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1.
BMC Public Health ; 20(1): 250, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32075611

RESUMO

BACKGROUND: Mental disorders are the most common reason for sick leave in Sweden. Knowledge about effective methods to help these individuals to return to work (RTW)/entry into work or studies is limited. Rehabilitation coordinators (RC's) have been introduced within healthcare with the purpose to promote cooperation, streamline the sick leave and rehabilitation process, and facilitate RTW for sick-listed patients. The function of RC's has shown positive results by reducing sick leave within primary healthcare. However, the function has not been evaluated in terms of specialist psychiatry. This paper describes the design of a study to evaluate effects of a RC intervention on sick leave and RTW/entry in work or studies in patients with moderate to severe affective and/or moderate to severe anxiety disorders within specialist psychiatric care. METHODS: A randomised controlled trial (RCT) comparing an intervention group receiving support from a RC with a control group receiving treatment as usual (TAU). The target group is patients on sick leave, treated for affective and/or anxiety disorder, aged 25-64, with or without employment. DISCUSSION: This study gives the possibility to evaluate a RC intervention for individuals with mental disorders. If the study has promising vocational outcomes, it may be of importance for the participants in many ways, e.g. increase participation in society, provide economic benefits and improve health and wellbeing. This would be valuable for the individual as well as for the society. TRIAL REGISTRATION: The study is registered at the Clinicaltrials.gov Register Platform (ID NCT03729050) in 2 November 2018.

2.
Scand J Immunol ; 91(1): e12839, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31630416

RESUMO

The humanized IgG1κ monoclonal antibody siplizumab and its rat parent monoclonal IgG2b antibody BTI-322 are directed against the CD2 antigen. Siplizumab is species-specific, reacting with human and chimpanzee cells but not with cells from any other species, including other non-human primates. Because siplizumab treatment has recently shown great potential in clinical transplantation, we now present the results of our previous pharmacokinetic, pharmacodynamic and safety studies of both antibodies. Fourteen chimpanzees received 1-3 doses of 0.143 to 5.0 mg/kg iv The effects were followed with flow cytometry on peripheral lymphocytes and staining of lymph nodes. Side effects were recorded. Serum antibody concentrations were followed. Across the doses, a rapid, transient depletion of CD2, CD3, CD4 and CD8 lymphocytes and NK cells was observed for both antibodies. Immune reconstitution was more rapid for BTI-322 compared to siplizumab. Paracortical lymph node T cell depletion was moderate, estimated at 45% with doses of >0.6 mg/kg. Restoration of lymph node architecture was seen after two weeks to two months for all animals. All four subjects receiving BTI-322 experienced AEs on the first dosing day, while the eight subjects dosed with siplizumab experienced few mild, transient AEs. Infusion with siplizumab and BTI-322 resulted in rapid depletion of CD2+ cells in circulation and tissue. Siplizumab had a longer t1/2 and fewer AEs compared to BTI-322.


Assuntos
Anticorpos Monoclonais/farmacocinética , Antígenos CD2/antagonistas & inibidores , Animais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacocinética , Anticorpos Monoclonais Humanizados/uso terapêutico , Biomarcadores , Biópsia , Citocinas/sangue , Feminino , Imunoglobulina G/administração & dosagem , Imunoglobulina G/farmacologia , Imunofenotipagem , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Depleção Linfocítica , Linfócitos/imunologia , Linfócitos/metabolismo , Masculino , Pan troglodytes , Ratos
3.
Transplantation ; 104(2): 270-279, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31385931

