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BMC Urology May 2024Patients with spinal cord injury have a relatively high risk for bladder cancer and often complicated with bladder cancer in advanced stages, and the degree of...
BACKGROUND
Patients with spinal cord injury have a relatively high risk for bladder cancer and often complicated with bladder cancer in advanced stages, and the degree of aggressiveness of malignancy is high. Most of the literature is based on disease clinical features while, our study reviews the clinical characteristics and molecular mechanisms of spinal cord injury patients with bladder cancer, so that it might help clinicians better recognize and manage these patients.
METHOD
We searched PubMed, Web of Science and Embase, using retrieval type like ("Neurogenic Lower Urinary Tract Dysfunction" OR "Spinal cord injury" OR "Spinal Cord Trauma") AND ("bladder cancer" OR "bladder neoplasm" OR "bladder carcinoma" OR "Urinary Bladder Neoplasms" OR "Bladder Tumor"). In Web of Science, the retrieval type was searched as "Topic", and in PubMed and Embase, as "All Field". The methodological quality of eligible studies and their risk of bias were assessed using the Newcastle-Ottawa scale. This article is registered in PROSPERO with the CBD number: CRD42024508514.
RESULT
In WOS, we searched 219 related papers, in PubMed, 122 and in Embase, 363. Thus, a total of 254 articles were included after passing the screening, within a time range between 1960 and 2023. A comprehensive analysis of the data showed that the mortality and incidence rates of bladder cancer in spinal cord injury patients were higher than that of the general population, and the most frequent pathological type was squamous cell carcinoma. In parallel to long-term urinary tract infection and indwelling catheterization, the role of molecules such as NO, MiR 1949 and Rb 1. was found to be crucial pathogenetically.
CONCLUSION
This review highlights the risk of bladder cancer in SCI patients, comprehensively addressing the clinical characteristics and related molecular mechanisms. However, given that there are few studies on the molecular mechanisms of bladder cancer in spinal cord injury, further research is needed to expand the understanding of the disease.
Topics: Spinal Cord Injuries; Humans; Urinary Bladder Neoplasms
PubMed: 38778291
DOI: 10.1186/s12894-024-01457-0 -
PloS One 2024In the search for better anticancer drugs, computer-aided drug design (CADD) techniques play an indispensable role in facilitating the lengthy and costly drug discovery...
BACKGROUND
In the search for better anticancer drugs, computer-aided drug design (CADD) techniques play an indispensable role in facilitating the lengthy and costly drug discovery process especially when natural products are involved. Anthraquinone is one of the most widely-recognized natural products with anticancer properties. This review aimed to systematically assess and synthesize evidence on the utilization of CADD techniques centered on the anthraquinone scaffold for cancer treatment.
METHODS
The conduct and reporting of this review were done in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2020 guideline. The protocol was registered in the "International prospective register of systematic reviews" database (PROSPERO: CRD42023432904) and also published recently. The search strategy was designed based on the combination of concept 1 "CADD or virtual screening", concept 2 "anthraquinone" and concept 3 "cancer". The search was executed in PubMed, Scopus, Web of Science and MedRxiv on 30 June 2023.
RESULTS
Databases searching retrieved a total of 317 records. After deduplication and applying the eligibility criteria, the final review ended up with 32 articles in which 3 articles were found by citation searching. The CADD methods used in the studies were either structure-based alone (69%) or combined with ligand-based methods via parallel (9%) or sequential (22%) approaches. Molecular docking was performed in all studies, with Glide and AutoDock being the most popular commercial and public software used respectively. Protein data bank was used in most studies to retrieve the crystal structure of the targets of interest while the main ligand databases were PubChem and Zinc. The utilization of in-silico techniques has enabled a deeper dive into the structural, biological and pharmacological properties of anthraquinone derivatives, revealing their remarkable anticancer properties in an all-rounded fashion.
CONCLUSION
By harnessing the power of computational tools and leveraging the natural diversity of anthraquinone compounds, researchers can expedite the development of better drugs to address the unmet medical needs in cancer treatment by improving the treatment outcome for cancer patients.
Topics: Anthraquinones; Humans; Neoplasms; Antineoplastic Agents; Drug Design; Molecular Docking Simulation; Computer-Aided Design; Drug Discovery
PubMed: 38776291
DOI: 10.1371/journal.pone.0301396 -
BMJ Open May 2024To assess the reporting and methodological quality of early-life policy intervention papers that applied difference-in-differences (DiD) analysis.
