Patient perspectives of the impact and long-term management of lymphoedema

Lymphoedema following cancer treatment is characterized by swelling, and adversely influences mobility, function and quality of life. There is no cure, but without treatment lymphedema may progress. Since lymphedema treatment options are costly and time consuming, understanding the influence of these, and other potential barriers, on treatment adherence is vital in reducing the public health burden of lymphedema. Complex physical therapy and compression are supported by scientific evidence and patients also perceive these treatments as effective for improving symptoms and function. Multiple treatments may be required to treat all aspects of the condition. Patients and health professionals should consider effect and costs when identifying optimal treatment strategies.

Role of intratumoural heterogeneity in cancer drug resistance : molecular and clinical perspectives

Drug resistance continues to be a major barrier to the delivery of curative therapies in cancer. Historically, drug resistance has been associated with over-expression of drug transporters, changes in drug kinetics or amplification of drug targets. However, the emergence of resistance in patients treated with new-targeted therapies has provided new insight into the complexities underlying cancer drug resistance. Recent data now implicate intratumoural heterogeneity as a major driver of drug resistance. Single cell sequencing studies that identified multiple genetically distinct variants within human tumours clearly demonstrate the heterogeneous nature of human tumours. The major contributors to intratumoural heterogeneity are (i) genetic variation, (ii) stochastic processes, (iii) the microenvironment and (iv) cell and tissue plasticity. Each of these factors impacts on drug sensitivity. To deliver curative therapies to patients, modification of current therapeutic strategies to include methods that estimate intratumoural heterogeneity and plasticity will be essential.

miR-126 in human cancers : clinical roles and current perspectives

miR-126 has been implicated in the processes of inflammation and angiogenesis. Through these processes, miR-126 is implicated in cancer biology, but its role there has not been well reviewed. The aim of this review is to examine the molecular mechanisms and clinicopathological significance of miR-126 in human cancers. miR-126 was shown to have roles in cancers of the gastrointestinal tract, genital tracts, breast, thyroid, lung and some other cancers. Its expression was suppressed in most of the cancers studied. The molecular mechanisms that are known to cause aberrant expression of miR-126 include alterations in gene sequence, epigenetic modification and alteration of dicer abundance. miR-126 can inhibit progression of some cancers via negative control of proliferation, migration, invasion, and cell survival. In some instances, however, miR-126 supports cancer progression via promotion of blood vessel formation. Downregulation of miR-126 induces cancer cell proliferation, migration, and invasion via targeting specific oncogenes. Also, reduced levels of miR-126 are a significant predictor of poor survival of patients in many cancers. In addition, miR-126 can alter a multitude of cellular mechanisms in cancer pathogenesis via suppressing gene translation of numerous validated targets such as PI3K, KRAS, EGFL7, CRK, ADAM9, HOXA9, IRS-1, SOX-2, SLC7A5 and VEGF. To conclude, miR-126 is commonly down-regulated in cancer, most likely due to its ability to inhibit cancer cell growth, adhesion, migration, and invasion through suppressing a range of important gene targets. Understanding these mechanisms by which miR-126 is involved with cancer pathogenesis will be useful in the development of therapeutic targets for the management of patients with cancer.

Signet-ring cell carcinoma of colorectum : current perspectives and molecular biology

PURPOSE Colorectal signet-ring cell carcinoma (SRCC) is rare, and very little detailed information on the molecular biology of the disease is available. METHODS The literature on the clinical, pathological and, in particular, the molecular biology of this rare entity was critically reviewed. The reviewed articles take into account a total of 1,817 cases of SRCC, but only 143 cases have molecular data available. The characteristics of two patients with colorectal SRCC were also discussed. RESULTS Colorectal SRCC mostly occurs in younger patients, is larger and has different site predilection compared with conventional colorectal adenocarcinoma. It can occur as one of the synchronous cancers in the colorectum. The cancer is usually diagnosed at advanced stages because of the late manifestation of symptoms, and aggressive treatment strategy is required. Limited reports in the literature have shown that the variant of colorectal cancer demonstrated a different pattern of genetic alterations of common growth kinase-related oncogenes (K-ras, BRAF), tumour suppressor genes (p53, p16), gene methylation and cell adhesion-related genes related to the Wingless signalling pathway (E-cadherin and beta-catenin) from conventional colorectal adenocarcinoma. Colorectal SRCC also showed high expression of mucin-related genes and genes related to the gastrointestinal system. There was also a higher prevalence of microsatellite instability-high tumours and low Cox-2 expression in colorectal SRCC as opposed to conventional adenocarcinoma. CONCLUSIONS Colorectal SRCC has unique molecular pathological features. The unique molecular profiles in SRCC may provide molecular-based improvements to patient management in colorectal SRCC.

