RESUMO
BACKGROUND: Diagnosing multiple sclerosis (MS) early is crucial to avoid future disability. However, potentially preventable delays in the diagnostic cascade from contact with a physician to definite diagnosis still occur and their causes are still unclear. OBJECTIVE: To identify the possible causes of delays in the diagnostic process. METHODS: We analyzed the data of the Swiss MS Registry. With logistic regression, we modeled the time from the first contact to the first consultation (contact-to-evaluation time, ⩽1 month/>1 month) and the evaluation-to-diagnosis time (⩽6 months/>6 months). Potential factors were health system characteristics, sociodemographic variables, first symptoms, and MS type. RESULTS: We included 522 participants. Mostly, general practitioners (67%) were contacted first, without delaying the diagnosis. In contrast, first symptoms and MS type were the major contributors to delays: gait problems were associated with longer contact-to-evaluation times, depression as a concomitant symptom with longer evaluation-to-diagnosis times, and having primary progressive MS prolonged both phases. In addition, living in mountainous areas was associated with longer contact-to-evaluation times, whereas diagnosis after 2000 was associated with faster diagnoses. CONCLUSION: For a quicker diagnosis, awareness of MS as a differential diagnosis of gait disorders and the co-occurrence of depression at onset should be raised, and these symptoms should be attentively followed.
Assuntos
Diagnóstico Tardio , Atenção à Saúde/estatística & dados numéricos , Depressão/diagnóstico , Transtornos Neurológicos da Marcha/diagnóstico , Esclerose Múltipla/diagnóstico , Médicos/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Características de Residência/estatística & dados numéricos , Adulto , Depressão/etiologia , Diagnóstico Precoce , Feminino , Transtornos Neurológicos da Marcha/etiologia , Humanos , Masculino , Medicina , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla Crônica Progressiva/diagnóstico , Medidas de Resultados Relatados pelo Paciente , Encaminhamento e Consulta , Suíça , Fatores de TempoRESUMO
BACKGROUND: Comorbidity patterns of childhood infections, atopic diseases, and adverse childhood experiences (ACE) are related to immune system programming conditions. The aim of this study was to make a step beyond the hygiene hypothesis and to comprehensively classify these patterns with latent class analysis (LCA). A second aim was to characterize the classes by associations with immunological, clinical, and sociodemographic variables. METHODS: LCA was applied to data from the CoLaus|PsyCoLaus study (N = 4874, age range 35-82 years) separately for men and women. It was based on survey information on chickenpox, measles, mumps, rubella, herpes simplex, pertussis, scarlet fever, hay fever, asthma, eczema, urticaria, drug allergy, interparental violence, parental maltreatment, and trauma in early childhood. Subsequently, we examined how immune-mediated classes were reflected in leukocyte counts, inflammatory markers (IL-1ß, IL-6, TNF-α, hsCRP), chronic inflammatory diseases, and mental disorders, and how they differed across social classes and birth cohorts. RESULTS: LCA results with five classes were selected for further analysis. Latent classes were similar in both sexes and were labeled according to their associations as neutral, resilient, atopic, mixed (comprising infectious and atopic diseases), and ACE class. They came across with specific differences in biomarker levels. Mental disorders typically displayed increased lifetime prevalence rates in the atopic, the mixed, and the ACE classes, and decreased rates in the resilient class. The same patterns were apparent in chronic inflammatory diseases, except that the ACE class was relevant specifically in women but not in men. CONCLUSIONS: This is the first study to systematically determine immune-mediated classes that evolve early in life. They display characteristic associations with biomarker levels and somatic and psychiatric diseases occurring later in life. Moreover, they show different distributions across social classes and allow to better understand the mechanisms beyond the changes in the prevalence of chronic somatic and psychiatric diseases.
