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Biologists try to understand the living world at large by zooming in on tractable portions of it and by constructing and studying models. If you want to study long-term evolution in real time, you can follow finch populations in their natural habitats in the Galápagos (Grant & Grant 1993) or you can evolve microbial models in flasks in a laboratory (Lenski et al. 1991). If you want to understand how multicellularity first emerged in eukaryotes, you cannot go back in time to examine that event directly. Instead, you can construct and study a variety of models: for example, agent-based computer simulations, model organisms such as yeast or volvox, or model-based phylogenetic reconstructions (Bonner et al. 2016).
To characterize the spectrum of BRCA1 and BRCA2 pathogenic germline variants in women from south-west Poland and west Ukraine affected with breast or ovarian cancer. Testing in women at high risk of breast and ovarian cancer in these regions is currently mainly limited to founder mutations.
Unrelated women affected with breast and/or ovarian cancer from Poland (n = 337) and Ukraine (n = 123) were screened by targeted sequencing. Excluded from targeted sequencing were 34 Polish women who had previously been identified as carrying a founder mutation in BRCA1. No prior testing had been conducted among the Ukrainian women. Thus, this study screened BRCA1 and BRCA2 in the germline DNA of 426 women in total.
We identified 31 and 18 women as carriers of pathogenic/likely pathogenic (P/LP) genetic variants in BRCA1 and BRCA2, respectively. We observed five BRCA1 and eight BRCA2 P/LP variants (13/337, 3.9%) in the Polish women. Combined with the 34/337 (10.1%) founder variants identified prior to this study, the overall P/LP variant frequency in the Polish women was thus 14% (47/337). Among the Ukrainian women, 16/123 (13%) women were identified as carrying a founder mutation and 20/123 (16.3%) were found to carry non-founder P/LP variants (10 in BRCA1 and 10 in BRCA2).
These results indicate that genetic testing in women at high risk of breast and ovarian cancer in Poland and Ukraine should not be limited to founder mutations. Extended testing will enhance risk stratification and management for these women and their families.
To assess the Framingham risk score as a prognostic tool for idiopathic sudden sensorineural hearing loss patients.
Medical records were reviewed for unilateral idiopathic sudden sensorineural hearing loss patients between January 2010 and October 2017. The 10-year risk of developing cardiovascular disease was calculated. Patients were subdivided into groups: group 1 – Framingham risk score of less than 10 per cent (n = 28); group 2 – score of 10 to less than 20 per cent (n = 6); and group 3 – score of 20 per cent or higher (n = 5).
Initial pure tone average and Framingham risk score were not significantly associated (p = 0.32). Thirteen patients in group 1 recovered completely (46.4 per cent), but none in groups 2 and 3 showed complete recovery. Initial pure tone average and Framingham risk score were significantly associated in multivariable linear regression analysis (R2 = 0.36). The regression coefficient was 0.33 (p = 0.003) for initial pure tone average and −0.67 (p = 0.005) for Framingham risk score.
Framingham risk score may be useful in predicting outcomes for idiopathic sudden sensorineural hearing loss patients, as those with a higher score showed poorer hearing recovery.
