Supported discharge service versus inpatient care evaluation (SITE): a randomised controlled trial comparing effectiveness of an intensive community care service versus inpatient treatment as usual for adolescents with severe psychiatric disorders: self-harm, functional impairment, and educational and clinical outcomes.

Clinical guidelines recommend intensive community care service treatment (ICCS) to reduce adolescent psychiatric inpatient care. We have previously reported that the addition of ICCS led to a substantial decrease in hospital use and improved school re-integration. The aim of this study is to undertake a randomised controlled trial (RCT) comparing an inpatient admission followed by an early discharge supported by ICCS with usual inpatient admission (treatment as usual; TAU). In this paper, we report the impact of ICCS on self-harm and other clinical and educational outcomes. 106 patients aged 12-18 admitted for psychiatric inpatient care were randomised (1:1) to either ICCS or TAU. Six months after randomisation, we compared the two treatment arms on the number and severity of self-harm episodes, the functional impairment, severity of psychiatric symptoms, clinical improvement, reading and mathematical ability, weight, height and the use of psychological therapy and medication. At six-month follow-up, there were no differences between the two groups on most measures. Patients receiving ICCS were significantly less likely to report multiple episodes (five or more) of self-harm (OR = 0.18, 95% CI: 0.05-0.64). Patients admitted to private inpatient units spent on average 118.4 (95% CI: 28.2-208.6) fewer days in hospitals if they were in the ICCS group compared to TAU. The addition of ICCS to TAU may lower the risk of multiple self-harm and may reduce the duration of inpatient stay, especially in those patients admitted for private care. Early discharge with ICCS appears to be a viable alternative to standard inpatient treatment.

Sexuality, risk, and organisational misbehaviour in a secure mental healthcare facility in England.

Sexuality in secure mental healthcare has been overlooked in both clinical praxis and academic research. In the UK, there exist no formal policies to inform staff approaches to managing inpatient sexuality. The limited research that has been undertaken in this field has found that often, prohibitive approaches are favoured, which may affect how inpatients conceptualise and experience their sexuality in the long-term. The aim of this study was to identify discursive constructions of inpatient sexuality, as articulated in semi-structured group interviews with inpatients and ward staff from a secure mental healthcare facility in England. The analysis identified constructions of inpatient sexuality within two overarching and conflicting discourses: one of the normalcy and legitimacy of sexual expression in human experience; and the other of risk, wherein sexuality needed to be regulated and obstructed. Inpatients' expressions of sexuality could often only be conceptualised in terms of 'organisational misbehaviour', acts that violated the implicit norms and codes of the institution. It is suggested that recoding inpatient sexuality as misbehaviour could have implications for inpatients' long-term recovery.

Cervical cancer - does the morphological subtype affect survival rates?

A retrospective population-based observational study using cancer registration data of women diagnosed with invasive cervical cancer between 2006 and 2010, in England, was carried out to explore how different morphological subtypes affect survival rates. Age-standardised net survival rates by morphological subtype are presented alongside with excess mortality modelling accounting for the impact of demographic, diagnostic and tumour factors. The three main morphological subtypes (squamous cell carcinoma (SCC), adenocarcinoma and adenosquamous carcinoma) have similar one-year net survival rates of approximately 85%. After adjusting for other important determinants of survival, there were no differences at five-years amongst the three main morphological subtypes, with unadjusted survival rates of 55-65%. As expected, women presenting with neuroendocrine tumours had a much poorer outcome than other epithelial cervical malignancies, with 1-year survival of up to 55%, five-year survival of 34% and excess mortality rates compared to SCC varying between 1.9 and 5.9. Impact Statement What is already known on this subject: This is the first study on survival by cervical cancer morphological subtype using national cancer data. What the results of this study add: This study uses excess mortality modelling to investigate the effects of the morphological subtypes whilst adjusting the other factors that affect cervical cancer survival such as stage, age and grade. What the implications are of these findings for clinical practice and/or further research: It is known that cervical neuroendocrine tumours have a poor prognosis and this is confirmed by this study. Squamous cell carcinomas (SCC), adenocarcinomas (AC) and adenosquamous carcinomas (ASC) have the highest net survival and when accounting for other factors there are no differences amongst these morphological subtypes in terms of survival.