Assuntos
Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/imunologia , Hipótese da Higiene , Fenômenos do Sistema Imunitário/fisiologia , Análise de Classes Latentes , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma/epidemiologia , Asma/imunologia , Criança , Comorbidade , Feminino , Humanos , Inflamação/complicações , Inflamação/epidemiologia , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Múltiplas Afecções Crônicas/epidemiologia , Prevalência , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Multiple sclerosis (MS) is one of the most frequently observed neurological conditions in Switzerland, but data sources for country-wide epidemiological trend monitoring are lacking. Moreover, while clinical and laboratory MS research are generally well established, there is a gap in patient-centered MS research to inform care management, or treatment decisions and policy making not only in Switzerland but worldwide. METHODS: In light of these research gaps, the Swiss Multiple Sclerosis Society initiated and funded the Swiss Multiple Sclerosis Registry (SMSR) an open-ended, longitudinal and prospective, nationwide, patient-centered study. The SMSR recruits adult persons with a suspected or confirmed MS diagnosis who reside or receive care in Switzerland. The SMSR has established a governance structure with clear rules and guidelines. It follows a citizen-science approach with direct involvement of persons with MS (PwMS), who contribute actively to registry development, operations, and research. Main scientific goals entail the study of MS epidemiology in Switzerland, health care access and provision, as well as life circumstances and wellbeing of persons with MS. The innovative study design ("layer model") offers several participation options with different time commitments. Data collection is by means of regular surveys and medical record abstraction. Survey participation is offered in different modes (web, paper & pencil) and in the three main national languages (German, French, Italian). Participants also receive regular data feedbacks for personal use and self-monitoring, contextualized in the whole population of study participants. Data feedbacks are also used to solicit data corrections of key variables from participants. DISCUSSION: The SMSR combines the advantages of traditional and novel research methods in medical research and has recruited over 1600 PwMS in its first year. The future-oriented design and technology will enable a response not only to future technological innovations and research trends, but also to challenges in health care provision for MS. TRIAL REGISTRATION: ClinicalTrials.gov NCT02980640 ; December 6, 2016; retrospectively registered.
Assuntos
Pesquisa Biomédica/métodos , Esclerose Múltipla/epidemiologia , Participação do Paciente , Assistência Centrada no Paciente , Sistema de Registros , Adolescente , Adulto , Protocolos Clínicos , Humanos , Esclerose Múltipla/terapia , Estudos Prospectivos , Projetos de Pesquisa , Inquéritos e Questionários , Suíça/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Previous research suggests that sleep disorders are highly associated with other mental health problems. However, sleep problems even below the diagnostic threshold of sleep disorders are very common in the general population, which highly affects wellbeing and functioning. In order to broaden the focus beyond those severe cases we explored empirical patterns across the whole spectrum of sleep problems as well as associated clinical and other factors. METHOD: A representative community sample of N=1274 residents from the canton of Zurich was interviewed for sleep problems and diagnostic criteria for mental disorders as well as was given a number of mental health-related psychometrical checklists. Based on a broader spectrum of sleep problems we conducted a latent class analysis (LCA) to derive distinct classes of such disturbances. Classes were compared regarding their associations to mental health-relevant and other risk factors. RESULTS: The LCA revealed four classes - no sleep disturbances (72.6%), difficulties initiating and maintaining sleep (15.8%), delayed sleep (5.3%), and severe sleep problems (6.4%). Severe sleep problems were related to female gender and generalized anxiety disorder, while depression was linked to all sleep problem classes. Persons with difficulties initiating and maintaining sleep and severe sleep problems reported higher levels of psychopathology, burnout and neuroticism, while all sleep problem types were tied to stress-related variables, but not alcohol use disorder. DISCUSSION: Sleep problems are highly prevalent among the young and middle-aged adults in our representative sample of young and middle-aged adults and as such represent a serious public mental health problem. Our findings indicate sleep problems to have a multi-dimensional structure with some differential associations. While all subtypes were associated with poorer mental health and particularly more depression, severe sleep problems appeared to be the sleep subtype seen in agoraphobia and GAD, while delayed sleep had no specific associations. The variety of associations assessed leads one to assume that likewise a variety of sleep interventions is required.
Assuntos
Transtornos Mentais/epidemiologia , Transtornos do Sono-Vigília/epidemiologia , Adolescente , Adulto , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Inquéritos e Questionários , Suíça/epidemiologia , Adulto JovemRESUMO
Interest in subtypes of mental disorders is growing in parallel with continuing research progress in psychiatry. The aim of this study was to examine pure animal phobia in contrast to other specific phobias and a mixed subtype. Data from three representative Swiss community samples were analysed: PsyCoLaus (n = 3720), the ZInEP Epidemiology Survey (n = 1500) and the Zurich Study (n = 591). Pure animal phobia and mixed animal/other specific phobias consistently displayed a low age at onset of first symptoms (8-12 years) and clear preponderance of females (OR > 3). Meanwhile, other specific phobias started up to 10 years later and displayed almost a balanced sex ratio. Pure animal phobia showed no associations with any included risk factors and comorbid disorders, in contrast to numerous associations found in the mixed subtype and in other specific phobias. Across the whole range of epidemiological parameters examined in three different samples, pure animal phobia seems to represent a different entity compared to other specific phobias. The etiopathogenetic mechanisms and risk factors associated with pure animal phobias appear less clear than ever.
