Emerging treatments in neurogastroenterology: a multidisciplinary working group consensus statement on opioid-induced constipation.

BACKGROUND: Opioids are effective for acute and chronic pain conditions, but their use is associated with often difficult-to-manage constipation and other gastrointestinal (GI) effects due to effects on peripheral µ-opioid receptors in the gut. The mechanism of opioid-induced constipation (OIC) differs from that of functional constipation (FC), and OIC may not respond as well to most first-line treatments for FC. The impact of OIC on quality of life (QoL) induces some patients to decrease or stop their opioid therapy to relieve or avoid constipation. PURPOSE: At a roundtable meeting on OIC, a working group developed a consensus definition for OIC diagnosis across disciplines and reviewed current OIC treatments and the potential of treatments in development. By consensus, OIC is defined as follows: 'A change when initiating opioid therapy from baseline bowel habits that is characterized by any of the following: reduced bowel movement frequency, development or worsening of straining to pass bowel movements, a sense of incomplete rectal evacuation, or harder stool consistency'. The working group noted the prior validation of a patient response outcome and end point for clinical trials and recommended future efforts to create treatment guidelines and QoL measures specific for OIC. Details from the working group's discussion and consensus recommendations for patient care and research are presented in this article.

A retrospective study to determine whether accessing frequency affects the incidence of microbial colonisation in peripheral arterial catheters.

Peripheral arterial catheters are used for the continuous monitoring of blood pressure and repeated blood sampling in critically ill patients, but can be a source of catheter-related bloodstream infection. A common assumption is that the more frequently an arterial catheter is accessed, the greater the likelihood of contamination and colonisation to occur We sought to determine whether the accessing frequency has an influence on the rate of colonisation in a peripheral arterial catheter A retrospective, unmatched, nested case control study was conducted in our intensive care unit. The intensive care unit charts of 96 arterial catheters from 83 patients were examined to measure the number of times each respective arterial catheter was accessed. Multivariate Cox proportional hazards regression was used to compare the rate of accessing of arterial catheters and account for varying arterial catheter in situ duration. Arterial catheters which had a high access rate of 8.1 or more times/day (five colonised of 32 patients: hazards ratio 1.69, 95% confidence interval 0.52 to 5.49; P = 0.77), or a medium access rate of 6.7 to 8.0 times/day (six colonised of 32 patients: hazards ratio, 1.35, 95% confidence interval, 0.37 to 4.92: P = 0.65) were not significantly more colonised when compared to arterial catheters which had a low access rate of O to 6.6 times/day (six colonised of 32 patients), adjusted for arterial catheter insertion site and place in hospital where the arterial catheter insertion was performed. We were unable to demonstrate that the accessing frequency of an arterial catheter was a major predisposing factor for the likelihood of colonisation. Other mechanisms other than hub colonisation should be investigated further.

A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: prevalence, severity and impact on quality of life.

PURPOSE: This systematic review aimed to assess the literature for prevalence, severity, and impact on quality of life of salivary gland hypofunction and xerostomia induced by cancer therapies. METHODS: The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. Two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results and conclusions for each article. RESULTS: The inclusion criteria were met by 184 articles covering salivary gland hypofunction and xerostomia induced by conventional, 3D conformal radiotherapy or intensity-modulated radiotherapy in head and neck cancer patients, cancer chemotherapy, total body irradiation/hematopoietic stem cell transplantation, radioactive iodine treatment, and immunotherapy. CONCLUSIONS: Salivary gland hypofunction and xerostomia are induced by radiotherapy in the head and neck region depending on the cumulative radiation dose to the gland tissue. Treatment focus should be on optimized/new approaches to further reduce the dose to the parotids, and particularly submandibular and minor salivary glands, as these glands are major contributors to moistening of oral tissues. Other cancer treatments also induce salivary gland hypofunction, although to a lesser severity, and in the case of chemotherapy and immunotherapy, the adverse effect is temporary. Fields of sparse literature included pediatric cancer populations, cancer chemotherapy, radioactive iodine treatment, total body irradiation/hematopoietic stem cell transplantation, and immunotherapy.

