Pharmacological interventions for pruritus in adult palliative care patients.

BACKGROUND: Pruritus is not the most prevalent but one of the most puzzling symptoms in palliative care patients. It can cause considerable discomfort and has a major impact on patients' quality of life. In the field of palliative care, pruritus is a symptom occurring in patients with disparate underlying diseases and based on different pathologic mechanisms but ending in the same phenomenon. The pathogenesis of pruritus is complex and not fully elucidated. Thus, it is still very difficult to treat pruritus effectively. Evidence-based treatment approaches are needed. OBJECTIVES: The objective was to evaluate the efficacy of different pharmacological treatments for preventing or treating pruritus in adult palliative care patients. SEARCH METHODS: A systematic literature search up to January 2012 was performed and it was updated in August 2012. The following databases were searched: The Cochrane Library (CENTRAL, DARE, CDSR) (2012, issue 8 of 12); MEDLINE (1950 to August 2012); EMBASE (1980 to August 2012) and three other databases. In addition, we searched trials registries and checked the reference lists of all relevant studies, key textbooks, reviews, and websites, and contacted investigators and specialists in pruritus and palliative care regarding unpublished data. SELECTION CRITERIA: We included randomised controlled trials assessing the effects of different pharmacological treatments on preventing or treating pruritus in palliative care patients. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed identified titles and abstracts. Three independent review authors performed assessment of all potentially relevant studies, data extraction, assessment of risk of bias and methodological quality. Results were summarised descriptively according to the different pharmacological interventions and the type of underlying pruritus. Where possible, results were presented in meta-analyses. MAIN RESULTS: In total, 38 reports comprising 40 studies and 1286 participants were included in the review. Altogether, 30 different treatments for pruritus in four different patient groups were included.The findings of this review indicated that the treatment of pruritus for palliative care patients is challenging and requires an individualistic approach. Results showed that effective therapeutic choices have to be guided by the pathophysiology of the pruritus. Various forms of pruritus occur, especially in the field of palliative care, and sometimes the origin of the pruritus is difficult to determine. Therefore, identifying the underlying cause of pruritus is of prime importance in order to develop tailored treatment plans, even if in palliative care the treatment is focused towards the symptom and not necessarily the underlying disease.Results show that in palliative care patients with pruritus of different natures, treatment with the drug paroxetine, a selective serotonin reuptake inhibitor, may be beneficial. For patients suffering from pruritus associated with HIV infection, indomethacin was described as the most effective drug, although the evidence was weak. For patients suffering from chronic kidney disease-associated pruritus, gabapentin may be an option. An alternative treatment for this patient group seems to be the κ-opioid receptor agonist nalfurafine, which has shown significant amelioration of pruritus and acceptable adverse effects. As they have exhibited a low incidence of adverse effects, rifampicin and flumecinol may be recommended for patients with cholestatic pruritus. The opioid antagonist naltrexone has been shown to offer a therapeutic alternative for patients suffering from uraemic or cholestatic pruritus. However, these drugs are often inappropriate in the palliative population because of the risk of reducing analgesia when giving high doses of naltrexone. AUTHORS' CONCLUSIONS: The findings of this review indicate that the number of systemic and topical drugs used for the different subforms of pruritus is increasing. Different interventions have been shown to be effective in the treatment of pruritus of different origins. Nevertheless, an optimal therapy for pruritus is constrained due to the limited understanding of crucial itch mediators and receptors in the various subforms of itch. Ideal antipruritic therapies are still lacking, especially for palliative care patients.This systematic review also indicates that there is insufficient evidence to give any concrete recommendations regarding treatment of pruritus in palliative care patients. Due to the very small sample sizes and poor methodological quality of the majority of studies that were included, the results of this review need to be interpreted with caution. Furthermore, the generalizability is questionable. Additional studies, and particularly carefully designed treatment trials, are needed to provide valid evidence for adequate treatment of pruritus in palliative care patients.

Peripherally acting opioid antagonists in the treatment of opiate-related constipation: a systematic review.

