Hospital-level variation in racial disparities in low-risk nulliparous cesarean delivery rates.

BACKGROUND: Nationally, rates of cesarean delivery are highest among Black patients compared with other racial/ethnic groups. These observed inequities are a relatively new phenomenon (in the 1980s, cesarean delivery rates among Black patients were lower than average), indicating an opportunity to narrow the gap. Cesarean delivery rates vary greatly among hospitals, masking racial disparities that are unseen when rates are reported in aggregate. OBJECTIVE: This study aimed to explore reasons for the current large Black-White disparity in first-birth cesarean delivery rates by first examining the hospital-level variation in first-birth cesarean delivery rates among different racial/ethnic groups. We then identified hospitals that had low first-birth cesarean delivery rates among Black patients and compared them with hospitals with high rates. We sought to identify differences in facility or patient characteristics that could explain the racial disparity. STUDY DESIGN: A population cross-sectional study was performed on 1,267,493 California live births from 2018 through 2020 using birth certificate data linked with maternal patient discharge records. Annual nulliparous term singleton vertex cesarean delivery (first-birth) rates were calculated for the most common racial/ethnic groups statewide and for each hospital. Self-identified race/ethnicity categories as selected on the birth certificate were used. Relative risk and 95% confidence intervals for first-birth cesarean delivery comparing 2019 with 2015 were estimated using a log-binomial model for each racial/ethnic group. Patient and hospital characteristics were compared between hospitals with first-birth cesarean delivery rates <23.9% for Black patients and hospitals with rates ≥23.9% for Black patients. RESULTS: Hospitals with at least 30 nulliparous term singleton vertex Asian, Black, Hispanic, and White patients each were identified. Black patients had a very different distribution, with a significantly higher rate (28.4%) and wider standard deviation (7.1) and interquartile range (6.5) than other racial groups (P<.01). A total of 29 hospitals with a low first-birth cesarean delivery rate among Black patients were identified using the Healthy People 2020 target of 23.9% and compared with 106 hospitals with higher rates. The low-rate group had a cesarean delivery rate of 19.9%, as opposed to 30.7% in the higher-rate group. There were no significant differences between the groups in hospital characteristics (ownership, delivery volume, neonatal level of care, proportion of midwife deliveries) or patient characteristics (age, education, insurance, onset of prenatal care, body mass index, hypertension, diabetes mellitus). Among the 106 hospitals that did not meet the target for Black patients, 63 met it for White patients with a mean rate of 21.4%. In the same hospitals, the mean rate for Black patients was 29.5%. Among Black patients in the group that did not meet the 23.9% target, there were significantly higher rates of all cesarean delivery indications: labor dystocia, fetal concern (spontaneous labor), and no labor (eg, macrosomia), which are all indications with a high degree of subjectivity. CONCLUSION: The statewide cesarean delivery rate of Black patients is significantly higher and has substantially greater hospital variation compared with other racial or ethnic groups. The lack of difference in facility or patient characteristics between hospitals with low cesarean delivery rates among Black patients and those with high rates suggests that unconscious bias and structural racism potentially play important roles in creating these racial differences.

Measuring Variation in Interpregnancy Interval: Identifying Hotspots for Improvement Initiatives.

OBJECTIVE: The study aimed to determine if single year birth certificate data can be used to identify regional and hospital variation in rates of short interpregnancy interval (IPI < 6 months). STUDY DESIGN: IPI was estimated for multiparous women ages 15 to 44 years with singleton live births between 2015 and 2016. Perinatal outcomes, place of birth, maternal race, and data for IPI calculations were obtained by using birth certificates. IPI frequencies are presented as observed rates. RESULTS: The cohort included 562,039 multiparous women. Short IPI rates were similar to those obtained with analyses by using linked longitudinal data and confirmed the association with preterm birth. Short IPI rates varied by race and Hispanic nativity. There was substantial hospital (0.8-9%) and regional (2.9-6.2%) variation in short IPI rates. CONCLUSION: IPI rates can be reliably obtained from current year birth certificate data. This can be a useful tool for quality improvement projects targeting interventions and rapidly assessing their progress to promote optimal birth spacing. KEY POINTS: · Near-real time regional and hospital IPI rates can be reliably obtained from current year birth certificate data.. · Substantial variations in rates of short IPI exist between hospital and perinatal regions.. · IPI rates from individual birth certificates can be a tool to target and assess interventions..