RESUMO

BACKGROUND: Cytomegalovirus (CMV) infection is a serious complication in immunosuppressed patients, specifically transplant recipients. Here, we describe the development and use of an assay to monitor the incidence and treatment of CMV viremia in a Cynomolgus macaque model of bone marrow transplantation (BMT) for tolerance induction. We address the correlation between the course of viremia and immune reconstitution. METHODS: Twenty-one animals received a nonmyeloablative conditioning regimen. Seven received cyclosporine A for 28 days and 14 received rapamycin. A CMV polymerase chain reaction assay was developed and run twice per week to monitor viremia. Nineteen recipients were CMV seropositive before BMT. Immune reconstitution was monitored through flow cytometry and CMV viremia was tracked via quantitative polymerase chain reaction. RESULTS: Recipients developed CMV viremia during the first month post-BMT. Two animals developed uncontrollable CMV disease. CMV reactivation occurred earlier in cyclosporine A-treated animals compared with those receiving rapamycin. Post-BMT, T-cell counts remained significantly lower compared with pretransplant levels until CMV reactivation, at which point they increased during the viremic phase and approached pretransplant levels 3 months post-BMT. Management of CMV required treatment before viremia reached 10 000 copies/mL; otherwise clinical symptoms were observed. High doses of ganciclovir resolved the viremia, which could subsequently be controlled with valganciclovir. CONCLUSIONS: We developed an assay to monitor CMV in Cynomolgus macaques. CMV reactivation occurred in 100% of seropositive animals in this model. Rapamycin delayed CMV reactivation and ganciclovir treatment was effective at high doses. As in humans, CD8 T cells proliferated during CMV viremia.

4.
Transpl Int ; 33(1): 98-107, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31523849

RESUMO

Anti-CD2 treatment provides targeted immunomodulatory properties that have demonstrated clinical usefulness to condition the immune system and to treat transplant rejection. The treatment is species-specific due to structural CD2 antigen differences between nonhuman primates and humans. Herein, we report the safety profile and efficacy of two modifications of the same anti-CD2 monoclonal antibody in cynomolgus macaques. Twelve subjects received one i.v. anti-CD2 (of rat or rhesus type) dose each, range 1-4 mg/kg, and were followed for 1-7 days. Treatment effects were evaluated with flow cytometry on peripheral blood and histopathological evaluation of secondary lymphoid organs. In vitro inhibitory activity on primary MHC disparate mixed lymphocyte reactions (MLRs) was determined. Upon anti-CD2 treatment, CD4+ , CD8+ memory subsets were substantially depleted. Naïve T cells and Tregs were relatively spared and exhibited lower CD2 expression than memory T cells. Early immune reconstitution was noted for naïve cells, while memory counts had not recovered after one week. Both antibodies displayed a concentration-dependent MLR inhibition. Lymph node examination revealed no significant lymphocyte depletion. None of the animals experienced any significant study drug-related adverse events. This study outlines the safety and pharmacodynamic profile of primate-specific anti-CD2 treatment, relevant for translation of anti-CD2-based animal models into clinical trials.

5.
Eur J Prev Cardiol ; : 2047487319886959, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31698965

RESUMO

BACKGROUND: A novel approach to determine the effect of a treatment is to calculate the delay of event, which estimates the gain of event-free time. The aim of this study was to estimate gains in event-free time for stroke or systemic embolism, death, bleeding events, and the composite of these events, in patients with atrial fibrillation randomized to either warfarin or apixaban in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial (ARISTOTLE). DESIGN: The ARISTOTLE study was a randomized double-blind trial comparing apixaban with warfarin. METHODS: Laplace regression was used to estimate the delay in time to the outcomes between the apixaban and the warfarin group in 6, 12, 18 and 22 months of follow-up. RESULTS: The gain in event-free time for apixaban versus warfarin was 181 (95% confidence interval 76 to 287) days for stroke or systemic embolism and 55 (-4 to 114) days for death after 22 months of follow-up. The corresponding gains in event-free times for major and intracranial bleeding were 206 (130 to 281) and 392 (249 to 535) days, respectively. The overall gain for the composite of all these events was a gain of 116 (60 to 171) days. CONCLUSIONS: In patients with atrial fibrillation, 22 months of treatment with apixaban, as compared with warfarin, provided gains of approximately 6 months in event-free time for stroke or systemic embolism, 7 months for major bleeding and 13 months for intracranial bleeding.

