Rate Versus Rhythm Control for Atrial Fibrillation.

Atrial fibrillation (AF) is an arrhythmia characterized by disorganized atrial activity with an associated unevenly irregular ventricular response on an electrocardiogram. It is the most common sustained arrhythmia, with a lifetime risk of 25% in patients older than 40 years old. The incidence of AF increases with age and is associated with an increased risk for heart failure, stroke, adverse cardiac events, and dementia. The 2 main aims of AF treatment include anticoagulation for thromboembolism prophylaxis as well as rate vs rhythm control. The focus of this article will be on the treatment strategies in managing AF. Rate control refers to the use of atrioventricular nodal blocking medications, including beta blockers and calcium channel blockers, to maintain a goal heart rate. Rhythm control, on the other hand, refers to a treatment strategy focused on the use of antiarrhythmic drugs (AAD), cardioversion, and ablation to restore and to maintain a patient in sinus rhythm. Currently, the ideal treatment strategy remains greatly debated. Thus, we hope to compare the risks and benefits of rate to rhythm control to highlight how patients with AF are managed here at Kaiser Permanente Northern California.

Psychiatric Diagnoses, Medication, and Service Use Among Patients Who Receive Emergency Care for Inflammatory Bowel Diseases.

This study examined relative psychiatric burden among patients who presented to the emergency department once or more than once for inflammatory bowel disease visits. Results highlight the need for integration of psychiatric and gastrointestinal care among high-risk inflammatory bowel disease patients.

Germline variants of uncertain significance, their frequency, and clinico-pathological features in a cohort of Sri Lankan patients with hereditary breast cancer.

BACKGROUND: Next-Generation Sequencing (NGS)-based testing in cancer patients has led to increased detection of variants of uncertain significance (VUS). VUS are genetic variants whose impact on protein function is unknown. VUS pose a challenge to clinicians and patients due to uncertainty regarding their cancer predisposition risk. Paucity of data exists on the pattern of VUS in under-represented populations. This study describes the frequency of germline VUS and clinico-pathological features in Sri Lankan hereditary breast cancer patients. METHODS: Data of 72 hereditary breast cancer patients who underwent NGS-based testing between January 2015 and December 2021 were maintained prospectively in a database and analyzed retrospectively. Data were subjected to bioinformatics analysis and variants were classified according to international guidelines. RESULTS: Germline variants were detected in 33/72(45.8%) patients, comprising 16(48.5%) pathogenic/likely pathogenic variants and 17(51.5%) VUS. Distribution of VUS in breast cancer predisposing genes were :APC:1(5.8%), ATM:2(11.7%), BRCA1:1(5.8%), BRCA2:5(29.4%), BRIP1:1(5.8%), CDKN2A:1(5.8%), CHEK2:2(11.7%), FANC1:1(5.8%), MET:1(5.8%), STK11:1(5.8%), NF2:1(5.8%). Mean age at cancer diagnosis in patients with VUS was 51.2 years. Most common tumour histopathology was ductal carcinoma 11(78.6%). 50% of tumours in patients having VUS in BRCA1/2 genes were hormone receptor negative. 73.3% patients had family history of breast cancer. CONCLUSIONS: A significant portion of patients had a germline VUS. Highest frequency was in BRCA2 gene. Majority had family history of breast cancer. This highlights the need to undertake functional genomic studies to determine the biological effects of VUS and identify potentially clinically actionable variants that would be useful for decision-making and patient management.

Unmasking Resident Physician Burnout During the COVID-19 Era.

Burnout is not a new concept in the health care field. Most, if not all, resident physicians (residents) experience burnout at least once during their training. However, the COVID-19 pandemic placed a large strain on the health care system and exacerbated stressors that contribute to burnout, including anxiety, depression, and work overload. The authors reviewed the literature on resident burnout in the era of COVID-19 to elucidate common stressors across the specialties and identify successful interventions or initiatives that may be most effective for residency programs.

Cardiovascular Disease Risk Factors Among Middle-Aged and Older Adult Vietnamese American Members of a Northern California Health Plan.

