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Atherosclerosis Aug 2022FH is still underdiagnosed. Cost-effectiveness results of preventive screening strategies vary. We aimed at systematically assessing the benefits, harms and cost... (Review)
Review
BACKGROUND AND AIMS
FH is still underdiagnosed. Cost-effectiveness results of preventive screening strategies vary. We aimed at systematically assessing the benefits, harms and cost effectiveness of screening for familial hypercholesterolemia (FH) and at providing an overview of the main characteristics and methodological approaches of applied decision-analytic models.
METHODS
A systematic literature search was conducted in MEDLINE, EconLit, CRD-databases and the CEA-registry for FH screening starting 2012. Earlier studies were included from a published systematic review. Results were reported in standardized semi-quantitative evidence tables. Costs were converted to current euros. Incremental cost-effectiveness ratios (ICERs) were recalculated according to economic guidelines.
RESULTS
Out of our 211 retrieved studies, eight were included in the review in addition to six studies from an earlier review. Studies were conducted in Europe (UK, The Netherlands, Spain, Poland), USA and Australia evaluating cascade (CS), opportunistic (OS), universal screening (UniS), or combinations using genetic testing, clinical criteria or combinations. Studies evaluating only CS identified strategies with an ICER of up to 37,100 EUR/quality-adjusted life-year (QALY) but some strategies were dominated depending on test combinations. UniS of newborns in combination with CS had an ICER≤15,000 EUR/QALY for sequential cholesterol-genetic screening. In other studies, UniS was dominated by OS/CS.
CONCLUSIONS
Our systematic review demonstrates the values of FH screening and provides an overview of potentially relevant screening strategies to be tested using a decision-analytic model for the respective country or region. Future research is needed on the transferability of results to other countries and modeling spillover effects to newborns.
Topics: Cost-Benefit Analysis; Genetic Testing; Humans; Hyperlipoproteinemia Type II; Infant, Newborn; Mass Screening; Quality-Adjusted Life Years
PubMed: 35870306
DOI: 10.1016/j.atherosclerosis.2022.06.1011 -
Genetics in Medicine : Official Journal... Jun 2022Interventions that decrease barriers and improve clinical processes can increase patient access to guideline-recommended cancer genetics services. We sought to identify... (Review)
Review
PURPOSE
Interventions that decrease barriers and improve clinical processes can increase patient access to guideline-recommended cancer genetics services. We sought to identify and describe interventions to improve patient receipt of guideline-recommended cancer genetics services in the United States.
METHODS
We performed a comprehensive search in Ovid MEDLINE and Embase, Scopus, and Web of Science from January 1, 2000 to February 12, 2020. Eligible articles reported interventions to improve the identification, referral, genetic counseling (GC), and genetic testing (GT) of patients in the United States. We independently screened titles and abstracts and reviewed full-text articles. Data were synthesized by grouping articles by clinical process.
RESULTS
Of 44 included articles, 17 targeted identification of eligible patients, 14 targeted referral, 15 targeted GC, and 16 targeted GT. Patient identification interventions included universal tumor testing and screening of medical/family history. Referral interventions included medical record system adaptations, standardizing processes, and provider notifications. GC interventions included supplemental patient education, integrated GC within oncology clinics, appointment coordination, and alternative service delivery models. One article directly targeted the GT process by implementing provider-coordinated testing.
CONCLUSION
This scoping review identified and described interventions to improve US patients' access to and receipt of guideline-recommended cancer genetics services.
Topics: Delivery of Health Care; Genetic Counseling; Genetic Testing; Humans; Mass Screening; Neoplasms; United States
PubMed: 35389342
DOI: 10.1016/j.gim.2022.03.002 -
BMJ Open Apr 2022To systematically synthesise available evidence on the nature and effectiveness of interventions for improving timely diagnosis of breast and cervical cancers in low and...
OBJECTIVES
To systematically synthesise available evidence on the nature and effectiveness of interventions for improving timely diagnosis of breast and cervical cancers in low and middle-income countries (LMICs).
DESIGN
A systematic review of published evidence. The review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses.
DATA SOURCES
A comprehensive search of published literature was conducted. In addition, relevant grey literature sources and bibliographical references of included studies were searched for potentially eligible evidence.
