No description available.

Thesis (M.D.)--University of Pennsylvania, 1805. / With a final blank leaf. Film 633 reel 41 is part of Research Publications Early American Medical Imprints collection (RP reel 41, no. 737). DNLM

Thesis (doctoral)--Westfälische Wilhelms-Universität zu Münster. / Includes bibliographical references (p. [25]-27).

Thesis (doctoral)--Westfälische Wilhelms-Universität zu Münster. / Includes bibliographical references (p. [25]-27).

No description available.

A dissertation submitted to the Faculty of Health Science, University of the Witwatersrand, Johannesburg, in fulfillment of the requirements for the degree of Master of Science in medicine. Johannesburg 2014 / Introduction: The presence of pain during sleep causes patients with chronic daily pain, such as in Rheumatoid and Osteoarthritis, to experience insomnia, fragmented sleep and an increased number of night-time awakenings. This poor sleep results in an increased sensitivity to pain during the day. The effect of improving sleep on pain, sleep and mood after taking Zolpidem MR was the aim of this study. Methods: 11 patients from Chris Hani Baragwanath Hospital in Soweto South Africa who reported insomnia and daily pain spent 4 weeks in this crossover design, double blinded, placebo controlled study. Week 1- baseline, week 2 and 4 were Intervention weeks – either placebo or Zolpidem MR, week 3 was a Washout week. Data collected included actigraphy, McGill Pain Questionnaire, PSQI, BDI, physical activity questionnaire and daily sleep and pain diaries containing VAS scales for sleep and pain. Results: No significant changes were found in the pain or physical activity levels in any of the patients. Sleep quality, as measured by an isolated PSQI question, was improved by Zolpidem MR (p=0.0075). PSQI was decreased in the final week of the study compared to baseline (8.7 vs. 11.3, p=0.0106) and BDI was lower in week 4 than baseline (7.7 vs. 15.85, p=0.0003), BDI was also lower in week 4 compared to week 2 (7.7 vs. 12.8, p<0.05). However the changes in PSQI and BDI were a result of the order of the weeks, with patients interacting with the researcher and were not due to either Zolpidem MR or placebo. Anecdotal reports include feeling more energised and capable of living life. Conclusion: This study has shown that human interaction is an important component of treatment for insomnia and chronic pain as there is a positive effect on sleep disruption and depression.

Objective. Since 2010, the rheumatology community has developed guidelines and tools to improve healthcare transition. In this study, we aimed to compare current transition practices and beliefs among Childhood Arthritis and Rheumatology Research Alliance (CARRA) rheumatology providers with transition practices from a provider survey published in 2010. Methods. In 2018, CARRA members completed a 25-item online survey about healthcare transition. Got Transition's Current Assessment of Health Care Transition Activities was used to measure clinical transition processes on a scale of 1 (basic) to 4 (comprehensive). Bivariate analyses were used to compare 2010 and 2018 survey findings. Results. Over half of CARRA members completed the survey (202/396), including pediatric rheumatologists, adult- and pediatric-trained rheumatologists, pediatric rheumatology fellows, and advanced practice providers. The most common target age to begin transition planning was 15-17 years (49%). Most providers transferred patients prior to age 21 years (75%). Few providers used the American College of Rheumatology transition tools (31%) or have a dedicated transition clinic (23%). Only 17% had a transition policy in place, and 63% did not consistently address healthcare transition with patients. When compared to the 2010 survey, improvement was noted in 3 of 12 transition barriers: availability of adult primary care providers, availability of adult rheumatologists, and pediatric staff transition knowledge and skills (P < 0.001 for each). Nevertheless, the mean current assessment score was < 2 for each measurement. Conclusion. This study demonstrates improvement in certain transition barriers and practices since 2010, although implementation of structured transition processes remains inconsistent.