OBJECTIVES
To assess the reporting and methodological quality of early-life policy intervention papers that applied difference-in-differences (DiD) analysis.
STUDY DESIGN
Systematic review.
DATA SOURCES
Papers applying DiD of early-life policy interventions in high-income countries as identified by searching Medline, Embase and Scopus databases up to December, 2022.
STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS
Studies evaluating policy interventions targeting expectant mothers, infants or children up to two years old and conducted in high income countries were included. We focused on seven critical conditions of DiD as proposed in a comprehensive checklist: data requirements, parallel trends, no-anticipation, standard statistical assumptions, common shocks, group composition and spillover.
RESULTS
The DiD included studies (n=19) evaluating early-life policy interventions in childhood development (n=4), healthcare utilisation and providers (n=4), nutrition programmes (n=3) and economic policies such as prenatal care expansion (n=8). Although none of the included studies met all critical conditions, the most reported and adhered to critical conditions were data requirements (n=18), standard statistical assumptions (n=11) and the parallel trends assumption (n=9). No-anticipation and spillover were explicitly reported and adhered to in two studies and one study, respectively.
CONCLUSIONS
This review highlights current deficiencies in the reporting and methodological quality of studies using DiD to evaluate early-life policy interventions. As the validity of study conclusions and consequent implications for policy depend on the extent to which critical conditions are met, this shortcoming is concerning. We recommend that researchers use the described checklist to improve the transparency and validity of their evaluations. The checklist should be further refined by adding order of importance or knock-out criteria and may also help facilitate uniform terminology. This will hopefully encourage reliable DiD evaluations and thus contribute to better policies relating to expectant mothers, infants and children.
Topics: Humans; Infant; Health Policy; Infant, Newborn; Child, Preschool; Child Development; Female; Prenatal Care
PubMed: 38760036
DOI: 10.1136/bmjopen-2024-083927 -
International Journal of Nursing... Dec 2023Negative symptoms, frequently experienced by people with schizophrenia, can impair functional outcomes and quality of life. Negative symptoms typically affect... (Review)
Review
BACKGROUND
Negative symptoms, frequently experienced by people with schizophrenia, can impair functional outcomes and quality of life. Negative symptoms typically affect motivation, communication, and the ability to live independently and are difficult to treat. Several meta-analyses suggest that cognitive behavioural therapy results in a modest reduction in negative symptoms. It is unclear if similar effects can be achieved using behavioural activation. Behavioural activation is a derivative of cognitive behavioural therapy that helps to improve social and emotional functioning by encouraging patients to engage in activities that they value whilst modifying the avoidance responses. Behavioural activation can be a standalone treatment for depressive symptoms that is equally as efficacious as cognitive behavioural therapy.
OBJECTIVE
This systematic review aimed to identify and summarise the evidence about the efficacy of behavioural activation in treating negative symptoms.
DESIGN
Systematic review.
SETTING/PARTICIPANTS
Two published studies conducted in South Korea and the United Kingdom recruited 55 patients.
METHOD
We searched five databases and four trial registries for clinical treatment trials of behavioural activation involving adults diagnosed with negative symptoms of schizophrenia. Studies were screened according to the inclusion criteria and assessed for quality.
RESULTS
We identified 5023 published studies. After removing duplicates and conducting screening, two studies were included in this review. One study used a parallel non-randomised trial design whilst the other adopted a single group test-re-test design. Fifty-five participants were recruited from hospital and community settings. Both studies delivered 10 face-to-face sessions of behavioural activation; these were individual in one study and group sessions in the other. One study involved behavioural activation as the treatment whilst the other delivered behavioural activation with motivational interviewing. Neither study reported harms or adverse events.
CONCLUSIONS
Based on the included studies, there is low-quality evidence that behavioural activation may be helpful in the treatment of negative symptoms. Key limitations of the studies include small sample sizes and overall low study quality.
STUDY REGISTRATION
The protocol covering this review was registered with Open Science on 18 February 2022 (Registration DOI 10.17605/OSF.IO/57QSW; Weblink: https://osf.io/57qsw).
TWEETABLE ABSTRACT
Behavioural activation holds promise in supporting patients experiencing negative symptoms of schizophrenia.
