Machine learning-enabled maternal risk assessment for women with pre-eclampsia (the PIERS-ML model): a modelling study.

BACKGROUND: Affecting 2-4% of pregnancies, pre-eclampsia is a leading cause of maternal death and morbidity worldwide. Using routinely available data, we aimed to develop and validate a novel machine learning-based and clinical setting-responsive time-of-disease model to rule out and rule in adverse maternal outcomes in women presenting with pre-eclampsia. METHODS: We used health system, demographic, and clinical data from the day of first assessment with pre-eclampsia to predict a Delphi-derived composite outcome of maternal mortality or severe morbidity within 2 days. Machine learning methods, multiple imputation, and ten-fold cross-validation were used to fit models on a development dataset (75% of combined published data of 8843 patients from 11 low-income, middle-income, and high-income countries). Validation was undertaken on the unseen 25%, and an additional external validation was performed in 2901 inpatient women admitted with pre-eclampsia to two hospitals in south-east England. Predictive risk accuracy was determined by area-under-the-receiver-operator characteristic (AUROC), and risk categories were data-driven and defined by negative (-LR) and positive (+LR) likelihood ratios. FINDINGS: Of 8843 participants, 590 (6·7%) developed the composite adverse maternal outcome within 2 days, 813 (9·2%) within 7 days, and 1083 (12·2%) at any time. An 18-variable random forest-based prediction model, PIERS-ML, was accurate (AUROC 0·80 [95% CI 0·76-0·84] vs the currently used logistic regression model, fullPIERS: AUROC 0·68 [0·63-0·74]) and categorised women into very low risk (-LR <0·1; eight [0·7%] of 1103 women), low risk (-LR 0·1 to 0·2; 321 [29·1%] women), moderate risk (-LR >0·2 and +LR <5·0; 676 [61·3%] women), high risk (+LR 5·0 to 10·0, 87 [7·9%] women), and very high risk (+LR >10·0; 11 [1·0%] women). Adverse maternal event rates were 0% for very low risk, 2% for low risk, 5% for moderate risk, 26% for high risk, and 91% for very high risk within 48 h. The 2901 women in the external validation dataset were accurately classified as being at very low risk (0% with outcomes), low risk (1%), moderate risk (4%), high risk (33%), or very high risk (67%). INTERPRETATION: The PIERS-ML model improves identification of women with pre-eclampsia who are at lowest and greatest risk of severe adverse maternal outcomes within 2 days of assessment, and can support provision of accurate guidance to women, their families, and their maternity care providers. FUNDING: University of Strathclyde Diversity in Data Linkage Centre for Doctoral Training, the Fetal Medicine Foundation, The Canadian Institutes of Health Research, and the Bill & Melinda Gates Foundation.

Associations between significant head injury in male juveniles in prison in Scotland UK and cognitive function, disability and crime: A cross sectional study.

BACKGROUND: Although the prevalence of head injury is estimated to be high in juveniles in prison, the extent of persisting disability is unknown and relationships with offending uncertain. This limited understanding makes it difficult to develop effective management strategies and interventions to improve health or reduce recidivism. This study investigates effects of significant head injury (SHI) on cognitive function, disability and offending in juvenile prisoners, and considers relationships with common comorbidities. METHODS: This cross-sectional study recruited male juvenile prisoners in Scotland from Her Majesty's Young Offenders Institute (HMYOI) Polmont (detaining approximately 305 of 310 male juveniles in prison in Scotland). To be included juveniles had to be 16 years or older, fluent in English, able to participate in assessment, provide informed consent and not have a severe acute disorder of cognition or communication. Head injury, cognition, disability, history of abuse, mental health and problematic substance use were assessed by interview and questionnaire. RESULTS: We recruited 103 (34%) of 305 juvenile males in HMYOI Polmont. The sample was demographically representative of juvenile males in prisons for young offenders in Scotland. SHI was found in 82/103 (80%) and head injury repeated over long periods of time in 69/82 (85%). Disability was associated with SHI in 11/82 (13%) and was significantly associated with mental health problems, particularly anxiety. Group differences on cognitive tests were not found. However the SHI group reported poorer behavioural control on the Dysexecutive Questionnaire and were more often reported for incidents in prison than those without SHI. Characteristics of offending, including violence, did not differ between groups. CONCLUSIONS: Although SHI is highly prevalent in juvenile prisoners, associated disability was relatively uncommon. There was no evidence for differences in cognitive test performance or offending in juveniles with and without SHI. However, signs of poorer behavioural control and greater psychological distress in juveniles with SHI suggest that they may be at greater risk of recidivism and of potentially becoming lifelong offenders. This implies a need for remedial programmes for juvenile prisoners to take account of persisting effects of SHI on mental health and self-control and education and to improve their understanding of the effects of SHI reduce the likelihood of cumulative effects from further SHI.

