Ablynx: Employment. Callewaert:Ablynx: Employment. De Winter:Ablynx: Employment.

scholarly journals Cost-effectiveness of cell salvage and donor blood transfusion during caesarean section: results from a randomised controlled trial

BMJ Open ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. e022352 ◽  
Author(s):  
Carol McLoughlin ◽  
Tracy E Roberts ◽  
Louise J Jackson ◽  
Philip Moore ◽  
Matthew Wilson ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Caesarean Section ◽  
Blood Transfusion ◽  
Controlled Trial ◽  
Mean Difference ◽  
Cell Salvage ◽  
Donor Blood ◽  
Intention To Treat ◽  
The Mean ◽  
Randomised Controlled

ObjectivesTo evaluate the cost-effectiveness of routine use of cell salvage during caesarean section in mothers at risk of haemorrhage compared with current standard of care.DesignModel-based cost-effectiveness evaluation alongside a multicentre randomised controlled trial. Three main analyses were carried out on the trial data: (1) based on the intention-to-treat principle; (2) based on the per-protocol principle; (3) only participants who underwent an emergency caesarean section.Setting26 obstetric units in the UK.Participants3028 women at risk of haemorrhage recruited between June 2013 and April 2016.InterventionsCell salvage (intervention) versus routine care without salvage (control).Primary outcome measuresCost-effectiveness based on incremental cost per donor blood transfusion avoided.ResultsIn the intention-to-treat analysis, the mean difference in total costs between cell salvage and standard care was £83. The estimated incremental cost-effectiveness ratio (ICER) was £8110 per donor blood transfusion avoided. For the per-protocol analysis, the mean difference in total costs was £92 and the ICER was £8252. In the emergency caesarean section analysis, the mean difference in total costs was £55 and the ICER was £13 713 per donor blood transfusion avoided. This ICER is driven by the increased probability that these patients would require a higher level of postoperative care and additional surgeries. The results of these analyses were shown to be robust for the majority of deterministic sensitivity analyses.ConclusionsThe results of the economic evaluation suggest that while routine cell salvage is a marginally more effective strategy than standard care in avoiding a donor blood transfusion, there is uncertainty in relation to whether it is a less or more costly strategy. The lack of long-term data on the health and quality of life of patients in both arms of the trial means that further research is needed to fully understand the cost implications of both strategies.Trial registration numberISRCTN66118656.

Efficacy of a quadrivalent HPV (types 6/11/16/18) L1 virus-like particle (VLP) vaccine against vaginal and vulvar pre-cancerous lesions: a combined analysis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5011-5011 ◽  
Author(s):  
J. Paavonen
Keyword(s):  
Placebo Group ◽  
Precancerous Lesions ◽  
Hpv 16 ◽  
Combined Analysis ◽  
Younger Women ◽  
Intention To Treat ◽  
Virus Like Particle ◽  
Hpv Types ◽  
The Impact

5011 Background: In the US, 6000 cases of vulvar or vaginal cancer are diagnosed annually. HPV is detected in 75–100% of vulvar cancers in younger women. The most common HPV type detected is HPV 16, followed by HPV 18. These two types also cause a majority of HPV-related vaginal cancers. Treatment to prevent progression to vaginal/vulvar cancer is challenging. Here, we present a combined analysis of 3 randomized, placebo-controlled trials to evaluate the impact of a prophylactic quadrivalent HPV vaccine on the rates of HPV 16- and 18-related vulvar and vaginal neoplasia grade 2/3 (VIN 2/3 and VaIN 2/3). Methods: 18,150 women (16–26 yrs) from the Americas, Europe and Asia were enrolled in 1 of 3 trials. Subjects were randomized to either quadrivalent HPV (Types 6, 11, 16, 18) L1 VLP vaccine or placebo. For all trials, vaccination occurred at day 1, and months 2 and 6. Genital tract specimens were obtained at day 1 and at 6–12 month intervals thereafter for a maximum of 48 months. Colposcopy referral was algorithm-based. Biopsies were HPV-typed. Cytology, histology, and HPV detection were conducted centrally. Analyses were done per protocol (PP) (subjects received 3 doses, had no major protocol violations, were HPV 16 or 18 seronegative at Day 1 and HPV 16 or 18 DNA negative Day 1 through month 7) and modified intention to treat (MITT) (received ≥1 dose and were HPV 16 or 18 negative at Day 1 by serology and DNA). Endpoint counts began after Month 7 and Day 30 in the PP and MITT analyses, respectively. Results: In PP analysis, after an average of 18 months of follow-up, the vaccine was 100% effective (95% CI: 56–100%) in preventing HPV 16- or 18-related VIN 2/3 or VaIN 2/3. There were 10 cases in the placebo group and 0 cases in the vaccine group. In the MITT population, after an average of 2 years of follow-up, there were 24 histologically confirmed cases of HPV 16- or 18-related VIN 2/3 or VaIN 2/3, all in the placebo group (100% efficacy; 95% CI: 83–100%). Conclusions: Quadrivalent HPV VLP vaccine prevented HPV 16 and 18-related vaginal and vulvar high-grade precancerous lesions for at least 2 years post-immunization. This intervention is expected to greatly reduce the risk of vulvar and vaginal cancers. [Table: see text]

