Percutaneous left atrial appendage occlusion and risk of stroke, hospitalized bleeding and death in Medicare beneficiaries.

PURPOSE: Among patients with atrial fibrillation (AF), a nonpharmacologic option (e.g., percutaneous left atrial appendage occlusion [LAAO]) is needed for patients with oral anticoagulant (OAC) contraindications. Among beneficiaries in the Medicare fee-for-service coverage 20% sample databases (2015-18) who had AF and an elevated CHA2DS2-VASc score, we assessed the association between percutaneous LAAO versus OAC use and risk of stroke, hospitalized bleeding, and death. METHODS: Patients undergoing percutaneous LAAO were matched to up to five OAC users by sex, age, date of enrollment, index date, CHA2DS2-VASc score, and HAS-BLED score. Overall, 17 156 patients with AF (2905 with percutaneous LAAO) were matched (average ± SD 78 ± 6 years, 44% female). Cox proportional hazards model were used. RESULTS: Median follow-up was 10.3 months. After multivariable adjustments, no significant difference for risk of stroke or death was noted when patients with percutaneous LAAO were compared with OAC users (HRs [95% CIs]: 1.14 [0.86-1.52], 0.98 [0.86-1.10]). There was a 2.94-fold (95% CI: 2.50-3.45) increased risk for hospitalized bleeding for percutaneous LAAO compared with OAC use. Among patients 65 to <78 years old, those undergoing percutaneous LAAO had higher risk of stroke compared with OAC users. No association was present in those ≥78 years. CONCLUSION: In this analysis of real-world AF patients, percutaneous LAAO versus OAC use was associated with similar risk of death, nonsignificantly elevated risk of stroke, and an elevated risk of bleeding in the post-procedural period. Overall, these results support results of randomized trials that percutaneous LAAO may be an alternative to OAC use for patients with contraindications.

Venous thromboembolism mortality and trends in older US adults, 2011-2019.

Venous thromboembolism (VTE) affects 1.2 million people per year in the United States. With several clinical changes in diagnosis and treatment approaches in the past decade, we evaluated contemporary post-VTE mortality risk profiles and trends. Incident VTE cases were identified from the 2011-2019 Medicare 20% Sample, which is representative of nearly all Americans aged 65 and older. The social deprivation index was linked from public data; race/ethnicity and sex were self-reported. The all-cause mortality risk 30 days and 1 year after incident VTE was calculated in demographic subgroups and by prevalent cancer diagnosis status using model-based standardization. Risks for major cancer types, risk differences by age, sex, race/ethnicity, and socio-economic status (SES), and trends over time are also reported. The all-cause mortality risk among older US adults following incident VTE was 3.1% (95% CI 3.0-3.2) at 30 days and 19.6% (95% CI 19.2-20.1) at 1 year. For cancer-related VTE events, the age-sex-race-standardized risk was 6.0% at 30 days and 34.7% at 1 year. The standardized 30-day and 1-year risks were higher among non-White beneficiaries and among those with low SES. One-year mortality risk decreased 0.28 percentage points per year (95% CI 0.16-0.40) on average across the study period, with no trend observed for 30-day mortality risk. In sum, all-cause mortality risk following incident VTE has decreased slightly in the last decade, but racial and socio-economic disparities persist. Understanding patterns of mortality among demographic subgroups and in cancer-associated events is important for targeting efforts to improve VTE management.

Hospital Safety-Net Burden Is Associated With Increased Inpatient Mortality and Perioperative Complications After Colectomy.

