Articles of interest in other scholarly journals

Click on the article headings to view abstracts

Discontinuation of antidepressants in people with dementia and neuropsychiatric symptoms (DESEP study): double blind, randomised, parallel group, placebo controlled trial

Sverre Bergh, Geir Selbæk, Knut Engedal

The effect of stopping SSRIs in patients with dementia, and neuropsychiatric symptoms (but no depression) in Norwegian nursing homes was assessed in a double blind, parallel group RCT.  In patients taking SSRIs for three months or more, SSRIs were discontinued in 63 patients, and continued in 68 patients. The patients who stopped SSRIs had higher scores on the Cornell scale for depression in dementia after 25 weeks. 54% of patients had at least a 30% worsening on the Cornell scale in the discontinuation group compared to 29% in the continuation group. Although this study showed that discontinuation of antidepressant treatment in patients with dementia and neuropsychiatric symptoms leads to an increase in depressive symptoms, a limitation is that 37% patients withdrew from the study early.

Combination therapy for neuropathic pain: a review of current evidence.

Vorobeychik Y, Gordin V, Mao J, Chen L.

This review of combination therapy for the treatment of neuropathic pain found only small numbers of clinical studies on this topic. There was clinical evidence that gabapentin and pregabalin combined with an opioid, cyclo-oxygenase-2 inhibitor or antidepressants improved responses compared with monotherapy for painful diabetic neuropathy and postherpetic neuropathy. Topical 8% capsaicin and 5% lidocaine patches were shown to be effective add-on therapies for several causes of painful neuropathy. There were only small clinical studies in cancer-related neuropathic pain, which showed that combination therapy enabled better pain control with reduced side effects. The authors recommend the development of further clinical evaluation tools and future clinical studies to compare single-drug and combination therapies and the combination of non-drug modalities such as physical, psychological and biofeedback therapies.

Sleep disturbance in relatives of palliative patients cared for at home.

Carlsson ME.

This questionnaire based cross-sectional pilot study investigated insomnia, sleep quality, and daytime sleepiness in 75 relatives of dying patients cared for at home in Sweden. The mean sleep duration was 6.5 hours with the need of sleep being 8 hours. 23% reported moderate or severe clinical insomnia with 15% reporting excessive daytime sleepiness. 4% had very poor sleep quality, whereas 39% reported very good sleep quality. Younger relatives had more insomnia and daytime sleepiness compared with older relatives and the sleep quality reported by women was less than that of men.  Although 73% reported getting less sleep than they wanted only a minority had clinical insomnia or excessive daytime sleepiness.

Depression and Survival in Metastatic Non-Small-Cell Lung Cancer: Effects of Early Palliative Care.

Pirl WF, Greer JA, Traeger L, Jackson V, Lennes IT, Gallagher ER, Perez-Cruz P, Heist RS, Temel JS.

To evaluate the effect of early palliative care (EPC) on depression and prognosis, 151 patients with newly diagnosed metastatic non-small-cell lung cancer (NSCLC) were randomised to standard oncology care with or without EPC. Depression was assessed at baseline and at 12 weeks with the Patient Health Questionnaire-9 (PHQ-9) and was scored using Diagnostic and Statistical Manual of Mental Disorders IV. Depression response was considered ≥ 50% reduction in PHQ-9 scores at 12 weeks. At baseline, 14% patients were diagnosed with depression which predicted worse survival. Patients assigned to EPC had greater improvements in depression at 12 weeks. However, improvement in depression was not associated with improved survival. EPC was associated with improved survival after adjusting for improvement in depression. Although EPC in patients with metastatic NSCLC has been shown to improve survival and EPC is associated with greater improvement in depression, this study does not indicate that it is the treatment of depression which mediates the survival benefit from EPC.

Articles of interest in other scholarly journals

Click on the article headings to view abstracts

Physicians’ self-assessment of cancer pain treatment skills-more training required.

Silvoniemi M, Vasankari T, Vahlberg T, Vuorinen E, Clemens KE, Salminen E.

In this study 720 Finnish physicians (59 oncologists) had their perception on their skills and training needs on palliative pain management assessed using a questionnaire. 46% of oncologists and 32% of other physicians knew the analgesic ladder. 46% of oncologists and 61% of other physicians considered pain treatment of cancer patients being well managed in Finland. 24% of oncologists and 5% of other physicians considered the current education in palliative care as satisfactory. Oncologists reported a training need in communication skills, ethical questions, and palliative home care, whereas the other physicians expressed need for training in pain management and palliative care.

The amygdala, a relay station for switching on and off pain.

Rouwette T, Vanelderen P, Roubos EW, Kozicz T, Vissers K.

This review outlines the role of corticotropin-releasing factor in pain processing and relates its up-regulation in the amygdala to neuropathic pain and mood disorders. The authors describe a possible mechanism by which the amygdala has a role in regulating chronic pain, by descending inhibitory pathways, and postulate that in neuropathic pain, this mechanism is dysregulated causing persistent hyperalgesia.