Introdução: As doenças reumáticas pediátricas compreendem um grupo heterogêneo de doenças cujas causas são multifatoriais. Pacientes portadores dessas doenças apresentam maior risco de desenvolver infecções devido ao comprometimento da resposta imune causado pela doença e também pelo uso de drogas com potencial imunossupressor. Em vista deste fato, a vacinação torna-se uma ferramenta eficaz na prevenção de doenças infecciosas e suas complicações. Contudo, ainda não existe consenso sobre as indicações e contra-indicações dessas vacinas neste grupo particular. Há poucos trabalhos publicados sobre imunogenicidade e segurança de vacinas em crianças e adolescentes com doenças reumáticas e freqüentemente esses pacientes não recebem as vacinas recomendadas para sua idade. Objetivo: Avaliar a situação vacinal de crianças e adolescentes com doenças reumáticas, as possíveis causas de atraso vacinal e o impacto da orientação específica feita pelo reumatologista pediátrico visando à atualização das vacinas segundo o calendário proposto pelo Ministério da Saúde. Materiais e Métodos: Foi realizado um inquérito com os pacientes e seus responsáveis, consulta dos cartões vacinais e revisão de prontuários dos pacientes em seguimento nos ambulatórios de Reumatologia Pediátrica do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto (HCFMRP-USP) durante o período de abril de 2008 a março de 2009, que possuíssem o cartão vacinal. Para os pacientes com atraso vacinal, prescrição específica de vacina foi feita pelo reumatologista pediátrico, e um novo registro da situação vacinal foi verificado após seis meses. O projeto foi submetido e aprovado pelo Comitê de Ética em Pesquisa do HCFMRP-USP. Resultados: Duzentos e sete pacientes (58% do sexo feminino; média de idade: 10,9 anos) foram incluídos e apresentavam os seguintes diagnósticos: 86 artrite idiopática juvenil (AIJ); 30 lúpus eritematoso sistêmico (LES); 21 dermatomiosite juvenil (DMJ); 10 esclerodermia; 20 vasculites; 10 síndrome de anticorpo anti-fosfolípide (SAAF); 6 doença mista do tecido conjuntivo ou síndrome de sobreposição (DMTC); 24 outras doenças. Anteriormente à intervenção, a cobertura vacinal segundo o calendário brasileiro de vacinação infantil foi: tuberculose (BCG): 100%; sarampo, caxumba e rubéola (SCR): 98,1%; poliomielite (Sabin - VOP): 95,2%; difteria, tétano e coqueluche: 92,8%; hepatite B: 89,4%; e febre amarela: 85%. Noventa dos 207 pacientes incluídos (43,5%) tinham atraso de pelo menos uma dose de alguma vacina recomendada. O atraso da imunização ocorreu, respectivamente, em 43%, 70%, 42,9%, 60%, 45%, 66,7% e 16,7% dos pacientes com AIJ, LES, DMJ, esclerodermia, vasculite, DMTC/síndrome de sobreposição e outras doenças reumáticas. As proporções de crianças que receberam vacinas fora do calendário básico (especiais) foram: hepatite A (9,6%); influenza (24%); meningocócica (10,6%); pneumocócica (15%), e 52,8% para varicela (38/72 pacientes suscetíveis). Em 20,8% dos pacientes a vacinação foi contraindicada pela equipe médica: 88,4% contra febre amarela e 11,6% contra SCR. O atraso da vacinação causado por receio das conseqüências das vacinas ocorreu em 25%. Prescrição específica das vacinas atrasadas foi fornecida a 44/60 pacientes (73,3%) com vacinação incompleta. A atualização completa da vacinação foi verificada após 6 meses em 75% destas crianças. Conclusão: A freqüência de atraso vacinal em pacientes com