Compliance with the breakthrough cancer pain European guidelines and impact on patients' quality of life: an observational prospective study.

Introduction: This study aimed to assess the percentage of patients treated according to the European Society for Medical Oncology (ESMO) 2018 guidelines for breakthrough cancer pain (BTcP) and the impact of guidelines adherence on patients' quality of life (QoL). Methods: Adult opioid-tolerant patients diagnosed with BTcP and locally advanced or recurrent metastatic cancer with a life expectancy of >3 months prospectively were included. Patients were followed up for 28 days. Results: Of 127 patients included, 37 were excluded due to the impossibility to establish adherence to the ESMO guidelines. Among the evaluable patients [51.1% female; with mean (SD) age of 66.4 (11.8) years], all were adherent. BTcP was diagnosed by the Association for Palliative Medicine algorithm in 47.8% of patients and by clinical experience in 52.2% of patients. The mean number of daily BTcP episodes ranged between 1 and 8, with a mean (95% CI) severity of 7.3 (7.0; 7.6) at week 0 and 6.2 (5.8; 6.6) at week 4. Time to maximum pain intensity was 3-15 min in 52.2% of patients, and BTcP lasted 30-60 min in 14.4% of patients at week 0 and 4.4% of patients at week 4. Mean (95% CI) treatment effectiveness was 6.6 (6.1; 7.1) at week 0 and 7.4 (7.0; 7.8) at week 4. Median (Q1-Q3) patients' global impression of clinical condition was 4.0 (4.0-4.0) at week 0 and 3.0 (2.0-3.0) at week 4. Conclusion: A clear BTcP assessment and strict follow-up could be crucial to guidelines adherence and for patient's QoL.

A historical perspective of biomedical explainable AI research.

The black-box nature of most artificial intelligence (AI) models encourages the development of explainability methods to engender trust into the AI decision-making process. Such methods can be broadly categorized into two main types: post hoc explanations and inherently interpretable algorithms. We aimed at analyzing the possible associations between COVID-19 and the push of explainable AI (XAI) to the forefront of biomedical research. We automatically extracted from the PubMed database biomedical XAI studies related to concepts of causality or explainability and manually labeled 1,603 papers with respect to XAI categories. To compare the trends pre- and post-COVID-19, we fit a change point detection model and evaluated significant changes in publication rates. We show that the advent of COVID-19 in the beginning of 2020 could be the driving factor behind an increased focus concerning XAI, playing a crucial role in accelerating an already evolving trend. Finally, we present a discussion with future societal use and impact of XAI technologies and potential future directions for those who pursue fostering clinical trust with interpretable machine learning models.

Effectivity of a Program for the Control and Prevention of COVID-19 Healthcare-Associated Infections in a Spanish Academic Hospital.

BACKGROUND: Although recommendations to prevent COVID-19 healthcare-associated infections (HAIs) have been proposed, data on their effectivity are currently limited. OBJECTIVE: The aim was to evaluate the effectivity of a program of control and prevention of COVID-19 in an academic general hospital in Spain. METHODS: We captured the number of COVID-19 cases and the type of contact that occurred in hospitalized patients and healthcare personnel (HCP). To evaluate the impact of the continuous use of a surgical mask among HCP, the number of patients with COVID-19 HAIs and accumulated incidence of HCP with COVID-19 was compared between the preintervention and intervention periods. RESULTS: Two hundred fifty-two patients with COVID-19 have been admitted to the hospital. Seven of them had an HAI origin (6 in the preintervention period and 1 in the intervention period). One hundred forty-two HCP were infected with SARS-CoV-2. Of them, 22 (15.5%) were attributed to healthcare (2 in the emergency department and none in the critical care departments), and 120 (84.5%) were attributed to social relations in the workplace or during their non-work-related personal interactions. The accumulated incidence during the preintervention period was 22.3 for every 1000 HCP and 8.2 for every 1000 HCP during the intervention period. The relative risk was 0.37 (95% confidence interval, 0.25 to 0.55) and the attributable risk was -0.014 (95% confidence interval, -0.020 to -0.009). CONCLUSIONS: A program of control and prevention of HAIs complemented with the recommendation for the continuous use of a surgical mask in the workplace and social environments of HCP effectively decreased the risk of COVID-19 HAIs in admitted patients and HCP.