Risk of mortality among individual antipsychotics in patients with dementia.

Kales HC, Kim HM, Zivin K, Valenstein M, Seyfried LS, Chiang C, Cunningham F, Schneider LS, Blow FC.

The 180-day mortality was compared for antipsychotic agents in this 10 year retrospective cohort study of more than 33,000 patients with dementia aged over 65. Haloperidol was associated with the highest mortality, especially in the first 30 days of use, followed by risperidone, olanzapine and valproic acid, with quetiapine having the lowest mortality risk. For risperidone, olanzapine, valproic acid and quetiapine mortality risk was greatest in the first 120 days of use.  Limitations of this study include a predominantly male cohort, use of administrative data, and the presence of Parkinson’s disease in a significantly higher proportion of patients taking quetiapine.

Effects of methylphenidate on fatigue and depression: a randomized, double-blind, placebo-controlled trial.

Kerr CW, Drake J, Milch RA, Brazeau DA, Skretny JA, Brazeau GA, Donnelly JP.

In this randomized, double-blind, placebo-controlled trial of 30 hospice patients, the effect of methylphenidate on fatigue and depression was assessed using several validated scales. Both groups had similar baseline values. Patients taking methylphenidate had lower fatigue scores (on all scales) at day 14 compared with baseline. This effect was dose-dependent, with an average effective dose of 10mg on Day 3 and 20mg on Day 14. There was no improvement in fatigue with placebo. For patients with depression on Day 0, treatment with methylphenidate was associated with an improvement in all indices for depressed mood. For the placebo group, the changes in measures of depression were inconsistent between assessment tools and were less than those detected in the methylphenidate group. There were no significant toxicities from methylphenidate.

By Jason Boland, Consultant in Palliative Medicine, Barnsley Hospice, United Kingdom

Professionals who care for people at the end of life do much more than prescribe drugs, a new study has shown. The qualitative analysis published last month in the journal PLoS Medicine revealed that the day-to-day activities of palliative caregivers throughout Europe are highly multifaceted and complex.

The study used qualitative research methods to identify types of Non-Pharmacological Caregiving Activities (NPCAs) undertaken at 16 different palliative care facilities in nine countries. The responses clearly indicated that the respondents undertook a huge variety of activities which went beyond pharmacological interventions.

The most common NCPA was carrying out or abstaining from bodily care or contact, with many respondents reporting holding hands to provide emotional support as well as maintaining the patient’s oral hygiene.

Somewhat surprisingly, another frequently reported activity was “creating an aesthetical, safe and pleasing environment”, which included applying perfume, making sure there is pleasant lighting, repositioning pictures so that they are visible to the patient and playing the patient’s favourite music. Respondents also indicated that they often provided support not just for the patient but for their loved ones, offering professional advice as well as practical assistance (such as arranging for medical equipment to be removed from the house so that they don’t have to see it after the patient has died).

Whilst the varied nature of palliative care may be obvious to those who work within the field, it is not always apparent to outsiders, and this paper paves the way for future research into the frequency and efficacy of NCPAs.

Articles of interest in other scholarly journals

Click on the article headings to view abstracts

Undetected Cognitive Impairment and Decision-Making Capacity in Patients Receiving Hospice Care.

Burton CZ, Twamley EW, Lee LC, Palmer BW, Jeste DV, Dunn LB, Irwin SA.

This study examined the prevalence of cognitive impairment and its impact on decision-making abilities in 110 hospice patients without a diagnosis of a cognitive disorder or clinical recognition of cognitive impairment. Using neuropsychological tests, assessment of decisional capacity, and interviews, it was found that 54% of patients had significant, previously undetected, cognitive impairment and performed worse on all neuropsychological and decisional measures. Verbal ability and cognitive function predicted decision-making capacity. This shows the need for cognitive assessment of hospice patients as this may enable interventions to improve decision making and patient autonomy.

Evaluation of the comparative analgesic effectiveness of transdermal and oral opioids in cancer patients: A propensity score analysis.

Apolone G, Deandrea S, Montanari M, Corli O, Greco MT, Cavuto S.

In an observational study of 266 patients starting strong opioids, the propensity score (to reduce selection bias) was used to compare the effectiveness of oral and transdermal opioids over 28 days, using pain intensity, dose increases, need for switching and safety. Adjusting for the propensity score, transdermal opioids were reported to give better pain control than oral opioids. No differences were reported in the frequency of most side effects, but cases of nausea and vomiting were more common in the transdermal opioid group.

Information of imminent death or not: does it make a difference?

Lundquist G, Rasmussen BH, Axelsson B.

