Introduction: Discontinuation of tyrosine kinase inhibitor (TKI) treatment is emerging as the main therapy goal for Chronic Myeloid Leukemia (CML) patients. The DESTINY trial showed that TKI dose reduction prior to cessation can lead to an increased number of patients achieving sustained treatment free remission (TFR). However, there has been no systematic investigation to evaluate how dose reduction regimens can further improve the success of TKI stop trials. Methods: Here, we apply an established mathematical model of CML therapy to investigate different TKI dose reduction schemes prior to therapy cessation and evaluate them with respect to the total amount of drug used and the expected TFR success. Results: Our systematic analysis confirms clinical findings that the overall time of TKI treatment is a major determinant of TFR success, while highlighting that lower dose TKI treatment for the same duration is equally sufficient for many patients. Our results further suggest that a stepwise dose reduction prior to TKI cessation can increase the success rate of TFR, while substantially reducing the amount of administered TKI. Discussion: Our findings illustrate the potential of dose reduction schemes prior to treatment cessation and suggest corresponding and clinically testable strategies that are applicable to many CML patients.

INTRODUÇÃO: O diabetes mellitus tipo 2 (DM2) é uma doença correlacionada com a obesidade mórbida. O paciente obeso apresenta efeito incretínico suprimido e consequente desbalanço da homeostase glicêmica. Diversos estudos evidenciam a melhora do DM2 após a confecção da Gastroplastia com derivação intestinal em Y de Roux (GDYR). Os mecanismos de controle da glicemia podem ser de longo e curto prazo. Os mecanismos de ação precoce estão ligados à restrição calorica, melhora da resistência insulínica, da função da célula beta pancreática e retorno do efeito incretínico pelo aumento do GLP1 e GIP, porém os dados são conflitantes. MÉTODOS: Onze pacientes obesos graves diabéticos foram submetidos à GDYR com confecção de gastrostomia no remanescente gástrico após perda de peso inicial de 10%. Os pacientes foram submetidos à coleta de entero-hormônios, perfil glicêmico e Teste de Tolerância Oral à glicose (TTOG) no pré-operatório em curva temporal que foi comparado ao pós-operatório por Via Oral e por Via da Gastrostomia em até 7 dias após o procedimento. RESULTADOS: A média da idade foi 46,09±7,08 anos. No pré-operatorio, o peso médio foi 120,97±17,02 quilogramas, altura 1,67±0,11 metros, IMC médio 44,06±6,59 kg/m2, glicemia de jejum média 194,55±62,45 mg/dl e hemoglobina glicada 8,74±1,64%. Em 77,7% dos pacientes, houve remissão precoce do DM2 no pós-operatório avaliado pelo TTOG. Também foi observada queda significante da glicemia, insulinemia e do HOMA-IR independente da via administrada. Ocorreu aumento significativo do GLP1 e redução do GIP pela Via Oral pós-operatória. A Grelina não apresentou alterações. CONCLUSÃO: Evidenciou-se redução da glicemia e da resistência periférica nos primeiros dias de pós-operatório da GDYR, independente da via de passagem do alimento. A alteração no efeito incretínico (aumento do GLP1 e redução do GIP) só foi observada na Via Oral pós-operatória / INTRODUCTION: Type 2 diabetes mellitus (DM2) is a disease correlated with morbidly obesity. The obese patient has a suppressed incretin effect and consequent inbalance of glycemic homeostasis. Several studies have shown an improvement in DM2 after Gastroplasty with Roux-en-Y gastric bypass (RYGB). The mechanisms of glycemic control may be long-term and shortterm. The mechanisms of early action are linked to caloric restriction, improvement of insulin resistance, pancreatic beta cell function and return of the incretin effect through the increase of GLP1 and GIP, but the data are conflicting. METHODS: Eleven diabetic obese patients underwent RYGB with gastrostomy in gastric remnant after initial 10% weight loss. Patients were submitted to assessment of enterohormones, glycemic profile and Oral Glucose Tolerance Test (OGTT) in the preoperative period in a time curve that was compared to the postoperative period by Oral Via and Gastrostomy Via up to 7 days after the procedure .RESULTS: The mean age of the group was 46.09 ± 7.08 years. In the preoperative the mean weight was 120.97 ± 17.02 kilograms, height