The complex polyploid genome architecture of sugarcane.

Sugarcane, the world's most harvested crop by tonnage, has shaped global history, trade and geopolitics, and is currently responsible for 80% of sugar production worldwide1. While traditional sugarcane breeding methods have effectively generated cultivars adapted to new environments and pathogens, sugar yield improvements have recently plateaued2. The cessation of yield gains may be due to limited genetic diversity within breeding populations, long breeding cycles and the complexity of its genome, the latter preventing breeders from taking advantage of the recent explosion of whole-genome sequencing that has benefited many other crops. Thus, modern sugarcane hybrids are the last remaining major crop without a reference-quality genome. Here we take a major step towards advancing sugarcane biotechnology by generating a polyploid reference genome for R570, a typical modern cultivar derived from interspecific hybridization between the domesticated species (Saccharum officinarum) and the wild species (Saccharum spontaneum). In contrast to the existing single haplotype ('monoploid') representation of R570, our 8.7 billion base assembly contains a complete representation of unique DNA sequences across the approximately 12 chromosome copies in this polyploid genome. Using this highly contiguous genome assembly, we filled a previously unsized gap within an R570 physical genetic map to describe the likely causal genes underlying the single-copy Bru1 brown rust resistance locus. This polyploid genome assembly with fine-grain descriptions of genome architecture and molecular targets for biotechnology will help accelerate molecular and transgenic breeding and adaptation of sugarcane to future environmental conditions.

Improving antenatal detection of small-for-gestational-age fetus: economic evaluation of Growth Assessment Protocol.

OBJECTIVE: To determine whether the Growth Assessment Protocol (GAP), as implemented in the DESiGN trial, is cost-effective in terms of antenatal detection of small-for-gestational-age (SGA) neonate, when compared with standard care. METHODS: This was an incremental cost-effectiveness analysis undertaken from the perspective of a UK National Health Service hospital provider. Thirteen maternity units from England, UK, were recruited to the DESiGN (DEtection of Small for GestatioNal age fetus) trial, a cluster randomized controlled trial. Singleton, non-anomalous pregnancies which delivered after 24 + 0 gestational weeks between November 2015 and February 2019 were analyzed. Probabilistic decision modeling using clinical trial data was undertaken. The main outcomes of the study were the expected incremental cost, the additional number of SGA neonates identified antenatally and the incremental cost-effectiveness ratio (ICER) (cost per additional SGA neonate identified) of implementing GAP. Secondary analysis focused on the ICER per infant quality-adjusted life year (QALY) gained. RESULTS: The expected incremental cost (including hospital care and implementation costs) of GAP over standard care was £34 559 per 1000 births, with a 68% probability that implementation of GAP would be associated with increased costs to sustain program delivery. GAP identified an additional 1.77 SGA neonates per 1000 births (55% probability of it being more clinically effective). The ICER for GAP was £19 525 per additional SGA neonate identified, with a 44% probability that GAP would both increase cost and identify more SGA neonates compared with standard care. The probability of GAP being the dominant clinical strategy was low (11%). The expected incremental cost per infant QALY gained ranged from £68 242 to £545 940, depending on assumptions regarding the QALY value of detection of SGA. CONCLUSION: The economic case for replacing standard care with GAP is weak based on the analysis reported in our study. However, this conclusion should be viewed taking into account that cost-effectiveness analyses are always limited by the assumptions made. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Lifestyle information and commercial weight management groups to support maternal postnatal weight management and positive lifestyle behaviour: the SWAN feasibility randomised controlled trial.

