The effect of palliative outpatient units on resource use for cancer patients in Finland.

BACKGROUND: As cancer incidences are increasing, the means to provide effective palliative care (PC) are called for. There is evidence, that PC may prevent futile treatment at the end of life (EOL) thus implicating that PC decreases resource use at the EOL, however, the effects of outpatient PC units remain largely unknown. We surveyed the national use of Finnish tertiary care PC units and their effects on resource use at the EOL in real-life environments. PATIENTS AND METHODS: Cancer patients treated in the departments of Oncology at all five Finnish university hospitals in 2013 and deceased by 31 December 2014 were identified; of the 6010 patients 2007 were randomly selected for the study cohort. The oncologic therapies received and the resource usage of emergency services and hospital wards were collected from the hospitals' medical records. RESULTS: A PC unit was visited by 37% of the patients a median 112 days before death. A decision to terminate all life-prolonging cancer treatments was more often made for patients visiting the PC unit (90% vs. 66%, respectively). A visit to a PC unit was associated with significantly fewer visits to emergency departments (ED) and hospitalization during the last 90 days of life; the mean difference in ED visits decreased by 0.48 (SD 0.33 - 0.62, p < 0.001), and the mean inpatient days by 7.1 (SD 5.93 - 8.25, p < 0.001). A PC visit unit was independently associated with decreased acute hospital resource use during the last 30 and 90 days before death in multivariable analyses. CONCLUSION: Cancer patients' contact with a PC unit was significantly associated with the reduced use of acute hospital services at the EOL, however; only one-third of the patients visited a PC unit. Thus, systematic PC unit referral practices for patients with advanced cancer are called for.

Spiritual well-being correlates with quality of life of both cancer and non-cancer patients in palliative care - further validation of EORTC QLQ-SWB32 in Finnish.

BACKGROUND: The European Organisation for Research and Treatment of Cancer (EORTC) has developed the Spiritual Well-being Questionnaire (EORTC QLQ-SWB32), a measure of spiritual well-being validated with people receiving palliative care for cancer, although its usefulness is not restricted to that population. We aimed to translate and validate this tool in Finnish and to study the relationship between spiritual well-being (SWB) and quality of life (QOL). METHODS: A Finnish translation was produced according to the guidelines of EORTC and included forward- and back-translations. Face, content, construct and convergence/divergence validity and reliability were studied in a prospective manner. QOL was assessed with EORTC QLQ-C30 and 15D questionnaires. Sixteen individuals participated in the pilot testing. 101 cancer patients drawn from oncology units, and 89 patients with other chronic diseases drawn from religious communities in different parts of the country participated in the validation stage. Retest was obtained from 16 individuals (8 cancer and 8 non-cancer patients). Inclusion criteria included patients with either a well-defined palliative care plan, or who would benefit from palliative care, as well as the capacity to understand and communicate in Finnish. RESULTS: The translation appeared understandable and acceptable. Factorial analysis identified four scoring scales with high Cronbach alfa values: Relationship with Self (0.73), Relationship with Others (0.84), Relationship with Something Greater (0.82), Existential (0.81), and, additionally, a scale on Relationship with God (0.85). There was a significant correlation between SWB and QOL in all participants. CONCLUSIONS: The Finnish translation of EORTC QLQ-SWB32 is a valid and reliable measure both for research and clinical practice. SWB is correlated with QOL in cancer and non-cancer patients undergoing palliative care or who are eligible for it.

Future palliative competence needs - a qualitative study of physicians' and registered nurses' views.