OBJECTIVE: There is increasing recognition that cardiovascular disease (CVD) risk factors vary by Asian subgroups. We examined CVD risk factor prevalence among Vietnamese adults in a northern California health plan. METHODS: We used electronic health record data to examine smoking, overweight/obesity (body mass index ≥23.0 kg/m2), obesity (body mass index ≥27.5 kg/m2), prediabetes, diabetes, and hypertension among middle-aged (n = 12 757; aged 45-64 years) and older (n = 3418; aged 65-84 years) Vietnamese adults, including 37.8% whose preferred language was Vietnamese. Findings were compared with East Asian adults. RESULTS: Current smoking prevalence was 20.3% for middle-aged men, 7.0% for older men, and <1% for women in both age groups. Obesity prevalence was 12.0% for older men, 17.9% for middle-aged men, and 10% for women in both age groups. Among middle-aged men and women, 20.9% and 17.0% had hypertension and 13.5% and 8.5% had diabetes, respectively. Among older men and women, 64.0% and 60.0% had hypertension and 32.8% and 29.3% had diabetes, respectively. In both age groups, Vietnamese language preference was associated with higher risk of smoking (men only) and of diabetes and hypertension (women only). Compared with East Asian adults, Vietnamese adults had lower obesity prevalence but similar prevalence of diabetes, prediabetes, and hypertension. Vietnamese men were more likely and Vietnamese women less likely than East Asian adults to be current smokers. CONCLUSIONS: Study results suggest that more research on health conditions, lifestyle, and social factors among Vietnamese American adults is needed to develop culturally competent interventions to reduce CVD risk in this growing ethnic group.

The Association of Chinese Ethnicity and Language Preference with Advance Directive Completion Among Older Patients in an Integrated Health System.

BACKGROUND: Little is known about possible differences in advance directive completion (ADC) based on ethnicity and language preference among Chinese Americans on a regional level. OBJECTIVE: To understand the association of ethnicity and language preference with ADC among Chinese Americans. DESIGN: Retrospective cohort analysis with direct standardization. PARTICIPANTS: A total of 31,498 Chinese and 502,991 non-Hispanic White members enrolled in Kaiser Permanente Northern California during the entire study period between 2013 and 2017 who were 55 or older as of January 1, 2018. MAIN MEASURES: We compared the proportion of ADC among non-Hispanic White and Chinese patients, and also analyzed the rates according to language preference within the Chinese population. We calculated ADC rates with direct standardization using covariates previously found in literature to be significant predictors of ADC such as age and utilization. KEY RESULTS: Among Chinese members, 60% preferred English, 16% preferred another language without needing an interpreter, and 23% needed an interpreter. After standardizing for age and utilization, non-Hispanic Whites were more than twice as likely to have ADC as Chinese members (20.6% (95% confidence interval (CI): 20.5-20.7%) vs. 10.0% (95% CI: 9.6-10.3%), respectively). Among Chinese members, there was an inverse association between preference for a language other than English and ADC (13.3% (95% CI: 12.8-13.8%) if preferring English, 6.1% (95% CI: 5.4-6.7%) if preferring non-English language but not needing an interpreter, and 5.1% (95% CI: 4.6-5.6%) if preferring non-English language and needing an interpreter). CONCLUSIONS: Chinese members are less likely to have ADC relative to non-Hispanic White members, and those preferring a language other than English are most affected. Further studies can assess reasons for lower ADC among Chinese members, differences in other Asian American populations, and interventions to reduce differences among Chinese members especially among those preferring a language other than English.

Prevalence of prediabetes and diabetes vary by ethnicity among U.S. Asian adults at healthy weight, overweight, and obesity ranges: an electronic health record study.

