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M Knapp

Publications and source records attributed to M Knapp.

At least 37 records · Page 2Linked to original sources
PubMed1998

Support for a chromosome 18p locus conferring susceptibility to functional psychoses in families with schizophrenia, by association and linkage analysis.

The action of antipsychotic drugs on dopamine receptors suggests that dopaminergic signal transmission may play a role in the development of schizophrenia. We tested eight candidate genes (coding for dopamine receptors, the dopamine transporter, and G-proteins) in 59 families from Germany and Israel, for association. A P value of .00055 (.0044 when corrected for the no. of markers tested) was obtained for the intronic CA-repeat marker G-olfalpha on chromosome 18p. The value decreased to .000088 (.0007) when nine sibs with recurrent unipolar depressive disorder were included. Linkage analysis using SSLP markers densely spaced around G-olfalpha yielded a maximum two-point LOD score of 3.1 for a marker 0.5 cM distal to G-olfalpha. Multipoint analysis under the assumption of heterogeneity supported this linkage-whether the affected pheotype was defined narrowly or broadly-as did nonparametric linkage (NPL). In 12 families with exclusively maternal transmission of the disease, the NPL value also supported linkage to this marker. In order to test for association/linkage disequilibrium in the presence of linkage, the sample was restricted to independent offspring. When this sample was combined with 65 additional simplex families (each of them comprising one schizophrenic offspring and his or her parents), the 124-bp allele of G-olfalpha was transmitted 47 times and was not transmitted 21 times (P=.009). These results suggest the existence, on chromosome 18p, of a potential susceptibility locus for functional psychoses.

Chromosomes, Human, Pair 18↗
PubMed1998

Cost-effectiveness evaluation of compliance therapy for people with psychosis.

BACKGROUND: Non-compliance rates with antipsychotic medication can be high, and the personal and societal costs are considerable. A new psychological intervention, compliance therapy seeks to improve compliance and patient outcomes and reduce treatment costs. METHOD: A randomised controlled study examined the cost-effectiveness of compliance therapy compared to non-specific counselling over 18 months for 74 people with psychosis admitted as inpatients at the Maudsley Hospital. Bivariate and multivariate analyses were conducted to test for differences and to explore inter-patient cost variations. RESULTS: Compliance therapy is more effective and is no more expensive. Consequently, compliance therapy is more cost-effective than non-specific counselling at six, 12 and 18 months. CONCLUSIONS: There are compliance, outcome and cost-effectiveness arguments in favour of compliance therapy in preference to non-specific counselling.

Adult↗
PubMed1998

Home-based versus hospital-based care for serious mental illness. Controlled cost-effectiveness study over four years.

BACKGROUND: The Daily Living Programme (DLP) offered intensive home-based care with problem-centred case management for seriously mentally ill people facing crisis admission to the Maudsley Hospital, London. The cost-effectiveness of the DLP was examined over four years. METHOD: A randomised controlled study examined cost-effectiveness of DLP versus standard in/out-patient hospital care over 20 months, followed by a randomised controlled withdrawal of half the DLP patients into standard care. Three patient groups were compared over 45 months: DLP throughout the period, DLP for 20 months followed by standard care, and standard care throughout. Bivariate and multivariate analyses were conducted (the latter to standardise for possible inter-sample differences stemming from sample attrition and to explore sources of within-sample variation). RESULTS: The DLP was more cost-effective than control care over months 1-20, and also over the full 45-month period, but the difference between groups may have disappeared by the end of month 45. CONCLUSIONS: The reduction of the cost-effectiveness advantage for home-based care was perhaps partly due to the attenuation of DLP care, although sample attrition left some comparisons under-powered.

Adolescent↗
PubMed1998

Economic burden of drug dependency. Social costs incurred by drug users at intake to the National Treatment Outcome Research Study.

BACKGROUND: The use of illegal drugs is seen as a major social problem. The social costs can be high. METHODS: Self-report data from interviews at intake to the National Treatment Outcome Research Study (NTORS) for 1075 drug users and cost data from various sources were used to estimate criminal behaviour and health and addiction service costs for a 12-month period. Multivariate statistical analysis was used to analyse cost variations. RESULTS: Total costs for one year for the drug users amounted to over 12 million Pounds, the majority attributable to self-reported criminal behaviour. Social costs were positively related to a variety of factors including instability in living circumstances, amount of heroin used and whether or not drugs were taken intravenously. CONCLUSIONS: The study clearly demonstrates the economic and social burden associated with heavy drug users and highlights the need for further investigations into the costs and benefits of policies that can reduce these social costs.

