Report of the National Advisory Committee on Palliative Care

Over thirty years ago, Prof. John Hinton voiced his criticisms of the standard of medical care offered to patients with advanced and life-threatening conditions. In the decades that followed, we have witnessed a remarkable renaissance in terms of our understanding of the needs of patients in the final stages of life. Developments in therapeutics and in our knowledge of pain and symptom management have spearheaded a quiet but very effective revolution. In parallel with developments in medical science, we have developed a much deeper understanding of the complex psychosocial and spiritual needs of patients and their families, as they seek to cope with the pain and suffering associated with progressive and inevitable loss Download the Report here

Treatment of symphysitis pubis with one unique iv injection of Ibandronate: report of two cases

Objective: Osteitis pubis is a noninfectious painful inflammatorydisorder of the symphysis pubis. Etiologic factors are numerous, themost common are: osseous extension of adductor, enthesis due tosport overuse, irritation after urological and abdominal procedures,and systemic inflammatory disorders in particularspondylarthropathies. Many cases are idiopathic. The symptomsconsist of regional chronic mechanical and sometime nocturnal pain.Diagnosis is usually confirmed by either bone scintigraphy or by MRI.There are no standard treatments but conservative approachesincluding rest and NSAIDS are generally recommended. In 2001, agood clinical and radiological response of three refractory cases with3 to 6 monthly perfusions of pamidronate was reported [1].Ibandronate is a much more powerful and long-lasting bisphosphonatethan pamidronate, and has not yet been reported in literature to ourknowledge in this indication.Patients and Methods: We present two cases of idiopathic origin:one woman (63 years old) and one man (36 years old).The symptomswere present >3 months in the first patient and one year in the second.The diagnosis was confirmed by MRI which showed bone edemaon both sizes of symphysis and in the second case bony erosionsadjacent to the joint were seen. Both cases failed to respond toconservative measures. Both patients received one single direct ivInjection of 3 mg of Ibandronate.Results: The injections resulted in a rapid (within a few days)resolution of pain that lasted more than 6 months in both patients.No side effects were observed. In the first case, an isotope bone scanperformed 4 months after the injection showed no residual uptake. Thesecond patient had a repeated MRI after 6 months. It demonstrated anattenuation of bone edema compared to the first MRI.Conclusion: IV Ibandronate may constitute a safe and effectivetreatment option for patients with refractory osteitis pubis.References1 Maksymowych WP, Aaron SL, Russell AS. Treatment of refractorysymphysitis pubis with intravenous pamidronate. J Rheumatol.2001;28(12):2754, 2001.

An international, randomized, double-blind, placebo-controlled, phase III trial of pregabalin monotherapy in treatment of patients with fibromyalgia.

OBJECTIVE: To evaluate the efficacy and safety of pregabalin monotherapy versus placebo for symptomatic pain relief and improvement of patient global assessment in patients with fibromyalgia (FM) enrolled from countries outside the United States. METHODS: This international, multicenter, double-blind, placebo-controlled trial randomly assigned 747 patients with FM to placebo or 300, 450, or 600 mg/day pregabalin twice daily for 14 weeks. Primary efficacy measures were endpoint mean pain scores and Patient Global Impression of Change (PGIC). Secondary outcomes included assessments of sleep and function. RESULTS: Patients in the 450 mg/day pregabalin group showed significant improvements versus placebo in endpoint mean pain score (-0.56; p = 0.0132), PGIC (73% improved vs 56% placebo; p = 0.0017), and function [Fibromyalgia Impact Questionnaire (FIQ) total score -5.85; p = 0.0012]. PGIC was also significant for 600 mg/day pregabalin (69% improved; p = 0.0227). Results for these endpoints were nonsignificant for pregabalin at 300 mg/day and for pain and FIQ score at 600 mg/day. Early onset of pain relief was seen, with separation from placebo detected by Week 1 in all pregabalin groups. All pregabalin doses demonstrated superiority to placebo on the Medical Outcomes Study-Sleep Scale Sleep Disturbance subscale and the Sleep Quality diary. Dizziness and somnolence were the most frequently reported adverse events. CONCLUSION: Pregabalin demonstrated modest efficacy in pain, global assessment, and function in FM at 450 mg/day, and improved sleep across all dose levels, but it did not provide consistent evidence of benefit at 300 and 600 mg/day in this study. Pregabalin was generally well tolerated for the treatment of FM. (Clinical trial registry NCT00333866).

