RESUMO
BACKGROUND: Matching treatment based on tumour molecular characteristics has revolutionized the treatment of some cancers and has given hope to many patients. Although personalized cancer care is an old concept, renewed attention has arisen due to recent advancements in cancer diagnostics including access to high-throughput sequencing of tumour tissue. Targeted therapies interfering with cancer specific pathways have been developed and approved for subgroups of patients. These drugs might just as well be efficient in other diagnostic subgroups, not investigated in pharma-led clinical studies, but their potential use on new indications is never explored due to limited number of patients. METHODS: In this national, investigator-initiated, prospective, open-label, non-randomized combined basket- and umbrella-trial, patients are enrolled in multiple parallel cohorts. Each cohort is defined by the patient's tumour type, molecular profile of the tumour, and study drug. Treatment outcome in each cohort is monitored by using a Simon two-stage-like 'admissible' monitoring plan to identify evidence of clinical activity. All drugs available in IMPRESS-Norway have regulatory approval and are funded by pharmaceutical companies. Molecular diagnostics are funded by the public health care system. DISCUSSION: Precision oncology means to stratify treatment based on specific patient characteristics and the molecular profile of the tumor. Use of targeted drugs is currently restricted to specific biomarker-defined subgroups of patients according to their market authorization. However, other cancer patients might also benefit of treatment with these drugs if the same biomarker is present. The emerging technologies in molecular diagnostics are now being implemented in Norway and it is publicly reimbursed, thus more cancer patients will have a more comprehensive genomic profiling of their tumour. Patients with actionable genomic alterations in their tumour may have the possibility to try precision cancer drugs through IMPRESS-Norway, if standard treatment is no longer an option, and the drugs are available in the study. This might benefit some patients. In addition, it is a good example of a public-private collaboration to establish a national infrastructure for precision oncology. Trial registrations EudraCT: 2020-004414-35, registered 02/19/2021; ClinicalTrial.gov: NCT04817956, registered 03/26/2021.
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Antineoplásicos , Neoplasias , Antineoplásicos/uso terapêutico , Humanos , Oncologia , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/terapia , Medicina de Precisão , Estudos ProspectivosRESUMO
BACKGROUND: A validated questionnaire to assess medication management of hip fracture patients within and outside the hospital setting was lacking. The study aims were to describe the hip fracture patient pathway, and develop a valid and feasible questionnaire to assess clinicians' experience with medication management of hip fracture patients in different care settings throughout the patient pathway. METHODS: This qualitative, descriptive methodological study used strategic and snowball sampling. The questionnaire was developed, and face and content validity explored through interviews with stakeholders. Phase I described the hip fracture patient pathway, and identified questionnaire dimensions in semi-structured interviews with management and clinicians (n = 37). The patient pathway was also discussed in six meetings (n = 70). Phase II refined a first draft of the questionnaire through cognitive interviews with future respondents (n = 23). The draft was modified after each interview. Post hoc, cognitive interview data were analysed using matrix analysis to condense problems and solutions into themes and subthemes. Phase III, converted the final version to a digital format, and tested its feasibility with a subset of the cognitive interview participants (n = 21) who completed the questionnaire and provided feedback. RESULTS: Phase I: Hip fracture patients were cared for in at least three different care settings, and went through at least four handovers between and within primary and secondary care. Three questionnaire dimensions were identified: 1) Medication reconciliation and review, 2) Communication of key information, and 3) Profession and setting. Phase II: The MedHipPro-Q was representative of how the different professions experienced medication management in all settings, and hence showed face and content validity. Post hoc analysis: Problem themes (with sub-themes) were Representativeness (-of patient pathway and -of respondent reality) and Presentation (Language and Appearance). Solution themes (with sub-themes) were: Content (added or deleted) and Presentation (modified appearance or corrected language). Phase III: Participants did not identify technical, linguistic or content flaws in the questionnaire, and the digital version was considered feasible for use. CONCLUSION: The novel MedHipPro-Q showed good face and content validity, and was feasible for use throughout the hip fracture patient pathway. The rigorous development process supports its construct validity and reliability.
