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Exploration of Targeted Anti-tumor... 2023Coronavirus disease 2019 (COVID-19) became pandemic on 11th March 2020 and it deeply stressed the healthcare system. Cancer patients represent a vulnerable population,...
AIM
Coronavirus disease 2019 (COVID-19) became pandemic on 11th March 2020 and it deeply stressed the healthcare system. Cancer patients represent a vulnerable population, so many recommendations have been approved to ensure optimal management. Clinical research was notably impacted by COVID too. This review aims to analyze the challenges occurred during a pandemic for the management of enrolled patients (enrollment, use of telemedicine visits, study procedures) and for the clinical trials system (from feasibility to selection visit, site initiation visit, monitorings, use of e-signature, deviations and discontinuations).
METHODS
The studies included in the present review were selected from PubMed/Google Scholar/ScienceDirect databases.
RESULTS
During the first phase of pandemic many clinical trials were suspended in accrual and, as the pandemic progressed, recommendations were established to guarantee the safety and the continuity of care of enrolled patients. In addition, lot of new strategies was found during the pandemic to reduce the negative consequences on clinical trial performance and to guarantee new opportunities of care in the respect of good clinical practice (GCP) in a bad scenario.
CONCLUSIONS
Among all modifiers, investigators would prefer to maintain the positive ones such as pragmatic and simplified trial designs and protocols, reducing in-person visits when not necessary and to minimizing sponsor and contract research organizations (CROs) visits.
PubMed: 38023994
DOI: 10.37349/etat.2023.00183 -
Frontiers in Immunology 2023The aim of this study was to systematically review the neuroimmunology literature to determine the average immune cell counts reported by flow cytometry in wild-type...
OBJECTIVE
The aim of this study was to systematically review the neuroimmunology literature to determine the average immune cell counts reported by flow cytometry in wild-type (WT) homogenized mouse brains.
BACKGROUND
Mouse models of gene dysfunction are widely used to study age-associated neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease. The importance of the neuroimmune system in these multifactorial disorders has become increasingly evident, and methods to quantify resident and infiltrating immune cells in the brain, including flow cytometry, are necessary. However, there appears to be no consensus on the best approach to perform flow cytometry or quantify/report immune cell counts. The development of more standardized methods would accelerate neuroimmune discovery and validation by meta-analysis.
METHODS
There has not yet been a systematic review of 'neuroimmunology' by 'flow cytometry' via examination of the PROSPERO registry. A protocol for a systematic review was subsequently based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) using the Studies, Data, Methods, and Outcomes (SDMO) criteria. Literature searches were conducted in the Google Scholar and PubMed databases. From that search, 900 candidate studies were identified, and 437 studies were assessed for eligibility based on formal exclusion criteria.
RESULTS
Out of the 437 studies reviewed, 58 were eligible for inclusion and comparative analysis. Each study assessed immune cell subsets within homogenized mouse brains and used flow cytometry. Nonetheless, there was considerable variability in the methods, data analysis, reporting, and results. Descriptive statistics have been presented on the study designs and results, including medians with interquartile ranges (IQRs) and overall means with standard deviations (SD) for specific immune cell counts and their relative proportions, within and between studies. A total of 58 studies reported the most abundant immune cells within the brains were TMEM119 microglia, bulk CD4 T cells, and bulk CD8 T cells.
CONCLUSION
Experiments to conduct and report flow cytometry data, derived from WT homogenized mouse brains, would benefit from a more standardized approach. While within-study comparisons are valid, the variability in methods of counting of immune cell populations is too broad for meta-analysis. The inclusion of a minimal protocol with more detailed methods, controls, and standards could enable this nascent field to compare results across studies.
Topics: Animals; Mice; Brain; CD8-Positive T-Lymphocytes; Flow Cytometry; Research Design; Systematic Reviews as Topic
PubMed: 38022545
DOI: 10.3389/fimmu.2023.1281705 -
Dental Research Journal 2023Previous systematic reviews indicate that there is an increased prevalence of caries in cleft patients in comparison to their healthy control group. To date, the... (Review)
Review
BACKGROUND
Previous systematic reviews indicate that there is an increased prevalence of caries in cleft patients in comparison to their healthy control group. To date, the prevalence of caries between unilateral cleft lip and palate (UCLP) and bilateral cleft lip and palate (BCLP) has not been quantitatively evaluated. This review aims to include published studies that examined caries prevalence in patients with UCLP and BCLP to find out whether a quantitative difference exists in caries experience among them.
