Intravenous lidocaine for refractory pain in patients with pancreatic ductal adenocarcinoma and chronic pancreatitis (LIDOPAN): a multicenter prospective non-randomized pilot study.

INTRODUCTION: Refractory pain is a major clinical problem in patients with pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). New, effective therapies to reduce pain are urgently needed. Intravenous lidocaine is used in clinical practice in patients with PDAC and CP, but its efficacy has not been studied prospectively. METHODS: Multicentre prospective non-randomized pilot study including patients with moderate or severe pain (NRS ≥ 4) associated with PDAC or CP in 5 Dutch centers. An intravenous lidocaine bolus of 1.5mg/kg, was followed by continuous infusion at 1.5 mg/kg/hour. The dose was raised every 15 minutes until treatment response (up to a maximum 2mg/kg/hour) and consecutively administered for two hours. Primary outcome was the mean difference in pain severity, pre-infusion and the first day after (Brief Pain Inventory [BPI] scale 1-10). A BPI decrease ≥ 1.3 points was considered clinically relevant. RESULTS: Overall, 30 patients were included, 19 with PDAC (63%) and 11 with CP (37%). The mean difference in BPI at day one was 1.1 (SD±1.3) points for patients with PDAC and 0.5 (SD±1.7) for CP patients. A clinically relevant decrease in BPI on day one was reported in 9/29 patients (31%), this response lasted up to one month. No serious complications were reported, and only three minor complications (vertigo, nausea, tingling of mouth). Treatment with lidocaine did not impact quality of life. CONCLUSION: Intravenous lidocaine in patients with painful PDAC and CP did not show an overall clinically relevant reduction of pain. However, this pilot study shows that the treatment is feasible in this patient group, and had a positive effect in a third of patients which lasted up to a month with only minor side effects. To prove or exclude the efficacy of intravenous lidocaine, the study should be performed in a study with a greater sample size and less heterogeneous patient group.

Sex Differences in Pain Sensitivity in a Dutch Cohort: Cross-Sectional and Web-Based Multidimensional Study.

BACKGROUND: Sex is an important factor influencing the development and treatment of chronic pain, but the extent of its influence is still unclear. Other demographic factors as well as nonpharmacological interventions might influence pain sensitivity differently in men and women. OBJECTIVE: In this study, we aimed to investigate the influence of sex and other demographic, lifestyle, behavioral, clinical, and environmental factors on pain sensitivity in the Dutch population. Different films were used to investigate how they would impact pain sensitivity and what influence sex and other variables have on the effect of this simple intervention. METHODS: We performed a study consisting of 2 parts: (1) a cross-sectional research to investigate pain sensitivity differences between men and women and the influence of other demographic variables on the pain sensitivity in a Dutch cohort and (2) an internet intervention study to determine whether a short film could skew pain sensitivity. RESULTS: All respondents filled in a web-based demographic questionnaire and were randomized into 4 groups. The control group filled in the Pain Sensitivity Questionnaire without watching a preliminary film. A cross-sectional analysis was performed in the control group (n=1746). The other 3 groups watched short films: one group watched a film with scenes of nature (n=2650), another group watched a film on laughing people (n=2735), and the last group watched a film on physically painful events (n=2708). Immediately after the film viewing, participants were directed to the Pain Sensitivity Questionnaire to measure their pain sensitivity. The Pain Sensitivity Questionnaire score was stated as a mean per question on the numeric rating scale from 0-1. The cross-sectional study revealed no significant differences between men and women but showed male-female differences in the Pain Sensitivity Questionnaire when specific background factors were present. Watching a short film had a positive impact on the pain sensitivity of the respondents who had chronic pain, with a higher effect observed in female respondents. CONCLUSIONS: Scientists performing pain research need to account for factors that can influence the outcome of their study and be aware that these factors can be sex-dependent, and pain sensitivity should be analyzed accordingly. Even relatively small interventions such as watching a film can impact pain sensitivity, especially in respondents with current chronic pain. This effect can vary as well when different background factors are present. Our findings warrant further explorations of the possibilities that simple interventions bring for patients in personalized medicine. TRIAL REGISTRATION: Landelijk Trial Register NTR-new NL8182; https://onderzoekmetmensen.nl/en/trial/29537.

Appropriate Timing of End-of-Life Care: A Dutch Policy Analysis and Opportunities for Improvement.

