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1.
Int J Qual Stud Health Well-being ; 18(1): 2250084, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37615270

RESUMO

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 , Conhecimento
2.
J Orthop Surg Res ; 18(1): 434, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37312222

RESUMO

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.


Assuntos
Fraturas do Quadril , Osteoporose , Humanos , Farmacêuticos , Assistência ao Convalescente , Estudos Prospectivos , Alta do Paciente , Fraturas do Quadril/tratamento farmacológico
4.
BMJ Open ; 12(11): e064868, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36379642

RESUMO

OBJECTIVE: Patients with hip fracture are at high risk of medication errors due to a combination of high age, comorbidities, polypharmacy and several care transitions after fracture. The aim was to study medication management tasks concerning patient safety: medication reconciliation, medication review and communication of key medication information in care transitions. DESIGN: Descriptive study comprising a self-administered clinician survey (MedHipPro-Q) and a retrospective review of hospital medical records of patients with hip fracture. SETTING: Regional hospital and the associated primary care units (South-Eastern Norway). PARTICIPANTS: The survey received responses from 253 clinicians, 61 medical doctors and 192 nurses, involved in the medication management of patients with hip fracture, from acute admittance to the regional hospital, through an in-hospital fast track, primary care rehabilitation and back to permanent residence. Respondents' representativeness was unknown, introducing a risk of selection and non-response bias, and extrapolating findings should be done with caution. The patient records review included a random sample of records of patients with hip fracture (n=50). OUTCOME MEASURES: Medication reconciliation, medication review and communication of medication information from two perspectives: the clinicians' (ie, experiences with medication management) and the practice (ie, documentation of completed medication management). RESULTS: In the survey, most clinicians stated they performed medication reconciliation (79%) and experienced that patients often arrived without a medication list after care transition (37%). Doctors agreed that more patients would benefit from medication reviews (86%). In the hospital patient records, completed medication reconciliation was documented in most patients (76%). Medication review was documented in 2 of 50 patients (4%). Discharge summary guidelines were followed fully for 3 of 50 patients (6%). CONCLUSION: Our study revealed a need for improved medication management for patients with hip fracture. Patients were at risk of medication information not being transferred correctly between care settings, and medication reviews seemed to be underused in clinical practice.


Assuntos
Reconciliação de Medicamentos , Conduta do Tratamento Medicamentoso , Humanos , Prontuários Médicos , Transferência de Pacientes , Hospitais , Inquéritos e Questionários , Alta do Paciente
6.
BMJ Open ; 12(6): e058473, 2022 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-35680250

RESUMO

OBJECTIVE: When discharged from hospital patients are often assumed to have sufficient health literacy (HL) to participate in their medical treatment and manage medical self-care after discharge. However, limited HL is a widespread concern and patient participation during discharge is lacking. In this study, we explore how HL influences medication communication during hospital discharge. DESIGN: A qualitative case study, comprising unstructured observations of patient-healthcare personnel (HCP) encounters followed by semistructured interviews. Data were analysed using content analysis. SETTING: An internal medicines ward at a university hospital in Norway. PARTICIPANT: Fifteen patients aged 40-89 years were included close to the day of discharge. RESULTS: The following themes describing dimensions of HL emerged: (1) access, (2) understand, (3) appraise and (4) apply. Most patients sought access to medication information from HCP, while some felt dependent on HCP to provide it. However, their abilities to understand, evaluate and make informed decisions were challenged, partly because HCPs' ability to adapt their communication to the patient's knowledgebase varied. CONCLUSION: The results give a broader understanding of how HL influences medication communication during hospital discharge. To consider central dimensions of HL is important to achieve optimal medication communication, as the communication only can be exercised within the frames of the patient's HL. The findings in this study support that HL should be described as a shared responsibility between the patients and HCP. Attention should be focused to the HCP's responsibility to adapt the communication to the patient's knowledgebase.


