Health care utilisation and characteristics of long-term breast cancer survivors: nationwide survey in Denmark.

AIM: To investigate long-term female breast cancer survivors' (BCS') health care utilisation, health, and employment. METHODS: An age-stratified random sample of 2000 female breast cancer survivors (BCS) 5-15 years after primary surgery without recurrence was drawn from the Danish Breast Cancer Cooperative Group register. A self-administered questionnaire assessed sociodemography, health care utilisation, employment, and health-related quality of life (HRQOL). Associations with breast cancer treatment were investigated. RESULTS: Response rate was 79%. Significantly more BCS than the general women population reported health care utilisation (61% versus. 56%; age-standardised risk ratio (SRR): 1.10; 95% confidence interval (CI) 1.05-1.15), but significantly fewer BCS were disability pensioners (15% versus 19%; SRR: 0.77; 95% CI 0.64-0.93). 'Daily activities limited due to sequelae' were reported by 20%, and 'stopped working/changed job due to sequelae' by 11% of BCS. In multiple logistic regression analysis, radiotherapy (odds ratio (OR) 2.54; 95% CI 1.34-4.80) and endocrine therapy (OR 2.48; 95% CI 1.13-5.45, postmenopausal women only) were significantly related to 'stopped working/changed job due to sequelae'. Time since surgery 5-10 years (versus >10 years) was significantly associated with 'daily activities limited due to sequelae' (OR 2.02; CI 1.43-2.84), which, in turn, was significantly related to poorer HRQOL (all p<0.05). Chemotherapy, receptor status, and protocol allocation did not show significant associations in any analyses. CONCLUSION: Significantly more BCS reported health care utilisation. Radiotherapy, shorter time since surgery, and endocrine therapy predicted daily activity and work limitations due to sequelae.

Chronic pain and other sequelae in long-term breast cancer survivors: nationwide survey in Denmark.

OBJECTIVES: To investigate self-reported chronic pain and other sequelae in a nationally representative sample of long-term breast cancer survivors (BCS). DESIGN: Age-stratified random sample of 2,000 female BCS 5 years after primary surgery without recurrence drawn from the Danish Breast Cancer Cooperative Group register, which is representative regarding long-term BCS in Denmark. ASSESSMENT: Self-administered questionnaire including questions on sociodemography, chronic pain (6 months), health-related quality of life (HRQOL) and other sequelae related to breast cancer. Associations with treatment were investigated. Report of chronic pain was compared to normative data. RESULTS: The response rate was 79%. Chronic pain prevalence of 42% was significantly higher in BCS compared to general population women (SRR: 1.32; 95% CI: 1.23-1.42). Sequelae related to breast cancer were paraesthesia 47%, chronic pain 29%, arm/shoulder swelling 25%, phantom sensations 19%, and allodynia 15%. Chronic pain related to breast cancer was significantly associated with poorer HRQOL and higher medicine consumption, and, in multiple logistic regression analysis, with age (<70 years), short education, being single (divorced, widowed, separated), radiotherapy, and time since operation <10 years. Radiotherapy and younger age were significantly associated with most sequelae. CONCLUSION: Chronic pain was more prevalent in BCS compared to the general population. Significant predictors for sequelae related to breast cancer were radiotherapy and younger age. Future research should therefore prioritize sequelae prevention.

Pain management of opioid-treated cancer patients in hospital settings in Denmark.

AIM: To evaluate the performance and quality of cancer pain management in hospital settings. METHODS: Anaesthesiologists specialised in pain and palliative medicine studied pain management in departments of oncology and surgery. Study days were randomly chosen and patients treated with oral opioids were included. Information regarding pain aetiology and mechanisms, pain medications and opioid side effects were registered from the medical records and by examining patients. Pain intensity was assessed using the Brief Pain Inventory. RESULTS: In total, 59 cancer patients were included. In 49 (83%) patients pain aetiology was assessed by the physicians of the departments of oncology and surgery. In only 19 (32%) patients they assessed pain mechanisms. The median oral morphine dose was 120 mg/day (range: 10-720 mg/day). Seventy-eight per cent of patients received opioids at adequate regular intervals according to the duration of action. In 88% of the patients supplemental short-acting oral opioids were given on demand and the median supplemental oral dose was 16.5% of the daily dose. Seven patients with neuropathic pain received adjuvant drugs, whereas six patients with non-neuropathic pain received adjuvant drugs. Regarding opioid side effects only constipation and nausea were treated in the majority of the patients. Average pain intensity in the last 24 h for the total number of patients (n=59) < or =5 cm was 88.1% (confidence interval 77.1-95.1). CONCLUSION: Cancer pain was prevalent in opioid-treated patients in hospital settings: however, focussing on average pain intensity, the outcome seems favourable compared with other countries. Pain mechanisms were seldom examined and adjuvant drugs were not specifically used for neuropathic pain. Opioid dosing intervals and supplemental opioid doses were most often adequate. However, opioid side effects were highly prevalent and most side effects were left untreated.