Nearly 14,000 cancer deaths from a national end-of-life register were reviewed to assess if patients with cancer who were informed about imminent death had different end-of-life care from patients who were not informed. Over 90% of patients had been given information about imminent death. Samples were matched to minimise bias, with nearly 1200 patients being analysed in each group. Compared with uninformed patients, informed patients more frequently had pre-emptive parenteral drugs prescribed, died in their preferred place, and had family who were offered bereavement support. There was no difference in pain, anxiety, confusion, nausea, and respiratory tract secretions between the groups.

Laxative management in ambulatory cancer patients on opioid therapy: a prospective, open-label investigation of polyethylene glycol, sodium picosulphate and lactulose.

Wirz S, Nadstawek J, Elsen C, Junker U, Wartenberg HC.

In a prospective, open-label randomised trial of 348 outpatients with cancer and opioid induced constipation, the laxatives polyethylene glycol, sodium picosulphate and lactulose were compared. Outcomes included the number of patients with a stool-free interval greater than 72h, numerical rating scale for constipation and quality of life questionnaire scores. In spite of opioid therapy, the incidence of constipation was low (5.7%) and laxative use correlated to the opioid dose. For prevention of constipation, polyethylene glycol and sodium picosulphate had a lower stool-free interval greater than 72h and lower numerical rating scale for constipation compared with lactulose.

By Jason Boland, Consultant in Palliative Medicine, Barnsley Hospice, United Kingdom

Articles of interest in other scholarly journals

Click on the article headings to view abstracts

The “no dialysis” option.

Murtagh FE, Cohen LM, Germain MJ.

As people are living longer, the number of patients with end-stage renal failure will increase and increasing numbers of patients who have a 6-month survival are starting dialysis. Furthermore, the rate of dialysis withdrawal has increased. Dialysis has its’ own risks and patients should be informed of the complex and challenging dialysis decisions. For a carefully selected group of patients, another option is not to dialyse and optimise medical and symptom management. This option would be based on clinician’s recommendations along with patient choice and family input. Age, co-morbidities and the patients’ functional capacity should be assessed as these are likely to indicate the patients’ survival and potential benefit from dialysis.

Potentiation of μ-opioid receptor-mediated signaling by ketamine.

Gupta A, Devi LA, Gomes I.

In this study the molecular mechanisms by which ketamine enhances opioid analgesia and prevents hyperalgesia are assessed. It was found that ketamine, via a non-NMDA receptor action, rapidly enhanced opioid-induced extracellular signal-regulated kinase (ERK) phosphorylation and increased resensitisation of opioid-mediated ERK signalling. This study indicates that ketamine might enhance opioid analgesia by increasing the effectiveness of opioid signalling.

Efficacy of small doses of ketamine with morphine to decrease procedural pain responses during open wound care.

Arroyo-Novoa CM, Figueroa-Ramos MI, Miaskowski C, Padilla G, Paul SM, Rodríguez-Ortiz P, Stotts NA, Puntillo KA.

this randomized, cross-over study investigated differences in pain and adverse effects when 11 male patients received either intravenous 0.1 mg/kg morphine or 0.05 mg/kg morphine and 0.25 mg/kg ketamine before an open wound care procedure. Although the pain intensity during wound care was less with the addition of ketamine, over 90% of patients had altered sensations, hallucinations, blurred vision and had an increased diastolic blood pressure. The authors suggest that further research is needed to determine the optimal dose of ketamine and if a benzodiazepine would alleviate the side effects of ketamine.

The role of paracetamol and nonsteroidal anti-inflammatory drugs in addition to WHO Step III opioids in the control of pain in advanced cancer. A systematic review of the literature.

Nabal M, Librada S, Redondo MJ, Pigni A, Brunelli C, Caraceni A.

This systematic review evaluated the evidence for the efficacy of adding non-steroidal anti-inflammatory drugs (NSAIDs) or paracetamol to strong opioids for the treatment of cancer pain. Five of the seven eligible studies showed an additive effect of NSAIDs when combined with opioids, by either improving analgesia or reducing the opioid dose. Paracetamol was only marginally effective in one study. Toxicities could not be evaluated due to the small number of patients and the short treatment duration. There is some clinical evidence that the addition of NSAIDs to strong opioids can improve analgesia or reduce opioid dose requirement, but insufficient evidence to support the use of paracetamol in combination with strong opioids.

Update on the role of palliative oxygen.

Davidson PM, Johnson MJ.

This article reviews the evidence for the efficacy and appropriateness of palliative oxygen in the management of malignant and non-malignant breathlessness. It takes into account the costs, treatment burden and potential dangers. Although, the benefits of long-term oxygen for chronic obstructive pulmonary disease patients with severe hypoxaemic are proven, oxygen is no better than medical air for the relief of refractory breathlessness in patients with mild or absent hypoxaemia. The authors suggest that palliative oxygen should only follow detailed assessment of pathogenesis and reversibility of symptoms. Use of a fan, exercise and psychological support for patients and carers, should be considered before oxygen therapy. If palliative oxygen is considered for patients with transient or mild hypoxaemia, a therapeutic trial should be conducted with clinical review after three days to assess the overall clinical benefit.

