The Importance of Estimating Excess Deaths Regionally During the COVID-19 Pandemic.

National or statewide estimates of excess deaths have limited value to understanding the impact of the COVID-19 pandemic regionally. We assessed excess deaths in a 9-county geographically defined population that had low rates of COVID-19 and widescale availability of testing early in the pandemic, well-annotated clinical data, and coverage by 2 medical examiner's offices. We compared mortality rates (MRs) per 100,000 person-years in 2020 and 2021 with those in the 2019 reference period and MR ratios (MRRs). In 2020 and 2021, 177 and 219 deaths, respectively, were attributed to COVID-19 (MR = 52 and 66 per 100,000 person-years, respectively). COVID-19 MRs were highest in males, older persons, those living in rural areas, and those with 7 or more chronic conditions. Compared with 2019, we observed a 10% excess death rate in 2020 (MRR = 1.10 [95% CI, 1.04 to 1.15]), with excess deaths in females, older adults, and those with 7 or more chronic conditions. In contrast, we did not observe excess deaths overall in 2021 compared with 2019 (MRR = 1.04 [95% CI, 0.99 to 1.10]). However, those aged 18 to 39 years (MRR = 1.36 [95% CI, 1.03 to 1.80) and those with 0 or 1 chronic condition (MRR = 1.28 [95% CI, 1.05 to 1.56]) or 7 or more chronic conditions (MRR = 1.09 [95% CI, 1.03 to 1.15]) had increased mortality compared with 2019. This work highlights the value of leveraging regional populations that experienced a similar pandemic wave timeline, mitigation strategies, testing availability, and data quality.

Ascertainment of Delirium Status Using Natural Language Processing From Electronic Health Records.

BACKGROUND: Delirium is underdiagnosed in clinical practice and is not routinely coded for billing. Manual chart review can be used to identify the occurrence of delirium; however, it is labor-intensive and impractical for large-scale studies. Natural language processing (NLP) has the capability to process raw text in electronic health records (EHRs) and determine the meaning of the information. We developed and validated NLP algorithms to automatically identify the occurrence of delirium from EHRs. METHODS: This study used a randomly selected cohort from the population-based Mayo Clinic Biobank (N = 300, age ≥65). We adopted the standardized evidence-based framework confusion assessment method (CAM) to develop and evaluate NLP algorithms to identify the occurrence of delirium using clinical notes in EHRs. Two NLP algorithms were developed based on CAM criteria: one based on the original CAM (NLP-CAM; delirium vs no delirium) and another based on our modified CAM (NLP-mCAM; definite, possible, and no delirium). The sensitivity, specificity, and accuracy were used for concordance in delirium status between NLP algorithms and manual chart review as the gold standard. The prevalence of delirium cases was examined using International Classification of Diseases, 9th Revision (ICD-9), NLP-CAM, and NLP-mCAM. RESULTS: NLP-CAM demonstrated a sensitivity, specificity, and accuracy of 0.919, 1.000, and 0.967, respectively. NLP-mCAM demonstrated sensitivity, specificity, and accuracy of 0.827, 0.913, and 0.827, respectively. The prevalence analysis of delirium showed that the NLP-CAM algorithm identified 12 651 (9.4%) delirium patients, the NLP-mCAM algorithm identified 20 611 (15.3%) definite delirium cases, and 10 762 (8.0%) possible cases. CONCLUSIONS: NLP algorithms based on the standardized evidence-based CAM framework demonstrated high performance in delineating delirium status in an expeditious and cost-effective manner.

A hybrid model to identify fall occurrence from electronic health records.

