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MedRxiv : the Preprint Server For... Sep 2023The objective of this study was to map place of cancer diagnosis in relation to Human Immunodeficiency Virus (HIV) care centre among people with HIV (PWH) within South...
OBJECTIVE
The objective of this study was to map place of cancer diagnosis in relation to Human Immunodeficiency Virus (HIV) care centre among people with HIV (PWH) within South Africa (SA) using national laboratory database.
DESIGN
We linked HIV and cancer laboratory data from 2004-2014 using supervised machine-learning algorithms. We performed a cross-sectional analysis comparing province where individuals accessed their HIV care versus where they had their cancer diagnosis.
SETTING
We used laboratory test records related to HIV diagnostics and care, such as CD4 cell counts and percentages, rapid tests, qualitative Polymerase Chain Reaction (PCR), antibody and antigen tests for HIV data that was documented as HIV positive and laboratory diagnosed cancer records from SA.
STUDY POPULATION
Our study population consisted of HIV records from the National Health Laboratory Service (NHLS) that linked to cancer record at the National Cancer Registry (NCR) between 2004- 2014.
PRIMARY AND SECONDARY OUTCOMES
We linked HIV records from NHLS to cancer records at NCR in order to study the inherent characteristics of the population with both HIV and cancer.
RESULTS
The study population was 68,284 individuals with cancer and documented HIV related laboratory test. The median age at cancer diagnosis was 40 [IQR, 33-48] years for the study population with most cancers in PWH diagnosed in females 70.9% [n=46,313]. Of all the PWH and cancer, 25% (n=16,364 p < 0.001) sought treatment outside their province of residence with 60.7% (n=10,235) travelling to Gauteng. KZN had 46.6% (n=4,107) of its PWH getting cancer diagnosis in Gauteng. Western Cape had 95% (n=6,200) of PWH getting cancer diagnosis within the province.
CONCLUSIONS
Our results showed health systems inequalities across provinces in South Africa with respect to cancer diagnosis. KZN for example had nearly half of the PWH getting cancer diagnosis outside the province while Western Cape is able to offer cancer diagnostic services to most of the PWH in the province. Gauteng is getting over burdened with referral for cancer diagnosis from other provinces. More effort is required to ensure equitable access to cancer diagnostic services within the country.
PubMed: 37745395
DOI: 10.1101/2023.09.10.23295338 -
Survey of Ophthalmology 2024I detail advances in funduscopy diagnostic systems integrating smartphones. Smartphone funduscopy devices are comprised of lens devices connecting with smartphones and... (Review)
Review
I detail advances in funduscopy diagnostic systems integrating smartphones. Smartphone funduscopy devices are comprised of lens devices connecting with smartphones and software applications to be used for mobile retinal image capturing and diagnosis of diabetic retinopathy. This is particularly beneficial to automate and mobilize retinopathy screening techniques and methods in remote and rural areas as those diabetes patients are often not meeting the required regular screening for diabetic retinopathy. Smartphone retinal image grading systems enable retinopathy to be screened remotely as teleophthalmology or as a stand-alone point-of-care-testing system. Smartphone funduscopy aims to avoid the need for patients to be seen by expert ophthalmologists, which can reduce patient travel, time taken for images to be processed, appointment backlog, health service overhead costs, and the workload burden for expert ophthalmologists.
