Association Between Insomnia, Stress Events, and Other Psychosocial Factors and Incident Atrial Fibrillation in Postmenopausal Women: Insights From the Women's Health Initiative.

Background The association between psychosocial factors and atrial fibrillation (AF) is poorly understood. Methods and Results Postmenopausal women from the Women's Health Initiative were retrospectively analyzed to identify incident AF in relation to a panel of validated psychosocial exposure variables, as assessed by multivariable Cox proportional hazard regression and hierarchical cluster analysis. Among the 83 736 women included, the average age was 63.9±7.0 years. Over an average of 10.5±6.2 years follow-up, there were 23 954 cases of incident AF. Hierarchical cluster analysis generated 2 clusters of highly correlated psychosocial variables: the Stress Cluster included stressful life events, depressive symptoms, and insomnia, and the Strain Cluster included optimism, social support, social strain, cynical hostility, and emotional expressiveness. Incident AF was associated with higher values in the Stress Cluster (hazard ratio [HR], 1.07 per unit cluster score [95% CI, 1.05-1.09]) and the Strain Cluster (HR, 1.03 per unit cluster score [95% CI, 1.00-1.05]). Of the 8 individual psychosocial predictors that were tested, insomnia (HR, 1.04 [95% CI, 1.03-1.06]) and stressful life events (HR, 1.02 [95% CI, 1.01-1.04]) were most strongly associated with increased incidence of AF in Cox regression analysis after multivariate adjustment. Subgroup analyses showed that the Strain Cluster was more strongly associated with incident AF in those with lower traditional AF risks (P for interaction=0.02) as determined by the cohorts for heart and aging research in genomic epidemiology for atrial fibrillation score. Conclusions Among postmenopausal women, 2 clusters of psychosocial stressors were found to be significantly associated with incident AF. Further research is needed to validate these associations.

Risk factors associated with adolescent suicidality before and during the COVID-19 pandemic.

OBJECTIVE: To evaluate the impact of the coronavirus disease 2019 pandemic on youth suicidal behaviors. METHOD: This study examined two national surveys of high school students, the 2019 Youth Risk Behavior Survey (YRBS) and the 2021 Adolescent Behaviors and Experiences Survey (ABES). RESULTS: The YRBS 2019 had 13,677 entries: 18.6% (17.5-19.8) (weighted percentage and 95% confidence intervals [CIs]) of youth had suicidal ideation (SI) and 8.9% (7.9-10.0) had at least one suicide attempt (SA). The ABES 2021 had 7705 entries: 19.9% (18.0-22.0) of youth had SI and 9.0% (7.7-10.5) had SA. In ABES 2021, both the percentage of youth with SI or SA was highest at age 14, at 21.8% (16.9-27.8) and 10.0% (6.6-14.8), respectively. The top factors associated with both SI and SA were parental abuse, sexual violence, illicit drug use, misuse of prescription pain medicine, and being bullied electronically. Screen time ≥3 h per day (not including schoolwork) was associated with a lower risk of SA (odds ratio [OR] 0.553, 95% CI: 0.382-0.799), but not SI (OR 1.011, 0.760-1.344). CONCLUSIONS: Earlier onset of adolescent suicidality, at age 14, was noted during the pandemic. The association of higher non-school work-related screen time with lower SA is unexpected and warrants validation.

Clinical Correlates and Outcomes of Methamphetamine-Associated Cardiovascular Diseases in Hospitalized Patients in California.