OBJECTIVES: To assess feasibility of a future randomised controlled trial (RCT) of clinical and cost-effectiveness of lifestyle information and commercial weight management groups to support postnatal weight management to 12 months post-birth. DESIGN: Two-arm feasibility trial, with nested mixed-methods process evaluation. SETTING: Inner-city unit, south England. POPULATION: Women with body mass indices (BMIs) ≥25 kg/m2 at pregnancy booking or normal BMIs (18.5-24.9 kg/m2 ) identified with excessive gestational weight gain at 36 weeks of gestation. METHODS: Randomised to standard care plus commercial weight management sessions commencing 8-16 weeks postnatally or standard care only. MAIN OUTCOMES: Feasibility outcomes included assessment of recruitment, retention, acceptability and economic data collation. Primary and secondary end points included difference between groups in weight 12 months postnatally compared with booking (proposed primary outcome for a future trial), diet, physical activity, smoking, alcohol, mental health, infant feeding, NHS resource use. RESULTS: In all, 193 women were randomised: 98 intervention and 95 control; only four women had excessive gestational weight gain. A slightly greater weight change was found among intervention women at 12 months, with greatest benefit. Among women attending ten or more weight management sessions. There was >80% follow up to 12 months, low risk of contamination and no group differences in trial completion. CONCLUSION: It was feasible to recruit and retain women with BMIs ≥25 kg/m2 to an intervention to support postnatal weight management; identification of excessive gestational weight gain requires consideration. Economic modelling could inform out-of-trial costs and benefits in a future trial. A definitive trial is an important next step. TWEETABLE ABSTRACT: A feasibility RCT of postnatal weight support showed women with BMIs ≥25 kg/m2 can be recruited and followed to 12 months postnatally.

Factors influencing attendance at structured education for Type 1 diabetes in south London.

AIM: To investigate the factors influencing uptake of structured education for people with Type 1 diabetes in our local population in order to understand why such uptake is low. METHODS: We conducted a cross-sectional database study of adults with Type 1 diabetes in two south London boroughs, analysed according to Dose Adjustment For Normal Eating (DAFNE) attendance or non-attendance. Demographics, glycaemic control and service use, with subset analysis by ethnicity, were compared using univariate analysis. An exploratory regression model was used to identify influencing factors. RESULTS: The analysis showed that 73% of adults had not attended the DAFNE programme. For non-attenders vs attenders, male gender (59 vs 48%; P = 0.002), older age (39 vs 35 years; P < 0.001), non-white ethnicity (30 vs 20%; P = 0.001) and coming from an area of social deprivation (index of multiple deprivation score 31 vs 28; P < 0.001) were associated with non-attendance. The difference in gender (88% men vs 70% women; P < 0.001) and age (43 vs 34 years) persisted in the non-white group. Regression analysis showed that higher baseline HbA1c level (odds ratio 1.96; P = 0.004), younger age (odds ratio 0.98; P = 0.001) and lower social deprivation (odds ratio 0.52; P = 0.001) was associated with attendance. CONCLUSION: Socio-economic status and factors perceived as indicating greater severity of disease (HbA1c ) influence attendance at DAFNE. More work is necessary to understand the demography of non-attenders to aid future service design and alternative engagement strategies for these groups.

Spontaneous spinal epidural haematoma mimicking meningitis in a 2-year-old child--a case report and literature review.

INTRODUCTION: We report the case of a 2-year-old boy with suspected meningitis who presented with acute onset neck pain and stiffness associated with right-sided weakness and ataxia. MANAGEMENT: Despite intravenous antibiotics and antiviral treatment, his condition deteriorated. Magnetic resonance imaging demonstrated spontaneous cervical epidural haematoma (C4-C7) extending down to thoracic (T7) level with associated compression of the spinal cord. He was treated successfully by neurosurgical decompression and made a complete recovery. DISCUSSION: Spinal epidural haematoma is a neurosurgical emergency characterised by extravasation of blood in the spinal epidural space. The clinical presentation particularly in young children can masquerade other conditions such as meningitis. In this article, we discuss our case and review the literature on spontaneous spinal epidural hematoma with an aim to improve awareness of this condition which if not recognised and treated early can lead to significant lifelong morbidity.

Off label use of devices and drugs in interventional radiology.

