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IntroductionStudies of hypertension in pregnancy that use electronic health care data generally identify hypertension using hospital diagnosis codes alone. We sought to compare results from this approach to an approach that included diagnosis codes, antihypertensive medications and blood pressure (BP) values.Materials and methodsWe conducted a retrospective cohort study of 1,45,739 pregnancies from 2009 to 2014 within an integrated healthcare system. Hypertensive pregnancies were identified using the “BP-Inclusive Definition” if at least one of three criteria were met: (1) two elevated outpatient BPs, (2) antihypertensive medication fill plus an outpatient hypertension diagnosis, or (3) hospital discharge diagnosis for preeclampsia or eclampsia. The “Traditional Definition” considered only delivery hospitalization discharge diagnoses. Outcome event analyses compared rates of preterm delivery and small for gestational age (SGA) between the two definitions.ResultsThe BP-Inclusive Definition identified 14,225 (9.8%) hypertensive pregnancies while the Traditional Definition identified 13,637 (9.4%); 10,809 women met both definitions. Preterm delivery occurred in 20.9% of BP-Inclusive Definition pregnancies, 21.8% of Traditional Definition pregnancies and 6.6% of non-hypertensive pregnancies; for SGA the numbers were 15.6, 16.3, and 8.6%, respectively (p < 0.001 for all events compared to non-hypertensive pregnancies). Analyses in women meeting only one hypertension definition (21–24% of positive cases) found much lower rates of both preterm delivery and SGA.ConclusionPrevalence of hypertension in pregnancy was similar between the two study definitions. However, a substantial number of women met only one of the study definitions. Women who met only one of the hypertension definitions had much lower rates of adverse neonatal events than women meeting both definitions.

ObjectiveTo compare maternal and infant outcomes with different antihypertensive medications in pregnancy.DesignRetrospective cohort study.SettingKaiser Permanente, a large healthcare system in the United States.PopulationWomen aged 15-49 years with a singleton birth from 2005-2014 treated for hypertension.MethodsWe identified medication exposure from automated pharmacy data based on the earliest dispensing after the first prenatal visit. Using logistic regression, we calculated weighted outcome prevalences, adjusted odds ratios (aORs) and 95% confidence intervals, with inverse probability of treatment weighting to address confounding.Main outcome measuresSmall for gestational age, preterm delivery, neonatal and maternal intensive care unit (ICU) admission, preeclampsia, and stillbirth or termination at > 20 weeks.ResultsAmong 6346 deliveries, 87% with chronic hypertension, the risk of the infant being small for gestational age (birthweight < 10th percentile) was lower with methyldopa than labetalol (prevalence 13.6% vs. 16.6%; aOR 0.77, 95% CI 0.63 to 0.92). For birthweight < 3rd percentile the aOR was 0.57 (0.39 to 0.80). Compared with labetalol (26.0%), risk of preterm delivery was similar for methyldopa (26.5%; aOR 1.10 [0.95 to 1.27]) and slightly higher for nifedipine (28.5%; aOR 1.25 [1.06 to 1.46]) and other β-blockers (31.2%; aOR 1.58 [1.07 to 2.23]). Neonatal ICU admission was more common with nifedipine than labetalol (25.9% vs. 23.3%, aOR 1.21 [1.02 to 1.43]) but not elevated with methyldopa. Risks of other outcomes did not differ by medication.ConclusionsRisk of most outcomes was similar comparing labetalol, methyldopa and nifedipine. Risk of the infant being small for gestational age was substantially lower for methyldopa, suggesting this medication may warrant further consideration.