The care of the very old in the last three days of life.

Rashidi NM, Zordan RD, Flynn E, Philip JA.

This retrospective review of medical records evaluated the symptoms and medications in the last three days of life for patients over 80 years old, dying in a palliative care unit. One hundred five Patients aged 80 years and older were compared with 100 aged 50 to 70 years. Patients over 80 had a shorter length of stay, had less parenteral opioids and benzodiazepines, but had similar symptom profiles. The authors highlight the need for prospective studies and suggest that this information should be used for service planning to improve care.

A longitudinal study of motor subtypes in delirium: Relationship with other phenomenology, etiology, medication exposure and prognosis.

Meagher DJ, Leonard M, Donnelly S, Conroy M, Adamis D, Trzepacz PT.

100 patients receiving palliative care with delirium (DSM-IV) were assessed throughout their delirium episodes using three delirium rating scales evaluating severity, motor subtype and aetiology. Motor subtypes were hypoactive (28%), mixed (18%), hyperactive (10%) and variable throughout the episode (38%). 6% had no subtype. Those with a mixed subtype were most severely affected. Benzodiazepine and antipsychotics were used more frequently in hyperactive patients. Patients with sustained hypoactive delirium had the poorest prognosis and were significantly more likely to die within one month.

A Multi-institutional Study Analyzing Effect of Prophylactic Medication for Prevention of Opioid-induced Gastrointestinal Dysfunction.

Ishihara M, Ikesue H, Matsunaga H, Suemaru K, Kitaichi K, Suetsugu K, Oishi R, Sendo T, Araki H, Itoh Y; The Japanese Study Group for the Relief of Opioid-induced Gastrointestinal Dysfunction (J-RIGID).

This multi-centre retrospective study investigated the effectiveness of prophylactic laxatives and antiemetics on the incidence of gastrointestinal toxicities in cancer patients who received opioids. Over 600 eligible hospitalised patients with cancer pain who received oral opioids for the first time were enrolled. The incidence of opioid-induced constipation was lower in patients receiving prophylactic laxatives, however, the incidence of nausea or vomiting was similar whether or not patients received prophylactic dopamine D2 blockers.

By Jason Boland, Consultant in Palliative Medicine, Barnsley Hospice, United Kingdom

Articles of interest in other scholarly journals

Click on the article headings to view abstracts

Antagonistic effects of ondansetron and tramadol? A randomised placebo and active drug controlled study.

Rauers NI, Stüber F, Lee EH, Musshoff F, Fimmers R, Barann M, Stamer UM.

This postoperative randomised, double-blinded study assessed if ondansetron and tramadol had opposing effects and if co-administration decreased their efficacy. It showed that using both drugs together did not increase tramadol use or emesis.

Undocumented alcoholism and its correlation with tobacco and illegal drug use in advanced cancer patients.

Dev R, Parsons HA, Palla S, Palmer JL, Del Fabbro E, Bruera E.

In this retrospective study of 665 patients, the frequency of undiagnosed alcoholism among patients with advanced cancer and its relationship to alcoholism, smoking and use of illegal drugs was assessed. 598 patients had completed the Cut Down, Annoyed, Guilty, Eye Opener (CAGE) questionnaire. The frequency of CAGE-positive results was 17%, of which only 13% had been identified before their palliative care consultation. These patients were more likely to have a current and past history of smoking, and illegal recreational drug use. Pain and dyspnea were worse in patients who had a history of nicotine use. Both CAGE-positive patients and patients who had a history of tobacco use more frequently were receiving strong opioids at the time of their palliative care consultation.

The use of crisis medication in the management of terminal haemorrhage due to incurable cancer: A qualitative study.

Harris D, Finlay I, Flowers S, Noble S.

The practice of relieving patient distress through sedative doses of anxiolytics or opioids in terminal haemorrhage was evaluated through Semi-structured interviews with 11 specialist nurses. This showed that anxiolytics and opioids rarely benefit the patient who is having a terminal haemorrhage as it is so rapid that patients died before it could be administered. Furthermore, it may remove nurses from giving patient care, as staying with and supporting the patient, as well as using dark-coloured towels to camouflage blood was reported to be of more practical use. The focus on administering medications was often to the detriment of these non-pharmacological approaches.

Unidirectional Cross-Activation of GRPR by MOR1D Uncouples Itch and Analgesia Induced by Opioids.

Liu XY, Liu ZC, Sun YG, Ross M, Kim S, Tsai FF, Li QF, Jeffry J, Kim JY, Loh HH, Chen ZF.

Spinal opioids can cause itch, which has previously been thought to result from pain inhibition. This study separates the sensation of itch from analgesia, demonstrating that morphine directly induces itch in a subset of spinal neurons by signalling through a heterodimer of opioid (μ-opioid receptor isoform 1D) and gastrin-releasing peptide receptors. In addition, blocking MOR1D-GRPR association attenuates itch but not analgesia. This study also evaluated the downstream effectors of GRPRs and suggests potential pharmacological targets.