Hospital Quality Improvement Interventions, Statewide Policy Initiatives, and Rates of Cesarean Delivery for Nulliparous, Term, Singleton, Vertex Births in California.

Importance: Safe reduction of the cesarean delivery rate is a national priority. Objective: To evaluate the rates of cesarean delivery for nulliparous, term, singleton, vertex (NTSV) births in California in the context of a statewide multifaceted intervention designed to reduce the rates of cesarean delivery. Design, Setting, and Participants: Observational study of cesarean delivery rates from 2014 to 2019 among 7 574 889 NTSV births in the US and at 238 nonmilitary hospitals providing maternity services in California. From 2016 to 2019, California Maternal Quality Care Collaborative partnered with Smart Care California to implement multiple approaches to decrease the rates of cesarean delivery. Hospitals with rates of cesarean delivery greater than 23.9% for NTSV births were invited to join 1 of 3 cohorts for an 18-month quality improvement collaborative between July 2016 and June 2019. Exposures: Within the collaborative, multidisciplinary teams implemented multiple strategies supported by mentorship, shared learning, and rapid-cycle data feedback. Partnerships among nonprofit organizations, state governmental agencies, purchasers, and health plans addressed the external environment through transparency, award programs, and incentives. Main Outcomes and Measures: The primary outcome was the change in cesarean delivery rates for NTSV births in California and a difference-in-differences analysis was performed to compare cesarean delivery rates for NTSV births in California vs the rates in the rest of the US. A mixed multivariable logistic regression model that adjusted for patient-level and hospital-level confounders also was used to assess the collaborative and the external statewide actions. The cesarean delivery rates for NTSV births at hospitals participating in the collaborative were compared with the rates from the nonparticipating hospitals and the rates in the participating hospitals prior to participation in the collaborative. Results: A total of 7 574 889 NTSV births occurred in the US from 2014 to 2019, of which 914 283 were at 238 hospitals in California. All California hospitals were exposed to the statewide actions to reduce the rates of cesarean delivery, including the 149 hospitals that had baseline rates of cesarean delivery greater than 23.9% for NTSV births, of which 91 (61%) participated in the quality improvement collaborative. The rate of cesarean delivery for NTSV births in California decreased from 26.0% (95% CI, 25.8%-26.2%) in 2014 to 22.8% (95% CI, 22.6%-23.1%) in 2019 (relative risk, 0.88; 95% CI, 0.87-0.89). The rate of cesarean delivery for NTSV births in the US (excluding California births) was 26.0% in both 2014 and 2019 (relative risk, 1.00; 95% CI, 0.996-1.005). The difference-in-differences analysis revealed that the reduction in the rate of cesarean delivery for NTSV births in California was 3.2% (95% CI, 1.7%-3.5%) higher than in the US (excluding California). Compared with the hospitals and the periods not exposed to the collaborative activities, and after adjusting for patient characteristics and time using a modified stepped-wedge analysis, exposure to collaborative activities was associated with a lower odds of cesarean delivery for NTSV births (24.4% vs 24.6%; adjusted odds ratio, 0.87 [95% CI, 0.85-0.89]). Conclusions and Relevance: In this observational study of NTSV births in California from 2014 to 2019, the rates of cesarean delivery decreased over time in the setting of the implementation of a coordinated hospital-level collaborative and statewide initiatives designed to support vaginal birth.

Hospital-Level Variation in the Frequency of Cesarean Delivery Among Nulliparous Women Who Undergo Labor Induction.

OBJECTIVE: To evaluate the use of administrative data for identification of labor induction and to estimate the variation in cesarean delivery rates among low-risk women who underwent labor induction. METHODS: A cross-sectional study was performed examining live births in California hospitals during 2016 and 2017 using birth certificate data linked with maternal patient discharge records. Initially, eight hospitals performed medical record reviews by using reVITALize definitions on 46,916 deliveries to assess the validity of induction identification by birth certificate or discharge diagnosis records or both. Hospital-level variation in cesarean delivery rates was then assessed among all California hospitals for women with low-obstetric-risk first births before and after further risk adjustment and after the exclusion of potential medical and obstetric indications for induction. Variation in physician-level cesarean delivery rates after induction at four large hospitals also was examined. The relationships between cesarean delivery rates among women with induced labors compared with noninduced labors and with the hospital rate of induction also were explored. RESULTS: Identifying induction by a combination of discharge diagnosis codes and birth certificate data had the highest accuracy (92.9%, 95% CI 92.7-93.2). Among 917,225 births at 238 birthing hospitals, there were 99,441 nulliparous women with term, singleton, vertex pregnancies who were induced. The median cesarean delivery rate after labor induction for nulliparous women with term, singleton, vertex pregnancies was 32.2%, with a range of 18.5-84.6%. This wide variation was not reduced after risk adjustment or after exclusion of all women with induction indications. A similar wide variation was noted within geographic regions, neonatal intensive care levels, and among individual physicians in the same facility. Only very weak associations were found for the cesarean delivery rate after labor induction and either the rate after noninduced labor (R<0.08) or the rate of nulliparous labor induction (R<0.12). CONCLUSION: The large variation of cesarean delivery rates after induction of labor suggests that clinical management plays an important role in achieving induction success.