of 1.67 ± 0.11 meters, mean BMI of 44.06 ± 6, 59 kg/m2, mean fasting blood glucose of 194.55 ± 62.45 mg/dl and glycated hemoglobin 8.74 ± 1.64%. In 77.7% of the patients there was remission of DM2 in postoperative evaluated by the OGTT. Significant decrease in glycemia, insulinemia and HOMA-IR was also observed, regardless of the route of administration. There was a significant increase in GLP1 and reduction of GIP by the postoperative oral route. Ghrelin did not change. CONCLUSION: A reduction in glycemia and peripheral insulinal resistance was observed in early postoperative days of RYGB, independent of the food route. The change in incretin effect (increase of GLP1 and reduction of GIP) was only observed in the postoperative oral route

Contexto: O tratamento da hepatite autoimune (HAI) composto por prednisona e azatioprina proporciona melhora clínico-laboratorial em até 90% dos pacientes. Entretanto, a remissão completa não é alcançável na maioria dos casos. Cloroquina é um antimalárico utilizado no tratamento de doenças reumatológicas autoimunes e em estudo aberto de manutenção da remissão da HAI foi sugerido menor risco de recidiva da doença com o uso da droga. Objetivos: Avaliar o uso da cloroquina em associação à prednisona no tratamento da HAI em estudo randomizado. Métodos: 57 pacientes com indicação de tratamento da HAI foram randomizados para receber azatioprina ou cloroquina associadas à prednisona, de 2003 a 2012. Para os que mantiveram normalização das transaminases por 18 meses, biópsia hepática foi realizada para avaliação histológica. O desfecho primário foi a remissão completa ao tratamento, composta por remissão bioquímica e histológica da doença. O valor de p < 0,05 foi considerado estatisticamente significativo. Resultados: Não houve diferença entre os grupos quanto às características clínicas, sorológicas, histológicas e de tratamento prévio, ao início do estudo. A idade média foi de 37,2 ± 16,84 anos, 43,8% com fibrose avançada (F3/4) no início do estudo. Não houve diferença estatística na taxa de resposta bioquímica (67% vs. 53,8%, p=0,413) ou histológica (32,2% vs. 15,4%, p=0,21), assim como na dose média de prednisona utilizada. Os pacientes que não atingiram remissão completa no estudo tiveram seguimento com nova terapia. Entre eles, quatro obtiveram remissão histológica com a associação de azatioprina, cloroquina e prednisona. Em relação aos efeitos adversos, houve maior taxa no grupo da cloroquina, porém com tendência a menor prevalência de comorbidades neste grupo. Conclusão: Quando bem toleradas, cloroquina e prednisona proporcionaram resposta completa em pacientes com AIH, sem diferença estatística em relação à terapia padrão. (ClinicalTrials.gov NCT 02463331) / Background: The treatment of autoimmune hepatitis (AIH) with prednisone and azathioprine provides disease remission. However, a complete biochemical and histological response is unreachable in most patients. Chloroquine is an antimalarial drug used for treating rheumatological diseases. It was studied as a single drug for the maintenance of AIH remission in an open study, which suggested a lower risk of relapse in the chloroquine group. Aims: To evaluate a possible role of chloroquine and prednisone for AIH treatment in a randomized study. Methods: 57 AIH adult patients with indication of treatment were enrolled to receive azathioprine or chloroquine, both with varying doses of prednisone, from 2003 to 2012. For those who had maintained biochemical remission for 18 months, liver biopsy was performed to evaluate histological remission. The primary outcome was the achievement of complete response to treatment. A p-value < 0.05 was considered statistically significant. Results: There were no significant differences between the groups concerning clinical, serological, histological, and treatment features at baseline. The average age was 37.2 ± 16.84 years, 43.8% with advanced fibrosis (F3/4) at baseline. There was no statistical differences in biochemical (67.7% vs. 53.8%, p=0.41) or histological response rate (32.26% vs. 15.38%, p = 0.217), as well as in the mean prednisone dose. There was a higher rate of adverse effects in the chloroquine group, but a lower frequency of comorbidities in this group. Conclusion: When well tolerated, chloroquine with prednisone provided a complete therapeutic response in AIH patients with no statistical difference when compared to the standard treatment. (ClinicalTrials.gov NCT 02463331)