MATERIALS AND METHODS
Medline/PubMed, Scopus, and EBSCOhost databases were searched from inception to November 2021. The protocol was registered with PROSPERO registration no. CRD2021292425. Prevalence-based studies that evaluated caries experience using the decayed-missing-filled teeth (DMFT) index in the permanent dentition or dmft in case of primary dentition in patients with UCLP or BCLP were included in the analysis with the outcome given in mean and standard deviation. Meta-analysis was performed using a random effect model through a forest plot. An adapted version of the Newcastle-Ottawa Scale for cross-sectional studies was modified to assess the quality of included studies.
RESULTS
Three studies were included in the review. The difference in caries prevalence was statistically significant in the permanent and primary dentition which were evaluated using DMFT and dmft scores with = 0.01 and = 0.03, respectively. Forest plot values were obtained for permanent dentition (DMFT) and primary dentition (dmft), 0.57 (95% confidence interval [CI]: 1.03-0.11) and 0.36 (95% CI: 0.69-0.03), respectively. The result of the meta-analysis indicates that patients with BCLP have higher caries prevalence.
CONCLUSION
The outcome of the study indicates a higher occurrence of caries in patients with BCLP than UCLP in both permanent and primary dentition.
PubMed: 38020250
DOI: No ID Found -
Naunyn-Schmiedeberg's Archives of... May 2024Daily administration of oral iron is considered the current treatment standard for treating iron deficiency anemia due to availability and reduced cost compared to... (Review)
Review
Daily administration of oral iron is considered the current treatment standard for treating iron deficiency anemia due to availability and reduced cost compared to intravenous iron therapy. But adverse effects like epigastric pain, heartburn, and constipation reduce compliance to daily oral iron. There is scanty evidence regarding compliance and efficacy with alternate-day iron therapy. As per our knowledge, this is the first systematic review to compare daily with alternate-day oral iron therapy. Six electronic databases including PubMed and EMBASE were searched for randomized controlled trials, quasi-experimental studies published between January 2000 to March 2023 that compared daily with alternate day iron therapy in individuals diagnosed with iron deficiency anemia. The primary outcome analyzed was a change in hemoglobin. The other hematological parameters were assessed as secondary outcomes. Risk of bias was assessed regarding randomization process, deviation from intended intervention, missing outcome data, measurement of the outcome, and selection of the reported result. Out of the 9 full-text articles, 2 were not included as one was an ongoing trial and the second one had a different study design. The reviewed trials involved 594 participants, and the study participants ranged from 19 to 200. The mean age of the participants in the reported trials was 21 ± 2 to 49 ± 16 years. There is no significant increase in hemoglobin level and also the iron indices namely ferritin, hepcidin, total iron binding capacity, and reticulocyte count between daily and alternate-day dosing of iron. However, the frequency of adverse effects especially nausea, metallic taste, and altered bowel habits are reduced with alternate-day dosing. Oral iron given daily or on alternate days did not have a significant difference in the hemoglobin levels though iron absorption may be affected in the initial few days.Trial registration: The review protocol was registered with PROSPERO (Prospero2023CRD42023393095).
Topics: Humans; Anemia, Iron-Deficiency; Administration, Oral; Iron; Hemoglobins; Drug Administration Schedule; Randomized Controlled Trials as Topic; Adult; Young Adult; Middle Aged; Treatment Outcome
PubMed: 37979057
DOI: 10.1007/s00210-023-02817-7 -
Sports Medicine - Open Nov 2023Understanding the physical qualities of male, adolescent rugby league players across age groups is essential for practitioners to manage long-term player development....
What Tests are Used to Assess the Physical Qualities of Male, Adolescent Rugby League Players? A Systematic Review of Testing Protocols and Reported Data Across Adolescent Age Groups.
