Use of metamizole and other non-opioid analgesics in Switzerland between 2014 and 2019: an observational study using a large health insurance claims database.

OBJECTIVE: To investigate claims patterns for metamizole and other non-opioid analgesics in Switzerland. To characterise users of these non-opioid analgesics regarding sex, age, comedications and canton of residence. METHODS: We conducted a retrospective descriptive study using administrative claims data of outpatient prescribed non-opioid analgesics of the Swiss health insurance company Helsana between January 2014 and December 2019. First, we evaluated the number of claims and defined daily doses  per year of metamizole, ibuprofen, diclofenac and paracetamol in adults aged 18 years or over. Second, we characterised new users of these non-opioid analgesics in terms of sex, age, claimed comedications and canton of residence. RESULTS: From 2014 to 2019, among the investigated non-opioid analgesics, metamizole showed the highest increase in claims (+9545 claims, +50%) and defined daily doses (+86,869 defined daily doses, +84%) per 100,000 adults. Metamizole users had the highest median age (62 years [IQR: 44-77]) compared to ibuprofen (47 years [IQR: 33-62]), diclofenac (57 years [IQR: 43-71]) and paracetamol (58 years [IQR: 39-75]) users. Metamizole users also more frequently claimed proton pump inhibitors, anticoagulants, platelet aggregation inhibitors and antihypertensive drugs than users of other non-opioid analgesics. While metamizole was most frequently claimed in German-speaking regions of Switzerland, ibuprofen and paracetamol were most frequently claimed in the French-speaking regions and diclofenac in German- and Italian-speaking regions. CONCLUSION: In Switzerland, metamizole was increasingly claimed between 2014 and 2019. Metamizole was most frequently claimed by older adults and patients with comedications suggestive of underlying conditions, which can be worsened or caused by use of nonsteroidal anti-inflammatory drugs. The lack of studies regarding the effectiveness and safety of metamizole in this population warrants further investigation.

Palliative sedation - revised recommendations.

Palliative sedation is defined as the monitored use of medications intended to induce a state of decreased or absent awareness (unconsciousness) to relieve the burden of otherwise intractable suffering in a manner ethically acceptable to the patient, their family, and healthcare providers. In Switzerland, the prevalence of continuous deep sedation until death increased from 4.7% in 2001 to 17.5% of all deceased in 2013, depending on the research method used and on regional variations. Yet, these numbers may be overestimated due to a lack of understanding of the term "continuous deep sedation" by for example respondents of the questionnaire-based study. Inadequately trained and inexperienced healthcare professionals may incorrectly or inappropriately perform palliative sedation due to uncertainties regarding its definitions and practice. Therefore, the expert members of the Bigorio group and the authors of this manuscript believe that national recommendations should be published and made available to healthcare professionals to provide practical, terminological, and ethical guidance. The Bigorio group is the working group of the Swiss Palliative Care Society whose task is to publish clinical recommendations at a national level in Switzerland. These recommendations aim to provide guidance on the most critical questions and issues related to palliative sedation. The Swiss Society of Palliative Care (palliative.ch) mandated a writing board comprising four clinical experts (three physicians and one ethicist) and two national academic experts to revise the 2005 Bigorio guidelines. A first draft was created based on a narrative literature review, which was internally reviewed by five academic institutions (Lausanne, Geneva, Bern, Zürich, and Basel) and the heads of all working groups of the Swiss Society of Palliative Care before finalising the guidelines. The following themes are discussed regarding palliative sedation: (a) definitions and clinical aspects, (b) the decision-making process, (c) communication with patients and families, (d) patient monitoring, (e) pharmacological approaches, and (f) ethical and controversial issues. Palliative sedation must be practised with clinical and ethical accuracy and competence to avoid harm and ethically questionable use. Specialist palliative care teams should be consulted before initiating palliative sedation to avoid overlooking other potential treatment options for the patient's symptoms and suffering.

Interventions that may increase control at the end of life in persons with dementia: the cross-cultural CONT-END acceptability study protocol and pilot-testing.