INTRODUCTION: Falls are a leading cause of unintentional injury in the elderly. Electronic health records (EHRs) offer the unique opportunity to develop models that can identify fall events. However, identifying fall events in clinical notes requires advanced natural language processing (NLP) to simultaneously address multiple issues because the word "fall" is a typical homonym. METHODS: We implemented a context-aware language model, Bidirectional Encoder Representations from Transformers (BERT) to identify falls from the EHR text and further fused the BERT model into a hybrid architecture coupled with post-hoc heuristic rules to enhance the performance. The models were evaluated on real world EHR data and were compared to conventional rule-based and deep learning models (CNN and Bi-LSTM). To better understand the ability of each approach to identify falls, we further categorize fall-related concepts (i.e., risk of fall, prevention of fall, homonym) and performed a detailed error analysis. RESULTS: The hybrid model achieved the highest f1-score on sentence (0.971), document (0.985), and patient (0.954) level. At the sentence level (basic data unit in the model), the hybrid model had 0.954, 1.000, 0.988, and 0.999 in sensitivity, specificity, positive predictive value, and negative predictive value, respectively. The error analysis showed that that machine learning-based approaches demonstrated higher performance than a rule-based approach in challenging cases that required contextual understanding. The context-aware language model (BERT) slightly outperformed the word embedding approach trained on Bi-LSTM. No single model yielded the best performance for all fall-related semantic categories. CONCLUSION: A context-aware language model (BERT) was able to identify challenging fall events that requires context understanding in EHR free text. The hybrid model combined with post-hoc rules allowed a custom fix on the BERT outcomes and further improved the performance of fall detection.

Identification of sex-specific genetic associations in response to opioid analgesics in a White, non-Hispanic cohort from Southeast Minnesota.

The study of sex-specific genetic associations with opioid response may improve the understanding of inter-individual variability in pain treatments. We investigated sex-specific associations between genetic variation and opioid response. We identified participants in the RIGHT Study prescribed codeine, tramadol, hydrocodone, and oxycodone between 01/01/2005 and 12/31/2017. Prescriptions were collapsed into codeine/tramadol and hydrocodone/oxycodone. Outcomes included poor pain control and adverse reactions within six weeks after prescription date. We performed gene-level and single-variant association analyses stratified by sex. We included 7169 non-Hispanic white participants and a total of 1940 common and low-frequency variants (MAF > 0.01). Common variants in MACROD2 (rs76026520), CYP1B1 (rs1056837, rs1056836), and CYP2D6 (rs35742686) were associated with outcomes. At the gene level, FAAH, SCN1A, and TYMS had associations for men and women, and NAT2, CYP3A4, CYP1A2, and SLC22A2 had associations for men only. Our findings highlight the importance of considering sex in association studies on opioid response.

Efficacy of anti-epidermal growth factor receptor agents in patients with RAS wild-type metastatic colorectal cancer ≥ 70 years.

PURPOSE: Colorectal cancer (CRC) affects many older adults. We investigated the efficacy and safety of adding anti-epidermal growth factor receptor (EGFR) agents to doublet chemotherapy (DC) in older patients. METHODS: Patients with RAS wild-type (WT) metastatic CRC (mCRC) receiving first-line DC + anti-EGFR (n = 1191) or DC alone (n = 729) from seven trials in the Aide de Recherche en Cancerologie Digestive database were included. The prognostic and predictive effects of age were investigated. Progression-free and overall survival (OS) were evaluated between age groups (≥70 vs <70) for DC + anti-EGFR. In addition, outcomes were compared between DC+/-anti-EGFR within age groups in three trials with a DC alone arm. Subsequently, the same analysis was conducted for left-sided tumours. Adverse events grade ≥3 (G3+) were compared between age groups. RESULTS: Older (vs younger) patients receiving DC + anti-EGFR had similar progression-free survival (PFS) (8.7 vs 10.3 months; hazard ratio (HR) = 1.20 [0.96-1.49];p = 0.107) but inferior OS (21.3 vs 26.3; HR = 1.36 [1.08-1.72];p = 0.011). DC + anti-EGFR (vs DC alone) improved OS (23.9 vs 20.3; HR = 0.82 [0.70-0.95];p = 0.008) and PFS (11.2 vs 8.9; HR = 0.70 [0.60-0.82];p < 0.001) in younger but not older patients: OS (24.7 vs 17.6; HR [95% confidence interval {CI}] = 0.77 [0.58-1.04];p = 0.092) and PFS (9.1 vs 8.7; HR [95% CI] = 0.85[0.63-1.15];p = 0.287). In left-sided 'only' tumours, the following outcomes for older (vs younger) patients were observed. For DC + anti-EGFR, PFS 9 versus 11.2 months; HR1.10 (95% CI 0.83-1.46); p = 0.52, OS 25.6 vs 30.3 HR 1.32 (95% CI 0.97-1.79), p = 0.086. For DC + anti-EGFR (vs DC alone), PFS and OS for younger patients were 11.9 vs 9.2 months HR 0.60 (95% CI 0.47-0.78) p < 0.001 and 24.1 versus 23.3 months HR 0.84 (95% CI 0.67-1.04), respectively. For older patients, PFS and OS were 13.1 versus 8.5 months, HR 0.51 (95% CI, 0.28-0.93), P = 0.027 and 26.3 versus 16.5 months HR 0.49 (95% CI, 0.28-0.85), respectively. There was no significant difference in toxicity among different age groups. CONCLUSIONS: Older (vs younger) patients with mCRC RAS WT patients had comparable toxicity and efficacy with the addition of anti-EGFR agents to chemotherapy.

