Effective treatment of neuropathic pain without unacceptable side effects is challenging. Cancer sufferers increasingly live with long-term treatment-related neuropathic pain, resulting from chemotherapy-induced peripheral neuropathy (CIPN) or surgical scars. This proof-of-concept study aimed to determine whether preclinical evidence for TRPM8 ion channels in sensory neurons as a novel analgesic target could be translated to clinical benefit in patients with neuropathic pain, using the TRPM8 activator menthol.

Background Although it is increasingly recognized that cancer patients often have sleep problems, we lack data on their prevalence and associations in representative clinical populations. We aimed to determine (i) the prevalence of sleep problems amongst outpatients of a cancer centre and (ii) the association with medical variables, emotional distress and pain. Methods Secondary analysis of self-report and medical data on 2862 cancer centre outpatients. Sleep problems were identified using the sleep item from the Patient Health Questionnaire-9: Over the last two weeks, how often have you been bothered by trouble falling or staying asleep or sleeping too much? scored on a four-point frequency scale. Emotional distress was measured using the Hospital Anxiety and Depression Scale and pain using the subscale of the European Organisation for Research and Treatment of Cancer Quality of Life Core 30 questionnaire. Medical data were obtained from the cancer centre clinical database. Results Sleep problems (bothered more than half the days during the previous 2?weeks) were reported by 30.2% (865/2862, 95% CI?=?28.5 to 31.9) of the patients. They were common in both patients with active cancer (34.5%) and in cancer survivors (28.0%). There was only a modest association with cancer site and treatment status, but there was a strong association with pain (odds ratio?=?2.7, 95% CI?=?2.2 to 3.4) and emotional distress (odds ratio?=?4.5, 95% CI?=?3.7 to 5.6). Conclusions Sleep problems are common in cancer outpatients and are strongly associated with pain and emotional distress. A combined approach to the management of sleep, pain and emotional distress is indicated. Copyright (c) 2011 John Wiley & Sons, Ltd.

BACKGROUND:Little is known about the prevalence and associations of clinically relevant fatigue (CRF) in recurrence-free prostate cancer survivors.PATIENTS AND METHODS:Four hundred and sixteen recurrence-free prostate cancer survivors who were >1 year post-radiotherapy or radical prostatectomy were surveyed. The prevalence of CRF (defined as Brief Fatigue Inventory >3) was determined and compared with a noncancer control group. Other measures included the Hospital Anxiety and Depression Scale, International Prostate Symptom Score, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Relationships between these factors and CRF were explored in univariate and multivariate analyses.RESULTS:Analyzable data were obtained from 91% (377/416) of patients. The prevalence of CRF was 29% (108/377) versus 16% (10/63) in the controls (P=0.031). CRF was more common in post-radiotherapy than in post-prostatectomy 33% (79/240) versus 22% (29/133), P=0.024. However, when other factors (current depression, anxiety, urinary symptoms, medical comorbidities, pain and insomnia) were controlled for, previous treatment did not predict CRF. Current depression [Hospital Anxiety and Depression Scale≥8 was by far the strongest association [odds ratio 9.9, 95% confidence interval 4.2-23.5)].CONCLUSIONS:Almost one-third of recurrence-free prostate cancer survivors report CRF. Depression, anxiety, urinary symptoms, pain and insomnia measured at outcome are more strongly associated than type of cancer treatment previously received.

BACKGROUND The purpose of the study was to determine the prevalence and associations of clinically relevant fatigue (CRF) in men with biochemically controlled prostate cancer on long-term androgen deprivation therapy (ADT). PATIENTS AND METHODS One hundred and ninety-eight men were surveyed and the prevalence of CRF (Brief Fatigue Inventory score >3) determined. Associations with other measures (Hospital Anxiety and Depression Scale; International Prostate Symptom Score; European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; Brief Pain Inventory worst pain; clinical and demographic information) were explored in univariate and multivariate analyses. RESULTS Eight-one per cent (160 of 198) of questionnaires were analysable. CRF prevalence was 43% (68 of 160). CRF associations included moderate/severe urinary symptoms, anxiety and medical co-morbidities; the strongest associations were depression [odds ratio (OR) 9.8, 95% confidence interval (CI) 4.3-22.8] and pain (OR 9.2, 95% CI 4.0-21.5). After controlling for other factors, the independent associations were depression (OR 4.7, 95% CI 1.6-14.0) and pain (OR 3.1, 95% CI 1.0-8.9). There was no association with age, disease burden or treatment duration. CONCLUSIONS Two-fifths of men with biochemically controlled prostate cancer on long-term ADT report CRF that interferes with function. Management aimed at improving CRF should address depression and pain.