6.
Virchows Arch ; 475(6): 781-788, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31691009

RESUMO

The use of clinical autopsy has been in decline for many years throughout healthcare systems of developed countries despite studies showing substantial discrepancies between autopsy results and pre-mortal clinical diagnoses. We conducted a study to evaluate over time the use and results of clinical autopsies in Sweden. We reviewed the autopsy reports and autopsy referrals of 2410 adult (age > 17) deceased patients referred to two University hospitals in Sweden during two plus two years, a decade apart. There was a decline in the number of autopsies performed over time, however, mainly in one of the two hospitals. The proportion of autopsy referrals from the emergency department increased from 9 to 16%, while the proportion of referrals from regular hospital wards was almost halved. The autopsies revealed a high prevalence of cardiovascular disease, with myocardial infarction and cerebrovascular lesion found in 40% and 19% of all cases, respectively. In a large proportion of cases (> 30%), significant findings of disease were not anticipated before autopsy, as judged from the referral document and additional data obtained in some but not all cases. In accordance with previous research, our study confirms a declining rate of autopsy even at tertiary, academic hospitals and points out factors possibly involved in the decline.


Assuntos
Autopsia , Causas de Morte , Erros de Diagnóstico/estatística & dados numéricos , Infarto do Miocárdio/mortalidade , Autopsia/métodos , Feminino , Hospitais Universitários/estatística & dados numéricos , Humanos , Masculino , Infarto do Miocárdio/diagnóstico , Prevalência , Estudos Retrospectivos , Suécia
7.
Anticancer Res ; 39(7): 3433-3442, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262867

RESUMO

BACKGROUND/AIM: DOG1 is a calcium-activated chloride channel that has gained attention as a promising drug target due to its involvement in several processes essential for tumor development and progression. DOG1 is overexpressed in >95% of gastrointestinal stromal tumors (GIST). The aim was to determine DOG1 inhibition antitumoral effects on GIST. MATERIALS AND METHODS: Human GIST (GIST-T1 and GIST882) cell lines were used to study the effect of DOG1 inhibitors on chloride currents, viability, colony formation, and cell cycle. RESULTS: CaCCinh-A01 decreased chloride currents. CaCCinh-A01 and T16inh-A01 reduced GIST cell viability and CaCCinh-A01 affected cell cycle distribution leading to G1 cell-cycle arrest. CaCCinh-A01 also increased the sub-G1 phase population, indicative of apoptosis, in GIST882. CaCCinh-A01 strongly reduced the colony forming ability of the cells, whereas T16inh-A01 did not. CONCLUSION: DOG1 inhibition has antitumoral effects in GIST cells in vitro, and could potentially serve as a target for GIST therapy.


Assuntos
Anoctamina-1/antagonistas & inibidores , Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Proteínas de Neoplasias/antagonistas & inibidores , Anoctamina-1/fisiologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Gastrointestinais/fisiopatologia , Tumores do Estroma Gastrointestinal/fisiopatologia , Humanos , Proteínas de Neoplasias/fisiologia , Pirimidinas/farmacologia , Tiazóis/farmacologia , Tiofenos/farmacologia
8.
Health Soc Care Community ; 27(5): 1260-1270, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31016806

RESUMO

Despite the well-known associations between local environment and health, few studies have focused on environment and healthcare utilisation, for instance healthcare seeking behaviour or adherence. This study was aimed at analysing housing type, behaviour based on perceived local outdoor safety, social support, informal caregiving, demographics, socioeconomics, and long-term illness, and associations with health-seeking and adherence behaviours at a population level. This study used data from the Swedish National Public Health Survey 2004-2014, an annually repeated, large sample, cross-sectional, population-based survey study. In all, questionnaires from 100,433 individuals were returned by post, making the response rate 52.9% (100,433/190,000). Descriptive statistics and multiple logistic regressions were used to investigate associations between explanatory variables and the outcomes of refraining from seeking care and non-adherence behaviour. Living in rented apartment, lodger, a dorm or other was associated with reporting refraining from seeking care (adjusted OR 1.16, 95% CI 1.00-1.22), and non-adherence (adjusted OR 1.22; 95% CI 1.13-1.31). Refraining from going out due to a perceived unsafe neighbourhood was associated with refraining from seeking care (adjusted OR 1.59, 95% CI 1.51-1.67) and non-adherence (adjusted OR 1.26, 95% CI 1.17-1.36). Social support and status as an informal caregiver was associated with higher odds of refraining from seeking medical care and non-adherence. This study suggests that living in rental housing, refraining from going out due to neighbourhood safety concerns, lack of social support or informal caregiver status are associated with lower health-seeking behaviour and non-adherence to prescribed medication.