A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact.

PURPOSE: This systematic review aimed to assess the literature for management strategies and economic impact of salivary gland hypofunction and xerostomia induced by cancer therapies and to determine the quality of evidence-based management recommendations. METHODS: The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. For each article, two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results, and conclusions. RESULTS: Seventy-two interventional studies met the inclusion criteria. In addition, 49 intensity-modulated radiation therapy (IMRT) studies were included as a management strategy aiming for less salivary gland damage. Management guideline recommendations were drawn up for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. CONCLUSIONS: There is evidence that salivary gland hypofunction and xerostomia induced by cancer therapies can be prevented or symptoms be minimized to some degree, depending on the type of cancer treatment. Management guideline recommendations are provided for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Fields of sparse literature identified included effects of gustatory and masticatory stimulation, specific oral mucosal lubricant formulas, submandibular gland transfer, acupuncture, hyperbaric oxygen treatment, management strategies in pediatric cancer populations, and the economic consequences of salivary gland hypofunction and xerostomia.

Parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy.

BACKGROUND: Salivary gland dysfunction is a predictable side effect of radiotherapy to the head and neck region. Pilocarpine hydrochloride (a choline ester) is licensed in many countries for the treatment of radiation-induced salivary gland dysfunction. Other parasympathomimetics have also been used 'off licence' in the treatment of this condition. OBJECTIVES: To determine the efficacy and tolerability of parasympathomimetic drugs in the treatment of radiation-induced salivary gland dysfunction. SEARCH STRATEGY: A detailed search strategy was developed for MEDLINE, and adapted for other databases (Cochrane Pain, Palliative and Supportive Care Group Register; Cochrane Oral Health Group Register; The Cochrane Controlled Trials Register; EMBASE; CINAHL; SIGLE; Dissertation Abstracts). The reference lists of identified studies, review articles and radiotherapy textbooks were checked for additional studies. Relevant pharmaceutical companies, clinical investigators, and professional organizations/journals were also contacted about additional studies. SELECTION CRITERIA: The selection criteria for the review were: 1) randomised controlled trials; 2) patients suffering from radiation-induced salivary gland dysfunction; 3) patients treated with parasympathomimetic drugs; and 4) assessable data available on primary outcome measures. DATA COLLECTION AND ANALYSIS: The two review authors independently collected data from the full text version of relevant papers including: 1) citation details; 2) patients; 3) interventions; 4) assessments; 5) outcomes (i.e. efficacy, tolerability); and 6) quality issues. We were unable to perform a meta-analysis, due to a lack of appropriate data. MAIN RESULTS: Only three studies, involving a total of 298 patients, fulfilled the entry criteria for the review. All three studies involved the use of pilocarpine hydrochloride. The data suggest that pilocarpine hydrochloride was more effective than placebo, and at least as effective as artificial saliva in those participants that responded. The response rate was 42 to 51%. The time to response was up to 12 weeks. The side effect rate was high, and side effects were the main reason for withdrawal (six to 15% patients taking 5 mg tds). The side effects were usually the result of generalised parasympathomimetic stimulation (e.g. sweating, headaches, urinary frequency, vasodilatation). Response rates were not dose dependent, but side effect rates were dose dependent. AUTHORS' CONCLUSIONS: There is limited evidence to support the use of pilocarpine hydrochloride in the treatment of radiation-induced salivary gland dysfunction. Currently, there is little evidence to support the use of other parasympathomimetic drugs in the treatment of this condition. Available studies suggest approximately half of patients will respond, but side effects to responders can be problematic. Adverse effects are dose dependent therefore it is important to keep dose to 5 mg tds.

A systematic review of the use of opioids in the management of dyspnoea.