General and age-specific fertility rates in non-affective psychosis: population-based analysis of Scottish women.

PURPOSE: Women diagnosed with non-affective psychosis have a lower general fertility rate (GFR) and age-specific fertility rate (ASFR) than women in the general population. Contemporary data on GFR in this group remain limited, despite substantive changes in prescribing and management. We calculated contemporary estimates of the GFR and ASFR for women diagnosed with non-affective psychosis compared with the general population of women without this diagnosis. METHODS: A population-based design combined routinely collected historical maternity and psychiatric data from two representative areas of Scotland. Women were included from the NHS Grampian or Greater Glasgow and Clyde areas and were aged 15-44 between 2005 and 2013 inclusive. The 'exposed' group had a diagnosis of non-affective psychosis (ICD-10 F20-F29) and was compared to the general population of 'unexposed' women in the same geographical areas. RESULTS: Annual GFR between 2005 and 2013 for women with non-affective psychosis varied from 9.6 to 21.3 live births/1000 women per year in the exposed cohort and 52.7 to 57.8 live births/1000 women per year in the unexposed cohort, a rate ratio (RR) of 0.28 [p < 0.001; 95% CI (0.24, 0.32)]. ASFR for all 5-year age groups was lower in the exposed cohort than amongst unexposed women. CONCLUSION: We highlight continued low fertility rates in women with a diagnosis of non-affective psychosis, despite widespread availability of prolactin-sparing atypical antipsychotics. Accurate estimation of fertility rates remains crucial in developing needs-matched perinatal care for these women. Methodological improvements using routine datasets to investigate perinatal mental health are also urgently needed.

Mapping Geographic Trends in Early Childhood Social, Emotional, and Behavioural Difficulties in Glasgow: 2010-2017.

Measuring variation in childhood mental health supports the development of local early intervention strategies. The methodological approach used to investigate mental health trends (often determined by the availability of individual level data) can affect decision making. We apply two approaches to identify geographic trends in childhood social, emotional, and behavioural difficulties using the Strengths and Difficulties Questionnaire (SDQ). SDQ forms were analysed for 35,171 children aged 4-6 years old across 180 preschools in Glasgow, UK, between 2010 and 2017 as part of routine monitoring. The number of children in each electoral ward and year with a high SDQ total difficulties score (≥15), indicating a high risk of psychopathology, was modelled using a disease mapping model. The total difficulties score for an individual child nested in their preschool and electoral ward was modelled using a multilevel model. For each approach, linear time trends and unstructured spatial random effects were estimated. The disease mapping model estimated a yearly rise in the relative rate (RR) of high scores of 1.5-5.0%. The multilevel model estimated an RR increase of 0.3-1.2% in average total scores across the years, with higher variation between preschools than between electoral wards. Rising temporal trends may indicate worsening social, emotional, and behavioural difficulties over time, with a faster rate for the proportion with high scores than for the average total scores. Preschool and ward variation, although minimal, highlight potential priority areas for local service provision. Both methodological approaches have utility in estimating and predicting children's difficulties and local areas requiring greater intervention.

Evaluations of heat action plans for reducing the health impacts of extreme heat: methodological developments (2012-2021) and remaining challenges.

The recent report of the Intergovernmental Panel on Climate Change is stark in its warnings about the changing climate, including future increases in the frequency and intensity of extremely hot weather. The well-established impacts of extreme heat on human health have led to widespread implementation of national and city-wide heat plans for mitigating such impacts. Evaluations of the effectiveness of some heat plans have been published, with previous reviews highlighting key methodological challenges. This article reviews methods used since and that address those challenges, so helping to set an agenda for improving evaluations of heat plans in terms of their effectiveness in reducing heat-health impacts. We examined the reviews that identified the methodological challenges and systematically searched the literature to find evaluations that had since been conducted. We found 11 evaluations. Their methods help address the key challenge of identifying study control groups and address other challenges to a limited extent. For future evaluations, we recommend: utilising recent evaluation methodologies, such as difference-in-differences quasi-experimental designs where appropriate; cross-agency working to utilise data on morbidity and confounders; adoption of a proposed universal heat index; and greater publication of evaluations. More evaluations should assess morbidity outcomes and be conducted in low- and middle-income countries. Evaluations of heat plans globally should employ robust methodologies, as demonstrated in existing studies and potentially transferrable from other fields. Publication of such evaluations will advance the field and thus help address some of the health challenges resulting from our changing climate.

