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Journal of Medical Internet Research Jun 2024Asia consists of diverse nations with extremely variable health care systems. Integrated real-world data (RWD) research warehouses provide vast interconnected data sets... (Review)
Review
BACKGROUND
Asia consists of diverse nations with extremely variable health care systems. Integrated real-world data (RWD) research warehouses provide vast interconnected data sets that uphold statistical rigor. Yet, their intricate details remain underexplored, restricting their broader applications.
OBJECTIVE
Building on our previous research that analyzed integrated RWD warehouses in India, Thailand, and Taiwan, this study extends the research to 7 distinct health care systems: Hong Kong, Indonesia, Malaysia, Pakistan, the Philippines, Singapore, and Vietnam. We aimed to map the evolving landscape of RWD, preferences for methodologies, and database use and archetype the health systems based on existing intrinsic capability for RWD generation.
METHODS
A systematic scoping review methodology was used, centering on contemporary English literature on PubMed (search date: May 9, 2023). Rigorous screening as defined by eligibility criteria identified RWD studies from multiple health care facilities in at least 1 of the 7 target Asian nations. Point estimates and their associated errors were determined for the data collected from eligible studies.
RESULTS
Of the 1483 real-world evidence citations identified on May 9, 2023, a total of 369 (24.9%) fulfilled the requirements for data extraction and subsequent analysis. Singapore, Hong Kong, and Malaysia contributed to ≥100 publications, with each country marked by a higher proportion of single-country studies at 51% (80/157), 66.2% (86/130), and 50% (50/100), respectively, and were classified as solo scholars. Indonesia, Pakistan, Vietnam, and the Philippines had fewer publications and a higher proportion of cross-country collaboration studies (CCCSs) at 79% (26/33), 58% (18/31), 74% (20/27), and 86% (19/22), respectively, and were classified as global collaborators. Collaboration with countries outside the 7 target nations appeared in 84.2% to 97.7% of the CCCSs of each nation. Among target nations, Singapore and Malaysia emerged as preferred research partners for other nations. From 2018 to 2023, most nations showed an increasing trend in study numbers, with Vietnam (24.5%) and Pakistan (21.2%) leading the growth; the only exception was the Philippines, which declined by -14.5%. Clinical registry databases were predominant across all CCCSs from every target nation. For single-country studies, Indonesia, Malaysia, and the Philippines favored clinical registries; Singapore had a balanced use of clinical registries and electronic medical or health records, whereas Hong Kong, Pakistan, and Vietnam leaned toward electronic medical or health records. Overall, 89.9% (310/345) of the studies took >2 years from completion to publication.
CONCLUSIONS
The observed variations in contemporary RWD publications across the 7 nations in Asia exemplify distinct research landscapes across nations that are partially explained by their diverse economic, clinical, and research settings. Nevertheless, recognizing these variations is pivotal for fostering tailored, synergistic strategies that amplify RWD's potential in guiding future health care research and policy decisions.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
RR2-10.2196/43741.
Topics: Humans; Delivery of Health Care; Asia; Vietnam; Philippines; Indonesia; Malaysia; Pakistan; Singapore; Databases, Factual
PubMed: 38749399
DOI: 10.2196/56686 -
European Stroke Journal May 2024There is a longstanding clinical uncertainty regarding the optimal timing of initiating oral anticoagulants (OAC) for non-valvular atrial fibrillation following acute...
INTRODUCTION
There is a longstanding clinical uncertainty regarding the optimal timing of initiating oral anticoagulants (OAC) for non-valvular atrial fibrillation following acute ischemic stroke. Current international recommendations are based on expert opinions, while significant diversity among clinicians is noted in everyday practice.