PubMed: 38746587
DOI: 10.1016/j.ijnsa.2023.100132 -
Clinical and Translational Science May 2024No systematic review of trial designs in patients with relapsing multiple sclerosis (RMS) was reported. This systematic review was conducted on the trial designs and... (Review)
Review
No systematic review of trial designs in patients with relapsing multiple sclerosis (RMS) was reported. This systematic review was conducted on the trial designs and primary end points (PEs) of phase II and III trials intended to modify the natural course of the disease in patients with RMS. The purpose of the study is to explore trends/topics and discussion points in clinical trial design and PE, comparing them to regulatory guidelines and expert recommendations. Three trial registration systems, ClinicalTrials.gov, the EU Clinical Trials Register, and the Japan Registry of Clinical Trials, were used and 60 trials were evaluated. The dominant clinical trial design was a randomized controlled parallel-arms trial and other details were as follows: in adult phase III confirmatory trials (n = 32), active-controlled double-blind trial (DBT) (53%) and active-controlled open-label assessor-masking trial (16%); in adult phase II dose-finding trials (n = 9), placebo- and active-controlled DBT (44%), placebo-controlled DBT (22%), and placebo-controlled add-on DBT (22%); and in pediatric phase III confirmatory trials (n = 8), active-controlled DBT (38%) and active-controlled open-label non-masking trial (25%). The most common PEs were as follows: in adult confirmatory trials, annual relapse rate (ARR) (56%) and no evidence of disease activity-3 (NEDA-3) (13%); in adult dose-finding trials, the cumulative number of T1 gadolinium-enhancing lesions (56%), combined unique active lesions (22%), and overall disability response score (22%); and in pediatric confirmatory trials, ARR (38%) and time to first relapse (25%). It was suggested that some parts of the regulatory guidelines and expert recommendations need to be revised.
Topics: Humans; Clinical Trials, Phase III as Topic; Clinical Trials, Phase II as Topic; Adult; Multiple Sclerosis, Relapsing-Remitting; Child; Research Design; Endpoint Determination; Randomized Controlled Trials as Topic
PubMed: 38708586
DOI: 10.1111/cts.13794 -
BMC Oral Health May 2024Successful endodontic treatment needs accurate determination of working length (WL). Electronic apex locators (EALs) were presented as an alternative to radiographic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Successful endodontic treatment needs accurate determination of working length (WL). Electronic apex locators (EALs) were presented as an alternative to radiographic methods; and since then, they have evolved and gained popularity in the determination of WL. However, there is insufficient evidence on the post-operative pain, adequacy, and accuracy of EALs in determining WL.
OBJECTIVE
The systematic review and meta-analysis aims to gather evidence regarding the effectiveness of EALs for WL determination when compared to different imaging techniques along with postoperative pain associated with WL determination, the number of radiographs taken during the procedure, the time taken, and the adverse effects.
METHODS
For the review, clinical studies with cross-over and parallel-arm randomized controlled trials (RCTs) were searched in seven electronic databases, followed by cross-referencing of the selected studies and related research synthesis. Risk of bias (RoB) assessment was carried out with Cochrane's RoB tool and a random-effects model was used. The meta-analysis was performed with the RevMan software 5.4.1.
RESULTS
Eleven eligible RCTs were incorporated into the review and eight RCTs into the meta-analysis, of which five had high RoB and the remaining six had unclear RoB. Following meta-analysis, no significant difference in postoperative pain was found among the EAL and radiograph groups (SMD 0.00, CI .29 to .28, 354 participants; P value = 0.98). Radiograph group showed better WL accuracy (SMD 0.55, CI .11 to .99, 254 participants; P value = 0.02), while the EAL group had 10% better WL adequacy (RR 1.10, CI 1.03-1.18, 573 participants; P value = 0.006).
CONCLUSION
We found very low-certainty evidence to support the efficacy of different types of EAL compared to radiography for the outcomes tested. We were unable to reach any conclusions about the superiority of any type of EAL. Well-planned RCTs need to be conducted by standardizing the outcomes and outcome measurement methods.
Topics: Humans; Dental Pulp Cavity; Odontometry; Radiography, Dental; Tooth Apex
PubMed: 38704529
DOI: 10.1186/s12903-024-04259-w -
La Medicina Del Lavoro Apr 2024Several antiblastic drugs (ADs) are classified as carcinogenic, mutagenic, and/or toxic for reproduction. Despite established guidelines and safe handling technologies,...