Feasibility study of peer-led and school-based social network Intervention (STASH) to promote adolescent sexual health.

BACKGROUND: Effective sex education is the key to good sexual health. Peer-led approaches can augment teacher-delivered sex education, but many fail to capitalise on mechanisms of social influence. We assessed the feasibility of a novel intervention (STASH) in which students (aged 14-16) nominated as influential by their peers were recruited and trained as Peer Supporters (PS). Over a 5-10-week period, they spread positive sexual health messages to friends in their year group, both in-person and via social media, and were supported to do so via weekly trainer-facilitated meetings. The aims of the study were to assess the feasibility of STASH (acceptability, fidelity and reach), to test and refine the programme theory and to establish whether the study met pre-set progression criteria for continuation to larger-scale evaluation. METHODS: The overall design was a non-randomised feasibility study of the STASH intervention in 6 schools in Scotland. Baseline (n=680) and follow-up questionnaires (approx. 6 months later; n=603) were administered to the intervention year group. The control group (students in year above) completed the follow-up questionnaire only (n=696), 1 year before the intervention group. The PS (n=88) completed a brief web survey about their experience of the role; researchers interviewed participants in key roles (PS (n=20); PS friends (n=22); teachers (n=8); trainers (n=3)) and observed 20 intervention activities. Activity evaluation forms and project monitoring data also contributed information. We performed descriptive quantitative analysis and thematic qualitative analysis. RESULTS: The PS role was acceptable; on average across schools >50% of students nominated as influential by their friends, signed up and were trained (n=104). This equated to 13% of the year group. Trained PS rarely dropped out (97% completion rate) and 85% said they liked the role. Fidelity was good (all bar one trainer-led activity carried out; PS were active). The intervention had good reach; PS were reasonably well connected and perceived as 'a good mix' and 58% of students reported exposure to STASH. Hypothesised pre-conditions, contextual influences and mechanisms of change for the intervention were largely confirmed. All bar one of the progression criteria was met. CONCLUSION: The weight of evidence supports continuation to full-scale evaluation. TRIAL REGISTRATION: Current controlled trials ISRCTN97369178.

Associations between significant head injury and persisting disability and violent crime in women in prison in Scotland, UK: a cross-sectional study.

BACKGROUND: The prevalence of head injury is estimated to be as high as 55% in women in prison and might be a risk factor for violent offending, but evidence is equivocal. The extent of persisting disability is unknown, making decisions about service needs difficult. The UN recognises vulnerabilities in women in prison, but does not include head injury. This study aimed to investigate relationships among head injury, comorbidities, disability, and offending in women in prison. METHODS: In this cross-sectional study, women were recruited between Feb 2, 2018, and Sept 30, 2019, from four prisons across Scotland, UK: Her Majesty's Prison (HMP) Cornton Vale, Her Majesty's Young Offenders Institute Polmont, HMP Edinburgh, and HMP Greenock (detaining approximately 355 individuals at the time of recruitment). Women were included if they were aged older than 16 years, fluent in English, able to participate in face-to-face assessment and provide informed consent, and did not have a severe acute disorder of cognition or communication. Head injury, cognition, disability, mental health, and history of abuse and problematic substance use were assessed by interview. History of head injury was assessed with the Ohio State University Traumatic Brain Injury Identification method and disability was assessed with the Glasgow Outcome at Discharge Scale. Comparisons were made between women with and without a history of significant head injury. FINDINGS: We recruited 109 (31%) of the 355 women in these prisons. The sample was demographically representative of the approximately 400 individuals in women's prisons in Scotland. Significant head injury (SHI) was found in 85 (78%) of 109 women, of whom 34 (40%) had associated disability. Repeat head injury was reported in 71 (84%) of the 85 women with SHI and, in most cases, this resulted from domestic abuse that had occurred over many years. Women with a history of SHI were significantly more likely to have a history of violent offences than those without a history of SHI (66 [79%] of 85 women in the SHI group vs 13 [54%] of 24 women in the no-SHI group had committed a violent offence; odds ratio [OR] 3·1, 95% CI 1·2-8·1). This effect remained significant after adjusting for current factors (3·1, 1·1-9·0), including comorbidities associated with post-traumatic stress disorder, and was no longer statistically significant after adjusting for historical factors (3·3, 1·0-10·9), such as abuse as a child or adult. Women with SHI had spent longer in prison than women without SHI after adjustment for current (rate ratio 3·4, 1·3-8·4) or historical (3·5, 1·3-9·2) risk factors. INTERPRETATION: It is recognised that women in prison are vulnerable because of histories of abuse and problematic substance use; however, history of SHI needs to be included when developing criminal justice policy, interventions to reduce mental health morbidity, and assessment and management of risk of violent offending. FUNDING: The Scottish Government.