BACKGROUND: Opioids are commonly used to treat dyspnoea in palliative medicine but there has been no formal evaluation of the evidence for their effectiveness in the treatment of dyspnoea. A systematic review was therefore carried out to examine this. METHODS: The criteria for inclusion required that studies were double blind, randomised, placebo controlled trials of opioids for the treatment of dyspnoea secondary to any cause. The methods used to identify suitable studies included electronic searching of the literature, hand searching of the literature, and personal contact with relevant individuals and organisations. Random effects meta-analyses were performed on all included studies and on various subgroups (studies involving nebulised opioids or patients with chronic obstructive pulmonary disease (COPD)). Subgroups were compared using meta-regression. Some studies included in the systematic review could not be included in the meta-analysis because insufficient data were presented. RESULTS: Eighteen studies fulfilled the criteria for the review. The meta-analysis showed a statistically significant positive effect of opioids on the sensation of breathlessness (p=0.0008). Meta-regression indicated a greater effect for studies using oral or parenteral opioids than for studies using nebulised opioids (p=0.02). The subgroup analysis failed to show a positive effect of nebulised opioids on the sensation of breathlessness. The results of the subgroup analysis of the COPD studies were essentially similar to the results of the main analysis. CONCLUSION: This review supports the continued use of oral and parenteral opioids to treat dyspnoea in patients with advanced disease. There are insufficient data from the meta-analysis to conclude whether nebulised opioids are effective, but the results from included studies that did not contribute to the meta-analysis suggest that they are no better than nebulised normal saline.

Oral yeast carriage in patients with advanced cancer.

The aim of this study was to investigate oral yeast carriage amongst patients with advanced cancer. Oral rinse samples were obtained from 120 subjects. Yeasts were isolated using Sabouraud's dextrose agar and CHROMagar Candida, and were identified using a combination of the API 20 C AUX yeast identification system, species-specific PCR and 26S rDNA gene sequencing. Oral yeast carriage was present in 66% of subjects. The frequency of isolation of individual species was: Candida albicans, 46%; Candida glabrata, 18%; Candida dubliniensis, 5%; others, < 5%. The increasing isolation of non-Candida albicans species is clinically important, since these species are often more resistant to antifungal drugs. Oral yeast carriage was associated with denture wearing (P = 0.006), and low stimulated whole salivary flow rate (P = 0.009). Identification of these risk factors offers new strategies for the prevention of oral candidosis in this group of patients.

Opioids for the palliation of breathlessness in terminal illness.

BACKGROUND: Breathlessness is a common symptom in people with advanced disease. The most effective treatments are aimed at treating the underlying cause of the breathlessness but this may not be possible and symptomatic treatment is often necessary. Strategies for the symptomatic treatment of breathlessness have never been systematically evaluated. Opioids are commonly used to treat breathlessness: the mechanisms underlying their effectiveness are not completely clear and there have been few good-sized trials in this area. OBJECTIVES: To determine the effectiveness of opioid drugs given by any route in relieving the symptom of breathlessness in patients who are being treated palliatively. SEARCH STRATEGY: An electronic search was carried out of Medline, Embase, Cinahl, the Cochrane library, Dissertation Abstracts, Cancercd and SIGLE. Review articles and reference lists of retrieved articles were hand searched. Date of most recent search: May 1999 SELECTION CRITERIA: Randomised double-blind, controlled trials comparing the use of any opioid drug against placebo for the relief of breathlessness were included. Patients with any illness suffering from breathlessness were included and the intervention was any opioid, given by any route, in any dose. DATA COLLECTION AND ANALYSIS: Studies identified by the search were imported into a reference manager database. The full texts of the relevant studies were retrieved and data were independently extracted by two reviewers. Studies were quality scored according to the Jadad scale. The primary outcome measure used was breathlessness and the secondary outcome measure was exercise tolerance. Studies were divided into non-nebulised and nebulised and were analysed both separately and together. A qualitative analysis was carried out of adverse effects of opioids. Where appropriate, meta-analysis was carried out. MAIN RESULTS: Eighteen studies were identified of which nine involved the non-nebulised route of administration and nine the nebulised route. A small but statistically significant positive effect of opioids was seen on breathlessness in the analysis of studies using non-nebulised opioids. There was no statistically significant positive effect seen for exercise tolerance in either group of studies or for breathlessness in the studies using nebulised opioids. REVIEWER'S CONCLUSIONS: There is evidence to support the use of oral or parenteral opioids to palliate breathlessness although numbers of patients involved in the studies were small. No evidence was found to support the use of nebulised opioids. Further research with larger numbers of patients, using standardised protocols and with quality of life measures is needed.