BACKGROUND: Colectomies are common yet costly, with high surgical-site infection rates. Safety-net hospitals (SNHs) carry a large proportion of uninsured or Medicaid-insured patients, which has been associated with poorer surgical outcomes. Few studies have examined the effect of safety-net burden (SNB) status on colectomy outcomes. We aimed to quantify the independent effects of hospital SNB and surgical site infection (SSI) status on colectomy outcomes, as well as the interaction effect between SSIs and SNB. METHODS: We used the Healthcare Cost and Utilization Project's State Inpatient Databases for California, Florida, New York, Maryland, and Kentucky. We included 459,568 colectomies (2009 to 2014) for analysis, excluding patients age <18 y and rectal cases. The primary and secondary outcomes were inpatient mortality and complications, respectively. RESULTS: Adjusting for patient, procedure, and hospital factors, colectomy patients were more likely to die in-hospital at high-burden SNHs (adjusted OR [aOR]: 1.38, 95% confidence interval [CI]: 1.25-1.51, P < 0.001), compared with low SNB hospitals and to experience perioperative complications (aOR: 1.12, 95% CI: 1.04-1.20, P < 0.01). Colectomy patients with SSIs also had greater odds of in-hospital mortality (aOR: 1.92, 95% CI: 1.83-2.02, P < 0.001) and complications (aOR: 3.65, 95% CI: 3.55-3.75, P < 0.001) compared with those without infections. Patients treated at SNHs who developed a SSI were even more likely to have an additional perioperative complication (aOR: 4.33, 95% CI: 3.98-4.71, P < 0.001). CONCLUSIONS: Our study demonstrated that colectomy patients at SNHs have poorer outcomes, and for patients with SSIs, this disparity was even more pronounced in the likelihood for a complication. SNB should be recognized as a significant hospital-level factor affecting colectomy outcomes, with SSIs as an important quality metric.

Racial, Ethnic, and Gender Diversity in Pediatric Anesthesiology Fellowship and Anesthesiology Residency Programs in the United States: Small Reservoir, Leaky Pipeline.

BACKGROUND: The critical question of racial and gender diversity in pediatric anesthesia training programs has not been previously explored. The primary objective of this study was to evaluate trends by race/ethnicity and gender in pediatric anesthesiology fellowship training programs in the United States for the years 2000 to 2018. METHODS: Demographic data on pediatric anesthesiology fellows and anesthesiology residents were obtained from the self-reported data collected for the Journal of the American Medical Association's annual report on Graduate Medical Education for the years 2000 to 2018. Diversity was assessed by calculating the proportions of trainees per year by gender and racial/ethnic groups in pediatric anesthesiology fellowship and anesthesiology residency programs. Logistic regression equations were developed to estimate the annual growth rate of each racial/ethnic groups. RESULTS: The number of pediatric anesthesiology fellows increased from 57 trainees in 2000-2001 to 202 in 2017-2018 at an average rate of 9 fellows per year (95% confidence interval [CI], 8-10). These increases were primarily due to white trainees (54.4%-63.4%) as the proportions of black (7.0%-4.5%), Asian (26.3%-21.3%), and other minority (12.3%-10.9%) trainees have remained low. The number of anesthesiology residents increased from 3950 trainees in 2000-2001 to 5940 in 2017-2018 at an average rate of 99 residents per year (95% CI, 88-111). Within all anesthesiology trainees, these increases were due to white trainees (55.7%-61.3%) as the proportion of black (5.0%-6.0%), Asian (25.8%-24.1%), and other minority trainees (8.2%-8.5%) has remained fairly constant over the time period. Despite the overall lower proportion of female anesthesiology residents (range: 27.0%-37.5%), a steady increase in the number of women in pediatric anesthesiology fellowship programs has reversed the gender imbalance in this population as of 2010. CONCLUSIONS: While historic gains have been made in gender diversity in pediatric anesthesiology, there is persistent underrepresentation of black and Hispanic trainees in pediatric anesthesiology. It appears that their low numbers in anesthesiology residency programs (the reservoir) may be partly responsible. Efforts to increase ethnic/racial diversity in pediatric anesthesiology fellowship and anesthesiology residency training programs are urgently needed.

A MinION™-based pipeline for fast and cost-effective DNA barcoding.