BACKGROUND: Interventions such as advance care planning (ACP), technology, or access to euthanasia may increase the sense of control over the end of life. In people with advanced dementia, the loss of cognitive and physical function limits the ability to control care. To date, little is known about the acceptability of these interventions from the perspective of persons with dementia and others involved. This study will examine the cross-cultural acceptability, and factors associated with acceptability, of four end-of-life interventions in dementia which contain an element of striving for control. Also, we report on the development and pilot testing of animation video vignettes that explain the interventions in a standardized manner. METHODS: Cross-sectional mixed-methods vignette study. We assess acceptability of two ACP approaches, technology use at the end of life and euthanasia in persons with dementia, their family caregivers and physicians in six countries (Netherlands, Japan, Israel, USA, Germany, Switzerland). We aim to include 80 participants per country, 50 physicians, 15 persons with dementia, and 15 family caregivers. After viewing each animation video, participants are interviewed about acceptability of the intervention. We will examine differences in acceptability between group and country and explore other potentially associated factors including variables indicating life view, personality, view on dementia and demographics. In the pilot study, participants commented on the understandability and clarity of the vignettes and instruments. Based on their feedback, the scripts of the animation videos were clarified, simplified and adapted to being less slanted in a specific direction. DISCUSSION: In the pilot study, the persons with dementia, their family caregivers and other older adults found the adapted animation videos and instruments understandable, acceptable, feasible, and not burdensome. The CONT-END acceptability study will provide insight into cross-cultural acceptability of interventions in dementia care from the perspective of important stakeholders. This can help to better align interventions with preferences. The study will also result in a more fundamental understanding as to how and when having control at the end of life in dementia is perceived as beneficial or perhaps harmful. TRIAL REGISTRATION: The CONT-END acceptability study was originally registered at the Netherlands Trial Register (NL7985) at 31 August, 2019, and can be found on the International Clinical Trials Registry Platform.

Effect of opioids for breathlessness in heart failure: a systematic review and meta-analysis.

BACKGROUND: For the treatment of breathlessness in heart failure (HF), most textbooks advocate the use of opioids. Yet, meta-analyses are lacking. METHODS: A systematic review was performed for randomised controlled trials (RCTs) assessing effects of opioids on breathlessness (primary outcome) in patients with HF. Key secondary outcomes were quality of life (QoL), mortality and adverse effects. Cochrane Central Register of Controlled Trials, MEDLINE and Embase were searched in July 2021. Risk of bias (RoB) and certainty of evidence were assessed by the Cochrane RoB 2 Tool and Grading of Recommendations Assessment, Development and Evaluation criteria, respectively. The random-effects model was used as primary analysis in all meta-analyses. RESULTS: After removal of duplicates, 1180 records were screened. We identified eight RCTs with 271 randomised patients. Seven RCTs could be included in the meta-analysis for the primary endpoint breathlessness with a standardised mean difference of 0.03 (95% CI -0.21 to 0.28). No study found statistically significant differences between the intervention and placebo. Several key secondary outcomes favoured placebo: risk ratio of 3.13 (95% CI 0.70 to 14.07) for nausea, 4.29 (95% CI 1.15 to 16.01) for vomiting, 4.77 (95% CI 1.98 to 11.53) for constipation and 4.42 (95% CI 0.79 to 24.87) for study withdrawal. All meta-analyses revealed low heterogeneity (I2 in all these meta-analyses was <8%). CONCLUSION: Opioids for treating breathlessness in HF are questionable and may only be the very last option if other options have failed or in case of an emergency. PROSPERO REGISTRATION NUMBER: CRD42021252201.

Inpatient Specialist Palliative Care in Patients With Left Ventricular Assist Devices (LVAD): A Retrospective Case Series.

