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Opioids depress breathing through two small brainstem sites. Bachmutsky Iris,Wei Xin Paul,Kish Eszter,Yackle Kevin eLife The rates of opioid overdose in the United States quadrupled between 1999 and 2017, reaching a staggering 130 deaths per day. This health epidemic demands innovative solutions that require uncovering the key brain areas and cell types mediating the cause of overdose- opioid-induced respiratory depression. Here, we identify two primary changes to murine breathing after administering opioids. These changes implicate the brainstem's breathing circuitry which we confirm by locally eliminating the µ-Opioid receptor. We find the critical brain site is the preBötzinger Complex, where the breathing rhythm originates, and use genetic tools to reveal that just 70-140 neurons in this region are responsible for its sensitivity to opioids. Future characterization of these neurons may lead to novel therapies that prevent respiratory depression while sparing analgesia. 10.7554/eLife.52694
Analgesic efficacy and safety of morphine in the Procedural Pain in Premature Infants (Poppi) study: randomised placebo-controlled trial. Lancet (London, England) BACKGROUND:Infant pain has immediate and long-term effects but is undertreated because of a paucity of evidence-based analgesics. Although morphine is often used to sedate ventilated infants, its analgesic efficacy is unclear. We aimed to establish whether oral morphine could provide effective and safe analgesia in non-ventilated premature infants for acute procedural pain. METHODS:In this single-centre masked trial, 31 infants at the John Radcliffe Hospital, Oxford, UK, were randomly allocated using a web-based facility with a minimisation algorithm to either 100 μg/kg oral morphine sulphate or placebo 1 h before a clinically required heel lance and retinopathy of prematurity screening examination, on the same occasion. Eligible infants were born prematurely at less than 32 weeks' gestation or with a birthweight lower than 1501 g and had a gestational age of 34-42 weeks at the time of the study. The co-primary outcome measures were the Premature Infant Pain Profile-Revised (PIPP-R) score after retinopathy of prematurity screening and the magnitude of noxious-evoked brain activity after heel lancing. Secondary outcome measures assessed physiological stability and safety. This trial is registered with the European Clinical Trials Database (number 2014-003237-25). FINDINGS:Between Oct 30, 2016, and Nov 17, 2017, 15 infants were randomly allocated to morphine and 16 to placebo; one infant assigned placebo was withdrawn from the study before monitoring began. The predefined stopping boundary was crossed, and trial recruitment stopped because of profound respiratory adverse effects of morphine without suggestion of analgesic efficacy. None of the co-primary outcome measures differed significantly between groups. PIPP-R score after retinopathy of prematurity screening was mean 11·1 (SD 3·2) with morphine and 10·5 (3·4) with placebo (mean difference 0·5, 95% CI -2·0 to 3·0; p=0·66). Noxious-evoked brain activity after heel lancing was median 0·99 (IQR 0·40-1·56) with morphine and 0·75 (0·33-1·22) with placebo (median difference 0·25, 95% CI -0·16 to 0·80; p=0·25). INTERPRETATION:Administration of oral morphine (100 μg/kg) to non-ventilated premature infants has the potential for harm without analgesic efficacy. We do not recommend oral morphine for retinopathy of prematurity screening and strongly advise caution if considering its use for other acute painful procedures in non-ventilated premature infants. FUNDING:Wellcome Trust and National Institute for Health Research. 10.1016/S0140-6736(18)31813-0
Management of Chronic Pain in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline. Paice Judith A,Portenoy Russell,Lacchetti Christina,Campbell Toby,Cheville Andrea,Citron Marc,Constine Louis S,Cooper Andrea,Glare Paul,Keefe Frank,Koyyalagunta Lakshmi,Levy Michael,Miaskowski Christine,Otis-Green Shirley,Sloan Paul,Bruera Eduardo Journal of clinical oncology : official journal of the American Society of Clinical Oncology PURPOSE:To provide evidence-based guidance on the optimum management of chronic pain in adult cancer survivors. METHODS:An ASCO-convened expert panel conducted a systematic literature search of studies investigating chronic pain management in cancer survivors. Outcomes of interest