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Genetics in Medicine : Official Journal... Jun 2024The aim of this study is to identify likely pathogenic (LP) and pathogenic (P) genetic results for autism that can be returned to participants in SPARK...
PURPOSE
The aim of this study is to identify likely pathogenic (LP) and pathogenic (P) genetic results for autism that can be returned to participants in SPARK (SPARKforAutism.org): a large recontactable cohort of people with autism in the United States. We also describe the process to return these clinically confirmed genetic findings.
METHODS
We present results from microarray genotyping and exome sequencing (ES) of 21,532 individuals with autism and 17,785 of their parents. We returned LP and P (American College of Medical genetics (ACMG) criteria) copy number variants (CNVs), chromosomal aneuploidies, and variants in genes with strong evidence of association with autism and intellectual disability.
RESULTS
We identified 1903 'returnable' LP/P variants in 1861 individuals with autism (8.6%). 89.5% of these variants were not known to participants. The diagnostic genetic result was returned to 589 participants (53% of those contacted). Features associated with a higher probability of having a returnable result include cognitive and medically complex features, being female, being White (versus non-White) and being diagnosed more than 20 years ago. We also find results among autistics across the spectrum, as well as in transmitting parents with neuropsychiatric features but no autism diagnosis.
CONCLUSION
SPARK offers an opportunity to assess returnable results among autistic people who have not been ascertained clinically. SPARK also provides practical experience returning genetic results for a behavioral condition at a large scale.
PubMed: 38958063
DOI: 10.1016/j.gim.2024.101202 -
Journal of the American Heart... Jul 2024Coronary atherosclerosis detected by imaging is a marker of elevated cardiovascular risk. However, imaging involves large resources and exposure to radiation. The aim...
BACKGROUND
Coronary atherosclerosis detected by imaging is a marker of elevated cardiovascular risk. However, imaging involves large resources and exposure to radiation. The aim was, therefore, to test whether nonimaging data, specifically data that can be self-reported, could be used to identify individuals with moderate to severe coronary atherosclerosis.
METHODS AND RESULTS
We used data from the population-based SCAPIS (Swedish CardioPulmonary BioImage Study) in individuals with coronary computed tomography angiography (n=25 182) and coronary artery calcification score (n=28 701), aged 50 to 64 years without previous ischemic heart disease. We developed a risk prediction tool using variables that could be assessed from home (self-report tool). For comparison, we also developed a tool using variables from laboratory tests, physical examinations, and self-report (clinical tool) and evaluated both models using receiver operating characteristic curve analysis, external validation, and benchmarked against factors in the pooled cohort equation. The self-report tool (n=14 variables) and the clinical tool (n=23 variables) showed high-to-excellent discriminative ability to identify a segment involvement score ≥4 (area under the curve 0.79 and 0.80, respectively) and significantly better than the pooled cohort equation (area under the curve 0.76, <0.001). The tools showed a larger net benefit in clinical decision-making at relevant threshold probabilities. The self-report tool identified 65% of all individuals with a segment involvement score ≥4 in the top 30% of the highest-risk individuals. Tools developed for coronary artery calcification score ≥100 performed similarly.
CONCLUSIONS
We have developed a self-report tool that effectively identifies individuals with moderate to severe coronary atherosclerosis. The self-report tool may serve as prescreening tool toward a cost-effective computed tomography-based screening program for high-risk individuals.
PubMed: 38958022
DOI: 10.1161/JAHA.124.034603 -
Health Services Research Jul 2024To examine changes in late- versus early-stage diagnosis of cancer associated with the introduction of mandatory Medicaid managed care (MMC) in Pennsylvania.
OBJECTIVE
To examine changes in late- versus early-stage diagnosis of cancer associated with the introduction of mandatory Medicaid managed care (MMC) in Pennsylvania.
DATA SOURCES AND STUDY SETTING
We analyzed data from the Pennsylvania cancer registry (2010-2018) for adult Medicaid beneficiaries aged 21-64 newly diagnosed with a solid tumor. To ascertain Medicaid and managed care status around diagnosis, we linked the cancer registry to statewide hospital-based facility records collected by an independent state agency (Pennsylvania Health Care Cost Containment Council).