Analgesic and anti-inflammatory activity of the aqueous extract of Rheedia longifolia Planch & Triana

Rheedia longifolia Planch et Triana belongs to the Clusiaceae family. This plant is widely distributed in Brazil, but its chemical and pharmacological properties have not yet been studied. We report here that leaves aqueous extract of R. longifolia (LAE) shows analgesic and anti-inflammatory effects. Oral or intraperitoneal administration of this extract dose-dependently inhibited the abdominal constrictions induced by acetic acid in mice. The analgesic effect and the duration of action were similar to those observed with sodium diclofenac, a classical non-steroidal analgesic. In addition to the effect seen in the abdominal constriction model, LAE was also able to inhibit the hyperalgesia induced by lipopolysaccharide from gram-negative bacteria (LPS) in rats. We also found that R. longifolia LAE inhibited an inflammatory reaction induced by LPS in the pleural cavity of mice. Acute toxicity was evaluated in mice treated with the extract for seven days with 50 mg/kg/day. Neither death, nor alterations in weight, blood leukocyte counts or hematocrit were noted. Our results suggest that aqueous extract from R. longifolia leaves has analgesic and anti-inflammatory activity with minimal toxicity and are therefore endowed with a potential for pharmacological control of pain and inflammation.

Anti-inflammatory and anti-nociceptive effects of Zeyheria montana (Bignoniaceae) ethanol extract

In this work, the analgesic and anti-inflammatory activities of Zeyheria montana Mart. ethanol leaf extract were investigated at doses of 75, 150 and 300 mg/kg body weight. In the analgesic assay, against a chemical stimulus in mice, acetic acid-induced writhes were significantly inhibited by the extract at doses of 75 mg/kg (67.27%), 150 mg/kg (49.38%) and 300 mg/kg (82.87%). Also, a vigorous decrease in hyperalgesia was observed when measured after 2 h and 6 h of lipopolysaccharide stimulation of rats for all doses of extract tested. Z. montana extract, at doses of 75 and 300 mg/kg, caused very slight central analgesia in rats submitted to thermal stimulus, particularly noticeable at 30 min following treatment. The anti-inflammatory activity of Z. montana extract on carrageenan-induced oedema in rats was evaluated. The oedema development, measured at 180 min following carrageenan intraplantar injection, was significantly reduced by all tested doses: 75 mg/kg (33.30%), 150 mg/kg (45.80%) and 300 mg/kg (75.00%). The LD50 value was greater than 2000 mg/kg. These results demonstrated that the ethanol extract from Z. montana leaf possesses anti-nociceptive and anti-inflammatory activities, which could be of relevance for the pharmacological control of pain and inflammatory processes.

Suture repair of umbilical hernia during caesarean section: a case-control study.

PURPOSE: The objective of this study was to investigate the additional burdens in terms of pain, prolongation of surgery and morbidity which is added to elective caesarean section if umbilical hernia suture repair is performed simultaneously. Secondly, patient's satisfaction and hernia recurrence rate were assessed. METHODS: Consecutive women with symptomatic umbilical hernia undergoing internal or external suture repair during elective caesarean were included in this retrospective cohort-control study. Data on post-operative pain, duration of surgery and morbidity of a combined procedure were collected. These patients were matched 1:10 to women undergoing caesarean section only. Additionally, two subgroups were assessed separately: external and internal suture hernia repair. These subgroups were compared for patient's satisfaction, cosmesis, body image and recurrence rate. RESULTS: Fourteen patients with a mean age of 37 years were analysed. Internal suture repair (n = 7) prolonged caesarean section by 20 min (p = 0.001) and external suture repair (n = 7) by 34 min (p < 0.0001). Suture repair did not increase morphine use (0.38 ± 0.2 vs. 0.4 ± 02 mg/kg body weight), had no procedure-related morbidity and prolonged hospitalization by 0.5 days (p = 0.01). At a median follow-up of 37 (5-125) months, two recurrences in each surgical technique, internal and external suture repair, occurred (28 %). Body image and cosmesis score showed a higher level of functioning in internal suture repair (p = 0.02; p = 0.04). DISCUSSION: Despite a high recurrence rate, internal suture repair of a symptomatic umbilical hernia during elective caesarean section should be offered to women if requested. No additional morbidity or scar is added to caesarean section. Internal repair is faster, and cosmetic results are better, additional skin or fascia dissection is avoided, and it seems to be as effective as an external approach. Yet, women must be informed on the high recurrence rate.