Long-Term Effectiveness and Tolerability of Pain Treatment with Tapentadol Prolonged Release.

BACKGROUND: The central analgesic tapentadol prolonged release (PR) has proven effective and generally well tolerated in a broad range of chronic pain conditions. Long-term data of its use are still scarce. OBJECTIVES: To evaluate long-term effectiveness, tolerability, and safety of tapentadol PR in patients with severe chronic osteoarthritis (OA) knee pain or low back pain (LBP) who responded to tapentadol in 1 of 4 preceding 12-week phase 3b clinical trials. STUDY DESIGN: Open-label, uncontrolled, observational extension study of up to 72 weeks. SETTING: Fourteen centers in Spain. Protocol approval by the reference ethics committee for all the participating centers. METHODS: Eligible patients started the extension trial on the tapentadol PR dosage optimized for them in the preceding trial; dose adjustments were permitted throughout the extension. Treatment effectiveness outcomes included changes in pain intensity, sleep, state of health, quality of life, patient and clinician global impression of change, and patients' satisfaction with treatment. Patients with OA knee pain also answered the Western Ontario and McMaster Universities OA index, and patients with LBP with a possible neuropathic pain component completed neuropathic pain-related questionnaires. RESULTS: Eighty-three patients were enrolled: 40 with OA knee pain, 43 with LBP. The full analysis set consisted of 81 patients. Mean pain intensity remained relatively stable over the 72-week extension period with mean increases from baseline of 0.44 (95% confidence interval [CI], -0.1,1.0; Numeric Rating Scale) for all patients, 0.2 (95% CI, -0.5, 0.9) for patients with OA, and 0.68 (95% CI, -0.2, 1.6) for patients with LBP. State of health and quality of life baseline ratings were maintained; overall impression of change was "improved." Most patients (88.9%) reported at least good treatment satisfaction at the end of treatment. Mean daily tapentadol PR doses slightly increased from 313.3 ± 139.5 mg at baseline to 315.7 ± 140.1 mg at end of study. Uptitration was required for 8.4% of the patients, 4.8% had a dose reduction during the trial. Adverse events considered probably/likely or certainly related to tapentadol PR treatment by the investigator were documented for 18.1% of all patients, most commonly constipation (7.2%). Seven patients (8.4%) experienced adverse events leading to premature discontinuation. LIMITATIONS: An open-label design, stable concomitant analgesics (World Health Organization step I), and dose adjustments were allowed during the study. All patients had benefitted from tapentadol PR in preceding trials. CONCLUSIONS: Sustained pain relief and quality of life for up to 72 treatment weeks under relatively stable dosing, as well as the good safety profile, indicate the usefulness of tapentadol PR for patients who suffer from severe chronic OA knee pain and LBP with limited risk for tolerance development.

Quality of life and functional outcomes with tapentadol prolonged release in chronic musculoskeletal pain: post hoc analysis.

Aims: To investigate quality of life (QOL) and functionality changes in chronic pain during tapentadol prolonged release (PR) treatment. Patients & methods: Post hoc analysis of data from three Phase III trials in patients with osteoarthritis knee pain or low back pain. QOL and functionality changes were assessed by SF-36 scores. Results: All SF-36 subdomain scores improved progressively to week 3 of tapentadol titration and were sustained during 12-week maintenance treatment. Improvements in SF-36 scores were similar between tapentadol dose groups (e.g., 200 to <300 mg vs ≥500 mg), with no greater effect from higher doses. QOL and functionality improvements were consistently greater with tapentadol PR than oxycodone controlled release. Conclusion: Tapentadol PR provides consistent, clinically relevant improvements in QOL and functionality in chronic pain.