STUDY SELECTION
Studies published between January 2010 and November 2020 were eligible for inclusion. To be eligible, studies had to report on interventions/strategies targeted at women, the general public or healthcare workers, aimed at improving the timely diagnosis of breast and/or cervical cancers in LMIC settings.
DATA EXTRACTION AND SYNTHESIS
Literature search, screening, study selection, data extraction and quality appraisal were conducted by two independent reviewers. Evidence was synthesised and reported using a global taxonomy framework for early cancer diagnosis.
RESULTS
From the total of 10 593 records identified, 21 studies conducted across 20 LMICs were included in this review. Most of the included studies (16/21) focused primarily on interventions addressing breast cancers; two focused on cervical cancer while the rest examined multiple cancer types. Reported interventions targeted healthcare workers (12); women and adolescent girls (7) and both women and healthcare workers (3). Eight studies reported on interventions addressing access delays; seven focused on interventions addressing diagnostic delays; two reported on interventions targeted at addressing both access and diagnostic delays, and four studies assessed interventions addressing access, diagnostic and treatment delays. While most interventions were demonstrated to be feasible and effective, many of the reported outcome measures are of limited clinical relevance to diagnostic timeliness.
CONCLUSIONS
Though limited, evidence suggests that interventions aimed at addressing barriers to timely diagnosis of breast and cervical cancer are feasible in resource-limited contexts. Future interventions need to address clinically relevant measures to better assess efficacy of interventions.
PROSPERO REGISTRATION NUMBER
CRD42020177232.
Topics: Adolescent; Developing Countries; Female; Humans; Income; Mass Screening; Poverty; Uterine Cervical Neoplasms
PubMed: 35470184
DOI: 10.1136/bmjopen-2021-054501 -
JAMA Oct 2022Depression, suicidal ideation, and self-harm behaviors in youth are associated with functional impairment and suicide.
IMPORTANCE
Depression, suicidal ideation, and self-harm behaviors in youth are associated with functional impairment and suicide.
OBJECTIVE
To review the evidence on screening for depression or suicide risk in children and adolescents to inform the US Preventive Services Task Force (USPSTF).
DATA SOURCES
PubMed, Cochrane Library, PsycINFO, CINAHL, and trial registries through July 19, 2021; references, experts, and surveillance through June 1, 2022.
STUDY SELECTION
English-language, randomized clinical trials (RCTs) of screening for depression or suicide risk; diagnostic test accuracy studies; RCTs of psychotherapy and first-line pharmacotherapy; RCTs, observational studies, and systematic reviews reporting harms.
DATA EXTRACTION AND SYNTHESIS
Two reviewers assessed titles/abstracts, full-text articles, and study quality and extracted data; when at least 3 similar studies were available, meta-analyses were conducted.
MAIN OUTCOMES AND MEASURES
Test accuracy, symptoms, response, remission, loss of diagnosis, mortality, functioning, suicide-related events, and adverse events.
RESULTS
Twenty-one studies (N = 5433) were included for depression and 19 studies (N = 6290) for suicide risk. For depression, no studies reported on the direct effects of screening on health outcomes, and 7 studies (n = 3281) reported sensitivity of screening instruments ranging from 0.59 to 0.94 and specificity from 0.38 to 0.96. Depression treatment with psychotherapy was associated with improved symptoms (Beck Depression Inventory pooled standardized mean difference, -0.58 [95% CI, -0.83 to -0.34]; n = 471; 4 studies; and Hamilton Depression Scale pooled mean difference, -2.25 [95% CI, -4.09 to -0.41]; n = 262; 3 studies) clinical response (3 studies with statistically significant results using varying thresholds), and loss of diagnosis (relative risk, 1.73 [95% CI, 1.00 to 3.00; n = 395; 4 studies). Pharmacotherapy was associated with improvement on symptoms (Children's Depression Rating Scale-Revised mean difference, -3.76 [95% CI, -5.95 to -1.57; n = 793; 3 studies), remission (relative risk, 1.20 [95% CI, 1.00 to 1.45]; n = 793; 3 studies) and functioning (Children's Global Assessment Scale pooled mean difference, 2.60 (95% CI, 0.78 to 4.42; n = 793; 3 studies). Other outcomes were not statistically significantly different. Differences in suicide-related outcomes and adverse events for pharmacotherapy when compared with placebo were not statistically significant. For suicide risk, no studies reported on the direct benefits of screening on health outcomes, and 2 RCTs (n = 2675) reported no harms of screening. One study (n = 581) reported on sensitivity of screening, ranging from 0.87 to 0.91; specificity was 0.60. Sixteen RCTs (n = 3034) reported on suicide risk interventions. Interventions were associated with lower scores for the Beck Hopelessness Scale (pooled mean difference, -2.35 [95% CI, -4.06 to -0.65]; n = 644; 4 RCTs). Findings for other suicide-related outcomes were mixed or not statistically significantly different.