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Reconciliação de Medicamentos , Conduta do Tratamento Medicamentoso , Comunicação , Humanos , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Despite extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), most patients with resectable peritoneal metastases from colorectal cancer experience disease relapse. MOC31PE immunotoxin is being explored as a novel treatment option for these patients. MOC31PE targets the cancer-associated epithelial cell adhesion molecule, and kills cancer cells by distinct mechanisms, simultaneously causing immune activation by induction of immunogenic cell death (ICD). METHODS: Systemic and local cytokine responses were analyzed in serum and intraperitoneal fluid samples collected the first three postoperative days from clinically comparable patients undergoing CRS-HIPEC with (n = 12) or without (n = 26) intraperitoneal instillation of MOC31PE. A broad panel of 27 pro- and antiinflammatory interleukins, chemokines, interferons, and growth factors was analyzed using multiplex technology. RESULTS: The time course and magnitude of the systemic and local postoperative cytokine response after CRS-HIPEC were highly compartmentalized, with modest systemic responses contrasting substantial intraperitoneal responses. Administration of MOC31PE resulted in changes that were broader and of higher magnitude compared with CRS-HIPEC alone. Significantly increased levels of innate proinflammatory cytokines, such as interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF) as well as an interesting time response curve for the strong T-cell stimulator interferon (IFN)-γ and its associated chemokine interferon gamma-induced protein/chemokine (C-X-C motif) ligand 10 (IP-10) were detected, all associated with ICD. CONCLUSIONS: Our study revealed a predominately local rather than systemic inflammatory response to CRS-HIPEC, which was strongly enhanced by MOC31PE treatment. The MOC31PE-induced intraperitoneal inflammatory reaction could contribute to improve remnant cancer cell killing, but the mechanisms remain to be elucidated in future studies.
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Neoplasias Colorretais , Hipertermia Induzida , Neoplasias Peritoneais , Neoplasias Colorretais/tratamento farmacológico , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Imunoconjugados , Neoplasias Peritoneais/tratamento farmacológicoRESUMO
BACKGROUND: Patients are expected to participate in the hospital discharge process, assume self-management after discharge and communicate relevant information to their general practitioner; however, patients report that they are not being sufficiently empowered to take on these responsibilities. The aim of this study was to explore and understand the discharge process with a focus on medicines communication, from the patient perspective. METHODS: Patients were included at a hospital ward, observed during health-care personnel encounters on the day of discharge and interviewed 1-2 weeks after discharge. A process analysis was performed, and a content analysis combined data from observations and data from patient interviews focusing on medicines communication in the discharge process. RESULTS: A total of 9 patients were observed on the day of discharge, equalling 67.5 hours of observations. The analysis resulted in the following themes: (a) the observed discharge process; (b) patient initiatives; and (c) the patient role. The medicines communication in the discharge process appeared unstructured. Various patient preferences and needs were revealed. The elements of the best practice structured discharge conversation were observed; however, some patients did not have a discharge conversation at all. CONCLUSIONS: The study contributes to a broader understanding of the discharge process, how patients experience it, including their role. It is evident that the discharge process is not always tailored to meet the patients' needs. More focus on early patient involvement and communication, in order to better prepare patients for self-management of their medications, is important for their health outcomes.
