Integration of oncology and palliative care: setting a benchmark.

BACKGROUND: Integration of oncology and palliative care (PC) should be the standard model of care for patients with advanced cancer. An expert panel developed criteria that constitute integration. This study determined whether the PC service within this Health Service, which is considered to be fully "integrated", could be benchmarked against these criteria. METHODS: A survey was undertaken to determine the perceived level of integration of oncology and palliative care by all health care professionals (HCPs) within our cancer centre. An objective determination of integration was obtained from chart reviews of deceased patients. Integration was defined as >70% of all respondents answered "agree" or "strongly agree" to each indicator and >70% of patient charts supported each criteria. RESULTS: Thirty-four HCPs participated in the survey (response rate 69%). Over 90% were aware of the outpatient PC clinic, interdisciplinary and consultation team, PC senior leadership, and the acceptance of concurrent anticancer therapy. None of the other criteria met the 70% agreement mark but many respondents lacked the necessary knowledge to respond. The chart review included 67 patients, 92% of whom were seen by the PC team prior to death. The median time from referral to death was 103 days (range 0-1347). The level of agreement across all criteria was below our predefined definition of integration. CONCLUSION: The integration criteria relating to service delivery are medically focused and do not lend themselves to interdisciplinary review. The objective criteria can be audited and serve both as a benchmark and a basis for improvement activities.

An open-label pilot study of oral vitamin C as an opioid-sparing agent in patients with chronic pain secondary to cancer.

PURPOSE: The purpose of this study is to assess the efficacy of oral Vitamin C as an opioid-sparing agent when used in conjunction with opioids and standard adjuvant therapy in the management of chronic cancer pain. METHODS: An open-label pilot study of patients ≥18 years of age with chronic pain secondary to cancer and/or its treatment and a Brief Pain Inventory average pain score of ≥3/10. In addition to opioid analgesia, patients received 1 g of vitamin C twice daily over 3 days (total daily dose of 2 g). Patients' usual medications, including breakthrough medications, were continued throughout the study period. The primary endpoint was total daily opioid use during vitamin C administration compared with that immediately prior to study. RESULTS: Thirty-four patients were enrolled in the study. Seven failed to complete the trial. Across the 17 evaluable patients, the median daily opioid consumption was 360 mg oral morphine equivalents (OME) on the days prior to vitamin C and 390 mg when administered with vitamin C. CONCLUSION: This study failed to demonstrate any clinically significant benefit from vitamin C in conjunction with opioids in cancer-related pain and does not provide support for embarking on a larger randomised trial to determine efficacy.

The inconstancy of the transient climate response parameter under increasing CO2.

In the Coupled Model Intercomparison Project Phase 5 (CMIP5), the model-mean increase in global mean surface air temperature T under the 1pctCO2 scenario (atmospheric CO(2) increasing at 1% yr(-1)) during the second doubling of CO(2) is 40% larger than the transient climate response (TCR), i.e. the increase in T during the first doubling. We identify four possible contributory effects. First, the surface climate system loses heat less readily into the ocean beneath as the latter warms. The model spread in the thermal coupling between the upper and deep ocean largely explains the model spread in ocean heat uptake efficiency. Second, CO(2) radiative forcing may rise more rapidly than logarithmically with CO(2) concentration. Third, the climate feedback parameter may decline as the CO(2) concentration rises. With CMIP5 data, we cannot distinguish the second and third possibilities. Fourth, the climate feedback parameter declines as time passes or T rises; in 1pctCO2, this effect is less important than the others. We find that T projected for the end of the twenty-first century correlates more highly with T at the time of quadrupled CO(2) in 1pctCO2 than with the TCR, and we suggest that the TCR may be underestimated from observed climate change.

Pharmacological options for the management of refractory cancer pain-what is the evidence?

Refractory cancer pain that does not respond to standard opioid and/or co-analgesic therapy occurs in 10-20 % of patients. Risk factors include young age, neuropathic pain type, incident pain, psychological distress, previous opioid use, high tolerance, a history of addiction and impaired cognition. The management of patients with refractory pain remains a challenge. Treatment options include opioid manipulation (parenteral delivery, rotation, combination, methadone and buprenorphine), non-opioids and co-analgesics (paracetamol, non-steroidal anti-inflammatory agents, antidepressants and anticonvulsants), NMDA receptor antagonists, cannabinoids, lignocaine and corticosteroids. The evidence of benefit for any of these agents is weak, and each additional agent increases the risk of adverse events. Evidence-based guidelines cannot, therefore, be developed at present. New approaches are recommended including targeted opioid therapy, multimodal analgesia, a goal-oriented approach to pain management and increasing use of the multidisciplinary team and support services.

Opioid conversion ratios used in palliative care: is there an Australian consensus?

