Search

Background: This study aimed to conduct a systematic review of the cost-effectiveness studies of interventions to increase cervical cancer screening uptake rates in underserved women in Europe., Methods: A search of Embase, Medline, Global Health, PsychINFO, and NHS Economic Evaluation Database was conducted for studies published between January 2000 and September 2022. Studies were eligible if they analysed the cost-effectiveness of any interventions to improve participation in cervical cancer screening among underserved women of any age eligible to participate in cervical cancer screening in European countries, in any language. Study characteristics and cost-effectiveness results were summarised. Study quality was assessed using the Drummond Checklist, and methodological choices were further compared., Results: The searches yielded 962 unique studies, with 17 of these (from twelve European countries) meeting the eligibility criteria for data extraction. All studies focused on underscreened women as an overarching group, with no identified studies focusing on specific subgroups of underserved women. Generally, self-HPV testing and reminder interventions were shown to be cost-effective to increase the uptake rates. There was also research showing that addressing access issues and adopting different screening modalities could be economically attractive in some settings, but the current evidence is insufficient due to the limited number of studies., Conclusion: This systematic review has revealed a gap in the literature on the cost-effectiveness of interventions to improve uptake rates of cervical cancer screening through tailored provision for specific groups of underserved women., (© 2023. The Author(s).)

Background: Neonatal disorders are facing serious public health challenges. Previous studies were based on limited data sources and had a narrow geographical scope. We aim to understand the trends of alteration in the burden of neonatal disorders from 1990 to 2019 in 204 countries and territories., Methods: Data were investigated from the Global Burden of Disease Study 2019. First, we visualized the burden of neonatal disorders using the number of cases and the age-standardized incidence rate (ASIR), death rate (ASDR), and disability-adjusted life years (ASR-DALYs) from 1990 to 2019. Second, estimated annual percentage changes (EAPCs) were used to evaluate the temporal trends of disease burden during different periods. Finally, the sociodemographic index (SDI) and human development index (HDI) were used to determine whether there exists a correlation between socioeconomic development level, human development level, and potential burden consequences., Results: Overall, in the past 30 years, the ASIR trends have remained relatively steady, whereas the ASDR and ASR-DALYs have declined. However, the burden of neonatal disorders varied greatly in various regions and countries. Among 21 regions, the ASIR trend had the largest increase in Central Latin America (EAPC = 0.42, 95%CI = 0.33-0.50). Conversely, the ASDR and ASR-DALYs experienced the largest decrease in Central Europe (EAPC = -5.10, 95%CI = -5.28 to 4.93) and East Asia (EAPC = -4.07, 95%CI = -4.41 to 3.73), respectively. Among 204 countries, the ASIR (EAPC = 3.35, 95%CI = 3.13-3.56) trend in Greece displayed the most significant increase, while the ASDR (EAPC = 1.26, 95%CI = 1.01-1.50) and ASR-DALYs (EAPC = 1.26, 95%CI = 1.03-1.49) trends in Dominica experienced the most substantial increase. Furthermore, there was a strong correlation between the EAPCs in ASIR, ASDR, ASR-DALYs, and SDI or HDI in 2019, with some exceptions. In addition, countries with elevated levels of HDI experienced a faster increase in ASDR and ASR-DALYs for neonatal disorders., Conclusion: Although the burden of neonatal disorders shows a downward trend from 1990 to 2019, it is still not optimistic. It is necessary to implement a multi-pronged approach to reduce the increasing burden of neonatal disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xin, Luo, Xiang, Zhu, Niu, Feng, Sun, Zhang, Zhou and Yang.)

Background: Charcot-Marie-Tooth disease and related inherited peripheral neuropathies (CMT&RIPNs) brings great suffering and heavy burden to patients, but its global prevalence rates have not been well described., Methods: We searched major English and Chinese databases for studies reporting the prevalence of CMT&RIPNs from the establishment of the databases to September 26, 2022. Based on the age, gender, study design, study region, and disease subtype, the included studies were correspondingly synthesized for meta-analyses on the overall prevalence and/or the subgroup analyses by using pool arcsine transformed proportions in the random-effects model., Results: Of the finally included 31 studies, 21 studied the whole age population and various types of CMT&RIPNs, and the others reported specific disease subtype(s) or adult or non-adult populations. The pooled prevalence was 17.69/100,000 (95% CI 12.32-24.33) for the whole age population and significantly higher for CMT1 [10.61/100,000 (95% CI 7.06-14.64)] than for other subtypes (P' < 0.001). Without statistical significance, the prevalence seemed higher in those aged ≥ 16 or 18 years (21.02/100,000) than in those aged < 16 years (16.13/100,000), in males (22.50/100,000) than in females (17.95/100,000), and in Northern Europe (30.97/100,000) than in other regions., Conclusion: CMT&RIPNs are relatively more prevalent as CMT1 in the disease subtypes, and probably prevalent in older ages, males, and Northern Europe. More studies on the epidemiological characteristics of CMT&RIPNs with well-defined diagnosis criteria are needed to improve the prevalence evaluation and to arouse more attention to health care support., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes 1 . Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel 2 ) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries., (© 2022. The Author(s).)