Introduction: Emergency Department (ED) utilization during pregnancy may be common, but data specific to universal healthcare systems like Canada are lacking, where pregnancy care is supposed to be standardized. The objective of this study was to quantify and characterize ED utilization among all Ontarian women who had a recognized pregnancy, including by trimester and within 42 days after pregnancy, and further stratified by pregnancy outcome. Methods: Utilizing provincial administrative health databases, this retrospective population-based cohort study included all recognized pregnancies in Ontario conceived between April 1, 2002 and March 31, 2017. Peri-pregnancy ED utilization was defined as any ED visit from 0-42 weeks’ gestation, or within 42 days after the end of pregnancy. Modified Poisson regression was used to generate relative risks (RR) and 95% confidence intervals (CI) for the outcome of any peri-pregnancy ED utilization in association with maternal characteristics. Results: Peri-pregnancy ED utilization occurred among 1,075,991 of 2,728,236 recognized pregnancies (39.4%), including among 35.8% of livebirths, 47.3% of stillbirths, 73.7% of miscarriages, and 84.8% of threatened abortions. There were 22,802 (0.84%) ectopic pregnancies among all pregnancies in the cohort. ED utilization peaked in the first trimester and in the first week postpartum. A dose-response effect was seen in the number of peri-pregnancy ED visits in relation to certain maternal characteristics. Women residing in rural areas had an odds ratio (OR) of 3.44 (95% CI 3.39 to 3.49) for ≥ 3 ED visits, compared to those in urban areas. Women with 3-5 (OR 1.99 95% CI 1.97-2.01), 5-6 (OR 3.55, 95% CI 3.49 to 3.61), or ≥ 7 (OR 7.59, 95% CI 7.39 to 7.78) pre-pregnancy comorbidities were more likely to have ≥ 3 peri-pregnancy ED visits than those with 0-2 comorbidities. Of all recognized pregnancies in the cohort, only 106,989 (3.9%) had an injury-related ED visit. Conclusion: Peri-pregnancy ED utilization occurs in nearly 40% of pregnancies, notably in the first trimester and immediately postpartum. Efforts are needed to streamline rapid access to ambulatory obstetrical care during these peak periods, when women are vulnerable to either a miscarriage, or a complication after a livebirth.
Out of area treatments (OAT) are expensive and contribute to social isolation of individuals with intellectual disabilities and challenging behaviour.
To identify the needs of those service users who are in OATs with the view of developing a process of assessment and relocation of those service users locally where possible. Finally we aim to reinvest financial flow in each locality to develop high quality services.
We undertook a scoping project over one year in five London boroughs. We reviewed the existing literature, surveyed mental health and challenging behaviour needs of sample, reviewed current treatment and run focus groups with various stakeholders. We presented a business case
205 service users were identified costing over £1300 per week. 65.4% were in OATs costing an estimated £403,740 a week across the five boroughs. High expenditure was associated with increased perceived severity of mental illness, complex physical disabilities and presence of autism. Those detained under the Mental Health Act were also in more expensive placements. Private sector placements were used in the majority of cases.
Despite the lack of high level evidence for specialist services for challenging behaviour, a multi-stranded approach with both inpatient spot purchasing, rehabilitation facilities and high quality accommodation with flexible community with variable purchasing patterns and specialist community input could substantially reduce the financial burden.
Stigma and social exclusion related to mental health are of substantial public health importance for Europe. As part of ROAMER (ROAdmap for MEntal health Research in Europe), we used systematic mapping techniques to describe the current state of research on stigma and social exclusion across Europe. Findings demonstrate growing interest in this field between 2007 and 2012. Most studies were descriptive (60%), focused on adults of working age (60%) and were performed in Northwest Europe—primarily in the UK (32%), Finland (8%), Sweden (8%) and Germany (7%). In terms of mental health characteristics, the largest proportion of studies investigated general mental health (20%), common mental disorders (16%), schizophrenia (16%) or depression (14%). There is a paucity of research looking at mechanisms to reduce stigma and promote social inclusion, or at factors that might promote resilience or protect against stigma/social exclusion across the life course. Evidence is also limited in relation to evaluations of interventions. Increasing incentives for cross-country research collaborations, especially with new EU Member States and collaboration across European professional organizations and disciplines, could improve understanding of the range of underpinning social and cultural factors which promote inclusion or contribute toward lower levels of stigma, especially during times of hardship.
Life events and accompanying psychological and behavioral reactions frequently have an impact upon people's daily lives and are believed to predispose them to disease. Psychological stressors impact many physiological and pathological disease outcomes, including mental illness. Positive social interactions have in turn been shown to exert powerful beneficial effects on health outcomes and longevity.
The Objective of this study was to analyze the relationships of Psychological Distress, Social Support, and Mental Fitness among patients of mental health services.
This article aims to discuss the evidence supporting the mediating effect of social support between psychological stress and mental health.