9.
Transplant Direct ; 5(3): e432, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30882037

RESUMO

Background: Biliary complications occur in 6% to 34% of liver transplant recipients, for which endoscopic retrograde cholangiopancreatography has become widely accepted as the first-line therapy. We evaluated long-term outcome of biliary complications in patients liver transplanted between 2004 and 2014 at Karolinska University Hospital, Stockholm. Methods: Data were retrospectively collected, radiological images were analyzed for type of biliary complication, and graft and patient survivals were calculated. Results: In 110 (18.5%) of 596 transplantations, there were a total of 153 cases of biliary complications: 68 (44.4%) anastomotic strictures, 43 (28.1%) nonanastomotic strictures, 24 (15.7%) bile leaks, 11 (7.2%) cases of stone- and/or sludge-related problems, and 7 (4.6%) cases of mixed biliary complications. Treatment success rates for each complication were 90%, 73%, 100%, 82% and 80%, respectively. When the endoscopic approach was unsatisfactory or failed, percutaneous transhepatic cholangiography or a combination of treatments was often successful (in 18 of 24 cases). No procedure-related mortality was observed. Procedure-related complications were reported in 7.7% of endoscopic retrograde cholangiopancreatography and 3.8% of percutaneous transhepatic cholangiography procedures. Patient survival rates, 1, 3, 5, and 10 years posttransplant in patients with biliary complications were 92.7%, 80%, 74.7%, and 54.1%, respectively, compared with 92%, 86.6%, 83.7%, and 72.8% in patients free from biliary complications (P < 0.01). Similarly, long-term graft survival was lower in the group experiencing biliary complications (P < 0.0001). Conclusions: Endoscopic and percutaneous approaches for treating biliary complications are safe and efficient and should be considered complementing techniques. Despite a high treatment success rate of biliary complications, their occurrence still has a significant negative impact on patient and graft long-term survivals.

10.
Transplantation ; 103(10): 2173-2182, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30817406

RESUMO

BACKGROUND: Donor-specific antibodies (DSAs) have a strong negative correlation with long-term survival in solid organ transplantation. Although the clinical significance of DSA and antibody-mediated rejection (AMR) in upper extremity transplantation (UET) remains to be established, a growing number of single-center reports indicate their presence and potential clinical impact. METHODS: We present a multicenter study assessing the occurrence and significance of alloantibodies in UET in reference to immunological parameters and functional outcome. RESULTS: Our study revealed a high prevalence and early development of de novo DSA and non-DSA (43%, the majority detected within the first 3 postoperative y). HLA class II mismatch correlated with antibody development, which in turn significantly correlated with the incidence of acute cellular rejection. Cellular rejections preceded antibody development in almost all cases. A strong correlation between DSA and graft survival or function cannot be statistically established at this early stage but a correlation with a lesser outcome seems to emerge. CONCLUSIONS: While the phenotype and true clinical effect of AMR remain to be better defined, the high prevalence of DSA and the correlation with acute rejection highlight the need for optimizing immunosuppression, close monitoring, and the relevance of an HLA class II match in UET recipients.