Background Methamphetamine misuse affects 27 million people worldwide and is associated with cardiovascular disease (CVD); however, risk factors for CVD among users have not been well studied. Methods and Results We studied hospitalized patients in California, captured by the Healthcare Cost and Utilization Project database, between 2005 and 2011. We studied the association between methamphetamine use and CVD (pulmonary hypertension, heart failure, stroke, and myocardial infarction). Among 20 249 026 persons in the Healthcare Cost and Utilization Project, 66 199 used methamphetamines (median follow-up 4.58 years). Those who used were more likely younger (33 years versus 45 years), male (63.3% versus 44.4%), smoked, misused alcohol, and had depression and anxiety compared with nonusers. Methamphetamine use was associated with the development of heart failure (hazard ratio [HR], 1.53 [95% CI, 1.45-1.62]) and pulmonary hypertension (HR, 1.42 [95% CI, 1.26-1.60]). Among users, male sex (HR, 1.73 [95% CI, 1.37-2.18]) was associated with myocardial infarction. Chronic kidney disease (HR, 2.38 [95% CI, 1.74-3.25]) and hypertension (HR, 2.26 [95% CI, 2.03-2.51]) were strong risk factors for CVD among users. When compared with nonuse, methamphetamine use was associated with a 32% significant increase in CVD, alcohol abuse with a 28% increase, and cocaine use with a 47% increase in CVD. Conclusions Methamphetamine use has a similar magnitude of risk of CVD compared with alcohol and cocaine. Prevention and treatment could be focused on those with chronic kidney disease, hypertension, and mental health disorders.

Socioeconomic Burden of Rising Methamphetamine-Associated Heart Failure Hospitalizations in California From 2008 to 2018.

BACKGROUND: Methamphetamine-associated cardiomyopathy/heart failure (MethHF) is an increasingly recognized disease entity in the context of a rising methamphetamine (meth) epidemic that most severely impacts the western United States. Using heart failure (HF) hospitalization data from the Office of Statewide Health Planning and Development, this study aimed to assess trend and disease burden of MethHF in California. METHODS: Adult patients (≥18 years old) with HF as primary hospitalization diagnosis between 2008 and 2018 were included in this study. The association with Meth (MethHF) and those without (non-MethHF) were determined by meth-related International Classification of Diseases-based secondary diagnoses. Statistical significance of trends in age-adjusted rates of hospitalization per 100 000 adults were evaluated using nonparametric analysis. RESULTS: Between 2008 and 2018, 1 033 076 HF hospitalizations were identified: 42 565 were MethHF (4.12%) and 990 511 (95.88%) were non-MethHF. Age-adjusted MethHF hospitalizations per 100 000 increased by 585% from 4.1 in 2008 to 28.1 in 2018, while non-MethHF hospitalizations decreased by 6.0% from 342.3 in 2008 to 321.6 in 2018. The rate of MethHF hospitalization increase more than doubled that of a negative control group with urinary tract infection and meth-related secondary diagnoses (7.82-fold versus 3.48-fold, P<0.001). Annual inflation-adjusted hospitalization charges because of MethHF increased by 840% from $41.5 million in 2008 to $390.2 million in 2018, as compared with an 82% increase for all HF hospitalization from $3.503 billion to $6.376 billion. Patients with MethHF were significantly younger (49.64±10.06 versus 72.20±14.97 years old, P<0.001), predominantly male (79.1% versus 52.4%, P<0.001), with lower Charlson Comorbidity Index, yet they had longer length of stay, more hospitalizations per patient, and more procedures performed during their stays. CONCLUSIONS: MethHF hospitalizations increased sharply during the study period and contributed significantly to the HF hospitalization burden in California. This emerging HF phenotype, which engenders considerable financial and societal costs, calls for an urgent and concerted public health response to contain its spread.

Genetic diversity of HLA system in two populations from Tlaxcala, Mexico: Tlaxcala city and rural Tlaxcala.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 1011 Mexicans from the state of Tlaxcala residing in the city of Tlaxcala (N = 181) and rural communities (N = 830), to obtain information regarding allelic and haplotypic frequencies. We find that the ten most frequent haplotypes in Tlaxcala are all of Native American origin. Admixture estimates revealed that the main genetic components are Native American (75.13 ±â€¯1.56% by ML; 69.24% based on of Native American haplotypes) and European (16.10 ±â€¯4.98% by ML; 19.74% of European haplotypes), with a less prominent African genetic component (8.78 ±â€¯4.09% by ML; 4.35% of African haplotypes).

