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BMC Endocrine Disorders Jun 2024Activating mutation in Ubiquitin-specific peptidase (USP8) is identified to enhance cell proliferation and adrenocorticotropic hormone (ACTH) secretion from corticotroph...
OBJECTIVE
Activating mutation in Ubiquitin-specific peptidase (USP8) is identified to enhance cell proliferation and adrenocorticotropic hormone (ACTH) secretion from corticotroph pituitary adenoma. We investigated the USP8 variant status in a population of Iranian people with functional corticotroph pituitary adenoma (FCPA). Moreover, a systematic review was conducted to thoroughly explore the role of USP8 variants and the related pathways in corticotroph adenomas, genotype-phenotype correlation in USP8-mutated individuals with FCPA, and the potential role of USP8 and epidermal growth factor receptor (EGFR) as targeted therapies in PFCAs.
METHODS
Genetic analysis of 20 tissue samples from 19 patients with PFCAs was performed using Sanger sequencing. Moreover, a systematic literature review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Scopus, web of Sciences, and Cochrane databases were searched. The last search was performed on 20 September 2023 for all databases.
RESULTS
In our series, we found two somatic mutations including a 7-bp deletion variant: c.2151_2157delCTCCTCC, p. Ser718GlnfsTer3, and a missense variant: c.2159 C > G, p. Pro720Arg (rs672601311) in exon 14. The Systematic review indicated USP8 variant in 35% of corticotroph adenomas, with the highest frequency (25%) in 720 code regions, p. Pro720Arg. Data regarding the impact of USP8 mutational status on clinical characteristics and outcomes in FCPAs are inconsistent. Moreover, Pasireotide as well as inhibitors of EGFR such as Gefitinib and Lapatinib, as well as USP8 inhibitors including -ehtyloxyimino9H-indeno (1, 2-b) pyrazine-2, 3-dicarbonitrile, DUBs-IN-2, and RA-9 indicated promising results in treatment of corticotroph adenomas.
CONCLUSION
Although the USP8-EGFR system has been identified as the main trigger and target of corticotroph tumorigenesis, more precise multicenter studies are required to yield more consistent information regarding the phenotype-genotype correlation and to develop effective targeted therapies.
Topics: Humans; Ubiquitin Thiolesterase; Iran; Endosomal Sorting Complexes Required for Transport; Pituitary ACTH Hypersecretion; Adult; Female; Male; Endopeptidases; Mutation; Middle Aged; ACTH-Secreting Pituitary Adenoma; Middle Eastern People
PubMed: 38862897
DOI: 10.1186/s12902-024-01619-z -
PloS One 2024Young people leaving state care often experience hardship in many areas of their life. At a population level, their outcomes in early adulthood are poorer compared to...
Understanding how young people transitioning from out-of-home care acquire and develop independent living skills and knowledge: A systematic review of longitudinal studies.
Young people leaving state care often experience hardship in many areas of their life. At a population level, their outcomes in early adulthood are poorer compared to general populations. Effective preparation for leaving care and post-care support systems is vital to improving outcomes. Individual and systemic support for young people to acquire Independent Living Skills (ILS) in the following eight ILS domains have been identified: Financial Management, Knowledge of Accessing Available Supports, Managing Housing, Education Planning, Job Seeking, Health Risk Management, Domestic and Self-help Task, and Managing Relationships. This systematic review aims to identify, summarise, and appraise longitudinal studies that address ILS across these ILS domains to understand better how outcomes could be improved. Seven databases (CINAHL, Embase, ProQuest, PsychINFO, PubMed, Scopus, and Web of Science) were searched on 20th July 2023. In total, twenty-seven studies published between 1994 and 2022 from various countries met the eligibility criteria. The included studies reported on 2-4 waves and adopted different methodological approaches. Study quality was scored using Qualsyst. Study characteristics and details of the interventions are presented in tables. Studies cover overlapping ILS domains, which are mapped in a matrix. Results revealed that nearly three-quarters (74% or 20 out of 27) of studies explored four or fewer of the eight ILS domains. The most frequent ILS domain covered was 'Knowledge of Accessing Available Supports' (19/27 studies). The main conclusion considers the concept of independence as a misnomer, with ILS covering multiple, intersecting, and interdependent domains, which ultimately help and hinder one another. Further research is required to adopt a more comprehensive approach encompassing all the domains to better inform policy, programs, and practice. A limitation is that a meta-analysis was not conducted for this review. This study registered a 'Protocol' with OSF Registries (DOI: 10.17605/OSF.IO/MJ3ZX) on June 5th, 2022.
