Withholding or withdrawing life-sustaining treatments in the COVID-19 pandemic: adherence to legal standards.

OBJECTIVES: In France, when the patient is unable to express his wishes, the decision to withhold or withdraw life-sustaining treatment (WWLST) is made following a collegial procedure described by a law. The aim of our study was to assess how closely this WWLST decision-making procedure in end of life patients was maintained during the COVID-19 pandemic. METHODS: This retrospective observational multicentre study compared the rate of non-compliance with WWLST decision-making procedures during the pandemic period from March to June 2020 with control period in 2019, in Clermont-Ferrand and Lyon Hospitals. Secondary objectives were to determine the factors associated with non-compliance. RESULTS: In 430 deceased patients included (176 in 2019 and 254 in 2020), the rate of non-compliance was 61.4% in 2019 and 59.1% in 2020 (p=0.63). In multivariable analysis, non-compliance was associated with immunosuppression status (OR 1.69, 95% CI (1.12 to 2.54), p=0.01) but was lower in intensive care unit (OR 0.54, 95% CI (0.36 to 0.82), p=0.003) and when the patient had visits from relatives (OR 0.41, 95% CI (0.22 to 0.75), p=0.004). CONCLUSION: In France, more than half of WWLST decisions do not comply with the law. The COVID-19 pandemic did not increase this non-compliance rate. Further studies are needed for a better understanding of the mechanisms underlying non-compliance with WWLST decision-making procedure. TRIAL REGISTRATION NUMBER: NCT04452487.

Incidence and risk factors of prolonged grief in relatives of patients with terminal cancer in French palliative care units: The Fami-Life multicenter cohort study.

OBJECTIVES: Psychological consequences of grief among relatives are insufficiently known. We reported incidence of prolonged grief among relatives of deceased patients with cancer. METHODS: Prospective cohort study of 611 relatives of 531 patients with cancer hospitalized for more than 72 hours and who died in 26 palliative care units was conducted. The primary outcome was prolonged grief in relatives 6 months after patient death, measured with the Inventory Complicated Grief (ICG > 25, range 0-76, a higher score indicates more severe symptoms) score. Secondary outcomes in relatives 6 months after patient death were anxiety and depression symptoms based on Hospital Anxiety and Depression Scale (HADS) score (range 0 [best]-42 [worst]), higher scores indicate more severe symptoms, minimally important difference 2.5. Post-traumatic stress disorder symptoms were defined by an Impact Event Scale-Revised score >22 (range 0-88, a higher score indicates more severe symptoms). RESULTS: Among 611 included relatives, 608 (99.5%) completed the trial. At 6 months, significant ICG scores were reported by 32.7% relatives (199/608, 95% CI, 29.0-36.4). The median (interquartile range ICG score) was 20.0 (11.5-29.0). The incidence of HADS symptoms was 87.5% (95% CI, 84.8-90.2%) at Days 3-5 and 68.7% (95% CI, 65.0-72.4) 6 months after patient's death, with a median (interquartile range) difference of -4 (-10 to 0) between these 2 time points. Improvement in HADS anxiety and depression scores were reported by 62.5% (362/579) relatives. SIGNIFICANCE OF RESULTS: These findings support the importance of screening relatives having risk factors of developing prolonged grief in the palliative unit and 6 months after patient's death.

The effects of foot reflexology on symptoms of discomfort in palliative care: a feasibility study.

BACKGROUND: In palliative care, the relief of discomfort is sought by an overall approach, combining prescribed medication and additional therapies, such as foot reflexology (FR). The main objective of this study was to assess the feasibility of FR in a population of inpatients in a palliative care unit (PCU).The precariousness of the patients led us to perform a feasibility study and not a cohort study from the outset. Its secondary objective was to assess the impact of an FR session on some symptoms of discomfort (anxiety, pain, troubled sleep, and psychological distress). METHODS: This is a feasibility study designed as a randomized controlled two-arm therapeutic trial. One arm tested FR, the other an active control, massage therapy (MT). The evaluators were blinded. RESULTS: FR was feasible for 14 patients out of the 15 included in the FR group (95% CI [68%; 100%]). These patients were in the palliative care phase of cancer, motor neuron disease, or terminal organ failure. Concerning the symptoms of discomfort, ESAS sleep quality score was on average 3.9 (± 2.5) before a session in the FR group. It was improved to an average of 3 (± 2.3) on the day after the session (effect-size = 0.38 [0.03; 0.73]). CONCLUSION: This study confirms the feasibility of an FR session for patients hospitalized in a PCU. It resulted in a slight improvement in sleep quality. For other discomfort symptoms such as anxiety, pain and distress, FR yielded a non-significant improvement. Significant results would have needed a larger cohort.