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Clínicos Gerais , Alta do Paciente , Comunicação , Hospitais , Humanos , Pesquisa QualitativaRESUMO
Introduction: In a recent phase I trial in a heterogeneous group of carcinoma patients with advanced disease, we did not observe objective responses by CT at 8 weeks in patients treated with either the anti-EpCAM immunotoxin MOC31PE alone or administered in combination with the immunosuppressor cyclosporin (CsA). We have now assessed overall survival (OS) data for the two groups to reveal potential differences, and to elucidate putative underlying mechanisms.Material and methods: The OS time of MOC31PE monotherapy (34 patients) and MOC31PE in combination with CsA (23 patients), was assessed. Pre- and post-treatment patient sera were analyzed in a multiplex immunoassay, and the immunogenic effects of MOC31PE were studied in vitro and in a dendritic cell maturation assay.Results: When the data were analyzed for all treated patients regardless of cancer type, the MOC31PE alone group had a median OS of 12.7 months (95% CI = 5.6-19.8 months) compared to 6.2 months (95% CI = 5.6-6.8 months) (p=.066) for the patients treated with MOC31PE + CsA group. For the subgroup of patients with colorectal cancer, the median OS survival was 16.3 months (95% CI = 5.6-27.0) for the MOC31PE only cohort (n = 15), compared to 6.0 months (CI = 5.8-6.2) (p < .001) for the combination group. The cytokine profile in patient sera and the in vitro immunological studies indicate that MOC31PE induced an immunogenic response leading to T-cell activation; a response that was suppressed in patients treated with MOC31PE + CsA.Conclusions: The results reveal a promising clinical benefit of anti-EpCAM immunotoxin treatment in patients with advanced disease, an effect apparently explained by a previously unknown immunogenic effect of MOC31PE.
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Neoplasias Colorretais/mortalidade , Ciclosporina/uso terapêutico , Molécula de Adesão da Célula Epitelial/antagonistas & inibidores , Imunoconjugados/uso terapêutico , Imunotoxinas/uso terapêutico , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Molécula de Adesão da Célula Epitelial/imunologia , Molécula de Adesão da Célula Epitelial/metabolismo , Humanos , Imunossupressores/uso terapêutico , Metástase Neoplásica , Prognóstico , Taxa de SobrevidaRESUMO
B7-H3 and EpCAM are overexpressed in cancer and play a role in tumorigenesis and metastasis. In this study, the membranous, cytoplasmic and nuclear expression levels of B7-H3 and EpCAM biomarkers were mapped in three major subtypes of renal cell carcinoma (RCC). Expression of B7-H3 and EpCAM were evaluated using immunohistochemistry in RCC samples on tissue microarrays (TMAs), including clear cell RCCs (ccRCCs), type I and II papillary RCCs (pRCCs), and chromophobe RCCs (chRCCs). The association between B7-H3 and EpCAM expression and clinicopathological features as well as survival outcomes was determined. There was a statistically significant difference between B7-H3 and EpCAM expression among the different RCC subtypes. In ccRCC, higher cytoplasmic expression of B7-H3 was significantly associated with increase in nucleolar grade, lymph node invasion (LNI), invasion of the Gerota's fascia, and tumor necrosis, while no association was found with the membranous and nuclear expression. Moreover tumors with cytoplasmic expression of B7-H3 tended to have a worse prognosis for disease-specific survival (DSS) than those with membranous expression. In case of EpCAM, increased membranous expression of EpCAM was associated with nucleolar grade and tumor necrosis in ccRCC. Additionally, membranous EpCAM expression added prognostic value in patients with ccRCC who had high nucleolar grade versus low nucleolar grade. Moreover, membranous EpCAM expression was found to be an independent favorable prognostic marker for progression-free survival (PFS) in ccRCC. Our results demonstrated that higher cytoplasmic B7-H3 and membranous EpCAM expression are clinically significant in ccRCC and are associated with more aggressiveness tumor behavior.
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Antígenos B7/biossíntese , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/patologia , Molécula de Adesão da Célula Epitelial/biossíntese , Neoplasias Renais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/mortalidade , Membrana Celular/metabolismo , Citoplasma/metabolismo , Feminino , Humanos , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
BACKGROUND: Nurses are frequently required to undertake generic substitution of drugs in hospitals. According to the prevailing regulations, nurses may only undertake such substitution based on the Norwegian Medicines Agency's substitution list or the local substitution list in the hospital's quality system. MATERIAL AND METHOD: A total of 600 nurses in 23 surgical and 28 medical wards in three health trusts were invited to participate in an online questionnaire survey on the generic substitution of drugs in hospitals. The study was undertaken to assess how current practice functions with regard to risk factors, documentation and potential improvements. RESULTS: The response rate for the survey was 52 %. A total of 57 % of nurses undertook generic substitution of drugs on a daily basis, while 8 % equally often left the decision to the doctor. In six hypothetical examples of generic substitution, the median number of incorrect responses by the nurses was two; the local substitution list was used as the only source of information in 23 % of cases, and none of the nurses used the Norwegian Medicines Agency's online substitution list. Altogether 37 % responded that generic substitution was recorded in 80 % or more of cases, while 18 % responded that a double-check was performed in 80 % or more of cases. INTERPRETATION: Generic substitution in hospitals entails a significant possibility of errors. Safety and documentation of generic substitution should primarily be taken care of by computerised solutions, with the introduction of an electronic medication chart. Alternatively, the approved substitution list should be the only source used for substitution.
