Mental health. Beyond the asylum.
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Aged↗
Biomedical subjects
M Knapp
Publications and source records attributed to M Knapp.
Screening for linkage and association in nuclear families.
We applied linkage analysis with a sib-pair method, which also takes into account information on unaffected siblings, and family-based methods of association analysis to determine the disease affecting loci in Problem 1. Whereas the first two disease loci were correctly identified by association analysis, the sib-pair linkage method failed to detect the disease loci 3 and 4. We therefore determined the data structure and sample size necessary for demonstrating linkage to these loci.
Alleles↗
Schizophrenia: shifting the balance of care.
Schizophrenia poses a major challenge to policy makers in health and social care in England. As deinstitutionalisation has progressed, public concern about people with the condition has increased owing to a small number of public incidents. This paper describes the overall balance of care or support for people with schizophrenia, particularly between different settings and the services received. Using these data we are able to provide a basic estimate of the current resource implications of schizophrenia care in England with respect to different public sector agencies, the voluntary sector and service users and their families. The targeting of public sector resources between different care settings is also considered. The discussion suggests that resources are still targeted at existing care facilities rather than on individuals, and examines the roles of individual care agencies and the relationships between them. Four broad resource guidelines are suggested that could improve the effective use of resources for schizophrenia care.
Health Care Costs↗
Community mental health care for former hospital in-patients. Predicting costs from needs and diagnoses.
BACKGROUND: In the UK the replacement of long-term in-patient care with community-based support has been part of central government health policy for many years. One of the challenges of implementing such a policy is the prediction of support and service needs in the community and the associated costs. METHOD: Using research data from north London analyses were undertaken to examine the associations between service use and costs in the community and the characteristics of hospital in-patients. RESULTS: Although clinical diagnosis was not a useful predictor of either service utilisation or costs, more than a third of the variation in community care costs could be explained by symptoms, behaviour and personal characteristics at least one year earlier.
Adult↗
Subtyping hepatitis C virus.
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Hepacivirus↗
The relative efficiency of the Hardy-Weinberg equilibrium-likelihood and the conditional on parental genotype-likelihood methods for candidate-gene association studies.
Selecting a control group that is perfectly matched for ethnic ancestry with a group of affected individuals is a major problem in studying the association of a candidate gene with a disease. This problem can be avoided by a design that uses parental data in place of nonrelated controls. Schaid and Sommer presented two new methods for the statistical analysis using this approach: (1) a likelihood method (Hardy-Weinberg equilibrium [HWE] method), which rests on the assumption that HWE holds, and (2) a conditional likelihood method (conditional on parental genotype [CPG] method) appropriate when HWE is absent. Schaid and Sommer claimed that the CPG method can be more efficient than the HWE method, even when equilibrium holds. It can be shown, however that in the equilibrium situation the HWE method is always more efficient than the CPG method. For a dominant disease, the differences are slim. But for a recessive disease, the CPG method requires a much larger sample size to achieve a prescribed power than the HWE method. Additionally, we show how the relative risks for the various candidate-gene genotypes can be estimated without relying on iterative methods. For the CPG method, we represent an asymptotic power approximation that is sufficiently precise for planning the sample size of an association study.
Genetic Diseases, Inborn↗
Association analysis of the dopamine D2 receptor gene in Tourette's syndrome using the haplotype relative risk method.
Comings et al. [1991: JAMA 266: 1793-1800] have recently reported a highly significant association between Tourette's syndrome (TS) and a restriction fragment length polymorphism (RFLP) of the dopamine D2 receptor gene (DRD2) locus. The A1 allele of the DRD2 Taq I RFLP was present in 45% of the Tourette patients compared with 25% of controls. We tried to replicate this finding by using the haplotype relative risk (HRR) method for association analysis. This method overcomes a major problem of conventional case-control studies, where undetected ethnic differences between patients and controls may result in a false-positive finding, by using parental alleles not inherited to the proband as control alleles. Sixty-one nuclear families encompassing an affected child and parents were typed for the DRD2 Taq I polymorphism. No significant differences in DRD2 A1 allele frequency were observed between TS probands, subpopulations of probands classified according to tic severity, or parental control alleles. Our data do not support the hypothesis that the DRD2 locus may act as a modifying gene in the expression of the disorder in TS probands.
Adolescent↗
Familial adenomatous polyposis: mutation at codon 1309 and early onset of colon cancer.
The clinical course of familial adenomatous polyposis (FAP) varies considerably between patients. Prediction of the severity of the disease is important in the interest of effective cancer prevention. We examined whether age at diagnosis of FAP due to gastrointestinal symptoms and age at death due to colorectal cancer are related to the site of mutation in the responsible gene. 225 families with FAP were screened for mutations. The deletion of 5 base pairs at codon 1309 within exon 15 (known to be the most common mutation) was identified in 20 families; other mutations within exons 7-15 were found in 49 families. In patients with the 5 base-pair deletion at codon 1309, gastrointestinal symptoms and death from colorectal cancer occurred about 10 years earlier than in patients with other mutations. The 1309 mutation leads to development of colonic polyps at a younger age, thus giving rise to an earlier malignant transformation. This relationship should be taken into account in strategies for preventing cancer in patients with FAP.