Xerostomia in patients with advanced cancer.

The aim of the study was to investigate the features of xerostomia in patients with advanced cancer. The protocol involved completion of the Memorial Symptom Assessment Scale, and measurement of the unstimulated whole salivary flow rate (UWSFR) and the stimulated whole salivary flow rate (SWSFR). One hundred twenty patients participated in the study. Xerostomia was the fourth most common symptom (78% of patients). It was associated with a poor performance status (P = 0.01). The usual cause of xerostomia was drug treatment. There was an association with the total number of drugs prescribed (P = 0.009): the median number of xerostomic drugs prescribed was 4. Xerostomia was ranked the third most distressing symptom. Its severity was correlated with the severity of oral discomfort, dysgeusia, dysmasesia, dysphagia, dysphonia, and anorexia. The UWSFR was a relatively sensitive, but nonspecific, investigation. In contrast, the SWSFR was a relatively specific, but insensitive, investigation.

On-line flash thermodesorption-GC-MS determination of PCB in sewage sludge.

A flash thermodesorption-gas chromatography-mass spectrometry technique has been developed for the determination of polychlorobiphenyls (PCB), especially the highly toxic planar species, in sewage sludge. A modified Curie-point pyrolyzer was used; in this the flash-desorption temperature was controlled by selecting specific metal alloys for the pyrolysis wire. Samples (3 mg) were loaded into a quartz tube with the special heating wire wound around the outer wall. By this means rapid thermal desorption (TDS) was achieved whereas uncontrolled catalytic breakdown of the analytes was avoided. The thermodesorption unit was connected via a custom-built interface to the GC-MS detection system. The average limit of detection was 15 microgram kg(-1) sludge more than one order of magnitude better than the legal requirement.

A comparison of artificial saliva and chewing gum in the management of xerostomia in patients with advanced cancer.

This was a prospective, randomized, open, crossover study comparing a mucin-based artificial saliva (Saliva Orthana) with a low-tack, sugar-free chewing gum (Freedent) in the management of xerostomia in patients with advanced cancer. The conclusions of this study were that both Saliva Orthana and Freedent are effective in the management of xerostomia in patients with advanced cancer, that both Saliva Orthana and Freedent cause some side-effects in this group of patients, and that patients with cancer think that chewing gum is an acceptable treatment. Sixty-nine per cent of the patients preferred the chewing gum to the artificial saliva. Furthermore, the chewing gum scored better than the artificial saliva on every measure of efficacy. However, none of these results reached statistical significance.

A comparison of artificial saliva and pilocarpine in the management of xerostomia in patients with advanced cancer.

This was a crossover study comparing a mucin-based artificial saliva (Saliva Orthana) and pilocarpine hydrochloride (Salagen) in the management of xerostomia in patients with advanced cancer. The pilocarpine was found to be more effective than the artificial saliva in terms of mean change in visual analogue scale scores for xerostomia (P = 0.003). Furthermore, more patients reported that it had helped their xerostomia, and more patients wanted to continue with it after the study. However, the pilocarpine was found to be associated with more side-effects than the artificial saliva (P < 0.001). These side-effects were usually reported as being mild. Of the patients who used both treatments, 50% preferred the artificial saliva, and 50% preferred the pilocarpine. The commonest reason for preferring the artificial saliva was the fact that it was a spray, rather than a tablet.

The management of xerostomia: a review.

Xerostomia causes a great deal of morbidity in patients with advanced cancer. However, it is an area which has received little attention. Indeed current management of xerostomia in palliative care units is based largely on anecdotal evidence. There are a number of studies in progress specifically looking at patients with advanced cancer, but until these are published we should take note of studies done in other patient groups. This article reviews the medical literature on the symptomatic management of xerostomia as a whole, with particular reference to treatments that are currently available in the United Kingdom.