Prevalence of Opioid Use Disorder among Patients with Cancer-Related Pain: A Systematic Review.

BACKGROUND: The opioid use disorder is an international public health problem. Over the past 20 years it has been the subject of numerous publications concerning patients treated for chronic pain other than cancer-related. Patients with cancer-related pain are also at risk of opioid use disorder. The primary objective of this literature review was to determine the prevalence of opioid use disorder in patients with cancer-related chronic pain. Its secondary objective was to identify the characteristics of these opioid users. METHODS: This is a literature review of studies published over the last twenty years, from 1 January 2000 to 31 December 2020 identified by searching the three main medical databases: Pubmed, Cochrane, and Embase. A meta-analysis took account of between and within-study variability with the use of random-effects models estimated by the DerSimonian and Laird method. RESULTS: The prevalence of opioid use disorder was 8% (1-20%) and of the risk of use disorder was 23.5% (19.5-27.8%) with I2 values of 97.8% and 88.7%, respectively. CONCLUSIONS: Further studies are now needed on the prevalence of opioid use disorder in patients treated for cancer-related chronic pain. A screening scale adapted to this patient population is urgently needed.

The Prevalence of Off-label Prescribing of Transmucosal Immediate-Release Fentanyl in France.

CONTEXT: The abuse of opioids and opioid-related harms, including deaths, in the United States are well documented. In the European Union, opioid use has also been increasing, particularly of fentanyl. OBJECTIVE: We assessed the prevalence of off-label prescribing of transmucosal immediate-release fentanyl (TIRF), in France, in 2019. We looked at the patients' and prescribers' characteristics and compared the population of patients who received TIRF in off-label prescriptions with those taking it on-label. We also examined the differences between the patients with and without cancer in the off-label use population. METHODS: This was a population-based cross-sectional study conducted in 2019, using the French national insurance claims database Système National d'Informations Inter-Régimes de l'Assurance Maladie, covering 98.8% of the French population, or 66 million people. RESULTS: We selected 224,000 patients with fentanyl prescriptions. Among them, 23,209 had at least one TIRF delivered. The median age was 71 years (59-85) and most patients were female (55.8%). The prevalence of off-label prescribing of TIRF was 51.8% (n = 12,031), corresponding to 9827 patients not diagnosed with cancer. The three main pharmaceutical TIRF specialties prescribed in two groups were Abstral, Pecfent, and Instanyl. Overall, TIRF was mainly prescribed by private general practitioners (64.8%). CONCLUSION: The prevalence of off-label prescribing of TIRF in France is extremely high. A field survey is now needed 1) to better understand why TIRF is used in conditions not indicated in its marketing authorization, and in what clinical situations, and 2) to determine whether the benefit/risk ratio of such use is favorable.

[Opioid prescriptions in bone metastatic cancer patients: A cross sectional nationwide pharmacoepidemiological study]. / Prescription d'opioïdes pour les patients atteints de cancer avec métastases osseuses ; étude pharmaco-épidémiologique nationale transversale.