Background: The Exceptional Medical Expenses Act (EMEA) guaranteed public financing for the costs of end-of-life care in The Netherlands until 2015. A life expectancy shorter than three months was a prerequisite for a patient to qualify. Objective: To estimate survival and its potential predictors using the start date of EMEA funded end-of-life care as time origin, and to calculate the ensuing costs. Design: Retrospective observational study using data retrieved from multiple datasets of the national statistical office Statistics Netherlands (https://www.cbs.nl/en-gb/). Setting: Included were all adult patients, who received EMEA funded end-of-life care in hospice units in nursing homes and homes for the elderly in The Netherlands between January 1, 2009, and December 31, 2014. Results: In 40,659 patients (median age 79 years), the distribution of survival was extremely skewed. Median, 95%, and maximum survival times were 15 (95% confidence interval [CI] = 15-15), 219 (210-226), and 2,006 days, respectively. The 90-day and 180-day survival rates were 12.4 (12.1-12.7)% and 6.2 (6.0-6.5)%, respectively. Although age, gender, diagnosis, and start year of end-of-life care were statistically significant independent predictors, clinical significance is limited. End-of-life care was delivered for a total of 1,720,002 days, costing almost 440 million Euros. Fifty-nine percent of the costs was for barely 11% of patients, i.e., those who received end-of-life care for more than 90 days. Conclusion: The use of life expectancy is a weak basis for the appropriate timing of end-of-life care. Further research should evaluate potential tools to improve the timing of end-of-life care, while using available resources efficiently.

Experiences with and needs for aftercare following the death of a loved one in the ICU: a mixed-methods study among bereaved relatives.

BACKGROUND: Bereaved relatives of intensive care unit (ICU) patients are at increased risk of psychological complaints. Aftercare might help them cope with processing the ICU admission and their loved one's death. There is little (qualitative) evidence on how bereaved relatives experience aftercare. Also, the COVID-19 pandemic likely impacted aftercare provision. We aim to examine how many relatives in Dutch ICUs received aftercare before and during the pandemic and to qualitatively describe their experiences and needs regarding aftercare. METHODS: A mixed-methods study among relatives of patients who died in an ICU before or during the COVID-19 pandemic. Bereaved relatives in six ICUs completed a questionnaire (n = 90), including two items on aftercare. These were analyzed using descriptive statistics and Chi-squared tests. Subsequently, both relatives that received and relatives that did not receive aftercare were interviewed about their experiences and needs regarding aftercare. The interviews were thematically analyzed. RESULTS: After the passing of a loved one, 44% of the relatives were asked by a healthcare professional from the hospital how they were doing, and 26% had had a follow-up conversation. Both happened more often during the first wave of the pandemic than during the second wave or before the pandemic. The most common reason for not having had a follow-up conversation was not knowing about this option (44%), followed by not feeling a need (26%). Regarding the latter, interviewed relatives explained that this would not revive their loved one or that they had already discussed everything they wanted. Relatives who wanted a follow-up conversation, wanted this because this would help them realize the severity of their loved one's illness, to exchange personal experiences, and/or to thank the ICU team. Those with a follow-up conversation said that they had reviewed the medical course of the admission and/or discussed their (mental) well-being. CONCLUSIONS: ICU healthcare professionals may play a vital role in addressing aftercare needs by asking relatives how they are doing in the weeks following the death of their loved one and offering them a follow-up conversation with an ICU physician. We recommend to include aftercare for bereaved relatives in ICU guidelines.

Varying (preferred) levels of involvement in treatment decision-making in the intensive care unit before and during the COVID-19 pandemic: a mixed-methods study among relatives.