Background Direct oral anticoagulants (DOACs) are widely used in patients with nonvalvular atrial fibrillation for stroke prevention. However, long‐term adherence to DOACs and clinical outcomes in real‐world clinical practice is not well understood. This study evaluated long‐term medication adherence patterns to DOAC therapy and clinical outcomes in a large US integrated health care system. Methods and Results We included adult patients with nonvalvular atrial fibrillation who newly initiated DOACs between 2012 and 2018 in Kaiser Permanente Southern California. Long‐term (3.5 years) adherence trajectories to DOAC were investigated using monthly proportion of days covered and group‐based trajectory models. Factors associated with long‐term adherence trajectories were investigated. Multivariable Poisson regression analyses were used to investigate thromboembolism and major bleeding events associated with long‐term adherence trajectories. Of 18 920 patients newly initiating DOACs, we identified 3 DOAC adherence trajectories: consistently adherent (85.2%), early discontinuation within 6 months (10.6%), and gradually declining adherence (4.2%). Predictors such as lower CHA2DS2‐VASc (0–1 versus ≥5) and previous injurious falls were associated with both early discontinuation and gradually declining adherence trajectories. Early discontinuation of DOAC therapy was associated with a higher risk of thromboembolism (rate ratio, 1.40; 95% CI, 1.05–1.86) especially after 12 months from DOAC initiation but a lower risk of major bleed compared with consistent adherence (rate ratio, 0.48; 95% CI, 0.30–0.75), specifically during the first 12 months following DOAC initiation. A gradual decline in adherence to DOACs was not statistically significantly associated with thromboembolism outcomes compared with consistent adherence. Conclusions Although a large proportion of patients with nonvalvular atrial fibrillation were adherent to DOAC therapy over 3.5 years, early discontinuation of DOAC was associated a higher risk of thromboembolic events. Future tailored interventions for early discontinuers may improve clinical outcomes.

Many epidemiology studies report that atopic conditions such as allergies are associated with reduced pancreas cancer risk. The reason for this relationship is not yet understood. This is the first study to comprehensively evaluate the association between variants in atopy-related candidate genes and pancreatic cancer risk.A population-based case-control study of pancreas cancer cases diagnosed during 2011-2012 (via Ontario Cancer Registry), and controls recruited using random digit dialing utilized DNA from 179 cases and 566 controls. Following an exhaustive literature review, SNPs in 180 candidate genes were pre-screened using dbGaP pancreas cancer GWAS data; 147 SNPs in 56 allergy-related immunologic genes were retained and genotyped. Logistic regression was used to estimate age-adjusted odd ratio (AOR) for each variant and false discovery rate was used to adjust Wald p-values for multiple testing. Subsequently, a risk allele score was derived based on statistically significant variants.18 SNPs in 14 candidate genes (CSF2, DENND1B, DPP10, FLG, IL13, IL13RA2, LRP1B, NOD1, NPSR1, ORMDL3, RORA, STAT4, TLR6, TRA) were significantly associated with pancreas cancer risk. After adjustment for multiple comparisons, two LRP1B SNPs remained statistically significant; for example, LRP1B rs1449477 (AA vs. CC: AOR=0.37, 95% CI: 0.22-0.62; p (adjusted)=0.04). Furthermore, the risk allele score was associated with a significant reduction in pancreas cancer risk (p=0.0007).Preliminary findings suggest certain atopy-related variants may be associated with pancreas cancer risk. Further studies are needed to replicate this, and to elucidate the biology behind the growing body of epidemiologic evidence suggesting allergies may reduce pancreatic cancer risk.