Purpose: Patients with myelofibrosis who are relapsed or refractory (R/R) to Janus-associated kinase inhibitors (JAKis) have poor clinical outcomes including dismal overall survival (OS) that ranges between 13 and 16 months. Imetelstat, a telomerase inhibitor, was evaluated in patients with intermediate-2 or high-risk myelofibrosis R/R to JAKi in a phase II multicenter study (ClinicalTrials.gov identifier: NCT02426086)., Patients and Methods: Patients were randomly assigned to receive either imetelstat 9.4 mg/kg or 4.7 mg/kg intravenous once every 3 weeks. Spleen response (≥ 35% spleen volume reduction) and symptom response (≥ 50% reduction in total symptom score) rates at week 24 were coprimary end points. Secondary end points included OS and safety., Results: Study enrollment was closed early, and patients treated with 4.7 mg/kg were permitted to continue treatment with 9.4 mg/kg. At week 24, spleen and symptom response rates were 10.2% and 32.2% in the 9.4-mg/kg arm and 0% and 6.3% in the 4.7-mg/kg arm. Treatment with imetelstat 9.4 mg/kg led to a median OS of 29.9 months and bone marrow fibrosis improvement in 40.5% and variant allele frequency reduction of driver mutations in 42.1% of evaluable patients. Fibrosis improvement and variant allele frequency reduction correlated with OS. Target inhibition was demonstrated by reduction of telomerase activity and human telomerase reverse transcriptase level and correlated with spleen response, symptom response, and OS. Most common adverse events on both arms were grade 3 or 4 reversible cytopenias., Conclusion: In this phase II study of two imetelstat doses, 9.4 mg/kg once every 3 weeks demonstrated clinical benefits in symptom response rate, with an acceptable safety profile for this poor-risk JAKi R/R population. Biomarker and bone marrow fibrosis assessments suggested selective effects on the malignant clone. A confirmatory phase III study is currently underway., Competing Interests: John MascarenhasConsulting or Advisory Role: Incyte, Geron, Celgene/Bristol Myers Squibb, Novartis, CTI BioPharma Corp, Kartos Therapeutics, Constellation Pharmaceuticals, Sierra Oncology, AbbVie, Roche/GenentechResearch Funding: Incyte, Pharmaessentia, Merck, Forbius, Geron, AbbVie, Kartos Therapeutics, Roche/Genentech, CTI BioPharma Corp Rami KomrokjiStock and Other Ownership Interests: AbbVieConsulting or Advisory Role: Novartis, Bristol Myers Squibb, Jazz Pharmaceuticals, AbbVie, Geron, Acceleron PharmaSpeakers' Bureau: Jazz Pharmaceuticals, Bristol Myers Squibb, AgiosTravel, Accommodations, Expenses: Jazz Pharmaceuticals, Bristol Myers Squibb, Agios Dietger NiederwieserConsulting or Advisory Role: Cellectis, Amgen, NovartisSpeakers' Bureau: NovartisResearch Funding: Daiichi Sankyo Andreas ReiterHonoraria: Novartis, Blueprint Medicines, Incyte, Celgene/Bristol Myers Squibb, AOP Orphan PharmaceuticalsConsulting or Advisory Role: Novartis, Blueprint Medicines, Incyte, Celgene/Bristol Myers Squibb, AOP Orphan PharmaceuticalsResearch Funding: Blueprint Medicines, Deciphera, Novartis, Incyte, AOP Orphan PharmaceuticalsExpert Testimony: NovartisTravel, Accommodations, Expenses: Novartis, Deciphera, Blueprint Medicines, Incyte Bart ScottHonoraria: Bristol Myers SquibbConsulting or Advisory Role: Celgene, Acceleron Pharma, Astex Pharmaceuticals, NovartisSpeakers' Bureau: Alexion Pharmaceuticals, Celgene, Jazz Pharmaceuticals, NovartisResearch Funding: Celgene Maria BaerResearch Funding: AbbVie, AI Therapeutics, FORMA Therapeutics, Kite, a Gilead company, Oscotec, Takeda Ronald HoffmanConsulting or Advisory Role: Protagonist Therapeutics, NovartisResearch Funding: Novartis, Scholar Rock, Turning Point Therapeutics Olatoyosi OdenikeConsulting or Advisory Role: AbbVie, Impact Biomedicines, Celgene, Novartis, BMS, Taiho PharmaceuticalResearch Funding: Celgene, Incyte, Astex Pharmaceuticals, NS Pharma, AbbVie, Janssen Oncology, OncoTherapy Science, Agios, AstraZeneca, CTI BioPharma Corp, Kartos Therapeutics, Aprea AB Alessandro VannucchiConsulting or Advisory Role: Novartis, AbbVie, Roche, Incyte, CelgeneSpeakers' Bureau: Novartis, AOP Orphan Pharmaceuticals, Incyte, Roche, Celgene Jacqueline BussolariEmployment: Johnson & Johnson, Bristol Myers Squibb, HotSpot TherapeuticsLeadership: HotSpot TherapeuticsStock and Other Ownership Interests: Johnson & Johnson, Bristol Myers Squibb, HotSpot TherapeuticsTravel, Accommodations, Expenses: Johnson & Johnson Eugene ZhuEmployment: Johnson & JohnsonStock and Other Ownership Interests: Johnson & Johnson Esther RoseEmployment: Janssen Research & DevelopmentStock and Other Ownership Interests: Johnson & JohnsonConsulting or Advisory Role: Geron CorpTravel, Accommodations, Expenses: Janssen Research & Development Laurie ShermanEmployment: Geron, JanssenStock and Other Ownership Interests: Janssen, Geron Souria DoughertyEmployment: GeronStock and Other Ownership Interests: Geron Libo SunEmployment: GeronStock and Other Ownership Interests: Geron, Johnson & Johnson, Moderna TherapeuticsTravel, Accommodations, Expenses: Geron Fei HuangStock and Other Ownership Interests: Bristol Myers Squibb, Geron, Johnson & Johnson Ying WanEmployment: GeronStock and Other Ownership Interests: Geron Faye FellerEmployment: Geron, JanssenStock and Other Ownership Interests: Geron, JanssenTravel, Accommodations, Expenses: Geron, Janssen Aleksandra RizoLeadership: GeronStock and Other Ownership Interests: Geron, Johnson & Johnson Jean-Jacques KiladjianConsulting or Advisory Role: Novartis, Incyte, BMS, AOP Orphan Pharmaceuticals, AbbVie, PharmaessentiaNo other potential conflicts of interest were reported.

