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Current Protocols Aug 2023Analytical method validation provides a means to ensure that data are credible and reproducible. This article will provide a brief introduction to analytical method...
Analytical method validation provides a means to ensure that data are credible and reproducible. This article will provide a brief introduction to analytical method validation as applied to cellular analysis by flow cytometry, along with practical procedures for four different types of validation. The first, Basic Protocol 1 (the limited validation protocol), is recommended for research and non-regulated laboratories. Next, Basic Protocol 2) presents a reasonable, fit-for-purpose validation approach appropriate for biopharma and research settings. Basic Protocol 3 addresses the type of validation performed in clinical laboratories for moderate-risk tests developed in house. Finally, Basic Protocol 4 describes the process that should be applied whenever a method is being transferred from one facility to another. All four validation plans follow the fit-for-purpose validation approach, in which the validation parameters are selected based on the intended use of the assay. These validation protocols represent the minimal requirement and may not be applicable for every intended use such as high-risk clinical assays or data to be used as a primary endpoint in a clinical trial. The recommendations presented here are consistent with the white papers published by the American Association of Pharmaceutical Scientists and the International Clinical Cytometry Society, as well as with Clinical Laboratory Standards Institute Guideline H62: Validation of Assays Performed by Flow Cytometry (CLSI, 2021). © 2023 Wiley Periodicals LLC. Basic Protocol 1: Limited validation Basic Protocol 2: Fit-for-purpose validation for biopharma and research settings Basic Protocol 3: Validation for moderate clinical risk laboratory developed tests Basic Protocol 4: Transfer validation.
Topics: Flow Cytometry; Research Design; Academies and Institutes; Biological Assay; Clinical Laboratory Services
PubMed: 37606503
DOI: 10.1002/cpz1.868 -
Biometrics Sep 2023Rerandomization discards assignments with covariates unbalanced in the treatment and control groups to improve estimation and inference efficiency. However, the...
Rerandomization discards assignments with covariates unbalanced in the treatment and control groups to improve estimation and inference efficiency. However, the acceptance-rejection sampling method used in rerandomization is computationally inefficient. As a result, it is time-consuming for rerandomization to draw numerous independent assignments, which are necessary for performing Fisher randomization tests and constructing randomization-based confidence intervals. To address this problem, we propose a pair-switching rerandomization (PSRR) method to draw balanced assignments efficiently. We obtain the unbiasedness and variance reduction of the difference-in-means estimator and show that the Fisher randomization tests are valid under PSRR. Moreover, we propose an exact approach to invert Fisher randomization tests to confidence intervals, which is faster than the existing methods. In addition, our method is applicable to both nonsequentially and sequentially randomized experiments. We conduct comprehensive simulation studies to compare the finite-sample performance of the proposed method with that of classical rerandomization. Simulation results indicate that PSRR leads to comparable power of Fisher randomization tests and is 3-23 times faster than classical rerandomization. Finally, we apply the PSRR method to analyze two clinical trial datasets, both of which demonstrate the advantages of our method.
Topics: Research Design; Computer Simulation; Sample Size
PubMed: 35758335
DOI: 10.1111/biom.13712 -
Brazilian Journal of Otorhinolaryngology 2023Oral H antihistamines are the first-line treatment for patients with allergic rhinitis, while it is uncertain which kind and dosage of the antihistamines are more... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Oral H antihistamines are the first-line treatment for patients with allergic rhinitis, while it is uncertain which kind and dosage of the antihistamines are more effective in improving symptoms of patients.
OBJECTIVE
To evaluate the efficacy of different oral H antihistamine treatments on patients with allergic rhinitis by performing a network meta-analysis.
METHODS
The search was executed in PubMed, Embase, OVID, the Cochrane Library and ClinicalTrials.gov for relevant studies. The network meta-analysis was performed by using Stata 16.0, and the outcome measures of the analysis were symptom score reductions of patients. Relative risks with 95% Confidence Intervals were used in the network meta-analysis to compare the clinical effect of treatments involved, and Surface Under the Cumulative Ranking Curves (SUCRAs) were also calculated to rank the treatments' efficacy.