Non-steroidal anti-inflammatory drugs and risk of pulmonary embolism.

Biere-Rafi S, Di Nisio M, Gerdes V, Porreca E, Souverein P, Boer A, Büller H, Kamphuisen P.

In a case-control study (of 4433 cases and 16,802 controls) using a Dutch registry the population based effect of non-steroidal anti-inflammatory drugs (NSAIDs) on pulmonary embolism (PE) was assessed. Current use of NSAIDs was associated with PE, with the overall risk for NSAIDs being highest in the first 30 days of use. Use of acetaminophen and tramadol also increased the risk of PE with a similar time trend. Although NSAIDs are associated with an increased risk of PE, this might be due to the underlying medical condition for which they are prescribed, as suggested by a similarly increased thrombotic risk in patients receiving paracetamol and tramadol.

Comparative clinical effects of hydromorphone and morphine: a meta-analysis.

Felden L, Walter C, Harder S, Treede RD, Kayser H, Drover D, Geisslinger G, Lötsch J.

In this meta-analysis of eight studies the analgesic effects of morphine and hydromorphone were compared. It suggested that hydromorphone (494 patients) provides slightly better (P=0.012) clinical analgesia than morphine (510 patients). The effect-size was small although the advantage of hydromorphone was more evident in studies of better quality. Nausea, vomiting and itching were similar. This suggests some advantage of hydromorphone over morphine for analgesia. The authors suggest that hydromorphone’s safety in renal failure or during acute analgesia titration, are based on limited evidence and require substantiation by further studies.

Methadone toxicity due to smoking cessation–a case report on the drug-drug interaction involving cytochrome P450 isoenzyme 1A2.

Wahawisan J, Kolluru S, Nguyen T, Molina C, Speake J.

To report the potential clinically significant pharmacokinetic interaction that may result from smoking cessation in patients on methadone maintenance therapy.

This case report describes a 46-year-old man with decreased respirations and altered mental status related to methadone toxicity, despite being on a stable dose of methadone for chronic back pain. These toxicities resolved by withholding and then reducing the methadone dose. It was subsequently noted that he had recently stopped smoking, which was thought to be the precipitating factor. The explanation for this effect is that tobacco smoke contains polycyclic aromatic hydrocarbons which induce the cytochrome P450 CYP1A2 enzymes which partly metabolise methadone and decreased smoking can lead to a reduction in methadone metabolism, resulting in higher serum concentrations

By Jason Boland, Consultant in Palliative Medicine, Barnsley Hospice, United Kingdom

Articles of interest in other scholarly journals

Click on the article headings to view abstracts

Harmful effects of NSAIDs among patients with hypertension and coronary artery disease.

Bavry AA, Khaliq A, Gong Y, Handberg EM, Cooper-Dehoff RM, Pepine CJ.

This was a post hoc analysis from the INternational VErapamil Trandolapril STudy (INVEST), in patients with hypertension and coronary artery disease. At each visit, patients were asked by the local site investigator if they were currently taking non-steroidal anti-inflammatory drugs (NSAIDs). Patients who reported NSAID use at every visit were defined as chronic NSAID users, while all others (occasional or never users) were defined as non-chronic NSAID users. The primary composite outcome was all-cause death, nonfatal myocardial infarction, or nonfatal stroke. Cox regression was used to construct a multivariate analysis for the primary outcome.

There were 882 chronic NSAID users and 21,694 non-chronic NSAID users (14,408 never users and 7286 intermittent users). At a mean follow-up of 2.7 years, all-cause mortality occurred at a rate of 4.4 events per 100 patient-years in the chronic NSAID group, versus 3.7 events per 100 patient-years in the non-chronic NSAID group. This was due to an increase in cardiovascular mortality. Long-term NSAID use had no significant effect on the risk for stroke. Among long-term NSAID users, a systolic blood pressure above 150 mm Hg was a strong risk factor for cardiovascular events. Gastrointestinal tract bleeding occurred among 0.8% of non-chronic NSAID users but in none of the chronic NSAID users. This may be accounted for by selection-bias, as chronic NSAID users in the study, had already shown they were able to tolerate these medications.

Increased clearance of morphine in sickle cell disease: implications for pain management.

Darbari DS, Neely M, van den Anker J, Rana S.

As patients with sickle cell disease (SCD) often require relatively high doses of morphine to achieve optimal analgesia, the pharmacokinetics of morphine in this group was studied. 21 SCD patients were administered a 0.1 mg/Kg infusion of morphine sulfate. Morphine clearance was 3-10 fold higher than published estimates in the non-SCD population. This suggests that due to increased clearance, SCD patients may require higher dose and frequency of morphine to achieve comparable plasma levels, although inter-individual variability of morphine metabolism highlights the importance of individualisation of therapy.