Orientador: João Pedro Pezzato / Resumo: A presente pesquisa tem como objetivo investigar e analisar a participação de leitores escritores presos e presas em três presídios do sul do estado de Minas Gerais, Brasil, que aderiram, durante os anos de 2015 e 2017, ao projeto “Remição pela Leitura”, no âmbito do sistema prisional brasileiro. Esse projeto integrador fundamenta-se na Lei Nº 12.433/2011, que dispõe sobre a remição de parte do tempo de execução da pena por estudo ou por trabalho, e na Portaria Conjunta JF/DEPEN N.º 276/2012, do Ministro Corregedor-geral da Justiça Federal e do Diretor-geral do Departamento Penitenciário Nacional, que disciplina o Projeto da “Remição pela Leitura” no Sistema Penitenciário Federal. Em Minas Gerais, o projeto “Remição pela Leitura” foi instituído pela Resolução Conjunta SEDS/TJMG N° 204/2016. A partir de uma perspectiva de pesquisa qualitativa, e adotando um caminho de investigação denominado Paradigma Indiciário, foram analisadas as resenhas elaboradas por presos leitores sob o ponto de vista da experiência de leitura e escrita. O paradigma indiciário busca interpretar os escritos mediante a observação de sinais e indícios reveladores de significados. A fundamentação teórica baseia-se em documentos legais (BRASIL, 2011, 2012; MINAS GERAIS, 2016) e produções teóricas de autores como Petit (2008; 2013), Iser (1996a; 1996b; 1999; 2002), Cândido (2004), Larrosa (2002a; 2002b), Jauss (1994; 2002), Manguel (1997; 2004), Calvino (1982; 1993; 1994; 2001) dentre outros. A questão que s... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The current research aims to investigate and analyze the participation of readers writers imprisoned in three prisons in the southern state of Minas Gerais, Brazil, that joined, during the years of 2015 and 2017, the project "Remission for Reading", within the brazilian prison system. This integrative project is based on the Law Nº 12.433/2011, which provides the remission of part of the penalty execution time due to study or work, and in the Joint Ordinance JF/DEPEN N.º 276/2012, of the Minister of the Comptroller General of the Federal Court and the general Director of the National Penitentiary Department, which disciplines the "Remission for Reading" Project in the Federal Penitentiary System. In Minas Gerais, the project "Remission for Reading" was instituted by the Joint Resolution SEDS/TJMG N° 204/2016. From a qualitative research perspective, and adopting an inquiry path entitled Indiciary Paradigm, were analyzed the reviews elaborated by imprisoned readers from the point of view of the experience of reading and writing. The indiciary paradigm seeks to interpret the writings through the observation of signs and evidence that reveal meanings. The theoretical construct is based on legal documents (BRASIL, 2011, 2012, MINAS GERAIS, 2016) and theoretical productions of authors such as Petit (2008; 2013), Iser (1996a; 1996b; 1999; 2002), Cândido (2004), Larrosa (2002a; 2002b), Jauss (1994; 2002), Manguel (1997; 2009), Calvino (1982; 1993; 1994; 2001), among others. The ques... (Complete abstract click electronic access below) / Resumen: La presente investigación tiene como objetivo investigar y analizar la participación de lectores escritores presos y presas en tres cárceles del sur del estado de Minas Gerais, Brasil, que se adhirieron, durante los años 2015 y 2017, al proyecto "Remisión por la lectura" en el marco del sistema penitenciario brasileño. Este proyecto integrador se fundamenta en la Ley Nº 12.433 / 2011, que dispone sobre la remisión de parte del tiempo de ejecución de la pena por estudio o por trabajo, y en la Portaria Conjunta JF / DEPEN Nº 276/2012, del Ministro Corregidor- de la Justicia Federal y del Director General del Departamento Penitenciario Nacional, que disciplina el Proyecto de la "Remisión por la Lectura" en el Sistema Penitenciario Federal. En Minas Gerais, el proyecto "Remisión por la Lectura" fue instituido por la Resolución Conjunta SEDS / TJMG N ° 204/2016. A partir de una perspectiva de investigación cualitativa, y adoptando un camino de investigación denominado Paradigma Indiciario, se analizaron las reseñas elaboradas por presos lectores desde el punto de vista de la experiencia de lectura y escritura. El paradigma indiciario busca interpretar los escritos mediante la observación de signos e indicios reveladores de significados. La fundamentación teórica se basa en documentos legales (BRASIL, 2011, 2012, MINAS GERAIS, 2016) y producciones teóricas de autores como Petit (2008, 2013), Iser (1996a, 1996b, 1999, 2002), Cándido (2004), (2002, 2002b), Jauss (1994; 2002), Manguel... (Resumen completo clicar acceso eletrônico abajo) / Doutor

