Low Referral Rates for Genetic Assessment of Patients With Multiple Adenomas in United Kingdom Bowel Cancer Screening Programs.

BACKGROUND: Approximately 1 in 20 cases of colorectal cancer are caused by monogenic syndromes. Published guidelines recommend that patients with 10 or more adenomas be referred for genetic testing, based on evidence that colorectal cancer risk is associated with adenoma multiplicity. OBJECTIVE: The aim of this study was to determine adherence to guidelines on referral for genetic screening in patients with 10 or more adenomas. DESIGN: A cross-sectional study was performed of prospectively collected data from the UK Bowel Cancer Screening Programme between May 2007 and June 2018. Only histologically confirmed adenomas were included. Clinicopathological data were recorded from patient records, and referrals to clinical genetics services were ascertained. SETTING: Data were obtained from 3 centers in London, United Kingdom. PATIENTS: A total of 17,450 subjects underwent colonoscopy following an abnormal fecal occult blood test. MAIN OUTCOME MEASURES: We quantified patients with 10 or more adenomas and the proportion referred for genetic screening. RESULTS: The adenoma detection rate was 50.6% among 17,450 patients who underwent colonoscopy (8831 had 1 or more adenomas). Three hundred forty-seven patients (2.0%) had 10 or more adenomas. Patients with 10 or more adenomas were more likely to be male than those with fewer than 10 adenomas (76.9% vs 53.4%; p < 0.0001). A family history was collected in 37.8% of the multiple adenoma population. Of 347 patients with 10 or more adenomas, 28 (8.1%) were referred for genetic assessment. LIMITATIONS: All 3 screening centers were in a single city. No genetic outcome data were available to permit analysis of actual rates of inherited cancer syndromes in this population. CONCLUSIONS: In this study, almost 1 in 50 patients had 10 or more adenomas. Despite guidelines advising genetic testing in this group, referral rates are low. A referral pathway and management strategies should be established to address this patient population. See Video Abstract at http://links.lww.com/DCR/B630. TASAS BAJAS DE DERIVACIN PARA LA EVALUACIN GENTICA DE PACIENTES CON ADENOMAS MLTIPLES EN LOS PROGRAMAS DE DETECCIN DEL CNCER DE INTESTINO DEL REINO UNIDO: ANTECEDENTES:Aproximadamente uno de cada veinte casos de cáncer colorrectal son causados por síndromes monogénicos. Las pautas publicadas recomiendan que los pacientes con diez o más adenomas sean derivados para pruebas genéticas, basándose en la evidencia de que el riesgo de cáncer colorrectal está asociado con la multiplicidad de adenomas.OBJETIVO:El objetivo de este estudio fue determinar la adherencia a las guías de derivación para cribado genético en pacientes con diez o más adenomas.DISEÑO:Se realizó un estudio transversal de datos recolectados prospectivamente del Programa de Detección de Cáncer de Intestino del Reino Unido entre mayo de 2007 y junio de 2018. Solo se incluyeron los adenomas confirmados histológicamente. Los datos clínico-patológicos se registraron a partir de los registros de los pacientes y se determinaron las derivaciones a los servicios de genética clínica.AJUSTE ENTORNO CLINICO:Los datos se obtuvieron de tres centros en Londres, Reino Unido.PACIENTES:Un total de 17.450 17450 sujetos pacientes se sometieron a una colonoscopia después de una prueba de sangre oculta en heces anormal positiva.PRINCIPALES MEDIDAS DE RESULTADO VOLARACION:cuantificamos los pacientes con diez o más adenomas y la proporción remitida para cribado genético.RESULTADOS:La tasa de detección de adenomas fue del 50,6% entre 17.450 17450 pacientes que se sometieron a colonoscopia (8.831 8831 tenían uno o más adenomas). 347 pacientes (2,0%) tenían 10 o más adenomas. Los pacientes con 10 o más adenomas tenían más probabilidades de ser hombres que aquellos con menos de 10 adenomas (76,9% frente versus a 53,4%; p <0,0001). Se recogieron antecedentes familiares en el 37,8% de la población de adenomas múltiples. De 347 pacientes con 10 o más adenomas, 28 (8,1%) fueron remitidos para evaluación genética.LIMITACIONES:Los tres centros de detección se encontraban en una sola ciudad. No se disponía de datos de resultados genéticos que permitieran el análisis de las tasas reales de síndromes de cáncer hereditario en esta población.CONCLUSIONES:En este estudio, casi uno de cada cincuenta pacientes tenía diez o más adenomas. A pesar de las pautas que recomiendan las pruebas genéticas en este grupo, las tasas de derivación son bajas. Se debe establecer una vía de derivación y estrategias de manejo para abordar esta población de pacientes. Consulte Video Resumen en http://links.lww.com/DCR/B630.