Topics: Humans; Longitudinal Studies; Independent Living; Adolescent; Young Adult
PubMed: 38861497
DOI: 10.1371/journal.pone.0304965 -
Cureus May 2024Anthracyclines are effective chemotherapeutic agents widely used to treat various cancers, but their use is limited by the risk of cardiotoxicity and heart failure.... (Review)
Review
Efficacy of Sodium-Glucose Cotransporter 2 Inhibitors in Preventing Heart Failure in Patients Receiving Anthracycline-Based Cancer Therapy: A Systematic Review and Meta-Analysis.
Anthracyclines are effective chemotherapeutic agents widely used to treat various cancers, but their use is limited by the risk of cardiotoxicity and heart failure. While strategies like dose reduction have been explored, there are no well-established therapies to mitigate this risk. Emerging evidence suggests sodium-glucose cotransporter 2 inhibitors (SGLT2i) may have cardioprotective effects, providing a rationale for investigating their potential utility in anthracycline-treated patients. We conducted a systematic review and meta-analysis to synthesize available evidence on the efficacy of SGLT2i in reducing heart failure incidence and mortality in patients undergoing anthracycline-based cancer therapy. Relevant studies were identified through comprehensive database searches and screened based on predefined criteria. Data extraction and quality assessment were performed independently by two reviewers. Four observational studies, encompassing 5,590 patients, were included. The pooled analysis showed a higher but non-significant risk of developing heart failure in the non-SGLT2i group compared to the SGLT2i group (RR = 0.67, 95% CI: 0.40-1.41). The risk of all-cause mortality was significantly lower in patients receiving SGLT2i (RR = 0.55, 95% CI: 0.39-0.77). This meta-analysis suggests SGLT2i are associated with a lower risk of mortality and heart failure incidence in anthracycline-treated patients, although larger studies are needed to confirm these findings. The mechanisms underlying these potential benefits require further elucidation. Despite limitations, this analysis highlights the promising role of SGLT2i as a cardioprotective strategy in this high-risk population.
PubMed: 38860078
DOI: 10.7759/cureus.60086 -
PLoS Neglected Tropical Diseases Jun 2024Despite its well-regarded vector control program, Singapore remains susceptible to dengue epidemics. To assist evaluation of dengue interventions, we aimed to synthesize...
BACKGROUND
Despite its well-regarded vector control program, Singapore remains susceptible to dengue epidemics. To assist evaluation of dengue interventions, we aimed to synthesize current data on the epidemiologic and economic burden of dengue in Singapore.
METHODOLOGY
We used multiple databases (PubMed, Embase, Cochrane, international/national repositories, surveillance) to search for published and gray literature (2000-2022). We included observational and cost studies, and two interventional studies, reporting Singapore-specific data on our co-primary outcomes, dengue incidence and dengue-related costs. Quality was assessed using the Newcastle-Ottawa Scale and an adapted cost-of-illness evaluation checklist. We performed a narrative synthesis and grouped studies according to reported outcomes and available stratified analyses.