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Substituição de Medicamentos/normas , Enfermeiras e Enfermeiros/normas , Documentação/normas , Hospitais , Humanos , Erros Médicos , Noruega , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
In recent years, the common and mundane dying has begun to take place in the public space of the Internet. Among the blogs about food, fashion, travel, and other joyful aspects of life, blogs about severe disease and dying have appeared. The aim of this article is to describe some characteristic features of a sample of cancer blogs and to discuss them in the light of Zygmunt Bauman's theory of the rationalization of death in modernity and theories about networked media, especially the theories about "affective labor" and "ambient intimacy" by McCosker, Darcy, and Pfister. It will then be argued that an affective communication is performed in and through these cancer blogs, where not only language but also the deficiencies of language-and what is called shared ineffability-might be valuable and meaningful (although not unproblematic) as part of a late modern approach to death, and in the practicing of the art of dying.
Assuntos
Atitude Frente a Morte , Blogging , Neoplasias/psicologia , Humanos , SuéciaAssuntos
Doença da Artéria Coronariana , Imagem de Perfusão do Miocárdio , Humanos , Doença da Artéria Coronariana/diagnóstico por imagem , Diagnóstico por Imagem , Perfusão , Decúbito Ventral , Decúbito Dorsal , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Imagem de Perfusão do Miocárdio/métodosRESUMO
BACKGROUND: MOC31PE immunotoxin was developed to rapidly kill cells expressing the tumor-associated epithelial cell adhesion molecule, which is highly expressed in colorectal cancer. Although cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may offer long-term survival to patients with peritoneal metastasis from colorectal cancer (PM-CRC), most patients experience disease relapse and novel therapeutic options are needed. On this basis, MOC31PE is being developed as a novel therapeutic principle to target PM-CRC. METHODS: This was a dose-escalating phase I trial to evaluate the safety and toxicity (primary endpoint), pharmacokinetic profile, and neutralizing antibody response (secondary endpoints) upon intraperitoneal administration of MOC31PE in patients with PM-CRC undergoing CRS-HIPEC with Mitomycin C. Fifteen patients received the study drug at four dose levels (3+3+3+6), administered intraperitoneally as a single dose the day after CRS-HIPEC. RESULTS: No dose-limiting toxicity was observed, and the maximum tolerated dose was not reached. There was negligible systemic absorption of the study drug. Drug concentrations in peritoneal fluid samples were in the cytotoxic range and increased in a dose-dependent manner. MOC31PE recovered from peritoneal cavity retained its cytotoxic activity in cell-based assays. All patients developed neutralizing antibodies. CONCLUSIONS: Intraperitoneal administration of MOC31PE was safe and well tolerated, and combined with low systemic uptake, MOC31PE seems ideal for local intraperitoneal treatment. The drug will be further evaluated in an ongoing phase II expansion cohort.
