The Effect of Opioid Therapy on Endocrine Function.

Brennan MJ.

This review summarises the major effects of opioids on the endocrine system, outlining the long-term effects of their use, which can include reduced libido and sexual function, infertility, mood disorders and bone demineralisation. Although the effects of opioids on the endocrine system are relatively common they might not be detected as many patients do not report these symptoms, thus specific questioning regarding the endocrine effects needs to guide clinical monitoring. The patients most at risk of these toxicities are probably those taking over 100 mg of morphine equivalent daily in the long term. If the patient on opioids has hypogonadism, diagnosing it as opioid-related can be challenging as pain, comorbidities, other medications and age can also influence endocrine function. If it is the opioid causing the endocrine dysfunction, management options include optimisation of non-opioid analgesics which may enable reducing or cessation of the opioid, changing to a different opioid, and hormone supplementation.

A Nationwide Analysis of Antibiotic Use in Hospice Care in the Final Week of Life.

Albrecht JS, McGregor JC, Fromme EK, Bearden DT, Furuno JP.

This study from the USA used data from the 2007 National Home and Hospice Care Survey, to estimate the use of antibiotics in the last week of life in 3884 patients who died in hospice care. During this time 27% of hospice patients received at least one antibiotic and 85% of these patients had no documented infectious diagnosis. The authors suggest that further research is needed to elucidate the role of antibiotics in patient in the last week of life to reduce the use of unnecessary antibiotics while maintaining goals care at the end of life.

 Am J Med. 2013 Mar;126(3S1):S12-S18.

J Pain Symptom Manage. 2013 Jan. [Epub ahead of print]

Symptom burden, palliative care need and predictors of physical and psychological discomfort in two UK hospitals.

Ryan T, Ingleton C, Gardiner C, Parker C, Gott M, Noble B.

In this prospective study which had complete data sets on 514 hospital inpatients, the gold standards framework was used to identify the 185 patients who met palliative care criteria. This cohort had increased physical, psychological and social burden. The most prevalent physical symptoms were tiredness (35%), pain (31%) and weakness (29%) whereas low mood (20%) and anxiety (16%) were the most prevalent psychological symptoms. Only 8% had specialist palliative care input and these were mostly patients with cancer. Dementia was a predictor of physical (OR 3.94) and psychological burden (OR 2.88), and being female was a predictor of psychological burden (OR 2.00). This study indicates that a large proportion of patients with high symptom burden are not receiving specialist palliative care especially patients with non-malignant illnesses, including dementia, who may experience high levels of symptoms.

 BMC Palliat Care. 2013 Feb 26;12:11.

Prevalence and natural history of pain in adults with multiple sclerosis: Systematic review and meta-analysis.

Foley PL, Vesterinen HM, Laird BJ, Sena ES, Colvin LA, Chandran S, Macleod MR, Fallon MT.

This systematic review with a meta-analysis included 28 prospective articles (7101 subjects) which assessed the prevalence of pain syndromes in multiple sclerosis (MS) both cross-sectionally at key milestones, and longitudinally during the MS disease course. The pooled overall pain prevalence (17 studies, 5319 subjects) was 63%, although this estimate contained unexplained heterogeneity. Individual pains were also explored with 43% having headache, 26% neuropathic extremity, 20% back pain, 15% painful spasms, 16% Lhermitte sign, and 4% had trigeminal neuralgia. Cross-sectional prevalence of pain prior to the onset of MS, at onset, and at relapse, and longitudinally were poorly described. It was concluded that although pain and specific pain syndromes are common in MS, the clinical associations and natural history of pain in MS require clarification in future studies.

Pain. 2012 Dec. [Epub ahead of print]

By Jason Boland

Rapid response teams, do not resuscitate orders, and potential opportunities to improve end-of-life care: a multicentre retrospective study.

Downar J, Rodin D, Barua R, Lejnieks B, Gudimella R, McCredie V, Hayes C, Steel A.