A dataset of attributes from papers of a machine learning conference.

In this work, we present a dataset which provides information on the scientific program of a set conferences of Machine Learning. Data were extracted from the IEEE Xplore Digital Library and the official web site of the International Conference on Machine Learning Applications (ICMLA). We include data of four different editions (from 2014 to 2017). Web scrapping techniques were used to mine the data contained in these web sites. The dataset covers 448 papers presented in the conference and every paper contains 6 attributes including information about the thematic session in which they were presented in the conference. The dataset is hosted in the Mendeley Dataset Repository.

Efectividad y farmacogenética en un protocolo de desprescripción en pacientes con dolor crónico y dependencia iatrogénica a opioides / Effectiveness and pharmacogenetics in a deprescription protocol in chronic pain patients and iatrogenic opioid dependence

Los protocolos de desprescripción deberían formar parte del cuidado de pacientes con dolor crónico no oncológico que hayan desarrollado dependencia iatrogénica a opioides. Nuestro objetivo es evaluar la implantación de un protocolo de desprescripción individualizado (PDI) incluyendo marcadores farmacogenéticos. Se llevó a cabo un estudio observacional prospectivo, de 6 meses de seguimiento con pacientes con dependencia iatrogénica a opioides (n=88). Una vez finalizado el PDI, los pacientes se agruparon en "respondedores" o "no respondedores" al protocolo. Las variantes de los genes OPRM1 (A118G), OPRD1 (T921C), COMT (G472A), ABCB1 (C3435T), ARRB2 (C8622T) y CYP2D6 se determinaron por PCR a tiempo real. Al concluir el estudio, el PDI alcanzó un 64% de respondedores con una reducción de dosis equivalente de morfina diaria (DEMD) significativa (visita basal vs. final, 167 vs. 87 mg/día, p=0.007) sin presentar síndrome de abstinencia, manteniendo un dolor, alivio, calidad de vida y funcionalidad moderados. El porcentaje de pacientes usando buprenorfina o sin opioides fue significativamente mayor en la visita final (65% vs. 22%, p<0.001). Los portadores del genotipo nativo 118-AA OPRM1 requirieron una DEMD menor en la visita inicial (modelo dominante, p=0.018 y superdominante, p=0.020) y en la final (modelo codominante, p=0.032 y recesivo, p=0.032). Nuestro PDI mostró efectividad y seguridad reduciendo la DEMD con una buena conversión a buprenorfina, especialmente en pacientes con genotipo 118-AA OPRM1

Deprescription protocols should be part of chronic non-cancer pain patients’ care in those cases where iatrogenic dependence is present. Our aim is to assess the implementation of a individualized deprescription protocol (IDP) including pharmacogenetic markers. An observational prospective study was carried out in patients presenting prescription opioid dependence (n=88) during 6 months of followup. Once the IDP was ended, patients were grouped in "responders" or "non-responders" to IDP. Genetic variants from OPRM1 (A118G), OPRD1 (T921C), COMT (G472A), ABCB1 (C3435T) and ARRB2 (C8622T) and CYP2D6 genes, were determined by real time PCR. At the end of the study, PDI achieved a 64 % of responders with a significant morphine equivalent daily dose (MEDD) reduction (basal visit vs. final, 167 vs. 87 mg/day, p=0.007) without presenting opiate withdrawal syndrome, keeping a moderate pain intensity, pain relief, quality of life and functionality. Frequency of patients using buprenorphine or without opioids was significantly higher in the last visit than in basal visit (65 % vs. 22 %, p<0.001). Carriers of wild type genotype 118-AA OPRM1 required lower MEDD in the basal visit (dominant, p=0.018 and overdominant models, p=0.020) and in the final visit (codominant, p=0.032 and recessive models, p=0.032). Our IDP showed efectiveness and security in reducing MEDD with a good conversion to buprenorphine, even more in naïve 118-AA OPRM1 genotype

Treatment for chronic low back pain: the focus should change to multimodal management that reflects the underlying pain mechanisms.