The contribution of Lynch syndrome to early onset malignancy in Ireland.

BACKGROUND: Lynch syndrome (LS) is an autosomal dominant hereditary cancer syndrome responsible for 2-4% of hereditary colorectal cancers (CRC). Mismatch repair protein deficiency (dMMR) is a characteristic feature of LS. It has been associated with a poor response to standard chemotherapy in metastatic colorectal cancer (mCRC). There is currently no LS database to monitor trends of disease in Ireland. We aim to centralise LS data in Ireland to assess the burden of LS in Ireland and guide improvements in prevention and treatment of LS-associated cancer. METHODS: A retrospective review was carried out including all medical records for LS patients from two of the three cancer genetics clinics in Ireland between 2000 and 2018 was carried out. Clinicopathological data of probands (n = 57) and affected family members including demographics, mutation status, cancer diagnosis and outcome was recorded. Statistical analysis was carried out using SPSS software. RESULTS: Fifty-seven families including three-hundred and forty-five individuals affected by cancer were identified. The most common cancers recorded were colorectal (53%), breast (12%) and endometrial (10%). One-hundred and thirty-eight confirmed carriers were identified: 65 path_MLH1 (47%), 43 path_MSH2 (31%), 11 path_MSH6 (8%), 17 path_PMS2 (12%) and two path_EPCAM (1%). Cancer type varied significantly by gene. Median age of first diagnosis was 44.5 years (range 23-81). Half of all deceased patients (n = 11) in this group died within 2.5 years of first diagnosis. These deaths were directly related to cancer in 59% of cases. CONCLUSIONS: Under diagnosis of LS misses a powerful preventive and therapeutic opportunity. LS causes early onset dMMR cancer diagnoses with substantial societal impact. Implementation of ICBs into treatment policy for this small cohort of dMMR mCRC is an achievable therapeutic goal that may significantly improve survival. A prospective database for LS in Ireland is necessary to maximise prevention in this population.

Symptom burden of atopic dermatitis in early childhood assessed from daily monitoring of symptoms and topical steroid use.

BACKGROUND: To our knowledge, disease burden of atopic dermatitis (AD) as number of days with symptoms and medical treatment has never been studied as measure of severity. OBJECTIVES: To investigate risk factors for AD burden in the first 3 years of life. METHODS: The Copenhagen Prospective Studies on Asthma in Childhood2010 included 700 children. AD burden was assessed by daily diary entries with information on AD and steroid days measuring 18 possible heritable, prenatal, and postnatal environmental exposures. RESULTS: The children with AD had a median (interquartile range) of 136 symptom days (61-294 days) and 72 steroid days (27-145 days) during the first 3 years of life, with the highest disease burden in the second year of life. The multivariable risk factor analysis showed that maternal AD and childhood allergic sensitization were associated with a higher number of AD days and maternal AD, filaggrin mutation, and allergic sensitization were associated with a higher number of steroid days. LIMITATIONS: Participants with a personal interest in atopic diseases could be more likely to participate. CONCLUSION: Children's burden of AD, assessed quantitatively as AD and steroid days, demonstrated positive associations with maternal AD, filaggrin mutation, and early-life allergic sensitization, with the highest disease burden in the second year of life.

Assessment of Posttraumatic Stress Disorder and Educational Achievement in Sweden.