doenças reumáticas é alta e preocupante. A prescrição específica de vacinas durante o seguimento clínico desses pacientes tem impacto positivo na cobertura vacinal e deve ser implementada com o objetivo de diminuir a morbidade associada às infecções preveníveis. / Background: Pediatric rheumatic diseases comprise a heterogeneous group of diseases with multifactorial causes. These patients present high risk of infection due to impaired immune response and use of immunosuppressive drugs and vaccination is an effective tool for preventing infectious diseases and their sequelae. However, there is still no consensus on the recommendations of vaccines in this group. There are limited data on safety and immunogenicity of vaccines in children and adolescents with rheumatic diseases and frequently these patients do not receive adequate age-recommended vaccines. Objective: To assess the immunization status and possible causes of delayed immunization in children and adolescents with rheumatic diseases, evaluating the impact of physician specific intervention for missing vaccines. Material and Methods: We performed a survey with patients/caregivers, review of charts and immunization cards of patients with rheumatic diseases who were receiving care in a Brazilian Pediatric Rheumatology Center (HCFMRP-USP) from April/08 to March/09 and had an immunization card. For patients with delayed immunization, specific vaccine prescription was made by the pediatric rheumatologist and the new immunization status was recorded after 6 months. Results: Two hundred and seven patients (58% women; mean age: 10.9 years) were enrolled: 86 with juvenile idiopathic arthritis (JIA); 30 systemic lupus erythematosus (SLE); 21 juvenile dermatomyositis (JDM); 10 scleroderma; 20 vasculitis; 10 antiphospholipid antibody syndrome (APS); 6 mixed connective tissue disease (MCTD); 24 with other diseases. Prior to intervention, vaccines of the routine Brazilian childhood immunization schedule had been received among these children as follows: tuberculosis (BCG): 100%; mumps, measles and rubella (MMR): 98.1%; poliomyelitis (Sabin): 95.2%; tetanus, pertussis and diphtheria: 92.8%; hepatitis B: 89.4%; and yellow fever: 85%. With respect to the routine schedule 90/207 (43.5%) enrolled patients missed at least one dose of any vaccine. Delayed immunization occurred, respectively, in 43%, 70%, 42.9%, 60%, 45%, 66.7%, and 16.7% of the patients with JIA, SLE, JDM, scleroderma, vasculitis, MCTD and other rheumatic diseases. The proportions of non-routinely scheduled (special) vaccines received amongst the 207 children were: hepatitis A (9.6%); influenza (24%); meningococcal (10.6%); pneumococcal (15%), and 52.8% for varicella (38/72 susceptible patients). In 20.8% of patients vaccination was contraindicated by the physician: 88.4% for yellow fever and 11.6% for MMR. Delayed immunization caused by family/patient fear or omission occurred in 25%. Specific prescription for the missing vaccines were given to 44/60 patients (73.3%) with incomplete immunization. The complete updated vaccination was verified after 6 months in 75% of these children. Conclusion: The frequency of delayed immunization in pediatric patients with rheumatic diseases is high and worrying. Specific vaccine prescription given during the follow-up is effective and should be performed with the aim of reducing complications associated with preventable infections.