Assuntos
Letramento em Saúde , Comunicação , Letramento em Saúde/métodos , Hospitais , Humanos , Alta do Paciente , Pesquisa Qualitativa
7.
J Transl Med ; 20(1): 225, 2022 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-35568909

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.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/uso terapêutico , Humanos , Oncologia , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/terapia , Medicina de Precisão , Estudos Prospectivos
8.
BMC Health Serv Res ; 22(1): 240, 2022 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-35193572

RESUMO

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.


Assuntos
Reconciliação de Medicamentos , Conduta do Tratamento Medicamentoso , Comunicação , Humanos , Reprodutibilidade dos Testes , Inquéritos e Questionários
9.
BMJ Open ; 11(6): e044850, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193483

RESUMO

OBJECTIVE: Effective communication and patient empowerment before hospital discharge are important steps to ensure medication safety. Patients discharged from hospitals are often expected to assume self-management, frequently without healthcare personnel (HCP) having ensured patients' knowledge, motivation and/or skills. In this substudy of a larger study, we explore how patients experience medication communication during encounters with HCPs and how they are empowered at hospital discharge. DESIGN: This is a qualitative case study. Data collection was done through qualitative observations of patient-HCP encounters, semistructured interviews with patients and drug reconciliation. Data were analysed using content analysis. SETTING: An internal medicines ward at a university hospital in Norway. PARTICIPANTS: Nine patients aged 49-90 years were included close to the day of discharge. RESULTS: The analysis revealed the following themes: (1) patient-centred care (PCC), which included 'understanding and involvement in the patient-as-person', 'establishment of a therapeutic alliance', and 'sharing power and responsibility'; and (2) biomedical (conventional) care, including the subthemes 'HCPs in power and control' and 'optimising medical outcomes, following guidelines'. Even though the elements of PCC were observed in several encounters, overall communication was not sufficiently fostering patient empowerment. Spending time with patients and building relations based on mutual trust seemed undervalued. CONCLUSIONS: The results provide a broader understanding of how patients experience medication communication at hospital discharge. Both the patients and the HCPs appear to be inculcated with biomedical traditions and are uncertain about the roles and opportunities associated with PCC. Attention should be paid to patient preferences and to the core elements of the PCC model from admission to discharge to empower patients in medication self-management.


Assuntos
Comunicação , Alta do Paciente , Hospitais , Humanos , Noruega , Poder Psicológico , Pesquisa Qualitativa
10.
Cancers (Basel) ; 13(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198773

RESUMO

Pseudomyxoma peritonei (PMP) is a rare, slow-growing cancer characterized by progressive accumulation of intraperitoneal mucinous tumor deposits. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) cures approximately 50% of patients, but in unresectable and recurrent cases, treatment options are limited. Anti-angiogenic treatment is being explored as a potential therapeutic option. Using PMP patient samples, microvessel densities (immunostaining for CD31 and CD105) and pro-angiogenic factors were analyzed, and the proliferative response upon incubation with human umbilical cord vascular endothelial cells (HUVEC) was determined. Growth inhibition by anti-angiogenic drugs was analyzed in patient-derived xenograft models of PMP. PMP tumor tissues were found to be highly vascularized and contained key pro-angiogenic factors, in particular related to vascular endothelial growth factor (VEGF) signaling, but interestingly, high levels of fibroblast growth factor 2 were also detected. HUVEC proliferation was stimulated upon incubation with fresh tumor samples and the observed proliferation could be inhibited by VEGF pathway inhibitor bevacizumab. In xenograft models the two VEGF pathway inhibitors, bevacizumab and aflibercept, inhibited tumor growth. This work reemphasizes the importance of angiogenesis as a major driver in PMP and strengthens the preclinical rationale for continued exploration of angiogenesis inhibition in the hope of providing novel treatment to a group of patients that have few other treatment options.