In this retrospective review from Canada, 300 in hospital Rapid response team (RRT) consultations were reviewed in the light that although RRTs were created to stabilise acutely ill inpatients a proportion of these will be patients in the last days of their life. The study showed that most consultation were for elderly patients with a chronic illness, with over 90% of patients being for resuscitation. After RRT review one third were admitted to the intensive care unit within 48 hours and 25% died. 9% had a patient/family meeting on the ward after the consultation, leading to nearly 90% changing their resuscitation status. Of these, less than 20% were referred to the palliative or spiritual care teams, or prescribed symptom control medications. Furthermore, 63% of these patients died before discharge. It was concluded that in the acute hospital setting RRT consultation is an important milestone for many patients approaching end-of-life.

J Crit Care. 2013 Jan. [Epub ahead of print]

Rehabilitation in Advanced, Progressive, Recurrent Cancer: A Randomized Controlled Trial.

Jones L, Fitzgerald G, Leurent B, Round J, Eades J, Davis S, Gishen F, Holman A, Hopkins K, Tookman A.

This two-arm, wait-list randomised controlled trial, assessed the clinical and cost-effectiveness of a rehabilitation intervention delivered by a hospice-based multidisciplinary team vs. usual care for patients with advanced, progressive, recurrent haematological and breast cancer, with a follow-up at three months. From the 41 enrolled participants, 36 completed the trial. There was improvement in the psychological subscale of the Supportive Care Needs Survey (primary outcome). There was also improvement in the physical and patient care subscales of the Supportive Care Needs Survey, and self-reported health state. The incremental cost-effectiveness ratio was calculated to be £19,390 per quality-adjusted life year. The authors recommend implementation alongside evaluation in wider clinical settings and patient populations.

J Pain Symptom Manage. 2012 Nov. [Epub ahead of print]

Parenteral hydration in patients with advanced cancer: a multicenter, double-blind, placebo-controlled randomized trial.

Bruera E, Hui D, Dalal S, Torres-Vigil I, Trumble J, Roosth J, Krauter S, Strickland C, Unger K, Palmer JL, Allo J, Frisbee-Hume S, Tarleton K.

In a randomized, placebo-controlled, double-blind trial of 129 patients with cancer from six hospices, patients who were mildly to moderately dehydrated and in the last weeks of life either received subcutaneous hydration (1 L of normal saline) or placebo (100 mL of normal saline subcutaneously) over 4 hours every day until the they became unresponsive or died. The effect of hydration on symptoms associated with dehydration, quality of life, and survival in patients with advanced cancer was determined at baseline and day 4±2 days for the first week and then every 3 to 5 days (fatigue and biochemistry tests were performed at baseline and day 7). There were no differences between the two groups for change in the sum of the scores of dehydration symptoms (fatigue, myoclonus, sedation and hallucinations); Edmonton Symptom Assessment Scale; Dehydration, Delirium, Fatigue and Myoclonus Assessment scales; creatinine, urea, and overall survival.

J Clin Oncol. 2013 Jan 1;31(1):111-8.

by Jason Boland

Gabapentin for refractory chronic cough: a randomised, double-blind, placebo-controlled trial.

Ryan NM, Birring SS, Gibson PG.

This study is the first double-blind, placebo-controlled RCT to investigate gabapentin for the treatment of refractory chronic cough. In it, 62 adults with refractory chronic cough of over 2 months, who did not have active respiratory disease, were randomised to take either gabapentin (titrated up to 600 mg three times a day) or placebo for 10 weeks. Compared with placebo, gabapentin improved cough-specific quality of life as measured by the Leicester cough questionnaire score within 4 weeks of commencement and maintained during the study, although this improvement was not sustained after the drug cessation. Ten patients (31%) had side-effects with gabapentin (most commonly nausea and fatigue) and three patients (10%) had side-effects with placebo. This study concluded that the treatment of refractory chronic cough with gabapentin is effective and well tolerated, and suggested that central reflex sensitisation is an important mechanism.

Lancet. 2012 Nov 3;380(9853):1583-9. doi: 10.1016/S0140-6736(12)60776-4. Epub 2012 Aug 28.

Hydration in Advanced Cancer: Can Bioelectrical Impedance Analysis Improve the Evidence Base? A Systematic Review of the Literature.

