Interpreting the Evidence of Body Mass Index in Relation to Mental Health Status in Community-Dwelling Older Adults.

INTRODUCTION: Maintaining a better physical and mental health status is an important issue for older adults in their later life. Thus, the study's purpose was to evaluate the association between body mass index (BMI) and mental health status in older adults aged 65 years old or above residing in communities of Taipei City, Taiwan. METHODS: We carried out secondary data analysis with data from a volunteer-based health examination project for older adults >65 years old residing in Taipei City from 2006 to 2010 with a retrospective study design. BMI, calculated by standardized measuring procedures for height and weight, and mental health status, evaluated by 5-item Brief Symptom Rating Scale (BSRS-5), were collected at their first visits of health examination. A BSRS-5 score ≥6 was considered an inferior mental health status for the outcome. In statistical analysis, univariable and multivariable logistic regressions were adopted to estimate the relative risk of inferior mental health status, treating BMI as the major exposure of interest. RESULTS: A total of 90,576 subjects were involved, with a mean age of 73.38 years old (SD = 6.64 years) and 49.21% females. With confounders controlled, compared to normal or overweight (23 ≤ BMI <30), an adjusted OR of 1.23 (95% CI: 1.18, 1.29) on inferior mental health status was detected for the underweight group (BMI <23) significantly. Adjusted OR for those obese (BMI ≧30) was 0.87 (95% CI: 0.79, 0.96). Significantly elevated ORs of underweight were found for both genders, but the significantly protective effect of obese was only detected for females. CONCLUSION: Keeping an appropriate weight or even being overweighted might be beneficial for older adults dwelling in the community, especially for males.

Orexin-a elevation in antipsychotic-treated compared to drug-free patients with schizophrenia: A medication effect independent of metabolic syndrome.

BACKGROUND/PURPOSE: Orexin-A levels are reportedly increased in antipsychotic (APD)-treated patients with schizophrenia compared to healthy controls and have been associated with metabolic abnormalities. It is not clear whether the orexin-A elevation is related specifically to the drug (APDs) effect, which should be clarified by including a drug-free group for comparison, or related to drug-induced metabolic abnormalities. METHODS: Blood orexin-A levels and metabolic profiles were compared between 37 drug-free, 45 aripiprazole-treated, and 156 clozapine-treated patients with schizophrenia. The association between orexin-A and metabolic outcomes were examined. We explored the effects of APDs treatment and metabolic status on orexin-A levels by linear regression. RESULTS: Patients under APDs treatment had increased orexin-A levels compared to drug-free patients, with aripiprazole-treated group having higher orexin-A levels than clozapine-treated group. Higher orexin-A levels reduced the risks of metabolic syndrome (MS) and type 2 diabetes mellitus, indicating a relationship between orexin-A levels and metabolic problems. After adjusting the effect from metabolic problems, we found APD treatment is still associated with orexin-A regulation, with aripiprazole more significantly than clozapine. CONCLUSION: With the inclusion of drug-free patients rather than healthy controls for comparison, we demonstrated that orexin-A is upregulated following APD treatment even after we controlled the potential effect from MS, suggesting an independent effect of APDs on orexin-A levels. Furthermore, the effect differed between APDs with dissimilar obesogenicity, i.e. less obesogenicity likely associated with higher orexin-A levels. Future prospective studies exploring the causal relationship between APDs treatment and orexin-A elevation as well as the underlying mechanisms are warranted.

How do ethnicity and deprivation impact on life expectancy at birth in people with serious mental illness? Observational study in the UK.

BACKGROUND: Across international contexts, people with serious mental illnesses (SMI) experience marked reductions in life expectancy at birth. The intersection of ethnicity and social deprivation on life expectancy in SMI is unclear. The aim of this study was to assess the impact of ethnicity and area-level deprivation on life expectancy at birth in SMI, defined as schizophrenia-spectrum disorders, bipolar disorders and depression, using data from London, UK. METHODS: Abridged life tables to calculate life expectancy at birth, in a cohort with clinician-ascribed ICD-10 schizophrenia-spectrum disorders, bipolar disorders or depression, managed in secondary mental healthcare. Life expectancy in the study population with SMI was compared with life expectancy in the general population and with those residing in the most deprived areas in England. RESULTS: Irrespective of ethnicity, people with SMI experienced marked reductions in life expectancy at birth compared with the general population; from 14.5 years loss in men with schizophrenia-spectrum and bipolar disorders, to 13.2 years in women. Similar reductions were noted for people with depression. Across all diagnoses, life expectancy at birth in people with SMI was lower than the general population residing in the most deprived areas in England. CONCLUSIONS: Irrespective of ethnicity, reductions in life expectancy at birth among people with SMI are worse than the general population residing in the most deprived areas in England. This trend in people with SMI is similar to groups who experience extreme social exclusion and marginalisation. Evidence-based interventions to tackle this mortality gap need to take this into account.

