Correction: Examining the construct and known-group validity of a composite endpoint for The Older Persons and Informal Caregivers Survey Minimum Data Set (TOPICS-MDS); A large-scale data sharing initiative.

[This corrects the article DOI: 10.1371/journal.pone.0173081.].

Examining the construct and known-group validity of a composite endpoint for The Older Persons and Informal Caregivers Survey Minimum Data Set (TOPICS-MDS); A large-scale data sharing initiative.

BACKGROUND: Preference-weighted multi-faceted endpoints have the potential to facilitate comparative effectiveness research that incorporates patient preferences. The Older Persons and Informal Caregivers Survey-Composite endpoint (TOPICS-CEP) is potentially a valuable outcome measure for evaluating interventions in geriatric care as it combines multiple outcomes relevant to older persons in a single metric. The objective of this study was to validate TOPICS-CEP across different study settings (general population, primary care and hospital). METHODS: Data were extracted from TOPICS Minimum Dataset (MDS), a pooled public-access national database with information on older persons throughout the Netherlands. Data of 17,603 older persons were used. Meta-correlations were performed between TOPICS-CEP indexed scores, EuroQol5-D utility scores and Cantril's ladder life satisfaction scores. Mixed linear regression analyses were performed to compare TOPICS-CEP indexed scores between known groups, e.g. persons with versus without depression. RESULTS: In the complete sample and when stratified by study setting TOPICS-CEP and Cantril's ladder were moderately correlated, whereas TOPICS-CEP and EQ-5D were highly correlated. Higher mean TOPICS-CEP scores were found in persons who were: married, lived independently and had an education at university level. Moreover, higher mean TOPICS-CEP scores were found in persons without dementia, depression, and dizziness with falls, respectively. Similar results were found when stratified by subgroup. CONCLUSION: This study supports that TOPICS-CEP is a robust measure which can potentially be used in broad settings to identify the effect of intervention or of prevention in elderly care.

Predictive validity of a frailty measure (GFI) and a case complexity measure (IM-E-SA) on healthcare costs in an elderly population.

OBJECTIVES: Measures of frailty (Groningen Frailty Indicator, GFI) and case complexity (INTERMED for the Elderly, IM-E-SA) may assist healthcare professionals to allocate healthcare resources. Both instruments have been evaluated with good psychometric properties. Limited evidence has been published about their predictive validity. Thus, our aim is to evaluate the predictive validity of both instruments on healthcare costs. METHODS: Multivariate linear regression models were developed to estimate associations between the predictors frailty (GFI) and/or case complexity (IM-E-SA) and the healthcare costs (in € log transformed) in the following year. All models were adjusted for demographics and the presence of morbidity. RESULTS: In the multivariate regression analyses the continuous scores of the GFI and IM-E-SA remained significant predictors for total healthcare costs. Adjusted ßs for GFI and IM-E-SA were respectively 0.14 (95% CI 0.10-0.18) and 0.06 (95% CI 0.04-0.07). The corresponding explained variance (R(2)) for both models was 0.40. Frailty remained a significant predictor of long-term care costs (adjusted ß 0.13 [95% CI 0.09-0.16]), while case complexity was a significant predictor of curative care costs (adjusted ß 0.03 [95% CI 0.02-0.05]). CONCLUSIONS: The GFI and IM-E-SA both accurately predict total healthcare costs in the following year.

The influence of age on health valuations: the older olds prefer functional independence while the younger olds prefer less morbidity.

BACKGROUND: To assess the effectiveness of geriatric interventions, The Older Persons and Informal Caregivers Survey - Composite Endpoint (TOPICS-CEP) has been developed based on health valuations of older persons and informal caregivers. This study explored the influence of the raters' age on the preference weights of TOPICS-CEP's components. METHODS: A vignette study was conducted with 200 raters (mean age ± standard deviation: 72.5±11.8 years; 66.5% female). Profiles of older persons were used to obtain the preference weights for all TOPICS-CEP components: morbidity, functional limitations, emotional well-being, pain experience, cognitive functioning, social functioning, self-perceived health, and self-perceived quality of life. The raters assessed the general wellbeing of these vignettes on a 0-10 scale. Mixed linear regression analysis with interaction terms was used to explore the effects of raters' age on the preference weights. RESULTS: Interaction effects between age and the TOPICS-CEP components showed that older raters gave significantly (P<0.05) more weight to functional limitations and social functioning and less to morbidities and pain experience, compared to younger raters. CONCLUSION: Researchers examining effectiveness in elderly care need to consider the discrepancies between health valuations of younger olds and older olds when selecting or establishing outcome measures. In clinical decision making, health care professionals need to be aware of this discrepancy as well. For this reason we highly recommend shared decision making in geriatric care.