AIM: To establish how often off-label device and drug use occurs in interventional radiology (IR) in a UK tertiary referral hospital and consider the wider implications for the interventional radiologist. MATERIALS AND METHODS: Prospective data were collected during interventional procedures for 1 working week in a university hospital. Out-of-hours procedures and procedures outside the department were excluded. Operators were asked to record the drugs and devices used, the indication, and method of use. The instructions for use/summary of product characteristics were then studied for each device/drug used to assess if the use was on or off-label. RESULTS: During the study period 52 cases were performed and data were available on 26 cases (50%). In 22 of the 26 cases (84%) there was evidence of off-label use of devices or drugs. Off-label use of drugs included treatment of venous malformations with Fibrovein(©) (sodium tetradecyl sulphate), which is licensed for the treatment of varicose veins in the leg, and intra-arterial injection of heparin, which is licensed for intravenous and subcutaneous use. Off-label device use included placing vascular sheaths in the urinary tract, using angiographic catheters to guide wires in the urinary tract, using sheaths for thrombosuction, reshaping of the tip of most guidewires, and using angioplasty balloons to dislodge the arterial plug at fistula thrombectomy. CONCLUSION: Off-label device and drugs use is common in a UK tertiary hospital IR department and literature suggests this is common in the wider IR community. There are important clinical and legal implications for off-label use for patients and physicians.

Clinical and instrumental parameters in patients with constipation and incontinence: their potential implications in the functional aspects of these disorders.

PURPOSE: The aims of this study were to evaluate several clinical and instrumental parameters in a large number of patients with constipation and incontinence as well as in healthy controls and discuss their potential implications in the functional aspects of these disorders. METHODS: Eighty-four constipated and 38 incontinent patients and 45 healthy controls were submitted to a protocol based on proctologic examination, clinico-physiatric assessment, and instrumental evaluation. RESULTS: Constipated and incontinent patients had significantly worse lumbar lordosis as well as lower rate in the presence of perineal defense reflex than controls. Constipated but not incontinent patients had a lower rate of puborectalis relaxation than controls. Furthermore, worse pubococcygeal tests and a higher rate of muscle synergies presence, either agonist or antagonist, were observed in both constipated and incontinent patients compared to controls. CONCLUSIONS: This study has demonstrated strong correlations between physiatric disorders and the symptoms of constipation and incontinence. Further studies designed to demonstrate a causal relationship between these parameters and the success of a specific treatment of the physiatric disorders on the proctology symptoms are warranted.

POPPIE: protocol for a randomised controlled pilot trial of continuity of midwifery care for women at increased risk of preterm birth.

BACKGROUND: High rates of preterm births remain a UK public health concern. Preterm birth is a major determinant of adverse infant and longer-term outcomes, including survival, quality of life, psychosocial effects on the family and health care costs. We aim to test whether a model of care combining continuity of midwife care with rapid referral to a specialist obstetric clinic throughout pregnancy, intrapartum and the postpartum period is feasible and improves experience and outcomes for women at increased risk of preterm birth. METHODS: This pilot, hybrid, type 2 randomised controlled implementation trial will recruit 350 pregnant women at increased risk of preterm birth to a midwifery continuity of care intervention or standard care. The intervention will be provided from recruitment (antenatal), labour, birth and the postnatal period, in hospital and community settings and in collaboration with specialist obstetric clinic care, when required. Standard care will be the current maternity care provision by NHS midwives and obstetricians at the study site. Participants will be followed up until 6-8 weeks postpartum. The composite primary outcome is the appropriate initiation of any specified interventions related to the prevention and/or management of preterm labour and birth. Secondary outcomes are related to: recruitment and attrition rates; implementation; acceptability to women, health care professionals and stakeholders; health in pregnancy and other complications; intrapartum outcomes; maternal and neonatal postnatal outcomes; psycho-social health; quality of care; women's experiences and health economic analysis. The trial has 80% power to detect a 15% increase in the rate of appropriate interventions (40 to 55%). The analysis will be by 'intention to treat' analysis. DISCUSSION: Little is known about the underlying reasons why and how models of midwifery continuity of care are associated with fewer preterm births, better maternal and infant outcomes and more positive experiences; nor how these models of care can be implemented successfully in the health services. This will be the first study to provide direct evidence regarding the effectiveness, implementation and evaluation of a midwifery continuity of care model and rapid access to specialist obstetric services for women at increased risk of preterm birth. TRIAL REGISTRATION: ISRCTN37733900 . Retrospectively registered on 21 August 2017.

Proton nuclear magnetic resonance spectroscopy of isolated rabbit fundic glands.