Invasive versus medically managed acute coronary syndromes with prior bypass (CABG-ACS): insights into the registry versus randomised trial populations.

BACKGROUND: Coronary artery bypass graft (CABG) patients are under-represented in acute coronary syndrome (ACS) trials. We compared characteristics and outcomes for patients who did and did not participate in a randomised trial of invasive versus non-invasive management (CABG-ACS). METHODS: ACS patients with prior CABG in four hospitals were randomised to invasive or non-invasive management. Non-randomised patients entered a registry. Primary efficacy (composite of all-cause mortality, rehospitalisation for refractory ischaemia/angina, myocardial infarction (MI), heart failure) and safety outcomes (composite of bleeding, stroke, procedure-related MI, worsening renal function) were independently adjudicated. RESULTS: Of 217 patients screened, 84 (39%) screenfailed, of whom 24 (29%) did not consent and 60 (71%) were ineligible. Of 133 (61%) eligible, 60 (mean±SD age, 71±9 years, 72% male) entered the trial and 73 (age, 72±10 years, 73% male) entered a registry (preferences: physician (79%), patient (38%), both (21%)).Compared with trial participants, registry patients had more valve disease, lower haemoglobin, worse New York Heart Association class and higher frailty.At baseline, invasive management was performed in 52% and 49% trial and registry patients, respectively, of whom 32% and 36% had percutaneous coronary intervention at baseline, respectively (p=0.800). After 2 years follow-up (694 (median, IQR 558-841) days), primary efficacy (43% trial vs 49% registry (HR 1.14, 95% CI 0.69 to 1.89)) and safety outcomes (28% trial vs 22% registry (HR 0.74, 95% CI 0.37 to 1.46)) were similar. EuroQol was lower in registry patients at 1 year. CONCLUSIONS: Compared with trial participants, registry participants had excess morbidity, but longer-term outcomes were similar. TRIAL REGISTRATION NUMBER: NCT01895751.

Invasive Versus Medical Management in Patients With Prior Coronary Artery Bypass Surgery With a Non-ST Segment Elevation Acute Coronary Syndrome.

BACKGROUND: The benefits of routine invasive management in patients with prior coronary artery bypass grafts presenting with non-ST elevation acute coronary syndromes are uncertain because these patients were excluded from pivotal trials. METHODS: In a multicenter trial, non-ST elevation acute coronary syndromes patients with prior coronary artery bypass graft were prospectively screened in 4 acute hospitals. Medically stabilized patients were randomized to invasive management (invasive group) or noninvasive management (medical group). The primary outcome was adherence with the randomized strategy by 30 days. A blinded, independent Clinical Event Committee adjudicated predefined composite outcomes for efficacy (all-cause mortality, rehospitalization for refractory ischemia/angina, myocardial infarction, hospitalization because of heart failure) and safety (major bleeding, stroke, procedure-related myocardial infarction, and worsening renal function). RESULTS: Two hundred seventeen patients were screened and 60 (mean±SD age, 71±9 years, 72% male) were randomized (invasive group, n=31; medical group, n=29). One-third (n=10) of the participants in the invasive group initially received percutaneous coronary intervention. In the medical group, 1 participant crossed over to invasive management on day 30 but percutaneous coronary intervention was not performed. During 2-years' follow-up (median [interquartile range], 744 [570-853] days), the composite outcome for efficacy occurred in 13 (42%) subjects in the invasive group and 13 (45%) subjects in the medical group. The composite safety outcome occurred in 8 (26%) subjects in the invasive group and 9 (31%) subjects in the medical group. An efficacy or safety outcome occurred in 17 (55%) subjects in the invasive group and 16 (55%) subjects in the medical group. Health status (EuroQol 5 Dimensions) and angina class in each group were similar at 12 months. CONCLUSIONS: More than half of the population experienced a serious adverse event. An initial noninvasive management strategy is feasible. A substantive health outcomes trial of invasive versus noninvasive management in non-ST elevation acute coronary syndromes patients with prior coronary artery bypass grafts appears warranted. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01895751.