BACKGROUND: Opioid switching or rotation is reported to be a common practice in palliative care. Published tables of opioid conversion ratios have been found to vary in their recommendations, potentially leading to significant differences in clinical practice. AIMS: To identify common practices in the calculation of opioid equianalgesia by specialist palliative medicine practitioners and trainees. METHOD: An anonymous, cross-sectional, online survey completed by 85 Australian palliative care specialists or advanced trainees. Questions focused on conversion ratios used in switching between oral and parenteral opioid doses; conversion ratios used when switching from other opioids to oral morphine; and practice of commencing methadone. RESULTS: The majority of respondents calculated equianalgesic doses for morphine, oxycodone and hydromorphone using the same conversion ratios. Methadone was used almost equally as either the sole opioid or as a 'co-opioid'. The majority surveyed converted slow-release hydromorphone differently to the manufacturer's recommendations. CONCLUSION: Further discussion among Australian palliative care specialist organisations is recommended in order to produce uniform conversion guidelines to improve consistency and safety in the prescribing of opioids.

Negotiating palliative care in the context of culturally and linguistically diverse patients.

There is an increasing emphasis on meeting the healthcare needs of culturally and linguistically diverse (CALD) communities in Australia. Negotiating the point of futility and the transition to specialist palliative care requires not only effective communication but also sensitivity to cultural and linguistic specificities. This can be a challenging process for clinicians, patients and families. Here, we outline some of the key challenges currently facing many clinicians in the context of CALD patients, with particular reference to the transitioning of patients to specialist palliative care. We suggest a focus on further research that can systematically document and model existing CALD-specific clinical processes and pathways, which can then support the development of targeted educational interventions. This includes developing a multi-stakeholder understanding of the CALD experience that moves beyond cultural stereotyping and predicting need.

Referral to specialist palliative care.

Recent literature has suggested that earlier referral to palliative care can improve quality of life and prognosis. The decision to refer to palliative care is a complex process that can involve an interplay of interpersonal, subjective and institutional factors. Negotiating this referral process can be challenging to a medical specialist from a professional and personal viewpoint. What remains unknown is what actually influences the individual clinician to refer a patient to palliative care.

Prioritising drugs for single patient (n-of-1) trials in palliative care.

Many of the drugs prescribed commonly to palliative care patients have potentially significant side-effects and are of unproven benefit. The acquisition of evidence to support the prescribing of these drugs has been very slow. Single patient trials (SPTs) (also known as n-of-1 trials) offer a potential means of obtaining the evidence necessary to support or refute the use of several of the drugs and interventions whose use is currently based on physician experience or anecdote alone. A list of SPTs considered "most urgent", for commonly employed treatments and for the most common and most troublesome symptoms in palliative care is presented. These are drugs for which the gap between evidence and practice is greatest, where the evidence of efficacy is most lacking, where significant side effects potentially lead to the greatest morbidity, or where cost is a major patient burden. Although not all the drugs used in palliative care are suitable, SPTs provide a potential alternative method of gathering evidence in palliative care.

Intranasal sufentanil for cancer-associated breakthrough pain.

The objective of this study was to demonstrate the efficacy, safety and patient acceptability of the use of intranasal sufentanil for cancer-associated breakthrough pain. This was a prospective, open label, observational study of patients in three inpatient palliative care units in Australia. Patients on opioids with cancer-associated breakthrough pain and clinical evidence of opioid responsiveness to their breakthrough pain were given intranasal (IN) Sufentanil via a GO Medical patient controlled IN analgesia device. The main outcome measures were pain scores, need to revert to previous breakthrough opioid after 30 min, number of patients who chose to continue using IN sufentanil, and adverse effects. There were 64 episodes of use of IN sufentanil for breakthrough pain in 30 patients. There was a significant reduction in pain scores at 15 (P < 0.0001) and 30 min (P < 0.0001). In only 4/64 (6%) episodes of breakthrough pain did the participants choose to revert to their prestudy breakthrough medication. Twenty-three patients (77%) rated IN sufentanil as better than their prestudy breakthrough medication. The incidence of adverse effects was low and most were mild. Our study showed that IN sufentanil can provide relatively rapid onset, intense but relatively short lasting analgesia and in the palliative care setting it is an effective, practical, and safe option for breakthrough pain.

High-resolution optical coherence tomography demonstration of membranes spanning optic disc pits and colobomas.