Aim: To examine whether tumor-specific and tumor-agnostic oncology trials produce comparable estimates of objective response rate (ORR) in BRAF-altered cancers. Materials & methods: Electronic database searches were performed to identify phase I–III clinical trials testing tyrosine kinase inhibitors from 2000 to 2021. A random-effects model was used to pool ORRs. A total of 22 cohorts from five tumor-agnostic trials and 41 cohorts from 27 tumor-specific trials had published ORRs. Results: There was no significant difference between pooled ORRs from either trial design for multitumor analyses (37 vs 50%; p = 0.05); thyroid cancer (57 vs 33%; p = 0.10); non-small-cell lung cancer (39 vs 53%; p = 0.18); or melanoma (55 vs 51%; p = 0.58). Conclusion: For BRAF-altered advanced cancers, tumor-agnostic trials do not yield substantially different results from tumor-specific trials. Two types of studies were sought, including studies that measured health outcomes in patients who were selected to receive medicine based on the location of their cancer (tumor), called tumor-specific studies; and studies that measured health outcomes in patients who were selected to receive cancer medicine regardless of the location of their cancer (tumor), called tumor-agnostic studies. From the studies found, only the studies that tested a specific type of cancer medicine (called tyrosine kinase inhibitors) on cancers with a specific genetic alteration (called BRAF-altered cancers) were identified. These studies were included in the analysis. The goal of the analysis was to determine if the two types of studies gave similar estimates of response rate, which is a type of trial outcome that measures whether the cancer shrinks or disappears. To do this, the results from the tumor-specific studies were combined with the results of the tumor-agnostic studies. No meaningful differences in the results from the tumor-specific studies compared with the tumor-agnostic studies were found. This suggests that tumor-specific studies do not yield very different results from tumor-agnostic studies. For BRAF-altered advanced cancers, tumor-agnostic clinical trials do not yield substantially different results from tumor-specific studies and may offer a more efficient method for efficacy across multiple tumor types simultaneously, with less between-study heterogeneity. [ABSTRACT FROM AUTHOR]

Introduction: In the United States, there has been controversy over whether treatment of mild‐to‐moderate hypertension during pregnancy conveys more benefit than risk. Objective: The objective of the study was to compare risks and benefits of treatment of mild‐to‐moderate hypertension during pregnancy. Methods: This retrospective cohort study included 11,871 pregnant women with mild‐to‐moderate hypertension as defined by blood pressure (BP) values from three Kaiser Permanente regions between 2005 and 2014. Data were extracted from electronic health records. Dynamic marginal structural models with inverse probability weighting and informative censoring were used to compare risks of adverse outcomes when beginning antihypertensive medication treatment at four BP thresholds (≥155/105, ≥150/100, ≥145/95, ≥140/90 mm Hg) compared with the recommended threshold in the United States at that time, ≥160/110 mm Hg. Outcomes included preeclampsia, preterm birth, small‐for‐gestational‐age (SGA), Neonatal Intensive Care Unit (NICU) care, and stillbirth. Primary analyses allowed 2 weeks for medication initiation after an elevated BP. Several sensitivity and subgroup (i.e., race/ethnicity and pre‐pregnancy body mass index) analyses were also conducted. Results: In primary analyses, medication initiation at lower BP thresholds was associated with greater risk of most outcomes. Comparing the lowest (≥140/90 mm Hg) to the highest BP threshold (≥160/110 mm Hg), we found an excess risk of preeclampsia (adjusted Risk Difference (aRD) 38.6 per 100 births, 95% Confidence Interval (CI): 30.6, 46.6), SGA (aRD: 10.2 per 100 births, 95% CI: 2.6, 17.8), NICU admission (aRD: 20.2 per 100 births, 95% CI: 12.6, 27.9), and stillbirth (1.18 per 100 births, 95% CI: 0.27, 2.09). The findings did not reach statistical significance for preterm birth (aRD: 2.5 per 100 births, 95% CI: −0.4, 5.3). These relationships were attenuated and did not always reach statistically significance when comparing higher BP treatment thresholds to the highest threshold (i.e., ≥160/110 mm Hg). Sensitivity and subgroup analyses produced similar results. Conclusions: Initiation of antihypertensive medication at mild‐to‐moderate BP thresholds (140–155/90–105 mm Hg; with the largest risk consistently associated with treatment at 140/90 mm Hg) may be associated with adverse maternal and neonatal outcomes. Limitations include inability to measure medication adherence. [ABSTRACT FROM AUTHOR]