Genetic diversity of HLA system in three populations from Coahuila, Mexico: Torreón, Saltillo and rural Coahuila.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 684 Mexicans from the state of Coahuila living in Saltillo (N = 72), Torreón (N = 396) and rural communities (N = 216), to obtain information regarding allelic and haplotypic frequencies. We find that the ten most frequent haplotypes found in the state of Coahuila include eight Native American and two European haplotypes. Admixture estimates revealed that the main genetic components in the state of Coahuila are European (49.72 ±â€¯4.18% by ML; 37.49% of European haplotypes) and Native American (45.01 ±â€¯2.69% by ML; 42.98% of Native American haplotypes), while African genetic component is less apparent (5.27 ±â€¯1.88% by ML; 9.92% of African haplotypes).

Comparison of Clinical Characteristics and Outcomes of Patients With Reversible Versus Persistent Methamphetamine-Associated Cardiomyopathy.

Anecdotal cases of reversible methamphetamine-associated cardiomyopathy (rMAC) have been reported, but not well understood. This study sought to determine the clinical characteristics, outcomes and predictors of reversibility among patients with rMAC as compared with patients with persistent MAC (pMAC). We retrospectively studied adult MAC patients with left ventricular ejection fraction (LVEF) ≤40% at a single center between 2004 and 2018. rMAC was defined as increase in LVEF by ≥20 points or to ≥50%. Those with persistent LVEF ≤40% constituted the pMAC group. 357 MAC cases were identified: 250 patients had pMAC and 107 had rMAC. After a median follow-up of 45 months (interquartile range 27 to 70), LVEF increased by 28.3 ± 6.9% in rMAC (p <0.001), whereas it was unchanged in pMAC (Δ: -0.5 ± 8.7%, p = 0.350). Heart failure hospitalizations and New York Heart Association Class III/IV heart failure were both significantly reduced for rMAC than the pMAC group. All-cause mortality was 21.6% overall, 28% in pMAC and 6.5% in the rMAC group (p <0.001). Kaplan-Meier survival curves demonstrated significantly higher cumulative survival for rMAC (Log Rank p <0.001). Multivariable logistic regression identified MA cessation (odds ratio/OR: 4.23, 95% confidence interval/CI: 2.47 to 7.38, p <0.001) and baseline right ventricular end systolic area (OR: 0.92, 95% CI: 0.87 to 0.97, p = 0.001) as strongly predictive of MAC reversal. In conclusion, MAC reversal is not uncommon and is associated with significant clinical improvement including reduced mortality. It can be facilitated by MA cessation when the cardiac chambers, especially the right ventricle, are not severely dilated.

Resolving mitochondrial haplogroups B2 and B4 with next-generation mitogenome sequencing to distinguish Native American from Asian haplotypes.

Mitochondrial haplogroup information can be useful in forensic contexts that rely primarily on mitochondrial DNA (mtDNA) testing, which often involve limited or degraded DNA. Due to the phylogeographic patterning of mtDNA in human populations, mitochondrial haplogroups are indicative of maternal ancestry (as mtDNA is a maternally inherited marker). In certain circumstances, maternal ancestry inferred from mitochondrial haplogrouping could be beneficial to forensic investigations. For example, ancestry information could assist in the identification of unknown service members from past conflicts, such as the World War II Battle of Tarawa involving American and Japanese forces. In this context, it could be useful to distinguish Native American mtDNA from Asian mtDNA to bolster the anthropological and circumstantial evidence leading to an identification or foreign national determination. Although most of the founding Native American haplogroups contain diagnostic variants in the mitochondrial control region (CR), haplogroup B2 does not, and this makes it more difficult to distinguish B2 from the parental B4 and closely related B4b haplogroups found in Asia. In this paper, the amount of mtDNA information required to distinguish Native American haplotypes from Asian haplotypes within haplogroup B was examined. Fifty-six samples belonging to subtypes of B2 and B4 were sequenced for the entire mitogenome. Haplogroups were estimated from three ranges of mitochondrial DNA (HV1 and 2, CR, and full mitogenome). Half of the samples could not be precisely haplogrouped without full mitogenome data, although enough variants were often provided to make an accurate B2 versus B4 distinction. Native American B2 haplotypes were distinguishable using CR data alone in 82% of samples, though the remaining samples required full mitogenome data for haplogroup B2 designation. The use of full mitogenome data consistently enables accurate haplogroup determination, and opens the possibility for gaining information on maternal ancestry.