Variations in Treatment of Cervical Cancer According to Tumor Morphology-Population-Based Cohort Analysis of English National Cancer Registration Data.

OBJECTIVE: This study aimed to investigate differences in the treatment of cervical cancer by tumor morphology after accounting for demographic, diagnostic, and tumor factors. METHODS: Retrospective population-based observational study using linked cancer registration and treatment data from administrative data sources of women diagnosed with cervical cancer (International Classification of Diseases, Tenth Edition C53, malignant behavior) during 2009 and 2010 in England. Descriptive analyses and multinomial regression modeling have been used to consider differences in treatment by morphological subtype. For each morphological subtype, number and percentage of cases are presented by demographic, diagnostic, and tumor factors and treatment modality. Relative risk ratios are provided for each treatment modality by morphological subtype and other specified factors. RESULTS: Forty-three percent of women were treated surgically; 36% by clinical oncology and only 8% by combination of surgery and clinical oncology. Compared with squamous cell carcinomas, both adenocarcinomas and adenosquamous carcinomas were more likely to be treated by trachelectomy, hysterectomy, radiotherapy with hysterectomy, or chemoradiotherapy with hysterectomy than by chemoradiotherapy without hysterectomy. These differences were explained mainly by a different stage distribution, but some difference remained after adjustment for other factors including stage. As clinically recommended, neuroendocrine tumors were not treated surgically. Further treatment differences were found by age, route to diagnosis, stage, and grade. Deprivation was not generally associated with treatment differences, with 1 exception that those from more deprived areas were less likely to be treated by trachelectomy. CONCLUSIONS: Important treatment differences according to tumor morphology remain after adjusting for relevant patient demographic, diagnostic, and tumor factors. In particular, the difference between the treatment of squamous cell carcinoma and adenocarcinoma is notable.

Factors Affecting Short-term Mortality in Women With Ovarian, Tubal, or Primary Peritoneal Cancer: Population-Based Cohort Analysis of English National Cancer Registration Data.

OBJECTIVE: International studies show lower survival rates in the United Kingdom than other countries with comparable health care systems. We report on factors associated with excess mortality in the first year after diagnosis of primary invasive epithelial ovarian, tubal, and primary peritoneal cancer. METHODS: Routinely collected national data were used for patients diagnosed in England in 2008 to 2010. A multivariate Poisson model was used to model excess mortality in 3 periods covering the first year after diagnosis, adjusting for various factors including age at diagnosis, route to diagnosis, tumor stage, tumor morphology, and treatment received. RESULTS: Of 14,827 women diagnosed as having ovarian cancer, 5296 (36%) died in the first year, with 1673 deaths in the first month after diagnosis. Age older than 70 years, diagnosis after an emergency presentation or by an unknown route, and unspecified or unclassified epithelial morphologies were strongly and independently associated with excess mortality in the first year after diagnosis. Of the 2100 (14%) women who fulfilled all 3 criteria, 1553 (74%) did not receive any treatment and 1774 (85%) died in the first year after diagnosis. In contrast, only 193 (4%) of the 4414 women without any of these characteristics did not receive any treatment, and only 427 (9%) died in the first year after diagnosis. CONCLUSIONS: Although our results are based on data from England, they are likely to have implications for cancer care pathways worldwide because most of the identified factors are not specific to the UK health care system. Our results suggest the need to increase symptom awareness, promote timely general practitioner referral, and optimize diagnostic and early treatment pathways within secondary care to increase access to treatment for women with advanced-stage invasive epithelial ovarian, tubal, and primary peritoneal cancer. This process should be pursued alongside continued efforts to develop primary prevention and screening strategies.

Specialist surgery for ovarian cancer in England.