11.
Artigo em Inglês | MEDLINE | ID: mdl-30384498

RESUMO

BACKGROUND: People on long-term sick leave often have a long-lasting process back to work, where the individuals may be in multiple and recurrent states; i.e., receiving different social security benefits or working, and over time they may shift between these states. The purpose of this study was to evaluate the effects of two vocational rehabilitation programs, compared to a control, on return-to-work (RTW) or increased employability in patients on long-term sick leave due to mental illness and/or chronic pain. METHODS: In this randomized controlled study, 427 women and men were allocated to either (1) multidisciplinary team management, i.e., multidisciplinary assessments and individual rehabilitation management, (2) acceptance and commitment therapy (ACT), or (3) control. A positive outcome was defined as RTW or increased employability. The outcome was considered negative if the (part-time) wage was reduced or ceased, or if there was an indication of decreased employability. The outcome was measured one year after entry in the project and analyzed using binary and multinomial logistic regressions. RESULTS: Participants in the multidisciplinary team group reported having RTW odds ratio (OR) 3.31 (95% CI 1.39⁻7.87) compared to the control group in adjusted models. Participants in the ACT group reported having increased employability OR 3.22 (95% CI 1.13⁻9.15) compared to the control group in adjusted models. CONCLUSIONS: This study of vocational rehabilitation in mainly female patients on long-term sick leave due to mental illness and/or chronic pain suggests that multidisciplinary team assessments and individually adapted rehabilitation interventions increased RTW and employability. Solely receiving the ACT intervention also increased employability.


Assuntos
Terapia de Aceitação e Compromisso , Dor Crônica/reabilitação , Transtornos Mentais/reabilitação , Serviços de Saúde do Trabalhador/métodos , Reabilitação Vocacional/métodos , Retorno ao Trabalho/psicologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento
12.
JCI Insight ; 3(22)2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30429370

RESUMO

Allograft tolerance, in which a graft is accepted without long-term immunosuppression, could overcome numerous obstacles in transplantation. Human allograft tolerance has been intentionally induced across HLA barriers via combined kidney and bone marrow transplantation (CKBMT) with a regimen that induces only transient chimerism. Tregs are enriched early after CKBMT. While deletional tolerance contributes to long-term tolerance, the role of Tregs remains unclear. We have optimized a method for identifying the donor-specific Treg repertoire and used it to interrogate the fate of donor-specific Tregs after CKBMT. We expanded Tregs with several different protocols. Using functional analyses and T cell receptor sequencing, we found that expanding sorted Tregs with activated donor B cells identified the broadest Treg repertoire with the greatest potency and donor specificity of suppression. This method outperformed both alloantigen stimulation with CTLA4Ig and sequencing of CFSElo cells from the primary mixed lymphocyte reaction. In 3 tolerant and 1 nontolerant CKBMT recipients, we sequenced donor-specific Tregs before transplant and tracked them after transplant. Preexisting donor-specific Tregs were expanded at 6 months after CKBMT in tolerant patients and were reduced in the nontolerant patient. These results suggest that early expansion of donor-specific Tregs is involved in tolerance induction following CKBMT.


Assuntos
Transplante de Rim , Linfócitos T Reguladores/transplante , Tolerância ao Transplante , Linfócitos B/imunologia , Linfócitos B/transplante , Transplante de Medula Óssea , Contagem de Linfócito CD4 , Antígeno CTLA-4/imunologia , Humanos , Teste de Cultura Mista de Linfócitos , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T Reguladores/imunologia , Doadores de Tecidos
13.
BMC Med Inform Decis Mak ; 18(1): 106, 2018 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-30458757