Comparing the health state preferences of older persons, informal caregivers and healthcare professionals: a vignette study.

BACKGROUND: The Older Persons and Informal Caregivers Survey-Minimum Dataset (TOPICS-MDS) collects uniform information from research projects funded under the Dutch National Care for the Elderly Programme. To compare the effectiveness of these projects a preference-weighted outcome measure that combined multidimensional TOPICS-MDS outcomes into a composite endpoint (TOPICS-CEP) was developed based on the health state preferences of older persons and informal caregivers. OBJECTIVES: To derive preference weights for TOPICS-CEP's components based on health state preferences of healthcare professionals and to investigate whether these weights differ between disciplines and differ from those of older persons and informal caregivers. MATERIALS AND METHODS: Vignette studies were conducted. Participants assessed the general wellbeing of older persons described in vignettes on a scale (0-10). Mixed linear analyses were used to obtain and compare the preference weights of the eight TOPICS-CEP components: morbidities, functional limitations, emotional wellbeing, pain experience, cognitive problems, social functioning, self-perceived health, and self-perceived quality of life (QOL). RESULTS: Overall, 330 healthcare professionals, 124 older persons and 76 informal caregivers participated. The preference weights were not significantly different between disciplines. However, the professionals' preference weights differed significantly from those of older persons and informal caregivers. Morbidities and functional limitations were given more weight by older persons and informal caregivers than by healthcare professionals [difference between preference weights: 0.12 and 0.07] while the opposite was true for pain experience, social functioning, and self-perceived QOL [difference between preference weights: 0.13, 0.15 and 0.26]. CONCLUSION: It is important to recognize the discrepancies between the health state preferences of various stakeholders to (1) correctly interpret results when studying the effectiveness of interventions in elderly care and (2) establish appropriate healthcare policies. Furthermore, we should strive to include older persons in our decision making process through a shared decision making approach.

[Frailty, disability and multi-morbidity: the relationship with quality of life and healthcare costs in elderly people]. / Kwetsbaarheid, dagelijkse beperkingen en ziektelast: samenhang met kwaliteit van leven en zorggebruik bij ouderen.

OBJECTIVE: To assess the independent and combined impact of frailty, multi-morbidity, and activities of daily living (ADL) limitations on self-reported quality of life and healthcare costs in elderly people. DESIGN: Cross-sectional, descriptive study. METHOD: Data came from The Older Persons and Informal Caregivers Minimum DataSet (TOPICS-MDS), a pooled dataset with information from 41 projects across the Netherlands from the Dutch national care for the Elderly programme. Frailty, multi-morbidity and ADL limitations, and the interactions between these domains, were used as predictors in regression analyses with quality of life and healthcare costs as outcome measures. Analyses were stratified by living situation (independent or care home). Directionality and magnitude of associations were assessed using linear mixed models. RESULTS: A total of 11,093 elderly people were interviewed. A substantial proportion of elderly people living independently reported frailty, multi-morbidity, and/or ADL limitations (56.4%, 88.3% and 41.4%, respectively), as did elderly people living in a care home (88.7%, 89.2% and 77,3%, respectively). One-third of elderly people living at home (31.9%) reported all three conditions compared with two-thirds of elderly people living in a care home (68.3%). In the multivariable analysis, frailty had a strong impact on outcomes independently of multi-morbidity and ADL limitations. Elderly people experiencing problems across all three domains reported the poorest quality-of-life scores and the highest healthcare costs, irrespective of their living situation. CONCLUSION: Frailty, multi-morbidity and ADL limitations are complementary measurements, which together provide a more holistic understanding of health status in elderly people. A multi-dimensional approach is important in mapping the complex relationships between these measurements on the one hand and the quality of life and healthcare costs on the other.

Self-reported fatigue and physical function in late mid-life.