Chronic low back pain: Chronic pain is the most common cause for people to utilize healthcare resources and has a considerable impact upon patients' lives. The most prevalent chronic pain condition is chronic low back pain (CLBP). CLBP may be nociceptive or neuropathic, or may incorporate both components. The presence of a neuropathic component is associated with more intense pain of longer duration, and a higher prevalence of co-morbidities. However, many physicians' knowledge of chronic pain mechanisms is currently limited and there are no universally accepted treatment guidelines, so the condition is not particularly well managed. DIAGNOSIS: Diagnosis should begin with a focused medical history and physical examination, to exclude serious spinal pathology that may require evaluation by an appropriate specialist. Most patients have non-specific CLBP, which cannot be attributed to a particular cause. It is important to try and establish whether a neuropathic component is present, by combining the findings of physical and neurological examinations with the patient's history. This may prove difficult, however, even when using screening instruments. Multimodal management: The multifactorial nature of CLBP indicates that the most logical treatment approach is multimodal: i.e. integrated multidisciplinary therapy with co-ordinated somatic and psychotherapeutic elements. As both nociceptive and neuropathic components may be present, combining analgesic agents with different mechanisms of action is a rational treatment modality. Individually tailored combination therapy can improve analgesia whilst reducing the doses of constituent agents, thereby lessening the incidence of side effects. CONCLUSIONS: This paper outlines the development of CLBP and the underlying mechanisms involved, as well as providing information on diagnosis and the use of a wide range of pharmaceutical agents in managing the condition (including NSAIDs, COX-2 inhibitors, tricyclic antidepressants, opioids and anticonvulsants), supplemented by appropriate non-pharmacological measures such as exercise programs, manual therapies, behavioral therapies, interventional pain management and traction. Surgery may be appropriate in carefully selected patients.

A holistic approach to chronic pain management that involves all stakeholders: change is needed.

Chronic pain affects a large proportion of the population, imposing significant individual distress and a considerable burden on society, yet treatment is not always instituted and/or adequate. Comprehensive multidisciplinary management based on the biopsychosocial model of pain has been shown to be clinically effective and cost-efficient, but is not widely available. A literature review of stakeholder groups revealed many reasons for this, including: i) many patients believe healthcare professionals lack relevant knowledge, and consultations are rushed, ii) general practitioners consider that pain management has a low priority and is under-resourced, iii) pain specialists cite non-adherence to evidence-based treatment, sub-optimal prescribing, and chronic pain not being regarded as a disease in its own right, iv) nurses', pharmacists' and physiotherapists' skills are not fully utilized, and v) psychological therapy is employed infrequently and often too late. Many of the issues relating to physicians could be addressed by improving medical training, both at undergraduate and postgraduate levels - for example, by making pain medicine a compulsory core subject of the undergraduate medical curriculum. This would improve physician/patient communication, increase the use of standardized pain assessment tools, and allow more patients to participate in treatment decisions. Patient care would also benefit from improved training for other multidisciplinary team members; for example, nurses could provide counseling and follow-up support, psychologists offer coping skills training, and physiotherapists have a greater role in rehabilitation. Equally important measures include the widespread adoption of a patient-centered approach, chronic pain being recognized as a disease in its own right, and the development of universal guidelines for managing chronic non-cancer pain. Perhaps the greatest barrier to improvement is lack of political will at both national and international level. Some powerful initiatives and collaborations are currently lobbying policy-making bodies to raise standards and reduce unnecessary pain - it is vital they continue.

Pain in the cancer patient: different pain characteristics CHANGE pharmacological treatment requirements.