1H-nuclear magnetic resonance spectroscopy (NMR) was adapted to isolated rabbit fundic glands and identification made of compounds responsible for several observed spectral resonances. A minimum gland concentration of 0.5 mg dry weight or 5 mg wet weight per 0.5 ml was needed for adequate signal-to-noise ratio. At physiological temperature and pH, the glands demonstrated reproducible spectra, stability for accumulation times greater than 30 min and responsiveness to histamine stimulation, as measured by oxygen consumption and aminopyrine uptake. The relatively anaerobic conditions favored use of proton compared to phosphorus NMR, since 1H-NMR allowed significantly shorter spectral accumulation times and therefore did not compromise glandular viability to the same extent as 31P-NMR. The most conspicuous resonance in the gland spectrum was assigned to the -N+(CH3)3 protons of choline and related compounds. In membrane-free lysates, several components of the signal were resolvable and assigned to choline, phosphatidylcholine, phosphocholine and L-alpha-glycerophosphocholine. Thin-layer chromatography verified that phosphatidylcholine and phosphatidylethanolamine were the major phospholipids present in gland lipid. Presumably, they represent the source of the surface-active phospholipids present in gastric juice, which may play a role in gastric cytoprotection.

Rapid and efficient method for cloning of blunt-ended DNA fragments.

We describe a system to generate cDNA or genomic libraries from DNA segments that have blunt termini. Background and rearrangement levels are low, but efficiencies are high and the procedural times very short. T4 ligase in the presence of polyethylene glycol produces high Mr oligomers of vector and insert. These concatemers are reduced to vector-insert monomers at a high frequency by subsequent cleavage with a restriction endonuclease, which recognises the insert rarely, if at all, and the vector once. The monomers are recircularised under standard ligation conditions prior to transformation. Thus insertion conditions are optimised independently of those for recircularisation. All reading frames for expression libraries are generated by short BAL 31 cleavage followed by the blunt-end cloning procedure. Similarly, genomic expression libraries can be made by BAL 31 or mung-bean nuclease treatment after cleavage with DNase I is the presence of Mn2+. The technique is suitable for any DNA segment that is blunt-ended or can be made so. When the vector is treated with alkaline phosphatase, recombinants are generated at a frequency greater than 90% and have single inserts. Yields are 3-5 X 10(6) colony-forming units per micrograms of insert.

Giardia intestinalis antigens expressed in Escherichia coli.

cDNA and genomic DNA of Giardia intestinalis have been cloned in pUC vectors and used to express Giardia antigens in Escherichia coli. Several expression libraries have been produced and positive clones identified by immuno-colony assays with antisera raised against whole parasites and partially purified antigen(s). Those clones which express G. intestinalis antigens have been used to raise antisera in mice and the antisera used in immunofluorescence assays. The proteins expressed by the clones have been shown to represent a 32 kDa protein of the flagellae and axonemes, a protein associated with the spiral part of the ventral disc, proteins covering the surface of the trophozoite or associated with the coat, and other proteins associated with axonemes of posterolateral flagellae, kinetosomes and funis, and the anterolateral axonemes. mRNA was purified from G. intestinalis and translated in a cell free lysate. A rabbit antiserum raised against trophozoites immunoprecipitated several translation products while an antiserum raised against a purified 32 kDa protein only immunoprecipitated this protein. G. intestinalis rRNA subunits also were examined in the course of mRNA purification. Two rRNA species were evident, the small rRNA and the post-transcriptionally processed large rRNA.

Chromosomal duplication in Giardia duodenalis.