Oncological situations represent the majority of palliative situations. Labeling the palliative stage often comes too late in oncology. Pain comes first among discomfort symptoms with the greatest impact on quality of life. We wondered whether the evolutionary stage of the cancer was linked with the prescriptions of opioid analgesics. We observed the prescriptions of strong opioids in patients suffering from metastatic bone cancer 3 months before and after identifying the situation as palliative. This is a cross-sectional observational study performed between January 1, 2012 and December 31, 2016 using data from the French (nationwide claims database). We included 38,399 patients with cancer with at least one metastatic bone location in a palliative situation. Seventeen percent (n=6544) of patients had a prescription of opioid analgesics after palliative care labeling, 19.8 % (n=7606) had a prescription before, 31.1 % (n=11 949) had a prescription before and after and 32.0 % had no prescription of opioid analgesics. An increase in the dosage of opioid analgesics is observed between before and after labeling the stage of the disease as palliative with an average dosage ranging from 99.6 to 142.3mg per day. This study shows that labeling a situation as palliative affects prescriptions of strong opioid analgesics. An early identification of the situation as palliative is essential to provide appropriate care.

[Advocacy for food and wine in palliative care]. / Plaidoyer pour la nourriture et le vin en soins palliatifs.

In the palliative care unit, the care and treatment provided are aimed at optimizing the quality of life and not the quantity of life. Food is adjusted to the patient's condition and is primarily oriented towards pleasure food.

Prevention, diagnosis and management of chemotherapy-induced peripheral neuropathy: a cross-sectional study of French oncologists' professional practices.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is challenging for oncologists. Many publications mention the high incidence of CIPN and the lack of effective preventive/management strategies and robust diagnostic tools. This cross-sectional study was aimed at assessing the practice of French oncologists for CIPN prevention, diagnosis and management. METHODS: This web-based survey was sent to French oncologists by the regional cancer networks. Incidence and impact of CIPN were assessed using visual analogue scales (VAS) and diagnostic strategies were recorded. Also recorded were the drugs used to prevent or manage CIPN and their perceived efficacy and safety (VAS). RESULTS: Among the 210 oncologists included, the perceived incidence of CIPN was about 36.2 ± 22.1% of patients. About 99.5% of oncologists declared that they assess CIPN during medical follow-up. The use of drugs to prevent CIPN was reported by 9.6% of oncologists (group B vitamins (35.0%) and calcium and magnesium infusion (25.0%)). In the case of CIPN, the therapeutic adjustment of neurotoxic anticancer drugs is performed by 99.0% of oncologists (chemotherapy change (49.8%), dose reduction (30.9%) or interruption (19.3%)). The pharmacological management of CIPN was declared by 72.9% of oncologists. The main drugs used are pregabalin (75.8%), amitriptyline (32.7%) and gabapentin (25.5%). Duloxetine (ASCO recommendation) is used by only 11.8% of oncologists. CONCLUSION: Oncologists were clearly aware of CIPN risks, but its incidence tended to be underestimated and the ASCO recommendations for the management of CIPN were not followed. The prevention, diagnosis and management of CIPN remain problematic in clinical practice in France. TRIAL REGISTRATION: ClinicalTrials.gov : NCT03854864.

Impact of advance directives on the variability between intensivists in the decisions to forgo life-sustaining treatment.

BACKGROUND: There is wide variability between intensivists in the decisions to forgo life-sustaining treatment (DFLST). Advance directives (ADs) allow patients to communicate their end-of-life wishes to physicians. We assessed whether ADs reduced variability in DFLSTs between intensivists. METHODS: We conducted a multicenter, prospective, simulation study. Eight patients expressed their wishes in ADs after being informed about DFLSTs by an intensivist-investigator. The participating intensivists answered ten questions about the DFLSTs of each patient in two scenarios, referring to patients' characteristics without ADs (round 1) and then with (round 2). DFLST score ranged from 0 (no-DFLST) to 10 (DFLST for all questions). The main outcome was variability in DFLSTs between intensivists, expressed as relative standard deviation (RSD). RESULTS: A total of 19,680 decisions made by 123 intensivists from 27 ICUs were analyzed. The DFLST score was higher with ADs than without (6.02 95% CI [5.85; 6.19] vs 4.92 95% CI [4.75; 5.10], p < 0.001). High inter-intensivist variability did not change with ADs (RSD: 0.56 (round 1) vs 0.46 (round 2), p = 0.84). Inter-intensivist agreement on DFLSTs was weak with ADs (intra-class correlation coefficient: 0.28). No factor associated with DFLSTs was identified. A qualitative analysis of ADs showed focus on end-of-life wills, unwanted things and fear of pain. CONCLUSIONS: ADs increased the DFLST rate but did not reduce variability between the intensivists. In the decision-making process using ADs, the intensivist's decision took priority. Further research is needed to improve the matching of the physicians' decision with the patient's wishes. Trial registration ClinicalTrials.gov Identifier: NCT03013530. Registered 6 January 2017; https://clinicaltrials.gov/ct2/show/NCT03013530 .