Non-pharmacological interventions for chronic pain in people with spinal cord injury.

BACKGROUND: Chronic pain is frequent in persons living with spinal cord injury (SCI). Conventionally, the pain is treated pharmacologically, yet long-term pain medication is often refractory and associated with side effects. Non-pharmacological interventions are frequently advocated, although the benefit and harm profiles of these treatments are not well established, in part because of methodological weaknesses of available studies. OBJECTIVES: To critically appraise and synthesise available research evidence on the effects of non-pharmacological interventions for the treatment of chronic neuropathic and nociceptive pain in people living with SCI. SEARCH METHODS: The search was run on the 1st March 2011. We searched the Cochrane Injuries Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), four other databases and clinical trials registers. In addition, we manually searched the proceedings of three major scientific conferences on SCI. We updated this search in November 2014 but these results have not yet been incorporated. SELECTION CRITERIA: Randomised controlled trials of any intervention not involving intake of medication or other active substances to treat chronic pain in people with SCI. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias in the included studies. The primary outcome was any measure of pain intensity or pain relief. Secondary outcomes included adverse events, anxiety, depression and quality of life. When possible, meta-analyses were performed to calculate standardised mean differences for each type of intervention. MAIN RESULTS: We identified 16 trials involving a total of 616 participants. Eight different types of interventions were studied. Eight trials investigated the effects of electrical brain stimulation (transcranial direct current stimulation (tDCS) and cranial electrotherapy stimulation (CES); five trials) or repetitive transcranial magnetic stimulation (rTMS; three trials). Interventions in the remaining studies included exercise programmes (three trials); acupuncture (two trials); self-hypnosis (one trial); transcutaneous electrical nerve stimulation (TENS) (one trial); and a cognitive behavioural programme (one trial). None of the included trials were considered to have low overall risk of bias. Twelve studies had high overall risk of bias, and in four studies risk of bias was unclear. The overall quality of the included studies was weak. Their validity was impaired by methodological weaknesses such as inappropriate choice of control groups. An additional search in November 2014 identified more recent studies that will be included in an update of this review.For tDCS the pooled mean difference between intervention and control groups in pain scores on an 11-point visual analogue scale (VAS) (0-10) was a reduction of -1.90 units (95% confidence interval (CI) -3.48 to -0.33; P value 0.02) in the short term and of -1.87 (95% CI -3.30 to -0.45; P value 0.01) in the mid term. Exercise programmes led to mean reductions in chronic shoulder pain of -1.9 score points for the Short Form (SF)-36 item for pain experience (95% CI -3.4 to -0.4; P value 0.01) and -2.8 pain VAS units (95% CI -3.77 to -1.83; P value < 0.00001); this represented the largest observed treatment effects in the included studies. Trials using rTMS, CES, acupuncture, self-hypnosis, TENS or a cognitive behavioural programme provided no evidence that these interventions reduce chronic pain. Ten trials examined study endpoints other than pain, including anxiety, depression and quality of life, but available data were too scarce for firm conclusions to be drawn. In four trials no side effects were reported with study interventions. Five trials reported transient mild side effects. Overall, a paucity of evidence was found on any serious or long-lasting side effects of the interventions. AUTHORS' CONCLUSIONS: Evidence is insufficient to suggest that non-pharmacological treatments are effective in reducing chronic pain in people living with SCI. The benefits and harms of commonly used non-pharmacological pain treatments should be investigated in randomised controlled trials with adequate sample size and study methodology.