Relationship of depression screening in cardiometabolic disease with vascular events and mortality: findings from a large primary care cohort with 4 years follow-up.

Aims: Benefits of routine depression screening for cardiometabolic disease patients remain unclear. We examined the association between depression screening and all-cause mortality and vascular events in cardiometabolic disease patients. Methods and results: 125 143 patients with cardiometabolic diseases (coronary heart disease, diabetes or previous stroke) in the UK participated in primary care chronic disease management in 2008/09, which included depression screening using the Hospital Anxiety and Depression Score. 10 670 receiving depression treatment exempted, 35 537 screened, while 78 936 not screened. We studied all-cause mortality and vascular events at 4 years, by electronic data linkage of 124 414 patients (99.4%) on primary care registers to hospital discharge and mortality records and used Cox proportional hazards on matched data using propensity score. Mean age for the screened and not screened population was 69 years (standard deviation-SD 11.9) and 67 years (SD 14.3), respectively; 58% (20 658) of the screened population were men and 65.3% (22 726) were socioeconomically deprived, compared with 54.2% (42 727) and 67.4% (51 686), respectively, in the not screened population. The screened population had lower all-cause mortality (Hazard Ratio-HR 0.89) and vascular events (HR 0.85) in the matched data of N = 21 893 patients each in the screened and the unscreened groups. Conclusion: Depression screening was associated with a reduction in all-cause mortality and vascular events in patients with cardiometabolic diseases. The uptake of screening was poor for unknown reasons. Reverse causality and confounding by disease severity and quality of care are important possible limitations. Further research to determine reproducibility and explore underlying mechanisms is merited.

Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium.

Observational studies on smoking and risk of hay fever and asthma have shown inconsistent results. However, observational studies may be biased by confounding and reverse causation. Mendelian randomization uses genetic variants as markers of exposures to examine causal effects. We examined the causal effect of smoking on hay fever and asthma by using the smoking-associated single nucleotide polymorphism (SNP) rs16969968/rs1051730. We included 231,020 participants from 22 population-based studies. Observational analyses showed that current vs never smokers had lower risk of hay fever (odds ratio (OR) = 0·68, 95% confidence interval (CI): 0·61, 0·76; P < 0·001) and allergic sensitization (OR = 0·74, 95% CI: 0·64, 0·86; P < 0·001), but similar asthma risk (OR = 1·00, 95% CI: 0·91, 1·09; P = 0·967). Mendelian randomization analyses in current smokers showed a slightly lower risk of hay fever (OR = 0·958, 95% CI: 0·920, 0·998; P = 0·041), a lower risk of allergic sensitization (OR = 0·92, 95% CI: 0·84, 1·02; P = 0·117), but higher risk of asthma (OR = 1·06, 95% CI: 1·01, 1·11; P = 0·020) per smoking-increasing allele. Our results suggest that smoking may be causally related to a higher risk of asthma and a slightly lower risk of hay fever. However, the adverse events associated with smoking limit its clinical significance.

Assessing Patient Progress in Psychological Therapy Through Feedback in Supervision: the MeMOS* Randomized Controlled Trial (*Measuring and Monitoring clinical Outcomes in Supervision: MeMOS).

BACKGROUND: Psychological therapy services are often required to demonstrate their effectiveness and are implementing systematic monitoring of patient progress. A system for measuring patient progress might usefully 'inform supervision' and help patients who are not progressing in therapy. AIMS: To examine if continuous monitoring of patient progress through the supervision process was more effective in improving patient outcomes compared with giving feedback to therapists alone in routine NHS psychological therapy. METHOD: Using a stepped wedge randomized controlled design, continuous feedback on patient progress during therapy was given either to the therapist and supervisor to be discussed in clinical supervison (MeMOS condition) or only given to the therapist (S-Sup condition). If a patient failed to progress in the MeMOS condition, an alert was triggered and sent to both the therapist and supervisor. Outcome measures were completed at beginning of therapy, end of therapy and at 6-month follow-up and session-by-session ratings. RESULTS: No differences in clinical outcomes of patients were found between MeMOS and S-Sup conditions. Patients in the MeMOS condition were rated as improving less, and more ill. They received fewer therapy sessions. CONCLUSIONS: Most patients failed to improve in therapy at some point. Patients' recovery was not affected by feeding back outcomes into the supervision process. Therapists rated patients in the S-Sup condition as improving more and being less ill than patients in MeMOS. Those patients in MeMOS had more complex problems.