OBJECTIVE: The aim of this study is to evaluate the impact of the 1999 national recommendations for ovarian cancer surgery in England to be performed by specialist surgeons in specialist centres. METHODS: A retrospective analysis of English cancer registry records, Hospital Episode Statistics (HES) data for all English NHS providers and General Medical Council (GMC) sub-specialty accreditation, to consider changes to the annual proportion of ovarian cancer (ICD10 C56-C57) patients undergoing major gynaecological surgery in gynaecological cancer centres (GCCs) or by specialist gynaecological oncologists (GOs). RESULTS: From 2000 to 2009, 2428 consultants were responsible for surgery on 30,753 patients. There were significant increases in the proportions of patients undergoing surgery at GCCs (43% to 76%, P<0.001), by GMC accredited GOs (5% to 36%, P<0.001), and by high ovarian cancer caseload (≥18 cases) surgeons (22% to 56%, P<0.001). CONCLUSION: There have been increased centralisation and specialisation of surgery for ovarian cancer patients since the NHS Cancer Plan (2000) and there has also been improved survival. However, by 2009, many ovarian cancer patients were still not receiving specialist surgery; the majority of patients were not operated on by GMC accredited gynaecological oncologists and there was considerable regional variation. Systems of accreditation should be reviewed and trusts should ensure that HES data accurately records clinical activity.

Incidence and survival of gynecologic sarcomas in England.

OBJECTIVE: Gynecologic sarcomas account for approximately 3% to 4% of all gynecologic malignancies and are associated with poor outcomes compared with gynecologic carcinomas. The aim of this study is to report the incidence and survival rates of the main gynecologic sarcomas using national English cancer registration data. METHODS/MATERIALS: Records of gynecologic sarcomas diagnosed between 1985 and 2008 were extracted from the English National Cancer Data Repository. ICD-O3 morphology codes were used to assign tumor records to specific histologic subgroups. Incidence and 5-year relative survival rates were calculated. RESULTS: There were 5316 new cases of gynecologic sarcoma diagnosed in England between 1985 and 2008. Incidence rates increased significantly in the early 1990s, probably due to coding changes. Age-specific incidence rates were highest in women aged between 45 and 64 years. In the most recent period studied (2001-2008), incidence rates fluctuated between 8 and 9.6 per million. The most common anatomical site was the uterus (83% of all diagnoses), and the most common histologic diagnosis was leiomyosarcoma (52% of all diagnoses). Overall 5-year relative survival increased significantly between 1985-1989 and 2000-2004, from 34% to 48%. CONCLUSIONS: Gynecologic sarcoma incidence rates have varied little since 1993, whereas survival has improved significantly. These results are consistent with previously published small series and case studies, and provide a more complete picture of gynecologic sarcoma incidence and survival patterns in England.

Ancient mtDNA genetic variants modulate mtDNA transcription and replication.

Although the functional consequences of mitochondrial DNA (mtDNA) genetic backgrounds (haplotypes, haplogroups) have been demonstrated by both disease association studies and cell culture experiments, it is not clear which of the mutations within the haplogroup carry functional implications and which are "evolutionary silent hitchhikers". We set forth to study the functionality of haplogroup-defining mutations within the mtDNA transcription/replication regulatory region by in vitro transcription, hypothesizing that haplogroup-defining mutations occurring within regulatory motifs of mtDNA could affect these processes. We thus screened >2500 complete human mtDNAs representing all major populations worldwide for natural variation in experimentally established protein binding sites and regulatory regions comprising a total of 241 bp in each mtDNA. Our screen revealed 77/241 sites showing point mutations that could be divided into non-fixed (57/77, 74%) and haplogroup/sub-haplogroup-defining changes (i.e., population fixed changes, 20/77, 26%). The variant defining Caucasian haplogroup J (C295T) increased the binding of TFAM (Electro Mobility Shift Assay) and the capacity of in vitro L-strand transcription, especially of a shorter transcript that maps immediately upstream of conserved sequence block 1 (CSB1), a region associated with RNA priming of mtDNA replication. Consistent with this finding, cybrids (i.e., cells sharing the same nuclear genetic background but differing in their mtDNA backgrounds) harboring haplogroup J mtDNA had a >2 fold increase in mtDNA copy number, as compared to cybrids containing haplogroup H, with no apparent differences in steady state levels of mtDNA-encoded transcripts. Hence, a haplogroup J regulatory region mutation affects mtDNA replication or stability, which may partially account for the phenotypic impact of this haplogroup. Our analysis thus demonstrates, for the first time, the functional impact of particular mtDNA haplogroup-defining control region mutations, paving the path towards assessing the functionality of both fixed and un-fixed genetic variants in the mitochondrial genome.

Anchor-based bisulfite sequencing determines genome-wide DNA methylation.