Objective: To compare maternal and infant outcomes with different antihypertensive medications in pregnancy. Design: Retrospective cohort study. Setting: Kaiser Permanente, a large healthcare system in the United States. Population: Women aged 15–49 years with a singleton birth from 2005–2014 treated for hypertension. Methods: We identified medication exposure from automated pharmacy data based on the earliest dispensing after the first prenatal visit. Using logistic regression, we calculated weighted outcome prevalences, adjusted odds ratios (aORs) and 95% confidence intervals, with inverse probability of treatment weighting to address confounding. Main outcome measures: Small for gestational age, preterm delivery, neonatal and maternal intensive care unit (ICU) admission, preeclampsia, and stillbirth or termination at > 20 weeks. Results: Among 6346 deliveries, 87% with chronic hypertension, the risk of the infant being small for gestational age (birthweight < 10th percentile) was lower with methyldopa than labetalol (prevalence 13.6% vs. 16.6%; aOR 0.77, 95% CI 0.63 to 0.92). For birthweight < 3rd percentile the aOR was 0.57 (0.39 to 0.80). Compared with labetalol (26.0%), risk of preterm delivery was similar for methyldopa (26.5%; aOR 1.10 [0.95 to 1.27]) and slightly higher for nifedipine (28.5%; aOR 1.25 [1.06 to 1.46]) and other β-blockers (31.2%; aOR 1.58 [1.07 to 2.23]). Neonatal ICU admission was more common with nifedipine than labetalol (25.9% vs. 23.3%, aOR 1.21 [1.02 to 1.43]) but not elevated with methyldopa. Risks of other outcomes did not differ by medication. Conclusions: Risk of most outcomes was similar comparing labetalol, methyldopa and nifedipine. Risk of the infant being small for gestational age was substantially lower for methyldopa, suggesting this medication may warrant further consideration. [ABSTRACT FROM AUTHOR]

Background Antibiotic stewardship programs (ASPs) have demonstrated success at reducing costs, yet there is limited quality evidence of their effectiveness in reducing infections of high-profile drug-resistant organisms. Methods This retrospective, cohort study included all Kaiser Permanente Southern California (KPSC) members aged ≥18 years hospitalized in 9 KPSC hospitals from 1 January 2008 to 31 December 2016. We measured the impact of staggered ASP implementation on consumption of 18 ASP-targeted antibiotics using generalized linear mixed-effects models. We used multivariable generalized linear mixed-effects models to estimate the adjusted effect of an ASP on rates of infection with drug-resistant organisms. Analyses were adjusted for confounding by time, cluster effects, and patient- and hospital-level characteristics. Results We included 765 111 hospitalizations (288 257 pre-ASP, 476 854 post-ASP). By defined daily dose, we found a 6.1% (−7.5% to −4.7%) overall decrease antibiotic use post-ASP; by days of therapy, we detected a 4.3% (−5.4% to −3.1%) decrease in overall use of antibiotics. The number of prescriptions increased post-ASP (1.04 [1.03–1.05]). In adjusted analyses, we detected an overall increase in vancomycin-resistant enterococci infections post-ASP (1.37 [1.10–1.69]). We did not detect a change in the rates of extended-spectrum beta-lactamase, carbapenem-resistant Enterobacteriaceae, and multidrug-resistant Pseudomonas aeruginosa infections post-ASP. Conclusions ASPs with successful reductions in consumption of targeted antibiotics may not see changes in infection rates with antibiotic-resistant organisms in the 2 to 6 years post-implementation. There are likely differing timescales for reversion to susceptibility across organisms and antibiotics, and unintended consequences from compensatory prescribing may occur. [ABSTRACT FROM AUTHOR]

