Comorbidities and clinical outcomes in adult- and juvenile-onset Huntington's disease: a study of linked Swedish National Registries (2002-2019).

BACKGROUND: Huntington's disease (HD) is a rare, neurodegenerative disease and its complex motor, cognitive and psychiatric symptoms exert a lifelong clinical burden on both patients and their families. OBJECTIVE: To describe the clinical burden and natural history of HD. METHODS: This longitudinal cohort study used data from the linked Swedish national registries to describe the occurrence of comorbidities (acute and chronic), symptomatic treatments and mortality in an incident cohort of individuals who either received the first diagnosis of HD above (adult onset HD; AoHD) or below (juvenile-onset HD; JoHD) 20 years of age, compared with a matched cohort without HD from the general population. Disease burden of all individuals alive in Sweden was described during a single calendar year (2018), including the occurrence of key symptoms, treatments and hospitalizations. RESULTS: The prevalence of HD in 2018 was approximately 10.2 per 100,000. Of 1492 individuals with a diagnosis of HD during 2002 and 2018, 1447 had AoHD and 45 had JoHD. Individuals with AoHD suffered a higher incidence of obsessive-compulsive disorder, acute psychotic episodes, pneumonia, constipation and fractures compared with matched controls. Individuals with JoHD had higher incidence rates of epilepsy, constipation and acute respiratory symptoms. Median time to all-cause mortality in AoHD was 12.1 years from diagnosis. Patients alive with HD in Sweden in 2018 displayed a pattern of increased clinical burden for a number of years since diagnosis. CONCLUSIONS: This study demonstrates the significant and progressive clinical burden in individuals with HD and presents novel insights into the natural history of JoHD.

Can the Positive and Negative Syndrome scale (PANSS) differentiate treatment-resistant from non-treatment-resistant schizophrenia? A factor analytic investigation based on data from the Pattern cohort study.

Treatment-Resistant Schizophrenia (TRS) and Non-Treatment-Resistant Schizophrenia (NTRS) may represent different subtypes of schizophrenia. However, few studies have investigated their PANSS symptom dimensions by Exploratory (EFA) or Confirmatory (CFA). Data from the present study are derived from 1429 patients of the Pattern study. TRS was defined by the use of clozapine in the previous year whereas NTRS by the use of non-clozapine antipsychotics ("by proxy"). Factors were chosen based on the Kaiser criterion and considered valid when loadings were greater than or equal to 0.5. The fit to the data was evaluated by CFA in comparison with well-established PANSS models, using fit indexes. The EFA yielded similar five-factor model in both groups: Negative, Positive, Anxiety/Depression, Cognitive and Excited. CFA showed a satisfactory, but not perfect, fit to the data, as compared with the previous PANSS factor analytic models. Despite the limitations regarding the 'by proxy' definition of TRS, the results of the present study show that there are no differences in the factorial structure of PANSS in patients with TRS and NTRS.

Health-related quality of life associated with different symptoms in women and in men who suffer from schizophrenia.

Health-related quality of life (HRQoL) in patients with schizophrenia is related to the severity of psychiatric symptoms. The objective of this study is to analyze whether the symptoms that influence HRQoL are similar in women and men. Data were part of the Pattern study, an international observational investigation which collected data from 1379 outpatients with schizophrenia. Patients were evaluated with the Mini International Neuropsychiatric Inventory, the Clinical Global Impression-Schizophrenia, and the Positive and Negative Syndrome Scale (PANSS), and reported their quality of life using the Schizophrenia Quality of Life Scale (SQLS), the Short Form-36 (SF-36), and the EuroQol-5 Dimension (EQ-5D). Men reported higher HRQoL on all scales. PANSS total score was 80.6 (SD 23.6) for women and 77.9 (SD 22.1) for men. In women, a higher PANSS negative score and a higher PANSS affective score were associated with a lower SQLS score. In men, a higher PANSS positive score and a higher PANSS affective score were associated with a lower SQLS score. The same pattern appeared with EQ-VAS and EQ-5D tariff. In women, greater age and higher PANSS affective score were associated with a lower SF-36 mental component score. In men, higher PANSS affective, positive, and cognitive scores were associated with a lower SF-36 mental component score. This study shows that HRQoL is influenced by different psychiatric symptoms in women and men. This may have significant implications when deciding the main treatment target in patients with schizophrenia.ClinicalTrials.gov Identifier: https://clinicaltrials.gov/ct2/show/NCT01634542.