BACKGROUND: In the intensive care unit (ICU) relatives play a crucial role as surrogate decision-makers, since most patients cannot communicate due to their illness and treatment. Their level of involvement in decision-making can affect their psychological well-being. During the COVID-19 pandemic, relatives' involvement probably changed. We aim to investigate relatives' involvement in decision-making in the ICU before and during the pandemic and their experiences and preferences in this regard. METHODS: A mixed-methods study among relatives of ICU patients admitted to an ICU before or during the COVID-19 pandemic. Relatives in six ICUs completed a questionnaire (n = 329), including two items on decision-making. These were analysed using descriptive statistics and logistic regression analyses. Subsequently, relatives (n = 24) were interviewed about their experiences and preferences regarding decision-making. Thematic analysis was used for analysing the qualitative data. RESULTS: Nearly 55% of the relatives indicated they were at least occasionally asked to be involved in important treatment decisions and of these relatives 97.1% reported to have had enough time to discuss questions and concerns when important decisions were to be made. During the first COVID-19 wave relatives were significantly less likely to be involved in decision-making compared to relatives from pre-COVID-19. The interviews showed that involvement varied from being informed about an already made decision to deliberation about the best treatment option. Preferences for involvement also varied, with some relatives preferring no involvement due to a perceived lack of expertise and others preferring an active role as the patient's advocate. Discussing a patient's quality of life was appreciated by relatives, and according to relatives healthcare professionals also found this valuable. In some cases the preferred and actual involvement was in discordance, preferring either a larger or a smaller role. CONCLUSIONS: As treatment alignment with a patient's values and preferences and accordance between preferred and actual involvement in decision-making is very important, we suggest that the treatment decision-making process should start with discussions about a patient's quality of life, followed by tailoring the process to relatives' preferences as much as possible. Healthcare professionals should be aware of relatives' heterogeneous and possibly changing preferences regarding the decision-making process.

Chronic temporomandibular disorder pain patients with a history of neuropathic pain treatment: a narrative research on their diagnosis and treatment history.

The aims of this qualitative research were (1) to gain more insight in the diagnostic and treatment history of patients with chronic temporomandibular disorder (TMD) pain; (2) to get a deeper understanding of possible factors that are involved in the possible delay in setting a TMD-pain diagnosis and receiving appropriate treatment; and (3) to get a deeper understanding of the perspectives and experiences of chronic TMD-pain patients on the possible improvement of various aspects of their diagnostic and treatment journey.MethodsIn this narrative research, semi-structured interviews took place with patients who experienced chronic orofacial pain (OFP) for at least three years before getting diagnosed with, and treated for, TMD pain by an OFP specialist in an interprofessional setting.ResultsIn total, ten patients were interviewed in-depth. Patients experienced their chronic OFP in different ways, but all reported a significant impact of their pain on their quality of life. All patients visited numerous health care professionals before their TMD diagnosis was set. Among others, they underwent anti-neuropathic pain medication therapies and invasive surgeries, which did not significantly reduce their chronic OFP. The interprofessional TMD-pain treatment reduced the suffering of the chronic OFP substantially, also 6 months after the start of therapy, and improved the quality of life for all patients. In most of them, the OFP intensity was also decreased.ConclusionChronic TMD-pain patients with a history of neuropathic pain treatment may experience a long journey until receiving the appropriate diagnosis and treatment. This stresses the need to improve the implementation of chronic TMD-pain guidelines.

Pulsed radiofrequency or surgery for anterior cutaneous nerve entrapment syndrome: Long-term results of a randomized controlled trial.

PURPOSE: Patients with anterior cutaneous nerve entrapment syndrome (ACNES) often require a step-up treatment strategy including abdominal wall injections, pulsed radiofrequency (PRF) or a neurectomy. Long-term success rates of PRF and surgery are largely unknown. The aim of the current study was to report on the long-term efficacy of PRF and neurectomy in ACNES patients who earlier participated in the randomized controlled PULSE trial. METHODS: Patients who completed the PULSE trial were contacted about pain status and additional treatments in the following years. Treatment success was based on numerical rating scale (NRS) following IMMPACT recommendations and Patient Global Impression of Change (PGIC) scores. RESULTS: A total of 44 of the original 60 patients were eligible for analysis (73.3%). Median follow-up was 71.5 months. One patient (4.3%) was still free of pain after a single PRF session, and five additional patients (21.7%) were free of pain by repetitive PRF treatments. By contrast, 13 patients (61.9%) in the neurectomy group were still free of pain without additional treatments. All pain recurrences and therefore primary re-interventions occurred in the first 2 years after the initial treatment. CONCLUSION: Approximately one in five ACNES patients undergoing PRF treatment reports long-term success obviating the need of surgical intervention. Surgery for ACNES is long-term effective in approximately two of three operated patients. Recurrent ACNES beyond 2 years after either intervention is rare.

Support for relatives in the intensive care unit: lessons from a cross-sectional multicentre cohort study during the COVID-19 pandemic.