Assuntos
Comorbidade , Transtornos Fóbicos/classificação , Transtornos Fóbicos/epidemiologia , Adulto , Idade de Início , Idoso , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Escalas de Graduação Psiquiátrica , Características de Residência , Suíça/epidemiologia , Adulto JovemRESUMO
Many people with mental health problems do not use mental health care, resulting in poorer clinical and social outcomes. Reasons for low service use rates are still incompletely understood. In this longitudinal, population-based study, we investigated the influence of mental health literacy, attitudes toward mental health services, and perceived need for treatment at baseline on actual service use during a 6-month follow-up period, controlling for sociodemographic variables, symptom level, and a history of lifetime mental health service use. Positive attitudes to mental health care, higher mental health literacy, and more perceived need at baseline significantly predicted use of psychotherapy during the follow-up period. Greater perceived need for treatment and better literacy at baseline were predictive of taking psychiatric medication during the following 6 months. Our findings suggest that mental health literacy, attitudes to treatment, and perceived need may be targets for interventions to increase mental health service use.
Assuntos
Atitude Frente a Saúde , Letramento em Saúde , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Comportamento de Busca de Ajuda , Transtornos Mentais/epidemiologia , Serviços de Saúde Mental/estatística & dados numéricos , Saúde Mental , Adulto , Estudos Transversais , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/psicologia , Transtorno Depressivo/terapia , Feminino , Humanos , Estudos Longitudinais , Masculino , Transtornos Mentais/psicologia , Transtornos Mentais/terapia , Pessoa de Meia-Idade , Psicoterapia/estatística & dados numéricos , Psicotrópicos/uso terapêutico , Inquéritos e Questionários , Suíça , Revisão da Utilização de Recursos de Saúde/estatística & dados numéricosRESUMO
Due to its heterogeneous phenomenology, obsessive-compulsive disorder (OCD) has been subtyped. However, these subtypes are not mutually exclusive. This study presents an alternative subtyping approach by deriving non-overlapping OCD subtypes. A pure compulsive and a mixed obsessive-compulsive subtype (including subjects manifesting obsessions with/without compulsions) were analyzed with respect to a broad pattern of psychosocial risk factors and comorbid syndromes/diagnoses in three representative Swiss community samples: the Zurich Study (n = 591), the ZInEP sample (n = 1500), and the PsyCoLaus sample (n = 3720). A selection of comorbidities was examined in a pooled database. Odds ratios were derived from logistic regressions and, in the analysis of pooled data, multilevel models. The pure compulsive subtype showed a lower age of onset and was characterized by few associations with psychosocial risk factors. The higher social popularity of the pure compulsive subjects and their families was remarkable. Comorbidities within the pure compulsive subtype were mainly restricted to phobias. In contrast, the mixed obsessive-compulsive subtype had a higher prevalence and was associated with various childhood adversities, more familial burden, and numerous comorbid disorders, including disorders characterized by high impulsivity. The current comparison study across three representative community surveys presented two basic, distinct OCD subtypes associated with differing psychosocial impairment. Such highly specific subtypes offer the opportunity to learn about pathophysiological mechanisms specifically involved in OCD.