Importance: Posttraumatic stress disorder (PTSD) has been associated with impaired educational performance. Previous studies on the disorder could not control for important measured and unmeasured confounders. Objective: To prospectively investigate the association between PTSD and objective indicators of educational attainment across the life span, controlling for familial factors shared by full siblings, psychiatric comorbidity, and general cognitive ability. Design, Setting, and Participants: This population-based cohort study included 2 244 193 individuals born in Sweden between January 1, 1973, and December 31, 1997, who were followed-up until December 31, 2013. Clusters of full siblings were used to account for familial factors. Data analyses were conducted between December 2018 and May 2020. Exposure: International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses of PTSD in the Swedish National Patient Register. Main Outcomes and Measures: Eligibility to access upper secondary education after finishing compulsory education, finishing upper secondary education, starting a university degree, and finishing a university degree. Results: Of the final cohort of 2 244 193 individuals (1 151 414 [51.3%] men) included in the analysis, 1 425 326 were assessed for finishing compulsory education (919 with PTSD), 2 001 944 for finishing upper secondary education (2013 with PTSD), and 1 796 407 and 1 356 741 for starting and finishing a university degree (2243 and 2254 with PTSD, respectively). Posttraumatic stress disorder was associated with lower odds of achieving each of the educational milestones during the study period, including 82% lower odds of finishing compulsory education (adjusted odds ratio [aOR], 0.18; 95% CI, 0.15-0.20), 87% lower odds of finishing upper secondary education (aOR, 0.13; 95% CI, 0.12-0.14), 68% lower odds of starting a university degree (aOR, 0.32; 95% CI, 0.28-0.35), and 73% lower odds of finishing a university degree (aOR, 0.27; 95% CI, 0.23-0.31). Estimates in the sibling comparison were attenuated (aOR range, 0.22-0.53) but remained statistically significant. Overall, excluding psychiatric comorbidities and adjusting for the successful completion of the previous milestone and general cognitive ability did not statistically significantly alter the magnitude of the associations. Conclusions and Relevance: Posttraumatic stress disorder was associated with educational impairment across the life span, and the associations were not entirely explained by shared familial factors, psychiatric comorbidity, or general cognitive ability. This finding highlights the importance of implementing early trauma-informed interventions in schools and universities to minimize the long-term socioeconomic consequences of academic failure in individuals with PTSD.

Under 10 mortality patterns, risk factors, and mechanisms in low resource settings of Eastern Uganda: An analysis of event history demographic and verbal social autopsy data.

BACKGROUND: Globally, the under-10 years of age mortality has not been comprehensively studied. We applied the life-course perspective in the analysis and interpretation of the event history demographic and verbal autopsy data to examine when and why children die before their 10th birthday. METHODS: We analysed a decade (2005-2015) of event histories data on 22385 and 1815 verbal autopsies data collected by Iganga-Mayuge HDSS in eastern Uganda. We used the lifetable for mortality estimates and patterns, and Royston-Parmar survival analysis approach for mortality risk factors' assessment. RESULTS: The under-10 and 5-9 years of age mortality probabilities were 129 (95% Confidence Interval [CI] = 123-370) per 1000 live births and 11 (95% CI = 7-26) per 1000 children aged 5-9 years, respectively. The top four causes of new-born mortality and stillbirth were antepartum maternal complications (31%), intrapartum-related causes including birth injury, asphyxia and obstructed labour (25%), Low Birth Weight (LBW) and prematurity (20%), and other unidentified perinatal mortality causes (18%). Malaria, protein deficiency including anaemia, diarrhoea or gastrointestinal, and acute respiratory infections were the major causes of mortality among those aged 0-9 years-contributing 88%, 88% and 46% of all causes of mortality for the post-neonatal, child and 5-9 years of age respectively. 33% of all causes of mortality among those aged 5-9 years was a share of Injuries (22%) and gastrointestinal (11%). Regarding the deterministic pattern, nearly 30% of the new-borns and sick children died without access to formal care. Access to the treatment for the top five morbidities was after 4 days of symptoms' recognition. The childhood mortality risk factors were LBW, multiple births, having no partner, adolescence age, rural residence, low education level and belonging to a poor household, but their association was stronger among infants. CONCLUSIONS: We have identified the vulnerable groups at risk of mortality as LBW children, multiple births, rural dwellers, those whose mother are of low socio-economic position, adolescents and unmarried. The differences in causes of mortalities between children aged 0-5 and 5-9 years were noted. These findings suggest for a strong life-course approach in the design and implementation of child health interventions that target pregnant women and children of all ages.

Use of a virtual patient simulation program to enhance the physical assessment and medical history taking skills of doctor of pharmacy students.