Background Urinary tract infections (UTIs) occur commonly, but recent data on UTI rates are scarce. It is unknown how the growth of virtual healthcare delivery affects outpatient UTI management and trends in the United States. Methods From 1 January 2008 to 31 December 2017, UTIs from outpatient settings (office, emergency, and virtual visits) were identified from electronic health records at Kaiser Permanente Southern California using multiple UTI definitions. Annual rates estimated by Poisson regression were stratified by sex, care setting, age, and race/ethnicity. Annual trends were estimated by linear or piecewise Poisson regression. Results UTIs occurred in 1 065 955 individuals. Rates per 1000 person-years were 53.7 (95% confidence interval [CI], 50.6–57.0) by diagnosis code with antibiotic and 25.8 (95% CI, 24.7–26.9) by positive culture. Compared to office and emergency visits, UTIs were increasingly diagnosed in virtual visits, where rates by diagnosis code with antibiotic increased annually by 21.2% (95% CI, 16.5%–26.2%) in females and 29.3% (95% CI, 23.7%–35.3%) in males. Only 32% of virtual care diagnoses had a culture order. Overall, UTI rates were highest and increased the most in older adults. Rates were also higher in Hispanic and white females and black and white males. Conclusions Outpatient UTI rates increased from 2008 to 2017, especially in virtual care and among older adults. Virtual care is important for expanding access to health services, but strategies are needed in all outpatient care settings to ensure accurate UTI diagnosis and reduce inappropriate antibiotic treatment. [ABSTRACT FROM AUTHOR]

Background: There is a global obesity crisis, particularly among women and disadvantaged populations. Early-life intervention to prevent childhood obesity is a priority for public health, global health, and clinical practice. Understanding the association between childhood obesity and maternal pre-pregnancy weight status would inform policy and practice by allowing one to estimate the potential for offspring health gain through channelling resources into intervention. This systematic review and meta-analysis aimed to examine the dose-response association between maternal body mass index (BMI) and childhood obesity in the offspring.Methods and Findings: Searches in MEDLINE, Child Development & Adolescent Studies, CINAHL, Embase, and PsycInfo were carried out in August 2017 and updated in March 2019. Supplementary searches included hand-searching reference lists, performing citation searching, and contacting authors. Two researchers carried out independent screening, data extraction, and quality assessment. Observational studies published in English and reporting associations between continuous and/or categorical maternal and child BMI or z-score were included. Categorical outcomes were child obesity (≥95th percentile, primary outcome), overweight/obesity (≥85th percentile), and overweight (85th to 95th percentile). Linear and nonlinear dose-response meta-analyses were conducted using random effects models. Studies that could not be included in meta-analyses were summarised narratively. Seventy-nine of 41,301 studies identified met the inclusion criteria (n = 59 cohorts). Meta-analyses of child obesity included 20 studies (n = 88,872); child overweight/obesity, 22 studies (n = 181,800); and overweight, 10 studies (n = 53,238). Associations were nonlinear and there were significantly increased odds of child obesity with maternal obesity (odds ratio [OR] 3.64, 95% CI 2.68-4.95) and maternal overweight (OR 1.89, 95% CI 1.62-2.19). Significantly increased odds were observed for child overweight/obesity (OR 2.69, 95% CI 2.10-3.46) and for child overweight (OR 1.80, 95% CI 1.25, 2.59) with maternal obesity. A limitation of this research is that the included studies did not always report the data in a format that enabled inclusion in this complex meta-analysis.Conclusions: This research has identified a 264% increase in the odds of child obesity when mothers have obesity before conception. This study provides substantial evidence for the need to develop interventions that commence prior to conception, to support women of childbearing age with weight management in order to halt intergenerational obesity. [ABSTRACT FROM AUTHOR]

To compare perioperative outcomes in the three most common partial nephrectomy modalities: robotic (RPN), laparoscopic (LPN), and open (OPN), matched for nephrometry scores. Patients aged 16-85 who underwent RPN, LPN, or OPN from 2007 to 2014 for localized renal carcinoma within our healthcare system were enrolled. Age, sex, body mass index, and Charlson Comorbidity Index (CCI) as well as perioperative outcomes of estimated blood loss (EBL), length of hospital stay (LOS), ischemia time (IT), change in eGFR, positive margin rate, operative time (OT), and emergency room visit rates were compared between RPN, LPN, and OPN using the R.E.N.A.L nephrometry score. A total of 862 patients underwent partial nephrectomy (523 LPN, 176 OPN, and 163 RPN). Patients who underwent OPN were significantly older, and had higher nephrometry scores and CCI. When matched for nephrometry scores, minimally invasive (LPN and RPN) compared to OPN had lower EBL (< 0.0001), shorter LOS (< 0.0001), shorter IT (< 0.001), and less change in eGFR (< 0.001), particularly in nephrometry scores higher than 8 (0.0099). Comparing RPN with LPN, RPN had significantly shorter OT in all nephrometry scores (< 0.001); shorter IT and LOS in nephrometry scores higher than 7. Our study suggests that minimally invasive partial nephrectomy may have superior outcomes to OPN when matched by nephrometry scores, particularly at higher scores and for RPN. This finding may contribute to a surgeon’s decision in the approach to partial nephrectomy. [ABSTRACT FROM AUTHOR]