Effect of cold spells and their modifiers on cardiovascular disease events: Evidence from two prospective studies.

OBJECTIVE: To investigate effects of cold weather spells on incidence of cardiovascular disease (CVD), and potential effect modification of socio-demographic, clinical, behavioural and environmental exposures. METHODS: Data from two prospective studies were analysed: the British Regional Heart Study (BRHS), a population-based study of British men aged 60-79years, followed for CVD incidence from 1998-2000 to 2012; and the PROSPER study of men and women aged 70-82 recruited to a trial of pravastatin vs placebo from 1997 to 9 (followed until 2009). Cold spells were defined as at least three consecutive days when daily mean temperature fell below the monthly 10th percentile specific to the closest local weather station. A time-stratified case-crossover approach was used to estimate associations between cold spells and CVD events. RESULTS: 921 of 4252 men from BRHS and 760 of 2519 participants from PROSPER suffered a first CVD event during follow-up. More CVD events were registered in winter in both studies. The risk ratio (RR) associated with cold spells was statistically significant in BRHS (RR=1.86, 95% CI 1.30-2.65, p<0.001), and independent of temperature level: results were similar whether events were fatal or non-fatal. Increased risk was particularly marked in BRHS for ever-smokers (RR of 2.44 vs 0.99 for never-smokers), in moderate/heavy drinkers (RR 2.59 vs 1.41), and during winter months (RR 3.28 vs 1.25). No increased risk was found in PROSPER. CONCLUSIONS: Although CVD risks were higher in winter in both BRHS and PROSPER prospective studies, cold spells increased risk of CVD events, independently of cold temperature, in the BRHS only.

Relationship Between Blood Pressure Values, Depressive Symptoms, and Cardiovascular Outcomes in Patients With Cardiometabolic Disease.

The authors studied the joint effect of blood pressure (BP) and depression on the risk of major adverse cardiovascular outcome in patients with existing cardiometabolic disease. A cohort of 35,537 patients with coronary heart disease, diabetes, or stroke underwent depression screening and BP measurement recorded concurrently. The authors used Cox's proportional hazards to calculate risk of major adverse cardiovascular event (MACE; myocardial infarction/heart failure/stroke or cardiovascular death) over 4 years associated with baseline BP and depression. A total of 11% (3939) had experienced a MACE within 4 years. Patients with very high systolic BP (160-240 mm Hg; hazard ratio, 1.28) and depression (hazard ratio, 1.22) at baseline had significantly higher adjusted risk. Depression had a significant interaction with systolic BP in risk prediction (P=.03). Patients with a combination of high systolic BP and depression at baseline had 83% higher adjusted risk of MACE, as compared with patients with reference systolic BP without depression. Patients with cardiometabolic disease and comorbid depression may benefit from closer monitoring of systolic BP.

The effects of anti-depressants on depression symptom scores at 12 months follow-up in patients with cardiometabolic disease: Results from a large primary care cohort.

BACKGROUND: Evidence on the long-term usefulness of anti-depressants in managing depression in cardiometabolic disease is limited. AIM: We examined the effects of anti-depressant prescribing on depressive symptoms at 12 months follow-up in patients with cardiometabolic disease and a positive depression screening result at baseline. DESIGN AND SETTING: We retrospectively reviewed routine UK primary care data for patients with coronary heart disease, diabetes and previous stroke for the year 2008-2009. 35,537 patients with one of the three above diseases underwent depression screening using the Hospital Anxiety and Depression Scale (HADS-D). Of 7080 patients with a positive screening result (HADS-D ≥ 8), 3933 (55.5%) patients had a repeat HADS-D recorded at 12 months follow-up. METHODS: We compared the change in HADS-D at follow-up and remission rate in those who were prescribed anti-depressants (n = 223) against those who were not (n = 3710). RESULTS: The mean change in HADS-D from baseline, for the nonprescribed group was similar to the reduction observed in patients who were continuously prescribed (n = 93) with anti-depressants during follow-up. Patients who were prescribed intermittently (n = 72) or only one (n = 58) prescription during follow-up had a lower reduction in HADS-D compared to the nonprescribed group. There was no difference in remission rates between continuously prescribed and the nonprescribed group, but remission was lower in patients prescribed intermittently and single prescription. CONCLUSION: Improvement in depressive symptoms in patients with cardiometabolic disease at 12 months was not any better in patients prescribed with anti-depressants compared to the nonprescribed group. The role of anti-depressants in the management of depression in cardiometabolic disease merits further investigation.