METHODS
We conducted an updated systematic review and meta-analysis including all available randomized-controlled clinical trials (RCTs) and observational cohort studies that investigated early versus later OAC-initiation for atrial fibrillation after acute ischemic stroke. The primary outcome was defined as the composite of ischemic and hemorrhagic events and mortality at follow-up. Secondary outcomes included the components of the composite outcome (ischemic stroke recurrence, intracranial hemorrhage, major bleeding, and all-cause mortality). Pooled estimates were calculated with random-effects model.
RESULTS
Nine studies (two RCTs and seven observational) were included comprising a total of 4946 patients with early OAC-initiation versus 4573 patients with later OAC-initiation following acute ischemic stroke. Early OAC-initiation was associated with reduced risk of the composite outcome (RR = 0.74; 95% CI:0.56-0.98; = 46%) and ischemic stroke recurrence (RR = 0.64; 95% CI:0.43-0.95; = 60%) compared to late OAC-initiation. Regarding safety outcomes, similar rates of intracranial hemorrhage (RR = 0.98; 95% CI:0.57-1.69; = 21%), major bleeding (RR = 0.78; 95% CI:0.40-1.51; = 0%), and mortality (RR = 0.94; 95% CI:0.61-1.45; = 0%) were observed. There were no subgroup differences, when RCTs and observational studies were separately evaluated.
CONCLUSIONS
Early OAC-initiation in acute ischemic stroke patients with non-valvular atrial fibrillation appears to have better efficacy and a similar safety profile compared to later OAC-initiation.
PubMed: 38742375
DOI: 10.1177/23969873241251931 -
Frontiers in Oncology 2024Early-onset colorectal cancer (CRC), defined as diagnosis before age 50, has increased in recent decades. Although more often diagnosed at advanced stage, associations...
BACKGROUND
Early-onset colorectal cancer (CRC), defined as diagnosis before age 50, has increased in recent decades. Although more often diagnosed at advanced stage, associations with other histological and molecular markers that impact prognosis and treatment remain to be clarified. We conducted a systematic review and meta-analysis concerning the prevalence of prognostic and predictive tumor markers for early- vs. late-onset CRC, including oncogene mutations, microsatellite instability (MSI), and emerging markers including immune cells and the consensus molecular subtypes.
METHODS
We systematically searched PubMed for original research articles published between April 2013-January 2024. Included studies compared the prevalence of tumor markers in early- vs. late-onset CRC. A meta-analysis was completed and summary odds ratios (ORs) with 95% confidence intervals (CIs) were obtained from a random effects model via inverse variance weighting. A sensitivity analysis was completed to restrict the meta-analysis to studies that excluded individuals with Lynch syndrome, a hereditary condition that influences the distribution of tumor markers for early-onset CRC.
RESULTS
In total, 149 articles were identified. Tumors from early-onset CRC are less likely to include mutations in (OR, 95% CI: 0.91, 0.85-0.98), (0.63, 0.51-0.78), (0.70, 0.58-0.84), and (0.88, 0.78-1.00) but more likely to include mutations in (1.68, 1.04-2.73) and (1.34, 1.24-1.45). After limiting to studies that excluded Lynch syndrome, the associations between early-onset CRC and (0.77, 0.64-0.92) and mutation (0.81, 0.67-0.97) were attenuated, while an inverse association with mutation was also observed (0.88, 0.78-0.99). Early-onset tumors are less likely to develop along the CpG Island Methylator Phenotype pathway (0.24, 0.10-0.57), but more likely to possess adverse histological features including high tumor grade (1.20, 1.15-1.25), and mucinous (1.22, 1.16-1.27) or signet ring histology (2.32, 2.08-2.57). A positive association with MSI status (1.31, 1.11-1.56) was also identified. Associations with immune markers and the consensus molecular subtypes are inconsistent.
DISCUSSION
A lower prevalence of mutations in and is consistent with extended survival and superior response to targeted therapies for metastatic disease. Conversely, early-onset CRC is associated with aggressive histological subtypes and and mutations, which may serve as therapeutic targets.