Targeted Genotyping in Clinical Pharmacogenomics: What Is Missing?

Clinical pharmacogenomic testing typically uses targeted genotyping, which only detects variants included in the test design and may vary among laboratories. To evaluate the potential patient impact of genotyping compared with sequencing, which can detect common and rare variants, an in silico targeted genotyping panel was developed based on the variants most commonly included in clinical tests and applied to a cohort of 10,030 participants who underwent sequencing for CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4, CYP3A5, DPYD, SLCO1B1, TPMT, UGT1A1, and VKORC1. The results of in silico targeted genotyping were compared with the clinically reported sequencing results. Of the 10,030 participants, 2780 (28%) had at least one potentially clinically relevant variant/allele identified by sequencing that would not have been detected in a standard targeted genotyping panel. The genes with the largest number of participants with variants only detected by sequencing were SLCO1B1, DPYD, and CYP2D6, which affected 13%, 6.3%, and 3.5% of participants, respectively. DPYD (112 variants) and CYP2D6 (103 variants) had the largest number of unique variants detected only by sequencing. Although targeted genotyping detects most clinically significant pharmacogenomic variants, sequencing-based approaches are necessary to detect rare variants that collectively affect many patients. However, efforts to establish pharmacogenomic variant classification systems and nomenclature to accommodate rare variants will be required to adopt sequencing-based pharmacogenomics.

Minnesota COVID-19 Lockdowns: The Effect on Acute Myocardial Infarctions and Revascularizations in the Community.

OBJECTIVE: To study associations between the Minnesota coronavirus disease 2019 (COVID-19) mitigation strategies on incidence rates of acute myocardial infarction (MI) or revascularization among residents of Southeast Minnesota. METHODS: Using the Rochester Epidemiology Project, all adult residents of a nine-county region of Southeast Minnesota who had an incident MI or revascularization between January 1, 2015, and December 31, 2020, were identified. Events were defined as primary in-patient diagnosis of MI or undergoing revascularization. We estimated age- and sex-standardized incidence rates and incidence rate ratios (IRRs) stratified by key factors, comparing 2020 to 2015-2019. We also calculated IRRs by periods corresponding to Minnesota's COVID-19 mitigation timeline: "Pre-lockdown" (January 1-March 11, 2020), "First lockdown" (March 12-May 31, 2020), "Between lockdowns" (June 1-November 20, 2020), and "Second lockdown" (November 21-December 31, 2020). RESULTS: The incidence rate in 2020 was 32% lower than in 2015-2019 (24 vs 36 events/100,000 person-months; IRR, 0.68; 95% CI, 0.62-0.74). Incidence rates were lower in 2020 versus 2015-2019 during the first lockdown (IRR, 0.54; 95% CI, 0.44-0.66), in between lockdowns (IRR, 0.70; 95% CI, 0.61-0.79), and during the second lockdown (IRR, 0.54; 95% CI, 0.41-0.72). April had the lowest IRR (IRR 0.48; 95% CI, 0.34-0.68), followed by August (IRR, 0.55; 95% CI, 0.40-0.76) and December (IRR, 0.56; 95% CI, 0.41-0.77). Similar declines were observed across sex and all age groups, and in both urban and rural residents. CONCLUSION: Mitigation measures for COVID-19 were associated with a reduction in hospitalizations for acute MI and revascularization in Southeast Minnesota. The reduction was most pronounced during the lockdown periods but persisted between lockdowns.