STUDY DESIGN
We leveraged a natural experiment arising from county-level variation in mandatory MMC in Pennsylvania. Using a stacked difference-in-differences design, we compared changes in the probability of late-stage cancer diagnosis among those residing in counties that newly transitioned to mandatory managed care to contemporaneous changes among those in counties with mature MMC programs.
DATA COLLECTION/EXTRACTION METHODS
N/A.
PRINCIPAL FINDINGS
Mandatory MMC was associated with a reduced probability of late-stage cancer diagnosis (-3.9 percentage points; 95% CI: -7.2, -0.5; p = 0.02), particularly for screening-amenable cancers (-5.5 percentage points; 95% CI: -10.4, -0.6; p = 0.03). We found no significant changes in late-stage diagnosis among non-screening amenable cancers.
CONCLUSIONS
In Pennsylvania, the implementation of mandatory MMC for adult Medicaid beneficiaries was associated with earlier stage of diagnosis among newly diagnosed cancer patients with Medicaid, especially those diagnosed with screening-amenable cancers. Considering that over half of the sample was diagnosed with late-stage cancer even after the transition to mandatory MMC, Medicaid programs and managed care organizations should continue to carefully monitor receipt of cancer screening and design strategies to reduce barriers to guideline-concordant screening or diagnostic procedures.
PubMed: 38958003
DOI: 10.1111/1475-6773.14348 -
American Journal of Epidemiology Jul 2024Non-benzodiazepine hypnotics ( "Z-drugs") are prescribed for insomnia, but might increase risk of motor vehicle crash (MVC) among older adults through prolonged...
Non-benzodiazepine hypnotics ( "Z-drugs") are prescribed for insomnia, but might increase risk of motor vehicle crash (MVC) among older adults through prolonged drowsiness and delayed reaction times. We estimated the effect of initiating Z-drug treatment on the 12-week risk of MVC in a sequential target trial emulation. After linking New Jersey driver licensing and police-reported MVC data to Medicare claims, we emulated a new target trial each week (July 1, 2007 - October 7, 2017) in which Medicare fee-for-service beneficiaries were classified as Z-drug-treated or untreated at baseline and followed for an MVC. We used inverse probability of treatment and censoring weighted pooled logistic regression models to estimate risk ratios (RR) and risk differences with 95% bootstrap confidence limits (CLs). There were 257,554 person-trials, of which 103,371 were Z-drug-treated and 154,183 untreated, giving rise to 976 and 1,249 MVCs, respectively. The intention-to-treat RR was 1.06 (95%CLs 0.95, 1.16). For the per-protocol estimand, there were 800 MVCs and 1,241 MVCs among treated and untreated person-trials, respectively, suggesting a reduced MVC risk (RR 0.83 [95%CLs 0.74, 0.92]) with sustained Z-drug treatment. Z-drugs should be prescribed to older patients judiciously but not withheld entirely over concerns about MVC risk.
PubMed: 38957996
DOI: 10.1093/aje/kwae168 -
Headache Jul 2024The small molecule calcitonin gene-related peptide receptor antagonists (gepants) are the only drug class with medicines indicated for both the acute and preventive...
The small molecule calcitonin gene-related peptide receptor antagonists (gepants) are the only drug class with medicines indicated for both the acute and preventive treatment of migraine. Given this dual capacity to both treat and prevent, along with their favorable tolerability profiles and lack of an association with medication-overuse headache, headache specialists have begun to use gepants in ways that transcend the traditional categories of acute and preventive treatment. One approach, called situational prevention, directs patients to treat during the interictal phase, before symptoms develop, in situations of increased risk for migraine attacks. Herein, we present three patients to illustrate scenarios of gepant use for situational prevention. In each case, a gepant was started in anticipation of a period of increased headache probability (vulnerability) and continued for a duration of 1 day to 5 consecutive days. Although this approach may expose patients to medication when headache may not have developed, the tolerability and safety profile and preventive effect of gepants may represent a feasible approach for some patients. Situational prevention is an emerging strategy for managing migraine before symptoms develop in individuals who can identify periods when the probability of headache is high. This paper is intended to increase awareness of this strategy and stimulate future randomized, placebo-controlled trials to rigorously assess this strategy.
PubMed: 38957980
DOI: 10.1111/head.14775 -
British Journal of Clinical Pharmacology Jul 2024The management of patients treated with direct oral anticoagulants (DOACs) during hospitalization is a common challenge in clinical practice. Although bridging is...