Time of Birth and the Risk of Severe Unexpected Complications in Term Singleton Neonates.

OBJECTIVE: To assess whether there is a relationship between evening, night, and weekend births and severe unexpected neonatal morbidity in low-risk term singleton births. METHODS: We conducted a population-based, cross-sectional analysis. Severe unexpected neonatal morbidity as defined by the National Quality Forum specification 0716 was derived from linked birth certificate and hospital discharge summaries for 1,048,957 low-risk singleton term Californian births during 2011 through 2013. The association between the nursing shift (7 am-3 pm vs 3-11 pm and 11 pm -7 am) and weekday compared with weekend birth and the risk of severe unexpected neonatal morbidity was estimated using mixed effects logistic regression models. RESULTS: Severe unexpected neonatal morbidity was higher among births during the 3-11 pm evening shift (2.1%) and the 11 pm-7 am night shift (2.1%), compared with those during the 7 am-3 pm day shift (1.8%). The adjusted odds ratios (ORs) were 1.10 (95% CI 1.06-1.13) for the evening shift and 1.15 (1.11-1.19) for the night shift. The adjusted ORs of severe unexpected neonatal morbidity were increased only on Sunday, as compared with other days (adjusted OR 1.08, 95% CI 1.02-1.14). When our analysis was by perinatal region, the increase was seen in four of the nine perinatal regions. CONCLUSION: After risk adjustment, the risk of severe unexpected morbidity in the low-risk singleton California birth cohort was significantly increased on Sundays and births during evening and night shifts. These elevations were detected in only four of California's nine perinatal regions. Further analysis at the individual hospital level is warranted.

Reduction in racial disparities in severe maternal morbidity from hemorrhage in a large-scale quality improvement collaborative.

BACKGROUND: Eliminating persistent racial/ethnic disparities in maternal mortality and morbidity is a public health priority. National strategies to improve maternal outcomes are increasingly focused on quality improvement collaboratives. However, the effectiveness of quality collaboratives for reducing racial disparities in maternity care is understudied. OBJECTIVE: To evaluate the impact of a hemorrhage quality-improvement collaborative on racial disparities in severe maternal morbidity from hemorrhage. STUDY DESIGN: We conducted a cross-sectional study from 2011 to 2016 among 99 hospitals that participated in a hemorrhage quality improvement collaborative in California. The focus of the quality collaborative was to implement the national maternal hemorrhage safety bundle consisting of 17 evidence-based recommendations for practice and care processes known to improve outcomes. This analysis included 54,311 women from the baseline period (January 2011 through December 2014) and 19,165 women from the postintervention period (October 2015 through December 2016) with a diagnosis of obstetric hemorrhage during delivery hospitalization. We examined whether racial/ethnic-specific severe maternal morbidity rates in these women with obstetric hemorrhage were reduced from the baseline to the postintervention period. In addition, we conducted Poisson Generalized Estimating Equation models to estimate relative risks and 95% confidence intervals for severe maternal morbidity comparing each racial/ethnic group with white. RESULTS: During the baseline period, the rate of severe maternal morbidity among women with hemorrhage was 22.1% (12,002/54,311) with the greatest rate observed among black women (28.6%, 973/3404), and the lowest among white women (19.8%, 3124/15,775). The overall rate fell to 18.5% (3553/19,165) in the postintervention period. Both black and white mothers benefited from the intervention, but the benefit among black women exceeded that of white women (9.0% vs 2.1% absolute rate reduction). The baseline risk of severe maternal morbidity was 1.34 times greater among black mothers compared with white mothers (relative risk, 1.34; 95% confidence interval, 1.27-1.42), and it was reduced to 1.22 (1.05-1.40) in the postintervention period. Sociodemographic and clinical factors explained a part of the black-white differences. After controlling for these factors, the black-white relative risk was 1.22 (95% confidence interval, 1.15-1.30) at baseline and narrowed to 1.07 (1.92-1.24) in the postintervention period. Results were similar when excluding severe maternal morbidity cases with transfusion alone. After accounting for maternal risk factors, the black-white relative risk for severe maternal morbidity excluding transfusion alone was reduced from a baseline of 1.33 (95% confidence interval, 1.16-1.52) to 0.99 (0.76-1.29) in the postintervention period. The most important clinical risk factor for disparate black rates for both severe maternal morbidity and severe maternal morbidity excluding transfusion alone was cesarean delivery, potentially providing another opportunity for quality improvement. CONCLUSION: A large-scale quality improvement collaborative reduced rates of severe maternal morbidity due to hemorrhage in all races and reduced the performance gap between black and white women. Improving access to highly effective treatments has the potential to decrease disparities for care-sensitive acute hospital-focused morbidities.