BACKGROUND: Support for relatives is highly important in the intensive care unit (ICU). During the first COVID-19 wave  support for relatives had to be changed considerably. The alternative support could have decreased the quality and sense of support. We aimed to evaluate how support for relatives in Dutch ICUs was organised during the first COVID-19 wave and how this was experienced by these relatives in comparison to relatives from pre-COVID-19 and the second wave. Additionally, we aimed to investigate which elements of support are associated with positive experiences. METHODS: We performed a cross-sectional multicentre cohort study in six Dutch ICUs in the Netherlands. Written questionnaires were distributed among relatives of ICU patients from pre-COVID-19, the first wave and the second wave. The questionnaire included questions on demographics, the organisation of support, and the experiences and satisfaction of relatives with the support. RESULTS: A total of 329 relatives completed the questionnaire (52% partner, 72% woman and 63% ICU stay of 11 days or longer). Support for relatives of ICU patients during the first COVID-19 wave differed significantly from pre-COVID-19 and the second wave. Differences were found in all categories of elements of support: who, when, how and what. Overall, relatives from the three time periods were very positive about the support. The only difference in satisfaction between the three time periods, was the higher proportion of relatives indicating that healthcare professionals had enough time for them during the first wave. Elements of support which were associated with many positive experiences and satisfaction were: fixed timeslot, receiving information (e.g. leaflets) on ≥ 2 topics, discussing > 5 topics with healthcare professionals, and being offered emotional support. CONCLUSIONS: Although, support for relatives in the ICU changed considerably during the COVID-19 pandemic, relatives were still positive about this support. The altered support gave insight into avenues for improvement for future comparable situations as well as for normal daily ICU practice: e.g. daily contact at a fixed timeslot, offering video calling between patients and relatives, and offering emotional support. ICUs should consider which elements need improvement in their practice.

The Effect of Preoperative Disability, Cognitive Impairment, Frailty and Opioid Use on Acute Postoperative Pain in Older Patients Undergoing Surgery A Prospective Cohort Study.

Globally, life expectancy is increasing, leading to more surgeries being performed in older patients. Postoperative pain is associated with complications after surgery. The aim of this study is to explore potential age-related risk factors for acute postoperative pain in older patients undergoing surgery. This was a prospective, single-center study. Patients ≥65 years, with and without disability, as defined by the WHO Disability Assessment Schedule 2.0, undergoing elective surgery, were compared. Primary outcome was the postoperative pain (ie, numeric rating scale (NRS) score) on the first postoperative day. Secondary outcomes were postoperative pain and pain trajectories in patients with and without mild cognitive impairment (MCI), frailty, preoperative opioid use, and new-onset disability after surgery. Between February 2019 and July 2020, 155 patients were enrolled. On the first day after surgery, postoperative pain did not differ between patients with and without disability. NRS scores differed between patients with-, and without MCI on the first (P = .01), and second postoperative day (P < .01). Patients who used opioids before surgery reported higher median NRS score on the first (P < .001) and second (P < .01) postoperative day. Out of a total of 1816 NRS scores, 2 pain clusters were identified. Acute postoperative pain did not differ between patients with or without preoperative disability and frailty in older patients undergoing surgery. Reduced postoperative pain in older patients with MCI warrants further investigation. The PIANO study (Comparison of Postoperative NeurocognitiveFunction in Older Adult Patients with and without Diabetes Mellitus) was registered with www.clinicaltrialregister.nl (search term: Which can predict memory problems after surgery better; blood sugar levels or memory before surgery?). PERSPECTIVE: This study explored risk factors for acute postoperative pain in older patients. No differences in postoperative pain were observed in patients with or without preexistent disability or frailty, however, patients with mild cognitive impairment experienced reduced pain. We suggest to simplify pain assessment in this group and take functional recovery into account.

Spinal Cord Stimulation for Failed Back Surgery Syndrome: to Trial or Not to Trial?