Several antiblastic drugs (ADs) are classified as carcinogenic, mutagenic, and/or toxic for reproduction. Despite established guidelines and safe handling technologies, ADs contamination of the work environments could occur in healthcare settings, leading to potential exposure of healthcare staff. This systematic review aims to investigate the main techniques and practices for assessing ADs occupational exposure in healthcare settings. The reviewed studies unveil that workplace contamination by ADs appears to be a still-topical problem in healthcare settings. These issues are linked to difficulties in guaranteeing: (i) the adherence to standardized protocols when dealing with ADs, (ii) the effective use of personal protective equipment by operators involved in the administration or management of ADs, (iii) a comprehensive training of the healthcare personnel, and (iv) a thorough health surveillance of exposed workers. A "multi-parametric" approach emerges as a desirable strategy for exposure assessment. In parallel, exposure assessment should coincide with the introduction of novel technologies aimed at minimizing exposure (i.e., risk management). Assessment must consider various departments and health operators susceptible to ADs contamination, with a focus extended beyond worst-case scenarios, also considering activities like surface cleaning and logistical tasks related to ADs management. A comprehensive approach in ADs risk assessment enables the evaluation of distinct substance behaviors and subsequent exposure routes, affording a more holistic understanding of potential risks.
Topics: Humans; Occupational Exposure; Risk Assessment; Health Personnel; Drug Compounding; Personal Protective Equipment; Health Facilities
PubMed: 38686575
DOI: 10.23749/mdl.v115i2.15609 -
Biomedical Reports Jun 2024Lurasidone is an atypical anti-psychotic approved by the US Food and Drug Administration. It is mainly used to treat schizophrenia in adults through its antagonistic...
Efficacy and safety of lurasidone for schizophrenia: A systematic review and meta‑analysis of eight short‑term, randomized, double‑blind, placebo‑controlled clinical trials.
Lurasidone is an atypical anti-psychotic approved by the US Food and Drug Administration. It is mainly used to treat schizophrenia in adults through its antagonistic action on dopamine and 5-hydroxytryptamine receptors. The present study systematically assessed the efficacy and safety of lurasidone in the treatment of schizophrenia. Clinical, double-blind, parallel, randomized controlled trials (RCTs) of lurasidone in the treatment of schizophrenia were retrieved from PubMed\Medline, EBSCO, Embase, Cochrane Library, OVID, Web of Science and related clinical trial registration websites up to May 2023. A total of two investigators independently screened the included references and evaluated their quality. RevMan 5.3 software was used for meta-analysis of each measure outcome. The present systematic review was registered in PROSPERO (ID=CRD42018108178). A total of eight RCTs were included in the present study, including a total of 2,456 patients with schizophrenia. All eight references were randomized, double-blind and parallel control trials. All eight references were evaluated as high quality. The meta-analysis results demonstrated that there were no significant change in total Positive and Negative Syndrome Scale (PANSS) score, Clinical Global Impression of Severity (CGI-S) score and Montgomery-Asberg Depression Rating Scale (MADRS) between the 40 mg lurasidone group and the placebo group (P>0.05). However, as the dosage increased, the 80, 120 and 160 mg lurasidone groups had significant changes in total PANSS score, CGI-S score and MADRS Compared with placebo (P<0.05), although changes in MADRS in the 120 mg lurasidone group were not statistically significant (P>0.05). In terms of safety, the changes in the incidence of agitation in the 40 mg lurasidone group (P<0.05), vomiting in the 80 mg group (P<0.05) and akathisia in the 160 mg group (P<0.05) were statistically significant and there were also statistically significant changes in the incidence of akathisia, nausea, somnolence and extrapyramidal disorder among the 40, 80 and 120 mg lurasidone groups (P<0.05); No statistically significant changes in the in the incidence of other adverse reactions (P>0.05). In conclusion, existing evidence suggests that the initial dose of lurasidone for schizophrenia can be adjusted to 80 mg. As the condition aggravates, the dose can be incrementally increased to 160 mg. A dose of 160 mg lurasidone is recommended as the most efficacious and safe dose for acute schizophrenia and the risk of occurrence of akathisia, nausea, somnolence and extrapyramidal disorder is still high when lurasidone is administered at a dose of 80-120 mg. The dose should be promptly adjusted or the drug should be withdrawn if the aforementioned adverse reactions worsen. Multi-center, high-quality and long-term clinical RCTs influenced by the included references are still necessary to support the aforementioned conclusions.