This Systematic Review evaluated the evidence for methods of hydration assessment, including bioelectrical impedance analysis to assess hydration in advanced cancer. It included 15 studies in the review. The findings from these studies show that clinical examination and biochemical tests are often used to assess hydration, however limitations exist with these and in patients with advanced cancer. Furthermore, there is not always consensus for the symptoms associated with dehydration in cancer. Although there are limitations with using bioelectrical impedance alone to assess hydration in advanced cancer (due to reduced intracellular water, making inaccurate calculations from equations based on healthy people), analysis of the raw bioelectrical impedance measurements by using vector analysismay have a role as a hydration assessment tool in patients with advanced cancer.

J Pain Symptom Manage. 2012 Nov 27. pii: S0885-3924(12)00499-X. doi: 10.1016/j.jpainsymman.2012.08.018. [Epub ahead of print]

High-inspired oxygen concentration further impairs opioid-induced respiratory depression.

Niesters M, Mahajan RP, Aarts L, Dahan A.

This study tested the influence of the inspired oxygen concentration on the effect of remifentanil on respiratory drive in 20 healthy volunteers. Each volunteer received 50 μg of intravenous remifentanil over 1 minute, under either normoxic (21% O₂) or hyperoxic (50% O₂) conditions. There was no difference in baseline respiratory parameters between normoxia and hyperoxia. Remifentanil decreased mean minute ventilation from 7.4 to 2.2 l/min during normoxia, whereas under hyperoxic conditions this decreased to 1.2 l/min. Respiratory rate decreased from 13.1 to 6.1 breaths per minute under normoxic conditions and down to 3.6 breaths per minute during hyperoxia. During normoxia, oxygen saturations decreased from 98.4% to 88.6%, and during hyperoxia decreased from 99.7% at baseline to 98.7% after remifentanil. Mean end-tidal Pco₂ increased from 5.1 to 5.7kPa after remifentanil in the normoxic group and from 5.2 to 6.1kPa under hyperoxic conditions. Apnoea developed in two subjects during normoxia and 10 during hyperoxia. This healthy volunteer study showed that respiratory depression, in terms of minute ventilation, end-tidal Pco₂, and RR from remifentanil is more pronounced during hyperoxia than normoxia. Furthermore, during, the initial stages of respiratory depression hyperoxia might not be detected by pulse oximetry.

Br J Anaesth. 2013 Jan 4. [Epub ahead of print]

Newer antidepressants and panic disorder: a meta-analysis.

Andrisano C, Chiesa A, Serretti A.

This systematic review assessed newer antidepressants as compared with placebo for the treatment of panic disorder. Fifty studies with a total of 5236 patients were included. The antidepressants which were superior to placebo for patients with panic disorder, in increasing order of effectiveness were citalopram, sertraline, paroxetine, fluoxetine, and venlafaxine for panic symptoms.  For overall anxiety symptoms these were paroxetine, fluoxetine, fluvoxamine, citalopram, venlafaxine, and mirtazapine. Other than reboxetine and fluvoxamine, all other drugs had lower dropout rates compared to placebo. However, because of inconsistencies between studies and limited evidence for some drugs, further comparisons between the drugs are needed.

Int Clin Psychopharmacol. 2012 Oct 29. [Epub ahead of print]

by Jason Boland

Cancer. 2012

Chemotherapy use and patient treatment preferences in advanced colorectal cancer: A prospective cohort study.

Zafar SY, Malin JL, Grambow SC, Abbott DH, Kolimaga JT, Zullig LL, Weeks JC, Ayanian JZ, Kahn KL, Ganz PA, Catalano PJ, West DW, Provenzale D; for the Cancer Care Outcomes Research & Surveillance (CanCORS) Consortium.

This national prospective, population-based cohort study from the USA assessed how patient preferences guide the course of palliative chemotherapy for 702 patients with metastatic colorectal cancer. Over 90% saw a medical oncologist, of whom 82% received chemotherapy. Patients over 65 or too sick to complete their own survey were less likely to visit an oncologist and patients over 75 with comorbidities were less likely to receive chemotherapy. However, of the patients that thought chemotherapy would not extend their life, would not help with cancer-related problems, or whose preferred treatment was comfort up to 90% still received chemotherapy, indicating that patient preferences were not associated with the administration of chemotherapy.

J Clin Oncol. 2012

Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Toxicity of Subcutaneous Ketamine in the Management of Cancer Pain.