Spinal cord stimulation (SCS) is a recommended therapy to treat failed back surgery syndrome (FBSS). A trial period is practiced to enhance patient selection. However, its fundamental evidence is limited, especially concerning long-term benefit and therapy safety. We compared the long-term (5.3 ± 4.0 years) clinical outcome and therapy safety of a trialed and nontrialed implantation strategy, including multidimensional variables and pain intensity fluctuations over time. A multicenter cohort analysis was performed in 2 comparable groups of FBSS patients. Regarding eligibility, patients had to be treated with SCS for at least 3 months. While the Trial group comprised patients who underwent an SCS implantation after a successful trial, the No-Trial group encompassed patients who underwent complete implantation within 1 session. The primary outcome measures were pain intensity scores and complications. The Trial and No-Trial groups consisted of 194 and 376 patients (N = 570), respectively. A statistically but not clinically significant difference in pain intensity (P = .003; effect = 0.506 (.172-.839)) was found in favor of the Trial group. No interaction between a time dependency effect and pain intensity was noted. Whereas trialed SCS patients were more likely to cease opioid usage (P = .003; OR = .509 (.326-.792)), patients in the No-Trial group endured fewer infections (P = .006; proportion difference = .43 (.007-.083)). Although the clinical relevance of our findings should be proven in future studies, this long-term real-world data study indicates that patient-centered assessments on whether an SCS trial should be performed have to be investigated. According to the current ambiguous evidence, SCS trials should be considered on a case-by-case basis. PERSPECTIVE: The currently available comparative evidence, together with our results, remains ambiguous on which SCS implantation strategy might be deemed superior. An SCS trial should be considered on a case-by-case basis, for which further investigation of its clinical utility in certain patient populations or character traits is warranted.

The effect of preferred music versus disliked music on pain thresholds in healthy volunteers. An observational study.

Pain is a prevalent and debilitating healthcare problem. Since pharmacological treatments have numerous side-effects, additional treatment could be beneficial. Music has been shown to affect the pain perception and the pain threshold. The objective of this observational study was to evaluate the effect of preferred music as opposed to disliked music on pain (tolerance) thresholds and perceived pain intensity in healthy volunteers. Pain thresholds were measured via quantitative sensory testing. The volunteers were randomly assigned to either handheld pressure algometry to assess the pressure pain threshold to or electrical measurements to assess the electrical pain tolerance threshold while listening to preferred and disliked music. The pain thresholds were administered on the dorsal side of the forearm. The perceived pain intensity was assessed via a numerical rating scale, ranging from 0 (no pain) to 10 (worst pain imaginable). In total 415 volunteers were included in this study. The pressure pain threshold was assessed in 277 volunteers and in the electrical pain tolerance threshold test 138 volunteers were entered. In both groups, preferred music yielded higher pain thresholds than disliked music (P<0.001) and lower perceived pain intensity during the stimulus (P = 0.003). Moreover, the highest pain thresholds of both pressure pain and electrical pain tolerance thresholds were obtained when the preferred music was preceded by disliked music. Listening to preferred music when receiving noxious stimuli leads to higher pain thresholds and lower perceived pain scores in comparison with disliked music. Preferred music could be beneficial for patients with pain or undergoing painful procedures.

Multimodal analgesia practices for knee and hip arthroplasties in the Netherlands. A prospective observational study from the PAIN OUT registry.

INTRODUCTION: Different multimodal pain management strategies following total hip arthroplasty(THA) and total knee arthroplasty (TKA) surgery are used in clinical practice. The optimal pain management strategy, however, remains unclear. This study aims to evaluate the differences in perioperative multimodal pain management strategies for THA and TKA in the Netherlands, and studies the associations between patient- and therapy related factors and pain outcomes. METHODS: Data from the Dutch hospitals in the PAIN OUT network were used in this study. Demographic data, pain management strategy including perioperative medication use and anesthetic techniques were recorded and used in a multivariable regression analysis to study the association with maximum pain intensity, the duration of severe pain, pain interference in bed and postoperative nausea. RESULTS: In 343 hip arthroplasty patients and 301 knee arthroplasty patients in seven hospitals, respectively 28 and 35 different combinations of analgesic regimens were used. The number of different drugs prescribed was not related to postoperative pain intensity. Female sex, younger age and spinal anesthesia were associated with higher postoperative maximum pain scores (Numeric Rating Scale (NRS) > 5). Hip surgery and ketamine use were associated with lower postoperative pain scores. The use of non-steroidal anti-inflammatory drugs (NSAIDs) and gabapentinoids, higher age, higher body mass index (BMI) and male gender were associated with less postoperative nausea (NRS < 3). CONCLUSION: In conclusion, our study demonstrated a large diversity of analgesic strategies following total joint arthroplasties in the Netherlands. Although no ideal strategy was identified, the use of NSAIDs, ketamine and dexamethasone were associated with less pain and less side effects.