INTRODUCTION: To evaluate if utilizing a virtual simulated patient program in a required pharmacy course improves the health history taking and physical assessment skills of first-year professional pharmacy students. METHODS: During a 14-week course students registered for a web-based virtual patient simulation program. Students were assigned a virtual patient case to complete during weeks one and 13 of the course. Scores from the pre- and post-interventions were compared focusing on the students' ability to perform a physical exam, take a medical history, provide patient education, and display empathy. Students were also asked to self-assess their skills after having been exposed to the virtual simulation program throughout the semester. RESULTS: The total number of paired observations used in the final analysis of the pre- and post-virtual patient test case was 171 students. The overall student performance index, which includes the scoring of subjective/objective data and patient education/empathy, improved from 52% at week one to 78.42% at week 14. The individual scoring of subjective/objective data and patient education/empathy significantly improved from week one to week 13. Approximately 76.54% of the class strongly agreed or agreed that the virtual simulation program made them feel more confident in their ability to obtain a medical history from patients. CONCLUSIONS: Virtual patient simulation programs are effective teaching methods for students to develop and improve upon their medical history taking and physical assessment skills.

Routine identification of patients with disabilities in primary care: A mixed-methods study.

BACKGROUND: People with disabilities experience barriers to receiving healthcare and often have worse health outcomes, but data on disability is rarely routinely collected in a standardized way. OBJECTIVE: This study examined how patients responded to being asked about disabilities as part of a routine, self-administered sociodemographic survey. METHODS: We conducted a mixed-methods study in a multi-site primary care organization. We compared the characteristics of people who responded to a question about disabilities to those who did not respond using logistic regression. We also compared survey responses to data available in medical charts. In-depth interviews were conducted with a sample of patients following survey completion. RESULTS: Over 28 months, 15,221 patients were offered the survey and 14,247 (93.6%) responded to at least one question. Of these, 11,275 (79.1%) patients answered the question about disabilities. Older patients, patients who rented their home, and non-White patients were less likely to respond to the question. When comparing survey responses to data from medical charts we identified discrepancies. Patients interviewed reported they had difficulty judging what constituted a disability. Stigma related to mental illness and substance use led them to avoid disclosing those conditions. CONCLUSIONS: Directly asking patients whether they have a disability may be challenging given confusion about what constitutes a disability and stigma associated with certain disabilities. Future research should examine whether asking about barriers faced in accessing health services could adequately identify patients with disabilities and also be used to identify tangible actions an organization could take to lower barriers to care.

Perinatal and familial risk factors for soft tissue sarcomas in childhood through young adulthood: A population-based assessment in 4 million live births.

Perinatal factors have been associated with soft tissue sarcomas (STS) in case-control studies. However, (i) the contributions of factors including fetal growth remain unknown, ( ii) these factors have not been examined in cohort studies and (iii) few assessments have evaluated risk in specific STS subtypes. We sought to identify the role of perinatal and familial factors on the risk of STS in a large population-based birth cohort. We identified 4,023,436 individuals in the Swedish Birth Registry born during 1973-2012. Subjects were linked to the Swedish Cancer Registry, where incident STS cases were identified. We evaluated perinatal and familial factors obtained from Statistics Sweden, including fetal growth, gestational age, and presence of a congenital malformation. Poisson regression was used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for associations between perinatal factors and STS overall, as well as by common subtypes. There were 673 individuals diagnosed with STS in 77.5 million person-years of follow-up. Having a congenital malformation was associated with STS (IRR = 1.70, 95% CI: 1.23-2.35). This association was stronger (IRR = 2.90, 95% CI: 1.25-6.71) in recent years (2000-2012). Low fetal growth was also associated with STS during the same time period (IRR = 1.86, 95% CI: 1.05-3.29). Being born preterm was associated with rhabdomyosarcoma (IRR = 1.74, 95% CI: 1.08-2.79). In our cohort study, those with congenital malformations and other adverse birth outcomes were more likely to develop a STS compared to their unaffected contemporaries. These associations may point to disrupted developmental pathways and genetic factors influencing the risk of STS.

Cohort profile: the clinical 'Psoriasis in Adolescents' (PIA) cohort in Denmark.