Hardy J, Quinn S, Fazekas B, Plummer J, Eckermann S, Agar M, Spruyt O, Rowett D, Currow DC.

This multisite, double-blind RCT assessed the effect of subcutaneous ketamine (in combination with opioids and co-analgesics) over 3 to 5 days compared to with placebo, in 185 patients with chronic uncontrolled cancer pain. It showed there was no significant difference between the proportion patients responding to ketamine (31%) or placebo (27%), irrespective of pain type (nociceptive vs. neuropathic). There were however twice as many adverse events with ketamine which were more severe. The number needed to treat for one additional positive outcome from ketamine was 25. The number needed to harm was six. The authors concluded that ketamine does not have net clinical benefit when used as an adjunct to opioids and standard co-analgesics in cancer pain.

Cochrane Database Syst Rev. 2012

Combination pharmacotherapy for the treatment of neuropathic pain in adults.

Chaparro LE, Wiffen PJ, Moore RA, Gilron I.

This Cochrane review identified double-blind RCTs of drug combinations for neuropathic pain compared to a comparator (including placebo) to assess the efficacy, tolerability and safety of analgesic combinations. 21 eligible studies were identified: five (604 participants) evaluated topical medications; four (578 participants) an opioid with gabapentin or pregabalin; three (90 participants) fluphenazine with a tricyclic antidepressant; three (90 participants) of an N-methyl-D-aspartate antagonist in combination with another analgesic; two (77 participants) evaluated an opioid with a tricyclic antidepressant; one (313 participants) of tramadol with paracetamol; one (120 participants) of gabapentin and alpha-lipoic acid; one (56 participants) of gabapentin and nortriptyline; and one (44 participants) of L-365,260 (a cholecystokinin antagonist) with morphine.

Meta-analysis was only possible for gabapentin with an opioid versus gabapentin alone (two studies, 386 participants) and showed modest, yet statistically significant, superiority of a gabapentin with an opioid over gabapentin alone, but produced more frequent side effect-related trial dropouts compared to gabapentin alone.

The authors concluded that although there are many, good-quality studies showing superiority of two-drug combinations, there are few studies for any one specific combination and recommend that future combination studies include comparisons with placebo and both single-agent components.

J Pain Symptom Manage. 2012

Frequency and Predictors of Patient Deviation From Prescribed Opioids and Barriers to Opioid Pain Management in Patients With Advanced Cancer.

Nguyen LM, Rhondali W, De la Cruz M, Hui D, Palmer L, Kang DH, Parsons HA, Bruera E.

This study surveyed 198 patients in the USA to evaluate self-reported opioid deviation (taking <70% or >130% of the prescribed dose) and the barriers to pain management with opioids in outpatients with advanced cancer. The median pain intensity (0-10) was 4 and morphine equivalent daily dose was 120 mg (interquartile range: 45-270 mg). Prescribed and patient-reported prescribed doses for opioids correlated, with 19 patients reporting deviation. Deviation was more frequent in males and non-whites. Low adherence was associated with higher barriers to pain management scores (as measured by the Barriers Questionnaire-II) for lower motivation and for lower knowledge. The frequency and predictors of opioid deviation need to be better characterize in this population.

by Jason Boland

Ann Surg Oncol. 2012 Nov 10. [Epub ahead of print]

Longitudinal Changes in Function, Symptom Burden, and Quality of Life in Patients with Early-Stage Lung Cancer.

Koczywas M, Williams AC, Cristea M, Reckamp K, Grannis Jr FW, Tiep BL, Uman G, Ferrell B.

This study evaluated the longitudinal changes (up to 1 year) in physical function, symptom burden, psychological distress and quality of life (QOL) in 103 patients with early-stage non-small cell lung cancer (34 stage I, 20 stage II and 49 stage III). At baseline there were no differences between these groups of patients demographically, clinically and functionally, however compared with stage III patients, stage I-II patients were more likely to complete the study. All groups were very symptomatic throughout the study, although over time there was a decrease in the number of symptoms and a decrease in physical QOL, whereas physical function and family QOL fluctuated irrespective of the stage of disease. Based on these findings a multidisciplinary palliative care intervention was developed, which included patient education and a multidisciplinary team meeting from which referrals to supportive care services are made.