Evaluation of a clinical score for predicting atrial fibrillation in cryptogenic stroke patients with insertable cardiac monitors: results from the CRYSTAL AF study.

BACKGROUND: The HAVOC score was previously developed to predict the risk of atrial fibrillation (AF) after cryptogenic stroke (CS) or transient ischemic attack (TIA). The purpose of this study was to apply the HAVOC score to patients who received insertable cardiac monitors (ICMs) in the CRYSTAL AF study. METHODS: All patients from the CRYSTAL AF study who received an ICM were included. HAVOC score (one point each for peripheral vascular disease and obesity with body mass index >30, two points each for hypertension, age ⩾ 75, valvular heart disease, and coronary artery disease, 4 points for congestive heart failure) was computed for all patients. The primary endpoint was AF detection by 12 months of ICM monitoring. RESULTS: A total of 214 patients who received ICM were included. AF was detected in 40 patients while the remaining 174 patients were AF negative. The HAVOC score was significantly higher among patients with AF [median 3.0 with interquartile range (IQR) 2-4] than those without AF [median 2.0 (IQR 0-3)], p = 0.01. AF increased significantly across the three HAVOC score groups: 11% in Group A (score 0-1), 18% in Group B (score 2-3), and 32 % in Group C (score ⩾ 4) with p = 0.02. CONCLUSIONS: The HAVOC score was shown in this post hoc analysis of CRYSTAL AF to successfully stratify AF risk post CS or TIA. The 11% AF rate in the lowest HAVOC score group highlights the significance of nontraditional contributors to AF and ischemic stroke.

How strong was the bottleneck associated to the peopling of the Americas? New insights from multilocus sequence data.

In spite of many genetic studies that contributed for a deep knowledge about the peopling of the Americas, no consensus has emerged about important parameters such as the effective size of the Native Americans founder population. Previous estimates based on genomic datasets may have been biased by the use of admixed individuals from Latino populations, while other recent studies using samples from Native American individuals relied on approximated analytical approaches. In this study we use resequencing data for nine independent regions in a set of Native American and Siberian individuals and a full-likelihood approach based on isolation-with-migration scenarios accounting for recent flow between Asian and Native American populations. Our results suggest that, in agreement with previous studies, the effective size of the Native American population was small, most likely in the order of a few hundred individuals, with point estimates close to 250 individuals, even though credible intervals include a number as large as ~4,000 individuals. Recognizing the size of the genetic bottleneck during the peopling of the Americas is important for determining the extent of genetic markers needed to characterize Native American populations in genome-wide studies and to evaluate the adaptive potential of genetic variants in this population.

Author Correction: A population-specific reference panel empowers genetic studies of Anabaptist populations.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Clinical Characteristics and Outcome of Methamphetamine-Associated Pulmonary Arterial Hypertension and Dilated Cardiomyopathy.

OBJECTIVES: This study sought to characterize patients with methamphetamine-associated pulmonary arterial hypertension (MA-PAH) and cardiomyopathy (MA-CMP), to compare with MA controls (MA-CTL), users with structurally normal hearts, with the aim of identifying risk factors for these conditions. BACKGROUND: MA-PAH and MA-CMP are 2 poorly understood cardiac complications in MA users. METHODS: We retrospectively studied the clinical characteristics and outcomes of 50 MA-PAH, 296 MA-CMP, and 356 MA-CTL patients, whom we evaluated between 2010 and 2017. RESULTS: After a median follow-up of 20.0 months (interquartile range [IQR]: 7.6 to 42.6 months), all-cause mortality was 18.0% for MA-PAH, 15.2% for MA-CMP, and 4.5% for MA-CTL group (p < 0.001). More women (58%) were in the MA-PAH group than in the MA-CMP (14%; p < 0.001) and MA-CTL (42%; p = 0.028) groups, whereas the MA-CMP group was predominantly male (86% vs. 58% in the MA-CTL group; p < 0.001). More MA-CMP patients had hypertension (p < 0.001) or alcoholism (p < 0.001) than MA-CTL patients. Logistic regression analyses identified male sex, alcoholism, and hypertension as independent factors associated with MA-CMP with the following respective adjusted odds ratios (OR) of 3.791 (95% confidence interval [CI]: 2.508 to 5.730), OR of 2.959 (95% CI: 2.084 to 4.203), and OR of 2.111 (95% CI: 1.486 to 2.999), whereas female sex was the only factor associated with MA-PAH. CONCLUSIONS: Both MA-PAH and MA-CMP patients carried significant disease burden and mortality risk. Male sex, hypertension, and alcoholism were strongly associated with MA-CMP, whereas female sex and other unknown factors may influence development of MA-PAH. This study adds to the understanding of MA-associated cardiac complications and highlights directions for future investigation.