PubMed: 38737895
DOI: 10.3389/fonc.2024.1349572 -
Brain : a Journal of Neurology Jun 2024Biallelic pathogenic variants in the PNPLA6 gene cause a broad spectrum of disorders leading to gait disturbance, visual impairment, anterior hypopituitarism and hair...
Biallelic pathogenic variants in the PNPLA6 gene cause a broad spectrum of disorders leading to gait disturbance, visual impairment, anterior hypopituitarism and hair anomalies. PNPLA6 encodes neuropathy target esterase (NTE), yet the role of NTE dysfunction on affected tissues in the large spectrum of associated disease remains unclear. We present a systematic evidence-based review of a novel cohort of 23 new patients along with 95 reported individuals with PNPLA6 variants that implicate missense variants as a driver of disease pathogenesis. Measuring esterase activity of 46 disease-associated and 20 common variants observed across PNPLA6-associated clinical diagnoses unambiguously reclassified 36 variants as pathogenic and 10 variants as likely pathogenic, establishing a robust functional assay for classifying PNPLA6 variants of unknown significance. Estimating the overall NTE activity of affected individuals revealed a striking inverse relationship between NTE activity and the presence of retinopathy and endocrinopathy. This phenomenon was recaptured in vivo in an allelic mouse series, where a similar NTE threshold for retinopathy exists. Thus, PNPLA6 disorders, previously considered allelic, are a continuous spectrum of pleiotropic phenotypes defined by an NTE genotype:activity:phenotype relationship. This relationship, and the generation of a preclinical animal model, pave the way for therapeutic trials, using NTE as a biomarker.
Topics: Animals; Female; Humans; Male; Mice; Acyltransferases; Carboxylic Ester Hydrolases; Mutation, Missense; Phenotype; Phospholipases; Retinal Diseases
PubMed: 38735647
DOI: 10.1093/brain/awae055 -
Complementary Therapies in Medicine Jun 2024Chronic Obstructive Pulmonary Disease (COPD) is a globally common chronic respiratory disease with a high morbidity and mortality rate. Acupuncture has been proven... (Meta-Analysis)
Meta-Analysis
Exploration of quantitative-effectiveness association between acupuncture temporal parameters and stable chronic obstructive pulmonary disease: A systematic review and dose-response meta-analysis of randomized controlled trials.
INTRODUCTION
Chronic Obstructive Pulmonary Disease (COPD) is a globally common chronic respiratory disease with a high morbidity and mortality rate. Acupuncture has been proven effective for COPD. A dose-response meta-analysis was conducted to assess the correlation between the acupuncture temporal parameters(session, frequency, and duration) and its effectiveness in patients with stable COPD.
METHODS
Acupuncture randomized controlled trials on COPD were searched in eight databases from their inception to June 2023. The "doses" were defined as the acupuncture session, frequency, and duration. The outcomes mainly included Forced Expiratory Volume in one-second rate (FEV1%) and Six-minute Walking Distance (6MWD). The assessment of bias risk and literature quality were conducted independently using the Cochrane risk of bias tool and the Standards for reporting interventions in clinical trials of acupuncture. The dose-response relationship was modeled using robust error element regression, and meta-analysis was operated by R 4.3.1 and Stata 15.0. The protocol was registered in PROSPERO with the registration number CRD42023401406.