Non-invasive interventions for improving well-being and quality of life in patients with lung cancer.

Rueda JR, Solà I, Pascual A, Subirana Casacuberta M.

This Cochrane review assessed the effectiveness of non-invasive interventions delivered by healthcare professionals in improving symptoms, psychological functioning and quality of life in patients with lung cancer. Fifteen trials were included but with variability of the interventions assessed and the approaches to measuring the considered outcomes, and the lack of data reported in the trials regarding allocation of patients to treatment groups and blinding. Three trials of a nursing intervention to manage breathlessness showed benefit in symptom experience, performance status and emotional functioning. Four trials assessed structured nursing programmes and found positive effects on delay in clinical deterioration, dependency and symptom distress. One trial assessing counselling showed a non-conclusive benefit for some emotional components of the illness. One trial found that coaching slightly increases the amount of pain data communicated to providers by patients with lung cancer. One trial compared telephone-based sessions of either caregiver-assisted coping skills training or education/support involving the caregiver and found that patients in both treatment conditions showed improvements in pain, depression, quality of life and self-efficacy. Two trials assessed exercise programmes, showing some benefit. One trial found some positive effects for increasing energy intake. Two small trials of reflexology showed short-lasting benefit on anxiety and pain intensity.

Restoring a sense of wellness following colorectal cancer: a grounded theory.

Beech N, Arber A, Faithfull S.

A longitudinal study using grounded theory was conducted with 12 individuals, who had received surgery for colorectal cancer. Semi-structured interviews were conducted over 1 year after surgery. Recovery is described in three phases: disrupting the self; repairing the self; restoring the self. The core category is restoring a sense of wellness through awareness and enjoyment of the physical, emotional, spiritual and social aspects of life. A sense of wellness exists as a duality with a sense of illness, where both perspectives may co-exist but one usually takes precedence. A sense of illness pervades when the individual is preoccupied with illness. Recovery takes time and energy, particularly when the individual is at home and in relative isolation from health professionals.

Uncovering new pharmacological targets to treat neuropathic pain by understanding how the organism r eacts to nerve injury.

Martin YB, Herradón G, Ezquerra L.

This is a review of recent advances identifying potential pharmacological targets in the treatment of the cause of neuropathic pain. Current drugs to treat the symptoms of neuropathic pain fail in up to 50% of patients. Recent progress in the experimental methods for understanding the neurobiology of neuropathic pain could result in significant advances. One possibility for the pharmaceutical development of new drugs could focus on mimicking what the organism does to limit nerve damage or to enhance the regeneration of injured axons. Following this strategy, neurotrophic factors such as nerve growth factor, brain-derived neurotrophic factor and pleiotrophin have been postulated as potential pharmacological targets to treat neuropathic pain and limit neuropathic pain development because of their remodeling and angiogenic actions in the injured area.

Cost analysis of adding pregabalin or gabapentin to the management of community-treated patients with peripheral neuropathic pain.

Sicras-Mainar A, Rejas-Gutiérrez J, Navarro-Artieda R, Planas-Comes A.

In this Spanish retrospective observational study of over 1000 patients, the cost of adding either pregabalin or gabapentin to the management of community-treated patients with peripheral neuropathic pain was compared. An economic evaluation included health care resource utilisation costs and costs due to sick leave. Concomitant use of analgesics was higher in the gabapentin cohort, mainly due to non-steroidal anti-inflammatory drugs and opioids. Adjusted total costs per patient were considerably lower in pregabalin-treated patients due to less sick leave and lower health care costs. The higher acquisition cost of pregabalin was compensated with lower costs in medical visits, physiotherapy, hospital stays and concomitant analgesics.

By Jason Boland, Consultant in Palliative Medicine, Barnsley Hospice, United Kingdom

Articles of interest in other scholarly journals

Click on the article headings to view abstracts

Gender differences in prevalence of depression among patients receiving palliative care: the role of dependency

Hayes RD, Lee W, Rayner L, et al. Palliat Med 2011. [Epub ahead of print]

In the community, depression is more common in women than in men; however, in patients receiving palliative care this is not seen. In this cross-sectional study, 300 patients were interviewed and depression evaluated. It was found that depending on others for help with basic tasks (eating, dressing, washing or using the toilet) was a risk factor for depression only in men, with 37.8% of dependent men being depressed compared to 2.4% of similarly affected women. Furthermore, in men, the level of dependency was related to the severity of the depression.

Effectiveness of vertebroplasty using individual patient data from two randomised placebo controlled trials: meta-analysis

Staples MP, Kallmes DF, Comstock BA, et al. BMJ 2011; 343:d3952

This study aimed to determine if selected subgroups (pain of recent onset or severe pain) with osteoporotic vertebral compression fractures would benefit from vertebroplasty. A meta-analysis of combined individual patient data from two placebo-controlled blinded trials was used. These studies, powered for subgroup analyses, failed to show an advantage of vertebroplasty over placebo for participants with recent onset fracture or severe pain and do not support the hypothesis that selected subgroups would benefit from vertebroplasty. At one month, those in the vertebroplasty group were also more likely to be taking opioids.