A pilot study of delayed versus immediate serial casting after botulinum toxin injection for partially reducible spastic equinus.

BACKGROUND: Serial casting is often prescribed after botulinum toxin injections to improve joint ranges of motion and to potentiate the decrease in hypertonia. The aim of this study was to compare delayed versus immediate serial casting as an adjunct to botulinum toxin therapy for partially reducible spastic equinus. METHODS: Twelve children who presented spastic equinus associated with mild gastrosoleus contracture took part. Five of them had a diagnosis of spastic diplegia, whereas 7 had a diagnosis of congenital hemiplegia. Children were randomized to immediate serial casting (same day) or delayed serial casting (4 weeks later) after botulinum toxin injection to their gastrosolei. Casts were replaced weekly for 3 weeks. RESULTS: Three children complained of pain that required recasting in the immediate casting group versus none in the delayed casting group (P = 0.08). At 3 months, there was a 27-degree improvement in the fast dorsiflexion angle (Tardieu R1) in the delayed casting group versus 17 degrees in the immediate casting group (P = 0.029). At 6 months, a 19-degree improvement persisted in the delayed group compared with 11 degrees in the immediate group (P = 0.010). CONCLUSIONS: There is a clear benefit in delaying serial casting after the injection of botulinum toxin in the recurrence of spasticity at the gastrosoleus that may also offer an advantage regarding the incidence of painful episodes associated with casting. Most importantly, reducing the recurrence of spasticity by delayed serial casting may offer the possibility of decreasing the frequency of botulinum toxin reinjections.

Breakthrough cancer pain - still a challenge.

Breakthrough cancer pain is defined as transient pain exacerbation in patients with stable and controlled basal pain. Although variable, the prevalence of breakthrough cancer pain is high (33%-95%). According to the American Pain Foundation, breakthrough pain is observed in 50%-90% of all hospitalized cancer patients, in 89% of all patients admitted to homes for the elderly and terminal-patient care centers, and in 35% of all ambulatory care cancer patients. The management of breakthrough cancer pain should involve an interdisciplinary and multimodal approach. The introduction of new fentanyl formulations has represented a great advance and has notably improved treatment. Among these, the pectin-based intranasal formulation adjusts very well to the profile of breakthrough pain attacks, is effective, has a good toxicity profile, and allows for convenient dosing - affording rapid and effective analgesia with the added advantage of being easily administered by caregivers when patients are unable to collaborate.

Wandering, verbally and physically abusive behaviour and their relation with pain in nursing homes residents

Backgrounds:¦Behavioural and psychological symptoms of dementia (BPSD) include, among others, hallucinations, delusions, depression, euphoria, agitation, aggression, sexual desinhibition, sleep disturbances, and apathy (1). To our knowledge, surprisingly few studies looked into the possible association between pain and BPSD in nursing home residents. Given this dearth of studies, we wondered whether or not there is an association, in nursing home residents, between pain and BPSD, in particular wandering as well as verbally and physically abusive behaviour, and whether or not this possible association changes with the degree of cognitive impairment.¦Method:¦All nursing home residents in the three Swiss cantons Aargau, Basel-City, and Solothurn (corresponding to 13.5%¦of the total Swiss population) receive a Resident Assessment Instrument Minimum Data Set (RAI-MDS)¦assessment within the first two weeks upon entry. This yielded a total sample of 16'430 nursing home residents considering that the residents' assessment took place between 1997 and 2007 and that we only took into account the admission RAI-MDS assessment. Only residents for whom data on pain was recorded were included in the study (n = 16'183).¦Results:¦Wandering correlated significantly with pain although the effect size was small (Spearman correlation coefficient = 0.052; p = 0.000), a result very similar to that found for VAB (Spearman correlation coefficient = 0.034; p = 0.000) and PAB (Spearman correlation coefficient = 0.043; p = 0.000). Likewise, using linear regression analyses, pain was very significantly associated with any of the three BPSD considered, but it predicted astonishingly little of the¦variance observed (wandering: B = 0.036; p = 0.000; R2 = 0.002; VAB: B = 0.021; p = 0.000; R2 = 0.001 PAB: B = 0.012; p = 0.000; R2 = 0.001). The interaction of pain and cognition had a significant effect on the three BPSD, suggesting that cognition was a moderator of the relationship between pain and all three behaviours.¦Conclusion:¦Wandering behaviours, VAB and PAB seem to be predicted by many factors. Although pain predicts only a small part of variance of these behaviours, it still remains important to recognise and treat pain in order to reduce these behaviours at least a little both in intensity and frequency. Given the dearth of studies and their somewhat contradictory results, further studies ought to investigate the role, the type and localisation of pain might play on the expression of different BPSD or how residents suffering from dementia perceive pain.