Age at start of using tobacco on the risk of head and neck cancer: Pooled analysis in the International Head and Neck Cancer Epidemiology Consortium (INHANCE).

BACKGROUND: Tobacco use is a well-established risk factor for head and neck cancer (HNC). However, less is known about the potential impact of exposure to tobacco at an early age on HNC risk. METHODS: We analyzed individual-level data on ever tobacco smokers from 27 case-control studies (17,146 HNC cases and 17,449 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random-effects logistic regression models. RESULTS: Without adjusting for tobacco packyears, we observed that younger age at starting tobacco use was associated with an increased HNC risk for ever smokers (OR<10 years vs. ≥30 years: 1.64, 95% CI: 1.35, 1.97). However, the observed association between age at starting tobacco use and HNC risk became null after adjusting for tobacco packyears (OR<10 years vs. ≥30 years: 0.97, 95% CI: 0.80, 1.19). In the stratified analyses on HNC subsites by tobacco packyears or years since quitting, no difference in the association between age at start and HNC risk was observed. CONCLUSIONS: Results from this pooled analysis suggest that increased HNC risks observed with earlier age at starting tobacco smoking are largely due to longer duration and higher cumulative tobacco exposures.

Safety Assessment of a Large-Scale Improvement Collaborative to Reduce Nulliparous Cesarean Delivery Rates.

OBJECTIVE: To evaluate maternal and neonatal safety measures in a large-scale quality improvement program associated with reductions in nulliparous, term, singleton, vertex cesarean delivery rates. METHODS: This is a cross-sectional study of the 2015-2017 California Maternal Quality Care Collaborative (CMQCC) statewide collaborative to support vaginal birth and reduce primary cesarean delivery. Hospitals with nulliparous, term, singleton, vertex cesarean delivery rates greater than 23.9% were solicited to join. Fifty-six hospitals with more than 119,000 annual births participated; 87.5% were community facilities. Safety measures were derived using data collected as part of routine care and submitted monthly to CMQCC: birth certificates, maternal and neonatal discharge diagnosis and procedure files, and selected clinical data elements submitted as supplemental data files. Maternal measures included chorioamnionitis, blood transfusions, third- or fourth-degree lacerations, and operative vaginal delivery. Neonatal measures included the severe unexpected newborn complications metric and 5-minute Apgar scores less than 5. Mixed-effect multivariable logistic regression model was used to calculate odds ratios (Ors) and 95% CIs. RESULTS: Among collaborative hospitals, the nulliparous, term, singleton, vertex cesarean delivery rate fell from 29.3% in 2015 to 25.0% in 2017 (2017 vs 2015 adjusted OR [aOR] 0.76, 95% CI 0.73-0.78). None of the six safety measures showed any difference comparing 2017 to 2015. As a sensitivity analysis, we examined the tercile of hospitals with the greatest decline (31.2%-20.6%, 2017 vs 2015 aOR 0.54, 95% CI 0.50-0.58) to evaluate whether they had greater risk of poor maternal and neonatal outcomes. Again, no measure was statistically worse, and the severe unexpected newborn complications composite actually declined (3.2%-2.2%, aOR 0.71, 95% CI 0.55-0.92). CONCLUSION: Mothers and neonates participating in a large-scale Supporting Vaginal Birth collaborative had no evidence of worsened birth outcomes, even in hospitals with large cesarean delivery rate reductions, supporting the safety of efforts to reduce primary cesarean delivery using American College of Obstetricians and Gynecologists and Society for Maternal-Fetal Medicine guidelines and enhanced labor support.