How strong was the bottleneck associated to the peopling of the Americas? New insights from multilocus sequence data

Abstract In spite of many genetic studies that contributed for a deep knowledge about the peopling of the Americas, no consensus has emerged about important parameters such as the effective size of the Native Americans founder population. Previous estimates based on genomic datasets may have been biased by the use of admixed individuals from Latino populations, while other recent studies using samples from Native American individuals relied on approximated analytical approaches. In this study we use resequencing data for nine independent regions in a set of Native American and Siberian individuals and a full-likelihood approach based on isolation-with-migration scenarios accounting for recent flow between Asian and Native American populations. Our results suggest that, in agreement with previous studies, the effective size of the Native American population was small, most likely in the order of a few hundred individuals, with point estimates close to 250 individuals, even though credible intervals include a number as large as ~4,000 individuals. Recognizing the size of the genetic bottleneck during the peopling of the Americas is important for determining the extent of genetic markers needed to characterize Native American populations in genome-wide studies and to evaluate the adaptive potential of genetic variants in this population.

A population-specific reference panel empowers genetic studies of Anabaptist populations.

Genotype imputation is a powerful strategy for achieving the large sample sizes required for identification of variants underlying complex phenotypes, but imputation of rare variants remains problematic. Genetically isolated populations offer one solution, however population-specific reference panels are needed to assure optimal imputation accuracy and allele frequency estimation. Here we report the Anabaptist Genome Reference Panel (AGRP), the first whole-genome catalogue of variants and phased haplotypes in people of Amish and Mennonite ancestry. Based on high-depth whole-genome sequence (WGS) from 265 individuals, the AGRP contains >12 M high-confidence single nucleotide variants and short indels, of which ~12.5% are novel. These Anabaptist-specific variants were more deleterious than variants with comparable frequencies observed in the 1000 Genomes panel. About 43,000 variants showed enriched allele frequencies in AGRP, consistent with drift. When combined with the 1000 Genomes Project reference panel, the AGRP substantially improved imputation, especially for rarer variants. The AGRP is freely available to researchers through an imputation server.

A Clinical Score for Predicting Atrial Fibrillation in Patients with Cryptogenic Stroke or Transient Ischemic Attack.

OBJECTIVES: Detection of atrial fibrillation (AF) in post-cryptogenic stroke (CS) or transient ischemic attack (TIA) patients carries important therapeutic implications. METHODS: To risk stratify CS/TIA patients for later development of AF, we conducted a retrospective cohort study using data from 1995 to 2015 in the Stanford Translational Research Integrated Database Environment (STRIDE). RESULTS: Of the 9,589 adult patients (age ≥40 years) with CS/TIA included, 482 (5%) patients developed AF post CS/TIA. Of those patients, 28.4, 26.3, and 45.3% were diagnosed with AF 1-12 months, 1-3 years, and >3 years after the index CS/TIA, respectively. Age (≥75 years), obesity, congestive heart failure, hypertension, coronary artery disease, peripheral vascular disease, and valve disease are significant risk factors, with the following respective odds ratios (95% CI): 1.73 (1.39-2.16), 1.53 (1.05-2.18), 3.34 (2.61-4.28), 2.01 (1.53-2.68), 1.72 (1.35-2.19), 1.37 (1.02-1.84), and 2.05 (1.55-2.69). A risk-scoring system, i.e., the HAVOC score, was constructed using these 7 clinical variables that successfully stratify patients into 3 risk groups, with good model discrimination (area under the curve = 0.77). CONCLUSIONS: Findings from this study support the strategy of looking longer and harder for AF in post-CS/TIA patients. The HAVOC score identifies different levels of AF risk and may be used to select patients for extended rhythm monitoring.