Strains of Giardia duodenalis from diverse parts of the world have three or four chromosomal bands in the range of 650-800 kb as defined by field inversion gel electrophoresis. The extra chromosome band in this range defined a group of strains which are geographically distinct from other strains missing this band. The cloned line WB-1B has three chromosome bands in this size range and chromosome band 3 was used to construct a library of chromosome-specific probes. In some strains examined, including BRIS/83/HEPU/106, a subset of these WB-1B probes hybridized to chromosome band 3 and to the extra chromosome band 4, indicating a partial duplication of chromosome 3 in BRIS/83/HEPU/106. This duplication was estimated to be at least 500 kb when the sizes of NotI chromosome segments which hybridized with chromosome band 3-specific probes were added. A second subset of WB-1B chromosome 3-specific probes hybridized to a fifth chromosome of strain BRIS/83/HEPU/106, in the size range 650-800 kb, which was not visible by ethidium bromide staining. The two subsets of WB-1B probes hybridized to a variety of chromosome combinations in this size range in other Giardia strains and included apparent reversal of chromosome 3 and 4 mobility as well as identification of other minor chromosomes. These data indicate that chromosome band 3 of the line WB-1B is a cluster of at least two different chromosomes that cannot be electrophoretically separated but genetic rearrangements in other strains allow separation of linkage groups carried by chromosome band 3 of WB-1B.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromosomes of Blastocystis hominis.

Three stocks of Blastocystis hominis were adapted to monophasic culture in minimal essential medium (MEM) and the chromosomes of these stocks separated by field inversion gel electrophoresis (FIGE). Ten-twelve chromosomes were distinguished in the electrophoretic karyotype of these three stocks over the range 200 kilobase pairs to greater than 1 megabase pairs. The karyotype of each stock was different. Three DNA probes, B10, B30 and B31, derived from the Netsky stock isolated in America were used as chromosome markers. Probe B10 hybridized to chromosomes of the same size in two of the stocks, one of which was isolated in the U.S.A. and the other in Queensland. B30 and B31 hybridized to a similar number of chromosomes of different sizes in these two stocks. The third stock, from Australia, did not hybridize at all with probes B10 and B30 and only weakly with probe B31.

The negative feedback action of progesterone on luteinizing hormone release is not associated with changes in GnRH mRNA expression in the Ewe.

Progesterone is the ovarian hormone that times events in the ovine reproductive cycle. When elevated, this ovarian hormone acts centrally to inhibit both the tonic and surge modes of gonadotrophin releasing hormone (GnRH) release. Two studies were performed to address the underlying neural mechanisms. The first tested the hypothesis that the rapid rise in GnRH release, that results from an acute fall in progesterone concentrations (such as occurs following luteolysis), is temporally associated with a rapid rise in the cellular content of GnRH mRNA. Three groups of ovariectomised (OVX) ewes were treated with exogenous progesterone for 10 days, while one remained steroid free (OVX, n=7). To determine the effects of acute progesterone (P) withdrawal, ewes were killed on day 10 while implants were still in place (OVX+P, n=6) or 4 (OVX-P4, n=7) or 12 h (OVX-P12, n=7) after progesterone removal. Coronal sections through the rostral portion of the medial preoptic area (rPOA) were processed for cellular in-situ hybridization for GnRH mRNA. An increase in progesterone concentrations markedly suppressed luteinizing hormone (LH) release, while removal of the implants caused progesterone concentrations to fall (P<0.01) within 1 h and LH pulse frequency to increase (P<0.05) within 4 h. Despite these progesterone-induced changes in LH/GnRH release there were no differences in the cellular content of GnRH mRNA among the four groups. In the second study, three groups of ovariectomised ewes were used to determined whether the inhibitory actions of early (EL; n=8) and mid-luteal (ML; n=8) phase concentrations of progesterone on LH release are accompanied by a decrease in GnRH mRNA expression. P inhibited the secretion of LH in a dose dependant manner; pulses of LH were virtually absent in the ML group. Despite this marked inhibitory steroid action, there was no significant difference in the cellular content of GnRH mRNA among the OVX, OVX (EL) and OVX (ML) groups. Thus, both the negative feedback actions of physiological concentrations of progesterone on GnRH release and the rapid escape from progesterone-inhibition are independent of changes in the cellular content of GnRH mRNA. These data suggest that the mechanism by which progesterone controls the timing of events in the ovine oestrous cycle is primarily by altering the secretion of GnRH rather than GnRH biosynthesis.

Objects and positions in visual scenes: effects of perirhinal and postrhinal cortex lesions in the rat.