Excess mortality and risk factors for mortality among patients with severe mental disorders receiving home care case management.

AIM: Home care case management (CM) is the main intervention for patients with severe mental disorders (SMDs) requiring outreach care. This study investigated the long-term mortality outcome and associated risk factors in patients who received home care CM. METHODS: This nationwide study enrolled patients who received home care CM (n = 10,255) between 1 January 1999 and 31 December 2010. Each patient was followed up from the baseline (when patients underwent home case CM for the first time during the study period) to the censor (i.e. mortality or the end of the study). We calculated the standardized mortality ratio (SMR) and presented by age and diagnosis. Multivariate regression was performed to assess independent risk factors for mortality. RESULTS: Among 10,255 patients who received home care CM, 1409 died during the study period; the overall SMR was 3.13. Specifically, patients with organic mental disorder had the highest SMR (4.98), followed by those with schizophrenia (3.89), major depression (2.98), and bipolar disorder (1.97). In the multivariate analysis, patients with organic mental disorder or dementia had the highest risk, whereas the mortality risk in patients with schizophrenia was comparable to that in patients with bipolar disorder or major depression. Deceased patients had a significantly higher proportion of acute or chronic physical illnesses, including cancer, chronic hepatic disease, pneumonia, diabetes mellitus, cardiovascular disease, and asthma. CONCLUSION: This study presented the gap of mortality in patients with SMDs receiving home care CM in Taiwan. We highlight the need for effective strategies to improve medical care for this specified population.

Orexin-A Levels in Relation to the Risk of Metabolic Syndrome in Patients with Schizophrenia Taking Antipsychotics.

Background: The role of orexin-A in regulating metabolic homeostasis has been recognized, but its association with antipsychotic-induced metabolic abnormalities remains unclear. We investigated the association between orexin-A levels and metabolic syndrome in patients with schizophrenia treated with clozapine or less obesogenic antipsychotics compared with nonpsychiatric controls. Methods: Plasma orexin-A levels and metabolic parameters were determined in 159 patients with schizophrenia: 109 taking clozapine; 50 taking aripiprazole, amisulpride, ziprasidone, or haloperidol; and 60 nonpsychiatric controls. Results: Orexin-A levels were significantly higher in the group taking less obesogenic antipsychotics, followed by the clozapine group and the controls (F=104.6, P<.01). Higher orexin-A levels were correlated with better metabolic profiles in the patient groups but not in the controls. Regression analyses revealed that the patients with higher orexin-A levels had significantly lower risk of metabolic syndrome (adjusted odds ratio [OR]=0.04, 95% CI: 0.01-0.38 for the 2nd tertile; OR=0.04, 95% CI: 0.01-0.36 for the 3rd tertile, compared with the first tertile), after adjustment for age, sex, smoking history, types of antipsychotics (clozapine vs less obesogenic antipsychotics), duration of antipsychotic treatment, and disease severity. Conclusions: Our results revealed that the orexin-A level was upregulated in patients with schizophrenia treated with antipsychotics, especially for the group taking less obesogenic antipsychotics. Furthermore, higher orexin-A levels were independently associated with better metabolic profiles. These observations suggest that an upregulation of orexin-A has a protective effect against the development of metabolic abnormalities in patients with schizophrenia receiving antipsychotic treatment.

Depression and cause-specific mortality in an ethnically diverse cohort from the UK: 8-year prospective study.