RESULTS
18 eligible randomized controlled studies, involving a total of 9419 participants, were included in this meta-analysis. All the antihistamine treatments outperformed placebo in total symptom score reduction and each individual symptom score reduction. According to the results of SUCRA, rupatadine 20 mg and rupatadine 10 mg were ranked relatively high in reductions of total symptom score (SUCRA: 99.7%, 76.3%), nasal congestion score (SUCRA: 96.4%, 76.4%), rhinorrhea score (SUCRA: 96.6%, 74.6%) and ocular symptom score (SUCRA: 97.2%, 88.8%); rupatadine 20 mg and levocetirizine 5 mg were ranked relatively high in reductions of nasal itching score (SUCRA: 84.8%, 83.4%) and sneezing score (SUCRA: 87.3%, 95.4%); loratadine 10 mg was ranked the lowest in each symptom score reduction besides placebo.
CONCLUSION
This study suggests that rupatadine is the most effective in alleviating symptoms of patients with allergic rhinitis among different oral H antihistamine treatments involved, and rupatadine 20 mg performs better than rupatadine 10 mg. While loratadine 10 mg has inferior efficacy for patients to the other antihistamine treatments.
Topics: Humans; Loratadine; Network Meta-Analysis; Randomized Controlled Trials as Topic; Histamine H1 Antagonists; Histamine Antagonists; Rhinitis, Allergic; Treatment Outcome
PubMed: 37271114
DOI: 10.1016/j.bjorl.2023.03.009 -
Transfusion and Apheresis Science :... Oct 2023Significant advances in procedural information displayed by current apheresis machines have been made, but analyses of cell collection efficiency (CE) still rely on...
Significant advances in procedural information displayed by current apheresis machines have been made, but analyses of cell collection efficiency (CE) still rely on calculations done by apheresis professionals. Accordingly, understanding CE equations can support the optimization of apheresis techniques and identification of incidents that could impact the procedure's effectiveness. This report summarizes classical and novel CE analyses applied to apheresis exemplified by an actual case of hematopoietic progenitor cell collection. In addition to the apheresis yield and most common CE and CE formulas, we present the instantaneous and corrected CE, fold enrichment, collection throughput, collection rate and its variants, average inlet rate, classical and adjusted captured cells, recruitment pool, recruitment factor, recruitment coefficient, blood component loss, predictive apheresis yield, and performance ratio calculations. Moreover, the mathematical relationship between these CE equations is also shown, which can be helpful in many apheresis procedures.
Topics: Humans; Leukapheresis; Blood Component Removal; Hematopoietic Stem Cells; Antigens, CD34
PubMed: 37438245
DOI: 10.1016/j.transci.2023.103758 -
Primary Dental Journal Sep 2023Dermal filler and botulinum toxin injections are among the most performed non-invasive procedures for rejuvenation and contouring, internationally. Although most dermal...
Dermal filler and botulinum toxin injections are among the most performed non-invasive procedures for rejuvenation and contouring, internationally. Although most dermal fillers and approved botulinum toxins are well tolerated with a high safety profile, adverse events and/or complications can happen. Injection-related sequelae and side effects are usually rare, mild, transient, and self-limiting in nature. However, devastating and life-changing complications, such as intravascular occlusion, skin necrosis, permanent visual impairment, and stroke, have been reported. Risk reduction measures include an in-depth knowledge of anatomy, physiology, and pharmacology, correct patient selection, correct identification of clinical indications, and, fundamentally, the importance of appropriate skill and training. In this paper, some of the complications are discussed and advice on how to minimise adverse events and complications from these injectables is provided.
Topics: Humans; Patient Selection; Esthetics
PubMed: 37705471
DOI: 10.1177/20501684231197717 -
Cureus Sep 2023This curriculum was designed to improve access to procedures for our internal medicine residents.
INTRODUCTION
This curriculum was designed to improve access to procedures for our internal medicine residents.
METHODS
We created an interdisciplinary procedure course (IDPC) composed of two simulation sessions and a one-week procedural rotation supervised by multiple specialties including nephrology, cardiology, cardiothoracic anesthesiology, general anesthesiology, and interventional radiology. After the course, residents completed two surveys documenting the number of procedures and their level of confidence on a Likert scale (1 = very unconfident to 5 = very confident) prior to and after completing the curriculum.
RESULTS
Sixteen residents participated in the course from September 2021 to June 2022. The collective number of procedures performed by these 16 residents increased from 176 to 343 after a one-week rotation. For arterial lines, the proportion of residents that reported an improvement in confidence scores was 0.44 (95% confidence interval 0.23 to 1, p-value of 0.60). The proportion of residents that had an increase in their confidence performing central lines was 0.63 (95% confidence interval 0.39 to 1, p-value of 0.23). For intubations, the proportion of residents that reported an improvement in confidence was 0.94 (95% confidence interval 0.72 to 1, p-value of 0.0006).