BACKGROUND: Globally, the need for palliative care will increase as a result of the ageing of populations and the rising burden of cancer, non-communicable diseases as well as some communicable diseases. Physicians and registered nurses working in palliative care should have a sufficient level of education and competence in managing the changing needs and requirements of palliative care. There is, however, need for evidence-based palliative care training and education of physicians and registered nurses. The purpose of this study was to describe the views of physicians and registered nurses regarding future competence needs within palliative care. METHODS: The study was conducted through use of a cross-sectional qualitative design. A total of 54 physicians and 110 registered nurses completed an open-ended questionnaire about the future competence needs of palliative care. The data were analyzed using inductive content analysis. RESULTS: The results revealed four main competence needs within palliative care for the coming decade: palliative care competence at all levels within healthcare and social welfare services; individualized palliative care competence; person-centered encounters competence; and systematic competence development within palliative care. CONCLUSIONS: The results offer cues for education and professional development, which can be used to support physicians and registered nurses when future palliative care competences are included in educational programs. Seamless cooperation between palliative care services and educational institutions is recommended to ensure that undergraduate and postgraduate education is based on a continuous assessment of competence requirements within the field of palliative care. Therefore, online multi-professional simulations, for example, could be used to enhance future competencies within palliative care; undergraduate medical, nursing and allied healthcare students as well as postgraduate palliative care professionals and experts of experience could work together during simulations.

The impact of the duration of the palliative care period on cancer patients with regard to the use of hospital services and the place of death: a retrospective cohort study.

BACKGROUND: In order to avoid unnecessary use of hospital services at the end-of-life, palliative care should be initiated early enough in order to have sufficient time to initiate and carry out good quality advance care planning (ACP). This single center study assesses the impact of the PC decision and its timing on the use of hospital services at EOL and the place of death. METHODS: A randomly chosen cohort of 992 cancer patients treated in a tertiary hospital between Jan 2013 -Dec 2014, who were deceased by the end of 2014, were selected from the total number of 2737 identified from the hospital database. The PC decision (the decision to terminate life-prolonging anticancer treatments and focus on symptom centered palliative care) and use of PC unit services were studied in relation to emergency department (ED) visits, hospital inpatient days and place of death. RESULTS: A PC decision was defined for 82% of the patients and 37% visited a PC unit. The earlier the PC decision was made, the more often patients had an appointment at the PC unit (> 180 days prior to death 72% and < 14 days 10%). The number of ED visits and inpatient days were highest for patients with no PC decision and lowest for patients with both a PC decision and an PC unit appointment (60 days before death ED visits 1.3 vs 0.8 and inpatient days 9.9 vs 2.9 respectively, p < 0.01). Patients with no PC decision died more often in secondary/tertiary hospitals (28% vs. 19% with a PC decision, and 6% with a decision and an appointment to a PC unit). CONCLUSIONS: The PC decision to initiate a palliative goal for the treatment had a distinct impact on the use of hospital services at the EOL. Contact with a PC unit further increased the likelihood of EOL care at primary care.

Assessing the utilization of the decision to implement a palliative goal for the treatment of cancer patients during the last year of life at Helsinki University Hospital: a historic cohort study.

Background: To avoid aggressive treatments at the end-of-life and to provide palliative care (PC), physicians need to terminate futile anti-cancer treatments and define the palliative goal of the treatment in time. This single center study assesses the practices used to make the decision that leads to treatment with a palliative goal, i.e., the PC decision and its effect on anti-cancer treatments at the end of life.Material and methods: Patients with a cancer diagnosis treated in tertiary hospital during 1st January 2013 - 31st December 2014 and deceased by the end of 2014 were identified in the hospital database (N = 2737). Of these patients, 992 were randomly selected for this study. The PC decision was screened from patient records, i.e., termination of cancer-specific treatments and a focus on symptom-centered PC.Results: The PC decision was defined in 82% of the patients during the last year of life (49% >30 days and 33% ≤30 days before death, 18% with no decision). The median time from the decision to death was 46 days. Systemic cancer therapy was given during the last month of life in 1%, 36% and 38% (p < .001) and radiotherapy 22%, 40% and 31% (p = .03) cases, respectively; referral to a PC unit was made in 62%, 22% and 11%, respectively (p < .001). In logistic regression analyses younger age, shorter duration of the disease trajectory and type of cancer (e.g., breast cancer) were associated with a lack or late timing of the PC decision.Conclusion: The decision to initiate a palliative goal for the treatment was frequently made for cancer patients but occurred late for every third patient. Younger age and certain cancer types were associated with late PC decisions, thus leading to anti-cancer treatments continuing until close to the death with low access to a PC unit.