Provision of survivorship care for patients with haematological malignancy at completion of treatment: a cancer nursing practice survey study

Purpose Many haematological cancer survivors report long-term physiological and psychosocial effects, which persist far beyond treatment completion. Cancer services have been required to extend care to the post-treatment phase to implement survivorship care strategies into routine practice. As key members of the multidisciplinary team, cancer nurses’ perspectives are essential to inform future developments in survivorship care provision. Methods This is a pilot survey study, involving 119 nurses caring for patients with haematological malignancy in an Australian tertiary cancer care centre. The participants completed an investigator developed survey designed to assess cancer care nurses’ perspectives on their attitudes, confidence levels, and practice in relation to post-treatment survivorship care for patients with a haematological malignancy. Results Overall, the majority of participants agreed that all of the survivorship interventions included in the survey should be within the scope of the nursing role. Nurses reported being least confident in discussing fertility and employment/financial issues with patients and conducting psychosocial distress screening. The interventions performed least often included, discussing fertility, intimacy and sexuality issues and communicating survivorship care with the patient’s primary health care providers. Nurses identified lack of time, limited educational resources, lack of dedicated end-of-treatment consultation and insufficient skills/knowledge as the key barriers to survivorship care provision. Conclusion Cancer centres should implement an appropriate model of survivorship care and provide improved training and educational resources for nurses to enable them to deliver quality survivorship care and meet the needs of haematological cancer survivors.

Australia’s first Allied Health Prescribing Program - exploring participants' perspectives on the study program's learning objectives

BACKGROUND The Queensland University of Technology in collaboration with Queensland Health pioneered development of the Allied Health Prescribing Training Program to assist allied health professionals (AHPs) to competently prescribe medicines within their scope of practice. The study program consisted of two modules: Introduction to Clinical Therapeutics for Prescribers and Prescribing and Quality Use of Medicines. METHODS Pre- and post- surveys were developed for both modules. Key themes explored were understanding and confidence in selecting therapeutic choices for patients. For module 2 the learning objectives for safe and effective prescribing were investigated. Data were collected from participants in weeks one and thirteen of the modules via online surveys. RESULTS In the pre-module survey for the first module, participants had a limited degree of understanding and confidence regarding safe and effective use of medicines and appropriate therapeutic choices for managing patients, particularly for complex patients. This improved significantly in the post-module survey. In the pre-module survey for module 2, participants had a moderate degree of understanding and confidence regarding various prescribing learning objectives (including safe and effective prescribing, professional, legal and ethical aspects, communicating medication orders, prescribing safely in their select areas of practice, prescribing safely for complex patients in their area of practice). This increased significantly in the post-module survey. DISCUSSION This training program was implemented to develop a framework of knowledge and skills for AHPs to undertake a prescribing role. The program delivered an increase in participants’ knowledge in the key prescribing areas; and increased participants’ confidence in prescribing safely for patients and for complex patients in their select practice areas. An important aspect of this program was inclusion of prescribing–related activities under supervision of a designated medical practitioner. In conclusion, this educational program for Queensland Health AHP prescribers was successfully developed and is in the final stages of delivery.