DNA barcodes are useful for species discovery and species identification, but obtaining barcodes currently requires a well-equipped molecular laboratory and is time-consuming, and/or expensive. We here address these issues by developing a barcoding pipeline for Oxford Nanopore MinION™ and demonstrating that one flow cell can generate barcodes for ~500 specimens despite the high basecall error rates of MinION™ reads. The pipeline overcomes these errors by first summarizing all reads for the same tagged amplicon as a consensus barcode. Consensus barcodes are overall mismatch-free but retain indel errors that are concentrated in homopolymeric regions. They are addressed with an optional error correction pipeline that is based on conserved amino acid motifs from publicly available barcodes. The effectiveness of this pipeline is documented by analysing reads from three MinION™ runs that represent three different stages of MinION™ development. They generated data for (i) 511 specimens of a mixed Diptera sample, (ii) 575 specimens of ants and (iii) 50 specimens of Chironomidae. The run based on the latest chemistry yielded MinION™ barcodes for 490 of the 511 specimens which were assessed against reference Sanger barcodes (N = 471). Overall, the MinION™ barcodes have an accuracy of 99.3%-100% with the number of ambiguous bases after correction ranging from <0.01% to 1.5% depending on which correction pipeline is used. We demonstrate that it requires ~2 hr of sequencing to gather all information needed for obtaining reliable barcodes for most specimens (>90%). We estimate that up to 1,000 barcodes can be generated in one flow cell and that the cost per barcode can be

Sorting specimen-rich invertebrate samples with cost-effective NGS barcodes: Validating a reverse workflow for specimen processing.

Biologists frequently sort specimen-rich samples to species. This process is daunting when based on morphology, and disadvantageous if performed using molecular methods that destroy vouchers (e.g., metabarcoding). An alternative is barcoding every specimen in a bulk sample and then presorting the specimens using DNA barcodes, thus mitigating downstream morphological work on presorted units. Such a "reverse workflow" is too expensive using Sanger sequencing, but we here demonstrate that is feasible with an next-generation sequencing (NGS) barcoding pipeline that allows for cost-effective high-throughput generation of short specimen-specific barcodes (313 bp of COI; laboratory cost <$0.50 per specimen) through next-generation sequencing of tagged amplicons. We applied our approach to a large sample of tropical ants, obtaining barcodes for 3,290 of 4,032 specimens (82%). NGS barcodes and their corresponding specimens were then sorted into molecular operational taxonomic units (mOTUs) based on objective clustering and Automated Barcode Gap Discovery (ABGD). High diversity of 88-90 mOTUs (4% clustering) was found and morphologically validated based on preserved vouchers. The mOTUs were overwhelmingly in agreement with morphospecies (match ratio 0.95 at 4% clustering). Because of lack of coverage in existing barcode databases, only 18 could be accurately identified to named species, but our study yielded new barcodes for 48 species, including 28 that are potentially new to science. With its low cost and technical simplicity, the NGS barcoding pipeline can be implemented by a large range of laboratories. It accelerates invertebrate species discovery, facilitates downstream taxonomic work, helps with building comprehensive barcode databases and yields precise abundance information.

Comparison of reminder methods in selected adolescents with records in an immunization registry.

PURPOSE: The aim of this study was to assess the effectiveness and cost efficiency of three reminder/recall methods for improving adolescent vaccination rates using the San Diego Immunization Registry. METHODS: Parents of 5,050 adolescents whose records indicated they lacked one or more adolescent vaccines were identified from the San Diego Immunization Registry and contacted by telephone. Based on their preference, consenting participants were enrolled to receive either postal mail (n = 282), e-mail (n = 963), or text (n = 552) reminders for vaccination. The intervention groups were sent a series of up to three reminders. The vaccination completion rate was compared between the intervention groups and two control groups-the enrollment phone call-only group who declined to participate and a no contact group-using logistic regression. RESULTS: The participants who received any reminder were more likely (24.6% vs. 12.4%; p < .001) to become up-to-date (UTD) than those in the enrollment phone call-only group. At the conclusion of the study observation, UTD status was reached by 32.1% of text message recipients, 23.0% of postcard recipients, and 20.8% of e-mail recipients compared to 12.4% for the enrollment phone call recipients. Only 9.7% of nonintervention adolescents became UTD. CONCLUSIONS: All three reminder interventions were effective in improving adolescent vaccination rates. Although postal mail reminders were preferred by most participants, text messaging and e-mail were the more effective reminder methods. Text messaging and e-mail as reminder methods for receiving vaccinations should be considered for use to boost vaccination completion among adolescents.