Background and Purpose: As outcomes for acute ischemic stroke (AIS) vary according to clinical profile and management approaches, we aimed to determine disparities in clinical outcomes between Asian and non-Asian participants of the international, Enhanced Control of Hypertension and Thrombolysis Stroke study (ENCHANTED)., Methods: ENCHANTED was a multicenter, prospective, partial-factorial, randomized, open trial of low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) alteplase, and intensive (target systolic blood pressure [SBP] 130-140 mm Hg) or guideline-recommended (<180 mm Hg) BP management, in thrombolysis-eligible AIS patients. Logistic regression models were used to examine the associations with outcomes of death or disability (modified Rankin scale [mRS] scores 2-6), major disability (mRS 3-5), death, and intracranial hemorrhage (ICH), with adjustment prognostic factors, alteplase dose, and mean SBP over 1-24 h., Results: Among 4,551 thrombolyzed AIS patients (mean age 66.7 years, 37.8% female), there were 65.4% Asians who were younger, fewer female, and with less atrial fibrillation, hypercholesterolemia, premorbid symptoms, and concomitant antihypertensive, antithrombotic and statin treatment, and more prior stroke, compared to non-Asians. Frequencies of hypertension, coronary artery disease, and diabetes mellitus were comparable between groups. Asian patients were less likely to be admitted to an acute stroke unit and receive early mobilization by a therapist or rehabilitation but more likely to receive intensive care. There were no significant differences between Asians and non-Asians in functional outcome (defined by mRS scores 2-6 or 3-5; adjusted odds ratio [OR] 1.00, 95% confidence interval [CI] 0.85-1.19 [p = 0.958] and OR 0.95, 95% CI 0.80-1.13 [p = 0.572], respectively), or death (OR 1.25, 95% CI 0.95-1.65; p = 0.116), despite Asians having greater odds of ICH (OR 1.51, 95% CI 1.23-1.86; p = 0.0001) and neurological deterioration within 24 h (OR 1.58, 95% CI 1.18-2.12; p = 0.002)., Conclusions: Within the context of an international clinical trial of thrombolyzed AIS patients, demography, risk factors, management, and odds of early neurological deterioration and ICH, all differ between Asian and non-Asian participants. However, patterns of functional recovery are similar between these major regional groups., (© 2021 S. Karger AG, Basel.)