Assuntos
Transtorno Obsessivo-Compulsivo/classificação , Transtorno Obsessivo-Compulsivo/epidemiologia , Características de Residência , Comorbidade , Feminino , Humanos , Entrevista Psicológica , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/diagnóstico , Prevalência , Escalas de Graduação Psiquiátrica , Suíça/epidemiologiaRESUMO
OBJECTIVE: The aim of the study was to compare subjects dually diagnosed with posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) to those with only one or none of these conditions regarding helpseeking needs and behaviors. METHOD: Data from a large community sample (N=3694) were used to assess the associations among lifetime PTSD and AUD, other psychiatric disorders, clinical characteristics and lifetime helpseeking behaviors derived from a semi-structured interview. RESULTS: Comorbid individuals had more severe clinical profiles and were more impaired than individuals with either PTSD or AUD alone or those with no/other psychiatric conditions. However, they did not differ in overall helpseeking behavior from any other group. Those with comorbid PTSD/AUD were even less likely than the other groups to seek help for depression and anxiety disorders through specific treatment facilities or the use of prescribed psychotropic drugs. CONCLUSIONS: Despite a greater need for treatment the comorbid group did not seek more help than the others. Their lower use of prescribed drugs supports the self-medication hypothesis, suggesting that those individuals relieve their symptoms through higher alcohol use instead. Our findings underline the need for health care facilities to encourage helpseeking behavior in the aftermath of stressful life events.
Assuntos
Transtornos Relacionados ao Uso de Álcool/psicologia , Comportamento de Busca de Ajuda , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto , Idoso , Transtornos de Ansiedade/psicologia , Estudos de Coortes , Comorbidade , Depressão/psicologia , Feminino , Humanos , Acontecimentos que Mudam a Vida , Masculino , Pessoa de Meia-Idade , SuíçaRESUMO
PURPOSE: Most people with mental health problems do not use mental health services, resulting in poor psychiatric outcomes and greater illness burden. Although perceiving the need for mental health care was identified to be a key factor for service use, factors that explain differences in perceived need for mental health care are incompletely understood. The present paper investigates the role of illness representations in predicting perceived need for mental health care. METHODS: In a community sample of 202 persons currently distressed by symptoms related to mental illness, illness representations were assessed using the Brief Illness Perception Questionnaire and perceived need for mental health care was measured by the Self-Appraisal of Illness Questionnaire. Multiple linear regression models were used to determine the association between a person's illness representations and the level of perceived need for mental health care. RESULTS: Two illness representations were positively associated with perceived need for mental health care: the belief that treatment could improve the current mental health problem and the attribution of experienced symptoms to a mental health problem. Increased perceived need for care was related to current mental health service use. CONCLUSIONS: Interventions that aim to increase mental health service use could focus on people's attitudes toward mental health treatment and enable people to recognize symptoms as a mental illness.
Assuntos
Serviços Comunitários de Saúde Mental , Autoavaliação Diagnóstica , Transtornos Mentais/psicologia , Avaliação das Necessidades , Adulto , Feminino , Humanos , Masculino , Transtornos Mentais/terapia , Modelos Psicológicos , Inquéritos e Questionários , Adulto JovemRESUMO
PURPOSE: Attention-deficit/hyperactivity disorder (ADHD), conduct disorder (CD), and oppositional defiant disorder (ODD) are common externalizing disorders of childhood. The common effects of these disorders on substance abuse need further investigation. The current study investigated the joint clusters of childhood/adolescence ADHD, CD, and ODD, and their influence on substance abuse/dependence in a population-based sample of adults. METHODS: The data were drawn from the PsyCoLaus study (n = 3,720) conducted in Lausanne, Switzerland. The population-based sample included 238 subjects meeting criteria for ADHD/ODD/CD diagnoses before the age of 15. Latent class analyses (LCA) were performed to derive comorbidity subtypes, which were subsequently characterized with respect to psychosocial correlates and substance use. RESULTS: The best fit in LCAs was achieved with three latent classes: an ADHD subtype (35.7 %); an externalizing multimorbid subtype (33.6 %) involving ODD, ADHD, and CD; and a third subtype with CD (30.7 %). The CD subtype showed the highest association with substance use. Apart from this, the externalizing multimorbid subtype was also significantly linked to substance use. The ADHD subtype had only elevated frequencies for alcohol dependence in comparison with subjects that had no history of ADHD, ODD, and CD during childhood or adolescence. Finally, important interactions between subtypes and sex were observed with regard to substance use. CONCLUSIONS: This study provides evidence showing that subtyping the externalizing disorders, ADHD, ODD and CD, along their comorbidity patterns leads to important differences regarding substance use. This could have implications for the etiology, prevention, and treatment of substance use disorders.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/epidemiologia , Transtorno da Conduta/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto , Idoso , Alcoolismo/epidemiologia , Comorbidade , Transtorno Distímico/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Distribuição por Sexo , Suíça/epidemiologiaRESUMO
Prospective studies investigating the long-term stability of depression symptom subtypes are rare. Moreover, sex has received little attention as a predictor. This study aimed to investigate the role of sex on stability and transition patterns of depressive symptom subtypes over 20 years. The data were drawn from three follow-ups (1988, 1999, and 2008) of the longitudinal Zurich Study. Latent transition analyses were fitted to the data of 322 subjects, using depressive symptoms from the face-to-face interviews. The stable classes were characterized by psychosocial correlates. Three subtypes were identified: 'severe atypical,' 'severe typical,' and 'moderate.' While stability of the severe atypical and moderate subtype was relatively high and increased over time (70-71; 45-90%), stability of the severe typical subtype was lower (45-48%). Females had a higher risk of being in the severe atypical subtype and exhibited more transitions, particularly with respect to the severe typical subtype. In contrast, males displayed more stable subtypes. The stable severe atypical subtype was associated with comorbid eating disorders as well as psychosis syndromes, whereas the stable severe typical subtype was associated only with psychosis syndromes. Our results provide first evidence for the notion that long-term stability and transition patterns differ by sex and depression subtypes. This finding has received too little attention in previous research and should be considered in treatments.