OBJECTIVES: To demonstrate the features of optic disc pits and colobomas revealed by high-resolution optical coherence tomography (OCT) and their association with the development of maculopathy. METHODS: Subjects with disc pits or colobomas and no other ocular history underwent full ophthalmic examinations including logMAR visual acuity and contrast sensitivity. Fundus photographs and high-resolution OCT images were obtained. RESULTS: Seven patients were identified with optic disc pits or colobomas aged 25 to 63 years. Five patients had a unilateral optic disc pit, one had a unilateral disc coloboma, and another had bilateral disc colobomas. Apart from one eye with a grossly anomalous disc, vision was logMAR 0.4 or better in all eyes. In three of five eyes without maculopathy, a complete membrane could be identified traversing the optic disc cup that was absent or deficient in the three eyes with maculopathy. One patient with optic disc pit and marked schisis-like separation of the retinal layers throughout the macula was asymptomatic with logMAR visual acuity of 0.0 and normal achromatic contrast sensitivity. CONCLUSIONS: In this small series of patients with optic disc pits or colobomas, it was possible to identify a membrane spanning the optic disc cup, and it is speculated that this may protect against the development of maculopathy. Schisis-like separation of retinal layers can be associated with normal visual function.

Medically assisted hydration for palliative care patients.

BACKGROUND: Many palliative care patients have reduced oral intake during their illness. The management of this can include the provision of medically assisted hydration with the aim of prolonging the length of life of a patient, improving their quality of life, or both. OBJECTIVES: To determine the effect of medically assisted hydration in palliative care patients on their quality and length of life. SEARCH STRATEGY: Studies were identified from searching CENTRAL, MEDLINE (1966 to 2008), EMBASE (1980 to 2008), CINAHL, CANCERLIT, Caresearch, Dissertation abstracts, SCIENCE CITATION INDEX and the reference lists of all eligible studies, key textbooks, and previous systematic reviews. The date of the latest search was February 2008. SELECTION CRITERIA: All relevant randomised controlled trials (RCTs) or prospective controlled studies of medically assisted hydration in palliative care patients. DATA COLLECTION AND ANALYSIS: Five relevant studies were identified. These included two RCTs (93 participants), and three prospective controlled trials (360 participants). These were assessed independently by two review authors for quality and validity. The small number of studies and the heterogeneity of the data meant that a quantitative analysis was not possible, so a description of the main findings was included only. MAIN RESULTS: One study found that sedation and myoclonus (involuntary contractions of muscles) were improved more in the intervention group (28 - hydration, 23 - placebo). Another study found that dehydration was significantly higher in the non-hydration group, but that some fluid retention symptoms (pleural effusion, peripheral oedema and ascites) were significantly higher in the hydration group (59 - hydration group, 167 - non -hydration group). The other three studies did not show significant differences in outcomes between the two groups. AUTHORS' CONCLUSIONS: There are insufficient good quality studies to make any recommendations for practice with regard to the use of medically assisted hydration in palliative care patients.

Does use of isotretinoin rule out a career in flying?

AIM: To evaluate whether previous isotretinoin use induces permanent, measurable, and clinically significant abnormalities in night vision such that flying is precluded, and whether potential military and civilian commercial aviators should be screened routinely. METHODS: A retrospective, non-interventional, consecutive case series of 47 individuals with a confirmed history of oral isotretinoin use were compared to 20 age and sex matched controls. RESULTS: 47 individuals (44 males and three females), age range 17-33, underwent Goldmann-Weekers dark adaptation (DA) and standard electroretinogram (ERG) according to ISCEV protocols. 34 patients showed no abnormality in any parameters. Two patients had abnormal DA and ERGs. The mean scotopic ERG b wave amplitude of the isotretinoin group was 496.5 microV (SD 51.3 microV) compared with 501.7 microV (62.3.1 microV) among the controls. The group mean a:b ratio was 0.55 (0.04) compared to 0.69 (0.08) in the controls. CONCLUSION: Previous use of isotretinoin may have caused retinal toxicity in two subjects and laboratory evidence of night blindness in 11 further subjects. One subject had subclinical changes remaining in the ERG 96 months after cessation of isotretinoin. This may justify the directed use of electrophysiological screening in professions that are night vision critical.

Neuropathic pain: are we out of the woods yet?

Patients suffering from neuropathic pain continue to pose challenges in clinical practice. This descriptive review discusses the continuing debate on the definition and concerns about increasing incidence of neuropathic pain. The clinical features of neuropathic pain are outlined, and the current understanding of the possible mechanisms of neuropathic pain is highlighted. Current management strategies are reviewed, and future advances in our understanding of the mechanisms, accurate clinical diagnosis and more effective treatment strategies are eagerly awaited.

Effects of opioids and sedatives on survival in an Australian inpatient palliative care population.