CONCLUSION
By collaborating with multiple specialties, residents almost doubled the number of procedures performed during training and reported an increased level of confidence in procedural performance for airway intubation. We learned residents want to improve their access to procedures and described a curriculum that was easily implemented.
PubMed: 37809158
DOI: 10.7759/cureus.44851 -
Pain Medicine (Malden, Mass.) Jul 2023Stellate ganglion block (SGB) is performed to relieve head, face, neck, or upper limb pain, and several non-pain indications for performing this block have emerged over... (Review)
Review
INTRODUCTION
Stellate ganglion block (SGB) is performed to relieve head, face, neck, or upper limb pain, and several non-pain indications for performing this block have emerged over the years. To date, there has been no attempt to synthesize evidence on SGB for treating non-pain indications. This scoping review presents a summary of the efficacy and adverse effects of SGB when performed for 6 non-pain indications.
METHODS
This scoping review was accomplished through the use of Arksey and O'Malley framework. A literature search was conducted for relevant articles in medical databases to identify publications on SGB and specified study types. Two reviewers independently assessed the risk of bias for randomized controlled trials, nonrandomized comparative studies, and case series. Results were summarized and recommendations were made on the basis of the strength of the available evidence according to the US Preventative Services Task Force grading system.
RESULTS
Twenty-four studies (19 randomized controlled trials and 5 nonrandomized studies) were included in this review. On the basis of the evidence, SGB is recommended for obtunding cardiovascular sympathetic stimulation, improving perfusion in limbs, and alleviating menopausal symptoms with a Grade B or C recommendation and a moderate-to-low level of certainty. There was insufficient evidence to recommend SGB for the other indications.
CONCLUSIONS
SGB can be considered for obtunding cardiovascular sympathetic stimulation and stress response, reducing vascular tone to improve vascular insufficiency in the limbs and perioperative hemodynamic stability, and alleviating hot flashes in menopause, in conditions refractory to conventional medical management.
Topics: Female; Humans; Stellate Ganglion; Autonomic Nerve Block; Pain; Research Design
PubMed: 36727500
DOI: 10.1093/pm/pnad011 -
Trials Oct 2023In this commentary, we discuss a recent article in Trials that raised concerns about the number of poorly performed randomised trials in the medical literature and...
In this commentary, we discuss a recent article in Trials that raised concerns about the number of poorly performed randomised trials in the medical literature and discuss the trials literature more widely. Although we all aim for higher methodological standards in trials, we argue that (i) the idea that 'most randomised trials are bad', which the recent article concludes is an overly simplistic representation of the situation, and (ii) the suggestion that an increased focus on methodological review during trial development (e.g. ethical boards performing some assessment of the methodologists on a trial), while well meaning, may have negative unintended consequences. We therefore propose that (a) trials should be assessed on their merits and weaknesses, including an assessment of risk of bias but placing that in a wider context; (b) we should recognise that although the methodological conduct of trials is of utmost importance, interventions that aim to improve this could have unintended consequences-such as bureaucracy-that have an overall negative effect; and (c) we should therefore generate an evidence base for policy interventions to improve conduct of trials rather than applying arbitrary rules.
Topics: Humans; Bias; Randomized Controlled Trials as Topic; Research Design
PubMed: 37864198
DOI: 10.1186/s13063-023-07706-1 -
Systematic Reviews Oct 2023Since 1997, several meta-analyses (MAs) of placebo-controlled randomised efficacy trials of homoeopathy for any indication (PRETHAIs) have been published with different...
BACKGROUND AND OBJECTIVE
Since 1997, several meta-analyses (MAs) of placebo-controlled randomised efficacy trials of homoeopathy for any indication (PRETHAIs) have been published with different methods, results and conclusions. To date, a formal assessment of these MAs has not been performed. The main objective of this systematic review of MAs of PRETHAIs was to evaluate the efficacy of homoeopathic treatment.
METHODS
The inclusion criteria were as follows: MAs of PRETHAIs in humans; all ages, countries, settings, publication languages; and MAs published from 1 Jan. 1990 to 30 Apr. 2023. The exclusion criteria were as follows: systematic reviews without MAs; MAs restricted to age or gender groups, specific indications, or specific homoeopathic treatments; and MAs that did not assess efficacy. We searched 8 electronic databases up to 14 Dec. 2020, with an update search in 6 databases up to 30 April 2023. The primary outcome was the effect estimate for all included trials in each MA and after restricting the sample to trials with high methodological quality, according to predefined criteria. The risk of bias for each MA was assessed by the ROBIS (Risk Of Bias In Systematic reviews) tool. The quality of evidence was assessed by the GRADE framework. Statistical analyses were performed to determine the proportion of MAs showing a significant positive effect of homoeopathy vs. no significant difference.