FINDINGS
In total, 333 reports (330 epidemiological, 3 economic) were included. Most published epidemiological studies (89%) and all economic studies were of good quality. All gray literature reports were from the Ministry of Health or National Environment Agency. Based predominantly on surveillance data, Singapore experienced multiple outbreaks in 2000-2021, attaining peak incidence rate in 2020 (621.1 cases/100,000 person-years). Stratified analyses revealed the highest incidence rates in DENV-2 and DENV-3 serotypes and the 15-44 age group. Among dengue cases, the risk of hospitalization has been highest in the ≥45-year-old age groups while the risks of dengue hemorrhagic fever and death have generally been low (both <1%) for the last decade. Our search yielded limited data on deaths by age, severity, and infection type (primary, secondary, post-secondary). Seroprevalence (dengue immunoglobulin G) increases with age but has remained <50% in the general population. Comprising 21-63% indirect costs, dengue-related total costs were higher in 2010-2020 (SGD 148 million) versus the preceding decade (SGD 58-110 million).
CONCLUSION
Despite abundant passive surveillance data, more stratified and up-to-date data on the epidemiologic and economic burden of dengue are warranted in Singapore to continuously assess prevention and management strategies.
Topics: Singapore; Humans; Dengue; Cost of Illness; Incidence; Dengue Virus; Hospitalization; Adult
PubMed: 38857260
DOI: 10.1371/journal.pntd.0012240 -
The Journal of Allergy and Clinical... Jun 2024The benefits and harms of adding antileukotrienes to H1-antihistamines for the management of urticaria (hives, itch, and/or angioedema) remain unclear.
BACKGROUND
The benefits and harms of adding antileukotrienes to H1-antihistamines for the management of urticaria (hives, itch, and/or angioedema) remain unclear.
OBJECTIVE
We sought to systematically synthesize the treatment outcomes of antileukotrienes in combination with H1-antihistamines versus H1-antihistamines alone for acute and chronic urticaria.
METHODS
As part of updating American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters urticaria guidelines, we searched MEDLINE, Embase, CENTRAL, LILACS, WPRIM, IBECS, ICTRP, CBM, CNKI, VIP, Wanfang, FDA, and EMA databases from inception to December 18, 2023 for randomized controlled trials (RCTs) evaluating antileukotrienes and H1-antihistamines versus H1-antihistamines alone in patients with urticaria. Paired reviewers independently screened citations, extracted data, and assessed risk of bias. Random effects models pooled effect estimates for urticaria activity, itch, wheal, sleep, quality of life, and harms. The GRADE approach informed certainty of evidence ratings. Open Science Framework registration: https://osf.io/h2bfx/.
RESULTS
Thirty-four RCTs enrolled 3,324 children and adults. Compared to H1-antihistamines alone, the combination of a leukotriene receptor antagonist (LTRA) with H1-antihistamines probably modestly reduces urticaria activity (mean difference: -5.04, 95%CI -6.36 to -3.71; 7-day Urticaria Activity Score) with moderate certainty. We made similar findings for itch and wheal severity, and quality of life. Adverse events were probably not different between groups (moderate certainty), however, no RCT reported on neuropsychiatric adverse events.
CONCLUSION
Among patients with urticaria, adding LTRAs to H1-antihistamines probably modestly improves urticaria activity with little to no increase in overall adverse events. The added risk of neuropsychiatric adverse events in this population with LTRAs is small and uncertain.
PubMed: 38852861
DOI: 10.1016/j.jaci.2024.05.026 -
International Journal of Health... Jun 2024Geographical environments influence people's active mobility behaviors, contributing to their physical and mental health. The use of Virtual Reality (VR) in experimental... (Review)
Review
BACKGROUND
Geographical environments influence people's active mobility behaviors, contributing to their physical and mental health. The use of Virtual Reality (VR) in experimental research can unveil new insights into the relationship between exposure to geographic environments and active mobility behaviors. This systematic review aims to (1) identify environmental attributes investigated in relation with walking and cycling, using VR, (2) assess their impacts on active mobility behaviors and attitudes, and (3) identify research gaps, strengths and limitations in VR-based experimental research.