Age Factors↗
PubMed1997

Evidence for DYT7 being a common cause of cervical dystonia (torticollis) in Central Europe.

Adult-onset focal idiopathic torsion dystonias (AFITD), such as torticollis, have a prevalence similar to that of multiple sclerosis and usually seem sporadic. Only recently has one large AFITD pedigree "K" with autosomal dominant inheritance and reduced penetrance from Northwest Germany provided the opportunity to identify a gene locus on chromosome 18p. We have now tested the relevance of this DYT7 gene locus in a collective of 18 nuclear AFITD families from Central Europe who were genotyped with chromosome 18p microsatellites. In three families, the affected relatives did not share a chromosome 18p haplotype, suggesting locus heterogeneity in AFITD. In the remaining 15 families, significant allelic association was observed for marker D18S1098. This result suggests that DYT7 is a common cause for AFITD at least in Central Europe, that many patients are descended from a common ancestor, and that the DYT7 gene is mapped in a 4.4 centimorgan subregion of chromosome 18p.

Adolescent↗
PubMed1997

Human 5-HT5A receptor gene: systematic screening for DNA sequence variation and linkage mapping on chromosome 7q34-q36 using a polymorphism in the 5' untranslated region.

Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter that mediates a wide range of sensory, motor, and cortical functions by activating multiple 5-HT receptor subtypes. In the present study we performed a systematic mutation scan of the complete coding region of the 5-HT5A receptor to explore its variability in the general population. Investigating 46 unrelated healthy subjects by single-strand conformation analysis no sequence changes of likely functional relevance were observed. The detection of a frequent G-->C substitution at position -19 was used for fine scale linkage mapping of the 5-HT5A gene. Employing a polymerase-chain-reaction based assay we genotyped 7 CEPH families (Centre d'Etude du Polymorphisme Humaine) and mapped the receptor to genetic markers on chromosome 7q34-q36.

Chromosome Mapping↗
PubMed1997

The "possible triangle" test for extreme discordant sib pairs.

For the analysis of quantitative traits in nuclear families, extreme discordant sib pairs proved to be more powerful than unselected sib pairs. Here, we present a test that makes use of selected pairs and, in addition, restricts the parameters of the identical-by-descent distribution analogously to the "possible triangle" for affected sib pairs. In the Problem 2A data, extreme discordant sib pairs are selected. The analysis allowed the detection of most simulated major genes.

Chromosome Mapping↗
PubMed1997

Sporadic focal dystonia in northwest Germany: molecular basis on chromosome 18p.

Idiopathic focal dystonia (IFD) is the most common form of idiopathic torsion dystonia in the Euroamerican population, with a prevalence of about 30 per 100,000. Although most patients claim a negative family history, we recently mapped this syndrome to chromosome 18p as an autosomal dominant trait in Family K from Northwest Germany. We now have investigated sporadic patients with IFD from the same geographic area both clinically and molecularly with chromosome 18p markers. The data indicate that most of these apparently sporadic patients have inherited the same mutation as Family K from a common ancestor and, in fact, owe their disease to autosomal dominant inheritance at low penetrance. The data also indicate that this dystonia mutation (DYT7) is the predominant cause of IFD, at least in this area of Northwest Germany, and that its location can be narrowed from a 30- to a 6-centimorgan region close to marker D18S1098.

Chromosomes, Human, Pair 18↗
PubMed1997

QALYs and mental health care.

Quality-adjusted life year measures (QALYs) have been fervently debated by researchers and decision makers concerned with resource allocation in the health care sector. They have been heralded as important aids to planning and priority setting, but also criticised on technical and ethical grounds. This paper examines these arguments with special reference to mental health care, the intention being to highlight the strengths and shortcomings of QALYs in this context. Issues pertinent to the application of QALYs in health care evaluation more generally are also reviewed. Whilst the rationale and underlying principles of the utility measurement approach are sound, the generic QALY as it is currently constructed represents an insensitive measure of the outcomes of mental health care. In the event of an increasingly QALY-driven priority-setting environment, however, abandonment of QALYs runs the risk of inappropriately marginalising people with mental illnesses in the resource allocation process. This opens up the possibility of developing a mental-health specific measure of utility that, in combination with cost data, would provide useful and appropriate summary information across treatments and programmes of mental health care.