included symptom relief, pain intensity, quality of life, functional outcomes, adverse events, misuse or diversion, and risk assessment or mitigation. RESULTS:A total of 63 studies met eligibility criteria and compose the evidentiary basis for the recommendations. Studies tended to be heterogeneous in terms of quality, size, and populations. Primary outcomes also varied across the studies, and in most cases, were not directly comparable because of different outcomes, measurements, and instruments used at different time points. Because of a paucity of high-quality evidence, many recommendations are based on expert consensus. RECOMMENDATIONS:Clinicians should screen for pain at each encounter. Recurrent disease, second malignancy, or late-onset treatment effects in any patient who reports new-onset pain should be evaluated, treated, and monitored. Clinicians should determine the need for other health professionals to provide comprehensive pain management care in patients with complex needs. Systemic nonopioid analgesics and adjuvant analgesics may be prescribed to relieve chronic pain and/or to improve function. Clinicians may prescribe a trial of opioids in carefully selected patients with cancer who do not respond to more conservative management and who continue to experience distress or functional impairment. Risks of adverse effects of opioids should be assessed. Clinicians should clearly understand terminology such as tolerance, dependence, abuse, and addiction as it relates to the use of opioids and should incorporate universal precautions to minimize abuse, addiction, and adverse consequences. Additional information is available at www.asco.org/chronic-pain-guideline and www.asco.org/guidelineswiki. 10.1200/JCO.2016.68.5206
Effects of Intravenous Eptinezumab vs Placebo on Headache Pain and Most Bothersome Symptom When Initiated During a Migraine Attack: A Randomized Clinical Trial. Winner Paul K,McAllister Peter,Chakhava George,Ailani Jessica,Ettrup Anders,Krog Josiassen Mette,Lindsten Annika,Mehta Lahar,Cady Roger JAMA Importance:Intravenous eptinezumab, an anti-calcitonin gene-related peptide antibody, is approved for migraine prevention in adults. It has established onset of preventive efficacy on day 1 after infusion. Objective:To evaluate the efficacy of and adverse events related to eptinezumab when initiated during a migraine attack. Design, Setting, and Participants:Phase 3, multicenter, parallel-group, double-blind, randomized, placebo-controlled trial conducted from November 4, 2019, to July 8, 2020, at 47 sites in the United States and the country of Georgia. Participants (aged 18-75 years) with a greater than 1-year history of migraine and migraine on 4 to 15 days per month in the 3 months prior to screening were treated during a moderate to severe migraine attack. Interventions:Eptinezumab, 100 mg (n = 238), or placebo (n = 242), administered intravenously within 1 to 6 hours of onset of a qualifying moderate to severe migraine. Main Outcomes and Measures:Co-primary efficacy end points were time to headache pain freedom and time to absence of most bothersome symptom (nausea, photophobia, or phonophobia). Key secondary end points were headache pain freedom and absence of most bothersome symptom at 2 hours after start of infusion. Additional secondary end points were headache pain freedom and absence of most bothersome symptom at 4 hours and use of rescue medication within 24 hours. Results:Of 480 randomized and treated patients (mean age, 44 years; 84% female), 476 completed the study. Patients treated with eptinezumab vs placebo, respectively, achieved statistically significantly faster headache pain freedom (median, 4 hours vs 9 hours; hazard ratio, 1.54 [P < .001]) and absence of most bothersome symptom (median, 2 hours vs 3 hours; hazard ratio, 1.75 [P < .001]). At 2 hours after infusion, in the respective eptinezumab and placebo groups, headache pain freedom was achieved by 23.5% and 12.0% (between-group difference, 11.6% [95% CI, 4.78%-18.31%]; odds ratio, 2.27 [95% CI, 1.39-3.72]; P < .001) and absence of most bothersome symptom by 55.5% and 35.8% (between-group difference, 19.6% [95% CI, 10.87%-28.39%]; odds ratio, 2.25 [95% CI, 1.55-3.25]; P < .001). Results remained statistically significant at 4 hours after infusion. Statistically significantly fewer eptinezumab-treated patients used rescue medication within 24 hours than did placebo patients (31.5% vs 