Background: Life expectancy (LE) and healthy life expectancy (HALE) are indicators measuring the national health level. GAP is the difference between them. This study systematically analyzed and projected LE, HALE, and GAP across global regions from 1995 to 2025., Methods: We obtained the data of 195 countries/regions on their LE, HALE, and influencing factors from 1995 to 2017. We compared the overall changes of LE, HALE, and GAP. Multiple linear regression analysis examined relationships among LE, HALE, GAP, and the associated factors. Using the Autoregressive Integrated Moving Average (ARIMA) model, we projected trends in LE, HALE, and GAP for 2017-2025., Results: During 1995-2017, LE, HALE, and their GAP in 195 countries/regions in the world showed overall increasing trends. Global average LE increased from 66.20 to 72.98 years, HALE from 57.59 to 63.25 years, and GAP from 8.62 to 9.72 years. LE and HALE in North America, Europe, and Australia were generally higher, while Africa had the lowest rates. Females' LE, HALE, and GAP were all higher than males', but females' growth rates of LE and HALE were lower. Different factors were included to project LE, HALE, and GAP, respectively, and prediction results showed that approximately 18% of the 195 countries/regions might achieve improved LE and HALE and lower GAP., Conclusions: LE, HALE will likely continue to increase in most of countries and regions worldwide in the future and GAP will further expand. While striving to improve LE and HALE, more attention needs be made to reduce GAP and improve quality of life., Competing Interests: Competing interests: The authors completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author), and declare no conflicts of interest., (Copyright © 2020 by the Journal of Global Health. All rights reserved.)

Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.

Most genome-wide association studies have been of European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we used an exome array to examine protein-coding genetic variants in 47,532 East Asian individuals. We identified 255 variants at 41 loci that reached chip-wide significance, including 3 novel loci and 14 East Asian-specific coding variant associations. After a meta-analysis including >300,000 European samples, we identified an additional nine novel loci. Sixteen genes were identified by protein-altering variants in both East Asians and Europeans, and thus are likely to be functional genes. Our data demonstrate that most of the low-frequency or rare coding variants associated with lipids are population specific, and that examining genomic data across diverse ancestries may facilitate the identification of functional genes at associated loci.

Objective: To investigate differences in genetic risk factors for rheumatoid arthritis (RA) in Han Chinese as compared with Europeans., Methods: A genome-wide association study was conducted in China with 952 patients and 943 controls, and 32 variants were followed up in 2,132 patients and 2,553 controls. A transpopulation meta-analysis with results from a large European RA study was also performed to compare the genetic architecture across the 2 ethnic remote populations., Results: Three non-major histocompatibility complex (non-MHC) loci were identified at the genome-wide significance level, the effect sizes of which were larger in anti-citrullinated protein antibody (ACPA)-positive patients than in ACPA-negative patients. These included 2 novel variants, rs12617656, located in an intron of DPP4 (odds ratio [OR] 1.56, P = 1.6 × 10(-21) ), and rs12379034, located in the coding region of CDK5RAP2 (OR 1.49, P = 1.1 × 10(-16) ), as well as a variant at the known CCR6 locus, rs1854853 (OR 0.71, P = 6.5 × 10(-15) ). The analysis of ACPA-positive patients versus ACPA-negative patients revealed that rs12617656 at the DPP4 locus showed a strong interaction effect with ACPAs (P = 5.3 × 10(-18) ), and such an interaction was also observed for rs7748270 at the MHC locus (P = 5.9 × 10(-8) ). The transpopulation meta-analysis showed genome-wide overlap and enrichment in association signals across the 2 populations, as confirmed by prediction analysis., Conclusion: This study has expanded the list of alleles that confer risk of RA, provided new insight into the pathogenesis of RA, and added empirical evidence to the emerging polygenic nature of complex trait variation driven by common genetic variants., (Copyright © 2014 by the American College of Rheumatology.)