RESULTS
Six MAs were included, covering individualised homoeopathy (I-HOM, n = 2), nonindividualised homoeopathy (NI-HOM, n = 1) and all homoeopathy types (ALL-HOM = I-HOM + NI-HOM, n = 3). The MAs comprised between 16 and 110 trials, and the included trials were published from 1943-2014. The median trial sample size ranged from 45 to 97 patients. The risk of bias (low/unclear/high) was rated as low for three MAs and high for three MAs. Effect estimates for all trials in each MA showed a significant positive effect of homoeopathy compared to placebo (5 of 5 MAs, no data in 1 MA). Sensitivity analyses with sample restriction to high-quality trials were available from 4 MAs; the effect remained significant in 3 of the MAs (2 MAs assessed ALL-HOM, 1 MA assessed I-HOM) and was no longer significant in 1 MA (which assessed NI-HOM).
DISCUSSION
The quality of evidence for positive effects of homoeopathy beyond placebo (high/moderate/low/very low) was high for I-HOM and moderate for ALL-HOM and NI-HOM. There was no support for the alternative hypothesis of no outcome difference between homoeopathy and placebo. The available MAs of PRETHAIs reveal significant positive effects of homoeopathy beyond placebo. This is in accordance with laboratory experiments showing partially replicable effects of homoeopathically potentised preparations in physico-chemical, in vitro, plant-based and animal-based test systems.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42020209661. The protocol for this SR was finalised and submitted on 25 Nov. 2020 and registered on 26 Dec. 2020.
Topics: Humans; Bias; Homeopathy; Research Design; Meta-Analysis as Topic; Randomized Controlled Trials as Topic
PubMed: 37805577
DOI: 10.1186/s13643-023-02313-2 -
Journal of the International Society of... Dec 2023Citrulline may amplify the effects of L-arginine and nitric oxide concentration, which may augment vasodilation and blood flow, thereby enhancing aerobic exercise... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Citrulline may amplify the effects of L-arginine and nitric oxide concentration, which may augment vasodilation and blood flow, thereby enhancing aerobic exercise performance. The purpose of this randomized, double-blind, placebo-controlled crossover study was to investigate effects of L-citrulline + Glutathione on aerobic exercise performance and blood flow in well-trained men.
METHODS
Twenty-five males (Mean ± SD; Age: 22.2 ± 2.4 yrs; Height: 177.0 ± 4.8 cm; Weight: 75.3 ± 6.9 kg) were randomly assigned to the L-citrulline + Glutathione (Setria Performance Blend: SPB; L-citrulline [2 g] + glutathione [200 mg], 6 capsules) or placebo (PL; 3.1 g cellulose, 6 capsules) group. Participants performed a maximal oxygen consumption treadmill test to determine peak velocity (PV) and returned after eight days of ingesting either PL or SPB. Three timed treadmill runs to exhaustion (TTE) were performed at 90%, 100%, and 110% PV. Brachial artery blood flow and vessel diameter were assessed using ultrasound at 1-hr prior to exercise (1hrPrEX), after each exercise bout, immediately post-exercise (immediate PEX), and 30 minutes post exercise (30minPEX) at visits 2 and 4. Blood analytes were assessed via venous blood draws at visit 1, visit 3, and 1hrPEX, immediate PEX, and 30minPEX at visits 2 and 4. After a 14-day washout, participants repeated the same procedures, ingesting the opposite treatment. Separate repeated measures ANOVAs were performed for TTE, vessel diameter, blood flow, and blood analytes.
RESULTS
Blood flow was significantly augmented 30minPEX ( = 0.04) with SPB in comparison with PL. L-citrulline and L-arginine plasma concentrations were significantly elevated immediately PEX ( = 0.001) and 30-minPEX ( = 0.001) following SPB in comparison to PL.
CONCLUSION
Acute ingestion of SPB after eight days may enhance blood flow, L-citrulline, and L-arginine plasma concentrations after high-intensity exercise, which may enhance performance.
CLINICAL TRIAL REGISTRATION
[https://clinicaltrials.gov/ct2/show/nct04090138], identifier [NCT04090138].
Topics: Male; Humans; Young Adult; Adult; Dietary Supplements; Citrulline; Cross-Over Studies; Capsules; Glutathione; Double-Blind Method; Arginine
PubMed: 37125500
DOI: 10.1080/15502783.2023.2206386