BACKGROUND: Depression is associated with increased mortality, however, little is known about its variation by ethnicity. METHODS: We conducted a cohort study of individuals with ICD-10 unipolar depression from secondary mental healthcare, from an ethnically diverse location in southeast London, followed for 8 years (2007-2014) linked to death certificates. Age- and sex- standardised mortality ratios (SMRs), with the population of England and Wales as a standard population were derived. Hazard ratios (HRs) for mortality were derived through multivariable regression procedures. RESULTS: Data from 20 320 individuals contributing 91 635 person-years at risk with 2366 deaths were used for analyses. SMR for all-cause mortality in depression was 2.55(95% CI 2.45-2.65), with similar trends by ethnicity. Within the cohort with unipolar depression, adjusted HR (aHRs) for all-cause mortality in ethnic minority groups relative to the White British group were 0.62(95% CI 0.53-0.74) (Black Caribbean), 0.53(95% CI 0.39-0.72) (Black African) and 0.69(95% CI 0.52-0.90) (South Asian). Male sex and alcohol/substance misuse were associated with an increased all-cause mortality risk [aHR:1.94 (95% CI 1.68-2.24) and aHR:1.18 (95% CI 1.01-1.37) respectively], whereas comorbid anxiety was associated with a decreased risk [aHR: 0.72(95% CI 0.58-0.89)]. Similar associations were noted for natural-cause mortality. Alcohol/substance misuse and male sex were associated with a near-doubling in unnatural-cause mortality risk, whereas Black Caribbean individuals with depression had a reduced unnatural-cause mortality risk, relative to White British people with depression. CONCLUSIONS: Although individuals with depression experience an increased mortality risk, marked heterogeneity exists by ethnicity. Research and practice should focus on addressing tractable causes underlying increased mortality in depression.

Psychiatric comorbidity as a risk factor for mortality in people with anorexia nervosa.

Anorexia nervosa (AN) is found associated with increased mortality. Frequent comorbidities of AN include substance use disorders (SUD), affective disorders (AD) and personality disorders (PD). We investigated the influence of these psychiatric comorbidities on all-cause mortality with demographic and socioeconomic factors considered as confounders in the observation window between January 2007 and March 2016 for 1970 people with AN, using data from the case register of the South London and Maudsley (SLaM) NHS Foundation Trust, an almost monopoly-secondary mental healthcare service provider in southeast London. We retrieved data from its Clinical Records Interactive Search (CRIS) system as data source. Mortality was ascertained through nationwide tracing by the UK Office for National Statistics (ONS) linked to CRIS database on a monthly basis. A total of 43 people with AN died during the observation period. Standardized Mortality Ratio (SMR) with England and Wales population in 2012 as standard population for our study cohort was 5.21 (95% CI 3.77, 7.02). In univariate analyses, the comorbidity of SUD or PD was found to significantly increase the relative risks of mortality (HRs = 3.10, 95% CI 1.21, 7.92; and 2.58, 95% CI 1.23, 5.40, respectively). After adjustment for demographic and socioeconomic covariates as confounders, moderately but not significantly elevated risks were identified for SUD (adjusted HR = 1.39, 95% CI 0.53, 3.65) and PD (adjusted HR = 1.58, 95% CI 0.70, 3.56). These results suggest an elevated mortality in people with AN, which might be, at least partially, explained by the existence of the comorbidities SUD or PD.

Psychiatric comorbidity as a risk factor for the mortality of people with bulimia nervosa.

BACKGROUND: Bulimia nervosa (BN) is associated with increased mortality. Frequent comorbidities of BN include substance use disorders, affective disorders and personality disorders (PD). These comorbidities may add an additional risk for mortality. METHODS: We investigated the influence of these psychiatric comorbidities on all-cause mortality with demographic and socioeconomic factors considered as confounders over an observation period from January 2007 to March 2016 for 1501 people with BN using anonymised health records data from the South London and Maudsley NHS Foundation Trust (SLaM), retrieved through its Clinical Records Interactive Search (CRIS) data resource. Mortality was ascertained through monthly linkages to the nationwide tracing system administered by the Office for National Statistics (ONS). We used Cox proportional hazards regression to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Multivariable analyses were also performed to estimate effects when controlling for confounding of age, sex, ethnicity, borough, marital status and deprivation score. RESULTS: A total of 18 patients with BN died during the observation period. The standardised mortality ratio (SMR) for our study cohort (against the population of England and Wales in 2012 as a standard) was 2.52 (95% CI 1.49-3.97). Cox regressions revealed significant associations of mortality with older age and male gender. Comorbid PD (HR: 3.36; 95% CI 1.05-10.73) was significantly associated with all-cause mortality, even after controlling for demographic and socioeconomic covariates. CONCLUSIONS: These results highlight increased mortality in patients with BN and the importance of recognising and treating PDs in patients with BN.