Correlation of Health-Related Quality of Life in Clinically Stable Outpatients with Schizophrenia.

BACKGROUND: Generic health-related quality of life (HRQoL) scales are increasingly being used to assess the effects of new treatments in schizophrenia. The objective of this study is to better understand the usefulness of generic and condition specific HRQoL scales in schizophrenia by analyzing their correlates. METHODS: Data formed part of the Pattern study, an international observational study among 1379 outpatients with schizophrenia. Patients were evaluated with the Mini International Neuropsychiatric Inventory, the Clinical Global Impression-Schizophrenia (CGI-SCH) Scale and the Positive and Negative Syndrome Scale (PANSS) and reported their HRQoL using the Schizophrenia Quality of Life Scale (SQLS), the Short Form-36 (SF-36), and the EuroQol-5 Dimension (EQ-5D). The two summary values of the SF-36 (the Mental Component Score and the Physical Component Score, SF-36 MCS and SF-36 PCS) were calculated. RESULTS: Higher PANSS positive dimension ratings were associated with worse HRQoL for the SQLS, EQ-5D VAS, SF-36 MCS, and SF-36 PCS. Higher PANSS negative dimension ratings were associated with worse HRQoL for the EQ-5D VAS, SF-36 MCS, and SF-36 PCS, but not for the SQLS or the EQ-5D tariff. PANSS depression ratings were associated with lower HRQoL in all the scales. There was a high correlation between the HRQoL scales. However, in patients with more severe cognitive/disorganized PANSS symptoms, the SQLS score was relatively higher than the EQ-5D tariff and SF-36 PCS scores. CONCLUSION: This study has shown substantial agreement between three HRQoL scales, being either generic or condition specific. This supports the use of generic HRQoL measures in schizophrenia. CLINICALTRIALSGOV IDENTIFIER: NCT01634542 (July 6, 2012, retrospectively registered).

Understanding the course of persistent symptoms in schizophrenia: Longitudinal findings from the pattern study.

The Pattern study was conducted to provide longitudinal observational data for individual patients with persistent symptoms of schizophrenia. Pattern is an international, multicenter, non-interventional, prospective cohort study of schizophrenia outpatients who were not considered to be in recovery. In the longitudinal phase reported herein, patients were assessed over 1 year using different clinical rating scales. Patient management followed routine local clinical practice. Primary outcome was disease state, defined by the Positive and Negative Syndrome Scale (PANSS), Negative Symptom Factor Score (NSFS), Positive Symptom Factor Score (PSFS), and Personal and Social Performance (PSP) Scale. In total, 1344 protocol-compliant patients (70.9% male) were included. Patients showed a high stability in disease state between consecutive study visits. Persistent negative persistent symptoms and symptomatic remission were the most prevalent and stable disease states. Patients in relapse generally transitioned to negative persistent symptoms or to symptomatic remission. PANSS, PSP, and quality of life ratings remained relatively stable. Relapses occurred in 10% of patients; probability of relapse was associated with younger age, extra-pyramidal symptoms, and more antipsychotic medications. Despite treatment, schizophrenia symptoms tend to remain stable over time, without overall improvement. One of the greatest challenges in schizophrenia is attainment of full symptom remission.

Health-related quality of life in outpatients with schizophrenia: factors that determine changes over time.

PURPOSE: The objective of this study was to analyze the clinical factors associated with changes in HRQoL in outpatients with schizophrenia using both generic and condition-specific HRQoL scales. METHODS: Adult outpatients with schizophrenia at least 18 years of age who did not have an acute psychotic exacerbation in the 3 months prior to baseline were recruited. PANSS dimensions were calculated based on Lindenmayer et al.'s five factors. HRQoL data were assessed by patients using the Schizophrenia Quality of Life Scale (SQLS), the Short Form-36 (SF-36), and the EuroQol-5 Dimension (EQ-5D) questionnaires. RESULTS: Out of the 1345 patients included at baseline, 1196 (89%) were evaluated at 12 months. Regression models showed that the factor most consistently associated with HRQoL at endpoint was change in the PANSS negative symptoms score. A decrease in the PANSS negative symptoms score from baseline to 1 year was associated with a decrease in HRQoL during the same period. There were also significant associations of the change in PANSS excitatory factor with all the HRQoL scales except the SF-36 PCS. Female gender was associated with a decrease in all HRQoL ratings. There was also a relationship between years since onset and HRQoL. The longer the time since illness onset, the larger the decrease in HRQoL. CONCLUSIONS: This study has found that, in outpatients with schizophrenia, changes in negative and excitement symptoms may have a greater an association with HRQoL than changes in positive, cognitive and depressive symptoms.