Adenomatous Polyposis Coli↗
Large linkage analysis in 100 families with autosomal recessive spinal muscular atrophy (SMA) and 11 CEPH families using 15 polymorphic loci in the region 5q11.2-q13.3.
The autosomal recessive proximal spinal muscular atrophy (SMA) gene was mapped to the region 5q11.2-q13.3 in 1990. Here, we present a large genetic linkage study of 100 SMA families and 11 CEPH families using 14 polymorphic simple sequence repeats (SSRs) and one RFLP in the region 5q11.2-q13.3. The genetic interval between the closest SMA flanking loci D5S435 and D5S557 comprises 1 cM at zmax = 27.94. Two recombinants were identified between the SMA gene and the closest telomeric marker D5S557 (theta = 0.02 at zmax = 8.63). The first places the SMA gene centromeric to this marker; the second suggests a double recombinant at D5S557, which is very unlikely. More likely explanations are discussed in the paper. No recombinant was found between D5S435 and the SMA gene (theta = 0.00 at zmax = 25.36). We localized a recently described polymorphic marker, D5S351 (Hudson et al., 1992), close to the SMA (theta = 0.00 at zmax = 19.01) and the 3'MAP1B gene (theta = 0.01 at zmax = 38.76). Due to its high PIC value of 0.70, it represents a very useful marker for prenatal diagnosis. In addition, we developed a new reverse primer for the nearest centromeric locus D5S435 (Soares et al., 1993), a useful marker for prenatal diagnosis, which has been very difficult to amplify in the past. Three of the markers presented here are newly developed polymorphic SSRs (one tetranucleotide repeat, D5S507/W15CATT, and two dinucleotide repeats, D5S544/C88.2GT and D5S682/C88.3GT). These markers are too far from the SMA gene to be relevant for cloning; nevertheless, as part of the human genome project, they are contributing to the fine genetic mapping of the region 5q11.2-q13.3. The most likely order of the loci based on two-point and multipoint linkage analyses as well as on specific recombination events and physical mapping studies is D5S76-D5S507- D5S6-D5S125-D5S680-D5S435-SMA-D5S557- D5S351-5'MAP1B-3'MAP1B-JK53CA1/2-(D5S127- D5S39)-(D5S544-D5S682). In general, the genetic distances obtained from the SMA and CEPH families are comparable.
Base Sequence↗
The costs of accommodation and care. Community provision for former long-stay psychiatric hospital patients.
The development of community services to replace two long-stay psychiatric hospitals in the North East Thames Health Authority region of the UK has been the subject of a research programme since 1985. The economic evaluation is conducted by the Personal Social Services Research Unit; research results relating to the first five cohorts of hospital leavers are reported in this paper. When followed up 1 year after discharge, almost half of the sample were living in highly supported residential care units, most of which were managed by district health authorities. More than 40 services provided outside the accommodation facility were used by clients and, although contact with certain professionals remained constant, some changes in service use over time were marked. The average total cost of community care for this group was 493 pounds per week (1992-93 prices), accommodation facility costs comprising approximately 85% of the total. In the new service configuration, district health authorities fund half of the costs of supporting the hospital leavers, 50% less than when they funded long-stay hospital placements. The rest of the funding burden is borne by a range of agencies, resulting in pressure on budgets and staff case loads.
Adult↗
Mapping of the gene for autosomal recessive polycystic kidney disease (ARPKD) to chromosome 6p21-cen.
Autosomal recessive polycystic kidney disease (ARPKD) is one of the major hereditary nephropathies in children predominantly presenting in early childhood. The clinical picture is variable but there is a fatal outcome in many cases. We have performed linkage analysis in 16 ARPKD families and localized the ARPKD gene to chromosomal region 6p21-cen with no evidence for genetic heterogeneity among different clinical phenotypes. Linkage was confirmed using six adjacent microsatellite markers and the highest lod score of 7.42 was obtained with D6S272 at theta = 0.00. Our findings should lead to more accurate forms of prenatal diagnosis than those currently available using ultrasound.
Base Sequence↗
Service use and costs of home-based versus hospital-based care for people with serious mental illness.