CONCLUSION AND RELEVANCE
Indirect evidence suggested that some screening instruments were reasonably accurate for detecting depression. Psychotherapy and pharmacotherapy were associated with some benefits and no statistically significant harms for depression, but the evidence was limited for suicide risk screening instruments and interventions.
Topics: Child; Humans; Adolescent; Depression; Mass Screening; Advisory Committees; Preventive Health Services; Suicide Prevention
PubMed: 36219399
DOI: 10.1001/jama.2022.16310 -
International Journal of Environmental... Jan 2022Hereditary cancer syndromes are inherited pathogenic genetic variants that significantly increase the risk of developing cancer. When individuals become aware of their... (Review)
Review
Hereditary cancer syndromes are inherited pathogenic genetic variants that significantly increase the risk of developing cancer. When individuals become aware of their increased probability of having cancer, the whole family is affected by this new reality and needs to adjust. However, adjustment to hereditary cancer syndromes has been mainly studied at an individual level, and research about familial adjustment remains dispersed and disorganized. To overcome this gap, this review aims to understand how families adjust to genetic testing and risk management, and to what extent the family's adjustment influences the psychological response and risk management behaviors of mutation carriers. We conducted searches on the PubMed/Med Line, PsycInfo, SCOPUS, and Google Scholar databases and used the Mixed Methods Appraisal Tool (MMAT-v2018) to assess the methodological quality of each selected study. Thirty studies met the inclusion criteria. Most results highlighted the interdependent nature of adjustment of pathogenic variant carriers and their families. The way carriers adjust to the syndrome is highly dependent on family functioning and related to how family members react to the new genetic information, particularly partners and siblings. Couples who share their worries and communicate openly about cancer risk present a better long-term adjustment than couples who use protective buffering (not talking about it to avoid disturbing the partner) or emotional distancing. Parents need help dealing with disclosing genetic information to their children. These findings reinforce the importance of adopting a family-centered approach in the context of genetic counseling and the necessity of involving family members in research.
Topics: Child; Family; Genetic Counseling; Genetic Testing; Humans; Neoplastic Syndromes, Hereditary; Risk
PubMed: 35162625
DOI: 10.3390/ijerph19031603 -
Human Reproduction (Oxford, England) May 2019Which genes are confidently linked to human monogenic male infertility?
STUDY QUESTION
Which genes are confidently linked to human monogenic male infertility?
SUMMARY ANSWER
Our systematic literature search and clinical validity assessment reveals that a total of 78 genes are currently confidently linked to 92 human male infertility phenotypes.
WHAT IS KNOWN ALREADY
The discovery of novel male infertility genes is rapidly accelerating with the availability of next-generating sequencing methods, but the quality of evidence for gene-disease relationships varies greatly. In order to improve genetic research, diagnostics and counseling, there is a need for an evidence-based overview of the currently known genes.
STUDY DESIGN, SIZE, DURATION
We performed a systematic literature search and evidence assessment for all publications in Pubmed until December 2018 covering genetic causes of male infertility and/or defective male genitourinary development.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Two independent reviewers conducted the literature search and included papers on the monogenic causes of human male infertility and excluded papers on genetic association or risk factors, karyotype anomalies and/or copy number variations affecting multiple genes. Next, the quality and the extent of all evidence supporting selected genes was weighed by a standardized scoring method and used to determine the clinical validity of each gene-disease relationship as expressed by the following six categories: no evidence, limited, moderate, strong, definitive or unable to classify.
MAIN RESULTS AND THE ROLE OF CHANCE
From a total of 23 526 records, we included 1337 publications about monogenic causes of male infertility leading to a list of 521 gene-disease relationships. The clinical validity of these gene-disease relationships varied widely and ranged from definitive (n = 38) to strong (n = 22), moderate (n = 32), limited (n = 93) or no evidence (n = 160). A total of 176 gene-disease relationships could not be classified because our scoring method was not suitable.