This study was performed on patients who visited the mental health services in Daejeon from October to December 2011. In total, 395 patients were evaluated with Mental Fitness Scale, Kessler Psychological Distress Scale(KPDS), and Multidimensional Scale of Perceived Social Support(MSPSS).
Correlations among variables of psychological distress and social support on subordinate variable of mental fitness of patients were significant. The result of the regression analysis, psychological distress and social support have a positively significant influence on mental fitness of patients. social support showed mediating effects between psychological distress and mental fitness.
These results suggest that health care providers ought to seek social support for patients, in order to provide positive mental fitness of patients.
Acute angle-closure glaucoma (AACG) is an ophthalmic emergency, accompanied with severe eye pain, headache, and visual changes because of acute intraocular pressure elevation. Among psychotropic drugs, several antidepressants, typical antipsychotics with strong anticholinergic effects, and topiramate have been known to increase a possibility of AACG. Benzodiazepines have been used widely in the treatment of mental and physical illnesses regardless of age or indication. Since benzodiazepines have some anticholinergic properties and affect pupillae muscles, their use could be theoretically a risk factor for AACG. However, it is unclear whether benzodiazepines actually increase the risk of AACG. To our knowledge, there was no population-based study on the risk of benzodiazepines to the occurrence of AACG.
To know whether benzodiazepines increase the risk of AACG in a geriatric population.
We will perform a case-control study using a geriatric cohort from the National Health Insurance database. Case subjects will be defined as cases diagnosed with AACG confirmed by the claim data of laser iridotomy, which is the definitive treatment of AACG. The controls, which were not diagnosed with AACG, will be matched with case subjects according to similar age, sex, and the scores of the Charlson comorbidity index.
The data handling and statistical analyses will be executed in autumn and winter 2016.
Any preliminary findings of this study will be presented at the EPA 2017. We will discuss the importance of a pharmaco-epidemiological study in the geriatric research.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Although a number of studies have examined the relationship between depression and obesity, it is still insufficient to establish the specific pattern of relationship between depression and body mass index (BMI) categories. Thus, this study was aimed to investigate the relationship between depression and BMI categories.
A cross-sectional study was conducted for a cohort of 159,390 Korean based on Kangbuk Samsung Health Study (KSHS). Study participants were classified into 5 groups by Asian-specific cut-off of BMI (18.5, 23, 25 and 30 kg/m2). The presence of depression was determined by Center for Epidemiologic Studies-Depression scales (CES-D) = 16 and = 25. The adjusted odd ratios (ORs) for depression were evaluated by multiple logistic regression analysis, in which independent variable was 5 categories of BMI and dependent variable was depression. Subgroup analysis was conducted by gender and age.
When normal group was set as a reference, the adjusted ORs for depression formed U-shaped pattern of relationship with BMI categories [underweight: 1.31 (1.14–1.50), overweight: 0.94 (0.85–1.04), obese group: 1.01 (0.91–1.12), severe obese group: 1.28 (1.05–1.54)]. This pattern of relationship was more prominent in female and young age group than male and elderly subgroup. BMI level with the lowest likelihood of depression was 18.5 kg/m2 to 25 kg/m2 in women and 23 kg/m2 to 25 kg/m2 in men.
There was a U-shaped relationship between depression and BMI categories. This finding suggests that both underweight and severe obesity are associated with the increased risk for depression.
The objective of this family-based whole exome sequencing (WES) is to examine genetic variants of autism spectrum disorder (ASD) in Korean population.
The probands with ASD and their biological parents were recruited in this study. We ascertained diagnosis based on DSM-5™ criteria, using Autism Diagnostic Observation Schedule and Autism Diagnostic Interview–Revised. We selected probands with typical phenotypes of ASD both in social interaction/communication and repetitive behaviour/limited interest domains, with intellectual disability (IQ < 70), for attaining homogeneity of the phenotypes. First, we performed WES minimum 50× for 13 probands and high-coverage pooled sequencing for their parents. We performed additional WES for 38 trio families, at least 100× depth. De novo mutations were confirmed by Sanger sequencing. All the sequence reads were mapped onto the human reference genome (hg19 without Y chromosome). Bioinformatics analyses were performed by BWA-MEM, Picard, GATK, and snpEff for variant annotation. We selected de novo mutation candidates from probands, which are neither detected in two pooled samples nor both parents.