Trends in Statin Use 2009-2015 in a Large Integrated Health System: Pre- and Post-2013 ACC/AHA Guideline on Treatment of Blood Cholesterol.

PURPOSE: Implementation of the 2013 ACC/AHA cholesterol treatment guideline is likely to vary by statin benefit group. The aim of this study was to document trends in statin use before and after introduction of the ACC/AHA guideline. METHODS: We conducted a retrospective study with annual cohorts from 2009 to 2015 among members of Kaiser Permanente Southern California aged ≥ 21 years. Members were categorized into four mutually exclusive statin benefit groups: atherosclerotic cardiovascular disease (ASCVD), LDL-C ≥ 190 mg/dL in the last year, diabetes (aged 40-75 years), and 10-year ASCVD risk ≥ 7.5% (aged 40-75 years). RESULTS: The cohorts ranged from 1,993,755 members in 2009 to 2,440,429 in 2015. Approximately 5% of patients had ASCVD, 1% had LDL-C ≥ 190 mg/dL, 6% had diabetes, and 10% had a 10-year ASCVD risk ≥ 7.5% each year. Trends in statin use were stable for adults with ASCVD (2009 78%; 2015 80%), recent LDL-C ≥ 190 mg/dL (2009 45%; 2015 44%), and diabetes (2009 74%; 2015 73%), but increased for patients with 10-year ASCVD risk ≥ 7.5% (2009 36%; 2015 47%). High-intensity statin use also increased 142% and 54% among patients with LDL-C ≥ 190 mg/dL and those with ASCVD ≤ 75 years of age, respectively. Moderate-to-high intensity statin utilization increased over 50% among those with a 10-year ASCVD risk ≥ 7.5%. CONCLUSIONS: Statin use increased substantially among patients with 10-year ASCVD risk ≥ 7.5% and use of appropriate statin dosage increased in each of the four statin benefit groups between 2009 and 2015; however, there is room for improvement.

Trends in Lipid Screening Among Adults in an Integrated Health Care Delivery System, 2009-2015.

BACKGROUND: Lipid screening determines eligibility for statins and other cardiovascular risk reduction interventions. OBJECTIVE: To examine trends in lipid screening among adults aged ≥20 years in a large, multiethnic, integrated health care delivery system in southern California. METHODS: Temporal trends in lipid screening were examined from 2009 to 2015 with an index date of September 30 of each year. Lipid screening was defined as the proportion of eligible members each year who (a) had ever been screened among those aged 20-39 years and (b) had been screened in the previous 6 years for those aged ≥ 40 years. Trends were analyzed by age, gender, and the presence of atherosclerotic cardiovascular disease (ASCVD) or diabetes without ASCVD status. RESULTS: More than 2 million individuals were included each year: 5%-6% had ASCVD (includes those with diabetes), 7%-8% had diabetes without ASCVD, and 87% had neither condition. Among the entire population, lipid screening increased from 79.8% in 2009 to 82.6% in 2015 (P < 0.0001). Among those with ASCVD or diabetes, lipid screening was 99% across all years. Among those without ASCVD or DM, screening increased from 76.9% in 2009 to 80.0% in 2015 (P < 0.0001), with higher screening among women compared with men and lower screening among individuals younger than 55 years. CONCLUSIONS: Consistently high rates of lipid screening were observed among individuals with ASCVD or diabetes. In individuals without these conditions, screening increased over time. However, there is room to further increase screening rates in adults younger than 55 years. DISCLOSURES: This manuscript and research work was supported by a contractual agreement between the Southern California Permanente Medical Group and Regeneron Pharmaceuticals and Sanofi U.S. Researchers from Regeneron and Sanofi collaborated on the study design, interpretation of data, and writing of the manuscript. Ling Grant, Harrison, Chang, Hsu, Cheetham, Wei, and Reynolds are employed by Kaiser Permanente Southern California. Scott is employed by Southern California Permanente Medical Group. Boklage is employed by Regeneron, and Romo-LeTourneau is employed by Sanofi. Preliminary results from this study were presented at the American Heart Association Scientific Sessions; November 12-16, 2016; New Orleans, LA.

Improving Maternal Safety at Scale with the Mentor Model of Collaborative Improvement.