BACKGROUND
Understanding the physical qualities of male, adolescent rugby league players across age groups is essential for practitioners to manage long-term player development. However, there are many testing options available to assess these qualities, and differences in tests and testing protocols can profoundly influence the data obtained.
OBJECTIVES
The aims of this systematic review were to: (1) identify the most frequently used tests to assess key physical qualities in male, adolescent rugby league players (12-19 years of age); (2) examine the testing protocols adopted in studies using these tests; and (3) synthesise the available data from studies using the most frequently used tests according to age group.
METHODS
A systematic search of five databases was conducted. For inclusion, studies were required to: (1) be original research that contained original data published in a peer-reviewed journal; (2) report data specifically for male, adolescent rugby league players; (3) report the age for the recruited participants to be between 12 and 19 years; (4) report data for any anthropometric quality and one other physical quality and identify the test(s) used to assess these qualities; and (5) be published in English with full-text availability. Weighted means and standard deviations were calculated for each physical quality for each age group arranged in 1-year intervals (i.e., 12, 13, 14, 15, 16, 17 and 18 years) across studies.
RESULTS
37 studies were included in this systematic review. The most frequently used tests to assess anthropometric qualities were body mass, standing height, and sum of four skinfold sites. The most frequently used tests to assess other physical qualities were the 10-m sprint (linear speed), 505 Agility Test (change-of-direction speed), Multistage Fitness Test (aerobic capacity), bench press and back squat one-repetition maximum tests (muscular strength), and medicine ball throw (muscular power). Weighted means calculated across studies generally demonstrated improvements in player qualities across subsequent age groups, except for skinfold thickness and aerobic capacity. However, weighted means could not be calculated for the countermovement jump.
CONCLUSION
Our review identifies the most frequently used tests, but highlights variability in the testing protocols adopted. If these tests are used in future practice, we provide recommended protocols in accordance with industry standards for most tests. Finally, we provide age-specific references for frequently used tests that were implemented with consistent protocols. Clinical Trial Registration This study was conducted in accordance with the Preferred Reporting Items of Systematic Review and Meta-analysis guidelines and was registered with PROSPERO (ID: CRD42021267795).
PubMed: 37947891
DOI: 10.1186/s40798-023-00650-z -
Disability and Rehabilitation Oct 2023This review investigated the effectiveness of adjuvant therapy combined with constraint-induced movement therapy (CIMT) in improving the paretic upper limb functionality... (Review)
Review
PURPOSE
This review investigated the effectiveness of adjuvant therapy combined with constraint-induced movement therapy (CIMT) in improving the paretic upper limb functionality in adults with stroke sequelae during the subacute to chronic rehabilitation phase.
MATERIALS AND METHODS
In this systematic review and meta-analysis of randomized controlled trials (RCT), electronic databases, including PubMed, Web of Science, CINAHL, and MEDLINE, were searched. We included RCTs that investigated the outcomes of adjuvant therapy (i.e. other therapies) added to CIMT compared with CIMT alone. Key trial findings were qualitatively synthesized and analyzed. This meta-analysis examined variables, such as mean scores and standard deviations, using the following outcome measures: Fugl-Meyer Assessment (FMA) upper limb items, Action Research Arm Test (ARAT), Amount of Use (AOU) of Motor Activity Log (MAL), and Quality of Movement (QOM) of MAL.
RESULTS
Eighteen eligible RCTs were included in the analysis. Adding CIMT to adjunctive therapy significantly improved FMA compared with CIMT alone (mean difference [MD] 4.02, 95% confidence interval [CI] 2.60-5.44; I = 85%; 15 studies; 330 participants). Similarly, the ARAT and MAL-AOU scores improved significantly.
CONCLUSIONS
CIMT combined with several adjunctive therapies effectively improved upper limb function.