Power analysis for generalized linear mixed models in ecology and evolution.

'Will my study answer my research question?' is the most fundamental question a researcher can ask when designing a study, yet when phrased in statistical terms - 'What is the power of my study?' or 'How precise will my parameter estimate be?' - few researchers in ecology and evolution (EE) try to answer it, despite the detrimental consequences of performing under- or over-powered research. We suggest that this reluctance is due in large part to the unsuitability of simple methods of power analysis (broadly defined as any attempt to quantify prospectively the 'informativeness' of a study) for the complex models commonly used in EE research. With the aim of encouraging the use of power analysis, we present simulation from generalized linear mixed models (GLMMs) as a flexible and accessible approach to power analysis that can account for random effects, overdispersion and diverse response distributions.We illustrate the benefits of simulation-based power analysis in two research scenarios: estimating the precision of a survey to estimate tick burdens on grouse chicks and estimating the power of a trial to compare the efficacy of insecticide-treated nets in malaria mosquito control. We provide a freely available R function, sim.glmm, for simulating from GLMMs.Analysis of simulated data revealed that the effects of accounting for realistic levels of random effects and overdispersion on power and precision estimates were substantial, with correspondingly severe implications for study design in the form of up to fivefold increases in sampling effort. We also show the utility of simulations for identifying scenarios where GLMM-fitting methods can perform poorly.These results illustrate the inadequacy of standard analytical power analysis methods and the flexibility of simulation-based power analysis for GLMMs. The wider use of these methods should contribute to improving the quality of study design in EE.

Risk assessment and predicting outcomes in patients with depressive symptoms: a review of potential role of peripheral blood based biomarkers.

Depression is one of the major global health challenges and a leading contributor of health related disability and costs. Depression is a heterogeneous disorder and current methods for assessing its severity in clinical practice rely on symptom count, however this approach is unreliable and inconsistent. The clinical evaluation of depressive symptoms is particularly challenging in primary care, where the majority of patients with depression are managed, due to the presence of co-morbidities. Current methods for risk assessment of depression do not accurately predict treatment response or clinical outcomes. Several biological pathways have been implicated in the pathophysiology of depression; however, accurate and predictive biomarkers remain elusive. We conducted a systematic review of the published evidence supporting the use of peripheral biomarkers to predict outcomes in depression, using Medline and Embase. Peripheral biomarkers in depression were found to be statistically significant predictors of mental health outcomes such as treatment response, poor outcome and symptom remission; and physical health outcomes such as increased incidence of cardiovascular events and deaths, and all-cause mortality. However, the available evidence has multiple methodological limitations which must be overcome to make any real clinical progress. Despite extensive research on the relationship of depression with peripheral biomarkers, its translational application in practice remains uncertain. In future, peripheral biomarkers identified with novel techniques and combining multiple biomarkers may have a potential role in depression risk assessment but further research is needed in this area.

Mortality from Head Injury over Four Decades in Scotland.

Although the causes of head injury, the population at risk, and approaches to prevention and treatment are continually evolving, there is little information about how these are reflected in patterns of mortality over time. We used population-based comprehensive data uniquely available in Scotland to investigate changes in the total numbers of deaths from 1974 to 2012, as well as the rates of head injury death, from different causes, overall and in relation to age and gender. Total mortality fell from an annual average of 503 to 339 with a corresponding annual decrease in rate from 9.6 to 6.4 per 100,000 population, the decline substantially occurring between 1974 and 1990. Deaths in children fell strikingly, but rose in older people. Deaths in males fell to a greater extent than females, but remained at a higher rate overall. Initially, a transport accident accounted for most deaths, but these fell by 80%, from 325 per year to 65 per year over the 39-year period. Deaths from falling and all other causes did not decline, coming to outnumber transport accident deaths by 1998, which accounts for the overall absence of change in total mortality in recent years. In order to reduce mortality in the future, more-effective measures to prevent falls are needed and these strategies will vary in younger adults (where alcohol is often a factor), as well as in older adults where infirmity can be a cause. In addition, measures to sustain reductions in transport accidents need to be maintained and further developed.