RESUMO

BACKGROUND: Common measures used to describe preventive treatment effects today are proportional, i.e. they compare the proportions of events in relative or absolute terms, however they are not easily interpreted from the patient's perspective and different magnitudes do not seem to clearly discriminate between levels of effect presented to people. METHODS: In this randomised cross-sectional survey experiment, performed in a Swedish population-based sample (n = 1041, response rate 58.6%), the respondents, aged between 40 and 75 years were given information on a hypothetical preventive cardiovascular treatment. Respondents were randomised into groups in which the treatment was described as having the effect of delaying a heart attack for different periods of time (Delay of Event, DoE): 1 month, 6 months or 18 months. Respondents were thereafter asked about their willingness to initiate such therapy, as well as questions about how they valued the proposed therapy. RESULTS: Longer DoE:s were associated with comparatively greater willingness to initiate treatment. The proportions accepting treatment were 81, 71 and 46% when postponement was 18 months, 6 months and 1 month respectively. In adjusted binary logistic regression models the odds ratio for being willing to take therapy was 4.45 (95% CI 2.72-7.30) for a DoE of 6 months, and 6.08 (95% CI 3.61-10.23) for a DoE of 18 months compared with a DoE of 1 month. Greater belief in the necessity of medical treatment increased the odds of being willing to initiate therapy. CONCLUSIONS: Lay people's willingness to initiate preventive therapy was sensitive to the magnitude of the effect presented as DoE. The results indicate that DoE is a comprehensible effect measure, of potential value in shared clinical decision-making.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Tomada de Decisões , Conhecimentos, Atitudes e Prática em Saúde , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Suécia , Fatores de Tempo
14.
Exp Cell Res ; 371(1): 287-296, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30149002

RESUMO

The use of imatinib mesylate has greatly improved the clinical outcome for gastrointestinal stromal tumor (GIST) patients. However, imatinib resistance is still a major clinical challenge, and the molecular mechanisms are not fully understood. We have previously shown that miR-125a-5p and its mRNA target PTPN18 modulate imatinib response in GIST cells. Herein, we evaluated phosphorylated FAK (pFAK) as a candidate downstream target of PTPN18 and the possible association of this regulation with imatinib resistance in GIST. FAK and pFAK expressions were evaluated in GIST882 cells transfected with short hairpin RNA or short interfering RNA targeting PTPN18 or miR-125a-5p mimic, imatinib-resistant GIST882R subclones and clinical samples using Western blot analyses. FAK phosphorylation was blocked using the FAK inhibitor 14 (FAKi) and the effects on cell viability and apoptosis were evaluated using WST-1 assay and cleaved PARP expression. Clinical associations of FAK and pFAK expression with imatinib resistance, KIT mutation and patient outcome were assessed by Fisher's exact test or log-rank test. Over-expression of miR-125a-5p and silencing of PTPN18 increased pFAK, but not FAK, expression in GIST cells. Higher pFAK expression was observed in the GIST882R subclones with acquired imatinib resistance compared to their imatinib-sensitive parental cells. Treatment with FAKi in imatinib-resistant GIST882R cells reduced cell viability and increased apoptosis upon imatinib treatment. Additionally, FAKi could rescue the imatinib resistance effect mediated by miR-125a-5p over-expression. In clinical samples, high FAK and pFAK expressions were associated with KIT mutation status, and high FAK expression was also associated with metastasis in GIST. Higher pFAK was found in cases with shorter overall survival. Our findings highlight an important role for miR-125a-5p regulation and its downstream target pFAK for imatinib resistance in GIST. pFAK and FAK may have prognostic values in GIST.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Quinase 1 de Adesão Focal/genética , Neoplasias Gastrointestinais/genética , Tumores do Estroma Gastrointestinal/genética , Regulação Neoplásica da Expressão Gênica , Mesilato de Imatinib/farmacologia , MicroRNAs/genética , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Quinase 1 de Adesão Focal/metabolismo , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/mortalidade , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/mortalidade , Humanos , MicroRNAs/metabolismo , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Fosforilação , Prognóstico , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Fosfatases não Receptoras/antagonistas & inibidores , Proteínas Tirosina Fosfatases não Receptoras/genética , Proteínas Tirosina Fosfatases não Receptoras/metabolismo , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Análise de Sobrevida
15.
Scand J Gastroenterol ; 53(7): 876-882, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29848142