PubMed: 37855247
DOI: 10.1080/09638288.2023.2269843 -
BMJ Open Oct 2023Prospectively registering study plans in a permanent time-stamped and publicly accessible document is becoming more common across disciplines and aims to reduce risk of... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Prospectively registering study plans in a permanent time-stamped and publicly accessible document is becoming more common across disciplines and aims to reduce risk of bias and make risk of bias transparent. Selective reporting persists, however, when researchers deviate from their registered plans without disclosure. This systematic review aimed to estimate the prevalence of undisclosed discrepancies between prospectively registered study plans and their associated publication. We further aimed to identify the research disciplines where these discrepancies have been observed, whether interventions to reduce discrepancies have been conducted, and gaps in the literature.
DESIGN
Systematic review and meta-analyses.
DATA SOURCES
Scopus and Web of Knowledge, published up to 15 December 2019.
ELIGIBILITY CRITERIA
Articles that included quantitative data about discrepancies between registrations or study protocols and their associated publications.
DATA EXTRACTION AND SYNTHESIS
Each included article was independently coded by two reviewers using a coding form designed for this review (osf.io/728ys). We used random-effects meta-analyses to synthesise the results.
RESULTS
We reviewed k=89 articles, which included k=70 that reported on primary outcome discrepancies from n=6314 studies and, k=22 that reported on secondary outcome discrepancies from n=1436 studies. Meta-analyses indicated that between 29% and 37% (95% CI) of studies contained at least one primary outcome discrepancy and between 50% and 75% (95% CI) contained at least one secondary outcome discrepancy. Almost all articles assessed clinical literature, and there was considerable heterogeneity. We identified only one article that attempted to correct discrepancies.
CONCLUSIONS
Many articles did not include information on whether discrepancies were disclosed, which version of a registration they compared publications to and whether the registration was prospective. Thus, our estimates represent discrepancies broadly, rather than our target of discrepancies between registered study plans and their associated publications. Discrepancies are common and reduce the trustworthiness of medical research. Interventions to reduce discrepancies could prove valuable.
REGISTRATION
osf.io/ktmdg. Protocol amendments are listed in online supplemental material A.
Topics: Humans; Prospective Studies; Prevalence; Bias; Publication Bias; Biomedical Research
PubMed: 37793922
DOI: 10.1136/bmjopen-2023-076264 -
Sports Medicine - Open Sep 2023Circulating biomarkers of bone formation and resorption are widely used in exercise metabolism research, but their responses to exercise are not clear. This study aimed...
BACKGROUND
Circulating biomarkers of bone formation and resorption are widely used in exercise metabolism research, but their responses to exercise are not clear. This study aimed to quantify group responses and inter-individual variability of P1NP and β-CTX-1 after prolonged, continuous running (60-120 min at 65-75% V̇O) in young healthy adult males using individual participant data (IPD) meta-analysis.
METHODS
The protocol was designed following PRISMA-IPD guidelines and was pre-registered on the Open Science Framework prior to implementation ( https://osf.io/y69nd ). Changes in P1NP and β-CTX-1 relative to baseline were measured during, immediately after, and in the hours and days following exercise. Typical hourly and daily variations were estimated from P1NP and β-CTX-1 changes relative to baseline in non-exercise (control) conditions. Group responses and inter-individual variability were quantified with estimates of the mean and standard deviation of the difference, and the proportion of participants exhibiting an increased response. Models were conducted within a Bayesian framework with random intercepts to account for systematic variation across studies.
RESULTS
P1NP levels increased during and immediately after running, when the proportion of response was close to 100% (75% CrI: 99 to 100%). P1NP levels returned to baseline levels within 1 h and over the next 4 days, showing comparable mean and standard deviation of the difference with typical hourly (0.1 ± 7.6 ng·mL) and daily (- 0.4 ± 5.7 ng·mL) variation values. β-CTX-1 levels decreased during and up to 4 h after running with distributions comparable to typical hourly variation (- 0.13 ± 0.11 ng·mL). There was no evidence of changes in β-CTX-1 levels during the 4 days after the running bout, when distributions were also similar between the running data and typical daily variation (- 0.03 ± 0.10 ng·mL).