RESULT
Out of 1669 records, 17 RCTs with 1165 participants were finally included in the meta-analysis. There was notable heterogeneity among the studies, but sensitivity analysis demonstrated good robustness. The findings revealed a significant improvement in the following outcomes for stable COPD patients in the acupuncture group: FEV1% (MD=3.50, 95%CI: 2.05-4.95), 6MWD (MD=47.39, 95%CI: 29.29-65.50), St. George's respiratory questionnaire (SGRQ; MD=-8.25, 95%CI: -11.38 to -5.12); COPD assessment test (CAT; MD=-2.91, 95%CI: -3.99 to -1.83). The relationship between the acupuncture session, duration, and FEV1%, 6MWD followed a "Λ" curve pattern, while the relationship between acupuncture frequency and FEV1%, 6MWD exhibited logarithmic growth. Firstly, After 12 acupuncture sessions, FEV1% and 6MWD increased by 7.06% (95%CI: 4.56-9.55) and 36.28 m (95%CI: 20.37-52.20), respectively. The peak improvement in FEV1% and 6MWD was observed after 18 acupuncture sessions (MD=7.89, 95% CI: 5.33-10.45) and 45 sessions (MD=125.43, 95% CI: 72.80-178.07) each. Additionally, weekly acupuncture resulted in a 4.14% improvement in FEV1% (95% CI: 2.55-5.72) and a 42.49 m increase in 6MWD (95%CI: 17.16-67.81). Notably, the maximum effects on FEV1% and 6MWD improvement were achieved with different acupuncture frequencies, specifically three times a week (MD=6.00, 95% CI: 5.34-6.66) and once a day(MD=112.41, 95% CI: 77.27-147.56), respectively. Furthermore, after a 28-day duration of acupuncture treatment, FEV1% increased by 4.74% (95% CI: 3.73-5.75) and 6MWD increased by 47.34 m (95%CI: 22.01-72.67). During 60 days of acupuncture treatment, the FEV1% and 6MWD improvement reached their highest levels at 8.76% (95% CI: 7.05-10.47) and 88.06 m (95% CI: 45.96-130.16), respectively.
CONCLUSION
Acupuncture was effective in improving FEV1%, 6MWD, SGRQ, and CAT in patients with stable COPD. There was a dose-response relationship between the time parameters of acupuncture (session, frequency, and duration) and the efficacy of COPD treatment (FEV1% and 6MWD). The minimal clinically important difference could be achieved after 12 acupuncture sessions. Acupuncture with a medium-frequency (2-3 times per week) over 60 days may result in the greatest improvement in FEV1%, while higher-frequency acupuncture (5-7 times per week) for 2 months may lead to the maximum improvements in 6MWD. It indicated that the optimal acupuncture duration for different indicators remains consistent, while the optimal frequencies may differ. To confirm these results, it is necessary to conduct multicenter, large-scale randomized controlled trials.
ETHICS AND DISSEMINATION
Ethical approval is not required for literature-based studies. The results will be published in peer-reviewed journals or conferences.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Acupuncture Therapy; Walk Test; Forced Expiratory Volume
PubMed: 38734186
DOI: 10.1016/j.ctim.2024.103048 -
International Journal of Molecular... Apr 2024Autism Spectrum Disorder (ASD) is an early onset neurodevelopmental disorder characterized by impaired social interaction and communication, and repetitive patterns of... (Review)
Review
Autism Spectrum Disorder (ASD) is an early onset neurodevelopmental disorder characterized by impaired social interaction and communication, and repetitive patterns of behavior. Family studies show that ASD is highly heritable, and hundreds of genes have previously been implicated in the disorder; however, the etiology is still not fully clear. Brain imaging and electroencephalography (EEG) are key techniques that study alterations in brain structure and function. Combined with genetic analysis, these techniques have the potential to help in the clarification of the neurobiological mechanisms contributing to ASD and help in defining novel therapeutic targets. To further understand what is known today regarding the impact of genetic variants in the brain alterations observed in individuals with ASD, a systematic review was carried out using Pubmed and EBSCO databases and following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This review shows that specific genetic variants and altered patterns of gene expression in individuals with ASD may have an effect on brain circuits associated with face processing and social cognition, and contribute to excitation-inhibition imbalances and to anomalies in brain volumes.