Perspectives on prescribing in nursing homes in Helsinki

Prescribing for older patients is challenging. The prevalence of diseases increases with advancing age and causes extensive drug use. Impairments in cognitive, sensory, social and physical functioning, multimorbidity and comorbidities, as well as age-related changes in pharmacokinetics and pharmacodynamics all add to the complexity of prescribing. This study is a cross-sectional assessment of all long-term residents aged ≥ 65 years in all nursing homes in Helsinki, Finland. The residents’ health status was assessed and data on their demographic factors, health and medications were collected from their medical records in February 2003. This study assesses some essential issues in prescribing for older people: psychotropic drugs (Paper I), laxatives (Paper II), vitamin D and calcium supplements (Paper III), potentially inappropriate drugs for older adults (PIDs) and drug-drug interactions (DDIs)(Paper IV), as well as prescribing in public and private nursing homes. A resident was classified as a medication user if his or her medication record indicated a regular sequence for its dosage. Others were classified as non-users. Mini Nutritional Assessment (MNA) was used to assess residents’ nutritional status, Beers 2003 criteria to assess the use of PIDs, and the Swedish, Finnish, INteraction X-referencing database (SFINX) to evaluate their exposure to DDIs. Of all nursing home residents in Helsinki, 82% (n=1987) participated in studies I, II, and IV and 87% (n=2114) participated in the study III. The residents’ mean age was 84 years, 81% were female, and 70% were diagnosed with dementia. The mean number of drugs was 7.9 per resident; 40% of the residents used ≥ 9 drugs per day, and were thus exposed to polypharmacy. Eighty percent of the residents received psychotropics; 43% received antipsychotics, and 45% used antidepressants. Anxiolytics were prescribed to 26%, and hypnotics to 28% of the residents. Of those residents diagnosed with dementia, 11% received antidementia drugs. Fifty five percent of the residents used laxatives regularly. In multivariate analysis, those factors associated with regular laxative use were advanced age, immobility, poor nutritional status, chewing problems, Parkinson’s disease, and a high number of drugs. Eating snacks between meals was associated with lower risk for laxative use. Of all participants, 33% received vitamin D supplementation, 28% received calcium supplementation, and 20% received both vitamin D and calcium. The dosage of vitamin D was rather low: 21% received vitamin D 400 IU (10 µg) or more, and only 4% received 800 IU (20 µg) or more. In multivariate analysis, residents who received vitamin D supplementation enjoyed better nutritional status, ate snacks between meals, suffered no constipation, and received regular weight monitoring. Those residents receiving PIDs (34% of all residents) more often used psychotropic medication and were more often exposed to polypharmacy than residents receiving no PIDs. Residents receiving PIDs were less often diagnosed with dementia than were residents receiving no PIDs. The three most prevalent PIDs were short-acting benzodiazepine in greater dosages than recommended, hydroxyzine, and nitrofurantoin. These three drugs accounted for nearly 77% of all PID use. Of all residents, less than 5% were susceptible to a clinically significant DDI. The most common DDIs were related to the use of potassium-sparing diuretics, carbamazepine, and codeine. Residents exposed to potential DDIs were younger, had more often suffered a previous stroke, more often used psychotropics, and were more often exposed to PIDs and polypharmacy than were residents not exposed to DDIs. Residents in private nursing homes were less often exposed to polypharmacy than were residents in public nursing homes. Long-term residents in nursing homes in Helsinki use, on average, nearly eight drugs daily. The use of psychotropic drugs in our study was notably more common than in international studies. The prevalence of laxatives equaled other prior international studies. Regardless of the known benefit and recommendation of vitamin D supplementation for elderly residing mostly indoors, the proportion of nursing home residents receiving vitamin D and calcium was surprisingly low. The use of PIDs was common among nursing home residents. PIDs increased the likelihood of DDIs. However, DDIs did not seem a major concern among the nursing home population. Monitoring PIDs and potential drug interactions could improve the quality of prescribing.

Fatigue self-management behaviors in patients with advanced cancer: A prospective longitudinal survey

Purpose: To explore the fatigue self-management behaviors and factors associated with effectiveness of these behaviors in patients with advanced cancer. Design: Prospective longitudinal interviewer-administered survey. Setting: A tertiary cancer center in Queensland Australia. Sample: One hundred fifty two outpatients with metastatic breast, lung, colorectal and prostate cancer experiencing fatigue (>3/10) were recruited. Main Research Variables: Fatigue self-management behaviors outcomes (perceived effectiveness, self-efficacy and frequency), medical/demographic characteristics (including sites of primary cancer and metastasis, comorbidity, performance status), social support, depressive, anxiety, and other symptoms were assessed. Findings: The participants reported moderate levels of fatigue at baseline (M=5.85, SD 1.44), and maintained moderate levels at 4 weeks and 8 weeks. On average, participants consistently used approximately nine behaviors at each time point. Factors significantly associated with higher levels of perceived effectiveness of fatigue self-management behaviors were higher self-efficacy (p<.001), higher education level (p=.02), and lower levels of depressive symptoms (p=.04). Conclusions: The findings of this study demonstrate that patients with cancer, even with advanced disease, still want and are able to use a number of behaviors to control their fatigue. Self-management interventions that aim to enhance self-efficacy and address any concurrent depressive symptoms have the potential to reduce fatigue severity. Implications for Nursing: Nurses are well positioned to play a key role in supporting patients in their fatigue self-management. Knowledge Translation: This study particularly focused on the perspectives of patients about fatigue self-management, highlighting a number of issues requiring further attention in clinical practice and the potential for future research.