Assuntos
Depressão/classificação , Depressão/epidemiologia , Caracteres Sexuais , Análise Fatorial , Feminino , Humanos , Estudos Longitudinais , Masculino , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Fatores de Tempo , Adulto JovemRESUMO
There is some evidence that fluid intelligence as well as empathy may be significantly related to personality disorders (PDs). To our knowledge, no study has addressed those issues simultaneously in all 10 DSM PDs in a sample of the general population. We analysed data from 196 participants aged 2041 from the Epidemiology Survey of the Zurich Programme for Sustainable Development of Mental Health Services (ZInEP), a comprehensive psychiatric survey in the general population of Zurich, Switzerland. We assessed the digit symbol-coding test (DSCT), the "reading the mind in the eyes" test (RMET) and the interpersonal reactivity index (IRI). Both measures of cognitive empathy (i.e. RMET and IRI perspective taking) were not related to any PD trait-score. The total PD trait-score was significantly associated with low scores on DSCT and IRI empathic concern and high scores on IRI personal distress, which indicates a doseresponse relationship in those measures. DSCT was particularly related to borderline PD, IRI empathic concern to schizoid and narcissistic PDs, and IRI personal distress to avoidant PD. The proportion of variance explained in the total PD trait-score accounted for by DSCT, IRI empathic concern and IRI personal distress was 2.6, 2.3 and 13.3 %, respectively. Symptomatology and severity of PDs are related to low fluid intelligence and reduced emotional empathy as characterized by low empathic concern and high personal distress towards emotional expressions of others. Further research is needed that examines the association between cognitive empathy and personality pathology as well as potential clinical applications.
Assuntos
Empatia , Inteligência , Relações Interpessoais , Transtornos da Personalidade/epidemiologia , Transtornos da Personalidade/psicologia , Adulto , Feminino , Inquéritos Epidemiológicos , Humanos , Modelos Lineares , Estudos Longitudinais , Masculino , Estudos Retrospectivos , Inquéritos e Questionários , Adulto JovemRESUMO
OBJECTIVE: The literature proposes a joint structure of normal and pathological personality with higher-order factors mainly based on the five-factor model of personality (FFM). The purpose of the present study was to examine the joint structure of the FFM and the DSM-IV personality disorders (PDs) and to discuss this structure with regard to higher-order domains commonly reported in the literature. METHODS: We applied a canonical correlation analysis, a series of principal component analyses with oblique Promax rotation and a bi-factor analysis with Geomin rotation on 511 subjects of the general population of Zurich, Switzerland, using data from the ZInEP Epidemiology Survey. RESULTS: The 5 FFM traits and the 10 DSM-IV PD dimensions shared 77% of total variance. Component extraction tests pointed towards a two- and three-component solution. The two-component solution comprised a first component with strong positive loadings on neuroticism and all 10 PD dimensions and a second component with strong negative loadings on extraversion and openness and positive loadings on schizoid and avoidant PDs. The three-component solution added a third component with strong positive loadings on conscientiousness and agreeableness and a negative loading on antisocial PD. The bi-factor model provided evidence for 1 general personality dysfunction factor related to neuroticism and 5 group factors, although the interpretability of the latter was limited. CONCLUSIONS: Normal and pathological personality domains are not isomorphic or superposable, although they share a substantial proportion of variance. The two and three higher-order domains extracted in the present study correspond well to equivalent factor-solutions reported in the literature. Moreover, these superordinate factors can consistently be integrated within a hierarchical structure of alternative four- and five-factor models. The top of the hierarchy presumably constitutes a general personality dysfunction factor which is closely related to neuroticism.