The authors assessed rats' encoding of the appearance or egocentric position of objects within visual scenes containing 3 objects (Experiment 1) or 1 object (Experiment 2A). Experiment 2B assessed encoding of the shape and fill pattern of single objects, and encoding of configurations (object + position, shape + fill). All were assessed by testing rats' ability to discriminate changes from familiar scenes (constant-negative paradigm). Perirhinal cortex lesions impaired encoding of objects and their shape; postrhinal cortex lesions impaired encoding of egocentric position, but the effect may have been partly due to entorhinal involvement. Neither lesioned group was impaired in detecting configural change. In Experiment 1, both lesion groups were impaired in detecting small changes in relative position of the 3 objects, suggesting that more sensitive tests might reveal configural encoding deficits.

Rats with hippocampal lesions learn about allocentric place cues in a non-navigational task.

Hippocampal-lesioned rats (HPC) and sham controls (SH) learned constant-negative visual discriminations among scenes in a Y-maze. Any arm could be start arm for a trial. Two choice scenes ("constant" and "variable") were shown in the other arms. In Experiment 1, each problem had 2 constants. One or the other constant appeared on every trial, and the variable changed every trial; choosing the variable was rewarded. There were 4 problem types. Each constant might be always in a given direction from the start arm (added egocentric [Ego] cue), always in a given maze arm (added allocentric [Allo] cue), both, or neither. SH rats' visual learning was enhanced by Ego and by Allo cues. HPC rats' visual learning was enhanced by Ego cues, and by Allo cues, but only if there was no Ego cue. Experiment 2 confirmed that Allo cues helped HPC rats as much as SH, in the absence of Ego cues. Rats with HPC lesions can learn about allocentric place cues when navigation and idiothetic cue control are not required.

Home treatment for mental health problems: a systematic review.