RESUMO

OBJECTIVE: To determine overall long-term patient and graft survival rates among the recipients liver transplanted due to acute liver failure (ALF). Secondary aims included assessment of whether diagnosis, donor-recipient blood group compatibility and time-era of transplantation affected the outcome, and whether prescription-free availability of acetaminophen increased the need for liver transplantation (LTx). MATERIALS AND METHODS: A Retrospective cohort study of 78 patients who underwent LTx for ALF at Karolinska University Hospital 1984-2014. Patients were divided into two cohorts according to two 15-year periods: early cohort transplanted 1984-1999 (n = 40) and late cohort transplanted 2000-2014 (n = 38). Survival rates were established using Kaplan-Meier analyses. RESULTS: ALF patient survival rates for 1-year, 5-years, 10-years and 20-years were 71%, 63%, 52% and 40%, respectively. Survival for the late cohort at 1, 5 and 10 years was 82%, 76% and 71%, respectively. A high early mortality rate was noted during the first three months after transplantation when compared to LTx patients with chronic disease. Long-term survival rates were comparable between patients with ALF and chronic liver disease. Prescription-free access to acetaminophen did not increase the need for LTx. There was a strong trend towards improved survival in blood group identical donor-recipient pairs and blood group O recipients may have benefitted from this. CONCLUSIONS: The high early mortality rate most likely reflects the critical pre-transplant condition in these patients and the urgent need to sometimes accept a marginal donor liver. Long-term survival improved significantly over time and variation in patient access to acetaminophen did not influence the rate of LTx in our region.


Assuntos
Acetaminofen/efeitos adversos , Falência Hepática Aguda/cirurgia , Transplante de Fígado/mortalidade , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Fígado/efeitos dos fármacos , Fígado/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Suécia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
17.
J Occup Rehabil ; 28(4): 691-700, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29318421

RESUMO

Purpose To investigate the effects of two vocational rehabilitation interventions on self-efficacy, for women on long-term sick leave ≥ 1 year due to chronic pain and/or mental illness. Methods This study uses data from a randomised controlled trial consisting of two phases and comprising 401 women on long-term sick leave. They were allocated to either (1) a multidisciplinary team assessment and multimodal intervention (TEAM), (2) acceptance and commitment therapy (ACT), or (3) control group. Data were collected through repeated measurements from self-reported questionnaires before intervention, 6 and 12 months later and registry data. Data from measurements of general self-efficacy, sociodemographics, anxiety and depression were analysed with linear regression analyses. Results During the intervention period, the women in the TEAM group's self-efficacy mean increased from 2.29 to 2.74. The adjusted linear regression model, which included group allocation, sociodemographics, self-efficacy pre-treatment, anxiety and depression showed increased self-efficacy for those in the TEAM intervention at 12 months (B = 0.25, 95% CI 0.10-0.41). ACT intervention had no effect on self-efficacy at 12 months (B = 0.02, 95% CI - 0.16 to 0.19). The results in the adjusted model also showed that higher self-efficacy at pre-treatment was associated with a higher level of self-efficacy at 12 months (B = 0.68, 95% CI 0.54-0.81). Conclusion A multidisciplinary team assessment and multimodal intervention increased self-efficacy in women on sick leave for an extremely long time (mean 7.8 years) who had a low mean level of self-efficacy prior to inclusion. Thus, self-efficacy needs to be addressed in vocational rehabilitation.


Assuntos
Dor Crônica/reabilitação , Transtornos Mentais/reabilitação , Reabilitação Vocacional/métodos , Reabilitação Vocacional/psicologia , Autoeficácia , Terapia de Aceitação e Compromisso , Adulto , Ansiedade/psicologia , Ansiedade/reabilitação , Dor Crônica/psicologia , Depressão/psicologia , Depressão/reabilitação , Feminino , Humanos , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente , Escalas de Graduação Psiquiátrica , Retorno ao Trabalho , Licença Médica , Inquéritos e Questionários , Fatores de Tempo
18.
Community Dent Oral Epidemiol ; 45(3): 258-265, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28169442