Acute general hospital admissions in people with serious mental illness.

BACKGROUND: Serious mental illness (SMI, including schizophrenia, schizoaffective disorder, and bipolar disorder) is associated with worse general health. However, admissions to general hospitals have received little investigation. We sought to delineate frequencies of and causes for non-psychiatric hospital admissions in SMI and compare with the general population in the same area. METHODS: Records of 18 380 individuals with SMI aged ⩾20 years in southeast London were linked to hospitalisation data. Age- and gender-standardised admission ratios (SARs) were calculated by primary discharge diagnoses in the 10th edition of the World Health Organization International Classification of Diseases (ICD-10) codes, referencing geographic catchment data. RESULTS: Commonest discharge diagnosis categories in the SMI cohort were urinary conditions, digestive conditions, unclassified symptoms, neoplasms, and respiratory conditions. SARs were raised for most major categories, except neoplasms for a significantly lower risk. Hospitalisation risks were specifically higher for poisoning and external causes, injury, endocrine/metabolic conditions, haematological, neurological, dermatological, infectious and non-specific ('Z-code') causes. The five commonest specific ICD-10 diagnoses at discharge were 'chronic renal failure' (N18), a non-specific code (Z04), 'dental caries' (K02), 'other disorders of the urinary system' (N39), and 'pain in throat and chest' (R07), all of which were higher than expected (SARs ranging 1.57-6.66). CONCLUSION: A range of reasons for non-psychiatric hospitalisation in SMI is apparent, with self-harm, self-neglect and/or reduced healthcare access, and medically unexplained symptoms as potential underlying explanations.

Mortality of people with chronic fatigue syndrome: a retrospective cohort study in England and Wales from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Clinical Record Interactive Search (CRIS) Register.

BACKGROUND: Mortality associated with chronic fatigue syndrome is uncertain. We investigated mortality in individuals diagnosed with chronic fatigue syndrome in secondary and tertiary care using data from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Clinical Record Interactive Search (CRIS) register. METHODS: We calculated standardised mortality ratios (SMRs) for all-cause, suicide-specific, and cancer-specific mortality for a 7-year observation period using the number of deaths observed in SLaM records compared with age-specific and sex-specific mortality statistics for England and Wales. Study participants were included if they had had contact with the chronic fatigue service (referral, discharge, or case note entry) and received a diagnosis of chronic fatigue syndrome. FINDINGS: We identified 2147 cases of chronic fatigue syndrome from CRIS and 17 deaths from Jan 1, 2007, to Dec 31, 2013. 1533 patients were women of whom 11 died, and 614 were men of whom six died. There was no significant difference in age-standardised and sex-standardised mortality ratios (SMRs) for all-cause mortality (SMR 1·14, 95% CI 0·65-1·85; p=0·67) or cancer-specific mortality (1·39, 0·60-2·73; p=0·45) in patients with chronic fatigue syndrome when compared with the general population in England and Wales. This remained the case when deaths from suicide were removed from the analysis. There was a significant increase in suicide-specific mortality (SMR 6·85, 95% CI 2·22-15·98; p=0·002). INTERPRETATION: We did not note increased all-cause mortality in people with chronic fatigue syndrome, but our findings show a substantial increase in mortality from suicide. This highlights the need for clinicians to be aware of the increased risk of completed suicide and to assess suicidality adequately in patients with chronic fatigue syndrome. FUNDING: National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London.

Alcohol-Related Dementia: A Systemic Review of Epidemiological Studies.