OBJECTIVE: This review investigates the effectiveness of 'home treatment' for mental health problems in terms of hospitalisation and cost-effectiveness. For the purposes of this review, 'home treatment' is defined as a service that enables the patient to be treated outside hospital as far as possible and remain in their usual place of residence. METHODS - SYSTEMATIC LITERATURE SEARCH: 'Home treatment' excluded studies focused on day, residential and foster care. The review was based on Cochrane methodology, but non-randomised studies were included if they compared two services; these were only analysed if they provided evidence of the groups' baseline clinical comparability. METHODS - REVIEW OF ECONOMIC EVALUATIONS: Economic evaluations among the studies found were reviewed against established criteria. METHODS - IDENTIFICATION OF SERVICE COMPONENTS: A three-round Delphi exercise ascertained the degree of consensus among expert psychiatrists concerning the important components of community-based services that enable them to treat patients outside hospital. The identified components were used to construct the follow-up questionnaire. METHODS - FOLLOW-UP OF AUTHORS: As a supplement to the information available in the papers, authors of all the studies were followed up for data on service components, sustainability of programmes and service utilisation. METHODS - DATA ANALYSIS: The outcome measure was mean days in hospital per patient per month over the follow-up period. (1) Comparative analysis - compared experimental to control services. It analysed all studies with available data, divided into 'inpatient-control' and 'community-control' studies, and tested for associations between service components and difference in hospital days. (2) Experimental services analysis - analysed only experimental service data and tested for associations between service components and hospital days. RESULTS - SYSTEMATIC LITERATURE SEARCH: A total of 91 studies were found, conducted over a 30-year period. The majority (87) focused on people with psychotic disorders. RESULTS - REVIEW OF ECONOMIC EVALUATIONS: Only 22 studies included economic evaluations. They provided little conclusive evidence about cost-effectiveness because of problems with the heterogeneity of services, sample size, outcome measures and quality of analysis. RESULTS - DELPHI EXERCISE: In all, 16 items were rated as 'essential', falling into six categories: home environment; skill-mix; psychiatrist involvement; service management; caseload size; and health/social care integration. There was consensus that caseloads under 25 and flexible working hours over 7 days were important, but little support for caseloads under 15 or for 24-hour services, and consensus that home visiting was essential, but not on teams being 'explicitly dedicated' to home treatment. RESULTS - RESPONSE TO FOLLOW-UP: A total of 60% of authors responded, supplying data on service components and hospital days in most cases. Other service utilisation data were far less readily available. RESULTS - SERVICE CHARACTERISATION AND CLASSIFICATION: The services were homogeneous in terms of 'home treatment function' but fairly heterogeneous in terms of other components. There was some evidence for a group of services that were multidisciplinary, had psychiatrists as integrated team members, had smaller caseloads, visited patients at home regularly and took responsibility for both health and social care. This was not a cohesive group, however. RESULTS - SUSTAINABILITY OF SERVICES: The sustainability of home treatment services was modest: less than half the services whose authors responded were still identifiable. Services were more likely to be operational if the study had found them to reduce hospitalisation significantly. RESULTS - META-ANALYSIS: Meta-analysis with heterogeneous studies is problematic. The evidence base for the effectiveness of services identifiable as 'home treatment' was not strong. Within the 'inpatient-control' study group, the mean reduction in hospitalisation was 5 days per patient per month (for 1-year studies only). No statistical significance could be measured for this result. For 'community-control' studies, the reduction in hospitalisation was negligible. Moreover, the heterogeneity of control services, the wide range of outcome measures and the limited availability of data might have confounded the analysis. Regularly visiting at home and dual responsibility for health and social care were associated with reduced hospitalisation. Evidence for other components was inconclusive. Few conclusions could be drawn from the analysis of service utilisation data. RESULTS - LOCATION: Studies were predominately from the USA and UK, more of them being from the USA. North American studies found a reduction in hospitalisation of 1 day per patient per month more than European studies. North American and European services differed on some service components, but this was unlikely to account for this finding, particularly as no difference was found in their experimental service results. CONCLUSIONS - STATE OF RESEARCH: There is a clear need for further studies, particularly in the UK. The benefit of home treatment over admission in terms of days in hospital was clear, but over other community-based alternatives was inconclusive. CONCLUSIONS - NON-RANDOMISED STUDIES: Difficulties in systematically searching for non-randomised studies may have contributed to the smaller number of such studies found (35, compared with 56 randomised controlled trials). This imbalance was compounded by a relatively poor response rate from non-randomised controlled trial authors. Including them in the analysis had little effect. CONCLUSIONS - LIMITATIONS OF THIS REVIEW: A broad area was reviewed in order to avoid the problem of analysing by service label. While reviews of narrower areas may risk implying a homogeneity of the services that is unwarranted, the current strategy has the drawback that the studies cover a range of heterogeneous services. The poor definition of control services, however, is ubiquitous in this field, however reviewed areas are defined. Inclusion of mean data for which no standard deviations were available was problematic in that it prevented measuring the significance of the main findings. The lack of availability of this data, however, is an important finding, demonstrating the difficulty in seeking certainty in this area. Only days in hospital and cost-effectiveness were analysed here. The range and lack of uniformity of measures used in this field made meta-analysis of other outcomes impossible. It should be noted, however, that the findings pertain to these aspects alone. The Delphi exercise reported here was limited in being conducted only with psychiatrists, rather than a multidisciplinary panel. Its findings were used as a framework for the follow-up and analysis. Their possible bias should be borne in mind when considering them as findings in themselves. CONCLUSIONS - IMPLICATIONS FOR CLINICIANS: The evidence base for home treatment compared with other community-based services is not strong, although it does show that home treatment reduces days spent in hospital compared with inpatient treatment. There is evidence that visiting patients at home regularly and taking responsibility for both health and social care each reduce days in hospital. CONCLUSIONS - IMPLICATIONS FOR CONSUMERS: Services that visit patients at home regularly and those that take responsibility for both health and social care are likely to reduce time spent in hospital. Psychiatrists surveyed in this review also considered support for carers to be essential. The evidence from this review, however, was that few services currently have protocols for meeting carers' needs. CONCLUSIONS - RECOMMENDATIONS FOR RESEARCH AND COMMISSIONERS: A centrally coordinated research strategy, with attention to study design, is recommended. Studies should include economic evaluations that report health and social service utilisation. Service components should be collected and reported for both experimental and control services. Studies should be designed with adequate power and longer durations of follow-up and use comparable outcome measures to facilitate meta-analysis. Research protocols should be adhered to throughout the studies. It may be advisable that independent researchers conduct studies in future. It is no longer recommended that home treatment be tested against inpatient care, or that small, localised studies replicate existing, more highly powered studies.