Efficacy of andrographolide in not active Progressive Multiple Sclerosis: A prospective exploratory double-blind, parallel-group, randomized, placebo-controlled trial

2020 ◽  
Author(s):  
Ethel Ciampi ◽  
Reinaldo Uribe-San-Martin ◽  
Claudia Carcamo ◽  
Juan Pablo Cruz ◽  
Ana Reyes ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trial ◽  
Placebo Group ◽  
Controlled Trial ◽  
Mean Difference ◽  
Relative Reduction ◽  
Disability Progression ◽  
Double Blind ◽  
The Mean ◽  
Anti Inflammatory

Abstract Background: Multiple sclerosis (MS) is a chronic immune mediated disease and the progressive phase appears to have significant neurodegenerative mechanisms. The classification of the course of progressive MS (PMS) has been re-organized into categories of active vs. not active inflammatory disease and the presence vs. absence of gradual disease progression. Clinical trial experience to date in PMS with anti-inflammatory medications has shown limited effect. Andrographolide is a new class of anti-inflammatory agent, that has been proposed as a potential drug for autoimmune disorders, including MS. In the present trial, we perform an exploratory pilot study on the efficacy and safety of andrographolide (AP) compared to placebo in not active PMS. Methods: A pilot clinical trial using 140mg oral AP or placebo twice daily for 24 months in patients with not active primary or secondary progressive MS was conducted. The primary efficacy endpoint was the mean percentage brain volume change (mPBVC). Secondary efficacy endpoints included 3-month confirmed disability progression (3-CDP) and mean EDSS change. Results: Forty-four patients were randomized: 23 were assigned to the AP group, and 21 were assigned to the placebo group. The median baseline EDSS of both groups was 6.0. Annualized mPBVC was -0.679% for the AP group and -1.069% for the placebo group (mean difference: -0.39; 95% CI [-0.836-0.055], p=0.08, relative reduction: 36.5%). In the AP group, 30% had 3-CDP compared to 41% in the placebo group (HR: 0.596; 95% CI [0.200 – 1.777], p=0.06). The mean EDSS change was -0.025 in the AP group and +0.352 in the placebo group (mean difference: 0.63, p=0.042). Adverse events related to AP were mild rash and dysgeusia. Conclusions: AP was well tolerated and showed a potential effect in reducing brain atrophy and disability progression, that need to be further evaluated in a larger clinical trial. Trial registration: ClinicalTrials.gov NCT02273635

scholarly journals A Wearable Technology Delivering a Web-Based Diabetes Prevention Program to People at High Risk of Type 2 Diabetes: Randomized Controlled Trial

10.2196/15448 ◽  
2020 ◽  
Vol 8 (7) ◽  
pp. e15448
Author(s):  
Emily Staite ◽  
Adam Bayley ◽  
Ebaa Al-Ozairi ◽  
Kurtis Stewart ◽  
David Hopkins ◽  
...  
Keyword(s):  
Physical Activity ◽  
Controlled Trial ◽  
Intervention Group ◽  
Diabetes Prevention Program ◽  
Mean Difference ◽  
Control Group ◽  
Web Based ◽  
The Mean

Background Intensive lifestyle interventions are effective in reducing the risk of type 2 diabetes, but the implementation of learnings from landmark studies is expensive and time consuming. The availability of digital lifestyle interventions is increasing, but evidence of their effectiveness is limited. Objective This randomized controlled trial (RCT) aimed to test the feasibility of a web-based diabetes prevention program (DPP) with step-dependent feedback messages versus a standard web-based DPP in people with prediabetes. Methods We employed a two-arm, parallel, single-blind RCT for people at high risk of developing diabetes. Patients with a hemoglobin A1c (HbA1c) level of 39-47 mmol/mol were recruited from 21 general practices in London. The intervention integrated a smartphone app delivering a web-based DPP course with SMS texts incorporating motivational interviewing techniques and step-dependent feedback messages delivered via a wearable device over 12 months. The control group received the wearable technology and access to the web-based DDP but not the SMS texts. As this was a feasibility study, the primary aim was to estimate potential sample size at different stages of the study, including the size of the target study population and the proportion of participants who consented, were randomized, and completed follow-up. We also measured the main outcomes for a full-scale RCT, namely, change in weight and physical activity at 6- and 12-month follow-ups, and secondary outcomes, including changes in the HbA1c level, blood pressure, waist circumference, waist-to-hip ratio, and lipid levels. Results We enrolled 200 participants: 98 were randomized to the intervention and 102 were randomized to the control group. The follow-up rate was higher in the control group (87/102, 85.3%) than in the intervention group (69/98, 70%) at 12 months. There was no treatment effect on weight at 6 months (mean difference 0.15; 95% CI −0.93 to 1.23) or 12 months (mean difference 0.07 kg; 95% CI −1.29 to 1.44) or for physical activity levels at 6 months (mean difference −382.90 steps; 95% CI −860.65 to 94.85) or 12 months (mean difference 92.64 steps; 95% CI −380.92 to 566.20). We did not observe a treatment effect on the secondary outcomes measured at the 6-month or 12-month follow-up. For the intervention group, the mean weight was 92.33 (SD 15.67) kg at baseline, 91.34 (SD 16.04) kg at 6 months, and 89.41 (SD 14.93) kg at 12 months. For the control group, the mean weight was 92.59 (SD 17.43) kg at baseline, 91.71 (SD 16.48) kg at 6 months, and 91.10 (SD 15.82) kg at 12 months. In the intervention group, the mean physical activity was 7308.40 (SD 4911.93) steps at baseline, 5008.76 (SD 2733.22) steps at 6 months, and 4814.66 (SD 3419.65) steps at 12 months. In the control group, the mean physical activity was 7599.28 (SD 3881.04) steps at baseline, 6148.83 (SD 3433.77) steps at 6 months, and 5006.30 (SD 3681.1) steps at 12 months. Conclusions This study demonstrates that it is feasible to successfully recruit and retain patients in an RCT of a web-based DPP. Trial Registration ClinicalTrials.gov NCT02919397; http://clinicaltrials.gov/ct2/show/NCT02919397