Long-term trends in Anopheles gambiae insecticide resistance in Côte d'Ivoire.

BACKGROUND: Malaria control is heavily dependent on the use of insecticides that target adult mosquito vectors via insecticide treated nets (ITNs) or indoor residual spraying (IRS). Four classes of insecticide are approved for IRS but only pyrethroids are available for ITNs. The rapid rise in insecticide resistance in African malaria vectors has raised alarms about the sustainability of existing malaria control activities. This problem might be particularly acute in Côte d'Ivoire where resistance to all four insecticide classes has recently been recorded. Here we investigate temporal trends in insecticide resistance across the ecological zones of Côte d'Ivoire to determine whether apparent pan-African patterns of increasing resistance are detectable and consistent across insecticides and areas. METHODS: We combined data on insecticide resistance from a literature review, and bioassays conducted on field-caught Anopheles gambiae mosquitoes for the four WHO-approved insecticide classes for ITN/IRS. The data were then mapped using Geographical Information Systems (GIS) and the IR mapper tool to provide spatial and temporal distribution data on insecticide resistance in An. gambiae sensu lato from Côte d'Ivoire between 1993 and 2014. RESULTS: Bioassay mortality decreased over time for all insecticide classes, though with significant spatiotemporal variation, such that stronger declines were observed in the southern ecological zone for DDT and pyrethroids than in the central zone, but with an apparently opposite effect for the carbamate and organophosphate. Variation in relative abundance of the molecular forms, coupled with dramatic increase in kdr 1014F frequency in M forms (An. coluzzii) seems likely to be a contributory factor to these patterns. Although records of resistance across insecticide classes have become more common, the number of classes tested in studies has also increased, precluding a conclusion that multiple resistance has also increased. CONCLUSION: Our analyses attempted synthesis of 22 years of bioassay data from Côte d'Ivoire, and despite a number of caveats and potentially confounding variables, suggest significant but spatially-variable temporal trends in insecticide resistance. In the light of such spatio-temporal dynamics, regular, systematic and spatially-expanded monitoring is warranted to provide accurate information on insecticide resistance for control programme management.

Revisiting the J shaped curve, exploring the association between cardiovascular risk factors and concurrent depressive symptoms in patients with cardiometabolic disease: Findings from a large cross-sectional study.

BACKGROUND: Depression is common in patients with cardiometabolic diseases but little is known about the relationship, if any, between cardiovascular risk factor values and depressive symptoms in patients with these conditions. The objective of this paper is to study the association between cardiovascular risk factors and concurrent depressive symptoms in patients with three common cardiometabolic conditions: coronary heart disease (CHD), stroke and diabetes. METHODS: We retrospectively reviewed primary care data for N = 35537 with 1 of the above 3 conditions who underwent depression screening using the depressive subscale of hospital anxiety and depression score (HADS-D). We reviewed 4 cardiometabolic risk factors (Systolic Blood Pressure [SBP], Diastolic Blood Pressure [DBP], BMI and total cholesterol) recorded concurrently in all patients and HbA1c in patients with diabetes (n = 18453). We analysed the association between individual risk factor value and a positive HADS-D screening result (>7) using logistic regression. RESULTS: SBP and BMI were noted to have a non-linear "J-shaped" relationship with the probability of having a positive HADS-D and observed nadirs (levels with the lowest probability) of 148 mm Hg and 30.70 kg/m2, respectively. Total cholesterol and DBP found to have a weaker curvilinear association with concurrent depression symptoms and nadirs of 3.60 mmol/l and 74 mmHg. Among patients with Diabetes, HbA1c was also found to have a "J-shaped" relationship with probability of having a positive HADS-D with an observed nadir of 7.06% DCCT. The above relationships remain significant after adjusting for age, sex, socio-economic status and number of co-morbid conditions. CONCLUSION: In patients with cardiometabolic disease, cardiovascular risk factor values at both extremes were associated with higher positive depression screening after adjusting for confounders. These findings have potentially important implications for clinical practice in relation to both risk stratification for depression and approaches to secondary prevention in individuals with cardiometabolic disease and merit further investigation to determine the nature and direction of the observed association.Please see related article: http://www.biomedcentral.com/1741-7015/12/199.