Assuntos
Carcinoma de Células em Anel de Sinete/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Imunoconjugados/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Idoso , Carcinoma de Células em Anel de Sinete/imunologia , Carcinoma de Células em Anel de Sinete/patologia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Imunoconjugados/farmacocinética , Injeções Intraperitoneais , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias Peritoneais/imunologia , Neoplasias Peritoneais/patologia , Prognóstico , Taxa de Sobrevida , Distribuição TecidualRESUMO
Prominin-1 (CD133) is one of the most commonly used markers for cancer stem cells (CSCs), which are characterized by their ability for self-renewal and tumorigenicity. However, the clinical and prognostic significance of CSCs in renal cell carcinoma (RCC) remains unclear. The aim of this study was to investigate the expression patterns and prognostic significance of the cancer stem cell marker CD133 in different histological subtypes of RCC. CD133 expression was evaluated using immunohistochemistry in 193 well-defined renal tumor samples on tissue microarrays, including 136 (70.5%) clear cell renal cell carcinomas (CCRCCs), 26 (13.5%) papillary RCCs, and 31 (16.1%) chromophobe RCCs. The association between CD133 expression and clinicopathological features as well as the survival outcomes was determined. There was a statistically significant difference between CD133 expression among the different RCC subtypes. In CCRCC, higher cytoplasmic expression of CD133 was significantly associated with increase in grade, stage, microvascular invasion (MVI) and lymph node invasion (LNI), while no association was found with the membranous expression. Moreover, on multivariate analysis, TNM stage and nuclear grade were independent prognostic factors for overall survival (OS) in cytoplasmic expression. We showed that higher cytoplasmic CD133 expression was associated with more aggressive tumor behavior and more advanced disease in CCRCC but not in the other examined subtypes. Our results demonstrated that higher cytoplasmic CD133 expression is clinically significant in CCRCC and is associated with increased tumor aggressiveness and is useful for predicting cancer progression.
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Antígeno AC133/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/secundário , Citoplasma/metabolismo , Neoplasias Renais/patologia , Recidiva Local de Neoplasia/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/metabolismo , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Neoplasias Renais/metabolismo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Recidiva Local de Neoplasia/metabolismo , Estadiamento de Neoplasias , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND: Locally advanced rectal cancer (LARC) comprises heterogeneous tumours with predominant hypoxic components. The hypoxia-inducible metabolic shift causes microenvironmental acidification generated by carbonic anhydrase IX (CAIX) and facilitates metastatic progression, the dominant cause of failure in LARC. METHODS: Using a commercially available immunoassay, circulating CAIX was assessed in prospectively archived serial serum samples collected during combined-modality neoadjuvant treatment of LARC patients and correlated to histologic tumour response and progression-free survival (PFS). RESULTS: Patients who from their individual baseline level displayed serum CAIX increase above a threshold of 224 pg/ml (with 96 % specificity and 39 % sensitivity) after completion of short-course neoadjuvant chemotherapy (NACT) prior to long-course chemoradiotherapy and definitive surgery had significantly better 5-year PFS (94 %) than patients with below-threshold post-NACT versus baseline alteration (PFS rate of 56 %; p < 0.01). This particular CAIX parameter, ΔNACT, was significantly correlated with histologic ypT0-2 and ypN0 outcome (p < 0.01) and remained an independent PFS predictor in multivariate analysis wherein it was entered as continuous variable (p = 0.04). CONCLUSIONS: Our results indicate that low ΔNACT, i.e., a weak increase in serum CAIX level following initial neoadjuvant treatment (in this case two cycles of the Nordic FLOX regimen), might be used as risk-adapted stratification to postoperative therapy or other modes of intensification of the combined-modality protocol in LARC. TRIAL REGISTRATION: ClinicalTrials.gov NCT00278694.
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Antígenos de Neoplasias/sangue , Anidrases Carbônicas/sangue , Terapia Neoadjuvante/métodos , Neoplasias Retais/enzimologia , Neoplasias Retais/terapia , Adulto , Idoso , Anidrase Carbônica IX , Quimiorradioterapia Adjuvante/métodos , Quimioterapia Adjuvante/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias Retais/sangue , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: The aim of this study was to investigate if specific clinical and histological findings can be related to biopsy complications to enable more closely monitoring patients at high risk. METHODS: Results from 1081 biopsies (994 patients, median age 54.5 years; 896 native and 185 transplant kidney biopsies) were included. Diagnostic quality, morphology, clinical data and complications were prospectively registered. RESULTS: In native kidney biopsies, the most common diagnosis was IgA-nephritis, while in transplant kidney biopsies it was rejection. Patients with IgA-nephritis had a higher risk of major complications (11.7 versus 6.4 %, Odds Ratio (OR) 1.8, Confidence Interval (CI) 1.1-3.2) when compared to patients with other diseases. In native kidney biopsies, patients who experienced major complications had higher degrees of glomerulosclerosis (31 versus 20 %, p = 0.008), whereas in transplant kidney biopsies, patients had higher degrees of interstitial fibrosis (82 versus 33 %, p < 0.001) when compared to patients without major complications. IgA-nephritis-patients had a higher risk of re-biopsies (4.7 versus 1.3 %, OR 4, CI 1.5-11) than patients with other diseases. Patients with native kidneys who needed re-biopsies were younger (42.6 versus 52.3 years, p = 0.031) and had a higher degree of interstitial fibrosis (63 versus 34 %, p = 0.046). CONCLUSIONS: Patients with IgA-nephritis have an increased risk of major biopsy complications. The risk of re-biopsies was higher in younger individuals and in patients with IgA-nephritis.