CONCLUSION
Transient increases in P1NP were likely biological artefacts (e.g., connective tissue leakage) and not reflective of bone formation. Comparable small decreases in β-CTX-1 identified in both control and running data, suggested that these changes were due to the markers' circadian rhythm and not the running intervention. Hence, prolonged continuous treadmill running did not elicit bone responses, as determined by P1NP and β-CTX-1, in this population.
PubMed: 37725246
DOI: 10.1186/s40798-023-00628-x -
The Cochrane Database of Systematic... Aug 2023Transjugular intrahepatic portosystemic shunt (TIPS) is a widely used procedure for management of uncontrolled upper gastrointestinal bleeding and refractory ascites in... (Review)
Review
BACKGROUND
Transjugular intrahepatic portosystemic shunt (TIPS) is a widely used procedure for management of uncontrolled upper gastrointestinal bleeding and refractory ascites in people with liver cirrhosis. However, nearly half of the people experience shunt dysfunction and recurrent symptoms within one year of the procedure. Expanded polytetrafluoroethylene (ePTFE)-covered stents are assumed to decrease shunt dysfunction by approximately 20% to 30%.
OBJECTIVES
To evaluate the benefits and harms associated with the use of expanded polytetrafluoroethylene (ePTFE)-covered stents versus bare stents in transjugular intrahepatic portosystemic shunts (TIPSs) for managing people with liver cirrhosis.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 28 February 2023.
SELECTION CRITERIA
Randomised clinical trials comparing ePTFE-covered stents versus bare stents in TIPS for treatment of people with liver cirrhosis.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. all-cause mortality, 2. procedure-related complications, and 3. health-related quality of life. Our secondary outcomes were 4. upper gastrointestinal bleeding, 5. recurrence of ascites, 6. hepatic encephalopathy, 7. kidney failure, 8. early thrombosis, 9. non-serious adverse events, and 10. shunt dysfunction. We used GRADE to assess certainty of evidence. We analysed outcome data at the maximum follow-up, except for the 'early thrombosis' outcome for which it was within 12 weeks after the TIPS procedure.
MAIN RESULTS
We included four trials with 565 randomised participants (age range: 18 to 75 years; male range: 63.6% to 75.0%). A total of 527 participants provided data for analyses because of losses to follow-up. Two trials were conducted in China; one in France; and one in France, Spain, and Canada. Participants were classified with cirrhosis Child-Pugh class A, B, or C, and for some, the class was not reported. We used intention-to-treat principle (four trials) and per-protocol analysis (one trial) to meta-analyse the data. One trial compared ePTFE-covered stents versus bare stents of the same diameter and three trials compared ePTFE-covered stents versus stents of different diameters. ePTFE-covered stents versus bare stents of the same diameter One trial with 258 participants compared 8 mm covered stent versus 8 mm bare stent. Mortality in the covered stent group is possibly lower than in the bare stent group (risk ratio (RR) 0.63, 95% confidence interval (CI) 0.43 to 0.92; low-certainty evidence). Upper gastrointestinal bleeding (RR 0.54, 95% CI 0.35 to 0.84), recurrence of ascites (RR 0.42, 95% CI 0.20 to 0.87), and shunt dysfunction (RR 0.42, 95% CI 0.28 to 0.61) occurred more often in the bare stent group than in the covered stent group (all low-certainty evidence). There was no difference in hepatic encephalopathy between groups (RR 1.10, 95% CI 0.76 to 1.61; very low-certainty evidence). The trial did not report data on procedure-related complications, health-related quality of life, early thrombosis, and segmental liver ischaemia (a non-serious adverse event). ePTFE-covered stents versus bare stents of different stent diameters Three trials compared ePTFE-covered stents versus bare stents of different diameters (10.5 (standard deviation (SD) 0.9) mm versus 11.7 (SD 0.8) mm; 8 mm versus 10 mm; and one trial used 10-mm stents that could be dilated from 8 mm to 10 mm). There was no evidence of a difference between the ePTFE-covered stents versus bare stents groups in mortality (RR 0.75, 95% CI 0.48 to 1.16; 3 trials, 269 participants), procedure-related complications (RR 0.53, 95% CI 0.05 to 5.57; 1 trial, 80 participants), upper gastrointestinal bleeding (RR 0.46, 95% CI 0.15 to 1.38; 3 trials, 269 participants), hepatic encephalopathy (RR 0.93, 95% CI 0.66 to 1.30; 3 trials, 269 participants), and kidney failure (RR 7.59, 95% CI 0.40 to 143.92; 1 trial, 121 participants) (all very low-certainty evidence). Recurrence of ascites (RR 0.30, 95% CI 0.11 to 0.85; 3 trials, 269 participants; low-certainty evidence), shunt dysfunction (RR 0.50, 95% CI 0.28 to 0.92; 3 trials, 269 participants; low-certainty evidence), and early thrombosis (RR 0.28, 95% CI 0.09 to 0.82; I = 0%; 3 trials, 261 participants; very low-certainty evidence) occurred more often in the bare stents group. There was no evidence of a difference in segmental liver ischaemia (RR 5.25, 95% CI 0.26 to 106.01; 1 trial, 80 participants; very low-certainty evidence). No trial presented data on health-related quality of life. Funding One trial did not clearly report funding sources. The remaining three trials declared that they had no funding with vested interests.