[Symptomatic treatment of a dying patient]. / Oireiden hoito elämän loppuvaiheessa.

The too late initiation of symptomatic treatment may increase the patient's suffering and even lead to premature death. Examinations and actions should be planned in a patient-centered and symptomatic manner. Neglecting or poor knowledge of symptom diagnostics may lead to undertreatment of the patient's ailments and on the other hand to the application of treatments that are mistimed and too intensive. In addition to medical aid the patient needs a treatment team that creates security and improves patient autonomy by supporting home care.

[Palliative (symptomatic) care of (imminently) dying patients]. / Kuolevan potilaan oireiden hoito.

The updated Current Care Guideline focuses on medical symptom treatment when curative treatment is no longer possible. Palliative care should be available to all dying patients at all health care levels. Pain should be treated prophylactically. Opioids are effective in cancer pain and should be chosen for moderate or severe pain in line with the WHO pain ladder. Treatment options for symptoms which call for acute interventions, such as intracranial hypertension, and options for dyspnoea, delirium, gastro-intestinal symptoms, ascites, dehydration and end-of-life treatment of elderly and demented patients are described.

Post-graduate Course in Palliative Medicine: Experiences from an E-Learning-Based Pilot Program, a Mixed Methods Study.

Objective: To study whether E-learning methods are feasible in the post-graduate education of palliative medicine. Methods: A mixed-methods study. Evaluations from pilot course attendees were analyzed numerically and answers to open-ended questions about E-learning were analyzed using inductive content analysis. A national pilot E-learning-based post-graduate course in palliative medicine with 24 participating physicians in Finland. The evaluation of teaching modules and different aspects of the course was achieved from the participants through numerical statements and open-ended questions. Results: The feedback on most aspects of the course was good. For example, issues of pain and symptom control, lectures, pre-exams, and group discussions were deemed suitable for E-learning, while studying communication and existential issues through E-learning was considered more challenging. The benefits of E-learning included efficacy, better accessibility, and the possibility to go back to the teaching material. Reduced networking and face-to-face interactions were stated as challenges of E-learning. Conclusions: E-learning is feasible in the post-graduate education of palliative medicine and can be 'surprisingly rewarding'. It allows easy access to learn many important topics, while social networking may fall short. Further studies are needed to assess the increase in competence by different learning methods.

Toll-like receptor 9 mediates CpG oligonucleotide-induced cellular invasion.

Toll-like receptor 9 (TLR9) belongs to the innate immune system and recognizes microbial and vertebrate DNA. We showed previously that treatment with the TLR9-agonistic ODN M362 (a CpG sequence containing oligonucleotide) induces matrix metalloproteinase-13-mediated invasion in TLR9-expressing human cancer cell lines. Here, we further characterized the role of the TLR9 pathway in this process. We show that CpG oligonucleotides induce invasion in macrophages from wild-type C57/B6 and MyD88 knockout mice and in human MDA-MB-231 breast cancer cells lacking MyD88 expression. This effect was significantly inhibited in macrophages from TLR9 knockout mice and in human MDA-MB-231 breast cancer cells stably expressing TLR9 small interfering RNA or dominant-negative tumor necrosis factor receptor-associated factor 6 (TRAF6). Sequence modifications to the CpG oligonucleotides that targeted the stem loop and other secondary structures were shown to influence the invasion-inducing effect in MDA-MB-231 cells. In contrast, methylation of the cytosine residues of the parent CpG oligonucleotide did not affect the TLR9-mediated invasion compared with the unmethylated parent CpG oligonucleotide. Finally, expression of TLR9 was studied in clinical breast cancer samples and normal breast epithelium with immunohistochemistry. TLR9 staining localized in epithelial cells in both cancer and normal samples. The mean TLR9 staining intensity was significantly increased in the breast cancer cells compared with normal breast epithelial cells. In conclusion, our results suggest that TLR9 expression is increased in breast cancer and CpG oligonucleotide-induced cellular invasion is mediated via TLR9 and TRAF6, independent of MyD88. Further, our findings suggest that the structure and/or stability of DNA may influence the induction of TLR9-mediated invasion in breast cancer.