11.
Res Social Adm Pharm ; 17(12): 2136-2144, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34312101

RESUMO

BACKGROUND: Observation studies are used in health care research, e.g. to explore behaviors of patients or health care professionals in hospitals. A methodological challenge in observation studies is the observer effect, as it can jeopardize the quality of a study. OBJECTIVES: To capture different dimensions of the observer effect through health care professionals' and patients' experiences, and their reactions to being observed in a hospital setting, and in addition, observers' experiences from performing an observation study. METHOD: Four focus group interviews (health care professionals and observers) and 10 individual interviews (patients) were conducted with participants from a Norwegian observation study focusing on medication communication at a hospital ward. In all 26 persons were interviewed, whereof 3 were observers (pharmacist, pharmacy students). Data were collected between September 2019 and January 2020 and analyzed by an inductive, thematic analysis approach. RESULTS: Five main themes were identified; Experiencing being observed; Temporarily adapting medication communication behavior; Consequences for the patients; To interact or not - reflections on the relations and Observing the observers. Respondents reported some observer effects, but also that these diminished with time. Even though minimal interaction was used as a strategy, observers and the observed still built rapport. CONCLUSIONS: The observer effect in relation to medication communication seemed to be small and temporary in this specific hospital setting, among other things as staff and patients were used to extra persons (e.g. students) being around. Medication communication in hospital settings is a complex behavior, and appears to not be strongly impacted by the presence of observers, especially with a long observation time. It is important for researchers to monitor and record the observer effect in the specific setting of the study. This can be done by interviews with the observed and the observers by someone not connected to the observation study.


Assuntos
Comunicação , Farmacêuticos , Atitude do Pessoal de Saúde , Grupos Focais , Hospitais , Humanos
12.
Ann Surg Oncol ; 28(9): 5252-5262, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34019185

RESUMO

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.


Assuntos
Neoplasias Colorretais , Hipertermia Induzida , Neoplasias Peritoneais , Neoplasias Colorretais/tratamento farmacológico , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Imunoconjugados , Neoplasias Peritoneais/tratamento farmacológico
13.
Health Expect ; 24(3): 892-904, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33761170

RESUMO

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.


Assuntos
Clínicos Gerais , Alta do Paciente , Comunicação , Hospitais , Humanos , Pesquisa Qualitativa
14.
Eur J Surg Oncol ; 47(1): 134-138, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-31036394

RESUMO

BACKGROUND: The ImmunoPeCa trial investigated the use of intraperitoneal MOC31PE immunotoxin as a novel therapeutic principle for the treatment of peritoneal metastasis from colorectal cancer (PM-CRC). We here report long-term outcome from the trial. METHODS: This was a dose-finding trial aiming to evaluate safety and toxicity (primary endpoint) upon a single dose of intraperitoneal MOC31PE in patients with PM-CRC undergoing CRS-HIPEC with mitomycin C. Overall survival (OS) and disease-free survival (DFS) were secondary endpoints. Twenty-one patients received the study drug at four dose levels on the first postoperative day, including six patients constituting an expansion cohort. RESULTS: With a 34-month follow-up, the median OS was not reached and the estimated 3-year OS was 78%. Median DFS for all patients was 21 months and the 3-year DFS was 33%, with a median follow-up of 31 months. When excluding patients with potential favorable characteristics from the analysis (n = 4), the median DFS was 13 months and the 3-year OS 72%. CONCLUSIONS: The promising long-term outcome combined with low systemic absorbance, high drug concentration and cytotoxic activity in peritoneal fluid support further investigations of clinical efficacy.


Assuntos
Neoplasias Colorretais/patologia , Imunoconjugados/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Adulto , Idoso , Antibióticos Antineoplásicos/uso terapêutico , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Masculino , Pessoa de Meia-Idade , Mitomicina/uso terapêutico , Noruega , Neoplasias Peritoneais/cirurgia
15.
Ann Diagn Pathol ; 46: 151483, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32143173

RESUMO

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.


Assuntos
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 , Prognóstico
16.
Acta Oncol ; 59(4): 404-409, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31876430

RESUMO

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.