The Fami-life study: protocol of a prospective observational multicenter mixed study of psychological consequences of grieving relatives in French palliative care units on behalf of the family research in palliative care (F.R.I.P.C research network).

BACKGROUND: Grieving relatives can suffer from numerous consequences like anxiety, depression, post-traumatic stress disorder (PTSD) symptoms, and prolonged grief. This study aims to assess the psychological consequences of grieving relatives after patients' death in French palliative care units and their needs for support. METHODS: This is a prospective observational multicenter mixed study. Relatives of adult patients with a neoplasia expected to be hospitalized more than 72 h in a palliative care unit for end-of-life issues will be included within 48 h after patient admission. End-of-life issues are defined by the physician at patient admission. Relatives who are not able to have a phone call at 6-months are excluded. The primary outcome is the incidence of prolonged grief reaction defined by an ICG (Inventory Complicate Grief) > 25 (0 best-76 worst) at 6 months after patient' death. Prespecified secondary outcomes are the risk factors of prolonged grief, anxiety and depression symptoms between day 3 and day 5 and at 6 months after patients' death based on an Hospital Anxiety and Depression score (range 0-42) > 8 for each subscale (minimal clinically important difference: 2.5), post-traumatic stress disorder symptoms 6 months after patient' death based on the Impact of Events Scale questionnaire (0 best-88 worst) score > 22, experience of relatives during palliative care based on the Fami-Life questionnaire, specifically built for the study. Between 6 and 12 months after the patient's death, a phone interview with relatives with prolonged grief reactions will be planned by a psychologist to understand the complex system of grief. It will be analyzed with the Interpretative Phenomenological Analysis. We planned to enroll 500 patients and their close relatives assuming a 25% prolonged grief rate and a 6-month follow-up available in 60% of relatives. DISCUSSION: This study will be the first to report the psychological consequences of French relatives after a loss of a loved one in palliative care units. Evaluating relatives' experiences can provide instrumental insights for means of improving support for relatives and evaluation of bereavement programs. TRIAL REGISTRATION: NCT03748225 registered on 11/19/2018. Recruiting patients.

[Chemotherapy-induced peripheral neuropathy: Symptomatology and epidemiology]. / Neuropathies périphériques chimio-induites : symptomatologie et épidémiologie.

Chemotherapy-induced peripheral neuropathy (CIPN) is common with specific semiological characteristics. When CIPN appears, there are many difficulties in guaranteeing sustained treatment, especially with optimal protocol. Moreover, CIPN have bad repercussions on quality of life after cancer disease. In this article, we have achieved a current state of CIPN and try to report details about semiological characteristics and topography. We have also produced some epidemiological data. Nonetheless, we have not voluntarily introduced treatment because it will be the topic of further work.

Reasons for transferral to emergency departments of terminally ill patients - a French descriptive and retrospective study.

BACKGROUND: Patients under palliative care and in hospital-at-home services are frequently transferred to emergency departments. We set out to identify the reasons for these presentations to determine the proportion that might be avoidable. METHODS: We conducted a retrospective study by assessment of patient files. We studied admissions to four emergency departments in an area of France (Puy-de-Dôme) between September 2011 and August 2013. Reasons for transfer and diagnostic conclusion by emergency doctors were noted. We collected date of admission, time spent, investigations and treatments performed and patients' outcomes after the medical conclusions. We also determined whether patients called the hospital-at-home service before going to the emergency department. From these data we discerned potentially avoidable and unavoidable consultations. RESULTS: We identified 52 transfers of patients from home to emergency departments. The most frequent reasons were: generalized weakness (11 cases), social isolation (8 cases) and end of life (7 cases). For 58 % of presentations, the investigations and treatments performed did not require presentation to an emergency department; 34 % of patients returned home after the visit, 41 % remained for simple observation and 20 % remained to receive special care. Two patients died in the emergency department. In 86 % of cases, presentations occurred when primary care was less readily available, and patients called home care services in only 42 % of cases before going to emergency departments. CONCLUSIONS: Half of the transfers to emergency departments were potentially avoidable for terminally ill patients in home care. To reduce this proportion we need to promote access to primary care, educate patients in hospital-at-home service and train care-givers and doctors in palliative medicine.