PURPOSE: Psoriasis is a chronic inflammatory skin disease that frequently debuts in childhood and adolescence. We wished to determine environmental and genetic risk factors for the development of psoriasis in children and adolescents, as well as to investigate debut type, trigger factors, course of disease, nature and influence of stress related to both child and family and risk factors for comorbidity. The 'Psoriasis in Adolescents' (PIA) cohort will provide data on the relationship between psoriasis and, respectively, genetic disposition, early-life exposures, quality of life and comorbidity. PARTICIPANTS: The PIA cohort is nested in the large general population Danish National Birth Cohort (DNBC). We invited 390 adolescents with psoriasis and corresponding maternally predisposed and non-predisposed controls. Participants underwent an interview and a clinical examination consisting of a skin inspection and physical measurements including blood sampling and microbiological swabs. Additionally, four self-administered questionnaires on physical and mental health were completed. FINDINGS TO DATE: The final PIA cohort consists of 81 adolescents with psoriasis, 110 parentally predisposed and 124 non-predisposed psoriasis-free adolescents. The validity of the maternally reported psoriasis status from the DNBC was found to be low on clinical examination (47.5%). In contrast, the self-reported psoriasis status of the DNBC mothers was clinically confirmed in 80.8% of the cases. FUTURE PLANS: The PIA cohort offers the possibility of assessing the clinical characteristics, course of psoriasis and development of comorbidities in adolescents with clinically confirmed disease from a general population. Comparison with predisposed and non-predisposed controls is possible and genetic analyses are scheduled. We plan to invite the participants for a follow-up in 5-10 years. Furthermore, we plan to include newly diagnosed adolescents with psoriasis from the 18-year DNBC follow-up. All information is linkable on the individual level with data from the DNBC and nationwide registries in Denmark.

Adult Health Status Among Native American Families Participating in the Growing Resilience Home Garden Study.

Northern Arapaho and Eastern Shoshone tribes sharing the Wind River Indian Reservation (WRIR) in Wyoming reportedly die 30 years earlier than whites in the state. We analyzed data on the health status of 176 adults from 96 families who participated in a randomized controlled trial to assess health effects of home gardens. Measures of body mass index, waist circumference, blood pressure, hemoglobin A1c, vitamin D, low-density lipoprotein cholesterol, and household food security were collected from participating adults before the intervention. Results indicated that this group has considerably worse health status than average US adults and also fares worse than average American Indians/Alaska Natives. To help improve these disparities, Native Americans need access to appropriate and effective means of health promotion.

Assessment of breast self- examination practice and associated factors among female workers in Debre Tabor Town public health facilities, North West Ethiopia, 2018: Cross- sectional study.

BACKGROUND: Although breast Self-Examination is no longer tenable as a standard method to detect early breast cancer, world health organization recommends breast self -examination for raising awareness of women about breast cancer. Secondary prevention through monthly breast self-examination is the best option to tackle the rising incidence of breast cancer. Therefore, the aim of this study was to assess breast self -examination practice and associated factors. METHODS: This cross-sectional study was conducted from April 23 to May 23, 2018. A total of 421 female workers in Debre Tabor Town public health facilities were included. The study participants were selected using simple random sampling technique from the study population. The collected data were checked for completeness. The data were entered and cleaned using EpiData version 3.1 then exported to SPSS version 20 for analysis. Crude odd ratio and probability value were identified for each independent variable and all independent variables with probability value of less than 0.2 were entered into multivariables logistic regression. Statistically significant associated factors were identified based on probability value (p-value) less than 0.05 and adjusted odd ratio with 95% confidence interval. RESULT: The mean age of participants was 25.2 (S.D = 4.12) and 137 (32.5%) of the participants had practiced breast self -examination and 64 (15.2%) of them performed it monthly. Family history of breast cancer (adjusted OR = 6.5, CI = 1.54-21.4), Knowledge about breast -self examination (adjusted OR = 5.74, CI = 2.3-14.4) and self- efficacy in practicing breast self -examination (adjusted OR = 4.7, CI = 1.84-12.11) were significantly associated with breast self -examination practice. CONCLUSIONS: The study showed that the prevalence of breast self-examination was low. Family history of breast cancer, knowledge about breast self -examination and self- efficacy in practicing breast self- examination did have statistically significant association with breast self-examination practice.

The impact of sociodemographic characteristics, lifestyle, work exposure and medical history on semen parameters in young Chinese men: A cross-sectional study.

There is an ongoing debate on the declining semen quality, and unfortunately, existing evidence is inconclusive and inconsistence. We evaluated the impact of sociodemographic characteristics, lifestyle, medical history and work exposure on semen quality. Univariate and multivariate analysis was used to investigate the association between different risk factors and semen quality parameters. Total sperm count (p = 0.041), sperm concentration (p = 0.007), normal morphology (p = 0.002), total motility (p = 0.004) and progressive motility (p = 0.009) decreased in men with varicocele. Sperm concentration increased in tea (p = 0.044); progressive and total motility increased in cola (p = 0.018, p = 0.012) consumers. Progressive and total motility decreased in urogenital surgery (p = 0.016, p = 0.014) and infection (p = 0.037, p = 0.022). However, age, coffee and alcohol drinking, physical activities, sleep duration and cell phone use were unrelated to any of semen parameters. Interestingly, semen volume (p < 0.0001), total sperm count (p < 0.0001) and concentration (p < 0.033) increased with longer abstinence period (>5 days); normal morphology (p = 0.013) improved in men with higher body mass index (BMI > 24), curvilinear velocity (p = 0.042) increased with smoking; semen volume (p = 0.050) increased in manual labourers. This study highlights the importance of sociodemographic characteristics, lifestyle, occupational exposure and medical history and provides time trends in semen quality, its clinical importance and direction for further research.