Whole Genome Bisulfite Sequencing (WGBS) is the current standard for DNA methylation profiling. However, this approach is costly as it requires sequencing coverage over the entire genome. Here we introduce Anchor-Based Bisulfite Sequencing (ABBS). ABBS captures accurate DNA methylation information in Escherichia coli and mammals, while requiring up to 10 times fewer sequencing reads than WGBS. ABBS interrogates the entire genome and is not restricted to the CpG islands assayed by methods like Reduced Representation Bisulfite Sequencing (RRBS). The ABBS protocol is simple and can be performed in a single day.

Evidence of integumentary scale diversity in the late Jurassic Sauropod Diplodocus sp. from the Mother's Day Quarry, Montana.

The life appearance of dinosaurs is a hotly debated topic in the world of paleontology, especially when it comes to dinosaur integument. In the case of sauropods, however, the topic is harder to properly discuss due to the limited amount of fossilized skin impressions that have been discovered. Thus far, the fossil record of sauropod integument fossils include titanosaur embryos from Patagonia, possible keratinous diplodocid dorsal spines, track ways with foot impressions, and other isolated skin impressions found in association with sauropod body fossils. Several prominent integument fossils have been found at the Mother's Day Quarry, located in the Bighorn Basin, Montana. These discoveries may bring new important information about diplodocids, specifically Diplodocus sp. Here we describe newly uncovered fossilized skin that gives evidence of scale diversity in the genus Diplodocus. The scales themselves represent tubercles, and exhibit various shapes including rectangular, ovoid, polygonal, and globular scales. The tubercles are small in size, the biggest of which only reach about 10mm in length. Considering how diverse the scale shapes are in such a small area of skin, it is possible that these distinct scale shapes may represent a transition on the body from one region to another: perhaps from the abdomen to dorsal side, or abdomen to shoulder. Based on analysis of extant integument and scale orientation of crocodilians, it is possible to hypothesize on the location of the integument relative to the body as well as the size and relative maturational status of the individual.

Multiplex analysis of mitochondrial DNA pathogenic and polymorphic sequence variants.

The mitochondrial DNA (mtDNA) encompasses two classes of functionally important sequence variants: recent pathogenic mutations and ancient adaptive polymorphisms. To rapidly and cheaply evaluate both classes of single nucleotide variants (SNVs), we have developed an integrated system in which mtDNA SNVs are analyzed by multiplex primer extension using the SNaPshot system. A multiplex PCR amplification strategy was used to amplify the entire mtDNA, a computer program identifies optimal extension primers, and a complete global haplotyping system is also proposed. This system genotypes SNVs on multiplexed mtDNA PCR products or directly from enriched mtDNA samples and can quantify heteroplasmic variants down to 0.8% using a standard curve. With this system, we have developed assays for testing the common pathogenic mutations in four multiplex panels: two genotype the 13 most common pathogenic mtDNA mutations and two genotype the 10 most common Leber Hereditary Optic Neuropathy mutations along with haplogroups J and T. We use a hierarchal system of 140 SNVs to delineate the major global mtDNA haplogroups based on a global phylogenetic tree of coding region polymorphisms. This system should permit rapid and inexpensive genotyping of pathogenic and lineage-specific mtDNA SNVs by clinical and research laboratories.

Clinical validation of qPCR Target Selector™ assays using highly specific switch-blockers for rare mutation detection.

AIMS: The identification of actionable DNA mutations associated with a patient's tumour is critical for devising a targeted, personalised cancer treatment strategy. However, these molecular analyses are typically performed using tissue obtained via biopsy, which involves substantial risk and is often not feasible. In addition, biopsied tissue does not always reflect tumour heterogeneity, and sequential biopsies to track disease progression (eg, emergence of drug resistance mutations) are not well tolerated. To overcome these and other biopsy-associated limitations, we have developed non-invasive 'liquid biopsy' technologies to enable the molecular characterisation of a patient's cancer using peripheral blood samples. METHODS: The Target Selector ctDNA platform uses a real-time PCR-based approach, coupled with DNA sequencing, to identify cancer-associated genetic mutations within circulating tumour DNA. This is accomplished via a patented blocking approach suppressing wild-type DNA amplification, while allowing specific amplification of mutant alleles. RESULTS: To promote the clinical uptake of liquid biopsy technologies, it is first critical to demonstrate concordance between results obtained via liquid and traditional biopsy procedures. Here, we focused on three genes frequently mutated in cancer: EGFR (Del19, L858, and T790), BRAF (V600) and KRAS (G12/G13). For each Target Selector assay, we demonstrated extremely high accuracy, sensitivity and specificity compared with results obtained from tissue biopsies. Overall, we found between 93% and 96% concordance to blinded tissue samples across 127 clinical assays. CONCLUSIONS: The switch-blocker technology reported here offers a highly effective method for non-invasively determining the molecular signatures of patients with cancer.