Background: Repeat hospitalizations, complications, and psychosocial burdens are common in patients with left ventricular assist devices (LVAD). Specialist palliative care (sPC) involvement supports patients during decision-making until end-of-life. In the United States, guidelines recommend early specialist palliative care (esPC) involvement prior to implantation. Yet, data about sPC and esPC involvement in Europe are scarce. Materials and Methods: This is a retrospective descriptive study of deceased LVAD patients who had received sPC during their LVAD-related admissions to two university hospitals in Duesseldorf, Germany and Basel, Switzerland from 2010 to 2021. The main objectives were to assess: To which extent have LVAD patients received sPC, how early is sPC involved? What are the characteristics of those, how did sPC take place and what are key challenges in end-of-life care? Results: In total, 288 patients were implanted with a LVAD, including 31 who received sPC (11%). Twenty-two deceased LVAD patients (19 male) with sPC were included. Mean patient age at the time of implantation was 67 (range 49-79) years. Thirteen patients (59%) received LVAD as destination therapy, eight patients (36%) were implanted as bridge to transplantation (BTT), and one as an emergency LVAD after cardiogenic shock (5%). None of the eight BTT patients received a heart transplantation before dying. Most (n = 13) patients lived with their family and mean Eastern Cooperative Oncology Group (ECOG) performance status was three. Mean time between LVAD implantation and first sPC contact was 1.71 years, with a range of first sPC contact from 49 days prior to implantation to more than 6 years after. Two patients received esPC before implantation. In Duesseldorf, mean time between first sPC contact and in-hospital death was 10.2 (1-42) days. In Basel, patients died 16 (0.7-44) months after first sPC contact, only one died on the external sPC unit. Based on thorough examination of two case reports, we describe key challenges of sPC in LVAD patients including the necessity for sPC expertise, ethical and communicative issues as well as the available resources in this setting. Conclusion: Despite unequivocal recommendations for sPC in LVAD patients, the integration of sPC for these patients is yet not well established.

Efficacy and Safety of Apatinib for Radiation-induced Brain Injury Among Patients With Head and Neck Cancer: An Open-Label, Single-Arm, Phase 2 Study.

PURPOSE: The treatment of radiation-induced brain injury (RI) caused by radiation therapy for head and neck cancer is challenging. Antiangiogenic therapy is a promising treatment. Apatinib is an oral tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptor 2. We aimed to assess the efficacy and safety of apatinib in patients with RI. METHODS AND MATERIALS: In this phase 2, open-label, single-arm, prospective study, we recruited patients aged 35 to 80 years with prior radiation therapy history for head and neck cancer who had newly diagnosed RI at the Sun Yat-sen Memorial Hospital, China. Apatinib was administered at a dosage of 250 mg once daily orally for 4 weeks. A Simon minimax 2-stage design was performed. The primary outcome was the proportion of patients with overall clinical efficacy, defined as a radiographic response of ≥25% reduction in baseline brain edema volume on magnetic resonance fluid attenuated inversion recovery images at week 4. Secondary end points were the overall improvement rate of brain necrosis, neurologic function, and safety. RESULTS: We screened 37 patients, 36 of whom were enrolled between October 17, 2019, and August 3, 2020. At the cutoff date, 36 patients were assessed for efficacy and safety (19 were enrolled in stage 1 and 17 in stage 2). Of the 36 patients evaluated for overall clinical efficacy, 22 patients (61.1%; 95% CI, 43.5%-76.9%) achieved the primary end point at week 4. Among the 31 patients with brain necrosis lesions, 19 patients (61.3%; 95% CI, 42.2%-78.2%) showed improvement of brain necrosis. The most common grade 1 to 2 adverse events were hand-foot syndrome, fatigue, and hypertension There were no treatment-related grade 4 to 5 toxic effects. CONCLUSIONS: Oral apatinib shows promising efficacy and is well-tolerated in patients with RI. Further randomized controlled studies are warranted.

Dexmedetomidine: a magic bullet on its way into palliative care-a narrative review and practice recommendations.