Assuntos
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 Sobrevida
17.
Sci Rep ; 9(1): 18021, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31792234

RESUMO

Intravitreal injections of antibody-based biologics targeting vascular endothelial growth factor (VEGF) are highly effective and have markedly decreased the risk of visual impairment associated with prevalent retinal diseases, such as neovascular age-related macular degeneration and diabetes macular oedema. The diseases are chronic in their nature, and most patients need long-term therapy to suppress disease activity. We previously reported a compounding method for repackaging and storage of aflibercept (Eylea), a commonly used anti-VEGF biologic, in silicone oil-coated plastic syringes without compromising drug stability or activity. In addition to improving safety and time spent per patient, compounding of anti-VEGF biologics enables single-dose vials to be split into multiple syringes, thereby considerably reducing waste and drug expenses. However, symptomatic silicone oil droplets may deposit in the eye's vitreous body after repetitive injections. To fully avoid this complication, we here report on a novel pharmaceutical compounding method using silicone oil-free syringes and a 33 G × 9 mm Low Dead Space Needle hub injection needle. We evaluate the method for three anti-VEGF biologics commonly used in ophthalmology: aflibercept, ranibizumab (Lucentis) and bevacizumab (Avastin). Our results show that compounding and storage for one week does not compromise the functional activity of the biologics and allows for safe and cost-effective compounding of anti-VEGF biologics for intravitreal injections in prefilled silicone oil-free syringes.


Assuntos
Inibidores da Angiogênese/química , Produtos Biológicos/química , Composição de Medicamentos/métodos , Armazenamento de Medicamentos/métodos , Seringas , Inibidores da Angiogênese/administração & dosagem , Produtos Biológicos/administração & dosagem , Química Farmacêutica , Retinopatia Diabética/tratamento farmacológico , Estabilidade de Medicamentos , Humanos , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Edema Macular/tratamento farmacológico , Oxirredução , Plásticos , Óleos de Silicone/química , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
18.
Tidsskr Nor Laegeforen ; 139(1)2019 01 15.
Artigo em Norueguês | MEDLINE | ID: mdl-30644679

RESUMO

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.


Assuntos
Substituição de Medicamentos/normas , Enfermeiras e Enfermeiros/normas , Documentação/normas , Hospitais , Humanos , Erros Médicos , Noruega , Fatores de Risco , Inquéritos e Questionários
19.
Omega (Westport) ; 79(4): 394-413, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28699836

RESUMO

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 , Suécia
20.
Front Oncol ; 9: 1302, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31921617

RESUMO

Cancer stem cells (CSCs) are a theorized small subpopulation of cells within tumors thought to be responsible for metastasis, tumor development, disease progression, treatment-resistance, and recurrence. The identification, isolation, and biological characterization of CSCs may therefore facilitate the development of efficient therapeutic strategies targeting CSCs. This study aims to compare the biology and telomerase activity of CSCs to parental cells (PCs) in renal cancer. Renal CSCs were enriched from the ACHN cell line using a sphere culture system. Spheroid-derived cells (SDCs) and their adherent counterparts were compared with respect to their colony and sphere formation, expression of putative CSC markers, tumorigenicity in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, and invasiveness. The expression of genes associated with CSCs, stemness, EMT, apoptosis, and ABC transporters was also compared between the two populations using quantitative real-time PCR (qRT-PCR). Finally, telomerase activity, hTERT expression, and sensitivity to MST-312, a telomerase inhibitor, was investigated between the two populations. We demonstrated that a subpopulation of ACHN cells was capable of growing as spheroids with many properties similar to CSCs, including higher clonogenicity, superior colony- and sphere-forming ability, and stronger tumorigenicity and invasiveness. In addition, SDCs demonstrated a higher expression of markers for CSCs, stemness, EMT, apoptosis, and ABC transporter genes compared to PCs. The expression of hTERT and telomerase activity in SDCs was significantly lower than PCs; however, the SDC population was more sensitive to MST-312 compared to PCs. These findings indicate that the SDC population exhibits stem-like potential and invasive characteristics. Moreover, the reduced expression of hTERT and telomerase activity in SDCs demonstrated that the expressions of hTERT and telomerase activity are not always higher in CSCs. Our results also showed that MST-312 treatment inhibited SDCs more strongly than PCs and may therefore be useful as a complementary targeted therapy against renal CSCs in the future.

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