Context: Screening for HIV infection in medical settings remains suboptimal. Objective: To examine the real-world effectiveness of an electronic clinician a lert on the same-day HIV testing rate and early diagnosis in high-risk populations. Design: We identified Kaiser Perm anente Southern California Health Plan members aged 14 years or older who received tests for sexually transmitted infections. Main Outcome Measures: Enc ounter-based same-day HIV testing rate, positive test result rate, and CD4+ cell count and HIV viral load at diagnosis. Results: We iden tified 1,800,948 patients who made 2,326,701 health care encounters eligible for HIV testing before implementation (January 1, 2008 - June 30, 2012) and 1,362,479 eligible encounters after implementation (January 1, 2013 - June 30, 2015). The same-day HIV testing rate increased from 36.7% to 44.1% (standardized mean difference = 0.15, significant difference). The alert was associated with a moderate difference and statistically significant increase in the HIV testing rate (adjusted odds ratio = 1.17, 95% confidence interval = 1.16-1.18). The positive test result rate increased from 0.02% to 0.04% (p < 0.001). During the postimplementation period, fewer HIV-infected patients had a CD4+ cell count below 200 and/or an HIV viral load of 10,000 copies/mL or higher at diagnosis. Conclusion: Implemen tation of a targeted electronic alert embedded in the electronic medical record improved same-day HIV screening rate and positive test result rates among patients receiving tests for sexually transmitted infections in a large health organization. This intervention has potential for facilitating frequent screening and early identification of HIV infection in high-risk populations. [ABSTRACT FROM AUTHOR]

Context: Traditional hepatitis C virus treatment was limited by low cure rates, side effects, and stringent monitoring requirements. Sofosbuvir, a direct-acting antiviral agent with a cure rate of 96%, was introduced in 2013. However, trials frequently excluded patients with advanced liver disease and prior treatment experience. This study aims to elucidate the real-world cure rates and sofosbuvir safety profile. Methods: A retrospective cohort study was conducted at Kaiser Permanente Southern California involving patients with hepatitis C virus who received sofosbuvir treatment. Patients age 18 years and older were included, and pregnant patients were excluded. The primary end point was sustained virologic response at 12 weeks posttreatment. Secondary end points were safety and medication adherence. Multiple logistic regression analysis was used to compare patients with genotypes 1 and 2 infections. Results: Of the 213 study patients, 42.3% had cirrhosis, and 38% were treatment-experienced. Most patients (69.5%) received dual therapy (sofosbuvir + ribavirin), whereas the remainder (30.5%) received triple therapy (sofosbuvir + ribavirin + interferon). The overall rate of sustained virologic response at 12 weeks posttreatment rate was 72.9% for genotype 1 infection, 64.7% in the treatment-experienced subgroup, and 66.7% in the cirrhosis subgroup. Rates of sustained virologic response at 12 weeks posttreatment for genotypes 2 and 3 were 90.8% and 55%, respectively. Most patients experienced anemia and fatigue. Women and patients with a lower baseline viral load were statistically more likely to be cured. Conclusion: Real-world cure rates were similar to rates seen in clinical trials for genotype 2 infection and lower for genotype 1 infection. Patients with genotype 1 and 3 infection did better with triple therapy compared with dual therapy. Patients tolerated therapy well with side effects, serious adverse events, and discontinuation rates similar to clinical trials. Women and patients with lower baseline hepatitis C viral load were more likely to achieve sustained virological response at 12 weeks posttreatment. [ABSTRACT FROM AUTHOR]