INTRODUÇÃO: O diabetes mellitus tipo 2 (DM2) é uma doença correlacionada com a obesidade mórbida. O paciente obeso apresenta efeito incretínico suprimido e consequente desbalanço da homeostase glicêmica. Diversos estudos evidenciam a melhora do DM2 após a confecção da Gastroplastia com derivação intestinal em Y de Roux (GDYR). Os mecanismos de controle da glicemia podem ser de longo e curto prazo. Os mecanismos de ação precoce estão ligados à restrição calorica, melhora da resistência insulínica, da função da célula beta pancreática e retorno do efeito incretínico pelo aumento do GLP1 e GIP, porém os dados são conflitantes. MÉTODOS: Onze pacientes obesos graves diabéticos foram submetidos à GDYR com confecção de gastrostomia no remanescente gástrico após perda de peso inicial de 10%. Os pacientes foram submetidos à coleta de entero-hormônios, perfil glicêmico e Teste de Tolerância Oral à glicose (TTOG) no pré-operatório em curva temporal que foi comparado ao pós-operatório por Via Oral e por Via da Gastrostomia em até 7 dias após o procedimento. RESULTADOS: A média da idade foi 46,09±7,08 anos. No pré-operatorio, o peso médio foi 120,97±17,02 quilogramas, altura 1,67±0,11 metros, IMC médio 44,06±6,59 kg/m2, glicemia de jejum média 194,55±62,45 mg/dl e hemoglobina glicada 8,74±1,64%. Em 77,7% dos pacientes, houve remissão precoce do DM2 no pós-operatório avaliado pelo TTOG. Também foi observada queda significante da glicemia, insulinemia e do HOMA-IR independente da via administrada. Ocorreu aumento significativo do GLP1 e redução do GIP pela Via Oral pós-operatória. A Grelina não apresentou alterações. CONCLUSÃO: Evidenciou-se redução da glicemia e da resistência periférica nos primeiros dias de pós-operatório da GDYR, independente da via de passagem do alimento. A alteração no efeito incretínico (aumento do GLP1 e redução do GIP) só foi observada na Via Oral pós-operatória / INTRODUCTION: Type 2 diabetes mellitus (DM2) is a disease correlated with morbidly obesity. The obese patient has a suppressed incretin effect and consequent inbalance of glycemic homeostasis. Several studies have shown an improvement in DM2 after Gastroplasty with Roux-en-Y gastric bypass (RYGB). The mechanisms of glycemic control may be long-term and shortterm. The mechanisms of early action are linked to caloric restriction, improvement of insulin resistance, pancreatic beta cell function and return of the incretin effect through the increase of GLP1 and GIP, but the data are conflicting. METHODS: Eleven diabetic obese patients underwent RYGB with gastrostomy in gastric remnant after initial 10% weight loss. Patients were submitted to assessment of enterohormones, glycemic profile and Oral Glucose Tolerance Test (OGTT) in the preoperative period in a time curve that was compared to the postoperative period by Oral Via and Gastrostomy Via up to 7 days after the procedure .RESULTS: The mean age of the group was 46.09 ± 7.08 years. In the preoperative the mean weight was 120.97 ± 17.02 kilograms, height of 1.67 ± 0.11 meters, mean BMI of 44.06 ± 6, 59 kg/m2, mean fasting blood glucose of 194.55 ± 62.45 mg/dl and glycated hemoglobin 8.74 ± 1.64%. In 77.7% of the patients there was remission of DM2 in postoperative evaluated by the OGTT. Significant decrease in glycemia, insulinemia and HOMA-IR was also observed, regardless of the route of administration. There was a significant increase in GLP1 and reduction of GIP by the postoperative oral route. Ghrelin did not change. CONCLUSION: A reduction in glycemia and peripheral insulinal resistance was observed in early postoperative days of RYGB, independent of the food route. The change in incretin effect (increase of GLP1 and reduction of GIP) was only observed in the postoperative oral route