Chronic postsurgical pain after minimally invasive adrenalectomy: prevalence and impact on quality of life.

BACKGROUND: Minimally invasive adrenalectomy is the standard of care for small adrenal tumours. Both the transperitoneal lateral approach and posterior retroperitoneal approach are widely used and have been proven to be safe and effective. However, the prevalence of chronic postsurgical pain has not been specifically investigated in previous studies. The primary goal of this study was to identify the prevalence of chronic postsurgical pain after minimally invasive adrenalectomy. METHODS: A cross-sectional study was performed among all consecutive patients who had undergone minimally invasive adrenalectomy in a single university medical centre. The primary outcome was the prevalence of chronic postsurgical pain. Secondary outcomes were the prevalence of localized hypoesthesia, risk factors for the development of chronic postsurgical pain, and the Health-Related Quality of Life. Three questionnaires were used to measure the prevalence and severity of chronic postsurgical pain, hypoesthesia, and Health-Related Quality of Life. Logistic regression analysis was performed to determine risk factors for development of chronic postsurgical pain. RESULTS: Six hundred two patients underwent minimally invasive adrenalectomy between January 2007 and September 2019, of whom 328 signed informed consent. The prevalence of chronic postsurgical pain was 14.9%. In the group of patients with chronic postsurgical pain, 33% reported hypoesthesia as well. Young age was a significant predictor for developing chronic postsurgical pain. The prevalence of localized hypoesthesia was 15.2%. In patients with chronic postsurgical pain, Health-Related Quality of Life was significantly lower, compared to patients without pain. CONCLUSIONS: The prevalence of chronic postsurgical pain following minimally invasive adrenalectomy is considerable. Furthermore, the presence of chronic postsurgical pain was correlated with a significant and clinically relevant lower Health-Related Quality of Life. These findings should be included in the preoperative counselling of the patient. In the absence of evidence for effective treatment in established chronic pain, prevention should be the key strategy and topic of future research.

Pain descriptors and determinants of pain sensitivity in knee osteoarthritis: a community-based cross-sectional study.

Objectives: The aim was to explore pain characteristics in individuals with knee OA (KOA), to compare pain sensitivity across individuals with KOA, individuals with chronic back pain (CBP) and pain-free individuals (NP) and to examine the relationship between clinical characteristics and pain sensitivity and between pain characteristics and pain sensitivity in KOA. Methods: We carried out a cross-sectional, community-based online survey. Two data sets were combined, consisting of Dutch individuals ≥40 years of age, who were experiencing chronic knee pain (KOA, n = 445), chronic back pain (CBP, n = 504) or no pain (NP, n = 256). Demographic and clinical characteristics, global health, physical activity/exercise and pain characteristics, including intensity, spreading, duration, quality (short-form McGill pain questionnaire) and sensitivity (pain sensitivity questionnaire), were assessed. Differences between (sub)groups were examined using analyses of variance or χ2 tests. Regression analyses were performed to examine determinants of pain sensitivity in the KOA group. Results: The quality of pain was most commonly described as aching, tender and tiring-exhausting. Overall, the KOA group had higher levels of pain sensitivity compared with the NP group, but lower levels than the CBP group. Univariately, pain intensity, its variability and spreading, global health, exercise and having co-morbidities were weakly related to pain sensitivity (standardized ß: 0.12-0.27). Symptom duration was not related to pain sensitivity. Older age, higher levels of continuous pain, lower levels of global health, and exercise contributed uniquely, albeit modestly, to pain sensitivity (P < 0.05). Conclusion: Continuous pain, such as aching and tenderness, in combination with decreased physical activity might be indicative for a subgroup of individuals at risk for pain sensitivity and, ultimately, poor treatment outcomes.

Study Design Characteristics and Endpoints for Enriched Enrollment Randomized Withdrawal Trials for Chronic Pain Patients: A Systematic Review.