AIMS: To assess whether opioid and sedative medication use affects survival (from hospice admission to death) of patients in an Australian inpatient palliative care unit. BACKGROUND: Retrospective audit. Newcastle Mercy Hospice--a tertiary referral palliative care unit. All patients who died in the hospice between 1 February and 31 December 2000. METHODS: Length of survival from hospice admission to death, and the median and mean doses of opioids and sedatives used in the last 24 h of life. Comparison of these with published studies outside of Australia. RESULTS: In this study, the use of opioids, benzodiazepines and haloperidol did not have an association with shortened survival and the only statistical significant finding was an increased survival in patients who were on 300 mg/day or more of oral morphine equivalent (OME). The proportion of patients requiring greater than or equal to 300 mg OME/day (at 28%) was higher than published studies, but the mean dose of 371 mg OME/day was within the range of other studies. The proportion of patients receiving sedatives (94%) was higher than other studies, but the median dose of parenteral midazolam equivalent of 12.5 mg per 24 h was lower than other studies from outside Australia. CONCLUSIONS: There was no association between the doses of opioids and sedatives on the last day of life and survival (from hospice admission to death) in this population of palliative care patients.

Prospective audit of short-term concurrent ketamine, opioid and anti-inflammatory ('triple-agent') therapy for episodes of acute on chronic pain.

AIM: This prospective audit was undertaken in order to document the analgesic response and adverse effects of concurrent short-term ('burst') triple-agent analgesic (ketamine, an opioid and an anti-inflammatory agent--either steroidal or non-steroidal) administration, for episodes of acute on chronic pain. The clinical hypothesis in this study is that better pain control may be obtained by simultaneous multiple target receptor blockade. METHOD: The response of 18 patients is reported. The pain and analgesic requirement data for the 24 h before starting triple-agent therapy were compared with the last 24 h on the triple-agent therapy. Patients were then classified as responders or non-responders. RESULTS: According to stringent clinical criteria, 12 out of the 18 patients were classified as responders. The response rate was highest for somatic pain (7/9) and appeared to decrease with duration of prior uncontrolled pain. Only four out of the 18 patients reported adverse effects and all of these were minor. CONCLUSIONS: The results suggest that this 'burst' triple-agent approach is safe and effective in an inpatient palliative care population during episodes of poorly controlled acute on chronic pain, and warrants further investigation to ascertain whether it gives superior results compared to the 'gold-standard' WHO ladder approach.

Biometry of the silicone oil-filled eye: II.

PURPOSE: In phakic silicone oil-filled eyes, removal of the silicone oil can be combined with phacoemulsification and intraocular lens (IOL) implantation. True axial length (AL) of the silicone oil-filled (viscosity 1300 centistokes) eye can be estimated from the measured AL (MAL) obtained on A and/or B scan echography, by multiplying MAL by a conversion factor of 0.71. IOL power can then be calculated using current biometry formulae (SRK/T). This study aims to evaluate the conversion factor in clinical practice. METHODS: Eleven patients undergoing combined removal of silicone oil and phacoemulsification with IOL implant were studied. Patients were divided into two groups. In Group 1 (seven patients), the IOL was placed in the capsular bag and in Group 2 (four patients) the IOL was placed in the ciliary sulcus. Calculated AL (CAL) was obtained by multiplying the MAL of the silicone oil-filled eye (as measured on A or B scan ultrasonagraphy) by the conversion factor of 0.71. IOL power was then estimated using the CAL in the SRK/T formula. The spherical equivalent of the postoperative refractive error was compared to predicted refractive error. RESULTS: The mean difference in actual and predicted refractive error was 0.74 dioptres (D) (standard deviation 0.75 D) for Group 1 and 1.31 D (standard deviation 1.4 D) for Group 2. CONCLUSIONS: The conversion factor of 0.71 corrects for the apparent increase in AL induced by silicone oil of viscosity 1300 centistokes. This allows accurate prediction of the required IOL power in eyes undergoing combined cataract extraction, removal of silicone oil and lens implant. Sulcus placement of the IOL gives a less predictable result than placement in the capsular bag.

TorsinA immunoreactivity in brains of patients with DYT1 and non-DYT1 dystonia.

A mutation of the DYT1 gene, which codes for torsinA, has been identified as the cause of one form of autosomal dominantly inherited dystonia. TorsinA immunohistochemistry was used to examine a case of DYT1, and several cases of non-DYT1, dystonia. No evidence was found for alterations of immunoreactivity at the light microscopic level, specifically neither cytoplasmic aggregations nor colocalization of torsinA immunoreactivity with a marker for endoplasmic reticulum. These findings contrast with results of recent cell culture studies of torsinA.

Cholinergic deficits in the brains of patients with parkinsonism-dementia complex of Guam.

Patients with parkinsonism-dementia complex (PDC) of Guam showed moderate loss of choline acetyl transferase activity in the midfrontal and inferior parietal cortex, and severe loss in the superior temporal cortex. This deficit was similar to that seen in Alzheimer's disease and less severe than Lewy body disease. Thus, cholinergic deficits in the neocortex might contribute to some of the cognitive alterations in PDC of Guam.