BACKGROUND: Asian adults develop Type 2 diabetes at a lower body mass index (BMI) compared to other racial/ethnic groups. We examined the variation in prevalence of prediabetes and diabetes among Asian ethnic groups within weight strata by comparing middle-aged Chinese, Filipino, South Asian, and White adults receiving care in the same integrated healthcare delivery system. METHODS: Our retrospective cross-sectional U.S. study examined data from 283,110 (non-Hispanic) White, 33,263 Chinese, 38,766 Filipino, and 17,959 South Asian adults aged 45-64 years who were members of a Northern California health plan in 2016 and had measured height and weight. Prediabetes and diabetes were classified based on laboratory data, clinical diagnoses, or diabetes pharmacotherapy. Age-standardized prevalence of prediabetes and diabetes were compared by race/ethnicity within healthy weight, overweight, and obesity categories, using standard BMI thresholds for White adults (18.5 to < 25, 25 to < 30, ≥ 30 kg/m2) and lower BMI thresholds for Asian adults (18.5 to < 23, 23 to < 27.5, ≥ 27.5 kg/m2). Prevalence ratios (PRs) were used to compare the prevalence of diabetes and prediabetes for Asian groups to White adults in each weight category, adjusted for age and BMI. RESULTS: Across all weight categories, diabetes prevalence was higher for Asian than White adults, and among Asian groups it was highest for Filipino and South Asian adults. Compared to White, PRs for South Asian men/women at healthy BMI were 1.8/2.8 for prediabetes and 5.9/8.0 for diabetes, respectively. The PRs for Filipino men/women at healthy BMI were 1.8/2.6 for prediabetes and 5.0/7.5 for diabetes, respectively. For Chinese men/women at healthy BMI, the PRs for prediabetes (2.1/2.9) were similar to Filipino and South Asian, but the PRs for diabetes were lower (2.1/3.4). CONCLUSION: Chinese, Filipino, and South Asian adults have higher prevalence of prediabetes and diabetes than White adults in all weight categories, despite using lower BMI thresholds for weight classification in Asian groups. Within Asian ethnic groups, Filipino and South Asian adults had considerably higher diabetes prevalence than Chinese adults. Our data emphasize the disproportionate metabolic risk among middle-aged Asian adults and underscore the need for diabetes screening among high-risk Asian groups at healthy BMI levels.

A recurrent homozygous missense DPM3 variant leads to muscle and brain disease.

Biallelic pathogenic variants in the genes encoding the dolichol-phosphate mannose synthase subunits (DPM) which produce mannosyl donors for glycosylphosphatidylinositols, N-glycan and protein O- and C-mannosylation, are rare causes of congenital disorders of glycosylation. Pathogenic variants in DPM1 and DPM2 are associated with muscle-eye-brain (MEB) disease, whereas DPM3 variants have mostly been reported in patients with isolated muscle disease-dystroglycanopathy. Thus far, only one affected individual with compound heterozygous DPM3 variants presenting with myopathy, mild intellectual disability, seizures, and nonspecific white matter abnormalities (WMA) around the lateral ventricles has been described. Here we present five affected individuals from four unrelated families with global developmental delay/intellectual disability ranging from mild to severe, microcephaly, seizures, WMA, muscle weakness and variable cardiomyopathy. Exome sequencing of the probands revealed an ultra-rare homozygous pathogenic missense DPM3 variant NM_018973.4:c.221A>G, p.(Tyr74Cys) which segregated with the phenotype in all families. Haplotype analysis indicated that the variant arose independently in three families. Functional analysis did not reveal any alteration in the N-glycosylation pathway caused by the variant; however, this does not exclude its pathogenicity in the function of the DPM complex and related cellular pathways. This report provides supporting evidence that, besides DPM1 and DPM2, defects in DPM3 can also lead to a muscle and brain phenotype.

Ethnic diversity and burden of polycystic ovary syndrome among US adolescent females.

OBJECTIVES: Polycystic Ovary Syndrome (PCOS) is a common female endocrine disorder presenting as early as adolescence. Recent data suggest that Asians may be at increased risk. This study examines PCOS prevalence by race/ethnicity in a large, diverse population of adolescent females. METHODS: This retrospective study included 244,642 females (ages 13-17) with well-child visits during 2012-2018 in a Northern California healthcare system. Race/ethnicity and Asian ethnicity were classified using self-reported data. Body mass index was classified as healthy, overweight, and moderate/severe obesity. PCOS was determined by clinical diagnosis within one year of the visit. RESULTS: The overall prevalence of PCOS was 0.7% and increased substantially with weight. Among those with obesity, PCOS prevalence was 4.2, 2.9, 2.4, 2.1% in Asian/Pacific Islander (PI), Hispanic/Latina, Non-Hispanic White, Black adolescents and 7.8, 6.7, 5.7, 3.4% in South Asian, Chinese, Filipina, Native Hawaiian/PI adolescents, respectively. Compared to White adolescents, Asian/PIs had two-fold higher risk of PCOS, and Hispanic/Latinas had 1.3-fold higher risk. Compared to Chinese adolescents, South Asians had 1.7-fold higher risk, while Native Hawaiian/PIs had half the risk. CONCLUSIONS: The increased burden of diagnosed PCOS in Asian/PI and Hispanic/Latina adolescents, especially those with obesity, calls for further examination and clinical surveillance of at-risk populations.

The Prevalence of Elevated Alanine Aminotransferase Levels Meeting Clinical Action Thresholds in Children with Obesity in Primary Care Practice.