BACKGROUND: Obstetric safety bundles, consisting of action steps shown to improve outcomes, have been developed to address the most common and preventable causes of maternal morbidity and mortality. Implementing these best practices across all birthing facilities remains an important and challenging clinical and public health priority. METHODS: The California Maternal Quality Care Collaborative (CMQCC) developed an innovative external mentor model for large-scale collaborative improvement in which participating organizations were subdivided into small teams of six to eight hospitals, led by a paired dyad of physician and nurse leaders. The mentor model preserves the active sharing that enhances improvement across a large group of facilities working on the same project while enabling individualized attention to teams. The mentor model was tested by implementing the obstetric hemorrhage safety bundle (which consists of 17 key practices in four domains) in multiple California hospitals. RESULTS: A total of 126 hospitals were engaged to simultaneously implement the safety bundle. The adoption rates for the recommended practices in the four action domains were (1) Readiness, 78.9%; (2) Recognition and Prevention, 76.5%; (3) Response, 63.1%; and (4) Reporting and Systems Learning, 58.7%. Mentors (31/40) and participating teams (48 responses from 39/126 hospitals) provided feedback in an exit survey. Among the respondents, 64.5% of mentors and 72.9% of participants agreed that compared to a traditional collaborative structure, the mentor model was better suited for quality improvement at scale. CONCLUSION: The mentor model was successful in providing individualized support to teams and enabled implementation of the hemorrhage safety bundle across a diverse group of 126 hospitals.

Ataxia Telangiectasia-Mutated (ATM)Polymorphisms and Risk of Lung Cancer in a Chinese Population.

BACKGROUND: The ataxia telangiectasia-mutated (ATM) gene has a key role in DNA repair including activation and stabilization of p53, which implicates the importance of ATM polymorphisms in the development of cancer. This study aims to investigate the association of two ATM single-nucleotide polymorphisms (SNPs) with lung cancer, as well as their potential interaction with p53 gene and other known risk factors of lung cancer. METHODS: A population-based case-control study was conducted in Taiyuan city, China with 399 cases and 466 controls matched on the distribution of age and sex of cases. The two ATM gene SNPs, ATMrs227060 and ATMrs228589 as well as p53 gene SNP, p53rs1042522 were genotyped using Sequenom platform. Unconditional logistic regression models were used to estimate crude and adjusted odds ratios (aOR) and 95% confidence intervals (CIs). Adjusted models controlled for age, sex, and smoking status. RESULTS: The study showed that TT genotype of ATMrs227060 (aOR = 1.58, 95% CI: 1.06-2.35) and AA genotype of ATMrs228589 were significantly associated with lung cancer (aOR = 1.50, 95% CI: 1.08-2.08) in a recessive model. Additionally, carrying variant genotypes of ATMrs227060 (TT), ATMrs228589 (AA), and p53rs1042522 (CC) concomitantly was associated with much higher risk (aOR = 3.68, 95% CI: 1.43-9.45) of lung cancer than carrying variant genotypes of any one of the above three SNPs. We also found multiplicative and additive interaction between tea drinking and ATMrs227060 in association with lung cancer. CONCLUSION: This study indicates that ATM gene variants might be associated with development of lung cancer in Chinese population. These results need to be validated in larger and different population samples.

Case-control study of cumulative cigarette tar exposure and lung and upper aerodigestive tract cancers.

The development of comprehensive measures for tobacco exposure is crucial to specify effects on disease and inform public health policy. In this population-based case-control study, we evaluated the associations between cumulative lifetime cigarette tar exposure and cancers of the lung and upper aerodigestive tract (UADT). The study included 611 incident cases of lung cancer; 601 cases of UADT cancers (oropharyngeal, laryngeal and esophageal cancers); and 1,040 cancer-free controls. We estimated lifetime exposure to cigarette tar based on tar concentrations abstracted from government cigarette records and self-reported smoking histories derived from a standardized questionnaire. We analyzed the associations for cumulative tar exposure with lung and UADT cancer, overall and according to histological subtype. Cumulative tar exposure was highly correlated with pack-years among ever smoking controls (Pearson coefficient = 0.90). The adjusted odds ratio (95% confidence limits) for the estimated effect of about 1 kg increase in tar exposure (approximately the interquartile range in all controls) was 1.61 (1.50, 1.73) for lung cancer and 1.21 (1.13, 1.29) for UADT cancers. In general, tar exposure was more highly associated with small, squamous and large cell lung cancer than adenocarcinoma. With additional adjustment for pack-years, positive associations between tar and lung cancer were evident, particularly for small cell and large cell subtypes. Therefore, incorporating the composition of tobacco carcinogens in lifetime smoking exposure may improve lung cancer risk estimation. This study does not support the claim of a null or inverse association between "low exposure" to tobacco smoke and risk of these cancer types.