AIMS
The management of patients treated with direct oral anticoagulants (DOACs) during hospitalization is a common challenge in clinical practice. Although bridging is generally not recommended, too often DOACs are switched to parenteral therapy with low molecular weight heparins. Our objectives were to update a local guideline for perioperative DOAC management and to develop a guideline for the anticoagulation management in non-surgical patients regarding temporary DOAC discontinuation.
METHODS
We executed a two-step modified Delphi study in a 1000-bed university hospital in Belgium. The Delphi questionnaires were developed based on a literature review and a telephone survey of prescribers. Two expert panels were established: one dedicated to perioperative DOAC management and the other to DOAC management in non-surgical patients. Both panels completed two rounds, commencing with an individual and online round, followed by a face-to-face group session.
RESULTS
After the two-round Delphi process, the updated perioperative guideline on DOAC management included reasons for delaying the resumption of DOACs following surgery, such as oral intake not possible, the probability of re-intervention within 3 days, and insufficient haemostasis (e.g. active clinically significant haematoma, haemorrhagic drains or wounds). Furthermore, a guideline for non-surgical hospitalized patients was developed, outlining possible reasons for interrupting DOAC therapy. Both guidelines offer clear anticoagulation therapy strategies corresponding to the identified scenarios.
CONCLUSIONS
We have updated and developed guidelines for DOAC management in surgical and non-surgical patients during hospitalization, which aim to support prescribers and to enhance targeted prescription review by hospital pharmacists.
PubMed: 38957976
DOI: 10.1111/bcp.16159 -
Foodborne Pathogens and Disease Jul 2024Despite heavy contamination of the Bogotá River with domestic and industrial waste, it remains vital for various purposes, including agricultural use at La Ramada...
Despite heavy contamination of the Bogotá River with domestic and industrial waste, it remains vital for various purposes, including agricultural use at La Ramada Irrigation District. There are important concerns regarding pathogen concentrations in irrigation water at La Ramada, including the presence of antibiotic-resistant spp. This study aimed to estimate the risk of -related illness from consuming lettuce irrigated with Bogotá River water at La Ramada. We collected lettuce samples from 4 different sites, all irrigated with water from La Ramada. The methodology involved a process to detach spp. from lettuce leaves, quantification through plate counts on SS agar, and establishment of antibiotic-resistant bacteria concentrations through growth on media supplemented with ampicillin or ciprofloxacin. The results showed concentrations of spp. of 10,10, and 10 CFU/g lettuce at sites 1, 2, and 3, respectively, and ampicillin-resistant spp. of 10, 10, and 10 CFU/g lettuce at sites 1, 2, and 3, respectively. No colonies were obtained from lettuce samples collected from site 4. Notably, we detected no isolates resistant to ciprofloxacin at any of the sites. spp. concentrations varied greatly among sampling sites. spp. concentrations were used to predict the daily probability of illness, with a probability of 0.59 (0.33 to 0.78, CI 95%) for spp. and 0.3 (0.03 to 0.53, CI 95%) for ampicillin-resistant spp.
PubMed: 38957952
DOI: 10.1089/fpd.2024.0015 -
Frontiers in Psychology 2024Psychological well-being (PWB) facilitates good health. Few studies have taken into consideration gender and how it can affect PWB within a sociocultural context. This...
BACKGROUND
Psychological well-being (PWB) facilitates good health. Few studies have taken into consideration gender and how it can affect PWB within a sociocultural context. This study aims to determine if relationships between social, health, behavioral, and socioeconomic factors on PWB among older Taiwanese adults are affected by gender.
METHODS
Data were obtained from the 2016 Taiwan Mental Health Survey. A representative sample, of 2,286 individuals, was created using multistage proportional probability. Participants were interviewed at their homes using a structured questionnaire. Inclusion criteria were Taiwanese citizenship, age ≥ 55 years, and the ability to provide informed consent. Participants 65 years and above were selected for the study sample = 1,533. An 18-item version of Ryff's PWB scale was used to determine PWB. The median value was used to categorize low and high PWB. Logistic regression analyses were used to examine predictors of PWB stratified by gender.
RESULTS
Chronic disease, unemployment, and financial dependence negatively impacted men's PWB. Satisfaction with living environment and family relationships positively impacted women's PWB. Unique characteristics of older men, women, and culture account for this.