[The "wine bar", or a different way of caring]. / Le "bar à vin" ou une autre façon de prendre soin.

The "wine bar" in the palliative care unit of Clermont-Ferrand general hospital is an example of a different way of providing care. It defends the right of patients at the end of life to treat themselves and others. Acknowledging that life is present right up until the end, patients are invited to drink wine at mealtimes and caregivers are encouraged to learn the basics of oenology.

[Consultations in oncological supportive care mono-, multi-, ou interdisciplinary: What should we favour?]. / Consultations en soins de support oncologiques mono-, multi-, ou interdisciplinaires : que privilégier ?

According to the point 7.6 and 7.7 of the Cancer Plan 2014, all cancer patients should have access to supportive care. Indeed, the supportive care consultation in oncology is an important tool for the symptom management of cancer patients at all times of treatment. This consultation can be mono-disciplinary or multi-disciplinary (with different professions: physician, nurse, psychologist, social service assistant…) with or without integration (multidisciplinary or interdisciplinary). There are few studies focusing on the types of consultations (mono- or multidisciplinary) to promote based on their expected outcomes. After describing the different types of consultations (initial, follow-up, unscheduled, discharge) and having highlighted the main issues of these consultations, we will present the possible configurations. Our discussion will concern then the advantages and disadvantages of monodisciplinarity and different types of multidisciplinary highlighting the possible improvements. At the end of this work, after a brief synthesis of the different outcomes associated with each type of consultation, we would like to discuss the type of consultation to choose according to the outcomes.

Characteristics of the neuropathy induced by thoracotomy: a 4-month follow-up study with psychophysical examination.

OBJECTIVES: To explore the role of neuropathy in persistent pain after thoracotomy, combining a clinical follow-up and a psychophysical examination of the operated area. METHODS: Seventy-three patients were followed and examined at their discharge from hospital, 6 weeks and 4 months after pneumonectomy under thoracotomy. Spontaneous and evoked pain was assessed by clinical examination, a 7-day pain score, and the Neuropathic Pain Symptom Inventory. At the fourth month follow-up, pain and tolerance thresholds to pinprick, heat, and warm sensation threshold were measured on both sides of the thorax. RESULTS: The rate of spontaneous pain was 40% at discharge and went up to 59% at the sixth week follow-up. Evoked pain was rare at discharge (11%), most cases appearing at the sixth week follow-up (47%). The evolution profiles of pain between the sixth week and the fourth month follow-up were heterogeneous with a tendency to decrease. Young age, female sex, and spontaneous pain observed at discharge from hospital were identified as early predictive factors of spontaneous pain persisting at the fourth month follow-up. On the side of operation, thresholds tended to increase for warm and hot stimuli, and to decrease for mechanical stimuli. At the fourth month follow-up, spontaneous pain and evoked pain were associated to static hyperalgesia, persisting hypoesthesia, low mechanical thresholds, altered sensation of heat, and impaired quality of life. DISCUSSION: Peripheral neuropathy is common after thoracotomy, with variant characteristics, ranging from subclinical disturbances to severe pain. The process seems to develop between the discharge from hospital and the sixth week after thoracotomy.

A prospective study of neuropathic pain induced by thoracotomy: incidence, clinical description, and diagnosis.

