Three-year results of phase I retinal gene therapy trial for CNGA3-mutated achromatopsia: results of a non randomised controlled trial

2021 ◽  
pp. bjophthalmol-2021-319067
Author(s):  
Felix Friedrich Reichel ◽  
Stylianos Michalakis ◽  
Barbara Wilhelm ◽  
Ditta Zobor ◽  
Regine Muehlfriedel ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Primary Endpoint ◽  
Statistical Power ◽  
Small Sample Size ◽  
Controlled Trial ◽  
Statistical Significance ◽  
Small Sample ◽  
Functional Improvement ◽  
Limiting Factor ◽  
Serious Adverse Events

AimsTo determine long-term safety and efficacy outcomes of a subretinal gene therapy for CNGA3-associated achromatopsia. We present data from an open-label, nonrandomised controlled trial (NCT02610582).MethodsDetails of the study design have been previously described. Briefly, nine patients were treated in three escalating dose groups with subretinal AAV8.CNGA3 gene therapy between November 2015 and October 2016. After the first year, patients were seen on a yearly basis. Safety assessment constituted the primary endpoint. On a secondary level, multiple functional tests were carried out to determine efficacy of the therapy.ResultsNo adverse or serious adverse events deemed related to the study drug occurred after year 1. Safety of the therapy, as the primary endpoint of this trial, can, therefore, be confirmed. The functional benefits that were noted in the treated eye at year 1 were persistent throughout the following visits at years 2 and 3. While functional improvement in the treated eye reached statistical significance for some secondary endpoints, for most endpoints, this was not the case when the treated eye was compared with the untreated fellow eye.ConclusionThe results demonstrate a very good safety profile of the therapy even at the highest dose administered. The small sample size limits the statistical power of efficacy analyses. However, trial results inform on the most promising design and endpoints for future clinical trials. Such trials have to determine whether treatment of younger patients results in greater functional gains by avoiding amblyopia as a potential limiting factor.

scholarly journals Randomized Controlled Trial of Strain-Specific Probiotic Formulation (Renadyl) in Dialysis Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Ranganathan Natarajan ◽  
Bohdan Pechenyak ◽  
Usha Vyas ◽  
Pari Ranganathan ◽  
Alan Weinberg ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Statistical Power ◽  
Small Sample Size ◽  
Controlled Trial ◽  
Statistical Significance ◽  
Venous Blood ◽  
Small Sample ◽  
Uremic Toxin ◽  
Double Blind

Background. Primary goal of this randomized, double-blind, placebo-controlled crossover study of Renadyl in end-stage renal disease patients was to assess the safety and efficacy of Renadyl measured through improvement in quality of life or reduction in levels of known uremic toxins. Secondary goal was to investigate the effects on several biomarkers of inflammation and oxidative stress.Methods. Two 2-month treatment periods separated by 2-month washout and crossover, with physical examinations, venous blood testing, and quality of life questionnaires completed at each visit. Data were analyzed with SAS V9.2.Results. 22 subjects (79%) completed the study. Observed trends were as follows (none reaching statistical significance): decline in WBC count(-0.51×109/L,P=0.057)and reductions in levels of C-reactive protein(-8.61 mg/L,P=0.071)and total indoxyl glucuronide(-0.11 mg%,P=0.058). No statistically significant changes were observed in other uremic toxin levels or measures of QOL.Conclusions. Renadyl appeared to be safe to administer to ESRD patients on hemodialysis. Stability in QOL assessment is an encouraging result for a patient cohort in such advanced stage of kidney disease. Efficacy could not be confirmed definitively, primarily due to small sample size and low statistical power—further studies are warranted.

scholarly journals Visual Outcomes of Plasma Exchange Treatment of Steroid-Refractory Optic Neuritis: A Retrospective Monocentric Analysis

2019 ◽  
Vol 46 (6) ◽  
pp. 417-422 ◽  
Author(s):  
Nic Skorupka ◽  
Andrei Miclea ◽  
Katarzyna Aleksandra Jalowiec ◽  
Christoph Bocksrucker ◽  
Nicole Kamber ◽  
...  
Keyword(s):  
Optic Neuritis ◽  
Plasma Exchange ◽  
Small Sample Size ◽  
Small Sample ◽  
University Hospital ◽  
Functional Improvement ◽  
High Dose ◽  
Serious Adverse Events ◽  
Insufficient Response ◽  
Steroid Refractory