Adverse outcome and resistance to adjuvant antiestrogen therapy in node-positive postmenopausal breast cancer patients-The role of p53.

The prognostic and predictive relevance of p53 immunoreactivity is used here as a tentative approach for defining more accurately the benefit of adjuvant hormonal therapy in postmenopausal node-positive breast cancer patients. Ninety-seven postmenopausal patients with axillary lymph node metastasis were treated with an antiestrogen for a period of 3 years after primary surgery and radiotherapy. The p53 status of the primary tumor was assessed by immunohistochemistry and 24% of the samples showed positive expression of p53. Within the average follow-up time of 59 months, disease recurrence was diagnosed in 34 patients (35%). Multivariate analysis showed high clinical stage, negative estrogen receptor status and p53 positivity to be independent prognostic factors predicting both shortened disease-free survival and worse overall survival. p53 immunoreactivity was associated with worse clinical outcome irrespective of hormone receptor status. The data suggest that adjuvant therapy with antiestrogens is insufficient in this patient population with p53-positive tumors.

Matrix metalloproteinase-9 (MMP-9) immunoreactive protein has modest prognostic value in locally advanced breast carcinoma patients treated with an adjuvant antiestrogen therapy.

BACKGROUND: Matrix metalloproteinases (MMPs) are involved with tumour invasion and metastasis. Controversial data exists concerning the prognostic value of MMP-9 in breast carcinoma. We examined, here, whether the MMP-9 immunoreactive protein would correlate with--the prognosis in breast carcinoma treated with hormonal adjuvant therapy. MATERIALS AND METHODS: The MMP-9 status was determined immunohistochemically from primary tumour specimens in 168 postmenopausal breast cancer patients with a locally advanced (N+) disease treated with antiestrogen for three years after the primary therapy. RESULTS: A positive immunostaining for MMP-9 was found in 61.3% of 168 primary tumours without any significant correlation to clinical stage, histology or hormone receptor status. MMP-9 immunoreactivity did not correlate with the survival when the entire study population was included in the analysis. There was, however, a compromised disease-free survival in a subgroup of patients presenting with an estrogen receptor-negative and MMP-9-positive tumour. The 5-year disease-free survival was only 37% in those patients, when it was 63% in the patients with a tumour negative for both estrogen receptor and MMP-9. CONCLUSION: We suggest that the prognostic value of MMP-9 immunoreactivity in the primary tumour is not generally strong in breast carcinoma, but it might correlate with the clinical benefit of an antiestrogen therapy, since MMP-9 positivity seemed to correlate with early recurrence in patients with an estrogen receptor-negative primary tumour.

Toll-like receptor-9 expression is inversely correlated with estrogen receptor status in breast cancer.

Toll-like receptor 9 (TLR9) recognizes microbial and vertebrate DNA. We previously demonstrated TLR9 expression in human breast cancer cell lines and showed that TLR9 ligands stimulate their in vitro invasion. The aim of this study was to characterize TLR9 expression in clinical breast cancer specimens. Immunohistochemical staining intensity was compared with known baseline prognostic factors and distant metastasis-free survival. TLR9 expression was detected in 98% of the tumors studied (n = 141). The mean TLR9 staining intensity was higher in ER- than in the highly ER+ breast cancers (p = 0.039). High-grade tumors had significantly increased TLR9 expression (p = 0.027) compared with lower-grade tumors. The highest TLR9 expression was detected in the mucinous and the lowest in the tubular breast cancers (p = 0.034). Distant metastasis-free survival was higher in the lower TLR9-expressing half of the cohort than in the higher TLR9-expressing group (p = 0.118). TLR9 expression did not correlate with menopausal, PgR or Her2 status, patient age, tumor proliferative or invasive characteristics.