J Pain Symptom Manage. 2012 Nov 7. pii: S0885-3924(12)00439-3. doi: 10.1016/j.jpainsymman.2012.07.014. [Epub ahead of print]

An Open-Label Extension Study to Investigate the Long-Term Safety and Tolerability of THC/CBD Oromucosal Spray and Oromucosal THC Spray in Patients With Terminal Cancer-Related Pain Refractory to Strong Opioid Analgesics.

Johnson JR, Lossignol D, Burnell-Nugent M, Fallon MT.

This open-label, multicenter follow-up study investigated the long-term safety and tolerability of Sativex [Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD)] oromucosal spray (n=39) and THC spray (n=4) in patients with cancer-related pain despite taking opioids, who had participated in a previous Sativex/THC/placebo RCT. There was a maintained improvement in insomnia, pain, fatigue and quality of life in the patients using Sativex spray, without any new safety concerns associated with its extended use. Patients who kept using Sativex spray did not increase their dose of this or other analgesics, suggesting that cannabinoids could have a role in cancer-related pain.

Palliat Med. 2012 Nov 5. [Epub ahead of print]

Preferences for end-of-life care: A nominal group study of people with dementia and their family carers.

Dening KH, Jones L, Sampson EL.

Using a nominal group technique it was explored if carers influenced the choices and preferences around end-of-life care made by people with dementia. Quality of care, family contact, dignity and respect were important in people with dementia and their carers when assessed both individually and together. Carers wanted control at the end of life and raised assisted dying and euthanasia. As people with dementia had difficulty considering their future selves and the preferences of people with dementia and their family carers may differ, the views of people with dementia should be sought early to ensure their wishes are respected.

PLoS One. 2012;7(11):e46327. doi: 10.1371/journal.pone.0046327. Epub 2012 Nov 7.

Symptoms and quality of life in late stage Parkinson syndromes: a longitudinal community study of predictive factors.

Higginson IJ, Gao W, Saleem TZ, Chaudhuri KR, Burman R, McCrone P, Leigh PN.

This study assessed how symptoms and quality of life changed over time in 82 patients with advanced Parkinson syndromes, by assessing then four times over one year. At baseline nearly 85% reported problems using their legs with over one third being immobile. Symptoms were highly prevalent in all conditions, with over 80% reporting pain, fatigue and sleepiness at baseline. Over the year, most patients showed a worsening or fluctuation for symptoms and in the Palliative care Outcome Scale. Over half of the patients with Multiple System Atrophy and Progressive Supranuclear Palsy died within the study period. The strongest predictors of higher levels of symptoms at the end of follow-up were initial scores on Palliative care Outcome Scale and a male gender. The authors suggest an early palliative assessment might help in screening patients in need of early intervention as patients with advanced Parkinson syndromes often have unresolved motor and non-motor symptoms and many patients are deteriorating. Further work is needed to test symptomatic treatments and psychological support for this cohort of patients.

Articles of interest in other scholarly journals

Pain outcomes in patients with advanced breast cancer and bone metastases: Results from a randomized, double-blind study of denosumab and zoledronic acid.

Cleeland CS, Body JJ, Stopeck A, von Moos R, Fallowfield L, Mathias SD, Patrick DL, Clemons M, Tonkin K, Masuda N, Lipton A, de Boer R, Salvagni S, Oliveira CT, Qian Y, Jiang Q, Dansey R, Braun A, Chung K.

The effect of denosumab versus zoledronic acid on pain, activities of daily life and need for a strong opioid were assessed in an international RCT of 2046 patients with advanced breast cancer and bone metastases. Denosumab demonstrated better pain prevention and less worsening of pain severity, with fewer patients needing a strong opioid. In patients who had no/mild pain at baseline, there was a 4-month delay in the development of moderate/severe pain with denosumab compared with zoledronic acid. However, in patients with pain, the time to pain improvement was similar with denosumab and zoledronic acid.

A comparative efficacy of amitriptyline, gabapentin, and pregabalin in neuropathic cancer pain: a prospective randomized double-blind placebo-controlled study.

Mishra S, Bhatnagar S, Goyal GN, Rana SP, Upadhya SP.