Fifty-one subjects with ASD (5 females, 40∼175 months, mean IQ 42) and their families were included in this study. We discovered 109 de novo variants from 46 families. Twenty-nine variants are expected to be amino acid changing, potentially causing deleterious effects. We assume CELSR3, MYH1, ATXN1, IDUA, NFKB1, and C4A/C4B may have adverse effect on central nerve system.
We observed novel de novo variants which are assumed to contribute to development of ASD with typical phenotypes and low intelligence in WES study.
Disclosure of interest
This work has been supported by Healthcare Technology R&D project (No: A120029) by Ministry of Health and Welfare, Republic of Korea.
Sleep disturbances are common among cancer patients. Especially during hospitalization, not only adverse medical conditions but also ward environments can affect sleep. We have developed a program of sleep-hygiene education and sleeping pill reduction for inpatients (the i-sleep program) and applied it to cancer patients. This study aimed to explore the effect of the program.
In a general hospital with 2,715 beds, we estimated the proportion of inpatients prescribed hypnotics at admission to and discharge from the department of oncology before (2014) and after (2015) the program. In addition, we estimated the proportion of inpatients prescribed hypnotics among all inpatients in the department of oncology on the first day of each month of 2014 and 2015.
A total of 12,382 patients (2014, before) and 12,313 patients (2015, after) were admitted to oncology department of Asan Medical Center. The proportion of inpatients prescribed hypnotics as discharge medication among inpatients who had been prescribed them at the time of admission decreased significantly, from 76.0% (2014) to 69.8% (2015), after the program (RR = 0.92, 95% CI: 0.87–0.98). The proportion of inpatients newly prescribed sleeping pills after admission to the hospital did not significantly decrease (4.03% to 3.98%; RR = 0.99, 95% CI: 0.87–1.12). The mean prescription rate of sleeping pills per day was 10.02% in 2014 and 7.99% in 2015 (P = 0.03).
Although the i-sleep program did not reduce the prescription rate of sleeping pills per day, it effectively reduced the proportion of cancer patients who continued to take sleeping pills from admission until discharge.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
To propose a new anthropometric index that can be employed to better predict percent body fat (PBF) among young adults and to compare with current anthropometric indices.
All measurements were taken in a controlled laboratory setting in Seoul (South Korea), between 1 December 2015 and 30 June 2016.
Eighty-seven young adults (18–35 years) who underwent dual-energy x-ray absorptiometry (DXA) were used for analysis. Multiple regression analyses were conducted to develop a body fat index (BFI) using simple demographic and anthropometric information. Correlations of DXA measured PBF (DXA_PBF) with previously developed anthropometric indices and the BFI were analysed. Receiver operating characteristic curve analyses were conducted to compare the ability of anthropometric indices to identify obese individuals.
BFI showed a strong correlation with DXA_PBF (r = 0·84), which was higher than the correlations of DXA_PBF with the traditional (waist circumference, r = 0·49; waist to height ratio, r = 0·68; BMI, r = 0·36) and alternate anthropometric indices (a body shape index, r = 0·47; body roundness index, r = 0·68; body adiposity index, r = 0·70). Moreover, the BFI showed higher accuracy at identifying obese individuals (area under the curve (AUC) = 0·91), compared with the other anthropometric indices (AUC = 0·71–0·86).
The BFI can accurately predict DXA_PBF in young adults, using simple demographic and anthropometric information that are commonly available in research and clinical settings. However, larger representative studies are required to build on our findings.