Randomized controlled trial of percutaneous vertebroplasty versus optimal medical management for the relief of pain and disability in acute osteoporotic vertebral compression fractures

Farrokhi MR, Alibai E, Maghami Z. Journal of Neurosurgery-Spine 2011; 14 (5)

This randomised controlled trial of 82 patients compared the efficacy of percutaneous vertebroplasty versus optimal medical therapy in controlling pain and improving the quality of life (QOL) in patients with osteoporotic vertebral compression fractures. Significant improvement in pain and QOL from vertebroplasty was detected at one week and maintained over two years, with improvement in vertebral body height and deformity. The incidence of new fractures was also less with vertebroplasty.

Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial

Banerjee S, Hellier J, Dewey M, et. al.The Lancet 2011; 378 (9789): 403 – 411

In this randomised, parallel-group, double-blind, placebo-controlled, Health Technology Assessment Study of the Use of Antidepressants for Depression in Dementia (HTA-SADD) trial, the effect of mirtazapine and sertraline was evaluated. The primary outcome, which was reduction in depression at 13 weeks, did not differ between control and either antidepressant groups. This was unchanged at 39 weeks. There were more adverse reactions with mirtazapine and sertraline compared with control. The authors suggest that due to the absence of benefit compared with placebo and increased risk of adverse events, the present practice of use of these antidepressants, with usual care, for first-line treatment of depression in Alzheimer’s disease should be reconsidered.

Assessing constipation in palliative care within a gastroenterology framework

Clark K, Currow DC. Palliat Med 2011.[Epub ahead of print]

A non-systematic review of the literature was undertaken to assess the approaches to assessment and treatment. This found that in palliative care, constipation is assessed by patients’ reports, physical examination and sometimes an abdominal x-ray. However, data in non-palliative care patients refutes the usefulness of self-reported symptoms to localise whether problems are due to colon dysfunction or structures of defaecation. Plain radiographs are most useful to exclude a bowel obstruction only. In patients with resistant constipation, gastroenterology guidelines recommend an assessment approach that includes measuring colon transit time and an assessment of the structures that facilitate defaecation. The authors suggest that a modified gastroenterology guideline approach may be tolerable to palliative care patients and offer the chance of developing targeted palliation.

A prevalence study of errors in opioid prescribing in a large teaching hospital

Davies ED, Schneider F, Childs S, et al. International Journal of Clinical Practice 2011. [Epub ahead of print]

Opioid prescribing errors were assessed in a teaching hospital prior to implementation of the National Patient Safety Agency ‘Reducing Dosing Errors with Opioid Medicines’ recommendations, using a one day snapshot of opioid prescriptions on inpatient drug charts. A total of 722 charts were reviewed, 330 had opioid prescriptions and 90 opioid prescribing errors were found. These were mostly either unclear prescription or missing information. There were four potentially lethal, 26 serious, 38 significant and 22 minor errors. By implementing new pain guidelines and e-learning package focused on these errors, patient safety is hoped to be improved.

Short Cuts by Jason Boland, Consultant in Palliative Medicine, Barnsley Hospice, United Kingdom

Articles of interest in other scholarly journals

Click on the article headings to view the abstracts

A systematic review of combination step III opioid therapy in cancer pain: An EPCRC opioid guideline project

Fallon MT, Laird BJ. Palliat Med 2011; 25 (5): 597-603

As the use of combinations of opioids is a common clinical practice a systematic review of the use of strong opioids in combination in cancer pain was conducted. Only two eligible studies, which were grade C and grade D evidence, were found. These examined morphine in combination with oxycodone or fentanyl/methadone.

Only a weak recommendation can be made to support combination opioid therapy. This recommendation also includes the caveat that the desirable effects of combination opioid therapy is outweighed by any disadvantages that this would confer. Prospective randomized trials are needed to clarify the benefits and safety of combination opioid therapy.

A systematic review of the use of opioid medication for those with moderate to severe cancer pain and renal impairment: A European Palliative Care Research Collaborative opioid guidelines project

King S, Forbes K, Hanks G, Ferro C, Chambers E. Palliat Med 2011; (25) (5) 525-552

This narrative systematic review without a meta-analysis identified 15 articles (8 prospective and 7 retrospective clinical studies). Overall evidence was of very low quality. The direct clinical evidence in cancer-related pain and renal impairment is suggestive of differences in risk between opioids. The authors recommend Fentanyl, alfentanil and methadone as they are the least likely to cause harm. Morphine may be associated with toxicity in patients with renal impairment, but can be reduced by increasing the dose or dosing interval or switching to an alternative opioid.