BACKGROUND AND OBJECTIVE: Dexmedetomidine is a potent adrenergic alpha-2 receptor agonist. It was first approved for sedation for mechanically ventilated patients. Being a sedative medication that is not associated with respiratory depression and holding analgesic properties fosters the interest for this drug in the palliative care field. The primary objectives of this review were to identify the key indications for the real-world use of dexmedetomidine in palliative care and other disciplines. METHODS: A narrative review after extensive PubMed search was performed from 1950 to present on October 21st 2021. The language of the publications was restricted to English, German, French and Italian. KEY CONTENT AND FINDINGS: (I) Current dexmedetomidine use. There is a growing body of evidence that dexmedetomidine may reduce the incidence and severity of delirium, reduce opioid-consumption and postoperative nausea in intensive care settings. It is also used to facilitate withdrawal from different substances (alcohol, opioids, heroin). Concerning safety aspects of the drug, some studies reported an increased rate of serious cardiovascular events in patients with pre-existing heart conditions due to bradycardia and arterial hypo- and hypertension. Since the drug has a main hepatic metabolism, dose reduction is mandatory in patients with hepatic impairment. (II) Dexmedetomidine and palliative care. There have been sporadic case reports about the successful use of dexmedetomidine in palliative care. Indications for symptom control included sedation for hyperactive delirium, cancer pain, opioid-induced-hyperalgesia, dystonia, cough, vomiting, shivering and dyspnea. It is mainly applied via the intravenous (i.v.), subcutaneous, but also nasal and, buccal routes. Admixture ("syringe-driver") studies showed that dexmedetomidine is compatible with morphine, hydromorphone, hyoscine and haloperidol. In 2021, a first prospective cohort study became available. Here, the authors reported promising result for dexmedetomidine use in hyperactive terminal delirium for reducing delirium intensity and agitation. Especially the unique "conscious sedation" or "awake sedation" that allows patients to arouse easily under sedation and report comfort or distress was discussed by the authors. CONCLUSIONS: In this review, we present the main findings for dexmedetomidine from palliative care settings and other disciplines. The potential benefits and criticalities of the drug are discussed and practical recommendations for its use are provided.

Quality of life after pulmonary stereotactic fractionated radiotherapy (SBRT): Results of the phase II STRIPE trial.

BACKGROUND AND PURPOSE: Preserving health related quality of life (HRQOL) plays an important role in considering stereotactic body fractionated radiotherapy (SBRT). The prospective monocenter phase II STRIPE trial investigated long-term HRQOL after SBRT, efficacy and toxicity. MATERIALS AND METHODS: Patients with ≤2 pulmonary lesions ≤5 cm were treated with 4DPET/CT-based SBRT (3 × 12.5 Gy or risk-adapted 5 × 7 Gy, to 60% isodose). Follow up (FU) was performed 2 and 7 weeks after SBRT, then 3-monthly for 2 years with assessment of response (primary endpoint: 2-year cumulative incidence of local progression (LP); secondary endpoints: local progression free survival (LPFS), overall survival (OS) and toxicity (CTCAE)). Impact of predefined patient and treatment related factors on HRQOL (EORTC QLQ-C30 and EORTC QLQ-LC13) was evaluated. RESULTS: Between 02/2011 and 11/2014, 100 patients were given SBRT for 56 NSCLC and 44 pulmonary metastases (M1). Long-term FU overall revealed stable Quality of Life (QoL)/Global health status (GHS), functions-scores and symptoms. For QoL/GHS, patients with low (

Transcutaneous electrical nerve stimulation for advanced cancer pain inpatients in specialist palliative care-a blinded, randomized, sham-controlled pilot cross-over trial.