BACKGROUND: Alcohol-related dementia (ARD) is a heterogeneous long-term cognitive problem that can develop in the course of alcoholism. Current understanding of ARD remains limited. METHODS: We conducted a systematic review to synthesize available data on the epidemiology of ARD, through searching the relevant studies in the PubMed, PsycINFO, and ALOIS. "Alcohol" and "dementia" were used as keywords. RESULTS: We included articles published between January 1, 1991 and February 29, 2016, where language was not limited. Of the 9 identified articles, the prevalence of ARD ranged from 1.19/1000 in multiday admission patients residing in the United Kingdom to 25.6% in elderly clinic alcoholics from the United States. The proportion of ARD in early-onset dementia taken from 3 studies was approximately 10%, whereas only 1.28% in late-onset dementia taken from 1 study. CONCLUSIONS: Considering the relatively high proportion of ARD in early-onset dementia and its potentially reversible course, future investigation into ARD is necessary.

Prenatal exposure to phthalate ester and pubertal development in a birth cohort in central Taiwan: a 12-year follow-up study.

Phthalate esters are widely used plasticizers that are present in many daily used products. Although some of their reproductive effects have been reported, pubertal development effects from prenatal exposure to phthalates awaits further investigations. A population based birth cohort was established (N=437 at baseline) with maternal exposure to phthalates assessed in urine collected at the third trimester of pregnancy in 2001 and 2002. Their 133 children with prenatal phthalates exposure were followed up for the outcomes of pubertal development by sequential physical examinations at eight and 11 years old in 2009 and 2012. Urinary concentrations of major phthalate metabolites (i.e., mono-2-ethylhexyl phthalate [MEHP], mono-(2-ethyl-5-hydroxyhexyl) phthalate [MEHHP], mono-(2-ethyl-5-oxohexyl) phthalate [MEOHP], mono-butyl phthalate [MBP], mono-benzyl phthalate [MBzP], monomethyl phthalate [MMP], and mono-ethyl phthalate [MEP]) were determined using liquid chromatography linked to tandem mass spectrometry. The reproductive development measurements included bone age (for both genders), testicle size (for boys), uterus size, and ovarian volume (for girls). We reported results of 133 children with complete data by applying generalized estimating equations for the repeated continuous outcomes. After controlling for Tanner stage, we detected a significant association between reduced uterus size and increasing phthalate exposure in the 2(nd) tertile relative to the 1st tertile of creatinine-corrected MEHP (B=-0.40; 95% C.I.: -0.73, -0.07, relative to the 1st tertile) and total DEHP (B=-0.39, 95% C.I.:-0.66, -0.01 for the 2nd tertile and B=0.34, 95% C.I.: -0.67, -0.01 for the 3rd tertile, relative to the 1st tertile) with a linear trend among girls. MBzP was also found negatively associated with bone age/chronological age ratio (B=-0.07, 95% CI: -0.13, -0.01 for the 3rd tertile, relative to the 1st tertile) with a linear trend for girls. We found no evidence of an association between phthalate exposure and ovarian volume or testicle size. This analysis suggests phthalate exposure may affect specific pubertal development characteristics in human beings. Further studies with larger sample sizes and longer follow-up period are warranted.

Extracting antipsychotic polypharmacy data from electronic health records: developing and evaluating a novel process.

BACKGROUND: Antipsychotic prescription information is commonly derived from structured fields in clinical health records. However, utilising diverse and comprehensive sources of information is especially important when investigating less frequent patterns of medication prescribing such as antipsychotic polypharmacy (APP). This study describes and evaluates a novel method of extracting APP data from both structured and free-text fields in electronic health records (EHRs), and its use for research purposes. METHODS: Using anonymised EHRs, we identified a cohort of patients with serious mental illness (SMI) who were treated in South London and Maudsley NHS Foundation Trust mental health care services between 1 January and 30 June 2012. Information about antipsychotic co-prescribing was extracted using a combination of natural language processing and a bespoke algorithm. The validity of the data derived through this process was assessed against a manually coded gold standard to establish precision and recall. Lastly, we estimated the prevalence and patterns of antipsychotic polypharmacy. RESULTS: Individual instances of antipsychotic prescribing were detected with high precision (0.94 to 0.97) and moderate recall (0.57-0.77). We detected baseline APP (two or more antipsychotics prescribed in any 6-week window) with 0.92 precision and 0.74 recall and long-term APP (antipsychotic co-prescribing for 6 months) with 0.94 precision and 0.60 recall. Of the 7,201 SMI patients receiving active care during the observation period, 338 (4.7 %; 95 % CI 4.2-5.2) were identified as receiving long-term APP. Two second generation antipsychotics (64.8 %); and first -second generation antipsychotics were most commonly co-prescribed (32.5 %). CONCLUSIONS: These results suggest that this is a potentially practical tool for identifying polypharmacy from mental health EHRs on a large scale. Furthermore, extracted data can be used to allow researchers to characterize patterns of polypharmacy over time including different drug combinations, trends in polypharmacy prescribing, predictors of polypharmacy prescribing and the impact of polypharmacy on patient outcomes.