59.9%, respectively; between-group difference, -28.4% [95% CI, -36.95% to -19.86%]; odds ratio, 0.31 [95% CI, 0.21-0.45]; P < .001). Treatment-emergent adverse events occurred in 10.9% of the eptinezumab group and 10.3% of the placebo group; the most common was hypersensitivity (eptinezumab, 2.1%; placebo, 0%). No treatment-emergent serious adverse events occurred. Conclusions and Relevance:Among patients eligible for preventive migraine therapy experiencing a moderate to severe migraine attack, treatment with intravenous eptinezumab vs placebo shortened time to headache and symptom resolution. Feasibility of administering eptinezumab treatment during a migraine attack and comparison with alternative treatments remain to be established. Trial Registration:ClinicalTrials.gov Identifier: NCT04152083. 10.1001/jama.2021.7665
Pain as a Predictor of Opioid Use Disorder in a Nationally Representative Sample. Blanco Carlos,Wall Melanie M,Okuda Mayumi,Wang Shuai,Iza Miren,Olfson Mark The American journal of psychiatry OBJECTIVE:The authors sought to ascertain the relationship between moderate and more severe pain and prescription opioid use disorders in the noninstitutionalized U.S. POPULATION: METHOD:A structural equation model was used to assess prospectively the interdependency of pain and prescription opioid use disorder at waves 1 (2001-2002) and 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions. Pain was measured with a 5-point scale of pain-related interference in daily activities and dichotomized as "no pain" (no or little interference) or "pain" (moderate to extreme interference). Prescription opioid use disorder was assessed with a structured interview (the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV version). Other covariates included age, sex, anxiety or mood disorders, and family history of drug, alcohol, and behavioral problems. RESULTS:In the structural equation model, pain and prescription opioid use disorders were significantly associated with one another at baseline and at 3-year follow-up. However, whereas pain at baseline was also significantly associated with prescription opioid use disorder at follow-up, prescription opioid use disorder at baseline was not associated with pain at follow-up. These associations were independent of several background demographic and clinical characteristics. The path for pain interference was associated with a 41% relative increase in the risk of developing a prescription opioid use disorder. CONCLUSIONS:Painful conditions contribute to the risk of prescription opioid use disorders. To help reduce the incidence of prescription opioid abuse and dependence among adults with moderate to severe pain, careful monitoring and consideration of nonopioid alternative treatments is warranted. 10.1176/appi.ajp.2016.15091179
Vital Signs: Prescription Opioid Pain Reliever Use During Pregnancy - 34 U.S. Jurisdictions, 2019. Ko Jean Y,D'Angelo Denise V,Haight Sarah C,Morrow Brian,Cox Shanna,Salvesen von Essen Beatriz,Strahan Andrea E,Harrison Leslie,Tevendale Heather D,Warner Lee,Kroelinger Charlan D,Barfield Wanda D MMWR. Morbidity and mortality weekly report BACKGROUND:Prescription opioid use during pregnancy has been associated with poor outcomes for mothers and infants. Studies using administrative data have estimated that 14%-22% of women filled a prescription for opioids during pregnancy; however, data on self-reported prescription opioid use during pregnancy are limited. METHODS:CDC analyzed 2019 data from the Pregnancy Risk Assessment Monitoring System (PRAMS) survey in 32 jurisdictions and maternal and infant health surveys in two additional jurisdictions not participating in PRAMS to estimate self-reported prescription opioid pain reliever (prescription opioid) use during pregnancy overall and by maternal characteristics among women with a recent live birth. This study describes source of prescription opioids, reasons for use, want or need to cut down or stop use, and receipt of health care provider counseling on how use during pregnancy can affect an infant. RESULTS:An estimated 6.6% of respondents reported prescription opioid use during pregnancy. Among these women, 21.2% reported misuse (a source other than a health care provider or a reason for use other than pain), 27.1% indicated wanting or needing to cut down or stop using, and 68.1% received counseling from a provider on how prescription opioid use during pregnancy could affect an infant. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE:Among respondents reporting opioid use during pregnancy, most indicated receiving prescription opioids from a health care provider and using for pain reasons; however, answers from one in five women indicated misuse. Improved screening for opioid misuse and treatment of opioid use disorder in pregnant patients might prevent adverse outcomes. Implementation of public health strategies (e.g., improving state prescription drug monitoring program use and enhancing provider training) can support delivery of evidence-based care for pregnant women. 10.15585/mmwr.mm6928a1