Assuntos
Modelos Psicológicos , Transtornos da Personalidade/psicologia , Personalidade , Adulto , Análise Fatorial , Feminino , Humanos , Inventário de Personalidade , Psicometria , Suíça , Adulto JovemRESUMO
Subtypes of comorbid conditions and their associated trauma and clinical characteristics in full and partial PTSD were examined. Data from 289 subjects from the general population that met criteria for full or partial PTSD were analyzed. Latent class analyses (LCA) were performed to derive homogeneous patterns of DSM-IV Axis-I disorders and anti-social personality comorbid to PTSD. Logistic regression models were conducted to characterize these classes by trauma-related and clinical features. The LCA revealed three classes: (1) low comorbidity; (2) high comorbidity with primarily substance-related disorders and a higher proportion of males; and (3) more severe PTSD-symptomatology and higher comorbid anxiety disorders and depression, almost entirely represented by females. Exposure to sexual abuse was more likely in the substance-dependent class and contributed strongly to the distinction between classes. Affective disorders tended to precede the onset of PTSD in the substance-dependent class, whereas phobias were more likely to follow PTSD in the depressed-anxious class. Posttrauma onset of alcohol use disorders in the substance dependent class confirmed the self-medication hypothesis. The three classes of comorbidity and their sequence of onset with PTSD suggest different mechanisms involved in their development. Our findings suggest that PTSD-related comorbidity subtypes also apply to individuals with partial PTSD.
Assuntos
Transtornos Mentais/epidemiologia , Transtornos Mentais/psicologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto , Idoso , Transtornos Relacionados ao Uso de Álcool/diagnóstico , Transtornos Relacionados ao Uso de Álcool/epidemiologia , Transtornos Relacionados ao Uso de Álcool/psicologia , Estudos de Coortes , Comorbidade , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Transtornos Mentais/diagnóstico , Pessoa de Meia-Idade , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Suíça/epidemiologiaRESUMO
PURPOSE: According to the DSM, functional impairment is a main criterion for the general definition of personality disorders (PDs), but research suggests that some PDs might not be related to impaired functioning. Occupational functioning has rarely been examined in all ten DSM PDs. METHODS: We analysed 511 adults aged 20-41 years from the general population of the canton of Zurich, Switzerland, using data from the Epidemiology Survey of the Zurich Programme for Sustainable Development of Mental Health Services. All PDs were assessed with dimensional trait-scores and associations with indicators of occupational functioning were analysed with generalised linear models. RESULTS: Each PD revealed at least a weak association with some form of occupational impairment. Most PDs, especially from cluster A and B, were significantly related to occupational dysfunction, in particular low education level, conflicts in the workplace, dismissal or demotion, and unemployment. In contrast, obsessive-compulsive PD was mostly unrelated to occupational functioning. A total personality pathology dose-response relationship was observed for low education level, conflicts in the workplace, dismissal or demotion, and unemployment. CONCLUSIONS: Impairment in occupational functioning is an important aspect particularly of cluster A and B PDs. Assuming that functional impairment is a predictor of illness severity, we advocate that clinicians should carefully explore indicators of occupational functioning in the diagnosis, prognosis, and treatment of PDs. The findings discussed herein have implications for general treatment, interventions in the work environment, or re-integration of patients into the labour force.