Suicide completion in secondary mental healthcare: a comparison study between schizophrenia spectrum disorders and all other diagnoses.

BACKGROUND: Suicide completion is a tragic outcome in secondary mental healthcare. However, the extent to which demographic and clinical characteristics, suicide method and service use-related factors vary across psychiatric diagnoses remains poorly understood, particularly regarding differences between 'schizophrenia spectrum disorders (SSD)' and 'all other diagnoses', which may have implications for suicide prevention in high risk groups. METHODS: 308 patients who died by suicide over 2007-2011 were identified from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre Case Register. Demographic, clinical, services use-related factors, 'full risk assessment' ratings and the Health of the Nation Outcome Scale (HONOS) scores were compared across psychiatric diagnoses. Specifically, differences between patients with and without SSD were investigated. RESULTS: Patients with SSD ended their lives at a younger age, were more frequently of Black ethnicity and had higher levels of social deprivation than other diagnoses. Also, these patients were more likely to have HONOS and 'risk assessment' completed. However, patients who had no SSD scored significantly higher on 'self-injury' and 'depression' HONOS items and they were more likely to have the following 'risk assessment' items: 'suicidal ideation', 'hopelessness', 'feeling no control of life', 'impulsivity' and 'significant loss'. Of note, 'disengagement' was more common in patients with SSD, although they had been seen by the staff closer to the time of suicide than in all-other diagnoses. Whilst 'hanging' was the most common suicide method amongst patients with non-SSD, most service users with a SSD diagnosis used 'jumping' (from heights or in front of a vehicle). CONCLUSIONS: Suicide completion characteristics varied between SSD and other diagnoses in patients receiving secondary mental healthcare. In particular, although clinicians tend to more frequently recognize suicide risk as a focus of concern in patients who have SSD, who are therefore more likely to have a detailed risk assessment documented; 'known' suicide risk factors appear to be more relevant in patients with non-SSD. Hence, the classic suicide prevention model might be of little use for SSD.

Higher orexin-A levels are associated with treatment response to clozapine in patients with schizophrenia: A cross-sectional study.

BACKGROUND: Clozapine is the primary antipsychotic (APD) for treatment-resistant schizophrenia (TRS). However, only 40% of patients with TRS respond to clozapine, constituting a subgroup of clozapine-resistant patients. Recently, the neuropeptide orexin-A was shown to be involved in the pathophysiology of schizophrenia. This study evaluated the association of orexin-A levels with the clozapine response in patients with TRS. METHODS: We recruited 199 patients with schizophrenia, including 37 APD-free and 162 clozapine-treated patients. Clozapine-treated patients were divided into clozapine-responsive (n = 100) and clozapine-resistant (n = 62) groups based on whether they had achieved psychotic remission defined by the 18-item Brief Psychiatric Rating Scale (BPRS-18). We compared blood orexin-A levels among the three groups and performed regression analysis to determine the association of orexin-A level with treatment response in clozapine-treated patients. We also explored the correlation between orexin-A levels and cognitive function, assessed using the CogState Schizophrenia Battery. RESULTS: Clozapine-responsive patients had higher orexin-A levels than clozapine-resistant and APD-free patients. Orexin-A level was the only factor significantly associated with treatment response after adjustment. Orexin-A levels were negatively correlated with BPRS-18 full scale and positive, negative, and general symptoms subscale scores. We also observed a positive correlation between orexin-A levels and verbal memory, visual learning and memory, and working memory function. CONCLUSIONS: This cross-sectional study showed that higher levels of orexin-A are associated with treatment response to clozapine in patients with TRS. Future prospective studies examining changes in orexin-A level following clozapine treatment and the potential benefit of augmenting orexin-A signaling are warranted.

Low colonocyte folate is associated with uracil misincorporation and global DNA hypomethylation in human colorectum.