PURPOSE: Transcutaneous electrical nerve stimulation (TENS) is a treatment option for cancer pain, but the evidence is inconclusive. We aimed to evaluate the efficacy and safety of TENS. METHODS: A blinded, randomized, sham-controlled pilot cross-over trial (NCT02655289) was conducted on an inpatient specialist palliative care ward. We included adult inpatients with cancer pain ≥ 3 on an 11-point numerical rating scale (NRS). Intensity-modulated high TENS (IMT) was compared with placebo TENS (PBT). Patients used both modes according to their preferred application scheme during 24 h with a 24-h washout phase. The primary outcome was change in average pain intensity on the NRS during the preceding 24 h. Responders were patients with at least a "slight improvement." RESULTS: Of 632 patients screened, 25 were randomized (sequence IMT-PBT = 13 and PBT-IMT = 12). Finally, 11 patients in IMT-PBT and 9 in PBT-IMT completed the study (N = 20). The primary outcome did not differ between groups (IMT minus PBT: - 0.2, 95% confidence interval - 0.9 to 0.6). However, responder rates were higher in IMT (17/20 [85%] vs. 10/20 [50%], p = 0.0428). Two patients experienced an uncomfortable feeling caused by the current, one after IMT and one after PBT. Seven patients (35%) desired a TENS prescription. Women and patients with incident pain were most likely to benefit from TENS. CONCLUSION: TENS was safe, but IMT was unlikely to offer more analgesic effects than PBT. Even though many patients desired a TENS prescription, 50% still reported at least "slight pain relief" from PBT. Differences for gender and incident pain aspects demand future trials.

Severe symptoms and very low quality-of-life among outpatients newly diagnosed with advanced cancer: data from a multicenter cohort study.

PURPOSE: The aim of this study was to identify symptoms of severe intensity or very low scores for quality of life (QoL) domains in newly diagnosed outpatients with advanced cancer. METHODS: This multicenter cohort study from a state-wide palliative care network included adult outpatients with advanced cancer diagnosed within the preceding 8 weeks from four comprehensive cancer centers (DRKS00006162, registered on 19 May 2014). We used the Palliative Outcome Scale (POS), Hospital Anxiety and Depression Scale, and European Organization for Research and Treatment of Cancer QoL Questionnaire-C30. For each questionnaire, cut-off scores defined symptoms and QoL domains that were considered "severe" or "very low." RESULTS: Of 3155 patients screened, 481/592 (81.3%) were analyzed (mean age 62.4; women n = 245, 50.9%). We identified 324/481 (67.4%) patients experiencing at least one severe symptom or a very low QoL domain (median 2; range 0 to 16). Role functioning (n = 180, 37.4%), fatigue (n = 162, 33.7%), and social functioning (n = 126, 26.2%) were most commonly affected. QoL was very low in 89 patients (18.5%). Women experienced more anxiety symptoms, fatigue, and had lower POS scores. Patients often mentioned physical symptoms and fears of adverse events resulting from disease-modifying therapies (e.g., chemotherapy) as most relevant problems. CONCLUSIONS: Already within the first 8 weeks after diagnosis, the majority of patients reported at least one severe symptom or a very low QoL domain. Gender differences were evident. The findings illustrate the value of early routine assessment of patient burden and the development of multi-professional and interdisciplinary palliative care.

Early palliative care and the opioid crisis: ten pragmatic steps towards a more rational use of opioids.

In palliative care, opioids and other controlled drugs are among the most commonly used and important medications. Opioids are associated with significant risk of dependence and misuse. In many developed countries, there is an epidemic of prescription opioid misuse and overdose deaths. Palliative care has a critical role educating patients about the safe use of opioids, providing universal screening and close monitoring, and prescribing opioids appropriately balancing the risks and benefits. This is particularly important in the era of early palliative care, when patients have much longer survival and potentially greater risk of misuse while on chronic opioid therapy. Here, we provided a critical appraisal of opioid use in the context of opioid crisis and early palliative care. We also present a pragmatic 10-step approach for the judicious use of opioids.

Benzodiazepines and/or neuroleptics for the treatment of delirium in palliative care?-a critical appraisal of recent randomized controlled trials.