Cancer stem cells in oesophageal squamous cell carcinoma: Identification, prognostic and treatment perspectives

Cancer stem cells (CSCs) are a vital subpopulation of cells to target for the treatment of cancers. In oesophageal squamous cell carcinoma (ESCC), there are several markers such as CD44, ALDH, Pygo2, MAML1, Twist1, Musashi1, Side population (SP), CD271 and CD90 that have been proposed to identify the cancer stem cells in individual cancer masses. It has also been demonstrated that stem cell markers like ALDH1, HIWI, Oct3/4, ABCG2, SOX2, SALL4, BMI-1, NANOG, CD133 and podoplanin are associated with patient's prognosis, pathological stages, cancer recurrence and therapy resistance. Finding new cancer stem cell targets or designing drugs to manipulate the known molecular targets in CSCs could be useful for improvements in clinical outcomes of the disease. To conclude, data suggest that CSCs in oesophageal squamous cell carcinoma are related to resistance to therapy and poor prognosis of patients with ESCC. Therefore, innovative insights into CSC biology and CSC-targeted therapies will help to achieve more effective management of patients with oesophageal squamous cell carcinoma.

Anti-TNF treatment in juvenile idiopathic arthritis and associated uveitis : Clinical perspectives on growth, uveitis, and drug survival

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of childhood chronic arthritides, associated with chronic uveitis in 20% of cases. For JIA patients responding inadequately to conventional disease-modifying anti-rheumatic drugs (DMARDs), biologic therapies, anti-tumor necrosis factor (anti-TNF) agents are available. In this retrospective multicenter study, 258 JIA-patients refractory to DMARDs and receiving biologic agents during 1999-2007 were included. Prior to initiation of anti-TNFs, growth velocity of 71 patients was delayed in 75% and normal in 25%. Those with delayed growth demonstrated a significant increase in growth velocity after initiation of anti-TNFs. Increase in growth rate was unrelated to pubertal growth spurt. No change was observed in skeletal maturation before and after anti-TNFs. The strongest predictor of change in growth velocity was growth rate prior to anti-TNFs. Change in inflammatory activity remained a significant predictor even after decrease in glucocorticoids was taken into account. In JIA-associated uveitis, impact of two first-line biologic agents, etanercept and infliximab, and second-line or third-line anti-TNF agent, adalimumab, was evaluated. In 108 refractory JIA patients receiving etanercept or infliximab, uveitis occurred in 45 (42%). Uveitis improved in 14 (31%), no change was observed in 14 (31%), and in 17 (38%) uveitis worsened. Uveitis improved more frequently (p=0.047) and frequency of annual uveitis flares was lower (p=0.015) in those on infliximab than in those on etanercept. In 20 patients taking adalimumab, 19 (95%) had previously failed etanercept and/or infliximab. In 7 patients (35%) uveitis improved, in one (5%) worsened, and in 12 (60%) no change occurred. Those with improved uveitis were younger and had shorter disease duration. Serious adverse events (AEs) or side-effects were not observed. Adalimumab was effective also in arthritis. Long-term drug survival (i.e. continuation rate on drug) with etanercept (n=105) vs. infliximab (n=104) was at 24 months 68% vs. 68%, and at 48 months 61% vs. 48% (p=0.194 in log-rank analysis). First-line anti-TNF agent was discontinued either due to inefficacy (etanercept 28% vs. infliximab 20%, p=0.445), AEs (7% vs. 22%, p=0.002), or inactive disease (10% vs. 16%, p=0.068). Females, patients with systemic JIA (sJIA), and those taking infliximab as the first therapy were at higher risk for treatment discontinuation. One-third switched to the second anti-TNF agent, which was discontinued less often than the first. In conclusion, in refractory JIA anti-TNFs induced enhanced growth velocity. Four-year treatment survival was comparable between etanercept and infliximab, and switching from first-line to second-line agent a reasonable therapeutic option. During anti-TNF treatment, one-third with JIA-associated anterior uveitis improved.