Contexto: O tratamento da hepatite autoimune (HAI) composto por prednisona e azatioprina proporciona melhora clínico-laboratorial em até 90% dos pacientes. Entretanto, a remissão completa não é alcançável na maioria dos casos. Cloroquina é um antimalárico utilizado no tratamento de doenças reumatológicas autoimunes e em estudo aberto de manutenção da remissão da HAI foi sugerido menor risco de recidiva da doença com o uso da droga. Objetivos: Avaliar o uso da cloroquina em associação à prednisona no tratamento da HAI em estudo randomizado. Métodos: 57 pacientes com indicação de tratamento da HAI foram randomizados para receber azatioprina ou cloroquina associadas à prednisona, de 2003 a 2012. Para os que mantiveram normalização das transaminases por 18 meses, biópsia hepática foi realizada para avaliação histológica. O desfecho primário foi a remissão completa ao tratamento, composta por remissão bioquímica e histológica da doença. O valor de p < 0,05 foi considerado estatisticamente significativo. Resultados: Não houve diferença entre os grupos quanto às características clínicas, sorológicas, histológicas e de tratamento prévio, ao início do estudo. A idade média foi de 37,2 ± 16,84 anos, 43,8% com fibrose avançada (F3/4) no início do estudo. Não houve diferença estatística na taxa de resposta bioquímica (67% vs. 53,8%, p=0,413) ou histológica (32,2% vs. 15,4%, p=0,21), assim como na dose média de prednisona utilizada. Os pacientes que não atingiram remissão completa no estudo tiveram seguimento com nova terapia. Entre eles, quatro obtiveram remissão histológica com a associação de azatioprina, cloroquina e prednisona. Em relação aos efeitos adversos, houve maior taxa no grupo da cloroquina, porém com tendência a menor prevalência de comorbidades neste grupo. Conclusão: Quando bem toleradas, cloroquina e prednisona proporcionaram resposta completa em pacientes com AIH, sem diferença estatística em relação à terapia padrão. (ClinicalTrials.gov NCT 02463331) / Background: The treatment of autoimmune hepatitis (AIH) with prednisone and azathioprine provides disease remission. However, a complete biochemical and histological response is unreachable in most patients. Chloroquine is an antimalarial drug used for treating rheumatological diseases. It was studied as a single drug for the maintenance of AIH remission in an open study, which suggested a lower risk of relapse in the chloroquine group. Aims: To evaluate a possible role of chloroquine and prednisone for AIH treatment in a randomized study. Methods: 57 AIH adult patients with indication of treatment were enrolled to receive azathioprine or chloroquine, both with varying doses of prednisone, from 2003 to 2012. For those who had maintained biochemical remission for 18 months, liver biopsy was performed to evaluate histological remission. The primary outcome was the achievement of complete response to treatment. A p-value < 0.05 was considered statistically significant. Results: There were no significant differences between the groups concerning clinical, serological, histological, and treatment features at baseline. The average age was 37.2 ± 16.84 years, 43.8% with advanced fibrosis (F3/4) at baseline. There was no statistical differences in biochemical (67.7% vs. 53.8%, p=0.41) or histological response rate (32.26% vs. 15.38%, p = 0.217), as well as in the mean prednisone dose. There was a higher rate of adverse effects in the chloroquine group, but a lower frequency of comorbidities in this group. Conclusion: When well tolerated, chloroquine with prednisone provided a complete therapeutic response in AIH patients with no statistical difference when compared to the standard treatment. (ClinicalTrials.gov NCT 02463331)

<p>Type 1 diabetes is caused by immuno-mediated β-cell destruction leading to insulin deficiency and hyperglycaemia. The decline in β-cell function and the clinical course after diagnosis vary. Whether the process of destruction of the β-cells is associated with markers of a non-specific inflammatory response is unknown. The aims of these studies were to identify factors of importance for clinical remission (low insulin need and normoglycaemia) and long-term β-cell function and estimate the degree of non-inflammatory response in type 1 diabetes in young adults. Clinical remission and β-cell function eight years after diagnosis were assessed and related to clinical, biochemical and immunological variables at diagnosis, including islet autoantibodies [ICA, GADA, IA-2A]. Markers of low-grade inflammation in plasma [CRP and IL-6] were estimated and the concentrations were related β-cell function [plasma C-peptide], glycaemic control and autoimmunity at diagnosis and the first year thereafter. The results showed that clinical remission occurred in about half of the patients with newly diagnosed type 1 diabetes. Preserved β-cell function eight years after diagnosis was observed in 16% of the patients classified at diagnosis as having autoimmune type 1 diabetes. Duration of remission was dependent on BMI, degree of metabolic derangement and presence of GADA at diagnosis. BMI at diagnosis was also of importance for preserved β-cell function after eight years of the disease, as were the amount of islet antibodies and presence of ICA. Elevated CRP levels were noted in the majority of cases at diagnosis and both CRP and IL-6 concentrations were stable the first year after clinical diagnosis. High concentrations of CRP and IL-6 did not relate to β-cell destruction or the degree of autoimmunity. CRP concentrations were higher in islet antibody negative than in positive patients. CRP also correlated positively to BMI, C-peptide at 12 months and to increasing HbA1c between six and 12 months. In general, females had shorter remissions, lower concentrations of serum bicarbonate and higher levels and prevalence of GADA at diagnosis, compared to males. Females also had higher HbA1c and CRP values the first year after diagnosis. In summary, BMI at diagnosis is a strong predictor of duration of remission and preservation of β-cell function. Elevated CRP concentrations are correlated to factors linked rather to insulin resistance than to β-cell destruction. Females appear to have a more acute onset and a more severe course of the disease than males.</p>

Type 1 diabetes is caused by immuno-mediated β-cell destruction leading to insulin deficiency and hyperglycaemia. The decline in β-cell function and the clinical course after diagnosis vary. Whether the process of destruction of the β-cells is associated with markers of a non-specific inflammatory response is unknown. The aims of these studies were to identify factors of importance for clinical remission (low insulin need and normoglycaemia) and long-term β-cell function and estimate the degree of non-inflammatory response in type 1 diabetes in young adults. Clinical remission and β-cell function eight years after diagnosis were assessed and related to clinical, biochemical and immunological variables at diagnosis, including islet autoantibodies [ICA, GADA, IA-2A]. Markers of low-grade inflammation in plasma [CRP and IL-6] were estimated and the concentrations were related β-cell function [plasma C-peptide], glycaemic control and autoimmunity at diagnosis and the first year thereafter. The results showed that clinical remission occurred in about half of the patients with newly diagnosed type 1 diabetes. Preserved β-cell function eight years after diagnosis was observed in 16% of the patients classified at diagnosis as having autoimmune type 1 diabetes. Duration of remission was dependent on BMI, degree of metabolic derangement and presence of GADA at diagnosis. BMI at diagnosis was also of importance for preserved β-cell function after eight years of the disease, as were the amount of islet antibodies and presence of ICA. Elevated CRP levels were noted in the majority of cases at diagnosis and both CRP and IL-6 concentrations were stable the first year after clinical diagnosis. High concentrations of CRP and IL-6 did not relate to β-cell destruction or the degree of autoimmunity. CRP concentrations were higher in islet antibody negative than in positive patients. CRP also correlated positively to BMI, C-peptide at 12 months and to increasing HbA1c between six and 12 months. In general, females had shorter remissions, lower concentrations of serum bicarbonate and higher levels and prevalence of GADA at diagnosis, compared to males. Females also had higher HbA1c and CRP values the first year after diagnosis. In summary, BMI at diagnosis is a strong predictor of duration of remission and preservation of β-cell function. Elevated CRP concentrations are correlated to factors linked rather to insulin resistance than to β-cell destruction. Females appear to have a more acute onset and a more severe course of the disease than males.