Delirium is a frequent condition in patients in a palliative care situation and most often associated with substantial burden or even danger for the persons concerned as well as caregivers and health-care-professionals. Despite the lack of randomized-controlled-trials (RCTs) benzodiazepines and neuroleptic agents are used extensively in palliative care for the pharmacological management of delirium. A focused review for RCTs assessing pharmacotherapy with benzodiazepines and neuroleptics for the treatment of delirium in patients treated in a palliative care or hospice setting published in 2017 was performed in PubMed. A narrative summary of the findings of the RCTs and practical recommendation are presented. Of 42 publications, two RCTs could be included. One trial assessed the use of lorazepam (in addition to haloperidol) in case of agitation, the other placebo or risperidone or haloperidol in delirious palliative care patients. Neither risperidone nor haloperidol were superior compared to placebo, but were associated with higher mortality and morbidity. Lorazepam (along with haloperidol) reduced agitation in patients with delirium compared to placebo (along with haloperidol), but was unable to reduce the severity and incidence of delirium. It is of importance to note that psychopharmacotherapy with antipsychotics is mainly indicated for the hyperactive form of delirium and psychotic symptoms (e.g., delusions or hallucinations) in the hyper- and hypoactive delirium. Severe agitation and aggressivity can be an indication for neuroleptics, when non-pharmacological interventions fail, whereas the use of benzodiazepines has to be limited to critical situations where neuroleptics cannot be applied and cases of delirium due to alcohol withdrawal. Both substances can aggravate, precipitate or mask delirium, result adverse events with substantial distress or unfavorable survival outcomes for the patients. Thus, they should only be used in severely symptomatic patients and the duration of the medication has to be limited in time. When delirium symptoms decay the psychopharmacotherapy has to be tapered. More important than psychopharmacotherapy, the thorough investigation and treatment of potentially reversible causes of delirium (e.g., pharmacotherapy, infection) and the routine identification of patients at risk for delirium along with prophylactic measures are essential. The recently published landmarks RCTs provide moderate evidence to adopt recommendations from other medical specialties (i.e., intensive care, geriatrics) to the field of palliative care.

PROutine: a feasibility study assessing surveillance of electronic patient reported outcomes and adherence via smartphone app in advanced cancer.

BACKGROUND: In advanced cancer, quality of life (QoL) is a major treatment goal. In order to achieve this, the identification of suffering by screening for patient-reported-outcomes (PROs, i.e., symptoms) is of utmost importance. The use of paper-pencil questionnaires is associated with significant shortcomings due to missing data, recall bias and transcription errors. Other than that, the electronic recording of PROs by mobile Health (mHealth) offers a number of advantages. The aim of this study was to test whether the routine assessment of PROs via a newly developed smartphone application (MeQoL®) is feasible. METHODS: A prospective, uncontrolled, multi-center, feasibility trial was performed in adult outpatients with advanced, solid cancer. Patients under anti-cancer therapy and with regular outpatient visits were eligible. Patients daily recorded the degree of perceived distress (NCCN Distress Thermometer®), pain intensity {average and worst [numerical rating scale (NRS), 0-10]}, the number of breakthrough pain episodes (BPE) and ten questions from a modified version of the Edmonton Symptom Assessment Scale (ESAS). Weekly, five questions concerning different domains of QoL from the short-form 8 (SF-8) questionnaire were obtained. Also, patients recorded the intake of their opioid rescue medication. According to the main scope of the trial (feasibility), no primary endpoint was defined. Rather, the following main feasibility criteria were assessed: missing data, drop-out- and acceptance-rate, patient satisfaction, patients' judgement of practicability, patients' and physicians' suggestions for improvement and basic clinical and demographic data of the participating patients. The study was registered in the German Clinical Trials Register (ID: DRKS00008761). RESULTS: In three German cancer centers, 40 patients {female: 28 (70%); average age, 57 years [range, 27-73 years; standard deviation (SD), 12]} were included. As three devices were lost on transport, 37 devices could be evaluated. The median investigation period per device was 99.5 days (SD, 31). Patient adherence in using the smartphone app to document their distress and symptoms was high and missing data were low: In median daily reviews were performed on 70 (SD, 29) of these days (70%) and median weekly recordings were 13 weeks (87%). Most often, patients recorded symptom intensity (89%, MIDOS) and distress (85%, NCCN thermometer). On feedback forms, patients reported a good to very good user friendliness of MeQoL® and a high motivation to use this tool again. CONCLUSIONS: Even though participants were asked to record PROs rather frequently (daily), missing data were low and patient satisfaction was high. Having in mind the findings of other working groups, such routine implementation of mHealth solutions may substantially improve outcomes of cancer therapy and increase the value of trials' findings. For the individual patient, MeQoL® allows for monitoring adherence to pharmacotherapy and can facilitate patient guidance.