Cost-Benefit Analysis↗
PubMed1997

The cost consequences of changing the hospital-community balance: the mental health residential care study.

BACKGROUND: Altering the balance of provision between hospital and community care is a key and often contentious component of mental health care policy in many countries. Implementation of this policy in the UK has been slowed by the apparent shortage of suitable community accommodation for people with long-term needs for care and support. Among the consequences could be the silting up of hospital beds by people who could be supported more appropriately elsewhere, in turn denying in-patient treatment to people with acute psychiatric problems and unnecessarily pushing up health service expenditure. METHODS: Using data collected in a survey of hospital and residential accommodation services and their residents in eight areas of England and Wales, the cost components of today's balance of care were explored. Comprehensive costs were calculated and their associations with resident characteristics examined using multiple regression analyses. RESULTS: On a like-with-like basis, the costs of hospital in-patient treatment for inappropriately placed patients greatly exceeded the costs of community-based care. CONCLUSION: Further reduction of hospital beds, however, is not the panacea for an appropriate balance of mental health care, given the unknown but potentially considerable extent of unmet demand, as well as the impact of previous in-patient bed reductions apparent in the services surveyed. Rather, service providers and purchasers should focus on developing community-based care (including increased provision of 24-hour nursed beds) by ensuring that resources released through earlier closure programmes have been redeployed for their intended use and by accessing additional pump-priming or bridging resources.

Chronic Disease↗
PubMed1997

The cost-effectiveness of community care for adults with learning disabilities leaving long-stay hospital in Northern Ireland.

Among the many questions concerning the replacement of long-stay hospital services with community-based care are those of cost and cost-effectiveness. Is community care more expensive than hospital care? Are levels of expenditure associated with clients' needs and changes in their well-being? By following a cohort of people discharged from seven long-stay hospitals in Northern Ireland, this wide-ranging evaluation was able to address such cost-related questions. Although nearly three-quarters of the sample were living in private sector residential or nursing homes, a six-fold variation in the total costs of support was found. However, at the mean, community care was less expensive than hospital care. For only ten people in our sample of 192 clients did the costs of community care exceed the average cost of long-stay inpatient care. Multivariate analysis revealed that the costs of community care 'packages' were linked to some client needs, but higher spending was not unequivocally associated with better client outcomes. Care in the community is reasonably cost-effective in Northern Ireland when compared with long-term hospital care. However, there is a case for increasing expenditure on community care for people with learning difficulties, to increase use of services provided outside the accommodation and enhance staffing arrangements within the accommodation facilities. Distributing resources appropriately and targeting resources on priority needs through coordination will hep to continue to improve clients' quality of life.

Community Health Services↗
PubMed1997

Economic evaluations and interventions for children and adolescents with mental health problems.

Economic evaluations of interventions for children and adolescents with mental health problems are comparatively rare, although the growing need for them is now quite widely recognized. This review paper first explains how demands for such evaluations have built up, and for what reasons, and then considers the response from evaluators. The various modes of economic evaluation are introduced and illustrated. Previous and current research is discussed by reference to five generic research questions commonly addressed in the wider health economics field: What treatment should be provided? When? Where? To whom? How? The review concludes with recommendations as to how economic evaluations should be taken forward in this increasingly important area of intervention.

Adolescent↗
PubMed1997

The use of a case register to evaluate the costs of psychiatric care.