Relationships of family history of disease and child weight status to child routines: Multi-mediating effect of parental feeding practices and perception of child's weight.

The present study is a secondary data analysis of a cross-sectional survey conducted among 129 parents of preschoolers from northwest Florida, USA. It examined the multi-mediating effect of parental feeding practices and parents' perception of child's weight in the relationships of family history of disease and child's weight to child routines. Children's height and weight were measured, and body mass index was calculated. Path analyses were performed to test the mediation model using AMOS 25.0. The mediating analysis revealed that restriction mediates the relationship between family history of disease and child routines. Restriction and monitoring were significant mediators between child's weight and routines. Given the critical impact of parents on childhood obesity, understanding the mediating roles of parental feeding practices is imperative, as such practices might be susceptible to intervention. Health-care providers should assess parental feeding practices in their practice settings.

Most associations of early-life environmental exposures and genetic risk factors poorly differentiate between eczema phenotypes: the Generation R Study.

BACKGROUND: Childhood eczema is variable in onset and persistence. OBJECTIVES: To identify eczema phenotypes during childhood, and their associations with early-life environmental and genetic factors. METHODS: In this study of 5297 children from a multiethnic population-based prospective cohort study, phenotypes based on parent-reported physician-diagnosed eczema from age 6 months to 10 years were identified using latent class growth analysis. Information on environmental factors was obtained using postal questionnaires. Four filaggrin mutations were genotyped and a risk score was calculated based on 30 genetic variants. Weighted adjusted multinomial models were used for association analyses. RESULTS: We identified the following five eczema phenotypes: never (76%), early transient (8%), mid-transient (6%) and late transient (8%) and persistent eczema (2%). Early transient and persistent eczema were most common in first-born children, those with a parental history of eczema, allergy or asthma and those with persistent wheezing [range of odds ratio (OR): 1.37, 95% confidence interval (CI) 1.07-1.74 and OR 3.38, 95%CI 1.95-5.85]. Early transient eczema was most common in male children only (OR 1·49, 95% CI 1·18-1·89). Children with late transient or persistent eczema were more often of Asian ethnicity (OR 2·04, 95% CI 1·14-3·65 and OR 3·08, 95% CI 1·34-7·10, respectively). Children with early, late transient and persistent eczema more often had a filaggrin mutation or additional risk alleles (range OR: 1.07, 95%CI 1.02-1.12 and OR 2.21, 95%CI 1.39-3.50). Eczema phenotypes were not associated with maternal education, breastfeeding, day care attendance and pet exposure. CONCLUSIONS: Five eczema phenotypes were identified in a multiethnic paediatric population with limited differences in risk profiles, except for sex and ethnicity. What's already known about this topic? Two previous studies in longitudinal birth cohorts identified four and six different eczema phenotypes, predominantly in children of European ethnicity. What does this study add? Five eczema phenotypes were identified in a multiethnic paediatric population using latent class growth analysis. Children with early transient and persistent eczema were most often first-born children and had persistent wheezing, filaggrin mutation or additional risk alleles. Previously known eczema risk factors had limited differentiating capabilities for eczema phenotypes, except for the association of early transient eczema with male children, and late transient and persistent eczema with Asian ethnicity.

Modified capture-recapture estimates of the number of families with Lynch syndrome in Central Ohio.