Assuntos
Determinação da Personalidade/estatística & dados numéricos , Transtornos da Personalidade/diagnóstico , Inventário de Personalidade/estatística & dados numéricos , Trabalho , Adolescente , Adulto , Feminino , Humanos , Entrevistas como Assunto , Masculino , Serviços de Saúde Mental , Pessoa de Meia-Idade , Transtornos da Personalidade/psicologia , Fatores Socioeconômicos , Inquéritos e Questionários , Suíça , Local de Trabalho , Adulto JovemRESUMO
PURPOSE: According to DSM, interpersonal functioning deficits are a main criterion for the general definition of personality disorders (PDs), but some PD diagnoses do not appear to be related to impaired interpersonal functioning. Social deficits have rarely been studied in all PD dimensions to date. METHODS: We analyzed 511 adults aged 20-41 years from the general population of the canton of Zurich, Switzerland, using data from the Epidemiology Survey of the Zurich Programme for Sustainable Development of Mental Health Services (ZInEP). PD dimensions were measured with a questionnaire and indicators of interpersonal functioning with a semi-structured interview. Associations were analyzed with generalized linear models. RESULTS: All PD dimensions were significantly associated with various indicators of interpersonal functioning deficits, such as distress and conflicts in friendships and partnership, feeling lonely, few close friends, and reduced social support. Schizotypal and borderline PD were relatively strongly associated with distress in friendships when compared with other PD dimensions. Furthermore, both dimensions were significantly related to all indicators of interpersonal functioning deficits. CONCLUSIONS: Subjects scoring high on any PD dimension reported considerable deficits in interpersonal functioning as characterized by a solitary lifestyle, conflictual and distressful social relations, and lack of social support. All DSM-IV PDs are associated with poor interpersonal functioning, but there is some evidence that schizotypal and borderline symptomatology affects deficits in social interactions even more profoundly and pervasively than other PD dimensions.
Assuntos
Relações Interpessoais , Transtornos da Personalidade/diagnóstico , Adulto , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Modelos Lineares , Masculino , Transtornos da Personalidade/epidemiologia , Qualidade de Vida , Comportamento Social , Apoio Social , Inquéritos e Questionários , Suíça/epidemiologiaRESUMO
MCL1 is a member of the BCL2 family of apoptosis regulators, which play a critical role in promoting cancer survival and drug resistance. We previously described PRT1419, a potent, MCL1 inhibitor with anti-tumor efficacy in various solid and hematologic malignancies. To identify novel biomarkers that predict sensitivity to MCL1 inhibition, we conducted a gene essentiality analysis using gene dependency data generated from CRISPR/Cas9 cell viability screens. We observed that clear cell renal cancer (ccRCC) cell lines with damaging PBRM1 mutations displayed a strong dependency on MCL1. PBRM1 (BAF180), is a chromatin-targeting subunit of mammalian pBAF complexes. PBRM1 is frequently altered in various cancers particularly ccRCC with ~40% of tumors harboring damaging PBRM1 alterations. We observed potent inhibition of tumor growth and induction of apoptosis by PRT1419 in various preclinical models of PBRM1-mutant ccRCC but not PBRM1-WT. Depletion of PBRM1 in PBRM1-WT ccRCC cell lines induced sensitivity to PRT1419. Mechanistically, PBRM1 depletion coincided with increased expression of pro-apoptotic factors, priming cells for caspase-mediated apoptosis following MCL1 inhibition. Increased MCL1 activity has been described as a resistance mechanism to Sunitinib and Everolimus, two approved agents for ccRCC. PRT1419 synergized with both agents to potently inhibit tumor growth in PBRM1-loss ccRCC. PRT2527, a potent CDK9 inhibitor which depletes MCL1, was similarly efficacious in monotherapy and in combination with Sunitinib in PBRM1-loss cells. Taken together, these findings suggest PBRM1 loss is associated with MCL1i sensitivity in ccRCC and provide rationale for the evaluation of PRT1419 and PRT2527 for the treatment for PBRM1-deficient ccRCC.
RESUMO
BACKGROUND: Informal and formal volunteering engagement is a proxy for social integration and may have beneficial effects for physical and mental well-being in persons with multiple sclerosis (pwMS). As literature on the topic among the pwMS is lacking, this study aimed to determine frequency and type of volunteering performed by pwMS and to identify factors associated with volunteering. METHODS: Cross-sectional, self-reported data of 615 pwMS participating in the Swiss Multiple Sclerosis Registry were analyzed using descriptive statistics to determine frequency and type of volunteering engagement. Univariable and multivariable generalized linear models with binomial distribution and log link function were used to identify factors associated with volunteering. Age, sex, employment status and gait disability were added to the multivariable model as fixed confounders. Sociodemographic, health-, work- and daily activity-related factors were included in the analysis. RESULTS: About one third (29.4%) of participants reported engagement in volunteering activities, most often through charities (16.02%) and cultural organizations (14.36%). In the multivariable model, participants who had a university degree were more likely to volunteer than those with lower level of education (RR = 1.48 95% CI [1.14; 1.91]). The ability to pursue daily activities (as measured by the EQ-5D subscale) was strongly associated with participation in volunteering among pwMS. Compared with pwMS who had no or only slight limitations in daily activities, those with severe problems were markedly less likely to engage in volunteering (RR = 0.41, 95% CI [0.21; 0.80]) . Finally, pwMS who reported caring for and supporting their family (i.e., being a homemaker) were more likely to engage in volunteering activities than those who did not (RR = 1.52, 95% CI [1.15; 2.01]). CONCLUSION: Nearly one in three pwMS engaged in diverse volunteering activities. Having a university degree, being less limited in daily activities and being a homemaker increased the probability of pursuing volunteering activities. Contingent on individual-level motivations, resources or physical abilities, pwMS who experience challenges in performing daily activities or social barriers should be made aware of barrier-free offers of socially inclusive and volunteering activities, often provided by the national MS societies and health leagues.