Inequalities in breast cancer stage at diagnosis in the Trent region, and implications for the NHS Breast Screening Programme.

BACKGROUND: This study investigates risk factors for diagnosis with late-stage breast cancer in order to identify inequalities and inform the understanding of barriers affecting access to mammography screening. METHODS: Data from the Trent Cancer Registry were used to identify all women with invasive breast cancer, diagnosed in 1998-2006. Risk of diagnosis with late-stage breast cancer was calculated to quantify strength of association between exposure and outcome. RESULTS: Women outside the age group for routine screening were approximately 30% [<50 years, relative risk (RR) = 1.34 (95% confidence interval, CI: 1.26-1.43) and >70 years, RR = 1.27 (95% CI: 1.19-1.36)] more likely to be diagnosed with late-stage breast cancer; the most deprived women were 37% [RR = 1.37 (95% CI: 1.01-2.56)] more likely to be diagnosed with Stage IV breast cancer; ethnic minority women were 15% [RR = 1.15 (95% CI: 1.09-1.22)] more likely to be diagnosed with late-stage breast cancer and women resident in 5 of 11 Trent Primary Care Trusts (PCT) had a greater than 30% increased risk of diagnosis with late-stage breast cancer than those in Nottingham City PCT. CONCLUSION: These findings highlight the need for appropriate targeted interventions to address compositional and contextual inequalities that are evident in breast cancer stage at diagnosis.

An enhanced MITOMAP with a global mtDNA mutational phylogeny.

The MITOMAP (http://www.mitomap.org) data system for the human mitochondrial genome has been greatly enhanced by the addition of a navigable mutational mitochondrial DNA (mtDNA) phylogenetic tree of approximately 3000 mtDNA coding region sequences plus expanded pathogenic mutation tables and a nuclear-mtDNA pseudogene (NUMT) data base. The phylogeny reconstructs the entire mutational history of the human mtDNA, thus defining the mtDNA haplogroups and differentiating ancient from recent mtDNA mutations. Pathogenic mutations are classified by both genotype and phenotype, and the NUMT sequences permits detection of spurious inclusion of pseudogene variants during mutation analysis. These additions position MITOMAP for the implementation of our automated mtDNA sequence analysis system, Mitomaster.

Analytical validation of the Target Selector ctDNA platform featuring single copy detection sensitivity for clinically actionable EGFR, BRAF, and KRAS mutations.

BACKGROUND: Personalized medicine requires accurate molecular profiling for targeted therapy decisions. Insufficient tissue yield or tumor heterogeneity frequently limits the correct tissue biomarker determination. As a noninvasive complement to traditional tissue biopsies, liquid biopsies detect and track cancer driver mutations from biofluids (e.g., blood, urine). Here we present the analytical validation of Target Selector™ ctDNA assays capable of single mutant DNA copy detection. METHODS: The Target Selector ctDNA assay applies a patented Switch-Blocker technology to suppress amplification of background (wild-type) WT alleles, while allowing specific amplification of very low frequency mutant alleles. In contrast to allele specific enrichment technologies like ddPCR, one Switch-Blocker inhibits amplification of a DNA target up to 15 bp in length (e.g., one Switch-Blocker covers all KRAS exon 2, codon 12 and 13 variants). Target enrichment is achieved through a quantitative PCR reaction; subsequent DNA sequencing confirms mutation identity. Analytical validation with cancer cell line DNA was conducted by three independent operators using five instruments across five days. RESULTS: A total of 3086 samples were tested on EGFR, BRAF and KRAS Target Selector ctDNA assays, with EGFR WT as a reference. All assays showed >99% analytical sensitivity and specificity. Single mutant copy detection is confirmed by experimental data and theoretical estimates. In the presence of 14000 WT DNA copies, limits of detection were: EGFR Del19, 0.01%; EGFR L858R, 0.02%; EGFR T790M, 0.01%; BRAF V600E, 0.01%; KRAS G12C, 0.02%. Inter- and intra-assay analyses showed r2>0.94, suggesting consistent performance among operational variables. Healthy donor samples (100 tests) showed clinical specificity at >99%. Finally, Target Selector clinical experience data of >2200 patient samples is consistent with published tissue mutation prevalence. CONCLUSIONS: Highly sensitive Target Selector ctDNA assays with single mutant copy detection and limit of detection at 0.02% or better enable accurate molecular profiling vital for disease management.