Twenty years ago, the main barriers to successful cancer pain management were poor assessment by physicians, and patients' reluctance to report pain and take opioids. Those barriers are almost exactly the same today. Cancer pain remains under-treated; in Europe, almost three-quarters of cancer patients experience pain, and almost a quarter of those with moderate to severe pain do not receive any analgesic medication. Yet it has been suggested that pain management could be improved simply by ensuring that every consultation includes the patient's rating of pain, that the physician pays attention to this rating, and a plan is agreed to increase analgesia when it is inadequate. After outlining current concepts of carcinogenesis in some detail, this paper describes different methods of classifying and diagnosing cancer pain and the extent of current under-treatment. Key points are made regarding cancer pain management. Firstly, the pain may be caused by multiple different mechanisms and therapy should reflect those underlying mechanisms - rather than being simply based on pain intensity as recommended by the WHO three-step ladder. Secondly, a multidisciplinary approach is required which combines both pharmacological and non-pharmacological treatment, such as psychotherapy, exercise therapy and electrostimulation. The choice of analgesic agent and its route of administration are considered, along with various interventional procedures and the requirements of palliative care. Special attention is paid to the treatment of breakthrough pain (particularly with fast-acting fentanyl formulations, which have pharmacokinetic profiles that closely match those of breakthrough pain episodes) and chemotherapy-induced neuropathic pain, which affects around one third of patients who receive chemotherapy. Finally, the point is made that medical education should place a greater emphasis on pain therapy, both at undergraduate and postgraduate level.

Managing chronic pain in elderly patients requires a CHANGE of approach.

In many countries, the number of elderly people has increased rapidly in recent years and this is expected to continue; it has been predicted that almost a quarter of the population in the European Union will be over 65 years of age in 2035. Many elderly people suffer from chronic pain but it is regularly under-treated, partly because managing these patients is often complex. This paper outlines the extent of untreated pain in this population and the consequent reduction in quality of life, before articulating the reasons why it is poorly or inaccurately diagnosed. These include the patient's unwillingness to complain, atypical pain presentations, multiple morbidities and cognitive decline. Successful pain management depends upon accurate diagnosis, which is based upon a complete history and thorough physical examination, as well as an assessment of psychosocial functioning. Poor physician/patient communication can be improved by using standardized instruments to establish individual treatment targets and measure progress towards them. User-friendly observational instruments may be valuable for patients with dementia. In line with the widely accepted biopsychosocial model of pain, a multidisciplinary approach to pain management is recommended, with pharmacotherapy, psychological support, physical rehabilitation and interventional procedures available if required. Declining organ function and other physiological changes require lower initial doses of analgesics and less frequent dosing intervals, and the physician must be aware of all medications that the patient is taking, in order to avoid drug/drug interactions. Non-adherence to treatment is common, and various strategies can be employed to improve it; involving the elderly patient's caregivers and family, using medication systems such as pill-boxes, or even sending text messages. In the long term, the teaching of pain medicine needs to be improved--particularly in the use of opioids--both at undergraduate level and after qualification.

Defining opioid tolerance and dependency.

This report is adapted from paineurope 2013; Issue 2, ©Haymarket Medical Publications Ltd., and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, LTD. and is distributed free of charge to healthcare professionals in Europe. Archival issues can be accessed via the website: http://www.paineurope.com at which European health professionals can register online to receive copies of the quarterly publication.

The association of pain with labor force participation, absenteeism, and presenteeism in Spain.