CONCLUSION
Gender-specific interventions aimed at promoting PWB in older adults are needed. Recommendations include educational programs, social support workshops, and community engagement initiatives.
PubMed: 38957879
DOI: 10.3389/fpsyg.2024.1392007 -
Ghana Medical Journal Dec 2023To determine the angiographic severity of coronary artery disease (CAD) and assess the influence of major cardiovascular risk factors (CVRF).
OBJECTIVE
To determine the angiographic severity of coronary artery disease (CAD) and assess the influence of major cardiovascular risk factors (CVRF).
STUDY DESIGN
a cross-sectional, hospital-based study.
SETTING
the catheterisation laboratory of the National Cardiothoracic Centre, Accra, Ghana.
PARTICIPANTS
for 12 months, consecutive patients admitted for coronary angiography were assessed for the presence of CVRFs. Those with significant CAD after angiography were recruited into the study.
INTERVENTION
The patient's angiograms were analysed, and the CAD severity was obtained using the SYNTAX scoring criteria.
MAIN OUTCOME MEASURE
The lesion overall severity (SYNTAX) score and the relationship with CVRFs present.
RESULTS
out of the 169 patients that had coronary angiography, 78 had significant CAD. The mean SYNTAX score was 20.18 (SD= 10.68), with a significantly higher value in dyslipidaemic patients (p < 0.001). Pearson's correlation between the score and BMI was weak (r= 0.256, p= 0.034). The occurrence of high SYNTAX score lesions in about 18% of the population was significantly associated with hypertension (OR= 1.304, 95% CI [1.13-1.50]; p= 0.017) dyslipidaemia (OR= 5.636, 95% CI [1.17-27.23]; p= 0.019), and obesity (OR= 3.960, 95% CI [1.18-13.34]; p= 0.021). However, after adjusting for confounding factors, only dyslipidaemia significantly influenced its occurrence (aOR= 5.256, 95% CI [1.03-26.96]; p= 0.047).
CONCLUSION
Even though the most severe form of CAD was found in about one-fifth of the study population, its occurrence was strongly influenced by the presence of dyslipidaemia.
FUNDING
None.
Topics: Humans; Coronary Artery Disease; Male; Female; Cross-Sectional Studies; Coronary Angiography; Middle Aged; Severity of Illness Index; Heart Disease Risk Factors; Aged; Hypertension; Dyslipidemias; Ghana; Adult; Risk Factors
PubMed: 38957846
DOI: 10.4314/gmj.v57i4.2 -
Ecology and Evolution Jul 2024Quantifying the cost-effectiveness of alternative sampling methods is crucial for efficient biodiversity monitoring and detection of population trends. In this study, we...
Quantifying the cost-effectiveness of alternative sampling methods is crucial for efficient biodiversity monitoring and detection of population trends. In this study, we compared the cost-effectiveness of three novel sampling methods for detecting changes in koala () occupancy: thermal drones, passive acoustic recorders and camera trapping. Specifically, we fitted single-season occupancy-detection models to data recorded from 46 sites in eight bioregions of New South Wales, Australia, between 2018 and 2022. We explored the effect of weather variables on daily detection probability for each method and, using these estimates, calculated the statistical power to detect 30%, 50% and 80% declines in koala occupancy. We calculated power for different combinations of sites (1-200) and repeat surveys (2-40) and developed a cost model that found the cheapest survey design that achieved 80% power to detect change. On average, detectability of koalas was highest with one 24-h period of acoustic surveys (0.32, 95% CI's: 0.26, 0.39) compared to a 25-ha flight of drone surveys (0.28, 95% 0.15, 0.48) or a 24-h period of camera trapping consisting of six cameras (0.019, 95% CI's: 0.014, 0.025). We found a negative quadratic relationship between detection probability and air temperature for all three methods. Our power and cost analysis suggested that 148 sites surveyed with acoustic recorders deployed for 14 days would be the cheapest method to sufficiently detect a 30% decline in occupancy with 80% power. We recommend passive acoustic recorders as the most efficient sampling method for monitoring koala occupancy compared to cameras or drones. Further comparative studies are needed to compare the relative effectiveness of these methods and others when the monitoring objective is to detect change in koala abundance over time.
PubMed: 38957698
DOI: 10.1002/ece3.11659