Introduction: In acute inflammatory optic neuritis (ON) as a typical onset of multiple sclerosis (MS), only few studies have investigated plasma exchange (PLEX) as a sequential treatment after insufficient response to high-dose intravenous glucocorticosteroids. Therefore, we aimed to investigate treatment outcome on visual acuity (VA) with PLEX in patients with steroid-refractory ON. Methods: In our retrospective monocentric study, medical records were screened for patients with acute ON as their first relapse with sequential MS diagnosis or with an established MS diagnosis from the Bern University Hospital (Switzerland) that were treated with PLEX between 2016 and 2018 due to lacking steroid response. VA prior to steroid administration, and before and after PLEX were assessed and compared using the Friedman multiple comparison test. Results: In total, 18 patients were included in the analysis. Interval from symptom onset to PLEX was 20.3 days (mean, 95% CI 14.8–25.9). Relevant functional improvement (VA of ≥0.5, after a mean of 15.9 (13.3–18.5) days after start of PLEX) was detected in 16/18 (88.9%) with a significant amelioration as compared to VA before glucocorticosteroids and before PLEX (p < 0.0001). VA improvement at a later time point (38.1 weeks, 25.2–51.0) was present in 15/16 (93.8%) patients. No serious adverse events were detected. PLEX could be performed via peripheral access in 13/18 patients (72.2%). Conclusion: Our study demonstrates significant improvements of VA with PLEX in a cohort of MS patients with steroid-refractory ON. High response rates may be due to the timely treatment initiation. Despite the small sample size, our data support the early use of PLEX in steroid-refractory ON with a favorable safety profile.

Safety and Tolerability of Ganoderma lucidum in Healthy Subjects: A Double-Blind Randomized Placebo-Controlled Trial

2007 ◽  
Vol 35 (03) ◽  
pp. 407-414 ◽  
Author(s):  
Sheila M. Wicks ◽  
Robin Tong ◽  
Chong-Zhi Wang ◽  
Michael O'Connor ◽  
Theodore Karrison ◽  
...  
Keyword(s):  
Ganoderma Lucidum ◽  
Small Sample Size ◽  
Controlled Trial ◽  
Statistical Significance ◽  
Blood Chemistry ◽  
Small Sample ◽  
Controlled Study ◽  
Double Blind ◽  
Human Volunteers ◽  
Complete Blood Counts

Ganoderma lucidum is a herbal medicine commonly used in oriental countries as a remedy for treating various medical conditions. In this controlled study, we evaluated the safety and tolerance of oral administration of Ganoderma lucidum in 16 human volunteers who received 2 grams of the extract or placebo twice daily for 10 consecutive days. During the study, information from subjective questionnaires were obtained, electrocardiograms, complete blood counts, blood chemistry analysis and urinalysis were performed. In addition, blood tests reflecting immunity were done. Our data showed that compared to placebo group, no adverse effects were observed after the extract intake. Although there were no obvious changes in CD4, CD8, and CD19 levels after the extract, CD56 cell count increased during the study and returned to baseline 10 days after the herbal intake. However, due to relatively high variability and small sample size, this CD56 increase did not achieve statistical significance, and remains to be re-evaluated in the future. It appears that an additional long-term safety and tolerance trial with herbal dose-escalating design is warranted.

Comprehensive Geriatric Care to Improve Mobility after Hip Fracture: An RCT

Gerontology ◽  
2020 ◽  
Vol 66 (6) ◽  
pp. 542-548
Author(s):  
Wendy L. Cook ◽  
Penelope M.A. Brasher ◽  
Pierre Guy ◽  
Stirling Bryan ◽  
Meghan G. Donaldson ◽  
...  
Keyword(s):  
Hip Fracture ◽  
Small Sample Size ◽  
Controlled Trial ◽  
Geriatric Care ◽  
Small Sample ◽  
Community Dwelling ◽  
Post Discharge ◽  
Mobility Performance ◽  
Discharge Care ◽  
Comprehensive Geriatric Care