Cerebral small vessel disease (SVD) is a distinct microvascular disorder that can lead to lacunar stroke, an important stroke subtype that accounts for a quarter of all ischaemic strokes. SVD is associated with imaging biomarkers such as white matter hyperintensities (WMH). The cause of SVD is largely unknown, although inflammation and blood-brain barrier failure via endothelial dysfunction have been implicated. Elevated plasma biomarkers of inflammation are associated with coronary heart disease and large vessel stroke but the role of inflammation in SVD is less well understood. Our hypothesis is that inflammation plays a role in SVD and we sought to examine this by reviewing the literature for evidence of this, and by conducting a brain imaging study of patients with a known inflammatory disease and reviewing the images for evidence of inflammation and SVD, and comparing findings with controls groups. Section A: This thesis begins with a systematic review and meta-analysis of 13 plasma biomarkers of four physiological processes (coagulation, fibrinolysis, endothelial dysfunction and inflammation) in lacunar stroke versus non-lacunar stroke (to control for having any stroke) and non-stroke (to compare to the general population). We sought to know if there were differences in these biomarkers between lacunar stroke and other stroke subtypes and non-stroke controls as a way of generating hypotheses for the disease mechanisms that might lead to lacunar stroke. Findings revealed differences in several biomarkers between lacunar stroke and healthy controls but only fibrinogen, D-dimer, von Willebrand factor and interleukin-6 were different (all significantly lower in lacunar stroke) between lacunar stroke and other stroke subtypes. There was heterogeneity between studies, including variations in the definition of lacunar stroke and most studies measured the biomarkers in the acute phase post stroke, which is potentially confounding. To further examine plasma biomarkers of inflammation and endothelial dysfunction in SVD, we used data from a prior study of mild stroke conducted at the Brain Research Imaging Centre, University of Edinburgh, UK. Lacunar stroke patients were compared to cortical stroke patients. The lacunar group had lower levels of tissue plasminogen activator independent of age, sex and vascular risk factors but we found no difference in the other plasma biomarkers. Section B: Non-resolving systemic inflammation is a feature of inflammatory autoimmune rheumatic diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). These patients are at increased risk of stroke but much knowledge relates to stroke in general; less is known about associations with stroke subtypes including SVD, or when in life stroke risk is greatest. Consequently, we sought to better understand the influence of inflammatory rheumatic diseases on stroke and SVD. The review and meta-analysis of cerebrovascular disease in rheumatic diseases showed an excess risk of stroke in RA, SLE, ankylosing spondylitis, gout and psoriasis over the general population. Meta-analyses of stroke subtypes (ischaemic and haemorrhagic) in RA and SLE showed an excess risk of stroke over the general population. Stroke risk across rheumatic diseases was highest in those aged < 50 years and reduced with ageing. We then requested data from NHS Lothian covering 15 years so that we could assess stroke, including stroke subtypes, among patients diagnosed with various arthropathies. We linked 6,613 rheumatology patients’ records with stroke admission records, grouped the various rheumatic diseases into the two main types of arthritis, inflammatory and non-inflammatory, and also compared the strokes in these rheumatology patients to general population data. There was no difference in stroke prevalence between inflammatory and degenerative (non-inflammatory) arthropathies, although the strokes occurred up to two decades earlier than in the general population. Section C: Lastly, we conducted MRI neuroimaging in patients with SLE and reviewed and meta-analysed diffusion tensor imaging (DTI) (an imaging technique used to assess sub-visible white matter microstructure damage) in SLE to place our findings into context. The research question here was to ascertain if patients with a known inflammatory disease had brain imaging evidence of SVD, and to compare findings to controls. We compared imaging markers of SVD and DTI between SLE patients and age-matched healthy controls and sought associations between the imaging biomarkers and plasma biomarkers of inflammation and endothelial dysfunction, measures of fatigue and cognition, and scores of rheumatic disease activity. Fifty-one patients were recruited. There was higher mean diffusivity in all white matter tracts versus controls indicating a diffuse increase in brain water mobility in SLE. Meta-analysis confirmed higher mean diffusivity in SLE patients versus controls. Fatigue in SLE was significantly higher than a normal reference range and was associated with depression, anxiety, higher body mass index, lower mean diffusivity and some blood markers of inflammation and endothelial dysfunction. The most fatigued were youngest which explained the association with lower mean diffusivity. Damage to the brain’s white matter microstructure may be accelerated in SLE as the age-related declines in the general population are normally seen much later in life. The aging pattern is consistent with inflammation-related microvascular-mediated brain damage where the inflammation is systemic in origin. Summary: This thesis has demonstrated an increase in SVD burden in the inflammatory rheumatic disease SLE and increased stroke risk at younger ages in other inflammatory rheumatic diseases. Thus, systemic inflammation as seen in inflammatory rheumatic diseases could have effects on the brain directly, including influencing stroke risk which is clinically noteworthy and would benefit from further testing in appropriately designed studies such as an inception cohort that follows inflammatory rheumatic patients from diagnosis, with regular brain imaging to track brain changes and correlates with inflammatory profiles and impact on cognition.