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Biópsia/efeitos adversos , Glomerulonefrite por IGA/complicações , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Fibrose , Glomerulonefrite por IGA/patologia , Glomerulosclerose Segmentar e Focal/etiologia , Glomerulosclerose Segmentar e Focal/patologia , Rejeição de Enxerto/patologia , Humanos , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Risco , Adulto JovemRESUMO
AIMS: The aim of this study was to estimate the self-reported domestic incidence of acute gastrointestinal illness in the Swedish population irrespective of route of transmission or type of pathogen causing the disease. Previous studies in Sweden have primarily focused on incidence of acute gastrointestinal illness related to consumption of contaminated food and drinking water. METHODS: In May 2009, we sent a questionnaire to 4000 randomly selected persons aged 0-85 years, asking about the number of episodes of stomach disease during the last 12 months. To validate the data on symptoms, we compared the study results with anonymous queries submitted to a Swedish medical website. RESULTS: The response rate was 64%. We estimated that a total number of 2744,778 acute gastrointestinal illness episodes (95% confidence intervals 2475,641-3013,915) occurred between 1 May 2008 and 30 April 2009. Comparing the number of reported episodes with web queries indicated that the low number of episodes during the first 6 months was an effect of seasonality rather than recall bias. Further, the result of the recall bias analysis suggested that the survey captured approximately 65% of the true number of episodes among the respondents. CONCLUSIONS: The estimated number of Swedish acute gastrointestinal illness cases in this study is about five times higher than previous estimates this study provides valuable information on the incidence of gastrointestinal symptoms in Sweden, irrespective of route of transmission, indicating a high burden of acute gastrointestinal illness, especially among children, and large societal costs, primarily due to production losses.
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Gastroenteropatias/epidemiologia , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Autorrelato , Suécia/epidemiologia , Adulto JovemRESUMO
We hypothesised that feeding the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) (dep. nr LMG P-17806) during weaning would program the metabolic and inflammatory profile and studied its association with previously assessed body composition. In a double-blind, placebo-controlled trial, 179 infants were randomised to daily feeding of cereals with or without LF19 10(8) CFU from 4 to 13 months of age. At age 8-9 years, 120 children were re-assessed. Using high-sensitivity multiplex immunoassay technology and ELISA, we found that overweight/obese children had increased plasma C-peptide, plasminogen activator inhibitor-1, leptin and serum high-sensitivity C-reactive protein (hsCRP) after overnight fasting compared with normal weight children, independently of LF19. After excluding the obese, leptin and hsCRP were still increased, revealing an aberrant metabolic and inflammatory state already in overweight, pre-pubertal children. Higher body mass index z-score, sagittal abdominal diameter, truncal and total body fat % were associated with an aberrant metabolic and inflammatory profile, emphasising the need for early prevention strategies although no programming effect of LF19 was observed.