Abstract Introduction/aims Oxaliplatin chemotherapy-induced peripheral neuropathy (OxCIPN) is a common post-treatment toxicity. Many patients are left with long-term pain and disability. Available systemic agents have limited efficacy, cause significant side-effects and take several weeks/months to work. Colleagues' preclinical work showed analgesic effects of topical transient receptor potential melastatin receptor activators in neuropathic pain. We therefore conducted a proof-of-concept study using menthol in patients with OxCIPN. Methods 21 patients a median of 19 months post-treatment (range 3–35) applied 1% topical menthol, twice daily to affected areas and skin overlying corresponding dorsal root ganglia. At baseline, 2 and 6 weeks, patients completed: Brief Pain Inventory (BPI), Hospital Anxiety and Depression Scale and underwent objective assessments of gait (electronic walkway), hand dexterity (peg-board) and Quantitative Sensory Testing. Analysis: Wilcoxon signed-rank test and Pearson product-moment correlation. Results Between baseline and 6 weeks, total BPI scores decreased (median 3.6 (range 1.1–7.9) versus 0.7 (0–8.3), p=0.002). 83% described less pain and 52% had ≤30% BPI decrease (deemed clinically significant). There were corresponding improvements in mood (r=0.442, p=0.045), walking velocity (r=-0.797, p=0.026) and cadence (r=-0.823, p=0.012) and trends for improved hand dexterity (r=0.487, p=0.065) and mechanical pain thresholds (r=0.447, p=0.072). Four patients discontinued treatment after 2 weeks: two had difficulty applying the cream, two described worse pain. BPI changes were predicted by pre-treatment mechanical detection thresholds (r=0.534, p=0.027). Conclusion Topical menthol appeared to improve OxCIPN pain and physical function. It also seems to be well tolerated, have minimal side-effects, works relatively quickly and warrants further study.

BACKGROUND:There is speculation that peripheral neuropathy (PN) with capecitabine and oxaliplatin (CapOx; 130 mg/m(2), day 1, every 21 days) may be more common than with FOLFOX4 (5-fluorouracil and oxaliplatin 85 mg/m(2), day 1, every 14 days). We aimed to determine PN incidence and associations during CapOx, and 6 and 12 months after CapOx.PATIENTS AND METHODS:Retrospective audit of 188 oxaliplatin-naive colorectal cancer patients (87 adjuvant, 101 palliative) who received at least one cycle of CapOx. Neurosensory Common Toxicity Criteria Adverse Events version 3 were applied.RESULTS:Overall, 94% experienced acute PN. Worst severities for adjuvant and palliative patients, respectively, were grade 1, 44% and 54%; grade 2, 35% and 32%; grade 3, 16% and 3%; grade 4, 0% and 1% and grade unclear 1% and 1%. Two patients developed PN after CapOx completion despite no symptoms during treatment. Chronic PN at 6 months affected 57% and 18% of adjuvant and palliative patients, respectively. At 12 months, 35% and 16% were affected. Chronic PN at 12 months was associated with cumulative oxaliplatin dose but not age, gender, acute myotonia, pseudolaryngospasm or grade 2 or more PN during treatment.CONCLUSION:Incidence of acute PN during CapOx appears similar to FOLFOX4 but chronic PN in adjuvant patients may be more common with CapOx.

BACKGROUNDFatigue is associated with cancer and its treatment but we know little about how many and which patients suffer fatigue of clinical severity. We aimed to determine the prevalence of clinically relevant fatigue (CRF) and its associations in outpatients with various cancer diagnoses.PATIENTS AND METHODSA survey of outpatients with colorectal, breast, gynaecological, genitourinary, sarcoma, melanoma and miscellaneous tumours at a regional cancer centre. Patients completed the European Organisation for Research and Treatment of Cancer (EORTC) fatigue subscale and the Hospital Anxiety and Depression Scale (HADS). These self-report data were linked to demographic and clinical variables. Data were available on 2867 outpatients.RESULTSThe prevalence of CRF (EORTC fatigue subscale > or =40) was 32% (95% confidence interval 31-34%). The variables independently associated with CRF were primary cancer site, having disease present, type of cancer treatment and emotional distress (total HADS score > or =15). Emotional distress had the strongest association with fatigue but half the cases of CRF were not distressed.CONCLUSIONCRF is common in cancer outpatients and is associated with type of disease and treatment, as well as with emotional distress. The association between CRF and emotional distress is strong but they are not equivalent conditions.

A technique is described for designing active low-pass linear-phase filters for pulse transmission, using Linvill's method of synthesis. The resulting networks are relatively immune to the effects of component variations and compare favourably with their passive counterparts. A desired amplitude/phase response may be obtained by cascading basic sections, each of which employs a single negative-imp...

The paper presents an introduction to existing methods of network synthesis which use active components. A detailed development of Linvill's method, using a negative-impedance convertor, is given. The advantages of using restricted solutions of the approximation problem are discussed, and are illustrated by practical examples. Emphasis is placed on minimising the sensitivity of the response of the...