LARGE SCALE DATA
Not applicable.
LIMITATIONS, REASONS FOR CAUTION
Our literature search was limited to Pubmed.
WIDER IMPLICATIONS OF THE FINDINGS
The comprehensive overview will aid researchers and clinicians in the field to establish gene lists for diagnostic screening using validated gene-disease criteria and help to identify gaps in our knowledge of male infertility. For future studies, the authors discuss the relevant and important international guidelines regarding research related to gene discovery and provide specific recommendations for the field of male infertility.
STUDY FUNDING/COMPETING INTEREST(S)
This work was supported by a VICI grant from The Netherlands Organization for Scientific Research (918-15-667 to J.A.V.), the Royal Society, and Wolfson Foundation (WM160091 to J.A.V.) as well as an investigator award in science from the Wellcome Trust (209451 to J.A.V.).
PROSPERO REGISTRATION NUMBER
None.
Topics: Biomarkers; DNA Copy Number Variations; DNA Mutational Analysis; Genetic Testing; High-Throughput Nucleotide Sequencing; Humans; Infertility, Male; Male; Reproducibility of Results; Exome Sequencing
PubMed: 30865283
DOI: 10.1093/humrep/dez022 -
Genetics in Medicine : Official Journal... Feb 2022Understanding the value of genetic screening and testing for monogenic disorders requires high-quality, methodologically robust economic evaluations. This systematic... (Review)
Review
PURPOSE
Understanding the value of genetic screening and testing for monogenic disorders requires high-quality, methodologically robust economic evaluations. This systematic review sought to assess the methodological quality among such studies and examined opportunities for improvement.
METHODS
We searched PubMed, Cochrane, Embase, and Web of Science for economic evaluations of genetic screening/testing (2013-2019). Methodological rigor and adherence to best practices were systematically assessed using the British Medical Journal checklist.
RESULTS
Across the 47 identified studies, there were substantial variations in modeling approaches, reporting detail, and sophistication. Models ranged from simple decision trees to individual-level microsimulations that compared between 2 and >20 alternative interventions. Many studies failed to report sufficient detail to enable replication or did not justify modeling assumptions, especially for costing methods and utility values. Meta-analyses, systematic reviews, or calibration were rarely used to derive parameter estimates. Nearly all studies conducted some sensitivity analysis, and more sophisticated studies implemented probabilistic sensitivity/uncertainty analysis, threshold analysis, and value of information analysis.
CONCLUSION
We describe a heterogeneous body of work and present recommendations and exemplar studies across the methodological domains of (1) perspective, scope, and parameter selection; (2) use of uncertainty/sensitivity analyses; and (3) reporting transparency for improvement in the economic evaluation of genetic screening/testing.
Topics: Cost-Benefit Analysis; Genetic Testing; Humans
PubMed: 34906467
DOI: 10.1016/j.gim.2021.10.008 -
The American Journal of Emergency... Sep 2022In the emergency department, delirium associated with serious adverse outcomes is common in geriatric patients. We performed a meta-analysis and estimated the prevalence... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In the emergency department, delirium associated with serious adverse outcomes is common in geriatric patients. We performed a meta-analysis and estimated the prevalence of delirium and its related factors among geriatric emergency department patients.
METHODS
PubMed, Embase, Web of Science, Cochrane Library, CINAHL, PsycINFO, and CBM databases were searched before November 7, 2021. The random-effects model was used to estimate the prevalence of delirium. In addition, subgroup analyses were performed based on continent or region, publication year, age, sample size, and diagnostic criteria or assessment methods.
RESULTS
30 studies involving 19,534 geriatric patients in the emergency department were included. The overall pooled crude prevalence estimate of delirium was 15.2% [95% confidence interval (CI) 12.5-18.0%]. Subgroup analyses revealed that the region, publication year, age, sample size, and delirium assessment methods were significantly correlated with the prevalence of delirium. Meta-regression analysis showed that the publication year was positively, while the sample size was negatively associated with the pooled prevalence of delirium.
CONCLUSION
In the emergency department, delirium is common in geriatric patients. We should pay specific attention to delirium screening, prevention, and treatment in geriatric patients. Overall appropriate interventions should be utilized to reduce the occurrence of delirium and the adverse outcomes.