Increased Access to Professional Interpreters in the Hospital Improves Informed Consent for Patients with Limited English Proficiency.

BACKGROUND: Language barriers disrupt communication and impede informed consent for patients with limited English proficiency (LEP) undergoing healthcare procedures. Effective interventions for this disparity remain unclear. OBJECTIVE: Assess the impact of a bedside interpreter phone system intervention on informed consent for patients with LEP and compare outcomes to those of English speakers. DESIGN: Prospective, pre-post intervention implementation study using propensity analysis. SUBJECTS: Hospitalized patients undergoing invasive procedures on the cardiovascular, general surgery or orthopedic surgery floors. INTERVENTION: Installation of dual-handset interpreter phones at every bedside enabling 24-h immediate access to professional interpreters. MAIN MEASURES: Primary predictor: pre- vs. post-implementation group; secondary predictor: post-implementation patients with LEP vs. English speakers. Primary outcomes: three central informed consent elements, patient-reported understanding of the (1) reasons for and (2) risks of the procedure and (3) having had all questions answered. We considered consent adequately informed when all three elements were met. KEY RESULTS: We enrolled 152 Chinese- and Spanish-speaking patients with LEP (84 pre- and 68 post-implementation) and 86 English speakers. Post-implementation (vs. pre-implementation) patients with LEP were more likely to meet criteria for adequately informed consent (54% vs. 29%, p = 0.001) and, after propensity score adjustment, had significantly higher odds of adequately informed consent (AOR 2.56; 95% CI, 1.15-5.72) as well as of each consent element individually. However, compared to post-implementation English speakers, post-implementation patients with LEP had significantly lower adjusted odds of adequately informed consent (AOR, 0.38; 95% CI, 0.16-0.91). CONCLUSIONS: A bedside interpreter phone system intervention to increase rapid access to professional interpreters was associated with improvements in patient-reported informed consent and should be considered by hospitals seeking to improve care for patients with LEP; however, these improvements did not eliminate the language-based disparity. Additional clinician educational interventions and more language-concordant care may be necessary for informed consent to equal that for English speakers.

Population History and Mitochondrial Genetic Substructure of the Rama Amerindians from Nicaragua.

The Rama are a coastal population from southern Nicaragua who in large part were able to resist, at least for a time, the cultural changes and social reorganization brought on by colonial and modern influences. Historical information leaves the Rama origins and biological relationships with nearby extinct and extant groups ambiguous. The objective of this study was to examine the internal genetic microdifferentiation based on the first hypervariable region of the mitochondrial DNA (mtDNA) from a sample of approximately 20% of the population, and to expand the few available historical and anthropological data on the Rama by exploring the effects of cultural practices and historical events on genetic structure, providing an integrative perspective on the Rama genetic history. When considering differences in the spatial distribution and genetic diversity of the mtDNA haplotypes together with historical information on the Rama, a noteworthy pattern emerges. (a) Haplotypes are differentially distributed among a central Rama community (Punta Águila) compared with the other five peripheral communities (analysis of molecular variance: FCT = 0.10, p < 0.001), and their distribution is consistent with the historical relocation of this population after their split from Punta Gorda in the 18th century. (b) Differential genetic signatures found among central and peripheral Rama communities resemble two population histories: one of stability (haplogroup A2) and other of expansion (haplogroup B2), supporting the possibility that these patterns of genetic microdifferentiation between central and peripheral populations resulted from the 18th-century unification in southern Nicaragua of the Rama and a group of Voto migrants from Costa Rica that later split off and moved to the Bay of Bluefields.