Management of persistent pain in the older patient: a clinical review. Makris Una E,Abrams Robert C,Gurland Barry,Reid M Carrington JAMA IMPORTANCE:Persistent pain is highly prevalent, costly, and frequently disabling in later life. OBJECTIVE:To describe barriers to the management of persistent pain among older adults, summarize current management approaches, including pharmacologic and nonpharmacologic modalities; present rehabilitative approaches; and highlight aspects of the patient-physician relationship that can help to improve treatment outcomes. This review is relevant for physicians who seek an age-appropriate approach to delivering pain care for the older adult. EVIDENCE ACQUISITION:Search of MEDLINE and the Cochrane database from January 1990 through May 2014, using the search terms older adults, senior, ages 65 and above, elderly, and aged along with non-cancer pain, chronic pain, persistent pain, pain management, intractable pain, and refractory pain to identify English-language peer-reviewed systematic reviews, meta-analyses, Cochrane reviews, consensus statements, and guidelines relevant to the management of persistent pain in older adults. FINDINGS:Of the 92 identified studies, 35 evaluated pharmacologic interventions, whereas 57 examined nonpharmacologic modalities; the majority (n = 50) focused on older adults with osteoarthritis. This evidence base supports a stepwise approach with acetaminophen as first-line therapy. If treatment goals are not met, a trial of a topical nonsteroidal anti-inflammatory drug, tramadol, or both is recommended. Oral nonsteroidal anti-inflammatory drugs are not recommended for long-term use. Careful surveillance to monitor for toxicity and efficacy is critical, given that advancing age increases risk for adverse effects. A multimodal approach is strongly recommended-emphasizing a combination of both pharmacologic and nonpharmacologic treatments to include physical and occupational rehabilitation, as well as cognitive-behavioral and movement-based interventions. An integrated pain management approach is ideally achieved by cultivating a strong therapeutic alliance between the older patient and the physician. CONCLUSIONS AND RELEVANCE:Treatment planning for persistent pain in later life requires a clear understanding of the patient's treatment goals and expectations, comorbidities, and cognitive and functional status, as well as coordinating community resources and family support when available. A combination of pharmacologic, nonpharmacologic, and rehabilitative approaches in addition to a strong therapeutic alliance between the patient and physician is essential in setting, adjusting, and achieving realistic goals of therapy. 10.1001/jama.2014.9405
U.S. Adults With Pain, a Group Increasingly Vulnerable to Nonmedical Cannabis Use and Cannabis Use Disorder: 2001-2002 and 2012-2013. Hasin Deborah S,Shmulewitz Dvora,Cerdá Magdalena,Keyes Katherine M,Olfson Mark,Sarvet Aaron L,Wall Melanie M The American journal of psychiatry OBJECTIVE:Given changes in U.S. marijuana laws, attitudes, and use patterns, individuals with pain may be an emerging group at risk for nonmedical cannabis use and cannabis use disorder. The authors examined differences in the prevalence of nonmedical cannabis use and cannabis use disorder among U.S. adults with and without pain, as well as whether these differences widened over time. METHODS:Data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC, 2001-2002; N=43,093) and NESARC-III (2012-2013; N=36,309) were analyzed using logistic regression. Risk differences of past-year nonmedical cannabis use, frequent (at least three times a week) nonmedical use, and DSM-IV cannabis use disorder were estimated for groups with and without moderate to severe pain, and these risk differences were tested for change over