Der Langzeitverlauf und die Häufigkeit sogenannter spontaner Remissionen wurde anhand von 77 Fallen mit einer Lifetime-Diagnose einer Angststörung untersucht. Die 77 Angstfälle wurden als Teil der Münchner Follow-up-Studie im Rahmen einer allgemeinen Bevölkerungsuntersuchung im Jahre 1974 identifiziert und wurden über einen Zeitraum von sieben Jahren (bis 1981) weiter untersucht. Die Diagnosen wurden einerseits durch ein standardisiertes diagnostisches Instrument (den DIS), andererseits über eine klinisch-psychiatrische Nachuntersuchung (1981) abgesichert. In Ergänzung hierzu wurde der Verlauf der psychopathologischen Symptome sowie die psychologische und psychosoziale Integration der Versuchspersonen beurteilt. Ergebnisse: Die Lebenszeit-Prävalenz, irgendeine Anststörung zu entwickeln, betrug 13,9%. Einfache und soziale Phobien wiesen eine Prävalenz von 8,0%, Agoraphobie von 5,7%, Zwangsstörungen von 2,0% und Panikstörungen von 2,4% auf. Die Inzidenz, d.h. das Auftreten neuer Fälle im Zeitraum zwischen der Erst- und Zweituntersuchung war niedrig, mit Ausnahme für Panikstörungen (1,2%, bei einer Gesamtprävalenz von 2,4%) und Agoraphobie (1,3% bei einer Gesamtprävalenz von 5,7%). Die Komorbidität war sowohl innerhalb der Angststörungen wie auch bezüglich anderer psychischer Störungen erhöht. 62% hatten mehr als eine Angstdiagnose, Major Depression und Abhängigkeit von Alkohol oder Medikamenten waren die häufigsten komorbiden Störungen, die in der überwiegenden Mehrzahl deutlich nach dem Beginn der Angststörung auftraten. Spontanremissionen wurden auf drei unterschiedlichen Ebenen definiert, von denen ein Kombinationsmaβ als Hauptergebnis interpretiert wurde. Danach war die symptomatische Remission in alien Angstgruppen niedrig, während die psychosoziale Remissionsrate ein günstigeres Bild mit Remissionsraten zwischen 28,6% für Panikstörung und 53,1% für einfache und soziale Phobien ergab. Das kombinierte spontane Remissionsmaβ ergab für keine der Zwangsstörungen, nur 14,3% der Panikstörungen, 19,2% der Agoraphobien und 18,8% der einfachen und sozialen Phobie eine voile Remission. Die Ergebnisse unterstreichen, daβ Angststörungen zumeist in der Kindheit oder frühen Adoleszenz beginnen und dazu neigen, chronisch über den Groβteil des Lebens zu persistieren und nur selten zu remittieren.

The aim of the present thesis was to examine the effectiveness of the Illness Management and Recovery (IMR) program for teaching clients with schizophrenia or schizoaffective disorder to better manage their illness and to promote recovery. This was accomplished through an examination of the program’s effects on psychosocial functioning and psychopathology, the evaluation of general and specific impact of neurocognition on learning the fundamentals of illness self-management, and the impact of symptom severity on outcome of the IMR program. The utility of the illness management and recovery scale to evaluate illness self-management of clients with schizophrenia and schizoaffective disorder was also investigated. The effects of the IMR program were evaluated in a randomized controlled trial that compared participants in the program to participants receiving treatment as usual. 41 participants were recruited at six psychiatric outpatient rehabilitation centers in Uppsala, Sweden, and were randomly assigned to IMR groups for approximately 40 sessions or to a treatment as usual control condition. The IMR program participants demonstrated greater improvement compared to participants in treatment as usual in illness self-management, reduced psychiatric symptoms, improved coping skills, and decreases in suicidal ideation. The findings suggest that the IMR program is effective in improving the ability of individuals with schizophrenia and schizoaffective disorder to better manage their illness. Possible association between neurocognitive functioning and the acquisition of illness self-management skills was investigated in a total of 53 participants who completed the IMR program. Speed of processing was related to client reported illness self-management skills acquisition, before and after controlling for psychiatric symptoms and medication, but neurocognitive functioning did not predict improvement in clinician ratings of client illness self-management skills. The findings suggest that compromised neurocognitive functioning does not reduce response to training in illness self-management. The impact of symptom severity on outcome of the IMR program was explored in 52 participants who completed the program. The results suggest that significantly more participants met the severity criterion of remission at post-treatment, and it appears that participants not reaching the severity criterion at post-treatment, also benefited from the IMR program, as indicated by the similar effect sizes of the two subgroups (meeting versus not meeting the severity criterion at post-treatment). The psychometric properties of the Illness Management and Recovery Scale (IMRS) were evaluated in 107 participants with a diagnosis of schizophrenia or schizoaffective disorder. And an item-by-item investigation was conducted in order