Purpose: A skilled assistant surgeon is presumed necessary during robot-assisted partial nephrectomy (RAPN) to minimize warm ischemia time (WIT) and to facilitate complex renorrhaphy. Studies observing impact of resident participation have focused on robotic prostatectomies, showing no impact on core surgical outcomes. Herein, we evaluated the level of experience of the bedside assistant and its impact on perioperative outcomes in RAPN. Materials and Methods: All RAPN cases in our healthcare system from January 2011 to December 2013 were retrospectively reviewed. The cases were divided into teaching and nonteaching hospitals. There were 18 fellowship-trained attending surgeons. At teaching hospitals, surgeries were performed by an attending physician and postgraduate year (PGY)-2 or PGY-3 resident at bedside; at nonteaching hospitals, surgeries were performed by two attending surgeons. We compared age, gender, body mass index, Charlson comorbidity index, operative difficulty by R.E.N.A.L. nephrometry score, and operative outcomes (WIT, estimated blood loss, operative time (OT), positive margin rate, length of stay (LOS), postoperative glomerular filtration rate, and readmission rate). Results: Of the 170 patients captured, 162 had R.E.N.A.L. nephrometry score and WIT: 112 from teaching hospitals and 50 from nonteaching hospitals. Patient characteristics were equivalent between both cohorts with the exception of the R.E.N.A.L. score, which was higher (6.3 vs 5.7, p = 0.046) in the teaching hospitals cohort. Regarding operative outcomes, we noted an overall increase in LOS by 1 day ( p = 0.001) and OT by 16 minutes ( p = 0.011) in the teaching hospitals. Conclusion: We observed that increased LOS was the only clinically relevant measure negatively impacted by resident physician involvement during RAPN. [ABSTRACT FROM AUTHOR]

Background: Many epidemiology studies report that atopic conditions such as allergies are associated with reduced pancreas cancer risk. The reason for this relationship is not yet understood. This is the first study to comprehensively evaluate the association between variants in atopy-related candidate genes and pancreatic cancer risk. Methods: A population-based case-control study of pancreas cancer cases diagnosed during 2011-2012 (via Ontario Cancer Registry), and controls recruited using random digit dialing utilized DNA from 179 cases and 566 controls. Following an exhaustive literature review, SNPs in 180 candidate genes were pre-screened using dbGaP pancreas cancer GWAS data; 147 SNPs in 56 allergy-related immunologic genes were retained and genotyped. Logistic regression was used to estimate age-adjusted odd ratio (AOR) for each variant and false discovery rate was used to adjust Wald p-values for multiple testing. Subsequently, a risk allele score was derived based on statistically significant variants. Results: 18 SNPs in 14 candidate genes (CSF2, DENND1B, DPP10, FLG, IL13, IL13RA2, LRP1B, NOD1, NPSR1, ORMDL3, RORA, STAT4, TLR6, TRA) were significantly associated with pancreas cancer risk. After adjustment for multiple comparisons, two LRP1B SNPs remained statistically significant; for example, LRP1B rs1449477 (AA vs. CC: AOR=0.37, 95% CI: 0.22-0.62; p (adjusted)=0.04). Furthermore, the risk allele score was associated with a significant reduction in pancreas cancer risk (p=0.0007). Conclusions: Preliminary findings suggest certain atopy-related variants may be associated with pancreas cancer risk. Further studies are needed to replicate this, and to elucidate the biology behind the growing body of epidemiologic evidence suggesting allergies may reduce pancreatic cancer risk. [ABSTRACT FROM AUTHOR]

The article presents abstracts on medical topics, which include studies on the effects of physical activity and healthy eating in reducing risk of gestational diabetes mellitus (GDM), the effects of maternal obesity, gestational diabetes, gestational weight gain, and breastfeeding on childhood obesity, and the maternal and neonatal outcomes in women with early diagnosis of gestational diabetes.