Written Cancer Narratives : An Ethnomedical Study of Cancer Patients' Thoughts, Emotions and Experiences

Since the second half of the 20th century, cancer has become a dominant disease in Western countries, endangering people regardless of age, gender, race or social status. Every year almost eight million people die of cancer worldwide. In Finland every fourth person is expected to fall ill with cancer at some stage of his or her life. During the 20th century, along with rapid changes in the medical system, people s awareness of cancer has increased a great deal. This has also influenced the image of cancer in popular discourse over the past decades. However, from the scientific point of view there is still much that is unclear about the disease. This thesis shows that this is a big problem for ordinary people, as, according to culture-bound illness ideology, people need an explanation about the origin of their illness in order to help them cope. The main aim of this thesis is to examine the process of being ill with cancer from the patient s point of view, in order to analyse attitudes and behaviour towards cancer and its significance and culture-bound images. This narrative-based study concentrates on patients voicings , which are important in understanding the cancer experience and when attempting to make it more open within current cultural and societal settings. The Kun sairastuin syöpään ( when I fell ill with cancer ) writing competition organised by Suomen Syöpäpotilaat ry (the Finnish Cancer Patients Association), Suomen Syöpäyhdistys ry (the Finnish Cancer Union), and Suomalaisen Kirjallisuuden Seuran kansanrunousarkisto (the Finnish Literary Society Folklore Archive) was announced on the 1st of May 1994 and lasted until the 30th of September 1994. As a result, a total of 672 cancer narratives, totalling 6384 pages, were received, filled with experiences relating to cancer. Written cancer narratives form a body of empirical data that is suitable for content or textual analysis. In this thesis, content analysis is adopted in order to become familiar with the texts and to preselect the themes and analytical units for further examination. I use multiple perspectives in order to interpret cancer patients ideas and reasoning. The ethnomedical approach unites popular health beliefs that originated in Finnish folk medicine, as well as connecting alternative medicine, which patients make use of, with biomedicine, the dominant form of medicine today. In addition to this, patients narratives, which are composed of various structural segments, are approached from the folklorist s perspective. In this way they can be seen as short pathographies, reconstructions of self-negotiation and individual decision making during the illness process. Above all, cancer patients writing describe their feelings, thoughts and experiences. Factors that appear insignificant to modern medicine, overwhelmed as it is by medical technologies that concentrate on dysfunctional tissue within diseased bodies. Ethnomedical study of cancer patients writings gives access to the human side of cancer discourse, and combines both medical, and popular, knowledge of cancer. In my view, the natural world and glimpses of tradition are bound together with one general aim within cancer narratives: to tackle the illness and mediate its meanings. Furthermore, the narrative approach reveals that participants write with the hope of offering a different interpretation of the cancer experience, and thus of confronting culturally pre-defined images and ideologies.

Déficits immunitaires primaires: diagnostic, prise en charge, quelques perspectives.

Severe primary immunodeficiencies (PID) are rare; their global incidence is comparable to that of childhood leukemia; they include more than 100 different entities. Clinical manifestations are: unusually severe or frequent infections or infections that do not respond to adequate treatment; an increased risk of certain malignancies; sometimes auto-immune manifestations. Delayed diagnosis and management of PID can lead to severe and irreversible complications or to death. PID can become manifest only in the adult; in common variable immune deficiency, the median age at diagnosis is between the 2nd and the 3rd decade of life. PID are often transmitted genetically; recent progresses in molecular biology have allowed more precise and earlier, including antenatal, diagnosis. Molecular treatment of 3 infants with a severe immunodeficiency has recently been achieved in April 2000. Those progresses were mostly based on the study of immunodeficiency databases. We present here the work of a Belgian group specialized in PID; meetings have started in June 1997. This group establishes guidelines for the diagnosis and treatment of PID, adapted to the local situation. The elaboration of a national register of PID is also underway; this has to provide all guaranties of anonymity to patients and families. Such a register already exists at the European level; it has provided the basis for new diagnostic and therapeutic possibilities. The inclusion of Belgian data in this register should allow essential progresses essential for our patients.