Factors Associated With Severe COVID-19 Infection Among Persons of Different Ages Living in a Defined Midwestern US Population.

OBJECTIVE: To identify risk factors associated with severe COVID-19 infection in a defined Midwestern US population overall and within different age groups. PATIENTS AND METHODS: We used the Rochester Epidemiology Project research infrastructure to identify persons residing in a defined 27-county Midwestern region who had positive results on polymerase chain reaction tests for COVID-19 between March 1, 2020, and September 30, 2020 (N=9928). Age, sex, race, ethnicity, body mass index, smoking status, and 44 chronic disease categories were considered as possible risk factors for severe infection. Severe infection was defined as hospitalization or death caused by COVID-19. Associations between risk factors and severe infection were estimated using Cox proportional hazard models overall and within 3 age groups (0 to 44, 45 to 64, and 65+ years). RESULTS: Overall, 474 (4.8%) persons developed severe COVID-19 infection. Older age, male sex, non-White race, Hispanic ethnicity, obesity, and a higher number of chronic conditions were associated with increased risk of severe infection. After adjustment, 36 chronic disease categories were significantly associated with severe infection. The risk of severe infection varied significantly across age groups. In particular, persons 0 to 44 years of age with cancer, chronic neurologic disorders, hematologic disorders, ischemic heart disease, and other endocrine disorders had a greater than 3-fold increased risk of severe infection compared with persons of the same age without those conditions. Associations were attenuated in older age groups. CONCLUSION: Older persons are more likely to experience severe infections; however, severe cases occur in younger persons as well. Our data provide insight regarding younger persons at especially high risk of severe COVID-19 infection.

Reasons to Pretend Orgasm, Mate Retention, and Relationship Satisfaction in Brazilian Women.

We investigated the relationship between Brazilian women's reported reasons for pretending orgasm, their performance of mate retention behaviors, and their relationship satisfaction. Additionally, we secured evidence of the validity and reliability of a Brazilian-Portuguese adaptation of the Reasons to Pretend Orgasm Inventory (RPOI). Participants were 295 Brazilian women in a heterosexual relationship (Mage = 24.9 years, SDage = 5.4 years). Participants completed a Brazilian-Portuguese adaptation of the Mate Retention Inventory-Short Form, and the translated RPOI (the Escala de Razões para Fingir Orgasmo; ERFO). The resulting 47-item ERFO represents well the original 63-item RPOI. The frequency with which Brazilian women pretend orgasm was negatively associated with their relationship satisfaction. Our sample size may not be sufficient to detect small effects. In addition, due to the exploratory nature of the study, the results should be interpreted with caution and future research may attempt to replicate these findings with larger samples and in other countries.

Sex differences in type and occurrence of adverse reactions to opioid analgesics: a retrospective cohort study.