Using a clinically actionable threshold for alanine aminotransferase to define suspected nonalcoholic fatty liver disease in US children with obesity, the risk of suspected nonalcoholic fatty liver disease was highest for Asian and Hispanic race/ethnicity, male sex, and severe obesity.

The effects of meditation on length of telomeres in healthy individuals: a systematic review.

BACKGROUND: Meditation-based practices have been suggested to result in many biological benefits which include reduction of attrition of telomeres, the protective nucleotide-protein complexes at termini of eukaryotic chromosomes. This systematic review evaluated the effects of meditation on telomere length (TL) in healthy adults. METHODS: Randomized controlled trials (RCTs) and observational studies conducted to determine the effects of meditation on TL in healthy individuals, published up to July 2020 were retrieved by searching seven electronic databases (PubMed, Scopus, PsycINFO, EMBASE, Cochrane Library, CINAHL and Google Scholar). The methodological quality of RCTs and observational studies was assessed using the Cochrane Collaboration Risk of Bias Tool and Joanna Briggs Institute critical appraisal checklist, respectively. The data was synthesized narratively and the effect estimates of TL in the RCTs were synthesized using alternative methods as a meta-analysis was not conducted. The certainty of evidence was classified according to the GRADE system. RESULTS: A total of 1740 articles were screened. Five studies comprising two RCTs and three case-control studies (CCS) were included in the final review based on the inclusion and exclusion criteria. The combined sample consisted of 615 participants with 41.7% males. Average age of participants was 47.7 years. One CCS and one RCT reported significant beneficial effects of meditation on TL while the two remaining CCS and the RCT showed positive effects of meditation on TL which were not significant. For all CCS and one RCT, the methodological quality was high while the remaining RCT was of moderate quality. The quality of evidence for the primary outcome was moderate in RCTs. CONCLUSION: The effect of meditation on TL per se is still unclear. Strictly designed and well-reported RCTs with larger sample sizes are required to provide evidence of higher quality. SYSTEMATIC REVIEW REGISTRATION: The protocol of this review was registered with the International Prospective Register of Systematic Reviews (PROSPERO) database (registration number: CRD42020153977 ).

Alterations in neurotransmitter levels and transcription factor expression following intranasal buprenorphine administration.

Buprenorphine is an opioid drug used in the management of pain and the treatment opioid addiction. Like other opioids, it is believed that it achieves these effects by altering functional neurotransmitter pathways and the expression of important transcription factors; cyclic AMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the brain. However, there is a lack of scientific evidence to support these theories. This study investigated the pharmacodynamic effects of BUP administration by assessing neurotransmitter and molecular changes in the healthy rodent brain. Sprague-Dawley rats (150-200 g) were intranasally administered buprenorphine (0.3 mg/mL) and sacrificed at different time points: 0.25, 0.5, 1, 2, 4, 6, 8 and 24 h post drug administration. LC-MS was used to quantify BUP and neurotransmitters (GABA, GLUT, DA, NE and 5-HT) in the brain, while CREB and BDNF gene expression was determined using qPCR. Results showed that BUP reached a Cmax of 1.21 ± 0.0523 ng/mL after 2 h, with all neurotransmitters showing an increase in their concentration over time, with GABA, GLUT and NE reaching their maximum concentration after 8 h. DA and 5-HT reached their maximum concentrations at 1 h and 24 h, respectively post drug administration. Treatment with BUP resulted in significant upregulation in BDNF expression throughout the treatment period while CREB showed patterns of significant upregulation at 2 and 8 h, and downregulation at 1 and 6 h. This study contributes to the understanding of the pharmacodynamic effects of BUP in opioid addiction by proving that the drug significantly influences NT pathways that are implicated in opioid addiction.

Frontometaphyseal dysplasia 1 in a patient from Sri Lanka.

A Sri Lankan male child with supraorbital hyperostosis, broad nasal bridge, small mandible, severe kyphoscoliosis, distal joint contractures of the hands and long second and third toes is described. A hemizygous pathogenic variant in exon 22 of the filamin A (FLNA) gene [NM_001110556.1: c.3557C>T; which leads to a nonsynonymous substitution of serine by leucine at codon 1186 in the FLNA protein; NP_001104026.1: p.Ser1186Leu] was identified. The clinical features observed in this patient were consistent with the cardinal manifestations seen in frontometaphyseal dysplasia 1 (FMD1). However, characteristic extra skeletal manifestations such as cardiac defects, uropathy, and hearing impairment which have previously been reported in association with this condition were absent in this patient.