Association between PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), GCKR (rs780094), and elevated transaminase levels in overweight/obese Mexican adults.

There is scarce information about the link between specific single-nucleotide polymorphisms (SNPs) and risk of liver disease among Latinos, despite the disproportionate burden of disease among this population. Our aim was to investigate nine SNPs in or near the following genes: PNPLA3, LYPLAL1, PPP1R3B, GCKR, NCAN, IRS1, PPARG, and ADIPOR2 and examine their association with persistently elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels in Mexican adults. Data and samples were collected from 741 participants in the Mexican Health Worker Cohort Study, in Cuernavaca, Mexico. We identified 207 cases who had persistently elevated levels of ALT or AST (≥40 U/L) and 534 controls with at least two consecutive normal ALT or AST results in a 6 month period, during 2004-2006 and 2011-2013. TaqMan assays were used to genotype the SNPs. The risk allele of PNPLA3 rs738409 was found to be associated with persistently elevated levels of ALT or AST, adjusting for age, sex, BMI, type 2 diabetes, and ancestry: (OR 2.28, 95 % CI 1.13, 4.58). A significant association was found between the LYPLAL1, PPP1R3B, and GCKR risk alleles and elevated ALT or AST levels among overweight/obese adults. These results suggest that among Mexicans, the PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), and GCKR (rs780094) polymorphisms may be associated with a greater risk of chronic liver disease among overweight adults. This study is the first to examine these nine SNPs in a sample of adults in Mexico.

MicroRNA-related polymorphisms and non-Hodgkin lymphoma susceptibility in the Multicenter AIDS Cohort Study.

BACKGROUND: MicroRNAs, small non-coding RNAs involved in gene regulation, are implicated in lymphomagenesis. We evaluated whether genetic variations in microRNA coding regions, binding sites, or biogenesis genes (collectively referred to as miRNA-SNPs) were associated with risk of AIDS-associated non-Hodgkin lymphoma (AIDS-NHL), and serum levels of four lymphoma-related microRNAs. METHODS: Twenty-five miRNA-SNPs were genotyped in 180 AIDS-NHL cases and 529 HIV-infected matched controls from the Multicenter AIDS Cohort Study (MACS), and real-time polymerase chain reaction was used to quantify serum microRNA levels. Adjusted odds ratios (ORs) estimated using conditional logistic regression evaluated associations between miRNA-SNPs and AIDS-NHL risk. A semi-Bayes shrinkage approach was employed to reduce likelihood of false-positive associations. Adjusted mean ratios (MR) calculated using linear regression assessed associations between miRNA-SNPs and serum microRNA levels. RESULTS: DDX20 rs197412, a non-synonymous miRNA biogenesis gene SNP, was associated with AIDS-NHL risk (OR=1.34 per minor allele; 95% CI: 1.02-1.75), and higher miRNA-222 serum levels nearing statistical significance (MR=1.21 per minor allele; 95% CI: 0.98-1.49). MiRNA-196a2 rs11614913 was associated with decreased central nervous system (CNS) AIDS-NHL (CT vs. CC OR=0.52; 95% CI: 0.27-0.99). The minor allele of HIF1A rs2057482, which creates a miRNA-196a2 binding site, was associated with systemic AIDS-NHL risk (OR=1.73 per minor allele; 95% CI: 1.12-2.67), and decreased CNS AIDS-NHL risk (OR=0.49 per minor allele; 95% CI: 0.25-0.94). CONCLUSIONS: This study suggests that a few miRNA-SNPs are associated with AIDS-NHL risk and may modulate miRNA expression. These results support a role for miRNA in AIDS-NHL and may highlight pathways to be targeted for risk stratification or therapeutics.

Genetic Risk Can Be Decreased: Quitting Smoking Decreases and Delays Lung Cancer for Smokers With High and Low CHRNA5 Risk Genotypes - A Meta-Analysis.