Effect of Pregabalin on Radiotherapy-Related Neuropathic Pain in Patients With Head and Neck Cancer: A Randomized Controlled Trial.

PURPOSE: Neuropathic pain is an unavoidable treatment-related adverse event among patients with head and neck cancer who are undergoing radiotherapy. We aimed to test the efficacy and safety of pregabalin versus placebo in the treatment of radiotherapy-related neuropathic pain. PATIENTS AND METHODS: This randomized, double-blind, placebo-controlled trial was conducted in four centers in China. Eligible patients with a mean pain intensity score of 4 or more on an 11-point numeric rating scale were randomly assigned to receive either active treatment with a flexible dose of pregabalin or placebo for 16 weeks. The primary efficacy outcome was pain reduction measured on the numeric rating scale. RESULT: There were 128 patients who received treatment as randomly assigned. Pain intensity reduction was 2.44 in the pregabalin arm and 1.58 in the placebo arm at week 16, yielding an adjusted mean difference of 0.87 (95% CI, 0.30 to 1.44; P = .003). In the pregabalin arm, 38 patients (59.4%) achieved at least 30% pain relief versus 21 (32.8%) in the placebo arm ( P = .006). Nineteen patients (29.7%) in the pregabalin group and five (7.8%) in the placebo group achieved 50% or greater pain relief ( P = .003). Total scores on the Profile of Mood States-Short Form, pain severity and functional interference of Brief Pain Inventory-Short Form, as well as the physiology and psychology domain of the WHO Quality of Life-BREF all were reduced significantly at week 16 in patients who received pregabalin compared with those who received placebo. There was no significant difference ( P = .29) in the incidence of experiencing at least one adverse event in the pregabalin arm (n = 35; 54.7%) versus the placebo arm (n = 29; 45.3%). CONCLUSION: Patients treated with pregabalin with radiotherapy-related neuropathic pain had greater pain alleviation, better mood states, and higher quality of life compared with patients in the placebo group, with a good tolerability.

Early Impact of Pulmonary Fractionated Stereotactic Body Radiotherapy on Quality of Life:Benefit for Patients With Low Initial Scores (STRIPE Trial).

INTRODUCTION: Quality of life (QoL) of comorbid patients with pulmonary malignancies is a key issue in considering fractionated stereotactic body radiotherapy (SBRT) indication. This study investigates the early impact of SBRT on QoL. METHODS: One hundred patients with pulmonary lesions were treated with SBRT from February 2011 to December 2014 within the prospective, monocenter, phase II STRIPE trial. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core module (EORTC QLQ-C30) and the QLQ-LC13 lung cancer-specific questionnaire were used to evaluate QoL before, 2 and 7 weeks after SBRT, then every 3 months for 2 years. We report on the analysis of early changes from baseline to 7-week follow-up exam. Impact of patient- and treatment-related factors on the change in QoL was analyzed. RESULTS: QoL was assessed in 97 patients; compliance was 92% and 85% at baseline and 7 weeks after SBRT, respectively. No clinically relevant changes greater than or equal to 10 in the QoL/global health status (GHS), function scores and inquired symptoms were observed. Patients with baseline QoL below the median showed clinically relevant improvement in QoL/GHS (Δ16.7 ± 25.3, p = 0.003), emotional function (Δ14.4 ± 25.4, p = 0.013), and fatigue (Δ -10.1 ± 26.5, p = 0.089) in contrast to patients with high initial scores. No changes were observed in the dichotomized subgroups of initial Karnofsky index, Charlson Comorbidity Index, age, diagnosis, and tumor localization. CONCLUSIONS: In short-term follow-up, QoL is well maintained after pulmonary SBRT. Especially patients with low initial QoL/GHS scores show benefit from SBRT with respect to QoL.

Testing the Implementation of a Pain Self-management Support Intervention for Oncology Patients in Clinical Practice: A Randomized Controlled Pilot Study (ANtiPain).