Topics: Humans; Autism Spectrum Disorder; Neuroimaging; Brain; Electroencephalography; Genetic Predisposition to Disease
PubMed: 38732157
DOI: 10.3390/ijms25094938 -
Journal of the American Heart... May 2024Fractional flow reserve (FFR) is the ratio of blood pressure measured distal to a stenosis and pressure proximal to a stenosis. FFR can be estimated noninvasively using... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fractional flow reserve (FFR) is the ratio of blood pressure measured distal to a stenosis and pressure proximal to a stenosis. FFR can be estimated noninvasively using computed tomography (CT) although the usefulness of this technique remains controversial. This meta-analysis evaluated the agreement of FFR estimated by CT (FFR-CT) with invasively measured FFR. The study also evaluated the diagnostic accuracy of FFR-CT, defined as the ability of FFR-CT to classify lesions as hemodynamically significant (invasive FFR ≤0.8) or insignificant (invasive FFR >0.8).
METHODS AND RESULTS
Forty-three studies reporting on 7291 blood vessels from 5236 patients were included. A moderate positive linear relationship between FFR-CT and invasively measured FFR was observed (Spearman correlation coefficient: 0.67). Agreement between the 2 measures increased as invasively measured FFR values approached 1. The overall diagnostic accuracy, sensitivity and specificity of FFR-CT were 82.2%, 80.9%, and 83.1%, respectively. Diagnostic accuracy of 90% could be demonstrated for FFR-CT values >0.90 and <0.49. The diagnostic accuracy of off-site tools was 79.4% and the diagnostic accuracy of on-site tools was 84.1%.
CONCLUSIONS
The agreement between FFR-CT and invasive FFR is moderate although agreement is highest in vessels with FFR-CT >0.9. Diagnostic accuracy varies widely with FFR-CT value but is above 90% for FFR-CT values >0.90 and <0.49. Furthermore, on-site and off-site tools have similar performance. Ultimately, FFR-CT may be a useful adjunct to CT coronary angiography as a gatekeeper for invasive coronary angiogram.
Topics: Fractional Flow Reserve, Myocardial; Humans; Coronary Stenosis; Coronary Angiography; Computed Tomography Angiography; Predictive Value of Tests; Cardiac Catheterization; Reproducibility of Results; Coronary Artery Disease; Coronary Vessels; Severity of Illness Index; Tomography, X-Ray Computed
PubMed: 38726901
DOI: 10.1161/JAHA.124.034552 -
CJC Open Apr 2024Use of a sodium-glucose cotransporter-2 inhibitor (SGLT2i) reduces hospitalization in heart failure (HF) patients across the spectrum of ejection fraction, but no study... (Review)
Review
BACKGROUND
Use of a sodium-glucose cotransporter-2 inhibitor (SGLT2i) reduces hospitalization in heart failure (HF) patients across the spectrum of ejection fraction, but no study has comprehensively explored their impact on quality of life (QoL) with respect to different subgroup populations. We aimed to explore the QoL impact of SGLT2i use in HF patients across the spectrum of ejection fraction and over time.
METHODS
We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) covering the period from 2019 to February 2022. We included placebo-controlled randomized controlled trials (RCTs) enrolling HF patients that evaluated QoL as an outcome. Two reviewers independently assessed studies for eligibility, extracted data, and assessed risk of bias (RoB), using the Cochrane RoB2 tool, and certainty of evidence, using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Primary and secondary outcomes were the mean difference in QoL, and clinically important improvement in QoL, as defined in the original study, respectively. We conducted subgroup analyses based on ejection fraction category, SGLT2i agent, and timing of QoL measurement.
RESULTS
From 1477 identified reports, we included 14 RCTs (n = 23,361). The mean age was 68 years, and 34% were female. All included RCTs reported QoL using the Kansas City Cardiomyopathy Questionnaire (KCCQ). SGLT2i use improved KCCQ-overall summary score, compared with placebo (mean difference 2.0, 95% confidence interval 1.6-2.5; high certainty). More patients receiving an SGLT2i achieved a clinically important QoL improvement (risk ratio 1.14, 95% confidence interval 1.02-1.28; moderate certainty). Similar improvements were observed in the KCCQ clinical summary and total symptom subscores, and across all subgroups and timeframes.