Topics: Humans; Diabetic Retinopathy; Smartphone; Ophthalmology; Telemedicine; Mass Screening; Diabetes Mellitus
PubMed: 37806567
DOI: 10.1016/j.survophthal.2023.10.006 -
European Thyroid Journal Jul 2023Thyroid hormone (TH) is indispensable for brain development in utero and during the first 2-3 years of life, and the negative effects of TH deficiency on brain... (Review)
Review
Thyroid hormone (TH) is indispensable for brain development in utero and during the first 2-3 years of life, and the negative effects of TH deficiency on brain development are irreversible. Detection of TH deficiency early in life by neonatal screening allows early treatment, thereby preventing brain damage. Inborn shortage of TH, also named congenital hypothyroidism (CH), can be the result of defective thyroid gland development or TH synthesis (primary or thyroidal CH (CH-T)). Primary CH is characterized by low blood TH and elevated thyroid-stimulating hormone (TSH) concentrations. Less frequently, CH is due to insufficient stimulation of the thyroid gland because of disturbed hypothalamic or pituitary function (central CH). Central CH is characterized by low TH concentrations, while TSH is normal, low or slightly elevated. Most newborn screening (NBS) programs for CH are primarily TSH based and thereby do not detect central CH. Only a few NBS programs worldwide aim to detect both forms of CH by different strategies. In the Netherlands, we have a unique T4-TSH-thyroxine-binding globulin (TBG) NBS algorithm for CH, which enables the detection of primary and central CH. Although the necessity of central CH detection by NBS is still under debate, it has been shown that most central CH patients have moderate-to-severe hypothyroidism instead of mild and that early detection of central CH by NBS probably improves its clinical outcome and clinical care for central CH patients with multiple pituitary hormone deficiency. We are therefore convinced that detection of central CH by NBS is of utmost importance.
Topics: Infant, Newborn; Humans; Congenital Hypothyroidism; Neonatal Screening; Thyrotropin; Thyroxine; Thyroid Hormones
PubMed: 37326450
DOI: 10.1530/ETJ-23-0041 -
Science Advances Dec 2023Trophectoderm (TE) and the inner cell mass are the first two lineages in murine embryogenesis and cannot naturally transit to each other. The barriers between them are...
Trophectoderm (TE) and the inner cell mass are the first two lineages in murine embryogenesis and cannot naturally transit to each other. The barriers between them are unclear and fascinating. Embryonic stem cells (ESCs) and trophoblast stem cells (TSCs) retain the identities of inner cell mass and TE, respectively, and, thus, are ideal platforms to investigate these lineages in vitro. Here, we develop a loss-of-function genetic screening in haploid ESCs and reveal many mutations involved in the conversion of TSCs. The disruption of either or (candidates) in ESCs facilitates the conversion of TSCs. According to transcriptome analysis, we find that the repression of activates totipotency, which is a possible reason for TE specification. -null ESCs can contribute to embryonic and extraembryonic tissues in chimeras and can efficiently form blastocyst-like structures, indicating their totipotent developmental abilities. These findings provide insights into the mechanisms underlying cell fate alternation in embryogenesis.
Topics: Animals; Mice; Blastocyst; Cell Differentiation; Embryonic Stem Cells; Genetic Testing; Haploidy
PubMed: 38117886
DOI: 10.1126/sciadv.adi5683 -
Annual Review of Genomics and Human... Aug 2023This article reviews evolving legal implications for clinicians and researchers as genomics is used more widely in both the clinic and in translational research,... (Review)
Review
This article reviews evolving legal implications for clinicians and researchers as genomics is used more widely in both the clinic and in translational research, reflecting rapid changes in scientific knowledge as well as the surrounding cultural and political environment. Professionals will face new and changing duties to make or act upon a genetic diagnosis, address direct-to-consumer genetic testing in patient care, consider the health implications of results for patients' family members, and recontact patients when test results change over time. Professional duties in reproductive genetic testing will need to be recalibrated in response to disruptive changes to reproductive rights in the United States. We also review the debate over who controls the flow of genetic information and who is responsible for its protection, considering the globally influential European Union General Data Protection Regulation and the rapidly evolving data privacy law landscape of the United States.
Topics: Humans; Ambulatory Care Facilities; Direct-To-Consumer Screening and Testing; European Union; Family; Genomics
PubMed: 36630592
DOI: 10.1146/annurev-genom-100722-021725 -
BMC Neurology Aug 2023Autism spectrum disorder (ASD) affects 1 in 100 children globally with a rapidly increasing prevalence. To the best of our knowledge, no data exists on the genetic...
BACKGROUND
Autism spectrum disorder (ASD) affects 1 in 100 children globally with a rapidly increasing prevalence. To the best of our knowledge, no data exists on the genetic architecture of ASD in India. This study aimed to identify the genetic architecture of ASD in India and to assess the use of whole exome sequencing (WES) as a first-tier test instead of chromosomal microarray (CMA) for genetic diagnosis.