OBJECTIVE: To determine the association between the 5 subscales of the Multidimensional Fatigue Inventory (MFI-20) and physical function in late mid-life. DESIGN: Cross-sectional study. SUBJECTS: A population-based sample of adults who participated in the Copenhagen Aging and Midlife Biobank population cohort (n = 4,964; age 49-63 years). METHODS: Self-reported fatigue was measured using the MFI-20 comprising: general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. Handgrip strength and chair rise tests were used as measures of physical function. Multiple logistic regression analyses were used to determine the associations between handgrip strength and the chair rise test with the MFI-20 subscales, adjusted for potential confounders. RESULTS: After adjustments for potential confounders, handgrip strength was associated with physical fatigue (adjusted odds ratio (OR) 0.75 (95% confidence interval (CI) 0.66-0.86); p ≤ 0.001) and reduced motivation (adjusted OR 0.85 (95% CI 0.75-0.96); p ≤ 0.05), but not with the other subscales. After these adjustments, the chair rise test was associated with physical fatigue (adjusted OR 0.61 (0.53-0.69); p ≤ 0.001), general fatigue (adjusted OR 0.72 (0.62-0.84); p ≤ 0.001), reduced activity (adjusted OR 0.79 (0.70-0.90); p ≤ 0.001) and reduced motivation (adjusted OR 0.84 (0.74-0.95); p ≤ 0.01), but not with mental fatigue. Subgroup analyses for sex did not show statistically significant different associations between physical function and fatigue. CONCLUSION: The present study supports the physiological basis of 4 subscales of the MFI-20. The association between fatigue and function was independent of gender.

Establishing a composite endpoint for measuring the effectiveness of geriatric interventions based on older persons' and informal caregivers' preference weights: a vignette study.

BACKGROUND: The Older Persons and Informal Caregivers Survey Minimal Dataset's (TOPICS-MDS) questionnaire which measures relevant outcomes for elderly people was successfully incorporated into over 60 research projects of the Dutch National Care for the Elderly Programme. A composite endpoint (CEP) for this instrument would be helpful to compare effectiveness of the various intervention projects. Therefore, our aim is to establish a CEP for the TOPICS-MDS questionnaire, based on the preferences of elderly persons and informal caregivers. METHODS: A vignette study was conducted with 200 persons (124 elderly and 76 informal caregivers) as raters. The vignettes described eight TOPICS-MDS outcomes of older persons (morbidity, functional limitations, emotional well-being, pain experience, cognitive functioning, social functioning, self-perceived health and self-perceived quality of life) and the raters assessed the general well-being (GWB) of these vignette cases on a numeric rating scale (0-10). Mixed linear regression analyses were used to derive the preference weights of the TOPICS-MDS outcomes (dependent variable: GWB scores; fixed factors: the eight outcomes; unstandardized coefficients: preference weights). RESULTS: The mixed regression model that combined the eight outcomes showed that the weights varied from 0.01 for social functioning to 0.16 for self-perceived health. A model that included "informal caregiver" showed that the interactions between this variable and each of the eight outcomes were not significant (p > 0.05). CONCLUSION: A preference-weighted CEP for TOPICS-MDS questionnaire was established based on the preferences of older persons and informal caregivers. With this CEP optimal comparing the effectiveness of interventions in older persons can be realized.

The development of the Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS): a large-scale data sharing initiative.

INTRODUCTION: In 2008, the Ministry of Health, Welfare and Sport commissioned the National Care for the Elderly Programme. While numerous research projects in older persons' health care were to be conducted under this national agenda, the Programme further advocated the development of The Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS) which would be integrated into all funded research protocols. In this context, we describe TOPICS data sharing initiative (www.topics-mds.eu). MATERIALS AND METHODS: A working group drafted TOPICS-MDS prototype, which was subsequently approved by a multidisciplinary panel. Using instruments validated for older populations, information was collected on demographics, morbidity, quality of life, functional limitations, mental health, social functioning and health service utilisation. For informal caregivers, information was collected on demographics, hours of informal care and quality of life (including subjective care-related burden). RESULTS: Between 2010 and 2013, a total of 41 research projects contributed data to TOPICS-MDS, resulting in preliminary data available for 32,310 older persons and 3,940 informal caregivers. The majority of studies sampled were from primary care settings and inclusion criteria differed across studies. DISCUSSION: TOPICS-MDS is a public data repository which contains essential data to better understand health challenges experienced by older persons and informal caregivers. Such findings are relevant for countries where increasing health-related expenditure has necessitated the evaluation of contemporary health care delivery. Although open sharing of data can be difficult to achieve in practice, proactively addressing issues of data protection, conflicting data analysis requests and funding limitations during TOPICS-MDS developmental phase has fostered a data sharing culture. To date, TOPICS-MDS has been successfully incorporated into 41 research projects, thus supporting the feasibility of constructing a large (>30,000 observations), standardised dataset pooled from various study protocols with different sampling frameworks. This unique implementation strategy improves efficiency and facilitates individual-level data meta-analysis.