Influenza vaccination and its association with clinic use of evidence-based practices and individual patient characteristics, San Diego County, 2009.

CONTEXT: In 2008, about 40% of the US population eligible for influenza vaccine was vaccinated, which was below Healthy People 2020 goals. Little emphasis has been put on late-season vaccination efforts by medical providers. OBJECTIVE: Evaluate use of evidence-based practices (EBP) and their association with influenza vaccination for children younger than 5 years and adults aged 50 years and older. DESIGN: Patient surveys and medical clinic information were collected between January and April 2009. Influenza coverage rates and logistic regressions are used to measure associations. SETTING: Nineteen medical clinics serving children, adults, or both in San Diego County participated. PARTICIPANTS: Parents of children aged 6 months to 5 years and adults aged 50 years and over seen by a primary care provider during January through March 2009. MAIN OUTCOME: Influence of clinic EBP use on child and adult influenza vaccination status. MEASURES: Patient-reported influenza vaccination and clinic coverage rates and clinics' use of EBP and patient demographic characteristics. RESULTS: Coverage rates varied by clinic; 50% to 82% (children) and 48% to 85% (adults). Child clinics using the immunization registry, or those that were private practices or medical groups and adult clinics that used influenza vaccination clinics, provider prompts, or electronic medical records had higher coverage. Surveys from 831 children and 1038 adults documented influenza vaccination rates of 64% and 63% respectively. Receiving a reminder or having two or more visits during influenza season was positively associated with child and adult influenza vaccination. Child vaccination was associated with children younger than 2 years. Adult vaccination was associated adults aged 65 years or older, having a high-risk condition, or being female. CONCLUSIONS: Given the low use of EBP, clinics have opportunities to implement EBP appropriate for their settings and patient populations. Along with other strategies, public health departments and medical groups should encourage medical providers to implement EBP to improve influenza vaccination rates.

A public health initiative to increase annual influenza immunization among hospital health care personnel: the San Diego Hospital Influenza Immunization Partnership.

BACKGROUND: A public health department-supported intervention to increase influenza immunization among hospital-based health care practitioners (HCPs) in San Diego County took place between 2005 and 2008. The study included all major hospitals in the county, with a population of approximately 3.5 million. METHODS: Information on hospital activities was collected from before, during and after initiative activities. Vaccination status and demographics were collected directly from HCP using hospital-based and random-dialed telephone surveys. RESULTS: Between 2006 and 2008, hospitals increased promotion activities and reported increases in vaccination rates. Based on the random-dialed surveys, HCP influenza vaccination coverage rates did not increase significantly. Vaccination rates were significantly higher in HCPs who reported that employers provided free vaccination and those who believed that their employers mandated influenza vaccination. CONCLUSIONS: This local public health initiative and concurrent state legislation were effective in increasing employer efforts to promote influenza vaccination; however, population-based surveys of HCPs did not show significant increases in influenza vaccination. Overall, this study suggests that public health leadership, intensive employer promotion activities, and state-required declinations alone were not sufficient to significantly increase HCP influenza vaccination. Policymakers and employers should consider mandates to achieve optimal influenza vaccination among HCPs.

When Do Fathers Care? Mothers' Economic Contribution and Fathers' Involvement in Child Care.

Previous literature suggests a tenuous link between fathers' care of children and maternal employment and earnings. This study shows that the link is stronger when measures of caregiving capture fathers' increased responsibility for children. The analysis of time diary data from 6,572 married fathers and 7,376 married mothers with children under age 13 indicates that fathers (1) engage in more "solo" care of children when their wives are employed, (2) are more likely to do the kind of child care associated with responsibility for their children when their wives spend more time in the labor market, and (3) participate more in routine care when their wives contribute a greater share of the couple's earnings. In addition, the "father care" to "mother care" ratio rises when mothers contribute a greater share of household earnings.