Factors associated with chronic pain in patients with bipolar depression: a cross-sectional study.

BACKGROUND While pain is frequently associated with unipolar depression, few studies have investigated the link between pain and bipolar depression. In the present study we estimated the prevalence and characteristics of pain among patients with bipolar depression treated by psychiatrists in their regular clinical practice. The study was designed to identify factors associated with the manifestation of pain in these patients. METHODS Patients diagnosed with bipolar disorder (n=121) were selected to participate in a cross-sectional study in which DSM-IV-TR criteria were employed to identify depressive episodes. The patients were asked to describe any pain experienced during the study, and in the 6 weeks beforehand, by means of a Visual Analogical Scale (VAS). RESULTS Over half of the bipolar depressed patients (51.2%, 95% CI: 41.9%-60.6%), and 2/3 of the female experienced concomitant pain. The pain was of moderate to severe intensity and prolonged duration, and it occurred at multiple sites, significantly limiting the patient's everyday activities. The most important factors associated with the presence of pain were older age, sleep disorders and delayed diagnosis of bipolar disorder. CONCLUSIONS Chronic pain is common in bipolar depressed patients, and it is related to sleep disorders and delayed diagnosis of their disorder. More attention should be paid to study the presence of pain in bipolar depressed patients, in order to achieve more accurate diagnoses and to provide better treatment options.

A comparative study of two methods of surgical treatment for painful neuroma.

Painful neuromas may follow traumatic nerve injury. We carried out a double-blind controlled trial in which patients with a painful neuroma of the lower limb (n = 20) were randomly assigned to treatment by resection of the neuroma and translocation of the proximal nerve stump into either muscle tissue or an adjacent subcutaneous vein. Translocation into a vein led to reduced intensity of pain as assessed by visual analogue scale (5.8 (SD 2.7) vs 3.8 (SD 2.4); p < 0.01), and improved sensory, affective and evaluative dimensions of pain as assessed by the McGill pain score (33 (SD 18) vs 14 (SD 12); p < 0.01). This was associated with an increased level of activity (p < 0.01) and improved function (p < 0.01). Transposition of the nerve stump into an adjacent vein should be preferred to relocation into muscle.

Predictors of return to work after a knee injury in patients hospitalized in vocational rehabilitation