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Inflamação/metabolismo , Lactobacillus/fisiologia , Metabolismo/fisiologia , Sobrepeso/prevenção & controle , Probióticos , Biomarcadores , Criança , Método Duplo-Cego , Grão Comestível , Feminino , Seguimentos , Regulação da Expressão Gênica , Humanos , Inflamação/sangue , Modelos Lineares , Masculino , Sobrepeso/sangue , Sobrepeso/metabolismo , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , DesmameRESUMO
BACKGROUND: In Sweden, native and transplant kidney biopsies are usually performed in major renal medical centers. PURPOSE: To clarify risk factors in native and transplant kidney biopsies to improve patient safety. MATERIAL AND METHODS: A total of 1001 biopsies (in 352 women and 565 men) were included. The median age was 54 years (range, 16-90 years). Data were derived from 826 native kidney biopsies (640 prospective and 186 retrospective) and 175 transplant kidney biopsies (170 prospective and 5 retrospective). Various factors and complications were registered while performing native and transplant kidney biopsies, focusing on major (e.g. blood transfusions, invasive procedures) and minor complications. The prospective protocol was used at six centers and at one center data were obtained retrospectively. RESULTS: Women were at greater risk of overall complications than men (12.2% vs. 6.5%; P = 0.003; odds ratio [OR], 2.0; confidence interval [CI], 1.3-3.1) as well as of major complications (9.6% vs. 4.5%; P = 0.002; OR, 2.2, CI 1.3-3.7). Major complications occurred more commonly after biopsies from the right kidney, in women than in men (10.8% vs. 3.1%; P = 0.005; OR, 3.7; CI, 1.5-9.5), and in patients with lower BMI (25.5 vs. 27.3, P = 0.016) and of younger age (45 years vs. 52.5 years; P = 0.001). Lower mean arterial pressure in transplant kidney biopsies indicated a risk of major complications (90 mmHg vs. 98 mmHg; P = 0.039). Factors such as needle size, number of passes, serum creatinine, and eGFR did not influence complication rates. CONCLUSION: The present findings motivate greater attention being paid to the risk of major side-effects after right-side biopsies from women's kidneys, as well as after biopsies from younger patients and patients with lower BMI.
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Fístula Arteriovenosa/epidemiologia , Hematúria/epidemiologia , Transplante de Rim/estatística & dados numéricos , Rim/patologia , Complicações Pós-Operatórias/epidemiologia , Insuficiência Renal Crônica/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha/estatística & dados numéricos , Comorbidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/patologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Suécia/epidemiologia , Adulto JovemRESUMO
Cytoreductive surgery and intraperitoneal (i.p.) chemotherapy constitute a curative treatment option in mucinous peritoneal surface malignancies of intestinal origin, but treatment outcome is highly variable and the search for novel therapies is warranted. Immunotoxins are attractive candidates for targeted therapy in the peritoneal cavity because of direct cytotoxicity, distinct mechanisms of action and tumor cell selectivity. The MOC31PE immunotoxin targets the tumor-associated adhesion protein EpCAM (Epithelial Cell Adhesion Molecule), and has been administered safely in early clinical trials. In our work, the efficacy of i.p. administration of MOC31PE alone and together with mitomycin C (MMC) was investigated in unique animal models of human mucinous peritoneal surface malignancies. In initial model validation experiments, clear differences in efficacy were demonstrated between MMC and oxaliplatin, favoring MMC in five investigated tumor models. Subsequently, MOC31PE and MMC were given as single i.p. injections alone and in combination. In the PMCA-2 model, moderate growth inhibition was obtained with both drugs, while the combination resulted in at least additive effects; whereas the PMP-2 model was highly sensitive to both drugs separately and in combination and intermediate sensitivity was found for the PMCA-3 model. Furthermore, results from ex vivo experiments on freshly obtained mucinous tumor tissue from animals and patients suggested that classic mechanisms of immunotoxin activity were involved, i.e., inhibition of protein synthesis and induction of apoptosis. The present results suggest that adding MOC31PE to MMC-based i.p. chemotherapy should be further explored for EpCAM-expressing peritoneal surface malignancies, and a phase I trial is in preparation.