Preliminary experience of ovarian tissue cryopreservation procedure: alternatives, perspectives and feasibility

Chemotherapy and radiotherapy induce premature ovarian failure in many patients treated for oncological or benign diseases. The present paper reviews the risk of developing premature ovarian failure according to the type of treatment and the different options to preserve fertility, focusing on the cryopreservation of ovarian tissue. This technique constitutes a promising approach to preserve the fertility of young patients and offers the advantage of storing a large number of follicles that could be subsequently transplanted or cultured in vitro to obtain mature oocytes. Based on 34 requests, from which 19 were performed, the feasibility of the ovarian cryopreservation procedure is evaluated. The medical and ethical approaches of this protocol are also discussed. Cryopreservation of ovarian tissue constitutes new hope for many patients, but must still be kept for selected cases, with a significant risk of premature ovarian failure after treatments such as bone marrow transplantation.

The challenge of patients’ unmet palliative care needs in the final stages of chronic illness.

Background: There is consensus in the literature that the end of life care for patients with chronic illness is suboptimal, but research on the specific needs of this population is limited. Aim: This study aimed to use a mixed methodology and case study approach to explore the palliative care needs of patients with a non-cancer diagnosis from the perspectives of the patient, their significant other and the clinical team responsible for their care. Patients (n 18) had a diagnosis of either end-stage heart failure, renal failure or respiratory disease. Methods: The Short Form 36 and Hospital and Anxiety and Depression Questionnaire were completed by all patients. Unstructured interviews were (n 35) were conducted separately with each patient and then their significant other. These were followed by a focus group discussion (n 18) with the multiprofessional clinical team. Quantitative data were analysed using simple descriptive statistics and simple descriptive statistics. All qualitative data were taped, transcribed and analysed using Colaizzi’s approach to qualitative analysis. Findings: Deteriorating health status was the central theme derived from this analysis. It led to decreased independence, social isolation and family burden. These problems were mitigated by the limited resources at the individual’s disposal and the availability of support from hospital and community services. Generally resources and support were perceived as lacking. All participants in this study expressed concerns regarding the patients’ future and some patients described feelings of depression or acceptance of the inevitability of imminent death. Conclusion: Patients dying from chronic illness in this study had many concerns and unmet clinical needs. Care teams were frustrated by the lack of resources available to them and admitted they were ill-equipped to provide for the individual’s holistic needs. Some clinicians described difficulty in talking openly with the patient and family regarding the palliative nature of their treatment. An earlier and more effective implementation of the palliative care approach is necessary if the needs of patients in the final stages of chronic illness are to be adequately addressed. Pa

The journey to concordance for patients with hypertension: a qualitative study in primary care

Objective: We aimed to explore, using qualitative methods, the perspectives of patients with hypertension on issues relating to concordance in prescribing.

Method: This study took place in NHS general practices in Northern Ireland. A purposeful sample of patients who had been prescribed anti-hypertensive medication for at least one year were invited to participate in focus groups or semi-structured interviews; data were analysed using constant comparison.

Main outcome measures: The perspectives of patients with hypertension on issues relating to concordance in prescribing.

Results: Twenty-five individuals participated in five focus groups; two participated in semi-structured interviews. Participants felt they could make valuable contributions to consultations regarding their management. They were prepared to negotiate with GPs regarding their medication, but most deferred to their doctor’s advice, perceiving doctors’ attitudes and time constraints as barriers to their greater involvement in concordant decision-making. They had concerns about taking anti-hypertensive drugs, were aware of lifestyle influences on hypertension and reported using personal strategies to facilitate adherence and reduce the need to take medication.

Conclusions: Participants indicated a willingness to be?involved in concordance in prescribing anti- hypertensive medication but needed health professionals to address their concerns and confusion about the nature of hypertension. These findings suggest that there is a need for doctors and other healthcare professionals with responsibility for prescribing to develop skills specifically to explore the beliefs and views underlying an individual’s medication use. Such skills may need to be developed through specific training programmes at both undergraduate and postgraduate level.