OBJECTIVES: Sex as a biological variable affects response to opioids. However, few reports describe the prevalence of specific adverse reactions to commonly prescribed opioids in men and women separately. A large cohort was used to investigate sex differences in type and occurrence of adverse reactions associated with use of codeine, tramadol, oxycodone and hydrocodone. DESIGN: Retrospective cohort study. SETTING: Participants in the Right Drug, Right Dose, Right Time (RIGHT) Study. PARTICIPANTS: The medical records of 8457 participants in the RIGHT Study who received an opioid prescription between 1 January 2004 and 31 December 2017 were reviewed 61% women, 94% white, median age (Q1-Q3)=58 (47-66). PRIMARY AND SECONDARY OUTCOME MEASURES: Adverse reactions including gastrointestinal, skin, psychiatric and nervous system issues were collected from the allergy section of each patient's medical record. Sex differences in the risk of adverse reactions due to prescribed opioids were modelled using logistic regression adjusted for age, body mass index, race and ethnicity. RESULTS: From 8457 participants (of which 449 (5.3%) reported adverse reactions), more women (6.5%) than men (3.4%) reported adverse reactions to at least one opioid (OR (95% CI)=2.3 (1.8 to 2.8), p<0.001). Women were more likely to report adverse reactions to tramadol (OR (95% CI)=2.8 (1.8 to 4.4), p<0.001) and oxycodone (OR (95% CI)=2.2 (1.7 to 2.9), p<0.001). Women were more likely to report gastrointestinal (OR (95% CI)=3.1 (2.3 to 4.3), p<0.001), skin (OR (95% CI)=2.1 (1.4 to 3.3), p=0.001) and nervous system issues (OR (95% CI)=2.3 (1.3 to 4.2), p=0.004). CONCLUSIONS: These findings support the importance of sex as a biological variable to be factored into pain management studies.

Impact of Pharmacogenomic Information on Values of Care and Quality of Life Associated with Codeine and Tramadol-Related Adverse Drug Events.

OBJECTIVE: To assess the potential impact of Pharmacogenomic (PGx) variation in cytochrome P450 2D6 (CYP2D6) enzyme function, using loss in quality-adjusted life years (QALYs) associated with treatment problems, and the willingness to pay to avoid treatment problems from patients' and payers' perspectives. PATIENTS AND METHODS: The study included patients prescribed tramadol or codeine, or both, between January 1, 2005, and December 31, 2017. Demographic information and adverse drug events, including adverse drug events and poor pain control, were collected from the electronic health records using natural language processing techniques and review by trained abstractors. Patients' willingness to pay and QALY estimates were based on comprehensive literature review. The CYP2D6 phenotypes were divided into 4 groups: ultra-rapid metabolizers, normal metabolizers, intermediate metabolizers, and poor metabolizers. RESULTS: Among the 2860 identified patients, 63 (2%) were ultrarapid metabolizers, 1449 (50%) were normal metabolizers, 1155 (40%) were intermediate metabolizers, and 193 (7%) were poor metabolizers. The patients' average estimated willingness-to-pay value to avoid treatment problems was $23 per month; poor metabolizers developed problems with the highest estimated willingness-to-pay value ($32 per month). The mean QALY loss among all patients was 0.024 QALYs (8.8 healthy days); poor metabolizers had the highest loss (0.027 QALYs, 9.9 healthy days). CONCLUSION: Patients with various phenotypes developed different treatment problem profiles. Poor CYP2D6 metabolizers developed problems with highest willingness to pay, and they might potentially benefit most from PGx-guided treatment and problem prevention.

Adverse event load, onset, and maximum grade: A novel method of reporting adverse events in cancer clinical trials.

BACKGROUND: Current adverse event reporting practices do not document longitudinal characteristics of adverse effects, and alternative methods are not easily interpretable and have not been employed by clinical trials. Introducing time parameters in the evaluation of safety that are comprehensive yet easily interpretable could allow for a better understanding of treatment quality. In this study, we developed and applied a novel adverse event reporting method based on longitudinal adverse event changes to aid describing, summarizing, and presenting adverse event profile. We termed it the "Adverse Event Load, Onset, and Maximum Grade" method. METHODS: We developed two adverse event summary metrics to complement the traditional maximum grade report. Onset time indicates the time period in which the maximum grade for a specific adverse event occurred and was defined as "early" (i.e. maximum grade happened for the first time before 6 weeks) or "late" (i.e. after the 6th week). Adverse event load indicates the overall severity of a specific adverse event over the entire treatment. Higher adverse event load indicates a worse overall experience. These metrics can be calculated for adverse events with different maximum grades, in treatments with planned changes (e.g. dosage changes), using data sets with different number of adverse event data points between treatments (e.g. treatments with longer cycle lengths may have less adverse event data points) and on data sets with different adverse event data availability (e.g. cycle basis and patient-outcome reports). We tested the utility of this method using individual patient data from two major backbone therapies ("Irinotecan" and "Oxaliplatin") from the N9741 trial available in the Fondation ARCAD database (fondationarcad.org). We investigated profiles of diarrhea, neutropenia/leukopenia, and nausea/vomiting. RESULTS: Our method provided additional information compared to traditional adverse event reports. For example, for nausea/vomiting, while patients in Irinotecan had a higher risk of experiencing maximum grade 3-4 (15.6% vs 7.6%, respectively; p < 0.001), patients in both groups experienced similar severity over time (adverse effect load = 0.102 and 0.096, respectively; p = 0.26), suggesting that patients in Oxaliplatin experienced a lower-grade but more persistent nausea/vomiting. For neutropenia/leukopenia, more patients in Irinotecan experienced their maximum grade for the first time early in the treatment compared to patients in Oxaliplatin (67.9% vs 41.7%; p < 0.001), regardless of maximum grade. Longitudinal information can help compare treatments or guide clinicians on choosing appropriate interventions for low-grade but persistent adverse event or early adverse event onset. CONCLUSION: We developed an adverse event reporting method that provides clinically relevant information about treatment toxicity by incorporating two longitudinal adverse event metrics to the traditional maximum grade approach. Future research should establish clinical benchmarks for metrics included in this adverse event reporting method.