Low folate status is a risk factor for colon carcinogenesis; mechanisms proposed to account for this relationship include uracil misincorporation into DNA and global DNA hypomethylation. We investigated whether such biomarkers are related to folate status in isolated colonocytes from colonoscopy patients. In cases with adenomatous polyps (n = 40) or hyperplastic polyps (n = 16), colonocytes were isolated from biopsies from the polyp, from a site adjacent to the polyp, and from normal mucosa 10-15 cm distal to the polyp. In polyp-free controls (n = 53), biopsies were taken from ascending, transverse, and descending areas of colon. Within adenoma cases, there was a trend (P-trend < 0.001) of decreasing colonocyte folate (pg/105 cells, mean ± CI) from the site distal to the polyp (16.9 ± 2.4), to the site adjacent to the polyp (14.7 ± 2.3), to the polyp (12.8 ± 2.0). Correspondingly, there were increases in uracil misincorporation (P-trend < 0.001) and global DNA hypomethylation (P-trend = 0.012) across the 3 sites. Colonocyte folate concentrations were significantly correlated with RBC folate concentrations, but only in individuals with generally lower (≤484 µg/L) RBC folate status (r = 0.54; P = 0.006; n = 24), and were also significantly lower in normal mucosa of cases with adenomatous polyps than in controls matched for colonic segment. In conclusion, localized folate deficiency in specific areas of colon might create carcinogenic fields and affect the development of colorectal polyps through uracil misincorporation and DNA hypomethylation; alternatively, the polyp itself might deplete folate in the surrounding tissue. Folate supplementation trials aimed at colon cancer prevention should target individuals with suboptimal folate status.

Temperature, nitrogen dioxide, circulating respiratory viruses and acute upper respiratory infections among children in Taipei, Taiwan: a population-based study.

OBJECTIVE: This study investigated whether outpatient visits of acute upper respiratory infections for children aged less than 15 years are associated with temperature, air pollutants and circulating respiratory viruses in Taipei, Taiwan, from 2003 to 2007. METHODS: Outpatient records for acute upper respiratory infections (ICD9 CM codes: 460, 462, 463,464, 465.9 and 487) in a randomly selected sample (n=39,766 children in 2005) was used to estimate the cumulative relative risks (RR) associated with average temperature lasting for 8 days (lag 0-7 days), air pollutants (NO2, O3 and PM(2.5)) lasting for 6 days (lag 0-5 days), and virus-specific positive isolation rate lasting for 11 days (lag 0-10 days) using distributed lag non-linear models after controlling for relative humidity, wind speed, day of week, holiday effects and long-term trend. RESULTS: Average temperature of 33 °C was associated with the lowest risk for outpatient visits of acute upper respiratory infections. Relative to 33 °C, cumulative 8-day RR was highest at 15 °C of ambient average temperature [RR=1.94; 95% confidence interval (CI): 1.78, 2.11]. With the first quartile as reference, cumulative 6-day RRs were 1.25 (95% CI: 1.21, 1.29) for NO2, 1.04 (95% CI: 1.01, 1.06) for O3, and 1.00 (95% CI: 0.98, 1.03) for PM(2.5) at the 95th percentile. Per-standard deviation (SD) increase of virus-specific isolation rate for influenza type A (SD=13.2%), type B (SD=8.76%), and adenoviruses (SD=5.25%) revealed statistical significance for overall 11-day RRs of 1.02 (95% CI: 1.01, 1.03), 1.05 (95% CI: 1.03, 1.06) and 1.04 (95% CI: 1.03, 1.05), respectively. CONCLUSIONS: Current study suggested a positive association between outpatient visits for acute upper respiratory infections and ambient environment factors, including average temperature, air pollutants, and circulating respiratory viruses.

The association between social relationships and self-harm: a case-control study in Taiwan.