scholarly journals Effects of vitamin B12 supplementation on neurodevelopment and growth in Nepalese Infants: A randomized controlled trial

PLoS Medicine ◽  
2020 ◽  
Vol 17 (12) ◽  
pp. e1003430
Author(s):  
Tor A. Strand ◽  
Manjeswori Ulak ◽  
Mari Hysing ◽  
Suman Ranjitkar ◽  
Ingrid Kvestad ◽  
...  
Keyword(s):  
At Risk ◽  
Placebo Group ◽  
Low Income ◽  
Metabolic Response ◽  
Controlled Trial ◽  
Hemoglobin Concentration ◽  
Mean Difference ◽  
Vitamin B ◽  
Trial Protocol ◽  
The Mean

Background Vitamin B12 deficiency is common and affects cell division and differentiation, erythropoiesis, and the central nervous system. Several observational studies have demonstrated associations between biomarkers of vitamin B12 status with growth, neurodevelopment, and anemia. The objective of this study was to measure the effects of daily supplementation of vitamin B12 for 1 year on neurodevelopment, growth, and hemoglobin concentration in infants at risk of deficiency. Methods and findings This is a community-based, individually randomized, double-blind placebo-controlled trial conducted in low- to middle-income neighborhoods in Bhaktapur, Nepal. We enrolled 600 marginally stunted, 6- to 11-month-old infants between April 2015 and February 2017. Children were randomized in a 1:1 ratio to 2 μg of vitamin B12, corresponding to approximately 2 to 3 recommended daily allowances (RDAs) or a placebo daily for 12 months. Both groups were also given 15 other vitamins and minerals at around 1 RDA. The primary outcomes were neurodevelopment measured by the Bayley Scales of Infant and Toddler Development 3rd ed. (Bayley-III), attained growth, and hemoglobin concentration. Secondary outcomes included the metabolic response measured by plasma total homocysteine (tHcy) and methylmalonic acid (MMA). A total of 16 children (2.7%) in the vitamin B12 group and 10 children (1.7%) in the placebo group were lost to follow-up. Of note, 94% of the scheduled daily doses of vitamin B12 or placebo were reported to have been consumed (in part or completely). In this study, we observed that there were no effects of the intervention on the Bayley-III scores, growth, or hemoglobin concentration. Children in both groups grew on an average 12.5 cm (SD: 1.8), and the mean difference was 0.20 cm (95% confidence interval (CI): −0.23 to 0.63, P = 0.354). Furthermore, at the end of the study, the mean difference in hemoglobin concentration was 0.02 g/dL (95% CI: −1.33 to 1.37, P = 0.978), and the difference in the cognitive scaled scores was 0.16 (95% CI: −0.54 to 0.87, P = 0.648). The tHcy and MMA concentrations were 23% (95% CI: 17 to 30, P < 0.001) and 30% (95% CI: 15 to 46, P < 0.001) higher in the placebo group than in the vitamin B12 group, respectively. We observed 43 adverse events in 36 children, and these events were not associated with the intervention. In addition, 20 in the vitamin B12 group and 16 in the placebo group were hospitalized during the supplementation period. Important limitations of the study are that the strict inclusion criteria could limit the external validity and that the period of vitamin B12 supplementation might not have covered a critical window for infant growth or brain development. Conclusions In this study, we observed that vitamin B12 supplementation in young children at risk of vitamin B12 deficiency resulted in an improved metabolic response but did not affect neurodevelopment, growth, or hemoglobin concentration. Our results do not support widespread vitamin B12 supplementation in marginalized infants from low-income countries. Trial registration ClinicalTrials.gov NCT02272842 Universal Trial Number: U1111-1161-5187 (September 8, 2014) Trial Protocol: Original trial protocol: PMID: 28431557 (reference [18]; study protocols and plan of analysis included as Supporting information).

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