PubMed: 38682090
DOI: 10.3892/br.2024.1779 -
Trials Apr 2024The fragility index is a statistical measure of the robustness or "stability" of a statistically significant result. It has been adapted to assess the robustness of...
Assessing fragility of statistically significant findings from randomized controlled trials assessing pharmacological therapies for opioid use disorders: a systematic review.
BACKGROUND
The fragility index is a statistical measure of the robustness or "stability" of a statistically significant result. It has been adapted to assess the robustness of statistically significant outcomes from randomized controlled trials. By hypothetically switching some non-responders to responders, for instance, this metric measures how many individuals would need to have responded for a statistically significant finding to become non-statistically significant. The purpose of this study is to assess the fragility index of randomized controlled trials evaluating opioid substitution and antagonist therapies for opioid use disorder. This will provide an indication as to the robustness of trials in the field and the confidence that should be placed in the trials' outcomes, potentially identifying ways to improve clinical research in the field. This is especially important as opioid use disorder has become a global epidemic, and the incidence of opioid related fatalities have climbed 500% in the past two decades.
METHODS
Six databases were searched from inception to September 25, 2021, for randomized controlled trials evaluating opioid substitution and antagonist therapies for opioid use disorder, and meeting the necessary requirements for fragility index calculation. Specifically, we included all parallel arm or two-by-two factorial design RCTs that assessed the effectiveness of any opioid substitution and antagonist therapies using a binary primary outcome and reported a statistically significant result. The fragility index of each study was calculated using methods described by Walsh and colleagues. The risk of bias of included studies was assessed using the Revised Cochrane Risk of Bias tool for randomized trials.
RESULTS
Ten studies with a median sample size of 82.5 (interquartile range (IQR) 58, 179, range 52-226) were eligible for inclusion. Overall risk of bias was deemed to be low in seven studies, have some concerns in two studies, and be high in one study. The median fragility index was 7.5 (IQR 4, 12, range 1-26).
CONCLUSIONS
Our results suggest that approximately eight participants are needed to overturn the conclusions of the majority of trials in opioid use disorder. Future work should focus on maximizing transparency in reporting of study results, by reporting confidence intervals, fragility indexes, and emphasizing the clinical relevance of findings.
TRIAL REGISTRATION
PROSPERO CRD42013006507. Registered on November 25, 2013.
Topics: Humans; Analgesics, Opioid; Data Interpretation, Statistical; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Research Design; Treatment Outcome
PubMed: 38678289
DOI: 10.1186/s13063-024-08104-x -
Archives of Dermatological Research Apr 2024Patient education in atopic dermatitis (AD) has worked in parallel to the gold standard of pharmacological treatment as a foundational component of therapeutic regimens.... (Meta-Analysis)
Meta-Analysis Review
Patient education in atopic dermatitis (AD) has worked in parallel to the gold standard of pharmacological treatment as a foundational component of therapeutic regimens. In addition to improving patient education, past investigations of educational interventions have demonstrated profound reductions in disease severity for patients living with AD. However, prior meta-analytical work has focused mostly on comparing in-person interventions, and thus the need to determine the effectiveness of virtual methodologies in the current post-COVID era remains. In this study, we conducted a systematic review of the literature to determine the effectiveness of online programming in AD education compared to in-person interventions. A comprehensive search was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions 2019. Studies were retrieved based on articles published up to 04 April 2023. Adherence to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Statement guided the reportage process for this systematic review and meta-analysis. The primary outcome of our meta-analysis was the effect of various educational modalities on atopic dermatitis severity as measured by multiple scales across the studies, the most common including SCORAD, Dermatology Life Quality Index (DLQI), Patient Oriented Eczema Measure (POEM), and Eczema Area and Severity Index (EASI). Most studies were randomized controlled trials, primarily from North America and Western Europe and focused on patient and/or caregiver education about disease management, self-care techniques, avoidance of triggers, and comprehensive understanding of the disease process. Our pooled analyses showed that targeted educational programs in understudied adult populations can be as impactful as those in pediatric groups. Moreover, virtual interventions can be employed as constructive tools for reducing barriers of access to patient education. Future research on educational interventions should utilize various methodologies to encourage individual learning preferences with a focus on adult cohorts.
Topics: Dermatitis, Atopic; Humans; Patient Education as Topic; Quality of Life; Severity of Illness Index; COVID-19
PubMed: 38662127
DOI: 10.1007/s00403-024-02871-y