<b><i>Background:</i></b> Comprehensive geriatric care (CGC) for older adults during hospitalization for hip fracture can improve mobility, but it is unclear whether CGC delivered after a return to community living improves mobility compared with usual post-discharge care. <b><i>Objective:</i></b> To determine if an outpatient clinic-based CGC regime in the first year after hip fracture improved mobility performance at 12 months. <b><i>Methods:</i></b> A two-arm, 1:1 parallel group, pragmatic, single-blind, single-center, randomized controlled trial at 3 hospitals in Vancouver, BC, Canada. Participants were community-dwelling adults, aged ≥65 years, with a hip fracture in the previous 3–12 months, who had no dementia and walked ≥10 m before the fracture occurred. Target enrollment was 130 participants. Clinic-based CGC was delivered by a geriatrician, physiotherapist, and occupational therapist. Primary outcome was the Short Physical Performance Battery (SPPB; 0–12) at 12 months. <b><i>Results:</i></b> We randomized 53/313 eligible participants with a mean (SD) age of 79.7 (7.9) years to intervention (<i>n</i> = 26) and usual care (UC, <i>n</i> = 27), and 49/53 (92%) completed the study. Mean 12-month (SD) SPPB scores in the intervention and UC groups were 9.08 (3.03) and 8.24 (2.44). The between-group difference was 0.9 (95% CI –0.3 to 2.0, <i>p</i> = 0.13). Adverse events were similar in the 2 groups. <b><i>Conclusion:</i></b> The small sample size of less than half our recruitment target precludes definitive conclusions about the effect of our intervention. However, our results are consistent with similar studies on this population and intervention.

Combination of AST to ALT and neutrophils to lymphocytes ratios as predictors of locally advanced disease in patients with bladder cancer subjected to radical cystectomy: Results from a single-institutional series

2021 ◽  
pp. 039156032110351
Author(s):  
Alessandro Uleri ◽  
Rodolfo Hurle ◽  
Roberto Contieri ◽  
Pietro Diana ◽  
Nicolòmaria Buffi ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Advanced Disease ◽  
Independent Predictor ◽  
Small Sample Size ◽  
Statistical Significance ◽  
Locally Advanced ◽  
Small Sample ◽  
Locally Advanced Disease ◽  
Increased Risk

Background: Bladder cancer (BC) staging is challenging. There is an important need for available and affordable predictors to assess, in combination with imaging, the presence of locally-advanced disease. Objective: To determine the role of the De Ritis ratio (DRR) and neutrophils to lymphocytes ratio (NLR) in the prediction of locally-advanced disease defined as the presence of extravescical extension (pT ⩾ 3) and/or lymph node metastases (LNM) in patients with BC treated with radical cystectomy (RC). Methods: We retrospectively analyzed clinical and pathological data of 139 consecutive patients who underwent RC at our institution. Logistic regression models (LRMs) were fitted to test the above-mentioned outcomes. Results: A total of 139 consecutive patients underwent RC at our institution. Eighty-six (61.9%) patients had a locally-advanced disease. NLR (2.53 and 3.07; p = 0.005) and DRR (1 and 1.17; p = 0.01) were significantly higher in patients with locally-advanced disease as compared to organ-confined disease. In multivariable LRMs, an increasing DRR was an independent predictor of locally-advanced disease (OR = 3.91; 95% CI: 1.282–11.916; p = 0.017). Similarly, an increasing NLR was independently related to presence of locally-advanced disease (OR = 1.28; 95% CI: 1.027–1.591; p = 0.028). In univariate LRMs, patients with DRR > 1.21 had a higher risk of locally advanced disease (OR = 2.83; 95% CI: 1.312–6.128; p = 0.008). Similarly, in patients with NLR > 3.47 there was an increased risk of locally advanced disease (OR = 3.02; 95% CI: 1.374–6.651; p = 0.006). In multivariable LRMs, a DRR > 1.21 was an independent predictor of locally advanced disease (OR = 2.66; 95% CI: 1.12–6.35; p = 0.027). Similarly, an NLR > 3.47 was independently related to presence of locally advanced disease (OR = 2.24; 95% CI: 0.95–5.25; p = 0.065). No other covariates such as gender, BMI, neoadjuvant chemotherapy or diabetes reached statistical significance. The AUC of the multivariate LRM to assess the risk of locally advanced disease was 0.707 (95% CI: 0.623–0.795). Limitations include the retrospective nature of the study and the relatively small sample size.