A large number of studies has investigated the hypothesis that DRD4 48 bp variable number of tandem repeat (VNTR) polymorphism is involved in the etiology of schizophrenia and bipolar disorder. However, the results are inconsistent likely due to genetic and phenotypic heterogeneity. Age at onset (AAO) is considered an important alternate phenotype for genetic investigations of psychiatric disorders. In the present study, the DRD4 VNTR 7 repeat allele (7R) was examined in 477 patients with major psychoses. Age at onset was defined as the age of first psychotic episode for schizophrenia and the age at appearance of first clinically recognized symptoms for the bipolar sample. Our results showed an interaction between sex and DRD4 genotypes among schizophrenia patients (n=203, β=.213, p=.017). On comparing AAO between carriers and non-carriers of the 7R, we observed that females with 7R present had later onset (p=.021). The effect was not observed for males. In the sample with bipolar disorder, we observed significant association between DRD4 7R-genotype and AAO (n=274, β=-.148, p=.012). No interaction was observed between sex and genotypic groups of the bipolar sample. The 7R was associated with early onset of the bipolar illness (p=.028). In summary, our results suggest that the 7R is associated with AAO in both schizophrenia and bipolar disorders. The effect was observed across both sexes in bipolar disorder, but specifically in females for schizophrenia., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Genetic association studies have shown the importance of variants in the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit gene cluster on chromosome 15q24-25.1 for the risk of nicotine dependence, smoking, and lung cancer in populations of European descent. We have carried out a detailed study of this region using dense genotyping in both European-Americans and African-Americans. We genotyped 75 known single nucleotide polymorphisms (SNPs) and one sequencing-discovered SNP in an African-American sample (N = 710) and in a European-American sample (N = 2,062). Cases were nicotine-dependent and controls were nondependent smokers. The nonsynonymous CHRNA5 SNP rs16969968 is the most significant SNP associated with nicotine dependence in the full sample of 2,772 subjects [P = 4.49 x 10(-8); odds ratio (OR), 1.42; 95% confidence interval (CI), 1.25-1.61] as well as in African-Americans only (P = 0.015; OR, 2.04; 1.15-3.62) and in European-Americans only (P = 4.14 x 10(-7); OR, 1.40; 1.23-1.59). Other SNPs that have been shown to affect the mRNA levels of CHRNA5 in European-Americans are associated with nicotine dependence in African-Americans but not in European-Americans. The CHRNA3 SNP rs578776, which has a low correlation with rs16969968, is associated with nicotine dependence in European-Americans but not in African-Americans. Less common SNPs (frequency

A trend in modern medicine is towards individualization of healthcare and, potentially, grid computing can play an important role in this by allowing sharing of resources and expertise to improve the quality of care. In this paper, we present a new test bed, the BIOPATTERN Grid, which aims to fulfil this role in the long term. The main objectives in this paper are 1) to report the development of the BIOPATTERN Grid, for biopattern analysis and bioprofiling in support of individualization of healthcare. The BIOPATTERN Grid is designed to facilitate secure and seamless sharing of geographically distributed bioprofile databases and to support the analysis of bioprofiles to combat major diseases such as brain diseases and cancer within a major EU project, BIOPATTERN (www.biopattern.org); 2) to illustrate how the BIOPATTERN Grid could be used for biopattern analysis and bioprofiling for early detection of dementia and for brain injury assessment on an individual basis. We highlight important issues that would arise from the mobility of citizens in the EU, such as those associated with access to medical data, ethical and security; and 3) to describe two grid services which aim to integrate BIOPATTERN Grid with existing grid projects on crawling service and remote data acquisition which is necessary to underpin the use of the test bed for biopattern analysis and bioprofiling.

Race, once the central concept in physical anthropology worldwide, now varies in the degree of support it receives in different regions. We present the currently available information on the status of the concept in the United States, the Spanish language areas, Poland, Europe, Russia, and China. Rejection of race ranges from high to low with the highest rejection occurring among anthropologists in the United States (and Canada). Rejection of race is moderate in Europe, sizeable in Poland and Cuba, and lowest in Russia and China. A discussion on the scientific and contextual reasons influencing these variations is presented. The tension between scientific evidence and social influences varies from region to region. The methods used in the studies reported here included questionnaires and content analysis. Response rates to questionnaires were often around 50 percent (with exception of the Polish studies). We discuss reasons for the low rates. Although a uniform method of data gathering is desirable, it may not suit scientists working in different traditions of theory and research. We conclude that it is once again timely to discuss the race concept in international meetings where all scientific and political changes occurring throughout the world in recent past decades are taken into account.