METHODS
Articles published between January 2010 and February 2022 within five databases (PubMed, Scopus, EBSCO, IEEE Xplore, and Cochrane Library) were explored using three keywords and their synonyms: Virtual Reality, Active mobility behavior, and Geographical environments. Studies focusing on indoor environments, driving simulation, disease-specific groups, non-relevant disciplines (e.g. military, emergency evacuation), VR methodology/software optimization, and those with static participants' involvement were excluded. The full protocol is available from PROSPERO (ID = CRD42022308366).
RESULTS
Out of 3255 articles, 18 peer-reviewed papers met the selection criteria, mostly focusing on walking (83%). Most studies used head-mounted displays (94%) and relied on convenience sampling (72% below 100 participants). Both static (33%) and dynamic (45%) environmental attributes have been investigated, with only 22% of them simultaneously in the same virtual environment. Greenness and crowd density were the most frequent attributes, rather consistently associated with emotional states and movement behaviors. Few studies have taken into account participant's previous VR experience (33%) and cybersickness (39%) while both are likely to affect an individual's perception and behavior.
CONCLUSIONS
Future research should explore a broader range of environmental attributes, including static and dynamic ones, as well as a more complex integration of these attributes within a single experiment to mimic the effect of realistic environments on people's active mobility behaviors and attitudes. Larger and more diverse population samples are deemed required to improve result generalizability. Despite methodological challenges, VR emerges as a promising tool to disentangle the effect of complex environments on active mobility behaviors.
Topics: Humans; Virtual Reality; Walking; Bicycling
PubMed: 38851727
DOI: 10.1186/s12942-024-00375-6 -
Gastrointestinal Endoscopy Jun 2024Serrated polyps (SPs) are precursors to 15-20% of colorectal cancers (CRCs). However, there are uncertainties regarding which SPs require surveillance and at what... (Review)
Review
BACKGROUND AND AIMS
Serrated polyps (SPs) are precursors to 15-20% of colorectal cancers (CRCs). However, there are uncertainties regarding which SPs require surveillance and at what intervals, with recommendations adapted from those for adenomas in the absence of solid evidence. Our aim was to assess which SP risk characteristics relate to a higher risk of metachronous CRC or advanced polyps.
METHODS
We systematically searched PubMed, EMBASE, and Cochrane for cohort, case-control studies, and clinical trials from inception to Dec 31, 2023, for CRC or advanced polyps [advanced adenoma (AA) or advanced SP] incidence at surveillance stratified by baseline SP size, dysplasia, location, and multiplicity. We defined advanced SPs as those >10mm or with dysplasia. CRC and advanced polyp incidence per 1,000 person-years (p-y) were estimated. We performed a meta-analysis by calculating pooled relative risks (RR) using a random-effects model.
RESULTS
5,903 studies were reviewed and 14 included, with 493,949 patients (mean age 59·5 years, 55% men). Mean follow-up was 4·9 years. CRC incidence per 1,000 p-y was 2·09 (95%CI 1·29-2·90) for advanced SP, 1·52 (0·78-2·25) for SP>10mm, 5·86 (2·16-9·56) for SP with dysplasia, 1·18 (0·77-1·60) for proximal SP, 0·52 (0·08-1·12) for >3SP, 0·50 (0·35-0·66) for non-advanced SP, and 0·44 (0·41-0·46) for normal colonoscopy. Metachronous CRC risk was higher in advanced SP vs non-advanced SP (RR 1·84, 95%CI 1·11-3·04), and vs normal colonoscopy (RR 2·92, 2·26-3·77); in SP>10mm vs <10mm (RR 2·61, 1·43-4·77), and vs normal colonoscopy (RR 3·52, 2·17-5·69); and in SP with dysplasia vs normal colonoscopy (RR 2·71, 2·00-3·67). No increase in CRC or advanced polyp risk was found in patients with proximal vs distal SP, nor in >3SP vs 1-2SP.