Development and measurement properties of the self assessment version of the INTERMED for the elderly to assess case complexity.

OBJECTIVES: The INTERMED for the Elderly Self Assessment (IM-E-SA) was developed to support health care professionals in providing demand driven elderly care. It assesses case complexity and health care needs as perceived by older adults themselves. By applying this instrument tailored care can be provided as it supports professionals in their allocation decisions. The aim was to evaluate the measurement properties of the IM-E-SA. METHODS: In this cross-sectional study 338 elderly people completed a postal questionnaire and participated in an interview. Feasibility of the IM-E-SA was assessed by determining the percentages of missing values per item. Reliability of the IM-E-SA was expressed as Cronbach's alpha. Intraclass correlation coefficients (ICCs) were calculated between the IM-E-SA and IM-E. Nonparametric tests were applied to assess if the IM-E-SA could distinguish between subgroups of elderly adults who differed on demographic characteristics and the prevalence of diseases/disorders. Convergent validity and discriminant validity were assessed using Spearman rank correlations between the IM-E-SA and IM-E, life satisfaction (Cantril's Ladder of Life), activities of daily living (Katz extended), quality of life (EQ-5D), mental health (SF-36) and prevalence of diseases/disorders. RESULTS: Percentages of missing values per IM-E-SA item ranged from 0 to 5%. Cronbach's alpha was .78. The ICC between the total scores of the IM-E-SA and the IM-E was .68. The IM-E-SA yielded statistically significant differences between subgroups (known-group validity). Correlations evaluating the convergent validity were moderate to strong (.50-.70). Those correlations assessing the discriminant validity were moderate (.38-.53). CONCLUSION: This study supports the feasibility, reliability and validity of the IM-E-SA.

Prevalence of frailty in community-dwelling older persons: a systematic review.

OBJECTIVES: To systematically compare and pool the prevalence of frailty, including prefrailty, reported in community-dwelling older people overall and according to sex, age, and definition of frailty used. DESIGN: Systematic review of the literature using the key words elderly, aged, frailty, prevalence, and epidemiology. SETTING: Cross-sectional data from community-based cohorts. PARTICIPANTS: Community-dwelling adults aged 65 and older. MEASUREMENTS: In the studies that were found, frailty and prefrailty were measured according to physical phenotype and broad phenotype, the first defining frailty as a purely physical condition and the second also including psychosocial aspects. RESULTS: Reported prevalence in the community varies enormously (range 4.0-59.1%). The overall weighted prevalence of frailty was 10.7% (95% confidence interval (CI) = 10.5-10.9; 21 studies; 61,500 participants). The weighted prevalence was 9.9% for physical frailty (95% CI = 9.6-10.2; 15 studies; 44,894 participants) and 13.6% for the broad phenotype of frailty (95% CI = 13.2-14.0; 8 studies; 24,072 participants) (chi-square (χ(2) ) = 217.7, degrees of freedom (df)=1, P < .001). Prevalence increased with age (χ(2) = 6067, df = 1, P < .001) and was higher in women (9.6%, 95% CI = 9.2-10.0%) than in men (5.2%, 95% CI = 4.9-5.5%; χ(2) = 298.9 df = 1, P < .001). CONCLUSION: Frailty is common in later life, but different operationalization of frailty status results in widely differing prevalence between studies. Improving the comparability of epidemiological and clinical studies constitutes an important step forward.

Measurement properties of the Groningen Frailty Indicator in home-dwelling and institutionalized elderly people.