Burden of illness of people with persistent symptoms of schizophrenia: A multinational cross-sectional study.

BACKGROUND: Few studies have examined the impact of persistent symptoms of schizophrenia, especially with respect to patient-reported outcomes (PROs), carer burden and health economic impact. AIMS: Analyse data relating to burden and severity of illness, functional impairment and quality of life for patients with persistent symptoms of schizophrenia. METHODS: A cohort of stable outpatients with persistent symptoms of schizophrenia across seven countries were assessed in a multicentre, non-interventional, cross-sectional survey and retrospective medical record review using PRO questionnaires, clinical rating scales and carer questionnaires. RESULTS: Overall, 1,421 patients and 687 carers were enrolled. Approximately two-thirds of patients had moderate/mild schizophrenia with more severe negative symptoms predominating. Patients showed impaired personal/social functioning and unsuitability for work correlated with various patient factors, most notably symptom-related assessments. Quality-of-life assessments showed 25% to ⩾30% of patients had problems with mobility, washing or dressing. Carer burden was also considerable, with carers having to devote an average of 20.5 hours per week and notable negative impact on quality-of-life measures. Healthcare resource utilisation for in-hospital, outpatient and other care provider visits was significant. CONCLUSION: These results demonstrate the significant burden of schizophrenia for patients, carers and society and highlight the need for improved treatment approaches.

Understanding the impact of persistent symptoms in schizophrenia: Cross-sectional findings from the Pattern study.

BACKGROUND: The high societal burden of schizophrenia is largely caused by the persistence of symptoms and accompanying functional impairment. To date, no studies have specifically assessed the course of persistent symptoms or the individual contributions of positive and negative symptoms to patient functioning. The cross-sectional analysis of the Pattern study provides an international perspective of the burden of schizophrenia. METHODS: Clinically stable outpatients from 140 study centers across eight countries (Argentina, Brazil, Canada, France, Germany, Italy, Spain and the United Kingdom) were assessed using clinical rating scales: Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Schizophrenia (CGI-SCH) Scale and the Personal and Social Performance (PSP) Scale. Additional measures included patient-reported outcomes, patient socio-demographic variables, living situation, employment and resource use. RESULTS: Overall, 1379 patients were assessed and analyzed and had similar sociodemographic characteristics across countries, with 61.6% having persistent positive and/or negative symptoms. Positive and negative symptoms had been persistent for a mean of 9.6 and 8.9 years (SD: 8.8 and 9.6), respectively. Approximately 86% of patients had a functional disability classified as greater than mild. Patients with a higher PANSS Negative Symptom Factor Score were more likely to have a poorer level of functioning. CONCLUSIONS: This analysis examines individual contributions of persistent positive and negative symptoms on patient functioning in different countries. A high prevalence of patients with persistent symptoms and functional impairment was a consistent finding across countries. Longitudinal observations are necessary to assess how to improve persistent symptoms of schizophrenia and overall patient functioning.

Defining therapeutic benefit for people with schizophrenia: focus on negative symptoms.

Schizophrenia is a complex, heterogeneous, multidimensional disorder within which negative symptoms are a significant and disabling feature. Whilst there is no established treatment for these symptoms, some pharmacological and psychosocial interventions have shown promise and this is an active area of research. Despite the effort to identify effective interventions, as yet there is no broadly accepted definition of therapeutic success. This article reviews concepts of clinical relevance and reports on a consensus conference whose goal was to apply these concepts to the treatment of negative symptoms. A number of key issues were identified and discussed including: assessment of specific negative symptom domains; defining response and remission for negative symptoms; assessment of functional outcomes; measurement of outcomes within clinical trials; and the assessment of duration/persistence of a response. The group reached a definition of therapeutic success using an achieved threshold of function that persisted over time. Recommendations were agreed upon with respect to: assessment of negative symptom domains of apathy-avolition and deficit of expression symptoms; thresholds for response and remission of negative symptoms based on level of symptomatology; assessing multiple domains of function including social occupation, activities of daily living, and socialization; the need for clinical trial data to include rate of change over time and converging sources of evidence; use of clinician, patient and caregiver perspectives to assess success; and the need for establishing criteria for the persistence of therapeutic benefit. A consensus statement and associated research criteria are offered as an initial step towards developing broad agreement regarding outcomes of negative symptoms treatment.