scholarly journals DIAGNOSIS OF ENDOCRINE DISEASE: The diagnostic performance of adrenal biopsy: a systematic review and meta-analysis

2016 ◽  
Vol 175 (2) ◽  
pp. R65-R80 ◽  
Author(s):  
Irina Bancos ◽  
Shrikant Tamhane ◽  
Muhammad Shah ◽  
Danae A Delivanis ◽  
Fares Alahdab ◽  
...  
Keyword(s):  
Systematic Review ◽  
Diagnostic Performance ◽  
Small Sample Size ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Small Sample ◽  
Cochrane Central Register ◽  
Moderate Risk ◽  
Adrenal Biopsy ◽  
Adrenocortical Carcinomas

ObjectiveTo perform a systematic review of published literature on adrenal biopsy and to assess its performance in diagnosing adrenal malignancy.MethodsMedline In-Process and Other Non-Indexed Citations, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trial were searched from inception to February 2016. Reviewers extracted data and assessed methodological quality in duplicate.ResultsWe included 32 observational studies reporting on 2174 patients (39.4% women, mean age 59.8 years) undergoing 2190 adrenal mass biopsy procedures. Pathology was described in 1621/2190 adrenal lesions (689 metastases, 68 adrenocortical carcinomas, 64 other malignancies, 464 adenomas, 226 other benign, 36 pheochromocytomas, and 74 others). The pooled non-diagnostic rate (30 studies, 2013 adrenal biopsies) was 8.7% (95%CI: 6–11%). The pooled complication rate (25 studies, 1339 biopsies) was 2.5% (95%CI: 1.5–3.4%). Studies were at a moderate risk for bias. Most limitations related to patient selection, assessment of outcome, and adequacy of follow-up. Only eight studies (240 patients) could be included in the diagnostic performance analysis with a sensitivity and specificity of 87 and 100% for malignancy, 70 and 98% for adrenocortical carcinoma, and 87 and 96% for metastasis respectively.ConclusionsEvidence based on small sample size and moderate risk of bias suggests that adrenal biopsy appears to be most useful in the diagnosis of adrenal metastasis in patients with a history of extra-adrenal malignancy. Adrenal biopsy should only be performed if the expected findings are likely to alter the management of the individual patient and after biochemical exclusion of catecholamine-producing tumors to help prevent potentially life-threatening complications.

Statistical Power Analysis can Improve Fisheries Research and Management

1990 ◽  
Vol 47 (1) ◽  
pp. 2-15 ◽  
Author(s):  
Randall M. Peterman
Keyword(s):  
Sample Size ◽  
Power Analysis ◽  
Statistical Power ◽  
Small Sample Size ◽  
Industrial Effluent ◽  
Small Sample ◽  
Detectable Effect ◽  
Type Ii ◽  
Sampling Variability ◽  
Statistical Power Analysis

Ninety-eight percent of recently surveyed papers in fisheries and aquatic sciences that did not reject some null hypothesis (H0) failed to report β, the probability of making a type II error (not rejecting H0 when it should have been), or statistical power (1 – β). However, 52% of those papers drew conclusions as if H0 were true. A false H0 could have been missed because of a low-power experiment, caused by small sample size or large sampling variability. Costs of type II errors can be large (for example, for cases that fail to detect harmful effects of some industrial effluent or a significant effect of fishing on stock depletion). Past statistical power analyses show that abundance estimation techniques usually have high β and that only large effects are detectable. I review relationships among β, power, detectable effect size, sample size, and sampling variability. I show how statistical power analysis can help interpret past results and improve designs of future experiments, impact assessments, and management regulations. I make recommendations for researchers and decision makers, including routine application of power analysis, more cautious management, and reversal of the burden of proof to put it on industry, not management agencies.