Past methods for estimating the population frequency of familial cancer syndromes have used cases and controls ignoring the familial nature of genetic disease. In this study we modified the capture-recapture method from ecology to estimate the number of families in central Ohio with Lynch syndrome (LS). We screened 1566 colorectal cancer cases and 545 endometrial cancer cases in central Ohio from 1999 to 2005 and identified 58 with LS. We screened an additional 3346 colorectal and 342 endometrial cancer cases from 2013 to 2016 and identified 149 with LS. We found 12 LS mutations shared between families observed in the first and second studies. We identified three individuals between studies who were closely related and eight who were more distantly related. We used identified family relationships and genetic test results to estimate family size and structure. Applying a modified capture-recapture method we estimate 1693 3-generation families in the area who have 288 unique LS causing mutations. Comprehensive colorectal and endometrial cancer screening will take about 20 years to identify 50% of families with LS. This is the first time that the capture-recapture method has been applied to estimate the burden of families with a specific heritable disease. Family structure reveals the potential extent of prevention and the time necessary to identify a proportion of families with LS.

Sex/gender bias in the management of chest pain in ambulatory care.

OBJECTIVE: Cardiovascular diseases (CVD) are the main cause of death worldwide and despite a higher prevalence in men, mortality from CVD is higher among women. Few studies have assessed sex differences in chest pain management in ambulatory care. The objective of this post hoc analysis of data from a prospective cohort study was to assess sex differences in the management of chest pain in ambulatory care. SETTING: We used data from the Thoracic Pain in Community cohort study that was realized in 58 primary care practices and one university ambulatory clinic in Switzerland. PARTICIPANTS: In total, 672 consecutive patients aged over 16 years attending a primary care practice or ambulatory care clinic with a complaint of chest pain were included between February and June 2001. Their mean age was 55.2 years and 52.5% were women. MAIN OUTCOME MEASURES: The main outcome was the proportion of patients referred to a cardiologist at 12 months follow-up. A panel of primary care physicians assessed the final diagnosis retained for chest pain at 12 months. RESULTS: The prevalence of chest pain of cardiovascular origin (n = 108, 16.1%) was similar for men and women (17.5% vs 14.8%, respectively, p = 0.4). Men with chest pain were 2.5 times more likely to be referred to a cardiologist than women (16.6% vs 7.4%, odds ratio: 2.49, 95% confidence interval: 1.52-4.09). After adjustment for the patients' age and cardiovascular disease risk factors, the estimates did not significantly change (odds ratio: 2.30, 95% confidence interval: 1.30-3.78). CONCLUSION: Although the same proportion of women and men present with a chest pain of cardiovascular origin in ambulatory care, there is a strong sex bias in their management. These data suggest that effort must be made to assure equity between men and women in medical care.

Menstrual History-Taking at Annual Well Visits for Adolescent Girls.

STUDY OBJECTIVE: To determine the rates at which primary care providers elicit menstrual histories from adolescent girls at well visits. DESIGN: Retrospective chart review. SETTING: The departments of Pediatrics, Adolescent Medicine, and Family Medicine of Cooper University Healthcare from January 1, 2010 to June 1, 2016. PARTICIPANTS: Women aged 12-21 years who were seen for a well visit in the described setting. INTERVENTIONS: None. MAIN OUTCOME MEASURES: We searched physician well visit notes for documentation of the following aspects of menstrual history: menarche, last menstrual period, usual length of cycle, and the presence or absence of associated symptoms (such as pain and cramps). The presence or absence of each aspect was recorded in a binary fashion in a deidentified data set. RESULTS: A total of 954 unique charts were analyzed: 415 from Adolescent Medicine, 289 from Family Medicine, and 250 from General Pediatrics at Cooper University Healthcare. Adolescent Medicine was 6.44 times more likely to take a complete menstrual history than Family Medicine (P < .0001) and 5.80 times more likely than Pediatrics (P < .0001). There was no statistical difference between Pediatrics and Family Medicine (odds ratio, 0.55; P = .3150). CONCLUSION: Menstrual history-taking is often incomplete and can vary between departments, even within the same institution. These results indicate opportunities to raise awareness about the importance of a complete menstrual history and to develop quality improvement initiatives to increase documentation of the complete menstrual history.

Hereditary Pancreatitis in the United States: Survival and Rates of Pancreatic Cancer.