Sexual Coercion, Mate Retention, and Relationship Satisfaction in Brazilian and American Romantic Relationships.

We investigated the relationships among men's sexual coercion, men's performance of mate retention behaviors, and their partner's relationship satisfaction in Brazil (Study 1) and the United States (Study 2). In addition, we adapted the Sexual Coercion in Intimate Relationships Scale (SCIRS) to the Brazilian context (Escala de Coerção Sexual em Relacionamentos Amorosos [ECSRA]; Study 1) and investigated the suitability of the adapted version in the American context (Sexual Coercion in Intimate Relationships Scale-Short Form [SCIRS-SF]; Study 2). Study 1 included 181 Brazilians, aged between 18 and 49 years (M = 23.5; SD = 5.1), mostly female (60.8%). Study 2 included 508 Americans, aged between 19 and 70 years (M = 34.7; SD = 9.7), mostly male (52.6%). Participants were in a heterosexual, romantic relationship for at least 3 months. Participants completed the SCIRS, a 34-item measure assessing how often participants experienced each sexually coercive behavior, the MRI-SF, a 38-item measure assessing how often participants performed each mate retention act, and several items regarding relationship satisfaction. The results indicated that American (but not Brazilian) men's sexual coercion is positively correlated with their performance of cost-inflicting and benefit-provisioning mate retention behaviors. Men's sexual coercion did not affect their partner's relationship satisfaction in either the American or Brazilian contexts. The SCIRS-SF (nine items) reliably represents the SCIRS (34 items) in the American context. We recommend the SCIRS-SF for assessing performance frequency of sexual coercion. The SCIRS-SF may be used as a screening tool to identify patterns of sexual coercion in couples from Brazil and the United States. We highlight limitations of the current research and identify directions for future research.

Most noninvasive prenatal screens failing due to inadequate fetal cell free DNA are negative for trisomy when repeated.

OBJECTIVE: We aimed to test for an association between the amount of circulating fetal cell-free DNA and trisomy, and whether NIPS failure due to low fetal fraction indicates trisomy risk. METHOD: Maternal BMI, maternal age, fetal sex, gestational age, fetal cfDNA fraction, and NIPS results was collected on 2374 pregnancies. Additional clinical information was available for 1180 research consented patients. We investigated associations between fetal fraction and available variables and determined the success rate of repeat NIPS testing. RESULTS: Fetal trisomy was marginally associated with decreased fetal fraction (P = .067). However, the proportions of trisomy events were not significantly increased in women who had failed NIPS due to low fetal fraction (<4%) (OR = 1.37 [0.3-7.4]; P = .714). 66% of repeated NIPS after a second blood draw were successful. CONCLUSION: Failure to meet the clinical cutoff of 4% fetal fraction established for NIPS accuracy did not suggest increased risk for trisomy in our cohort. Because repeat testing was successful in the majority of cases and most failures were explained by high BMI and low gestational age, a redraw may be an appropriate next step before invasive screening due to concerns for trisomic pregnancies.