[Novel potential uses of thalidomide in the management of pain? A review of the literature]. / Neue Indikation für Thalidomid in der Schmerztherapie. Eine Literaturübersicht.

Thalidomide was introduced as a sedative and antiemetic agent to the European market in the late 1950s. However, it soon became clear that a hitherto unheard-of incidence of severe birth defects was due to the maternal use of thalidomide and the drug was withdrawn from the market. Despite its teratogenesis, thalidomide is currently being rediscovered because of its known spectrum of anticachectic, antiemetic, mildly hypnotic, anxiolytic, anti-inflammatory, antiangiogenic, and analgesic properties. The mechanism of action of thalidomide is probably based on its immunomodulatory effect, namely the suppression of production of tumor necrosis factor alpha and the modulation of interleukins. A striking but not well-known finding is the effectiveness of thalidomide as an analgesic or analgesic adjuvant. During the early era of thalidomide use, the drug was shown to enhance the analgesic efficacy of a combined treatment with acetylsalicylic acid, phenacetin, and caffeine (APC) by testing "normal volunteers, using electrical stimulation of teeth." The combination of thalidomide and APC was superior to other combinations (APC alone, APC and codeine) with respect to both the total analgesic effect and the duration of this analgesic effect. In 1965 thalidomide was found to be effective in treating the painful subcutaneous manifestations of the leprosy-associated erythema nodosum leprosum, a condition for which it eventually was approved by the United States Food and Drug Administration in 1998. In an animal model of neuropathic pain (chronic constriction injury), thalidomide was shown to reduce both mechanical allodynia and thermal hyperalgesia. Recent studies documented the analgesic efficacy of thalidomide in treating painful mucocutaneous aphthous ulcers associated with HIV syndrome and Behcet's disease.However, to date there are no recent clinical trials that are specifically designed to explore the analgesic potential of thalidomide. In view of the current basic research and clinical findings,we suggest to investigate the potential benefits of thalidomide in severe pain conditions that respond poorly to common pain management approaches such as neuropathic pain, postherpetic neuralgia, or central pain phenomena. Because its mechanism of action is distinct from that of other drugs such as steroids, thalidomide offers the possibility of a combined treatment with other agents with nonoverlapping toxicities. We conclude that thalidomide, when used properly,may enrich the therapeutic regimen in the management of some pain-related conditions.

Potential novel uses of thalidomide: focus on palliative care.

Thalidomide, after being banned from the market in the early 1960s because of the worldwide teratogenesis disaster, is currently being rediscovered because of its multiple therapeutic effects in various serious diseases and symptoms. Original studies examined the anxiolytic, mild hypnotic, anti-emetic and adjuvant analgesic properties of this drug. Subsequently, thalidomide was found to be highly effective in managing the cutaneous manifestations of leprosy (erythema nodosum leprosum) and even to be superior to aspirin (acetylsalicylic acid) in controlling leprosy-associated fever. Recent research shows promising results with thalidomide in patients with progressive bodyweight loss related to advanced cancer and HIV infection. Thalidomide therapy of diseases such as tuberculosis, sarcoidosis, aphthous ulcers in HIV syndrome and Behcet's disease, rheumatoid arthritis, multiple myeloma, graft-versus-host disease, pyoderma gangrenosum, inflammatory bowel disease, Sjögren's syndrome, lupus erythematosus and a variety of solid tumours is currently being explored. Furthermore, in preliminary studies, thalidomide has been found to be effective in several syndromes related to advanced cancer, such as the cancer cachexia syndrome, chronic nausea, insomnia, profuse sweating and pain. Whether thalidomide has a therapeutic effect on neoplastic fever has yet to be elucidated. These intriguing features make the use of the drug potentially attractive for palliative care. In addition, by a distinct mechanism of action compared with most other drugs, thalidomide offers the possibility of combined treatment with other agents with non-overlapping toxicities. The mechanism of action of thalidomide is probably based on the suppression of tumour necrosis factor-alpha and the modulation of interleukins. However, it is not possible to identify a single dominant mechanism, since the action of cytokines and the effect of thalidomide appear to be complex. This review article discusses the original uses and teratogenic effects of thalidomide within its historical context and, linking recent research at the molecular level with clinical findings, aims to provide the reader with insight into the current understanding of its biological actions, toxicities and potential benefits.