Internet-based intervention compared to brief intervention for smoking cessation in Brazil: a pilot study (Preprint)

2021 ◽  
Author(s):  
Nathalia Machado ◽  
Henrique Gomide ◽  
Heder Bernardino ◽  
Telmo Ronzani
Keyword(s):  
Smoking Cessation ◽  
Brief Intervention ◽  
Small Sample Size ◽  
Statistical Significance ◽  
Healthcare Providers ◽  
Intervention Group ◽  
Small Sample ◽  
The Internet ◽  
Intention To Treat ◽  
Internet Based Intervention

BACKGROUND Smoking is still the leading cause of preventable death. Governments and healthcare providers should make available more and accessible resources to help tobacco users stop. OBJECTIVE This study describes a pilot longitudinal study that evaluated the efficacy of a computerized intervention compared to the brief intervention for smoking cessation among Brazilians. METHODS Smokers were recruited and randomly assigned to one of the two intervention groups. RESULTS The results showed similar rates of cessation and reduction for both intervention groups. The internet-based intervention was a little more effective for smoking cessation, while the brief intervention was more effective in reducing the number of cigarettes smoked per day. Despite this, this difference was small and had no statistical significance even after adjusting for intention-to-treat analysis. These results should be interpreted with caution, especially due to the small sample size. CONCLUSIONS Forty-nine smokers were enrolled in this study (25 in the brief intervention group; 24 in the internet-based intervention group). The mean age was 44.46 years old; most were male (59.2%), had elementary school (44.9%), smoked an average of 14.5 cigarettes per day, had a mean score of 4.65 for nicotine dependence, and score of 5.7 for motivation to quit. Measures were drawn from comparing cessation rate, motivation score and sought treatment between groups. Thirty-five participants answered the follow up 1 and 19 answered to the second.

Nipple Confusion

PEDIATRICS ◽  
1993 ◽  
Vol 92 (2) ◽  
pp. 300-301
Author(s):  
DOREN FREDRICKSON
Keyword(s):  
Breast Feeding ◽  
Statistical Power ◽  
White Women ◽  
Small Sample Size ◽  
False Negative ◽  
Small Sample ◽  
Bottle Feeding ◽  
Feeding Duration ◽  
Breast Feed ◽  
The Impact

To the Editor.— I wish to comment on the study reported by Cronenwett et al,1 which was a fascinating prospective study among married white women who planned to breast-feed. Women were randomly selected to perform either exdusive breast-feeding or partial breast-feeding with bottled human milk supplements to determine the impact of infant temperament and limited bottle-feeding on breast-feeding duration. The authors admit that small sample size and lack of statistical power make a false-negative possible.

Abstract 3725: Simvastatin but Not Pravastatin Affects Sleep: Findings from the UCSD Statin Study

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Beatrice A Golomb ◽  
Edwin K Kwon ◽  
Michael H Criqui ◽  
Joel E Dimsdale
Keyword(s):  
Sleep Quality ◽  
Rating Scale ◽  
Sleep Problems ◽  
Small Sample Size ◽  
Case Reports ◽  
Controlled Trial ◽  
Small Sample ◽  
T Test ◽  
Secondary Outcome ◽  
Regression Analyses

Background : Case reports have suggested possible effects of lipophilic statins on sleep in some subjects. Most randomized studies evaluating the effect of statins on sleep have had small sample size and short duration (≤ 6 weeks). Whether statins affect sleep on average, favorably or adversely, has been unclear. Goal : To assess the effects of lipophilic and hydrophilic statins on sleep. Subjects : 1016 adult men and women without diabetes or heart disease, with LDL-cholesterol 115–190mg/dL. Design : Randomized double blind placebo-controlled trial of simvastatin 20mg, pravastatin 40mg or placebo for 6 months. Sleep was a prespecified secondary outcome. It was assessed by both an adaptation of the Leeds sleep scale (a visual analog scale of sleep quality); and a rating scale of sleep problems. Both items were measured at baseline and on-treatment. Analysis : Baseline comparability of randomization groups including sleep measures was affirmed. T-test of mean on-treatment sleep scores across randomization groups was performed. This complemented regression analyses, adjusted for baseline values of the respective sleep assessment. Results : Groups were comparable at baseline on variables including both sleep measures. Simvastatin use was associated with significantly worse sleep quality, and significantly greater reported sleep problems than either pravastatin or placebo, by t-test and regression analyses. Pravastatin did not differ significantly from placebo on any sleep outcome. Conclusion : Findings were compatible with the hypothesis that statins may impair sleep in some subjects, and that this impairment may arise selectively with lipophilic statins. Table 1. Effects of Statins on Sleep: Regression Analysis

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