OBJECTIVES: To enable prevention of poor outcome in elderly people, a valid instrument is required to detect individuals at high risk. The concept of frailty is a better predictor than age alone. The Groningen Frailty Indicator (GFI) has been developed to identify frailty. We assessed feasibility, reliability, and construct validity of the self-assessment version of the GFI. DESIGN: Cross-sectional. SETTING: Community-based. PARTICIPANTS: Home-dwelling and institutionalized elderly persons were included in the study (n = 353) who met the following inclusion criteria: persons 65 years and older who were able to fill out questionnaires. MEASUREMENTS: The feasibility of the GFI was assessed by determining the proportion of missing values per item. The internal consistency reliability of the GFI was established by calculating the KR-20. Mann-Whitney and Kruskal-Wallis tests were applied to assess discrimination between specific subgroups (known group validity). Convergent and discriminant validity was assessed using Spearman Rank correlations between GFI and diseases and disorders, case complexity, and health care needs (INTERMED), life satisfaction (Cantril Ladder of Life), activities of daily living (Katz), quality of life (EQ-5D), and mental health (SF-36). Finally, we used multivariate regression analyses to evaluate the cutoff score of the GFI (<4 versus ≥4). RESULTS: A total of 296 (84%) of the participants completed all items of the GFI; the internal consistency was 0.68. The GFI yielded statistically significant GFI scores for subgroups (known group validity). The correlations for the convergent (range 0.45 to 0.61) and discriminant validity (range 0.08 to 0.50) were also as hypothesized. In contrast with nonfrail participants, frail older persons had higher levels of case complexity, disability, and lower quality of life and life satisfaction. CONCLUSIONS: This study supports the feasibility, reliability, and validity of the self-assessment version of the GFI in home-dwelling and institutionalized elderly people.

Antipsychotic drug treatment in first-episode psychosis: should patients be switched to a different antipsychotic drug after 2, 4, or 6 weeks of nonresponse?

Patients with schizophrenia show symptom reduction early after the initiation of drug treatment, but no consensus has been reached on the number of weeks after which a nonresponding patient should be switched to an alternative treatment. We aimed to test whether patients should be switched to an alternative treatment at 2, 4, or 6 weeks from treatment initiation. Remission within 12 months was assessed in 299 first-episode patients who completed the full 12-month European First-Episode Schizophrenia Trial. Logistic regression analyses were used to test whether the prediction of remission was improved by including assessments obtained 4 or 6 weeks from treatment initiation compared with a prediction based on baseline and 2-week measures only. Based on baseline and 2-week assessments, remission status was correctly predicted in 61% of the patients (positive and negative predictive power, 0.61 and 0.58, respectively; sensitivity, 0.94; and specificity, 0.12). This percentage increased to 63% (positive and negative predictive power, 0.67 and 0.55, respectively; sensitivity, 0.73; and specificity, 0.47) and 68% (positive and negative predictive power, 0.73 and 0.61, respectively; sensitivity, 0.73; and specificity, 0.60) by the inclusion of 4- and 6-week assessments, respectively. Although we confirmed earlier findings that 2-week measures of response are associated with remission, the prediction of remission is significantly improved by the inclusion of 4- and 6-week assessments. However, as the increase in prediction accuracy is modest, it is uncertain whether this improvement is clinically relevant.

Generalizability of the results of efficacy trials in first-episode schizophrenia: comparisons between subgroups of participants of the European First Episode Schizophrenia Trial (EUFEST).

OBJECTIVE: Most randomized drug trials in schizophrenia exclude patients with comorbidities such as suicidality or substance use, which may limit the generalizability of the results. We aimed to evaluate the generalizability of the results of these trials in participants of a randomized clinical trial with broad inclusion criteria. METHOD: In 50 sites in 14 countries, 498 patients with first-episode psychosis (DSM-IV schizophrenia, schizoaffective disorder, or schizophreniform disorder) were recruited between December 2002 and January 2006 in an open, randomized clinical drug trial with 12 months of follow-up. Baseline characteristics and follow-up data were compared between patients with versus patients without baseline suicidality and/or substance use. RESULTS: Of the 489 participants with data on baseline suicidality and substance use, 153 (31%) patients were suicidal and/or using substances. Groups differed on only a few of the many baseline characteristics tested: comorbid patients were younger (25.1 vs 26.5 years of age; P < .01), less often female (25% vs 47%; P < .001) or married (4% vs 17%; P < .001), had fewer years of education (11.8 vs 12.8; P < .001), and experienced lower levels of overall psychosocial functioning (Global Assessment of Functioning; 38.4 vs 40.8; P

Effectiveness of antipsychotics in first-episode schizophrenia and schizophreniform disorder on response and remission: an open randomized clinical trial (EUFEST).