BACKGROUND: Recent meta-analyses show that individuals with high risk variants in CHRNA5 on chromosome 15q25 are likely to develop lung cancer earlier than those with low-risk genotypes. The same high-risk genetic variants also predict nicotine dependence and delayed smoking cessation. It is unclear whether smoking cessation confers the same benefits in terms of lung cancer risk reduction for those who possess CHRNA5 risk variants versus those who do not. METHODS: Meta-analyses examined the association between smoking cessation and lung cancer risk in 15 studies of individuals with European ancestry who possessed varying rs16969968 genotypes (N=12,690 ever smokers, including 6988 cases of lung cancer and 5702 controls) in the International Lung Cancer Consortium. RESULTS: Smoking cessation (former vs. current smokers) was associated with a lower likelihood of lung cancer (OR=0.48, 95%CI=0.30-0.75, p=0.0015). Among lung cancer patients, smoking cessation was associated with a 7-year delay in median age of lung cancer diagnosis (HR=0.68, 95%CI=0.61-0.77, p=4.9∗10-10). The CHRNA5 rs16969968 risk genotype (AA) was associated with increased risk and earlier diagnosis for lung cancer, but the beneficial effects of smoking cessation were very similar in those with and without the risk genotype. CONCLUSION: We demonstrate that quitting smoking is highly beneficial in reducing lung cancer risks for smokers regardless of their CHRNA5 rs16969968 genetic risk status. Smokers with high-risk CHRNA5 genotypes, on average, can largely eliminate their elevated genetic risk for lung cancer by quitting smoking- cutting their risk of lung cancer in half and delaying its onset by 7years for those who develop it. These results: 1) underscore the potential value of smoking cessation for all smokers, 2) suggest that CHRNA5 rs16969968 genotype affects lung cancer diagnosis through its effects on smoking, and 3) have potential value for framing preventive interventions for those who smoke.

Association of sugary beverages with survival among patients with cancers of the upper aerodigestive tract.

PURPOSE: The role of consumption of added sugars in cancers of the upper aerodigestive tract (UADT) is unclear. We examined associations between sugary beverages and susceptibility to UADT cancer as well as overall survival among UADT cancer patients. METHODS: The association between dietary added sugar and susceptibility to UADT cancers or overall survival among 601 UADT cancer cases was evaluated using data from a population-based case-control study conducted in Los Angeles County. Unconditional logistic regression was used to estimate odds ratios and 95 % confidence intervals (CI) for cancer susceptibility, and Cox regression was used to estimate hazards ratios (HRs) with 95 % CIs for survival, adjusting for relevant confounders. RESULTS: A total of 248 deaths were observed during follow-up (median 12.1 years). A positive association was observed with consumption of grams of sugar from beverages, including soft drinks and fruit juices, and poorer survival among UADT cancer cases (aHR, Q4 vs. Q1:1.88; 95 % CI 1.29, 2.72; p for trend = 0.002), as well as servings of sugary beverages (aHR, Q4 vs. Q1: 95 % CI 1.97, 95 % CI 1.32-2.93). This was due largely to consumption of sugars from soft drinks. Particularly, high consumption of sugary beverages was associated with poorer survival among esophageal cancer cases, driven by squamous cancers. No association was observed between sugary beverages and cancer susceptibility. CONCLUSION: These findings suggest that consumption of sugary beverages may decrease survival associated with UADT cancers. Additional studies should be conducted to examine survival among cancer patients consuming high amounts of added or refined sugars. Such studies may highlight prognostic factors for UADT cancers.

Associations of red and processed meat with survival among patients with cancers of the upper aerodigestive tract and lung.

The effect of red and processed meats on cancer survival is unclear. We sought to examine the role of total and processed red meat consumption on all-cause mortality among patients with cancers of the upper aerodigestive tract (UADT) and lung, in order to test our hypothesis that red or processed meat was associated with overall mortality in these patients. Using data from a population-based case-control study conducted in Los Angeles County, we conducted a case-only analysis to examine the association of red or processed meat consumption on mortality after 12 years of follow-up, using a diet history questionnaire. Cox regression was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), adjusting for potential confounders. Of 601 UADT cancer cases and 611 lung cancer cases, there were 248 and 406 deaths, respectively, yielding crude mortality rates of 0.07 and 0.12 deaths per year. Comparing the highest with lowest quartile of red meat consumption, the adjusted HR was 1.64 (95% CI, 1.04-2.57) among UADT cancer cases; for red or processed meat, the adjusted HR was 1.76 (95% CI, 1.10-2.82). A dose-response trend was observed. A weaker association was observed with red meat consumption and overall mortality among lung cancer cases. In conclusion, this case-only analysis demonstrated that increased consumption of red or processed meats was associated with mortality among UADT cancer cases and WAS weakly associated with mortality among lung cancer cases.