Assessment of a micropatterned hepatocyte coculture system to generate major human excretory and circulating drug metabolites.

Metabolism is one of the important determinants of the overall disposition of drugs, and the profile of metabolites can have an impact on efficacy and safety. Predicting which drug metabolites will be quantitatively predominant in humans has become increasingly important in the research and development of new drugs. In this study, a novel micropatterned hepatocyte coculture system was evaluated for its ability to generate human in vivo metabolites. Twenty-seven compounds of diverse chemical structure and subject to a range of drug biotransformation reactions were assessed for metabolite profiles in the micropatterned coculture system using pooled cryopreserved human hepatocytes. The ability of this system to generate metabolites that are >10% of dose in excreta or >10% of total drug-related material in circulation was assessed and compared to previously reported data obtained in human hepatocyte suspensions, liver S-9 fraction, and liver microsomes. The micropatterned coculture system was incubated for up to 7 days without a change in medium, which offered an ability to generate metabolites for slowly metabolized compounds. The micropatterned coculture system generated 82% of the excretory metabolites that exceed 10% of dose and 75% of the circulating metabolites that exceed 10% of total circulating drug-related material, exceeds the performance of hepatocyte suspension incubations and other in vitro systems. Phase 1 and phase 2 metabolites were generated, as well as metabolites that arise via two or more sequential reactions. These results suggest that this in vitro system offers the highest performance among in vitro metabolism systems to predict major human in vivo metabolites.

The San Diego Immunization Survey: a model for local vaccination coverage assessment.

OBJECTIVES: Assessing vaccination coverage as part of a comprehensive intervention has been demonstrated to result in increased coverage rates. The National Immunization Survey provides coverage estimates at the national level and selected urban areas. However, it is important for other localities to understand vaccination coverage in their areas. The San Diego Immunization Branch conducts the San Diego Immunization Survey (SDIS) to gather vaccination coverage information in San Diego County. This article describes the methodology and results of the SDIS. METHODS: The SDIS is a two-phase immunization survey. The first phase is a random-digit-dialing survey in which vaccination information is obtained by phone. The second phase involves the verification of this information and/or obtaining vaccination information via the registry or the child's provider(s). RESULTS: In 2005, the sample size included 839 respondents. From 1995 to 2005, coverage for the following individual vaccines increased: diphtheria and tetanus toxoids, and acellular pertussis (92.0% to 96.5% for > or = 3 doses, and 75.0% to 89.0% for > or = 4 doses), polio (83.0% to 94.7%), measles-mumps-rubella (85.0% to 95.8%), Haemophilus influenzae type b (87.0% to 93.2%), and hepatitis B (67.0% to 93.6%). CONCLUSION: The results of the SDIS demonstrate that San Diego County has exceeded the Healthy People 2010 goal to reach at least 80% coverage for the series of universally recommended vaccinations.

Early detection and risk assessment: proceedings and recommendations from the Workshop on Epigenetics in Cancer Prevention.

Recent advances in molecular biology that have provided a greater understanding of multistage carcinogenesis include the use of biomarkers of early detection and risk assessment. Prominent among such biomarkers are epigenetic changes. The field of epigenetics has seen a recent surge of interest among cancer researchers since alterations in DNA methylation have emerged as one of the most consistent molecular alterations in multiple neoplasms. Chromatin condensation, histone deacetylation, and promoter methylation are major steps in the epigenetic regulation of gene expression. Epigenetic changes may occur due to environmental factors, aging, and genomic imprinting. An important distinction between genetic and epigenetic alterations in cancer prevention is that the latter might be more easily reversed using therapeutic interventions. In the workshop the following areas of research were recognized for emphasis in future work: (1) basic epigenetic mechanisms in cancer need further investigation; (2) technology development in the area of epigenetics, such as high-throughput quantitative assays and increased sensitivity/specificity, is essential for the early detection and risk assessment of cancer; (3) the clinical application of epigenetic changes to cancer prevention and risk assessment needs further investigation. Further research will lead to the identification of new targets for cancer prevention.