120 patients with severe neuropathic cancer pain were randomised to receive amitriptyline, gabapentin, pregabalin or placebo. Oral morphine was used if pain persisted. Pregabalin decreased the pain score more than the other drugs/placebo. Reduction in burning, lancinating pain and dysesthesia was best with pregabalin and then gabapentin. All the patients taking placebo needed rescue morphine, which was needed least in those taking pregabalin. The maximum improvement in ECOG and global satisfaction score was observed with pregabalin. Although amitriptyline, gabapentin, pregabalin and morphine (incrementally dosed in the placebo group), were effective in relieving pain, there was a morphine sparing effect of pregabalin along with a reduction in neuropathic symptoms compared to amitriptyline, gabapentin and placebo. Pregabalin also had the least severe side effects.

 Management of Moderate-to-Severe Dyspnea in Hospitalized Patients Receiving Palliative Care.

Gomutbutra P, O’Riordan DL, Pantilat SZ.

A 115 patients with moderate to severe dyspnoea from mixed aetiologies, had dyspnoea scores measured before and after a palliative care review. 74% had an improvement in dyspnoea, of which 42% only received opioids, 37% had opioids and benzodiazepines, 2% only received benzodiazepines, and 19% had neither. Opioids and benzodiazepines in combination were associated with improvement in dyspnoea, with most patients reported improvement in dyspnoea 1 day after palliative care review.

Compiled by Jason Boland

Articles of interest in other scholarly journals.

Diagnosis and management of people with venous thromboembolism and advanced cancer: how do doctors decide? a qualitative study

Miriam J Johnson, Laura Sheard, Anthony Maraveyas, Simon Noble, Hayley Prout, Ian Watt and Dawn Dowding

Using think aloud exercises and interviews of oncologists, palliative physicians and general practitioners, this study explored why clinicians did not always use low molecular weight heparin for cancer associated thrombosis, despite high level evidence. It found that clinicians are concerned with the patients’ prognosis, increased bleeding risk and burden of self-injection. Furthermore, the diagnosis and management of cancer associated thrombosis can be complex and should be individualised on the risks/benefit for the patient. It was also found that, logistic and organisational issues also influenced investigation and treatment with low molecular weight heparin and the authors suggest that services are optimised to ensure that these do not hinder the appropriate investigation and management of patients.

 Dissociable influences of opiates and expectations on pain

Lauren Y. Atlas, Robert A. Whittington, Martin A. Lindquist, Joe Wielgosz, Nomita Sonty and Tor D. Wager

The relationship between expectations and opioid analgesia were evaluated in healthy volunteers using a thermal pain model. Remifentanil was administered and participants’ knowledge of drug delivery was manipulated using an open-hidden design. Although remifentanil and expectancy both reduced pain, the effects of remifentanil on pain and fMRI activity did not interact with expectancy. fMRI activity showed opioid-induced modulation during both open and hidden conditions, with no differences in the effect of opioid caused by expectation, which followed a different time course from the opioid. The authors conclude that both opioids and placebo influence pain reports and fMRI activity but that the effects of opioids and expectations did not interact.

Comparative health care use patterns of people with schizophrenia near the end of life: A population-based study in Manitoba, Canada                   

Harvey M. Chochinov, Patricia J. Martens, Heather J. Prior, Maia S. Kredentser

Using the data repository at the Manitoba Centre for Health Policy, patients with and without schizophrenia in the last six months of life were compared for usage of the health care services, including palliative care. Compared to a matched cohort, schizophrenics were over twice as likely to be in a nursing home and for over twice as long, they had more visits to general practitioners and psychiatrists but had less visits to other specialists, including palliative care and were less likely to be prescribed opioids, indicating poor end-of-life care for patients with schizophrenia.

Articles of interest in other scholarly journals.

Meta-analysis: non-steroidal anti-inflammatory drugs in biliary colic.

Colli A, Conte D, Valle SD, Sciola V, Fraquelli M.

This systematic review with meta-analysis assessed the analgesic benefits and reduction of complications, as well as the potential harms from randomised clinical trials (RCTs) evaluating non-steroid anti-inflammatory drugs (NSAIDs) in biliary colic. Eleven RCTs with over 1000 subjects were included. In comparison with placebo, patients on NSAIDs were more likely to have complete pain relief and a lower rate of complications. In comparison with other drugs, NSAIDs were more efficacious in controlling pain than spasmolytics but there was no difference between NSAIDs and opioids. The authors conclude that NSAIDs are the first-line analgesic for patients with biliary colic as they control pain with the same efficacy of opioids and also reduce complications, but acknowledge the limitation of the lack of high-quality evidence with heterogeneity in the studies.