BACKGROUND: Predefined response and remission criteria may hold more clinical relevance than mean scores on rating scales. We compared the effectiveness of low doses of haloperidol and regular doses of second generation antipsychotics (SGAs) on >or=50% response and remission. METHODS: In an open randomized clinical trial in 14 countries, 498 unselected first-episode patients with schizophrenia were assigned to haloperidol (1-4 mg/d; n=103), amisulpride (200-800 mg/d; n=104), olanzapine (5-20mg/d; n=105), quetiapine (200-750 mg/d; n=104), or ziprasidone (40-160 mg/d; n=82). Primary outcomes were >or=50% response and remission within 12 months, as measured with the Positive and Negative Syndrome Scale. Analysis was by intention-to-treat. RESULTS: Within 12 months, the proportions of patients with >or=50% response were 37% for haloperidol, 67% for amisulpride, 67% for olanzapine, 46% for quetiapine, and 56% for ziprasidone. Comparisons with haloperidol showed a higher likelihood for >or=50% response with amisulpride (hazard ratio [HR] 2.27, [95% CI 1.51-3.42]), olanzapine (HR 2.07 [1.38-3.10]), and ziprasidone (HR 1.62 [1.02-2.56]). Within 12 months, the proportions of patients in remission were 17% for haloperidol, 40% for amisulpride, 41% for olanzapine, 24% for quetiapine, and 28% for ziprasidone. Comparisons with haloperidol showed a better chance for remission on amisulpride (HR 2.49, [95% CI 1.43-4.35]), olanzapine (HR 2.58 [1.48-4.48]), quetiapine (HR 1.96 [1.06-3.64]), and ziprasidone (HR 2.03 [1.07-3.87]). CONCLUSIONS: Substantial proportions of first-episode patients with schizophrenia showed clinically meaningful response and remission rates within 12 months. The proportions of response and remission were higher for most SGAs as compared to haloperidol.

Correlates of cognitive impairment in first episode schizophrenia: the EUFEST study.

BACKGROUND: Profile and correlates of cognitive deficits in first episode (FE) schizophrenia patients are still debated. The present study is aimed to clarify in a large sample of FE patients the extent of impairment in key cognitive domains and its relationships with demographic and clinical variables. METHOD: The European First Episode Schizophrenia Trial collected demographic, clinical and neurocognitive baseline data in 498 FE patients with minimal or no prior exposure to antipsychotics. Two-hundred-twenty healthy subjects (HS) were also evaluated. Neurocognitive assessment included the Rey Auditory Verbal Learning Test; Trail Making A and B, Purdue Pegboard and Digit-Symbol Coding. RESULTS: Patients performed worse than HS on all tests (effect sizes from -0.88 to -1.73). Correlations with psychopathological dimensions were weak and involved reality distortion and disorganization. The duration of untreated psychosis (DUP) was not associated with cognitive impairment. Subjects living alone had a better neurocognitive performance, while the occupation status did not reveal any association with cognition. CONCLUSIONS: A moderate/severe impairment of processing speed, motor dexterity, verbal memory and cognitive flexibility was found in the largest sample of FE patients analyzed so far. The impairment was largely independent from psychopathology and not associated with DUP.

Cognitive effects of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: a randomized, open-label clinical trial (EUFEST).

OBJECTIVE: Cognitive impairment, manifested as mild to moderate deviations from psychometric norms, is present in many but not all schizophrenia patients. The purpose of the present study was to compare the effect of haloperidol with that of second-generation antipsychotic drugs on the cognitive performance of patients with schizophreniform disorder or first-episode schizophrenia. METHODS: Subjects were 498 patients with schizophreniform disorder or first-episode schizophrenia who were randomly assigned to open-label haloperidol (1 to 4 mg/day [N=103]), amisulpride (200 to 800 mg/day [N=104]), olanzapine (5 to 20 mg/day [N=105]), quetiapine (200 to 750 mg/day [N=104]), or ziprasidone (40 to 160 mg/day [N=82]). The Rey Auditory Verbal Learning Test, Trail Making Test Part A and Part B, WAIS Digit Symbol Test, and Purdue Pegboard Test were administered at baseline and the 6-month follow-up evaluation. RESULTS: Compared with scores at baseline, composite cognitive test scores improved for all five treatment groups at the 6-month follow-up evaluation. However, there were no overall differences among the treatment groups. In addition, there was a weak correlation between the degree of cognitive improvement and changes in Positive and Negative Syndrome Scale scores. CONCLUSION: Treatment with antipsychotic medication is associated with moderate improvement in the cognitive test performance of patients who have schizophreniform disorder or who are in their first episode of schizophrenia. The magnitude of improvement does not differ between treatment with haloperidol and treatment with second-generation antipsychotics. Moreover, cognitive improvement is weakly related to symptom change.

Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial.

BACKGROUND: Second-generation antipsychotic drugs were introduced over a decade ago for the treatment of schizophrenia; however, their purported clinical effectiveness compared with first-generation antipsychotic drugs is still debated. We aimed to compare the effectiveness of second-generation antipsychotic drugs with that of a low dose of haloperidol, in first-episode schizophrenia. METHODS: We did an open randomised controlled trial of haloperidol versus second-generation antipsychotic drugs in 50 sites, in 14 countries. Eligible patients were aged 18-40 years, and met diagnostic criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder. 498 patients were randomly assigned by a web-based online system to haloperidol (1-4 mg per day; n=103), amisulpride (200-800 mg per day; n=104), olanzapine (5-20 mg per day; n=105), quetiapine (200-750 mg per day; n=104), or ziprasidone (40-160 mg per day; n=82); follow-up was at 1 year. The primary outcome measure was all-cause treatment discontinuation. Patients and their treating physicians were not blinded to the assigned treatment. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN68736636. FINDINGS: The number of patients who discontinued treatment for any cause within 12 months was 63 (Kaplan-Meier estimate 72%) for haloperidol, 32 (40%) for amisulpride, 30 (33%) for olanzapine, 51 (53%) for quetiapine, and 31 (45%) for ziprasidone. Comparisons with haloperidol showed lower risks for any-cause discontinuation with amisulpride (hazard ratio [HR] 0.37, [95% CI 0.24-0.57]), olanzapine (HR 0.28 [0.18-0.43]), quetiapine (HR 0.52 [0.35-0.76]), and ziprasidone (HR 0.51 [0.32-0.81]). However, symptom reductions were virtually the same in all the groups, at around 60%. INTERPRETATION: This pragmatic trial suggests that clinically meaningful antipsychotic treatment of first-episode of schizophrenia is achievable, for at least 1 year. However, we cannot conclude that second-generation drugs are more efficacious than is haloperidol, since discontinuation rates are not necessarily consistent with symptomatic improvement.

Regional differences in the use of out-patient services by stroke patients after hospitalisation.

BACKGROUND: To improve the quality of life in stroke patients, outreach care programmes are developed and assessed for effectiveness. The generalisability of the trials' results is uncertain since information on the comparability of the conventional out-patient services is lacking. This study intended to assess the use of 11 types of conventional out-patient services by stroke patients in the United States and a predefined set of Western European countries. METHODS: Review of the literature from 1990 to 2001. RESULTS: We found 11 studies, which contained data on 1,875 patients of 6 countries. Large differences in the use of out-patient services within and between countries prohibited pooling of the data. CONCLUSIONS: The paucity of data on the use of conventional out-patient services by stroke patients and the regional differences found do not substantiate generalisability of the results from studies on outreach care for stroke patients.

Multicenter randomized controlled trial of an outreach nursing support program for recently discharged stroke patients.

BACKGROUND AND PURPOSE: Many stroke patients and informal carers experience a decreased quality of life after discharge home and are dissatisfied with the care received. We assessed the effectiveness of an outreach nursing care program. METHODS: In a multicenter trial, 536 stroke patients were randomized at discharge to standard care (n=273) or standard care plus outreach care (n=263). The outreach care consisted of 3 telephone calls and 1 home visit within 5 months after discharge by 1 of 13 stroke nurses. Patients were masked for the trial objectives. Six months after discharge, they assessed the 2 primary outcomes: quality of life (Short Form 36 [SF-36]) and dissatisfaction with care. Secondary measures of outcome were disability, handicap, depression, anxiety, and use of health care services and secondary prevention drugs. Informal carers assessed strain, and social support. Analysis was by intention to treat. RESULTS: Twelve patients died before follow-up, 38 declined outcome assessment, and 486 completed the primary outcome assessments. Outreach care patients had better scores on the SF-36 domain "Role Emotional" than controls (mean difference 7.9 [95% confidence limit, 0.1 to 15.7]). No statistically significant differences were found on the other primary outcome measures. For secondary outcomes, no statistically significant differences were found, except that intervention patients used fewer rehabilitation services (relative risk, 0.66 [0.44 to 1.00]) and had lower anxiety scores (median difference 1 [0.19 to 2.79]). CONCLUSIONS: This outreach nursing stroke care was not effective in improving quality of life and dissatisfaction with care of recently discharged patients.