Introduction.- Knee injuries are frequent in a young and active population. Most of the patients resume their professional activity but few studies were interested in factors that predict a return to work. The aim of this study is to identify these predictors from a large panel of bio-psychosocial variables. We postulated that the return to work 3 months and 2 years after discharge is mostly predicted by psychosocial variables.Patients and methods.- Prospective study, patients hospitalized for a knee injury. Variables measured: the abbreviated injury score (AIS) for the gravity of the injuries, analog visual scale for the intensity of pain, INTERMED for the bio-psychosocial complexity, SF-36 for the quality of life, HADs for the anxiety/depression symptoms and IKDC score for the knee function. Univariate logistic regressions, adjusted for age and gender, were performed in order to predict return to work.Results.- One hundred and twenty-six patients hospitalized during 8 months after the accident were included into this prospective study. A total of 73 (58%) and 75 (59%) questionnaires were available after 3 months and 2 years, respectively. The SF-36 pain was the sole predictor of return to work at 3 months (odds Ratio 1.06 [1.02-1.10], P = 0.01; for a one point increase) and 2 years (odds Ratio 1.06 [1.02-1.10], P = 0.01). At three months, other factors are SF-36 (physic sub-scale), IKDC score, the presence of a work contract and the presence of litigation. The bio-psychosocial complexity, the presence of depressive symptoms predicts the return to work at two years.Discussion.- Our working hypothesis was partially confirmed: some psychosocial factors (i.e. depressive symptoms, work contract, litigation, INTERMED) predict the return to work but the physical health and the knee function, perceived by the patient, are also correlated. Pain is the sole factor isolated at both times (i.e. 3 months and 2 years) and, consequently, appears a key element in the prediction of the return to work. Some factors are accessible to the rehabilitation program but only if an interdisciplinary approach is performed.

Analysis of significant factors influencing visual acuity in ocular syphilis.

BACKGROUND: The aim of this study is to determine whether statistical associations can be demonstrated in ocular syphilis between baseline clinical and laboratory parameters with visual acuity at presentation and with any change in visual acuity after treatment. METHODS: Charts of 26 patients (42 eyes) with ocular syphilis presenting to the Uveitis clinic of the Jules-Gonin Eye Hospital were reviewed. A baseline cross-sectional analysis was performed in order to identify any association between visual acuity at presentation and demographic, clinical or laboratory parameters. After treatment, any analogy between these parameters and a change in visual acuity was subsequently assessed in a series of univariate comparisons. RESULTS: The following factors were associated with worse initial visual acuity: severity of visual field impairment at presentation (p=0.012), macular oedema (p=0.004) and optic neuropathy (p=0.031). There was a borderline association with the presence of vasculitis on fluroangiography (p=0.072). Improvement in best corrected visual acuity after treatment was significantly associated with the presence of vasculitis on fluroangiography (p=0.005), neurosyphilis, according to lumbar puncture findings (p=0.037) and marginally with anterior uveitis (p=0.070). Inflammation relapse was associated with the coexistence of pain as presenting sign (p<0.001) and with a longer duration of symptoms prior to the initial visit (p=0.023). CONCLUSIONS: Severe ocular inflammation associated with vasculitis, vitritis or anterior uveitis in ocular syphilis would appear to be a reversible phenomenon that responds well to appropriate antibiotic treatment, resulting in improvement in visual acuity. Prompt treatment enables a good visual prognosis, while any delay in therapy increases the risk of subsequent relapse.

Endometriosis: alternative methods of medical treatment.

Endometriosis is an inflammatory estrogen-dependent disease defined by the presence of endometrial glands and stroma at extrauterine sites. The main purpose of endometriosis management is alleviating pain associated to the disease. This can be achieved surgically or medically, although in most women a combination of both treatments is required. Long-term medical treatment is usually needed in most women. Unfortunately, in most cases, pain symptoms recur between 6 months and 12 months once treatment is stopped. The authors conducted a literature search for English original articles, related to new medical treatments of endometriosis in humans, including articles published in PubMed, Medline, and the Cochrane Library. Keywords included "endometriosis" matched with "medical treatment", "new treatment", "GnRH antagonists", "Aromatase inhibitors", "selective progesterone receptor modulators", "anti-TNF α", and "anti-angiogenic factors". Hormonal treatments currently available are effective in the relief of pain associated to endometriosis. Among new hormonal drugs, association to aromatase inhibitors could be effective in the treatment of women who do not respond to conventional therapies. GnRH antagonists are expected to be as effective as GnRH agonists, but with easier administration (oral). There is a need to find effective treatments that do not block the ovarian function. For this purpose, antiangiogenic factors could be important components of endometriosis therapy in the future. Upcoming researches and controlled clinical trials should focus on these drugs.