Assuntos
Esclerose Múltipla , Humanos , Suíça/epidemiologia , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/terapia , Estudos Transversais , Atividades Cotidianas , Saúde MentalRESUMO
The aim of our study was to investigate whether self-reported feeling of loneliness (FoL) and COVID-19-specific health anxiety were associated with the presence of depressive symptoms during the first coronavirus disease 2019 (COVID-19) wave. Questionnaires of 603 persons of the Swiss Multiple Sclerosis Registry (SMSR) were cross-sectionally analyzed using descriptive and multivariable regression methods. The survey response rate was 63.9%. Depressive symptoms were assessed by the Beck Depression Inventory-Fast Screen (BDI-FS). COVID-19-specific health anxiety and FoL were measured using two 5-item Likert scaled pertinent questions. High scoring FoL (2.52, 95% confidence interval (CI) (2.06-2.98)) and/or COVID-19 specific health anxiety (1.36, 95% CI (0.87-1.85)) were significantly associated with depressive symptoms. Further stratification analysis showed that the impact of FoL on depressive symptoms affected all age groups. However, it was more pronounced in younger PwMS, whereas an impact of COVID-19 specific health anxiety on depressive symptoms was particularly observed in middle-aged PwMS. FoL and COVID-19-specific health anxiety were age-dependently associated with depressive symptoms during the first COVID-19 wave in Switzerland. Our findings could guide physicians, health authorities, and self-help groups to better accompany PwMS in times of public health crises.
Assuntos
COVID-19 , Esclerose Múltipla , Pessoa de Meia-Idade , Humanos , COVID-19/epidemiologia , Solidão , Depressão/epidemiologia , Esclerose Múltipla/complicações , Esclerose Múltipla/epidemiologia , Suíça/epidemiologia , Ansiedade/epidemiologiaRESUMO
BACKGROUND: While comorbidities increase with age, duration of multiple sclerosis (MS) leads to disability accumulation in persons with MS. The influence of ageing vis-a-vis MS duration remains largely unexplored. We studied the independent associations of ageing and MS duration with disability and comorbidities in the Swiss MS Registry participants. METHODS: Self-reported data was cross-sectionally analyzed using confounder-adjusted logistic regression models for 6 outcomes: cancer, type 2 diabetes (T2D), hypertension, cardiac diseases, depression, and having at least moderate or severe gait disability. Using cubic splines, we explored non-linear changes in risk shapes. RESULTS: Among 1615 participants age was associated with cardiac diseases (OR 1.05, 95% CI [1.02, 2.08]), hypertension (OR 1.08, 95% CI [1.06, 2.10]), T2D (OR 1.10, 95%CI [1.05, 1.16]) and cancer (OR 1.04, 95% CI [1.01, 1.07]). MS duration was not associated with comorbidities, except for cardiac diseases (OR 1.03, 95% CI [1.00, 1.06]). MS duration and age were independently associated with having at least moderate gait disability (OR 1.06, 95% CI [1.04, 1.07]; OR 1.04, 95% CI [1.02, 1.05], respectively), and MS duration was associated with severe gait disability (OR 1.05, 95% CI [1.03, 1.08]). The spline analysis suggested a non-linear increase of having at least moderate gait disability with age. CONCLUSIONS: Presence of comorbidities was largely associated with age only. Having at least moderate gait disability was associated with both age and MS duration, while having severe gait disabity was associated with MS duration only.