Assuntos
ADP Ribose Transferases/uso terapêutico , Antígenos de Neoplasias/imunologia , Toxinas Bacterianas/uso terapêutico , Moléculas de Adesão Celular/imunologia , Exotoxinas/uso terapêutico , Imunotoxinas/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Fatores de Virulência/uso terapêutico , Animais , Modelos Animais de Doenças , Molécula de Adesão da Célula Epitelial , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Mitomicina/uso terapêutico , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina , Neoplasias Peritoneais/patologia , Exotoxina A de Pseudomonas aeruginosaRESUMO
OBJECTIVE: Based on the principle of the autonomy of the patient, shared decision-making (SDM) is the ideal approach in clinical encounters. In SDM, patients and healthcare professionals (HCPs) share knowledge and power when faced with the task of making decisions. However, patients are often not involved in the decision-making process. In this study, we explore medication decision-making during hospitalization and how power in the specific patient-HCP relationship is articulated, as analysed by Foucauldian theory. METHODS: A qualitative case study, comprising observations of patient-HCP encounters at an internal medicines ward at a university hospital in Norway, followed by semi-structured interviews. The narratives (n = 4 patients) were selected from a larger study (n = 15 patients). The rationale behind the choice of these patients was to include diverse and rich accounts. The four patients in their 40s-70s were included close to the day of presumed discharge. RESULTS: The narratives provide an insight into the patients as persons, their perspectives, including what mattered to them during their hospitalization, especially in relation to medications. Overall, SDM was not observed in this study. Even though all the participants actively tried to keep their autonomous capacity and to resist the HCPs' use of power, they were not able to change the established dynamics. Moreover, they were not allowed an equal voice to those of HCPs and thus not to escape the system's objectification and subjectification of them. CONCLUSION: There is a need for HCPs to get more familiarized with SDM. The healthcare system and the individual HCP need to make more room for dialogue with the patients about their preferences. A part of this is also how health care systems are structured and scheduled, thus, it is important to empower patients and HCPs alike.
Assuntos
Hospitalização , Alta do Paciente , Humanos , Hospitais , Pessoal de Saúde , ConhecimentoRESUMO
BACKGROUND: Hip fracture patients face a patient safety threat due to medication discrepancies and adverse drug reactions when they have a combination of high age, polypharmacy and several care transitions. Consequently, optimised pharmacotherapy through medication reviews and seamless communication of medication information between care settings is necessary. The primary aim of this study was to investigate the impact on medication management and pharmacotherapy. The secondary aim was to evaluate implementation of the novel Patient Pathway Pharmacist intervention for hip fracture patients. METHODS: Hip fracture patients were included in this nonrandomised controlled trial, comparing a prospective intervention group (n = 58) with pre-intervention controls who received standard care (n = 50). The Patient Pathway Pharmacist intervention consisted of the steps: (A) medication reconciliation at admission to hospital, (B) medication review during hospitalisation, (C) recommendation for the medication information in the hospital discharge summary, (D) medication reconciliation at admission to rehabilitation, and (E) medication reconciliation and (F) review after hospital discharge. The primary outcome measure was quality score of the medication information in the discharge summary (range 0-14). Secondary outcomes were potentially inappropriate medications (PIMs) at discharge, proportion receiving pharmacotherapy according to guidelines (e.g. prophylactic laxatives and osteoporosis pharmacotherapy), and all-cause readmission and mortality. RESULTS: The quality score of the discharge summaries was significantly higher for the intervention patients (12.3 vs. 7.2, p < 0.001). The intervention group had significantly less PIMs at discharge (- 0.44 (95% confidence interval - 0.72, - 0.15), p = 0.003), and a higher proportion received prophylactic laxative (72 vs. 35%, p < 0.001) and osteoporosis pharmacotherapy (96 vs. 16%, p < 0.001). There were no differences in readmission or mortality 30 and 90 days post-discharge. The intervention steps were delivered to all patients (step A, B, E, F = 100% of patients), except step (C) medication information at discharge (86% of patients) and step (D) medication reconciliation at admission to rehabilitation (98% of patients). CONCLUSION: The intervention steps were successfully implemented for hip fracture patients and contributed to patient safety through a higher quality medication information in the discharge summary, fewer PIMs and optimised pharmacotherapy. TRIAL REGISTRATION: NCT03695081.