Enriched enrollment randomized withdrawal (EERW) pain trials are designed to include only responders with considerable pain relief without unacceptable side effects into the randomized phase. There are no recommendations for primary endpoints in such trials. Our objective was to propose recommendations based on assessment of trial characteristics, endpoints and effect sizes in EERW pain trials. We conducted a systematic review by searching electronic databases up to June 2020 for EERW trials comparing an analgesic with a placebo in adults suffering from chronic pain. A total of 28 trials met our criteria, involving 13662 patients in the open or single-blind phase and 7937 patients in the double-blind phase. As primary endpoint 18 trials used pain intensity measured with the visual analogue scale (VAS) or the 11-point numerical rating scale (NRS); 1 trial used a 4-point NRS. Loss of therapeutic response (LTR) was used in 1 trial and time to LTR was used in 8 trials as primary endpoint. Definitions of time to LTR differed considerably between trials. Only 2 out of 8 trials using time to LTR as primary endpoint reported the percentage of patients experiencing a minimum pain relief of 50%, compared to 14 out of 18 trials using NRS or VAS. Due to the complexity and diversity of time to LTR in EERW pain trials, we propose to use the NRS as primary endpoint with conservative imputation methods, and to use time to LTR as secondary endpoint.

Use of antithrombotics at the end of life: an in-depth chart review study.

BACKGROUND: Antithrombotics are frequently prescribed for patients with a limited life expectancy. In the last phase of life, when treatment is primarily focused on optimizing patients' quality of life, the use of antithrombotics should be reconsidered. METHODS: We performed a secondary analysis of a retrospective review of 180 medical records of patients who had died of a malignant or non-malignant disease, at home, in a hospice or in a hospital, in the Netherlands. All medication prescriptions and clinical notes of patients using antithrombotics in the last three months of life were reviewed manually. We subsequently developed case vignettes based on a purposive sample, with variation in setting, age, gender, type of medication, and underlying disease. RESULTS: In total 60% (n=108) of patients had used antithrombotics in the last three months of life. Of all patients using antithrombotics 33.3 % died at home, 21.3 % in a hospice and 45.4 % in a hospital. In total, 157 antithrombotic prescriptions were registered; 30 prescriptions of vitamin K antagonists, 60 of heparins, and 66 of platelet aggregation inhibitors. Of 51 patients using heparins, 32 only received a prophylactic dose. In 75.9 % of patients antithrombotics were continued until the last week before death. Case vignettes suggest that inability to swallow, bleeding complications or the dying phase were important factors in making decisions about the use of antithrombotics. CONCLUSIONS: Antithrombotics in patients with a life limiting disease are often continued until shortly before death. Clinical guidance may support physicians to reconsider (dis)continuation of antithrombotics and discuss this with the patient.

Physicians' Opinions on Anticoagulant Therapy in Patients with a Limited Life Expectancy.

Patients with a limited life expectancy have an increased risk of thromboembolic and bleeding complications. Anticoagulants are often continued until death, independent of their original indication. We aimed to identify the opinions of physicians about the use of anticoagulants at the end of life. A mixed-method research design was used. A secondary analysis was performed on data from a vignette study and an interview study. Participants included general practitioners and clinical specialists. Physicians varied in their opinions: some would continue and others would stop anticoagulants at the end of life because of the risk of thromboembolic or bleeding complications. The improvement or preservation of patients' quality of life was a reason for both stopping and continuing anticoagulants. Other factors considered in the decision-making were the types of anticoagulant, the indication for which the anticoagulant was prescribed, underlying diseases, and the condition and life expectancy of the patient. Factors that made decision-making difficult were the lack of evidence on either strategy, uncertainty about patients' life expectancy, and the fear of harming patients. Which decision was eventually made seems largely dependent on the choice of the patient. In conclusion, there is a substantial variation in physicians' opinions regarding the use of anticoagulants in patients with a limited life expectancy. Physicians agree that the primary goal of medical care at end of life is the improvement or preservation of patients' quality of life. An important barrier to decision-making is the lack of evidence about the risks and benefits of stopping anticoagulants.

The Effect of Protein Supplementation versus Carbohydrate Supplementation on Muscle Damage Markers and Soreness Following a 15-km Road Race: A Double-Blind Randomized Controlled Trial.