AUTHORS' CONCLUSIONS
Based on the small number of trials with insufficient sample size and events, and study limitations, we assessed the overall certainty of evidence in the predefined outcomes as low or very low. Therefore, we are uncertain which of the two interventions (ePTFE-covered stents or bare stents of the same diameter and ePTFE-covered stents versus bare stents of different stent diameters) is effective for the evaluated outcomes. None of the four trials reported data on health-related quality of life, and data on complications were either missing or rarely reported. We lack high-quality trials to evaluate the role of ePTFE-covered stents for TIPS for managing people with liver cirrhosis.
Topics: Adolescent; Adult; Aged; Humans; Male; Middle Aged; Young Adult; Ascites; Gastrointestinal Hemorrhage; Hepatic Encephalopathy; Liver Cirrhosis; Polytetrafluoroethylene; Portasystemic Shunt, Transjugular Intrahepatic; Quality of Life; Stents; Female; Randomized Controlled Trials as Topic
PubMed: 37531575
DOI: 10.1002/14651858.CD012358.pub2 -
The Knee Oct 2023Autologous chondrocyte implantation (ACI) is primarily performed in active, young patients to treat knee pain and functional limitations resulting from articular... (Review)
Review
PURPOSE
Autologous chondrocyte implantation (ACI) is primarily performed in active, young patients to treat knee pain and functional limitations resulting from articular cartilage injury. Nevertheless, the functional outcomes of ACI remain poorly understood. This systematic review aimed to evaluate the biomechanical and functional outcomes of ACI.
METHODS
Ovid MEDLINE, Embase, and Web of Science were systematically searched using the terms 'Knee OR Knee joint AND Autologous chondrocyte implantation OR ACI'. Inclusion and exclusion criteria were used to screen publications by title, abstract, and full text. Study quality and bias were assessed by two reviewers. Means and standard deviations of all collected variables were calculated and presented in the review.
PROSPERO ID
CRD42021238768.
RESULTS
Nineteen articles including 20 ACI cohorts were included. In general, the average range of motion (ROM) improved with clinical (>5°) and statistical significance (p < 0.05) postoperatively: 130.5 ± 14.8° to 136.1 ± 10.2°. Knee strength significantly improved within the first two postoperative years but remained poorer than control groups at final follow-up. No statistical differences were found between ACI and control groups in their ability to perform functional activities like the 6-minute walk test.
CONCLUSION
Knee range of motion generally improved following ACI. Although, some studies reported that knee strengths remained significantly poorer than healthy controls, particularly >2-years postoperatively, implying that longer-term strength training may benefit patients.However, the volume of research and current level of evidence remain low, thus further research is required to better understand the impact of ACI on knee function and guide future rehabilitative protocols.
Topics: Humans; Cartilage, Articular; Chondrocytes; Transplantation, Autologous; Knee Joint; Cartilage Diseases
PubMed: 37516029
DOI: 10.1016/j.knee.2023.07.004