BACKGROUND: The Daily Living Programme (DLP) offered problem-oriented, home-based care for people aged 17-64 with severe mental illness facing emergency admission to the Bethlem-Maudsley Hospital. The multidisciplinary DLP team acted as direct provider and link with other services. Each patient had a key worker. Cost-effectiveness was assessed. METHOD: The comprehensive costs of DLP and standard in-patient care were compared within a randomised controlled trial. Cost measures ranged over all service inputs and living expenses. The costs of informal care and lost employment were also considered. Assessments of service use, costs and outcomes were conducted at referral, 4, 11 and 20 months. RESULTS: The DLP was significantly less costly than standard treatment in both short and medium term (P = 0.000). Cost savings accrued almost exclusively to the NHS, with no other agency's costs being higher. CONCLUSIONS: Coupled with mildly encouraging outcome results over the 20 month period, the DLP was clearly cost-effective in this medium term.
Absenteeism↗
Community psychiatric nurse teams: cost-effectiveness of intensive support versus generic care.
BACKGROUND: Part of the community psychiatric nurse (CPN) service was reorganised into a community support team (CST), with staff acting as case managers. An economic evaluation ran parallel to the comparison with generic CPN care. METHOD: Eighty-two clients were randomly allocated to experimental and control groups. Costs were comprehensively measured over a pre-referral period (three months), and then at 6, 12, and 18 months. RESULTS: The economic evaluation found a cost difference between the groups. Generic group costs averaged 89 pounds per patient per week more than CST group costs. The difference was only significant for the first six months. Changes in the burden of cost across agencies were observed. CONCLUSIONS: Although CPN inputs and costs were higher for the CST group, there was a significant short-term reduction in total cost. Beyond the short term, the CST did not confer cost or cost-effectiveness advantages.
Adult↗
Acute care gerontological nursing: its time has come.
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Acute Disease↗
Two-locus disease models with two marker loci: the power of affected-sib-pair tests.
Recently, Schork et al. found that two-trait-locus, two-marker-locus (parametric) linkage analysis can provide substantially more linkage information than can standard one-trait-locus, one-marker-locus methods. However, because of the increased burden of computation, Schork et al. do not expect that their approach will be applied in an initial genome scan. Further, the specification of a suitable two-locus segregation model can be crucial. Affected-sibpair tests are computationally simple and do not require an explicit specification of the disease model. In the past, however, these tests mainly have been applied to data with a single marker locus. Here, we consider sib-pair tests that make it possible to analyze simultaneously two marker loci. The power of these tests is investigated for different (epistatic and heterogeneous) two-trait-locus models, each trait locus being linked to one of the marker loci. We compare these tests both with the test that is optimal for a certain model and with the strategy that analyzes each marker locus separately. The results indicate that a straightforward extension of the well-known mean test for two marker loci can be much more powerful than single-marker-locus analysis and that is power is only slightly inferior to the power of the optimal test.
Alleles↗
The effect of misspecifying allele frequencies in incompletely typed families.
To examine the effect of a misspecified marker allele frequency, the segregation of a marker unlinked to Alzheimer's disease was simulated for the typed members of the GAW8-FAD4 pedigree. Lod scores were calculated for different assumed marker allele frequencies. The results show that a misspecification of marker frequency can lead to spuriously high lod scores. The affecteds-only method for linkage analysis is even more sensitive in regard to marker frequency misspecification. Therefore, we recommend estimation of marker allele frequencies from the actual family data. The simple estimator we considered in this paper seems to be sufficient.
Alleles↗
Reduced list costings: examination of an informed short cut in mental health research.
The demands for cost information in health services are many and various but the supply of such information is less than might be expected and is compounded by the expense of undertaking costs research. This paper examines a short cut to mental health research which, if certain rules and conventions are obeyed, can still produce valid costs data. By distilling evidence from previous research a reduced list of services is identified which accounts for the greater part of the total costs of care packages. By concentrating on these key services, 94 per cent of the total costs of care were predicted for discharged long-stay patients and no less than 91 per cent for people supported by community psychiatric nurses. The results suggest that this reduced list method can work well where the aim is to obtain broad orders of magnitude for the costs of care. By reducing the resources required for research, the approach could expand the current costs information base and move towards meeting the pressing practice demands for costs data.
Combined Modality Therapy↗
Fine mapping and narrowing of the genetic interval of the spinal muscular atrophy region by linkage studies.
The gene for autosomal recessive proximal spinal muscular atrophy (SMA) has recently been mapped to chromosome 5q12.2-q13, within a genetic distance of about 6 cM, and is proximally flanked by the locus D5S6 and distally by D5S112. Here, we report linkage analyses in 64 SMA families with nine polymorphic markers closely linked to the SMA gene, which allowed us to narrow the SMA region to about 4 cM and to define a new proximal genetic border by the locus D5S125 (EF(TG/AG)n. Based on haplotype analysis and specific recombination events, the following order of the loci was determined: 5cen-D5S76-D5S6-D5S125-SMA-(5'MAP-1B-3'MAP- 1B)/D5S112-JK53CA1/2-(D5S39-D5S127)-5qter. The location of the SMA gene between D5S125 and MAP-1B is further supported by multipoint linkage analysis.
Cell Line, Transformed↗