Topics: Aged; Delirium; Emergency Service, Hospital; Humans; Mass Screening; Prevalence
PubMed: 35841845
DOI: 10.1016/j.ajem.2022.05.058 -
Journal of Medical Internet Research Dec 2015Direct-to-consumer genetic tests (DTC-GT) are easily purchased through the Internet, independent of a physician referral or approval for testing, allowing the retrieval... (Review)
Review
BACKGROUND
Direct-to-consumer genetic tests (DTC-GT) are easily purchased through the Internet, independent of a physician referral or approval for testing, allowing the retrieval of genetic information outside the clinical context. There is a broad debate about the testing validity, their impact on individuals, and what people know and perceive about them.
OBJECTIVE
The aim of this review was to collect evidence on DTC-GT from a comprehensive perspective that unravels the complexity of the phenomenon.
METHODS
A systematic search was carried out through PubMed, Web of Knowledge, and Embase, in addition to Google Scholar according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist with the key term "Direct-to-consumer genetic test."
RESULTS
In the final sample, 118 articles were identified. Articles were summarized in five categories according to their focus on (1) knowledge of, attitude toward use of, and perception of DTC-GT (n=37), (2) the impact of genetic risk information on users (n=37), (3) the opinion of health professionals (n=20), (4) the content of websites selling DTC-GT (n=16), and (5) the scientific evidence and clinical utility of the tests (n=14). Most of the articles analyzed the attitude, knowledge, and perception of DTC-GT, highlighting an interest in using DTC-GT, along with the need for a health care professional to help interpret the results. The articles investigating the content analysis of the websites selling these tests are in agreement that the information provided by the companies about genetic testing is not completely comprehensive for the consumer. Given that risk information can modify consumers' health behavior, there are surprisingly few studies carried out on actual consumers and they do not confirm the overall concerns on the possible impact of DTC-GT. Data from studies that investigate the quality of the tests offered confirm that they are not informative, have little predictive power, and do not measure genetic risk appropriately.
CONCLUSIONS
The impact of DTC-GT on consumers' health perceptions and behaviors is an emerging concern. However, negative effects on consumers or health benefits have yet to be observed. Nevertheless, since the online market of DTC-GT is expected to grow, it is important to remain aware of a possible impact.
Topics: Adult; Direct-To-Consumer Screening and Testing; Genetic Testing; Humans; Internet; Male
PubMed: 26677835
DOI: 10.2196/jmir.4378 -
Social Science & Medicine (1982) Dec 2022Health economic assessments are used to determine whether the resources needed to generate net benefit from a screening programme, driven by multiple complex benefits...
Benefits and harms adopted by health economic assessments evaluating antenatal and newborn screening programmes in OECD countries: A systematic review of 336 articles and reports.
BACKGROUND
Health economic assessments are used to determine whether the resources needed to generate net benefit from a screening programme, driven by multiple complex benefits and harms, are justifiable. We systematically identified the benefits and harms incorporated within economic assessments evaluating antenatal and newborn screening programmes.
METHODS
For this systematic review and thematic analysis, we searched the published and grey literature from January 2000 to January 2021. Studies that included an economic evaluation of an antenatal or newborn screening programme in an OECD country were eligible. We identified benefits and harms using an integrative descriptive analysis, and illustrated a thematic framework. (Systematic review registration PROSPERO, CRD42020165236).
FINDINGS
The searches identified 52,244 articles and reports and 336 (242 antenatal and 95 newborn) were included. Eighty-six subthemes grouped into seven themes were identified: 1) diagnosis of screened for condition, 2) life years and health status adjustments, 3) treatment, 4) long-term costs, 5) overdiagnosis, 6) pregnancy loss, and 7) spillover effects on family members. Diagnosis of screened for condition (115 studies, 47.5%), life-years and health status adjustments (90 studies, 37.2%) and treatment (88 studies, 36.4%) accounted for most of the benefits and harms evaluating antenatal screening. The same themes accounted for most of the benefits and harms included in studies assessing newborn screening. Overdiagnosis and spillover effects tended to be ignored.
INTERPRETATION
Our proposed framework can be used to guide the development of future health economic assessments evaluating antenatal and newborn screening programmes, to prevent exclusion of important potential benefits and harms.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Cost-Benefit Analysis; Neonatal Screening; Organisation for Economic Co-Operation and Development; Prenatal Diagnosis
PubMed: 36272385
DOI: 10.1016/j.socscimed.2022.115428