We assessed whether a protein supplementation protocol could attenuate running-induced muscle soreness and other muscle damage markers compared to iso-caloric placebo supplementation. A double-blind randomized controlled trial was performed among 323 recreational runners (age 44 ± 11 years, 56% men) participating in a 15-km road race. Participants received milk protein or carbohydrate supplementation, for three consecutive days post-race. Habitual protein intake was assessed using 24 h recalls. Race characteristics were determined and muscle soreness was assessed with the Brief Pain Inventory at baseline and 1-3 days post-race. In a subgroup (n = 149) muscle soreness was measured with a strain gauge algometer and creatine kinase (CK) and lactate dehydrogenase (LDH) concentrations were measured. At baseline, no group-differences were observed for habitual protein intake (protein group: 79.9 ± 26.5 g/d versus placebo group: 82.0 ± 26.8 g/d, p = 0.49) and muscle soreness (protein: 0.45 ± 1.08 versus placebo: 0.44 ± 1.14, p = 0.96). Subjects completed the race with a running speed of 12 ± 2 km/h. With the Intention-to-Treat analysis no between-group differences were observed in reported muscle soreness. With the per-protocol analysis, however, the protein group reported higher muscle soreness 24 h post-race compared to the placebo group (2.96 ± 2.27 versus 2.46 ± 2.38, p = 0.039) and a lower pressure muscle pain threshold in the protein group compared to the placebo group (71.8 ± 30.0 N versus 83.9 ± 27.9 N, p = 0.019). No differences were found in concentrations of CK and LDH post-race between groups. Post-exercise protein supplementation is not more preferable than carbohydrate supplementation to reduce muscle soreness or other damage markers in recreational athletes with mostly a sufficient baseline protein intake running a 15-km road race.

Experiences From the Patient Perspective on Spinal Cord Stimulation for Failed Back Surgery Syndrome: A Qualitatively Driven Mixed Method Analysis.

INTRODUCTION: When neither pharmacological therapies nor alternative interventions provide sufficient pain relief, spinal cord stimulation (SCS) can be used to treat Failed Back Surgery Syndrome (FBSS). Although it seems reasonable that quality of life (QoL)- and psychosocial-related factors contribute to the outcome of SCS since pain is a multidimensional experience, few qualitative studies have explored the expectations of SCS and experiences on SCS to treat FBSS from the patient perspective. OBJECTIVES: The aim of this study was to qualitatively and quantitatively map the FBSS patients' experiences with SCS and the effects of SCS on low back pain caused by FBSS. MATERIALS AND METHODS: A qualitative study with in-depth semi-structured interviews, assisted by the Brief Pain Inventory (BPI)-questionnaire. RESULTS: Seven themes regarding patients' experiences, subdivided into 15 categories, were identified, including an understudied theme within this field of research, Spiritual Well-Being. "Acceptance" and "coping" emerged as pre-eminent motifs throughout these themes. Moreover, the realization of patients' expectations were variable throughout the presented themes. According to the BPI Questionnaire, four out of 13 patients (31%) had significant pain relief (≥50%). Seven out of 13 (54%) reported a ≥50% increase regarding enjoyment of life. CONCLUSION: Multiple QoL- and psychosocial-related themes are related to SCS-outcomes. In order to improve SCS-outcomes for both short- and long-term, these themes should be implemented as a multidimensional approach, both prior to implantation as during follow-up.

Qualitative Evaluation of the Influence of Acute Oxaliplatin-Induced Peripheral Neuropathy on Quality of Life and Activities of Daily Life.

INTRODUCTION/AIMS: Oxaliplatin often causes acute or chronic peripheral neuropathy in patients with an intestinal or pancreatic tumor, but in-depth insights in its influence on quality of life (QoL) are lacking. We explored the influence of acute oxaliplatin-induced peripheral neuropathy (OIPN) on daily QoL in these patients. METHODS: We performed semistructured interviews with a purposive sample of patients receiving oxaliplatin and possibly experiencing acute OIPN. Interviews were audio-recorded, transcribed verbatim, and coded by two researchers. Data were analyzed by using the constant comparative method for content analysis with ATLAS.ti software. RESULTS: After nine patients, saturation took place. In total, 11 patients were interviewed. Four themes were extracted from the data: (1) adverse effects, (2) physical (un)well-being, (3) emotional aspects, and (4) treatment aspects. All participants were suffering from acute OIPN to a certain extent, leading to restrictions in daily activities such as household chores, but also to a decrease in mobility and independency. Other adverse effects such as general malaise and gastrointestinal side effects also influenced the participants' well-being, as did the diagnosis and prognosis of their disease. CONCLUSION: Acute OIPN, together with other side effects of chemotherapeutic treatment and the difficulties that come with the diagnosis of cancer and its prognosis, largely influences patients' daily QoL. Managing expectations (by patient education) seems important.