Infectious diseases, such as Helicobacter pylori, which produce systemic inflammation may be one key factor in the onset of autoimmunity. The association between H. pylori and antinuclear antibodies (ANA), a marker of autoimmunity, has been understudied. Data from the 1999–2000 National Health and Nutrition Examination Survey were used to evaluate the cross-sectional association between H. pylori seroprevalence and ANA positivity in US adults aged ≥20 years. ANA was measured in a 1:80 dilution of sera by indirect immunofluorescence using HEp-2 cells (positive ⩾3). H. pylori immunoglobulin G enzyme-linked immunosorbent assays were used to categorise individuals as seropositive or seronegative. H. pylori seropositivity and ANA positivity were common in the adult US population, with estimated prevalences of 33.3% and 9.9%, respectively. Both were associated with increasing age. H. pylori seropositivity was associated with higher odds of ANA (prevalence odds ratio = 1.89, 95% confidence interval = 1.08–3.33), adjusted for age, sex, race/ethnicity, educational attainment and body mass index. H. pylori infection may be one key factor in the loss of self-tolerance, contributing to immune dysfunction.
To investigate the association between parity and the risk of incident dementia in women.
We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)).
Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02–1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1–4 parities (HR = 1.30, 95% CI = 1.02–1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02–1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00–2.55), but the risk of AD was not significantly associated with parity.
Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.
Common mental disorders are highly prevalent among Syrian refugees. Problem Management Plus (PM+) is a brief, transdiagnostic, non-specialist helper delivered, psychological intervention targeting psychological distress. This single-blind pilot randomised controlled trial (RCT) on PM+ delivered by peer-refugees examined trial procedures in advance of a definitive RCT, evaluated PM+ 's acceptability and feasibility, and investigated its likely effectiveness and cost-effectiveness among Syrian refugees in the Netherlands.
Adult Syrian refugees (N = 60) with elevated psychological distress (Kessler Psychological Distress Scale (K10) score >15) and reduced pychosocial functioning (WHO Disability Assessment Schedule 2.0 (WHODAS) score >16) were randomised into PM+ in addition to care as usual (CAU) (PM+/CAU; n = 30) or CAU alone (n = 30). Primary outcomes were symptoms of depression and anxiety (Hopkins Symptom Checklist; HSCL-25) at 3-month follow-up. Secondary outcomes were pychosocial functioning (WHO Disability Assessment Schedule; WHODAS 2.0), symptoms of posttraumatic stress disorder (PTSD) (PTSD Checklist for DSM 5; PCL-5) and self-identified problems (Psychological Outcomes Profiles; PSYCHLOPS). Changes in service utilisation and time out of employment and/or adult education were estimated (adapted version of the Client Service Receipt Inventory; CSRI). Semi-structured interviews on the implementation of PM+ were conducted with stakeholders (i.e. six PM+ participants, five non-specialist helpers and five key informants).
Recruitment, randomization and blinding procedures were successful. PM+ was generally perceived positively by stakeholders, especially regarding the intervention strategies, accommodation of the intervention and the helpers. Two serious adverse events not attributable to the trial were reported. At 3-month follow-up, the HSCL-25 total score was significantly lower for the PM+/CAU group (n = 30) than CAU group (n = 30) (p = 0.004; d = 0.58). Significant differences in favour of PM+/CAU were also found for WHODAS psychosocial functioning (p = 0.009, d = 0.73), PCL-5 symptoms of PTSD (p = 0.006, d = 0.66) and PSYCHLOPS self-identified problems (p = 0.005, d = 0.81). There were no significant differences in mean health service costs (p = 0.191) and the mean costs of lost productive time (p = 0.141). This suggests PM+ may potentially be cost-effective with an incremental cost from a health system perspective of €5047 (95% CI €0–€19 773) per additional recovery achieved.
Trial procedures and PM+ delivered by non-specialist peer-refugee helpers seemed acceptable, feasible and safe. Analyses indicate that PM+ may be effective in improving mental health outcomes and psychosocial functioning, and potentially cost-effective. These results support the development of a definitive RCT with a larger sample of refugees and a longer follow-up period.