BACKGROUND: In oncology, pain control is a persistent problem. Significant barriers to cancer pain management are patient related. Pain self-management support interventions have shown to reduce pain intensity and patient-related barriers. Comparative effectiveness research is a suitable approach to test whether effects are sustained in clinical practice. OBJECTIVE: In this pilot randomized controlled trial, the implementation of the ANtiPain intervention into clinical practice was tested to assess the effects on pain intensity, function-related outcomes, self-efficacy, and patient-related barriers to pain management to prepare a larger effectiveness trial. METHODS: Within 14 months, 39 adult oncology patients with pain scores of 3 or higher on a 10-point numeric rating scale were recruited in an academic comprehensive cancer center in Southern Germany. Patients in the control group (n = 19) received standard care. Patients in the intervention group (n = 20) received ANtiPain, a cancer pain self-management support intervention based on 3 key strategies: provision of information, skill building, and nurse coaching. An intervention session was performed in-hospital. After discharge, follow-up was provided via telephone calls. Data were collected at baseline and 1 and 6 weeks after discharge. Effect sizes were calculated for all outcomes. RESULTS: Large effects were found for activity hindrance (Cohen d = 0.90), barriers (d = 0.91), and self-efficacy (d = 0.90). Small to moderate effects were found for average and worst pain (Cohen d = 0.17-0.45). CONCLUSIONS: Key findings of this study involved function-related outcomes and self-efficacy. IMPLICATIONS FOR PRACTICE: Because these outcomes are particularly meaningful for patients, the integration of ANtiPain to routine clinical practice may be substantial. A larger study will be based on these findings.

Effect of specialist palliative care services on quality of life in adults with advanced incurable illness in hospital, hospice, or community settings: systematic review and meta-analysis.

Objective To assess the effect of specialist palliative care on quality of life and additional outcomes relevant to patients in those with advanced illness.Design Systematic review with meta-analysis.Data sources Medline, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and trial registers searched up to July 2016.Eligibility criteria for selecting studies Randomised controlled trials with adult inpatients or outpatients treated in hospital, hospice, or community settings with any advanced illness. Minimum requirements for specialist palliative care included the multiprofessional team approach. Two reviewers independently screened and extracted data, assessed the risk of bias (Cochrane risk of bias tool), and evaluated the quality of evidence (GRADE tool).Data synthesis Primary outcome was quality of life with Hedges' g as standardised mean difference (SMD) and random effects model in meta-analysis. In addition, the pooled SMDs of the analyses of quality of life were re-expressed on the global health/QoL scale (item 29 and 30, respectively) of the European Organization for Research and Treatment of Cancer QLQ-C30 (0-100, high values=good quality of life, minimal clinically important difference 8.1).Results Of 3967 publications, 12 were included (10 randomised controlled trials with 2454 patients randomised, of whom 72% (n=1766) had cancer). In no trial was integration of specialist palliative care triggered according to patients' needs as identified by screening. Overall, there was a small effect in favour of specialist palliative care (SMD 0.16, 95% confidence interval 0.01 to 0.31; QLQ-C30 global health/QoL 4.1, 0.3 to 8.2; n=1218, six trials). Sensitivity analysis showed an SMD of 0.57 (-0.02 to 1.15; global health/QoL 14.6, -0.5 to 29.4; n=1385, seven trials). The effect was marginally larger for patients with cancer (0.20, 0.01 to 0.38; global health/QoL 5.1, 0.3 to 9.7; n=828, five trials) and especially for those who received specialist palliative care early (0.33, 0.05 to 0.61, global health/QoL 8.5, 1.3 to 15.6; n=388, two trials). The results for pain and other secondary outcomes were inconclusive. Some methodological problems (such as lack of blinding) reduced the strength of the evidence.Conclusions Specialist palliative care was associated with a small effect on QoL and might have most pronounced effects for patients with cancer who received such care early. It could be most effective if it is provided early and if it identifies though screening those patients with unmet needs.Systematic review registration PROSPERO CRD42015020674.