Sex Differences in Associations Between CYP2D6 Phenotypes and Response to Opioid Analgesics.

BACKGROUND: Several small studies have previously investigated associations between the cytochrome P450 2D6 (CYP2D6) metabolism and response to opioids. We used a large sample of patients to study associations between CYP2D6 phenotypes and estimated CYP2D6 enzymatic activity scores with pain control and adverse reactions related to codeine and tramadol use. We conducted additional analyses to determine whether our results were consistent among men and women. METHODS: We used data from 2,877 participants in the RIGHT Protocol who were prescribed codeine and/or tramadol between 01/01/2005 and 12/31/2017 and who were not prescribed CYP2D6 inhibitors within 1 year prior to the opioid prescription. CYP2D6 phenotype categories were condensed into four groups: (1) Ultra-rapid and Rapid (n = 61), (2) Normal and Intermediate to Normal (n = 1,448), (3) Intermediate and Intermediate to Poor (n = 1,175), and (4) Poor metabolizer status (n = 193). Opioid-related outcomes included indications of poor pain control or adverse reactions related to medication use. We modeled the risk of each outcome using logistic regression, adjusting for age, sex, race, and ethnicity. RESULTS: The results revealed a trend from poor to ultra-rapid and rapid CYP2D6 phenotypes in which the risk of adverse reactions incrementally increased and the risk of poor pain control incrementally decreased. This trend reached statistical significance among female (but not male) participants. Among normal and intermediate to normal metabolizers, a larger proportion of women experienced adverse reactions relative to men. DISCUSSION: We replicated and extended the findings of previous research indicating associations between CYP2D6 phenotypes and response to opioids. In addition, the observed associations were stronger in women than in men. We recommend sex differences to be factored in future research investigating associations between pharmacogenomics and response to medications.

FANCM, RAD1, CHEK1 and TP53I3 act as BRCA-like tumor suppressors and are mutated in hereditary ovarian cancer.

Although 25% of ovarian cancer cases are due to inherited factors, most of the genetic risk remains unexplained. We previously identified candidate genes through germline whole exome sequencing of BRCA1/BRCA2 negative ovarian cancer patients with familial risk. Here, we performed functional assessment to determine whether they act as BRCA-like tumor suppressors. Seven candidate risk genes were targeted by siRNA for mRNA depletion followed by functional assays for clonogenic survival, cytotoxicity to DNA damaging agents, and involvement in homologous recombination repair. BRCA1 and BRCA1 were targeted as standards for loss of function outcome. Knockdown of various candidate genes led to tumor suppressor phenotypes also observed in BRCA1/BRCA2 deficient cells. Deficiency of CHEK1, FANCM and TP53I3 led to reduced homologous recombination repair efficiency. Knockdown of RAD1, CHEK1 or FANCM led to a decrease in cellular viability and cells deficient in CHEK1, RAD1 or TP53I3 displayed increased sensitivity to cisplatin. Functional studies of candidate genes identified by whole exome sequencing complements bioinformatics techniques and aid the implication of novel risk loci. The results of this study suggest that genes found mutated in hereditary ovarian cancer, FANCM, RAD1, CHEK1 and TP53I3, act as BRCA-like tumor suppressors.

Life history correlates of human (Homo sapiens) ejaculate quality.

Life history strategies reflect resource allocation decisions, which manifest as physiological, psychological, and behavioral traits. We investigated whether human ejaculate quality is associated with indicators of relatively fast (greater resource allocation to mating effort) or slow (greater resource allocation to parenting effort) life history strategies in a test of two competing hypotheses: (a) The phenotype-linked fertility hypothesis, which predicts that men pursuing a relatively fast life history strategy will produce higher quality ejaculates, and (b) the cuckoldry-risk hypothesis, which predicts that men pursuing a relatively slow life history strategy will produce higher quality ejaculates. Men (n = 41) completed a self-report measure assessing life history strategy and provided two masturbatory ejaculate samples. Results provide preliminary support for the cuckoldry-risk hypothesis: Men pursuing a relatively slow life history strategy produced higher quality ejaculates. Ejaculate quality may therefore reflect resource allocation decisions for greater parenting effort, as opposed to greater mating effort. The findings contribute informative data on correlations between physiological and phenotypic indicators of human life history strategies. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Do Men Produce Higher Quality Ejaculates When Primed With Thoughts of Partner Infidelity?