Milk feeding and dietary patterns predict weight and fat gains in infancy.

Current guidelines recommend that infants are exclusively breast fed for the first 6 months of life, with particular solid foods being gradually introduced from 6 months. Our objective was to compare the growth of infants whose feeding most closely followed current guidelines with the growth of infants with other feeding practices. Participants were 1740 infants in a prospective cohort study in Southampton, UK. At 6 and 12 months, infants' milk feeding was recorded, diets assessed using food frequency questionnaires (FFQ), and anthropometry performed. Principal components analysis was used to identify patterns of foods in the diet using the food intakes assessed by the FFQs. Two patterns ('infant guidelines' and 'adult foods') explained most variance in infant diet at 6 and 12 months of age. The main outcomes were conditional growth in weight, length and skinfold thickness from 0-6 and 6-12 months. Infants who were breast fed from 0-6 months gained weight, length and adiposity more slowly than formula-fed infants, independent of age at introduction of solids and maternal factors: compared with infants who were breast fed from 0-6 months, formula-fed infants gained 0.21 standard deviation scores (SDS) in weight [95% confidence interval (CI) 0.00, 0.42]. Infants whose dietary pattern was most similar to current feeding guidelines, with high frequencies of fresh fruit and vegetables, home-prepared foods and breast milk, gained weight and skinfold thickness more rapidly from 6 to 12 months than other infants, independent of milk feeding, age at introduction of solids and maternal factors. Compared with infants in the lowest quarter, infants in the highest 'infant guidelines' score quarter gained 0.24 SDS [95% CI 0.06, 0.43] in weight and 0.26 SDS [95% CI 0.07, 0.45] in skinfold thickness. Conversely, infants whose diets had the highest frequencies of breads and processed foods gained weight less rapidly from 6 to 12 months than other infants. The extent to which the patterns of diet and growth we have described will influence the current or later health of infants is unknown. We are following up the infants in this study to assess the impact of these patterns beyond the first year of life. These associations should also be examined in other settings and populations.

Comparison of effectiveness and cost-effectiveness of an intensive community supported discharge service versus treatment as usual for adolescents with psychiatric emergencies: a randomised controlled trial.

BACKGROUND: Intensive community treatment to reduce dependency on adolescent psychiatric inpatient care is recommended in guidelines but has not been assessed in a randomised controlled trial in the UK. We designed a supported discharge service (SDS) provided by an intensive community treatment team and compared outcomes with usual care. METHODS: Eligible patients for this randomised controlled trial were younger than 18 years and had been admitted for psychiatric inpatient care in the South London and Maudsley NHS Foundation Trust. Patients were assigned 1:1 to either the SDS or to usual care by use of a computer-generated pseudorandom code with random permuted blocks of varying sizes. The primary outcome was number of inpatient bed-days, change in Strengths and Difficulties Questionnaire (SDQ) scores, and change in Children's Global Assessment Scale (CGAS) scores at 6 months, assessed by intention to treat. Cost-effectiveness was explored with acceptability curves based on CGAS scores and quality-adjusted life-years (QALYs) calculated from the three-level EuroQol measure of health-related quality of life (EQ-5D-3L), taking a health and social care perspective. This study is registered with the ISRCTN Registry, number ISRCTN82129964. FINDINGS: Hospital use at 6 months was significantly lower in the SDS group than in the usual care group (unadjusted median 34 IQR 17-63 vs 50 days, 19-125, p=0·04). The ratio of mean total inpatient days for usual care to SDS was 1·67 (95% CI 1·02-2·81, p=0·04), which decreased to 1·65 (0·99-2·77, p=0·057) when adjusted for differences in hospital use before randomisation. Scores for SDQ and CGAS did not differ between groups. The cost-effectiveness acceptability curve based on QALYs showed that the probability of SDS being cost-effective compared with usual care was around 60% with a willingness-to-pay threshold of £20 000-30 000 per QALY, and that based on CGAS showed at least 58% probability of SDS being cost-effective compared with usual care irrespective of willingness to pay. We recorded no adverse events attributable to SDS or usual care. INTERPRETATION: SDS provided by an intensive community treatment team reduced bed usage at 6 months' follow-up but had no effect on functional status and symptoms of mental health disorders compared with usual care. The possibility of preventing admissions, particularly through features such as reduced self-harm and improved reintegration into school, with intensive community treatment should be investigated in future studies. FUNDING: South London and Maudsley NHS Trust.