Many patients treated with opioids suffer from constipation. Opiate- or opioid-related constipation is not only a frequent but also a distressing symptom and difficult to treat. There is emerging evidence regarding a novel approach to the management of opiate-related constipation. The aim of this paper is to collect, critically appraise, and summarize the evidence on the effectiveness of recently developed peripherally acting micro-receptor antagonists in the treatment of opiate-related constipation. A comprehensive search of 11 computerized databases was conducted and efforts were made to identify unpublished and ongoing research. Twenty studies were identified; 13 were randomized controlled trials (RCTs) and 7 were Phase II studies assessing toxicity. Studies were mainly executed in healthy volunteers or members of methadone programs with opioid-induced constipation as a model to mimic the condition of patients on opioids. Two RCTs were conducted in hospice patients. Quality of study design and validity of the findings was assessed in all studies. Data show proof of concept but do not allow a definitive answer concerning the effectiveness of the peripherally acting micro-opioid antagonists methylnaltrexone and alvimopan in managing opiate-related constipation. Further research is needed. If future Phase III trials provide supportive data, opioid antagonists may become a standard therapeutic option for the treatment of opiate-related constipation in patients with advanced cancer.

The demise of the randomised controlled trial: bibliometric study of the German-language health care literature, 1948 to 2004.

BACKGROUND: In order to reduce systematic errors (such as language bias) and increase the precision of the summary treatment effect estimate, a comprehensive identification of randomised controlled trials (RCT), irrespective of publication language, is crucial in systematic reviews and meta-analyses. We identified trials in the German general health care literature. METHODS: Eight German language general health care journals were searched for randomised controlled trials and analysed with respect to the number of published RCTs each year and the size of trials. RESULTS: A total of 1618 trials were identified with a median total number of 43 patients per trial. Between 1970 and 2004 a small but constant rise in sample size from a median number of 30 to 60 patients per trial can be observed. The number of published trials was very low between 1948 and 1970, but increased between 1970 and 1986 to a maximum of 11.2 RCTs per journal and year. In the following time period a striking decline of the number of RCTs was observed. Between 1999 and 2001 only 0.8 RCTs per journal and year were published, in the next three years, the number of published trials increased to 1.7 RCTs per journal and year. CONCLUSION: German language general health care journals no longer have a role in the dissemination of trial results. The slight rise in the number of published RCTs in the last three years can be explained by a change of publication language from German to English of three of the analysed journals.

Malignant ascites: systematic review and guideline for treatment.

A guideline on the management of symptomatic malignant ascites by abdominal paracentesis, diuretics and peritoneovenous shunting, based on a systematic review of the literature is presented. Thirty-two relevant studies were identified. None were randomized control trials, one was a non-randomized open controlled trial, five were cohort studies or prospective uncontrolled trials, 26 studies were non-analytic studies like case series. Although paracentesis, diuretics and shunting are commonly used procedures, the evidence is weak. Available data show good, although temporary effect of paracentesis on symptom relief. Fluid withdrawal speed and concurrent intravenous hydration is not sufficiently studied. Peritoneovenous shunts can control ascites in patients with malignant ascites, but have to be balanced by the potential risks of this procedure. The available data about diuretics in treatment of malignant ascites are controversial. The use of diuretics therefore should be considered in all patients, but has to be evaluated individually.

The contribution of handsearching European general health care journals to the Cochrane Controlled Trials Register.

A fundamental aim of any systematic review is that all relevant studies should be identified and considered for inclusion. Limitations with searching bibliographic databases led the Cochrane Collaboration to search journals by hand for reports of trials. This article presents the results of a 3-year project to identify and make accessible reports of randomized trials published in European general health care journals. Overall, 21,620 reports of controlled trials were identified from 119 journals from 16 countries. More than three quarters (76%) were published in U.K. or German journals. Only 3,640 (17%) reports were indexed in MEDLINE as controlled trials, and 6,554 (30%) were not indexed in MEDLINE at all. Bibliographic details for all reports are available by searching The Cochrane Controlled Trials Register in The Cochrane Library. This project has ensured that a large proportion of trial reports not previously identifiable has been made accessible to those preparing systematic reviews.