This study evaluated prospectively the incidence of neuropathic pain after thoracotomy, described its clinical characteristics, and delineated landmarks for its diagnosis in daily practice. We evaluated clinically painful symptoms and sensory deficits in 54 patients after lateral/posterolateral thoracotomy for broncho-pulmonary carcinoma with standardized surgical and analgesic procedures. At 2months, 49 patients suffered from non malignant thoracic pain, and at 6months 38 patients (loss to follow-up for 7) reported persisting pain. In 35 patients, painful symptoms and sensory deficits could be evaluated using a standardized clinical bedside procedure. According to the grading system proposed by Treede et al. [41], neuropathic pain was considered probable in 21 patients, while use of the DN4 questionnaire concluded that neuropathic pain was probable in 17 patients. The two diagnostic procedures provided similar conclusions in 16 patients. Morphine consumption during the early post-operative period (mean 111.3±30.8mg/day) and pain intensity (VAS: mean 5.71±2.1) were significantly higher in patients suffering from neuropathic pain than in other patients with pain (mean 80±21.4mg/day; VAS: mean 3.9±2.4). The clinical picture in most patients with neuropathic pain included electric shocks and severe multimodal hypoesthesia in the sensory area of 5th/6th intercostal nerves. Thus, our results indicate a minimal incidence of chronic post-thoracotomy pain at 70% and that of neuropathic pain at 29%, this latter being clinically suggested by a combination of certain symptoms and reinforced by the DN4 questionnaire when sensory deficit at scar is present.

Perioperative ketamine does not prevent chronic pain after thoracotomy.

Thoracotomy is often responsible for chronic pain, possibly of neuropathic origin. To confirm preclinical studies, the preventive effects of perioperative ketamine were tested in a randomized, double-blind, placebo-controlled clinical trial on persistent neuropathic pain after thoracotomy. Eighty-six patients scheduled for thoracotomy under standardised general anaesthesia were randomised to receive either ketamine (1 mg kg(-1) at the induction, 1 mg kg(-1) h(-1) during surgery, then 1 mg kg(-1) during 24 h; n=42) or normal saline (n=44). Postoperative analgesia included a single dose of intrapleural ropivacaine, intravenous paracetamol and nefopam, and patient-controlled intravenous morphine. Vital parameters and analgesia were recorded during the 48 first postoperative hours. Seventy-three patients were followed up. The patient's chest was examined 1-2 weeks, 6 weeks and 4 months after surgery. At the last two observations, spontaneous pain score over a one-week period (visual analogue scale), neuropathic pain score (NPSI), and intake of analgesics, were assessed. No drug affecting neuropathic pain (except opiates) was given during the follow-up. Two patients in each group were lost to follow-up after the 6 week visit. Ketamine improved immediate postoperative pain, but the groups were similar in terms of neuropathic pain and intake of analgesics, 6 weeks (NPSI score: ketamine: 1.25 [0-4.125]; placebo: 1 [0-4]) and 4 months after surgery. Thus, ketamine given in 24-h infusion failed to prevent chronic neuropathic pain after thoracotomy. Other perioperative preventive long-lasting treatments or techniques could be tested in this context.

[Non pharmacologic treatment of neuropathic pain]. / Traitements non médicamenteux de la douleur neuropathique.

Nondrug treatments of neuropathic pain should always begin at the same time as pharmacologic treatment. There are three types of nondrug treatment for neuropathic pain: physical, surgical, and "psychocorporal" and psychotherapeutic treatment. Transcutaneous electrical nerve stimulation (TENS) is a simple physical treatment that strengthens local inhibitory controls and is indicated in focal neuropathic pain when upstream stimulation is possible for a superficial sensitive nerve trunk. Destructive surgery is represented today by "DREZotomy", destruction of nociceptive fibers and their dorsal root entry zones. It is indicated essentially in intractable pain due to plexus avulsion. Functional surgery is implanted electric stimulation--either spinal or central (encephalic)--of structures that exert inhibitory control on the pain pathways. Spinal stimulation is performed at the level of the posterior spinal cord and is indicated essentially in segmental mononeuropathies refractory to drug treatment. Central stimulation is performed at the motor cortex and is indicated for refractory central pain. "Psychocorporal" techniques (relaxation, sophrology, hypnosis) are useful to reduce anxiety and neurovegetative hypertonicity, both factors that aggravate neuropathic pain.