Introdução: As doenças reumáticas pediátricas compreendem um grupo heterogêneo de doenças cujas causas são multifatoriais. Pacientes portadores dessas doenças apresentam maior risco de desenvolver infecções devido ao comprometimento da resposta imune causado pela doença e também pelo uso de drogas com potencial imunossupressor. Em vista deste fato, a vacinação torna-se uma ferramenta eficaz na prevenção de doenças infecciosas e suas complicações. Contudo, ainda não existe consenso sobre as indicações e contra-indicações dessas vacinas neste grupo particular. Há poucos trabalhos publicados sobre imunogenicidade e segurança de vacinas em crianças e adolescentes com doenças reumáticas e freqüentemente esses pacientes não recebem as vacinas recomendadas para sua idade. Objetivo: Avaliar a situação vacinal de crianças e adolescentes com doenças reumáticas, as possíveis causas de atraso vacinal e o impacto da orientação específica feita pelo reumatologista pediátrico visando à atualização das vacinas segundo o calendário proposto pelo Ministério da Saúde. Materiais e Métodos: Foi realizado um inquérito com os pacientes e seus responsáveis, consulta dos cartões vacinais e revisão de prontuários dos pacientes em seguimento nos ambulatórios de Reumatologia Pediátrica do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto (HCFMRP-USP) durante o período de abril de 2008 a março de 2009, que possuíssem o cartão vacinal. Para os pacientes com atraso vacinal, prescrição específica de vacina foi feita pelo reumatologista pediátrico, e um novo registro da situação vacinal foi verificado após seis meses. O projeto foi submetido e aprovado pelo Comitê de Ética em Pesquisa do HCFMRP-USP. Resultados: Duzentos e sete pacientes (58% do sexo feminino; média de idade: 10,9 anos) foram incluídos e apresentavam os seguintes diagnósticos: 86 artrite idiopática juvenil (AIJ); 30 lúpus eritematoso sistêmico (LES); 21 dermatomiosite juvenil (DMJ); 10 esclerodermia; 20 vasculites; 10 síndrome de anticorpo anti-fosfolípide (SAAF); 6 doença mista do tecido conjuntivo ou síndrome de sobreposição (DMTC); 24 outras doenças. Anteriormente à intervenção, a cobertura vacinal segundo o calendário brasileiro de vacinação infantil foi: tuberculose (BCG): 100%; sarampo, caxumba e rubéola (SCR): 98,1%; poliomielite (Sabin - VOP): 95,2%; difteria, tétano e coqueluche: 92,8%; hepatite B: 89,4%; e febre amarela: 85%. Noventa dos 207 pacientes incluídos (43,5%) tinham atraso de pelo menos uma dose de alguma vacina recomendada. O atraso da imunização ocorreu, respectivamente, em 43%, 70%, 42,9%, 60%, 45%, 66,7% e 16,7% dos pacientes com AIJ, LES, DMJ, esclerodermia, vasculite, DMTC/síndrome de sobreposição e outras doenças reumáticas. As proporções de crianças que receberam vacinas fora do calendário básico (especiais) foram: hepatite A (9,6%); influenza (24%); meningocócica (10,6%); pneumocócica (15%), e 52,8% para varicela (38/72 pacientes suscetíveis). Em 20,8% dos pacientes a vacinação foi contraindicada pela equipe médica: 88,4% contra febre amarela e 11,6% contra SCR. O atraso da vacinação causado por receio das conseqüências das vacinas ocorreu em 25%. Prescrição específica das vacinas atrasadas foi fornecida a 44/60 pacientes (73,3%) com vacinação incompleta. A atualização completa da vacinação foi verificada após 6 meses em 75% destas crianças. Conclusão: A freqüência de atraso vacinal em pacientes com doenças reumáticas é alta e preocupante. A prescrição específica de vacinas durante o seguimento clínico desses pacientes tem impacto positivo na cobertura vacinal e deve ser implementada com o objetivo de diminuir a morbidade associada às infecções preveníveis. / Background: Pediatric rheumatic diseases comprise a heterogeneous group of diseases with multifactorial causes. These patients present high risk of infection due to impaired immune response and use of immunosuppressive drugs and vaccination is an effective tool for preventing infectious diseases and their sequelae. However, there is still no consensus on the recommendations of vaccines in this group. There are limited data on safety and immunogenicity of vaccines in children and adolescents with rheumatic diseases and frequently these patients do not receive adequate age-recommended vaccines. Objective: To assess the immunization status and possible causes of delayed immunization in children and adolescents with rheumatic diseases, evaluating the impact of physician specific intervention for missing vaccines. Material and Methods: We performed a survey with patients/caregivers, review of charts and immunization cards of patients with rheumatic diseases who were receiving care in a Brazilian Pediatric Rheumatology Center (HCFMRP-USP) from April/08 to March/09 and had an immunization card. For patients with delayed immunization, specific vaccine prescription was made by the pediatric rheumatologist and the new immunization status was recorded after 6 months. Results: Two hundred and seven patients (58% women; mean age: 10.9 years) were enrolled: 86 with juvenile idiopathic arthritis (JIA); 30 systemic lupus erythematosus (SLE); 21 juvenile dermatomyositis (JDM); 10 scleroderma; 20 vasculitis; 10 antiphospholipid antibody syndrome (APS); 6 mixed connective tissue disease (MCTD); 24 with other diseases. Prior to intervention, vaccines of the routine Brazilian childhood immunization schedule had been received among these children as follows: tuberculosis (BCG): 100%; mumps, measles and rubella (MMR): 98.1%; poliomyelitis (Sabin): 95.2%; tetanus, pertussis and diphtheria: 92.8%; hepatitis B: 89.4%; and yellow fever: 85%. With respect to the routine schedule 90/207 (43.5%) enrolled patients missed at least one dose of any vaccine. Delayed immunization occurred, respectively, in 43%, 70%, 42.9%, 60%, 45%, 66.7%, and 16.7% of the patients with JIA, SLE, JDM, scleroderma, vasculitis, MCTD and other rheumatic diseases. The proportions of non-routinely scheduled (special) vaccines received amongst the 207 children were: hepatitis A (9.6%); influenza (24%); meningococcal (10.6%); pneumococcal (15%), and 52.8% for varicella (38/72 susceptible patients). In 20.8% of patients vaccination was contraindicated by the physician: 88.4% for yellow fever and 11.6% for MMR. Delayed immunization caused by family/patient fear or omission occurred in 25%. Specific prescription for the missing vaccines were given to 44/60 patients (73.3%) with incomplete immunization. The complete updated vaccination was verified after 6 months in 75% of these children. Conclusion: The frequency of delayed immunization in pediatric patients with rheumatic diseases is high and worrying. Specific vaccine prescription given during the follow-up is effective and should be performed with the aim of reducing complications associated with preventable infections.