METHODS
Between 2020 and 2022, 101 patient-parent trios of Indian origin diagnosed with ASD according to the Diagnostic and Statistical Manual, 5th edition, were recruited. All probands underwent a sequential genetic testing pathway consisting of karyotyping, Fragile-X testing (in male probands only), CMA and WES. Candidate variant validation and parental segregation analysis was performed using orthogonal methods.
RESULTS
Of 101 trios, no probands were identified with a gross chromosomal anomaly or Fragile-X. Three (2.9%) and 30 (29.7%) trios received a confirmed genetic diagnosis from CMA and WES, respectively. Amongst diagnosis from WES, SNVs were detected in 27 cases (90%) and CNVs in 3 cases (10%), including the 3 CNVs detected from CMA. Segregation analysis showed 66.6% (n = 3 for CNVs and n = 17 for SNVs) and 16.6% (n = 5) of the cases had de novo and recessive variants respectively, which is in concordance with the distribution of variant types and mode of inheritance observed in ASD patients of non-Hispanic white/ European ethnicity. MECP2 gene was the most recurrently mutated gene (n = 6; 20%) in the present cohort. Majority of the affected genes identified in the study cohort are involved in synaptic formation, transcription and its regulation, ubiquitination and chromatin remodeling.
CONCLUSIONS
Our study suggests de novo variants as a major cause of ASD in the Indian population, with Rett syndrome as the most commonly detected disorder. Furthermore, we provide evidence of a significant difference in the diagnostic yield between CMA (3%) and WES (30%) which supports the implementation of WES as a first-tier test for genetic diagnosis of ASD in India.
Topics: Child; Humans; Male; Autism Spectrum Disorder; Exome Sequencing; Pathology, Molecular; Genetic Testing; Microarray Analysis
PubMed: 37543562
DOI: 10.1186/s12883-023-03341-0 -
Missouri Medicine 2024The incidence of diabetes and hyperlipidemia are increasing at rapid rates in children. These conditions are associated with increased risk of macrovascular and... (Review)
Review
The incidence of diabetes and hyperlipidemia are increasing at rapid rates in children. These conditions are associated with increased risk of macrovascular and microvascular complications causing major morbidity and mortality later in life. Early diagnosis and treatment can reduce the lifelong risk of complications from these diseases, exemplifying the importance of screening in the pediatric population. The following article presents a summary of the current guidelines for diabetes and hyperlipidemia screening in pediatric patients.
Topics: Humans; Child; Dyslipidemias; Mass Screening; Practice Guidelines as Topic; Diabetes Mellitus; Pediatrics; Hyperlipidemias; Adolescent
PubMed: 38854609
DOI: No ID Found -
Genome Medicine Sep 2023Many families and individuals do not meet criteria for a known hereditary cancer syndrome but display unusual clusters of cancers. These families may carry pathogenic...
BACKGROUND
Many families and individuals do not meet criteria for a known hereditary cancer syndrome but display unusual clusters of cancers. These families may carry pathogenic variants in cancer predisposition genes and be at higher risk for developing cancer.
METHODS
This multi-centre prospective study recruited 195 cancer-affected participants suspected to have a hereditary cancer syndrome for whom previous clinical targeted genetic testing was either not informative or not available. To identify pathogenic disease-causing variants explaining participant presentation, germline whole-genome sequencing (WGS) and a comprehensive cancer virtual gene panel analysis were undertaken.
RESULTS
Pathogenic variants consistent with the presenting cancer(s) were identified in 5.1% (10/195) of participants and pathogenic variants considered secondary findings with potential risk management implications were identified in another 9.7% (19/195) of participants. Health economic analysis estimated the marginal cost per case with an actionable variant was significantly lower for upfront WGS with virtual panel ($8744AUD) compared to standard testing followed by WGS ($24,894AUD). Financial analysis suggests that national adoption of diagnostic WGS testing would require a ninefold increase in government annual expenditure compared to conventional testing.
CONCLUSIONS
These findings make a case for replacing conventional testing with WGS to deliver clinically important benefits for cancer patients and families. The uptake of such an approach will depend on the perspectives of different payers on affordability.