OBJECTIVES: The aims of this paper are to generate estimates of the association between the severity and frequency of pain in Spain and (i) labor force participation and workforce status and (ii) patterns of absenteeism and presenteeism for the employed workforce. METHODS: Data are from the internet-based 2010 National Health and Wellness Survey (NHWS). This survey covers both those who report experiencing pain in the last month as well as the no-pain population. An estimated 17.25% of adults in Spain report experiencing pain in the past month. A series of regression models are developed with the no-pain group as the reference category. The impact of pain, categorized by severity and frequency, is assessed within a labor supply framework for (i) labor force participation and (ii) absenteeism and presenteeism. Both binomial and multinomial logistic models are estimated. RESULTS: The results demonstrate that severe and moderate pain has a significant, substantive, and negative association with labor force participation and, together with the experience of mild pain, a substantive impact on absenteeism and presenteeism within the employed workforce. Compared to no-pain controls, the strongest association is seen in the case of severe pain, notably severe daily pain and labor force participation (odds ratio 0.363; 95% CI: 0.206-0.637). The association of severe pain with labor force participation is also significant (odds ratio 0.356; 95% CI: 0.217-0.585). There is a clear gradient in the association of pain severity and frequency with labor force participation. The impact of pain is far greater than the potential impact of other health status measures (e.g., chronic comorbidities and BMI). Labor force participation is also adversely associated with pain experience. Persons reporting severe daily pain are far more likely not to be in the labor force (relative probabilities 0.339 vs 0.611). The experience of pain, notably severe and frequent pain, also outstrips the impact of other health status factors in absenteeism and presenteeism. In the former case, the odds ratio associated with severe daily pain is 16.216 (95% CI: 5.127-51.283), which contrasts to the odds ratio for the Charlson comorbidity index of 1.460 (95%CI: 1.279-1.666). Similar results hold for presenteeism. The contribution of moderate and mild pain to absenteeism and presenteeism is more marked than for labor force participation. CONCLUSIONS: The experience of pain, in particular severe daily pain, has a substantial negative impact both on labor force participation in Spain as well as reported absenteeism and presenteeism. As a measure of health status, it clearly has an impact that outstrips other health status measures. Whether or not pain is considered as a disease in its own right, the experience of chronic pain, as defined here, presents policy-makers with a major challenge. Programs to relieve the burden of pain in the community clearly have the potential for substantial benefits from societal, individual, and employer perspectives.

Pain, health related quality of life and healthcare resource utilization in Spain.

OBJECTIVES: The aim of this paper is to consider the relationship between the experience of pain, health related quality of life (HRQoL) and healthcare resource utilization in Spain. METHODS: The analysis contrasts the contribution of pain severity and frequency of pain reported against respondents reporting no pain in the previous month. Data are from the 2010 National Health and Wellness Survey (NHWS) for Spain. Single equation generalized linear regression models are used to evaluate the association of pain with the physical and mental component scores of the SF-12 questionnaire as well as health utilities generated from the SF-6D. In addition, the role of pain is assessed in its association with self-reported healthcare provider visits, emergency room visits and hospitalizations in the previous 6 months. RESULTS: The results indicate that the experience of pain, notably severe and frequent pain, is substantial and is significantly associated with the SF-12 physical component scores, health utilities and all aspects of healthcare resource utilization, which far outweighs the role of demographic and socioeconomic variables, health risk factors (in particular body mass index) and the presence of comorbidities. In the case of severe daily pain, the marginal contribution of the SF-12 physical component score is a deficit of -17.86 compared to those reporting no pain (population average score 46.49), while persons who are morbidly obese report a deficit of only -6.63 compared to those who are normal weight. The corresponding association with health utilities is equally dramatic with a severe daily pain deficit of -0.186 compared to those reporting no pain (average population utility 0.71). The impact of pain on healthcare resource utilization is marked. Severe daily pain increases traditional provider visits by 208.8%, emergency room visits by 373.0% and hospitalizations by 348.5%. LIMITATIONS: As an internet-based survey there is the possibility of bias towards those with internet access, although telephone sampling is used to supplement responses. Respondents are asked to describe their experience of pain; there is no independent check on the accuracy of responses. Finally, while certain acute pain categories are omitted, the study focuses on pain in the last month and not on pain chronicity. CONCLUSIONS: The societal burden of severe and frequent pain in Spain is substantial. Although not reported on before, at a national level, the deficit impact of the experience of pain far outweighs the contribution of more traditional explanations of HRQoL deficits as well as being the primary factor associated with increased provider visits, emergency room visits and hospitalizations.