to establish their utility in monitoring the clients' progress in the IMR program. Both the client and clinician version of the IMRS demonstrated satisfactory internal consistency, large test-retest reliability, and convergent validity with conceptually related measures of psychiatric symptoms, quality of life, and perception of recovery. The findings support the utility of the IMRS as a measure of illness self-management and recovery in clients with schizophrenia and schizoaffective disorder. The general findings of this thesis support the IMR program to be effective in improving the ability of the participants to manage their disorder. The impact of neurocognitive dysfunction on the participants’ ability to learn the fundamentals of illness self-management seems to be limited, and symptom severity did not limit the benefits of the IMR program. Support for the utility of the IMRS to monitor the participants’ progress in the program was also found, providing a brief and economical method for assessing outcome of the IMR program. / Syftet med föreliggande avhandlingsarbete var att undersöka Illness Management and Recovery (IMR) programmets effekter av att lära klienter att bättre hantera negativa konsekvenser av schizofreni eller schizoaffektiv sjukdom och att främja återhämtning. Detta åstadkoms genom en utvärdering av IMR programmets inverkan på psykosocial funktion och psykopatologi, en undersökning av specifik och generell påverkan av neurokognition avseende deltagarnas möjligheter att lära in grundläggande sjukdomshanteringsfärdigheter (illness self-management), samt en undersökning av huruvida schizofrenisymtomens svårighetsgrad inverkar på programutfallet. Vidare undersöktes Illness Management and Recovery Skalans (IMRS) användbarhet för att utvärdera sjukdomshantering och återhämtning (illness self-management and recovery) hos personer med schizofreni eller schizoaffektiv sjukdom. IMR programmets effekter utvärderades genom en randomiserad kontrollerad studie i vilken 41 programdeltagare jämfördes med deltagare i kontrollgrupp vilka fick enbart sedvanlig psykiatrisk behandling. Deltagarna rekryterades vid sex subspecialiserade psykiatriska öppenvårdsmottagningar och slumpades till att antingen delta i IMR programmet eller kontrollgrupp. IMR programmets deltagare uppvisade i jämförelse med kontrollgruppen förbättring i sjukdomshantering, minskade psykiatriska symtom, förbättrade coping-färdigheter samt minskade självmordsbeteenden. Resultaten stöder antagandet att IMR programmet är effektivt vad gäller att förbättra deltagarnas förmåga att hantera negativa effekter av schizofreni och schizoaffektiv sjukdom. Möjliga associationer mellan neurokognitiv funktion och förmågan att tillägna sig färdigheter för sjukdomshantering undersöktes hos 53 deltagare som genomförde IMR programmet. Resultaten pekar på att neurokognitiva svårigheter inte inverkar på deltagarnas möjligheter att lära sig sjukdomshantering enligt IMR modellen. Processhastighet var relaterad till klientrapporterad sjukdomshantering men inte till klinikerrapporterad sjukdomshantering. Processhastighet tycks vara relevant för klientens upplevelse av hur väl han eller hon tillägnat sig programmets strategier och färdigheter, snarare än sjukdomshantering per se. Huruvida schizofrenisymtomens svårighetsgrad inverkar på utfallet av IMR programmet undersöktes hos 52 deltagare som genomförde IMR programmet. Resultaten pekar på att signifikant fler deltagare uppfyllde svårighetsgradskriteriet för remission av schizofrenisymtom efter genomfört IMR program. Även deltagare som inte uppfyllde svårighetsgradskriteriet har nytta av IMR programmet något som indikeras av de båda gruppernas (uppfyllde jämfört med uppfyllde inte svårighetsgradskriteriet) likartade effektstorlekar. Illness Management and Recovery Skalans (IMRS) psykometriska egenskaper undersöktes för 107 deltagare med en schizofreni eller schizoaffektiv diagnos. Skalans enskilda frågor analyserades för att undersöka skalans användbarhet för att utvärdera deltagares progress och utfall i IMR programmet. Både klient och kliniker versionen av skalan uppvisade tillfredsställande intern konsistens, stor test-retest reliabilitet och konvergent validitet med konceptuellt relaterade instrument för psykiatriska symtom, livskvalité och återhämtning. Resultaten stöder antagandet att IMRS är ett användbart instrument för att utvärdera sjukdomskontroll och återhämtning för personer med schizofreni eller schizoaffektiv sjukdom. Avhandlingsarbetets resultat stöder antagandet att IMR programmet är effektivt vad gäller att förbättra deltagarnas förmåga att hantera de negativa konsekvenserna av schizofreni och schizoaffektiv sjukdom. Neurokognitiva svårigheter inverkar i begränsad utsträckning på deltagarnas möjligheter att lära sig sjukdomshantering och schizofrenisymtom tycks ha begränsad inverkan på programutfallet. Resultaten stöder även antagandet att IMRS är ett användbart instrument för att utvärdera sjukdomskontroll och återhämtning för personer med schizofreni eller schizoaffektiv sjukdom, vilket erbjuder en kortfattad och ekonomisk metod att utvärdera effekterna av IMR.