CONCLUSIONS
CRC risk is significantly higher in patients with baseline advanced SP after 4·9 years of follow-up, with risk magnitudes similar to those described for AA, supporting the current recommendation for 3-year surveillance in patients with advanced SP.
PubMed: 38851458
DOI: 10.1016/j.gie.2024.05.021 -
BMC Health Services Research Jun 2024Community health workers (CHWs) had important roles mitigating the impact of the COVID-19 pandemic in vulnerable communities. We described how CHWs supported the...
BACKGROUND
Community health workers (CHWs) had important roles mitigating the impact of the COVID-19 pandemic in vulnerable communities. We described how CHWs supported the dissemination of COVID-19 information and services during the early pandemic response.
METHODS
Online article searches were conducted across five scientific databases, with review article reference lists hand searched to identify grey/unpublished literature. Articles were included if they reported on a program that engaged CHWs and aimed to prevent/control COVID-19.
RESULTS
Nineteen relevant programs were identified from 18 included articles. CHWs were widely engaged in the pandemic response, especially in low- and middle-income countries and in vulnerable communities. CHWs' ability to effectively disseminate COVID-19 information/services was enabled by community trust and understanding community needs. CHWs were often underfunded and required to work in difficult conditions. Pre-existing services incorporating CHWs rapidly adapted to the new challenges brought by the pandemic.
CONCLUSIONS
We recommend establishing programs that employ CHWs to disseminate health information and services in communities at-risk of misinformation and poor health outcomes during non-pandemic times. CHWs are well-placed to deliver interventions should an infectious disease outbreak arise. Having pre-existing trusted relationships between CHWs and community members may help protect vulnerable groups, including when outbreaks occur.
Topics: Humans; COVID-19; Community Health Workers; Information Dissemination; Pandemics; SARS-CoV-2
PubMed: 38849842
DOI: 10.1186/s12913-024-11165-y -
The Lancet. Planetary Health Jun 2024Different approaches have been used for translation of the EAT-Lancet reference diet into dietary scores that can be used to assess health and environmental impact. Our... (Review)
Review
Different approaches have been used for translation of the EAT-Lancet reference diet into dietary scores that can be used to assess health and environmental impact. Our aim was to compare the different EAT-Lancet diet scores, and to estimate their associations with all-cause mortality, stroke incidence, and greenhouse gas emissions. We did a systematic review (PROSPERO, CRD42021286597) to identify different scores representing adherence to the EAT-Lancet reference diet. We then qualitatively compared the diet adherence scores, including their ability to group individuals according the EAT-Lancet reference diet recommendations, and quantitatively assessed the associations of the diet scores with health and environmental outcome data in three diverse cohorts: the Danish Diet, Cancer and Health Cohort (DCH; n=52 452), the Swedish Malmö Diet and Cancer Cohort (MDC; n=20 973), and the Mexican Teachers' Cohort (MTC; n=30 151). The DCH and MTC used food frequency questionnaires and the MDC used a modified diet history method to assess dietary intake, which we used to compute EAT-Lancet diet scores and evaluate the associations of scores with hazard of all-cause mortality and stroke. In the MDC, dietary greenhouse gas emission values were summarised for every participant, which we used to predict greenhouse gas emissions associated with varying diet adherence scores on each scoring system. In our review, seven diet scores were identified (Knuppel et al, 2019; Trijsburg et al, 2020; Cacau et al, 2021; Hanley-Cook et al, 2021; Kesse-Guyot et al, 2021; Stubbendorff et al, 2022; and Colizzi et al, 2023). Two of the seven scores (Stubbendorff and Colizzi) were among the most consistent in grouping participants according to the EAT-Lancet reference diet recommendations across cohorts, and higher scores (greater diet adherence) were associated with decreased risk of mortality (in the DCH and MDC), decreased risk of incident stroke (in the DCH and MDC for the Stubbendorff score; and in the DCH for the Colizzi score), and decreased predicted greenhouse gas emissions in the MDC. We conclude that the seven different scores representing the EAT-Lancet reference diet had differences in construction, interpretation, and relation to disease and climate-related outcomes. Two scores generally performed well in our evaluation. Future studies should carefully consider which diet score to use and preferably use multiple scores to assess the robustness of estimations, given that public health and environmental policy rely on these estimates.