Topics: Humans; Prospective Studies; Neoplastic Syndromes, Hereditary; Oncogenes; Genetic Testing; Germ Cells
PubMed: 37723522
DOI: 10.1186/s13073-023-01223-1 -
European Heart Journal Dec 2023Hypertrophic cardiomyopathy (HCM) is characterized by phenotypic heterogeneity that is partly explained by the diversity of genetic variants contributing to disease....
AIMS
Hypertrophic cardiomyopathy (HCM) is characterized by phenotypic heterogeneity that is partly explained by the diversity of genetic variants contributing to disease. Accurate interpretation of these variants constitutes a major challenge for diagnosis and implementing precision medicine, especially in understudied populations. The aim is to define the genetic architecture of HCM in North African cohorts with high consanguinity using ancestry-matched cases and controls.
METHODS AND RESULTS
Prospective Egyptian patients (n = 514) and controls (n = 400) underwent clinical phenotyping and genetic testing. Rare variants in 13 validated HCM genes were classified according to standard clinical guidelines and compared with a prospective HCM cohort of majority European ancestry (n = 684). A higher prevalence of homozygous variants was observed in Egyptian patients (4.1% vs. 0.1%, P = 2 × 10-7), with variants in the minor HCM genes MYL2, MYL3, and CSRP3 more likely to present in homozygosity than the major genes, suggesting these variants are less penetrant in heterozygosity. Biallelic variants in the recessive HCM gene TRIM63 were detected in 2.1% of patients (five-fold greater than European patients), highlighting the importance of recessive inheritance in consanguineous populations. Finally, rare variants in Egyptian HCM patients were less likely to be classified as (likely) pathogenic compared with Europeans (40.8% vs. 61.6%, P = 1.6 × 10-5) due to the underrepresentation of Middle Eastern populations in current reference resources. This proportion increased to 53.3% after incorporating methods that leverage new ancestry-matched controls presented here.
CONCLUSION
Studying consanguineous populations reveals novel insights with relevance to genetic testing and our understanding of the genetic architecture of HCM.
Topics: Humans; Consanguinity; Prospective Studies; Ethnicity; Genetic Testing; Cardiomyopathy, Hypertrophic; Mutation
PubMed: 37431535
DOI: 10.1093/eurheartj/ehad372 -
Global Health Action Dec 2023Colorectal cancer (CRC) is the third most common cancer worldwide. The incidence of CRC is rising in low- and middle-income countries but decreasing in high-income... (Review)
Review
BACKGROUND
Colorectal cancer (CRC) is the third most common cancer worldwide. The incidence of CRC is rising in low- and middle-income countries but decreasing in high-income countries due to the widespread use of surveillance colonoscopy. In Africa, the implementation of screening programs remains a challenge, even in countries, such as Ghana that have established CRC screening guidelines.
OBJECTIVE
The purpose of this review was to identify the barriers and recommend strategies for implementing CRC screening in African countries.
METHODS
A literature search using PubMed was conducted with the following search terms: colorectal neoplasm, early detection of cancer, mass screening, colonoscopy, faecal occult blood test, faecal immunochemical test (FIT) and Africa. After inclusion and exclusion criteria were applied, a total of 13 articles were reviewed.
RESULTS
The most common barriers reported were limited endoscopic capacity, poor knowledge of CRC and CRC screening, health care factors, cultural factors and sociodemographic factors. Recommendations to increase the availability of CRC screening tests were to include the use of FITs, to provide more training for health care providers, and to expand educational programs for patients, physicians, and religious/community leaders.
CONCLUSION
The primary barrier to screening for CRC in Africa is the limited endoscopic capacity, specifically the lack of infrastructure and trained personnel, which requires systematic changes by governing bodies. In addition, health care professionals should be involved in educating patients about CRC and CRC screening. Further research is needed to clarify the factors related to subtypes of CRC and to explore the feasibility of using FITs in Africa.
Topics: Humans; Early Detection of Cancer; Colorectal Neoplasms; Colonoscopy; Mass Screening; Ghana
PubMed: 36820646
DOI: 10.1080/16549716.2023.2181920