The adverse event profile of pregabalin: A systematic review and meta-analysis of randomized controlled trials

Zaccara G, Gangemi P, Perucca P, Specchio L. Epilepsia 2011; 52 (4): 826–836

This systematic review with a meta-analysis of adverse events (AEs) from pregabalin assessed all RCTs, including neurologic and psychiatric disorders. From the 38 RCTs there were 20 AEs associated with pregabalin, especially cognition and coordination AEs (none serious). Some AEs occured at lower doses than others (i.e. dizziness and somnolence). Most AEs displayed a dose-response pattern, especially balance disorders, cognitive functions and constipation.

This data is from a range of patient groups with heterogeneous diseases, including several studies from various pain disorders (including diabetic and post herpetic neuropathy)

Memory functions in chronic pain: examining contributions of attention and age to test performance

Oosterman JM, Derksen LC, van Wijck AJ, Veldhuijzen DS, Kessels RP.Clinical Journal of Pain 2011; 27 (1): 70–75

34 participants with chronic pain and 32 pain-free participants completed tests of episodic, semantic, and working memory to assess memory performance and a test of attention. Chronic pain adversely affected working memory and verbal episodic memory, which was partly accounted for by a decline in attention. An increase in age in combination with the presence of chronic pain did not additionally affect memory performance.

Primary thromboprophylaxis for hospice inpatients: Who needs it?

Gillon S, Noble S, Ward J, Lodge KM, Nunn A, Koon S, Johnson MJ.  Palliat Med 2011 Feb 10 [Epub ahead of print]

In this study 300 case notes were reviewed before and 350 after the implementation of the Pan Birmingham Cancer Network venous thromboembolism (PBCNVTE) prophylaxis prevention guidelines in 3 hospices. Just under half of all patients had a contraindication to anticoagulation and 9% had a temporary increased risk of VTE. However, only 3.6% before and 6.3% after implementation had a temporary increased risk of VTE without contraindication to primary thromboprophylaxis (PTP). Patients receiving PTP increased from 1% to 3.6% and documentation of PTP decisions increased from 5% to 81%. The authors suggest that quality clinical trials including patients with advanced disease are needed to help inform decision making about PTP.

Short Cuts by Jason Boland, Consultant in Palliative Medicine, Barnsley Hospice, United Kingdom

Articles of interest in other scholarly journals

Click on the article headings to view the abstracts

A comprehensive review of opioid-induced hyperalgesia

Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. Pain Physician 2011; 14:145-161

In this review of opioid-induced hyperalgesia, it is suggested that this phenomenon may result from neuroplastic changes in the peripheral and central nervous system that lead to sensitisation of pronociceptive pathways from central glutaminergic system, spinal dynorphins, descending facilitation and decreased re-uptake and enhanced nociceptive response. NMDA receptors, glutamate transporter system and protein kinase C may be involved. It should be suspected when the effect of opioids decrease in the absence of disease progression, particularly if found in the context of unexplained pain reports or diffuse allodynia and increased levels of pain with increasing dosages. The treatment involves reducing the opioid dose, or NMDA blockade.

Pregabalin for peripheral neuropathic pain: a multicenter, enriched enrollment randomised withdrawal placebo-controlled trial

Gilron I, Wajsbrot D, Therrien F, Lemay J. Clinical Journal of Pain 2011; 27(3):185–193

Neuropathic pain randomised controlled trials of pregabalin have involved primarily diabetic peripheral neuropathy (DPN) and postherpetic neuralgia (PHN). This multicentre trial evaluated pregabalin in a broader range of neuropathic pain etiologies. In this enriched enrolment randomised withdrawal trial, 256 patients received single blind, flexible dose pregabalin for 4 weeks. Of those patients,165 had a 30% pain improvement and 157 were randomised and treated, double blind, to either continue pregabalin (n=80) or to receive placebo (n=77) for 5 weeks. At the double-blind endpoint, mean pain scores were 2.9 (1.9) in the pregabalin group and 3.5 (1.7) in the placebo group (P=0.002).

A Strategy for Conversion From Subcutaneous to Oral Ketamine in Cancer Pain Patients: Effect of a 1:1 Ratio

Benítez-Rosario MA, Salinas-Martín A, González-Guillermo T, Feria M. Journal of Pain and Symptom Management 2011; 41 (6):  1098-1105

The 29 patients who responded to subcutaneous (s.c.) ketamine injection for cancer pain were given an infusion and then changed to oral ketamine with a 1:1 dose conversion. Pain and side effects were assessed throughout and 27 remained pain-controlled. The other two patients needed a dose increase to maintain pain control. The median oral ketamine dose was 300mg/day. In this group a 1:1 dose ratio for conversion from s.c. to oral ketamine was safe and effective.

Short Cuts prepared by Jason Boland, Consultant in Palliative Medicine, Barnsley Hospice, United Kingdom