Topics: Humans; Greenhouse Gases; Stroke; Diet; Cohort Studies; Denmark; Sweden; Male; Mexico; Female; Mortality; Middle Aged
PubMed: 38849181
DOI: 10.1016/S2542-5196(24)00094-9 -
JAMA Health Forum Jun 2024The five 1997 Office of Management and Budget races in the US include American Indian or Alaska Native, Asian, Black or African American, Native Hawaiian or Other...
IMPORTANCE
The five 1997 Office of Management and Budget races in the US include American Indian or Alaska Native, Asian, Black or African American, Native Hawaiian or Other Pacific Islander, and White, with Hispanic ethnicity. Despite the Affordable Care Act mandating Office of Management and Budget-based collecting and reporting standards, race and ethnicity publishing in medical journals is inconsistent, despite being necessary to achieve health equity.
OBJECTIVE
To quantify race and ethnicity reporting rates and calculate representation quotients (RQs) in published oncology clinical trials.
EVIDENCE REVIEW
In this systematic review, PubMed and Embase were queried for phase 2/3 clinical trials of the 6 most common noncutaneous solid cancers, published between January 1, 2012, and December 31, 2022, in 4 high-impact journals. Trial characteristics were recorded. The RQs for each race and ethnicity were calculated by dividing the percent of representation in each clinical trial publication by the percent of year-matched, site-specific incident cancers in the US, compared with Kruskal-Wallis tests with Bonferroni correction (BC). Reporting was compared between journal publications and ClinicalTrials.gov.
FINDINGS
Among 1202 publications evaluated, 364 met inclusion criteria: 16 JAMA, 241 Journal of Clinical Oncology, 19 Lancet, and 88 New England Journal of Medicine. Publications included 268 209 patients (171 132 women [64%]), with a median of 356 (IQR, 131-800) patients per publication. Reported race and ethnicity included American Indian or Alaska Native in 52 (14%) publications, Asian in 196 (54%), Black or African American in 215 (59%), Hispanic in 67 (18%), Native Hawaiian or Other Pacific Islander in 28 (8%), and White in 254 (70%). Median RQ varied across race (P < .001 BC), with 1.04 (IQR, 0.09-4.77) for Asian, 0.98 (IQR, 0.86-1.06) for White, 0.42 (IQR, 0.12-0.75) for Black or African American, and 0.00 (IQR, 0.00-0.00) for both American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander patients. Sensitivity analyses showed similar findings on subset analysis for US-only clinical trials. There was significantly less race and ethnicity reporting in the clinical trial publications compared with ClinicalTrials.gov documentation for American Indian or Alaska Native (14% vs 45%; P < .001 per McNemar χ2 test with continuity correction [MC]) and Native Hawaiian or Other Pacific Islander (8% vs 43%; P < .001 MC).
CONCLUSIONS AND RELEVANCE
While most phase 2/3 oncology clinical trials published in high-impact journals report race and ethnicity, most did not report American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander racial categories. Our findings support a call to action for consistent journal policies and transparent race and ethnicity reporting, in alignment with Affordable Care Act-concordant race and ethnicity federal reporting requirements.
Topics: Humans; Racial Groups; Clinical Trials, Phase III as Topic; Clinical Trials, Phase II as Topic; United States; Neoplasms; Ethnicity
PubMed: 38848090
DOI: 10.1001/jamahealthforum.2024.1388