Health-related job loss: findings from a community-based survey.

AIMS: To explore the frequency, nature, determinants and outcome of health-related job loss (HRJL) in men sampled from the general population of three rural areas. METHODS: Data on lifetime occupational history, including any HRJL, were obtained as part of a postal survey of men aged 24-70 years in three rural areas of England and Wales. Incidence rates were calculated for first health-related loss of a job that had been held for >or=1 year. Associations with risk factors were examined by Poisson regression, and by application of conditional logistic regression in a nested case-control study. RESULTS: HRJL was reported by 1408 (13%) of the 10 559 men who had held long-term jobs. The incidence rose steeply with age for cardiorespiratory and neurological disorders, but for accidents and poisoning the trend was, if anything, in the reverse direction. An increase in incidence over time was most marked for musculoskeletal disorders and mental illness, and much less prominent for cardiorespiratory and neurological disease. In comparison with other occupations, the risk was lower in agricultural workers (odds ratio (OR) 0.6, 95% CI 0.5 to 0.8), and higher in policemen (OR 2.4, 95% CI 1.6 to 3.7) and teachers (OR 2.0, 95% CI 1.5 to 2.7), this differential being even greater for HRJL caused by mental illness. Risk was also increased in employees relative to the self-employed (OR 2.0, 95% CI 1.7 to 2.3). Shift work was associated with a higher incidence of job loss caused by mental illness (OR 1.5, 95%CI 1.1-2.2), and heavy lifting with HRJL caused by musculoskeletal disorders (OR 2.6, 95% CI 2.0 to 3.5). After HRJL, 61% of subjects had subsequently obtained further long-term employment, usually within 1 year. CONCLUSIONS: In the population studied, HRJL has become increasingly common, especially in relation to musculoskeletal disorders and mental illness. In addition to being associated with ergonomic stresses in the workplace, it may be importantly influenced by cultural and economic factors. Future research should focus on the minority of workers who leave a job for health reasons and do not rapidly return to further work.

Non-fatal occupational injuries in British agriculture.

OBJECTIVES: To investigate the incidence, nature and determinants of non-fatal occupational injuries in British agriculture. METHODS: As part of a postal survey, data on lifetime histories of work in agriculture and occupational accidents were obtained from men born between 1933 and 1977 and residing in three rural areas of England and Wales. Incidence rates for different categories of accident were compared with those derived from statutory reporting. Associations with risk factors were explored by Poisson regression, and summarised by incidence rate ratios (IRRs). RESULTS: Of the 10 765 responders (response rate = 31%), 3238 (30%) reported at least one occupational accident at the ages of 14-64 years, leading to absence from work for >or=3 days, including 1492 accidents that could be linked to a specific job listed in the history of agricultural work. The reported incidence of injuries in agriculture was markedly higher than that derived from statutory reporting, particularly for self-employed farmers. During 1996-2003, the highest rates of agricultural accidents were from handling, lifting or carrying (4.9/1000 person-years), falls from a height (4.6/1000 person-years) and injury by animals (3.4/1000 person-years). After adjustment for calendar period and age, the risk of accidents was elevated in men who had only recently entered agricultural work (IRR 3.7, 95% CI 2.7 to 5.1 for men who had worked in agriculture for up to 1 year relative to those who had entered the industry >25 years earlier), and in those who carried out forestry (IRR 1.7, 95% CI 1.5 to 1.9). CONCLUSION: Our findings confirm the substantial underascertainment of serious accidental injuries in agriculture through statutory reporting, particularly for the self-employed. The risk of accidents is highest in new recruits to the industry and in those undertaking forestry, and these groups should be a target for further preventive action.