Longitudinal assessment of symptom severity among hospitalized elders diagnosed with cancer, heart failure, and chronic obstructive pulmonary disease.

Pantilat SZ, O’Riordan DL, Dibble SL, Landefeld CS.

In a prospective cohort study the prevalence, severity, burden and predictors of common symptoms during hospitalisation and 2 weeks after discharge in patients over 65 with cancer, heart failure and chronic obstructive pulmonary disease were determined. On admission, 54% reported moderate or severe pain, 53% dyspnoea and 62% anxiety. 64% had 2 or more symptoms at a moderate or severe intensity. The prevalence of moderate or severe symptoms decreased by around 50% during admission and at the 2 week follow-up. There was no association between diagnosis and symptom severity at or during admission but at 2-weeks more patients with chronic obstructive pulmonary disease had moderate or severe pain, dyspnoea and symptom burden compared to those with cancer or heart failure.

Emergency department visits for symptoms experienced by oncology patients: a systematic review.

Vandyk AD, Harrison MB, Macartney G, Ross-White A, Stacey D.

This systematic review explored symptoms caused by cancer and its treatment at presentation to the emergency department. It included six prospective and 12 retrospective studies. 28 symptoms were reported, the most common being febrile neutropenia, infection, pain, fever, and dyspnoea, although symptoms definitions were inconsistent. 16 studies reported admission rates and showed that on average 58 % of patients were admitted to hospital. 11 studies reported mortality rates and showed an average of 13 % (in multi-symptom studies) and 20 % (in targeted symptoms studies) of emergency department presentations resulted in death.

Perspectives of patients, family caregivers and physicians about the use of opioids for refractory dyspnea in advanced chronic obstructive pulmonary disease.

Rocker G, Young J, Donahue M, Farquhar M, Simpson C.

As opioids are recommended for the treatment of refractory dyspnoea in patients with advanced chronic obstructive pulmonary disease (COPD) but not always prescribed, this Canadian study used interviews to explore the views of eight patients and 12 family caregivers as well as 28 physicians toward opioids for dyspnoea in COPD. Patients reported that opioids provided calm and relief from shortness of breath as well as improvements in their quality of life. Caregivers felt that opioids helped patients to breathe more “normally,” improved anxiety and depression, and reduced their level of stress. All patients and family caregivers wanted opioid therapy to continue. The majority of physicians were hesitant to use opioids for dyspnoea, due to a lack of knowledge and experience, as well as fears of adverse effects. The authors suggest the use of initiatives to improve the uptake of guidelines and to increase confidence in prescribing opioids for dyspnoea.

Update on combined modalities for the management of breathlessness.

Clemens KE, Faust M, Bruera E.

The evidence for combined modalities of palliative management for breathlessness is reviewed and a structure for its management is devised in this article. Although there are many trials evaluating breathlessness treatment, few of these are well designed, large prospective randomised trials combining pharmacological and non-pharmacological treatments and no trial evaluated the effects of combining treatment modalities. There are also only a few recent treatment recommendations for dyspnoea. The authors recommend the combination of opioids, anxiolytics and corticosteroids alongside physiotherapeutic treatment options and oxygen if indicated.

Topical Analgesics.

Flores MP, de Castro AP, Nascimento JD.

Topical administration of drugs may reduce side effects associated with systemically administered drugs. This article reviews the mechanisms of action and clinical efficacy of topical non-steroidal anti-inflammatory Drugs (NSAIDs), local anaesthetics, capsaicin, clonidine, tricyclic antidepressants, ketamine, opioids and cannabinoids. It reports that there is evidence to suggest benefit from topical local anaesthetics, NSAIDs and capsaicin, but little data to support the use of topical clonidine, tricyclic antidepressants, ketamine, opioids and cannabinoids. The authors suggest that studies are needed to investigate combination topical therapies.

Articles of interest in other scholarly journals

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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.