OBJECTIVES: Hereditary pancreatitis (HP), an autosomal dominant disease typically caused by mutations in PRSS1, has a broad range of clinical characteristics and high cumulative risk of pancreatic cancer. We describe survival and pancreatic cancer risk in the largest HP cohort in the US. METHODS: HP probands and family members prospectively recruited from 1995 to 2013 completed medical and family history questionnaires, and provided blood for DNA testing. Overall survival (until 12/31/2015) was determined from the Social Security Death Index (SSDI), National Death Index (NDI), and family members. Cause of death was obtained from the NDI. RESULTS: 217 PRSS1 carriers (181 symptomatic) formed the study cohort. The most frequently detected mutations were p.R122H (83.9%) and p.N29I (11.5%). Thirty-seven PRSS1 carriers (30 symptomatic, 7 asymptomatic) were deceased at conclusion of the study (5 from pancreatic cancer). Median overall survival was 79.3 years (IQR 72.2-85.2). Risk of pancreatic cancer was significantly greater than age- and sex- matched SEER data (SIR 59, 95% CI 19-138), and cumulative risk was 7.2% (95% CI 0-15.4) at 70 years. DISCUSSION: We confirm prior observations on survival and pancreatic cancer SIR in PRSS1 subjects. Although risk of pancreatic cancer was significantly high in these patients, its cumulative risk was much lower than previous reports.

Assessment of Neurocognitive Functions in 7-Year-Old Children at Familial High Risk for Schizophrenia or Bipolar Disorder: The Danish High Risk and Resilience Study VIA 7.

Importance: Children at familial high risk of schizophrenia spectrum disorders (FHR-SZ) or bipolar disorder (FHR-BP) exhibit neurocognitive impairments. Large studies of neurocognition in young children at familial high risk at the same age are important to differentiate the pathophysiology and developmental trajectory of these 2 groups. Objective: To characterize neurocognitive functions in 7-year-old children with FHR-SZ or FHR-BP and a control population. Design, Setting, and Participants: This multisite population-based cohort study collected data from January 1, 2013, to January 31, 2016, in the first wave of the Danish High Risk and Resilience Study VIA 7 at 2 university hospital research sites in Copenhagen and Aarhus using Danish registries. Participants (n = 514) included 197 children with FHR-SZ, 118 with FHR-BP, and 199 controls matched with the FHR-SZ group for age, sex, and municipality. Assessors were blinded to risk status. Exposures: Parents with schizophrenia, bipolar disorder, or neither diagnosis. Main Outcomes and Measures: Neurocognitive functions were measured across 23 tests. Four neurocognitive domains were derived by principal component analysis, including processing speed and working memory, verbal functions, executive and visuospatial functions, and declarative memory and attention. Results: A total of 514 children aged 7 years were included in the analysis (46.3% girls), consisting of 197 children with FHR-SZ (46.2% girls), 118 with FHR-BP (46.6% girls), and 199 controls (46.2% girls). Children with FHR-SZ were significantly impaired compared with controls on processing speed and working memory (Cohen d = 0.50; P < .001), executive and visuospatial functions (Cohen d = 0.28; P = .03), and declarative memory and attention (Cohen d = 0.29; P = .02). Compared with children with FHR-BP, children with FHR-SZ performed significantly poorer in processing speed and working memory (Cohen d = 0.40; P = .002), executive and visuospatial functions (Cohen d = 0.35; P = .008), and declarative memory and attention (Cohen d = 0.31; P = .03). Children with FHR-BP and controls did not differ. Conclusions and Relevance: Children with FHR-SZ had widespread neurocognitive impairments, supporting the hypothesis of neurocognitive functions as endophenotypes of schizophrenia. The absence of neurocognitive deficits in children with FHR-BP suggests distinct neurodevelopmental manifestations in these familial high-risk groups at this age. Early detection of children with FHR-SZ and cognitive impairments is warranted to investigate associations of neurocognition with transition to psychosis, add to the knowledge of their developmental pathophysiology, and inform early intervention programs.

Quality of Care for Work-Associated Carpal Tunnel Syndrome.

OBJECTIVE: To evaluate the quality of care provided to individuals with workers' compensation claims related to Carpal tunnel syndrome (CTS) and identify patient characteristics associated with receiving better care. METHODS: We recruited subjects with new claims for CTS from 30 occupational clinics affiliated with Kaiser Permanente Northern California. We applied 45 process-oriented quality measures to 477 subjects' medical records, and performed multivariate logistic regression to identify patient characteristics associated with quality. RESULTS: Overall, 81.6% of care adhered to recommended standards. Certain tasks related to assessing and managing activity were underused. Patients with classic/probable Katz diagrams, positive electrodiagnostic tests, and higher incomes received better care. However, age, sex, and race/ethnicity were not associated with quality. CONCLUSIONS: Care processes for work-associated CTS frequently adhered to quality measures. Clinical factors were more strongly associated with quality than demographic and socioeconomic ones.