The aim of this study was to show the usefulness of adding cost information to a routine data collection provided by a case register for analysing the association between patients' characteristics and the direct costs of the psychiatric care actually provided. All patients (n = 706) who in 1992 had at least one contact with services which report to the South Verona psychiatric case register and who received an ICD-10 diagnosis were included in the study. The costs of specialist psychiatric care provided during the 365 days following the first contact in 1992 were calculated using a unit cost list. A bespoke software, linked to the case register, was designed to produce the individual information on costs directly. For each patient, costs were categorized as in-patient costs, sheltered accommodation costs, day-care costs, out-patient costs and community costs. All costs, grouped by service type, were found to differ significantly (P < 0.01) between diagnostic groups (affective disorders, neurotic and somatoform disorders, schizophrenia and related disorders, and other diagnoses). The multivariate analyses showed that costs are significantly higher for patients with a diagnosis of schizophrenia and related disorders than for patients belonging to the other diagnostic groups. However, only 6% of the variation could be explained by diagnostic group alone. On the other hand, between 40 and 50% of the costs of mental health care was predicted by patients' personal characteristics and other measures recorded on the case register. The results of the present study show that, where service use is monitored regularly, the base from which decisions on community provision and placement are made can be informed by careful analysis of routinely or easily available data on direct costs.

Adolescent↗
PubMed1997

Characterization of a lipopeptide-resistant strain of Candida albicans.

Lipopeptides are antifungal agents that inhibit cell wall beta-(1,3)-glucan biosynthesis in fungal organisms. A mutant resistant to lipopeptides was generated by UV mutagenesis and characterized. The Candida albicans mutant (LP3-1) was stable and showed resistance specificity to a broad range of lipopeptides and certain glycolipid inhibitors. Other antifungal agents with diverse modes of action had a normal minimum inhibitory concentration profile for LP3-1 compared with the wild-type strain (CCH 442). In the in vitro beta-(1,3)-glucan synthase assay, both the lipopeptides and papulacandin-related agents had considerably higher 50% inhibitory concentration values in the LP3-1 strain than in the wild-type strain. In reconstitution assays, the resistance factor was associated with the integral membrane pellet rather than the peripheral GTP-binding protein. The LP3-1 strain had a membrane lipid profile similar to that of the parent strain and was virulent in a murine model of systemic candidiasis. Taken together, these results indicate that the resistance factor is associated with the integral membrane component of beta-(1,3)-glucan synthase. Lipopeptides are common antifungal agents encountered during screening of natural products. The LP3-1 strain was resistant to natural product extracts known to contain various lipopeptides. Thus, LP3-1 can be used in a dereplication assay.

Animals↗
PubMed1997

Costs of schizophrenia.

BACKGROUND: Schizophrenia is a common and burdensome illness, with implications not only for the health service but for a host of other care agencies--public and private--as well as for patients, families and the wider society. METHOD: The paper reviews available UK evidence on the cost of schizophrenia (broadly defined) and on the cost-effectiveness of treatment options and alternative care arrangements. New evidence potentially alters our view of the costs of this illness. RESULTS: Aggregating the identifiable direct and indirect costs of schizophrenia for England suggests an annual cost of 2.6 billion pounds, but even this sum omits some indirect impacts which cannot currently be costed. Just over half the identified total is accounted for by the direct costs falling to the NHS, local authorities, charities and the criminal justice system. In helping to tackle this cost burden, there is now a body of evidence on cost-effective community care arrangements, antipsychotic drugs and psychological interventions. CONCLUSIONS: Although the costs of schizophrenia are considerable, there are treatments and care arrangements which can reduce this aggregate burden while maintaining or improving effectiveness.

Antipsychotic Agents↗
PubMed1996

Systematic search for variation in the human norepinephrine transporter gene: identification of five naturally occurring missense mutations and study of association with major psychiatric disorders.

The complete coding region of the norepinephrine transporter (NET) gene was systematically screened for genetic variants in 137 unrelated individuals (including 46 probands with bipolar affective disorder and 45 schizophrenic probands, as well as 46 blood donors) using single-strand conformation analysis. We identified 13 DNA sequence variants, among them five missense substitutions. The missense substitutions Val69Ile, Thr99Ile, Val245Ile, Val449Ile, and Gly478Ser are located at putative transmembrane domains (TMD) 1, 2, 4, 9, and 10, respectively. The Thr99Ile substitution is at the 5th position of the putative leucine-zipper in TMD2. In a case-control study distribution of missense substitutions was found to be similar in 103 patients with bipolar affective disorder, in 228 schizophrenia patients and in 187 controls, indicating that presence of these variants is not causally related to major psychiatric diseases. The detection of a highly polymorphic silent 1287G/A polymorphism was utilized to demonstrate biallelic expression of the NET in adult human brain.

Adult↗