CONCLUSIONS
Use of an SGLT2i consistently provides a clinically important improvement in QoL among patients with HF, regardless of ejection fraction, with noticeable improvements seen as early as week 2.
PubMed: 38708049
DOI: 10.1016/j.cjco.2023.12.002 -
Preventive Medicine Jun 2024Limited evidence shows culturally and linguistically diverse (CALD) children and adolescents are less active, compared to the general population. It is unclear, how... (Review)
Review
OBJECTIVE
Limited evidence shows culturally and linguistically diverse (CALD) children and adolescents are less active, compared to the general population. It is unclear, how physical activity interventions have been adapted for CALD children and adolescents to enhance engagement. This study aimed to review culturally adapted physical activity interventions targeting CALD children and adolescents.
METHODS
All studies recruited children and adolescents (i.e., aged ≥5 to <18 years old) from CALD backgrounds, targeted physical activity, and included cultural adaptations. Cultural adaptations were defined as surface structures (i.e., observable characteristics of a targeted population) or deep structures (i.e., rooted in core ethnic values derived from individual cultures.
RESULTS
Twenty studies were included. Ten studies used a combination of surface and deep structure adaptations. Of these 10 studies, 3 found a significant between-group difference in physical activity favouring the intervention group. Among studies (n = 6) that used surface structure adaptations (e.g., language adjustments to information sheets, consent forms, and resources), 1 found a significant intervention effect on physical activity. With studies (n = 4) that used deep structure adaptations (e.g., incorporating traditional songs and dances relevant to cultural groups), 1 study found a significant intervention effect on physical activity.
CONCLUSION
A small number of studies found significant changes to increase physical activity levels. We found there is a lack of consistent evidence indicating that incorporating surface and/or deep structure adaptations result in significant changes in physical activity. Future research should focus on establishing higher quality methodology when developing culturally adapted interventions for CALD populations.
Topics: Humans; Exercise; Adolescent; Child; Cultural Diversity; Health Promotion; Female; Male; Language
PubMed: 38697226
DOI: 10.1016/j.ypmed.2024.107979 -
Maternal Health, Neonatology and... May 2024Blood pressure is a vital hemodynamic marker during the neonatal period. However, normative values are often derived from small observational studies. Understanding the...
BACKGROUND
Blood pressure is a vital hemodynamic marker during the neonatal period. However, normative values are often derived from small observational studies. Understanding the normative range would help to identify ideal thresholds for intervention to treat hypotension or hypertension. Therefore, the aim of this study was to assess observed blood pressure values in neonates who have not received any blood-pressure modifying treatments from birth to three months postnatal age and whether these vary according to birth weight, gestational age and postnatal age.
METHODS
This was a systematic review. A literature search was conducted in MEDLINE, PubMed, Embase, Cochrane Library, and CINAHL from 1946 to 2017 on blood pressure in neonates from birth to 3 months of age (PROSPERO ID CRD42018092886). Unpublished data were included where appropriate.
RESULTS
Of 3,587 non-duplicate publications identified, 30 were included (one unpublished study). Twelve studies contained data grouped by birth weight, while 23 contained data grouped by gestational age. Study and clinical heterogeneity precluded meta-analyses thus results are presented by subgroup. A consistent blood pressure rise was associated with increasing birth weight, gestational age, and postnatal age. In addition, blood pressure seemed to rise more rapidly in the most preterm and low birth weight neonates.
CONCLUSION
Despite blood pressure increasing with birth weight, gestational age, and postnatal age, there was marked blood pressure variability observed throughout. To better define hypotension and hypertension, future studies should develop consistent approaches for factors related to blood pressure variability, including the method and timing of measurement as well as statistical control of relevant patient characteristics.
PubMed: 38689326
DOI: 10.1186/s40748-024-00180-w