Sperm competition theory can be used to generate the hypothesis that men alter the quality of their ejaculates as a function of sperm competition risk. Using a repeated measures experimental design, we investigated whether men produce a higher quality ejaculate when primed with cues to sperm competition (i.e., imagined partner infidelity) relative to a control prime. Men ( n = 45) submitted two masturbatory ejaculates-one ejaculate sample for each condition (i.e., sperm competition and control conditions). Ejaculates were assessed on 17 clinical parameters. The results did not support the hypothesis: Men did not produce higher quality ejaculates in the sperm competition condition relative to the control condition. Despite the null results of the current research, there is evidence for psychological and physiological adaptations to sperm competition in humans. We discuss methodological limitations that may have produced the null results and present methodological suggestions for research on human sperm competition.

Endorsement of Social and Personal Values Predicts the Desirability of Men and Women as Long-Term Partners.

A prospective romantic partner's desirability as a long-term partner may be affected by the values that he or she endorses. However, few studies have examined the effects of "values" on a person's desirability as a long-term partner. We hypothesized that individuals who endorse social values (vs. personal values) will be perceived as more desirable long-term partners (Hypothesis 1) and that the endorsement of social values will be especially desirable in a male (vs. female) long-term partner (Hypothesis 2). The current study employed a 2 (sex of prospective partner: male vs. female) × 2 (values of prospective partner: personal vs. social) × 2 (physical attractiveness of prospective partner: unattractive vs. highly attractive) mixed-model design. Participants were 339 undergraduates (174 men, 165 women), with ages varying between 18 and 33 years ( M = 19.9, SD = 3.6), and mostly in a romantic relationship (53.7%). Participants reported interest in a long-term relationship with prospective partners depicted in four scenarios (within subjects), each varying along the dimensions of values (personal vs. social) and physical attractiveness (unattractive vs. highly attractive). Individuals endorsing personal values (vs. social values) and men (vs. women) endorsing personal values were rated as less desirable as long-term partners. The current research adds to the partner preferences literature by demonstrating that an individual's ascribed values influence others' perceptions of desirability as a long-term partner and that these effects are consistently sex differentiated, as predicted by an evolutionary perspective on romantic partner preferences.

Endoscopic Therapeutic Option for Weight Loss and Control of Type 2 Diabetes: the Duodenal-Jejunal Bypass Liner.

For a long time, obesity has been known as a risk factor for cardiovascular disease, which is one of the main causes of death in developed countries. This risk is due to the coexistence of other factors associated with obesity, such as hypertension, dyslipidemia, nonalcoholic fatty liver disease, and abnormalities in glycemic metabolism. Obesity is also a major risk factor for type 2 diabetes, and it is not surprising that the global prevalence of this disease continues to increase. Surgical intervention is now the most effective modality to treat severe obesity and its comorbidities. However, endoluminal interventions performed entirely through the gastrointestinal tract by using endoscopic devices offer the potential for an outpatient weight loss procedure that may be safer, less invasive, and more cost-effective, compared with current surgical approaches. Given the emerging role of endoscopic procedures in the treatment of obesity and rapid changes in endoscopic technologies and techniques, this review considers the current state of endoscopic management of obesity and type 2 diabetes. Endoscopic techniques attempt to mimic some of the anatomic features of bariatric surgery and rely on gastric restriction and duodenal exclusion. The endoscopic placement of the duodenal-jejunal bypass liner in morbidly obese patients induces significant weight loss. Additionally, early studies reported significant improvements in several parameters of glucose homeostasis in morbidly obese patients with type 2 diabetes. In this article we will review the available results obtained with the duodenal-jejunal bypass liner.