BACKGROUND: Although suicide has been postulated as a result of social breakdown, relatively little attention has been paid to the association between social relationships and non-fatal self-harm. We sought to investigate the extent to which social factors correlate with self-harm in this case-control study. METHODS: The primary outcome was self-harm with hospital presentation. Cases of self-harm from the Emergency Department in a general hospital in Northern Taiwan were recruited, and individually age-and-gender-matched control participants were recruited from non-psychiatric outpatient clinics at the same hospital. The Close Persons Questionnaire was administered and its social support and social network subscales were used to measure social relationships in the 12 months prior to the interview. Other covariates, comprising sociodemographic factors, major life events, physical and mental health, were adjusted in conditional logistic regression models. RESULTS: A total of 124 case-control pairs were recruited. The mean (standard deviation) age of the case group was 34.7 (12.8) years and 80.6% were female. Higher social isolation score remained significantly associated with self-harm after adjustment (adjusted odds ratio per standard deviation increase 2.92, 95% confidence interval 1.44-5.95) and household size was negatively associated with the outcome (adjusted odds ratio per unit increase 0.54, 95% CI 0.32-0.94). CONCLUSIONS: More limited social networks were associated with self-harm after adjustment for potential confounders. Enhancing social structure and effective networking of people with self-harm to community resources may be important for self-harm management in Asian societies and elsewhere.

Socioeconomic disadvantage, mental disorders and risk of 12-month suicide ideation and attempt in the National Comorbidity Survey Replication (NCS-R) in US.

PURPOSE: We aim to explore the distinctive interrelationships between family income and mental disorders on suicidality in recent 12 months. METHODS: A stratified random subsample of adults in a household survey in US, National Comorbidity Survey Replication, was used for analyses. The ratio of family income to poverty threshold (RoFIPT) per capita was the primary predictor of interest to 12-month occurrence of suicide ideation and attempt. Effect modification by mental disorders was further explored. RESULTS: A total of 4,724 subjects were analyzed. Inverse associations were found with RoFIPT for both suicidal outcomes after confounding control. Furthermore, effect modification was revealed that RoFIPT was more strongly associated with suicide ideation for those with mental disorders (OR 0.87; 95 % CI 0.79, 0.95). CONCLUSIONS: An inverse gradient of RoFIPT was shown with suicide ideation and attempt. Moreover, having mental disorders was found to be an effect modifier for the relationships between family income and suicidality.

Development and evaluation of a de-identification procedure for a case register sourced from mental health electronic records.

BACKGROUND: Electronic health records (EHRs) provide enormous potential for health research but also present data governance challenges. Ensuring de-identification is a pre-requisite for use of EHR data without prior consent. The South London and Maudsley NHS Trust (SLaM), one of the largest secondary mental healthcare providers in Europe, has developed, from its EHRs, a de-identified psychiatric case register, the Clinical Record Interactive Search (CRIS), for secondary research. METHODS: We describe development, implementation and evaluation of a bespoke de-identification algorithm used to create the register. It is designed to create dictionaries using patient identifiers (PIs) entered into dedicated source fields and then identify, match and mask them (with ZZZZZ) when they appear in medical texts. We deemed this approach would be effective, given high coverage of PI in the dedicated fields and the effectiveness of the masking combined with elements of a security model. We conducted two separate performance tests i) to test performance of the algorithm in masking individual true PIs entered in dedicated fields and then found in text (using 500 patient notes) and ii) to compare the performance of the CRIS pattern matching algorithm with a machine learning algorithm, called the MITRE Identification Scrubber Toolkit - MIST (using 70 patient notes - 50 notes to train, 20 notes to test on). We also report any incidences of potential breaches, defined by occurrences of 3 or more true or apparent PIs in the same patient's notes (and in an additional set of longitudinal notes for 50 patients); and we consider the possibility of inferring information despite de-identification. RESULTS: True PIs were masked with 98.8% precision and 97.6% recall. As anticipated, potential PIs did appear, owing to misspellings entered within the EHRs. We found one potential breach. In a separate performance test, with a different set of notes, CRIS yielded 100% precision and 88.5% recall, while MIST yielded a 95.1% and 78.1%, respectively. We discuss how we overcome the realistic possibility - albeit of low probability - of potential breaches through implementation of the security model. CONCLUSION: CRIS is a de-identified psychiatric database sourced from EHRs, which protects patient anonymity and maximises data available for research. CRIS demonstrates the advantage of combining an effective de-identification algorithm with a carefully designed security model. The paper advances much needed discussion of EHR de-identification - particularly in relation to criteria to assess de-identification, and considering the contexts of de-identified research databases when assessing the risk of breaches of confidential patient information.