RESUMO

BACKGROUND: Social inequities are considered to affect healthcare utilization, whereas less is known about the factors associated with refraining from seeking dental care. This study aimed to investigate whether people with no social support, long-term illness, caregiver burden and low socioeconomic status (SES) refrained from seeking dental care in higher proportion than the general Swedish population. METHODS: This study used cross-sectional questionnaire data from repeated nationwide health surveys during 2004-2013 of a total of 90 845 people. The questionnaire included questions on demographic characteristics, social support, long-term illness, caregiving burden, SES and dental care-seeking behaviour. Descriptive statistics, chi-square tests, correlation analyses and logistic regressions were used to investigate associations between independent variables and dental care-seeking behaviour. RESULTS: In the total sample, 15.1% of respondents reported refraining from seeking dental care. Having no emotional social support or having no instrumental social support was separately associated with reporting refraining from seeking dental care in adjusted multivariate models (odds ratio [OR] 1.26, 95% confidence interval [CI] 1.18-1.34 and OR: 1.89, 95% CI: 1.67-2.13, respectively). Having a long-term illness was associated with refraining from seeking dental care in adjusted models (adjusted OR: 1.43, 95% CI: 1.35-1.51). Furthermore, being an informal caregiver was associated with refraining from seeking dental care (adjusted OR: 1.15, 95% CI: 1.07-1.23). Low SES was associated with higher refraining from seeking dental care; the strongest association was with having financial problems (adjusted OR: 3.57, 95% CI: 3.19-4.00). Interaction effects were found between education level and SES, and between social support and long-term illness, and the outcome. CONCLUSIONS: The findings in this study imply that having no social support, having long-term illness, being informal caregiver or having financial problems are factors associated with reporting refraining from seeking dental care, on a population basis.


Assuntos
Assistência Odontológica/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Cuidadores/psicologia , Cuidadores/estatística & dados numéricos , Distribuição de Qui-Quadrado , Doença Crônica/epidemiologia , Doença Crônica/psicologia , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Apoio Social , Fatores Socioeconômicos , Inquéritos e Questionários , Suécia/epidemiologia
19.
20.
Transfus Apher Sci ; 55(3): 333-337, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27720587

RESUMO

BACKGROUND: Platelet lysate is a readily available source of growth factors, and other mediators, which has been used in a variety of clinical applications. However, the product remains poorly standardized and the present investigation evaluates the composition of platelet lysate obtained from either fresh or stored pathogen-inactivated platelet units. MATERIALS AND METHODS: Platelet pooled units (n = 10) were obtained from healthy blood donors and tested according to standard procedures. All units were pathogen inactivated using amotosalen hydrochloride and UVA exposure. Platelet lysate was subsequently produced at two separate time-points, either from fresh platelet units or after 5 days of storage, by repeated freeze-thaw cycles. The following mediators were determined at each time-point: EGF, FGF-2, VEGF, IGF-1, PDGF-AB/BB, BMP-2, PF4, TGF-ß isoform 1, IL-1ß, IL-2, IL-6, IL-10, IL-12p70, 1L-17A, TNF-α, and IFN-γ. RESULTS: The concentration of growth factors and cytokines was affected by time in storage. Notably, TGF-ß, PDGF-AB/BB, and PF4 showed an increase of 27.2% (p < 0.0001), 29.5% (p = 0.04) and 8.2% (p = 0.0004), respectively. A decrease was seen in the levels of IGF-1 and FGF-2 with 22% (p = 0.041) and 11% (p = 0.01), respectively. Cytokines were present only in very low concentrations and all other growth factors remained stable with time in storage. CONCLUSION: The composition of mediators in platelet lysate obtained from pathogen-inactivated platelet units differs when produced from fresh and stored platelet units, respectively. This underscores the need for further standardization and optimization of this important product, which potentially may influence the clinical effects.


Assuntos
Plaquetas/metabolismo , Preservação de Sangue/métodos , Extratos Celulares/química , Citocinas/análise , Peptídeos e Proteínas de Sinalização Intercelular/análise , Viabilidade Microbiana , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Garantia da Qualidade dos Cuidados de Saúde , Fatores de Tempo
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