time. RESULTS:Any nonmedical cannabis use was more prevalent in respondents with than without pain (2001-2002: 5.15% compared with 3.74%; 2012-2013: 12.42% compared with 9.02%), a risk difference significantly greater in the 2012-2013 data than in the 2001-2002 data. The prevalence of frequent nonmedical cannabis use did not differ by pain status in the 2001-2002 survey, but was significantly more prevalent in those with than without pain in the 2012-2013 survey (5.03% compared with 3.45%). Cannabis use disorder was more prevalent in respondents with than without pain (2001-2002: 1.77% compared with 1.35%; 2012-2013: 4.18% compared with 2.74%), a significantly greater risk difference in the data from 2012-2013 than from 2001-2002. CONCLUSIONS:The results suggest that adults with pain are a group increasingly vulnerable to adverse cannabis use outcomes, warranting clinical and public health attention to this risk. Psychiatrists and other health care providers treating patients with pain should monitor such patients for signs and symptoms of cannabis use disorder. 10.1176/appi.ajp.2019.19030284
A personalized approach to assessing and managing pain in patients with cancer. Hui David,Bruera Eduardo Journal of clinical oncology : official journal of the American Society of Clinical Oncology Pain is one of the most common and distressing symptoms in patients with cancer. In this review, we discuss an evidence-based approach to personalized pain assessment and management. Recent insights into the pain expression pathway have led to a paradigm shift in pain management, allowing clinicians to deliver personalized treatments tailored to the individual's needs. Personalized pain management begins with systematic screening, followed by comprehensive pain assessment. Impeccable characterization of pain informs its etiology and the mechanism to guide treatment choices. Identification of modulators of pain expression such as psychological distress, alcoholism, substance use, and delirium allow clinicians to further tailor treatment recommendations. Documentation of a personalized pain goal provides an individualized response criterion. A multidimensional treatment plan is then formulated targeting the pain mechanism, etiologic factors, and modulators. Finally, longitudinal monitoring customized to the individual's needs allows clinicians to improve adherence and, ultimately, to optimize pain control over time. 10.1200/JCO.2013.52.2508
Consensus-Based Guidance on Opioid Management in Individuals With Advanced Cancer-Related Pain and Opioid Misuse or Use Disorder. JAMA oncology Importance:Opioid misuse and opioid use disorder (OUD) are important comorbidities in people with advanced cancer and cancer-related pain, but there is a lack of consensus on treatment. Objective:To develop consensus among palliative care and addiction specialists on the appropriateness of various opioid management strategies in individuals with advanced cancer-related pain and opioid misuse or OUD. Design, Setting, and Participants:For this qualitative study, using ExpertLens, an online platform and methodology for conducting modified Delphi panels, between August and October 2020, we conducted 2 modified Delphi panels to understand the perspectives of palliative and addiction clinicians on 3 common clinical scenarios varying by prognosis (weeks to months vs months to years). Of the 129 invited palliative or addiction medicine specialists, 120 participated in at least 1 round. A total of 84 participated in all 3 rounds. Main Outcomes and Measures:Consensus was investigated for 3 clinical scenarios: (1) a patient with a history of an untreated opioid use disorder, (2) a patient taking more opioid than prescribed, and (3) a patient using nonprescribed benzodiazepines. Results:Participants were mostly women (47 [62%]), White (94 (78 [65%]), and held MD/DO degrees (115 [96%]). For a patient with untreated OUD, regardless of prognosis, it was deemed appropriate to begin treatment with buprenorphine/naloxone and inappropriate to refer to a methadone clinic. Beginning split-dose methadone was deemed appropriate for patients with shorter prognoses and of uncertain appropriateness for those with longer prognoses. Beginning a full opioid agonist was deemed of uncertain appropriateness for those with a short prognosis and inappropriate for those with a longer prognosis. Regardless of prognosis, for a patient with no medical history of OUD taking more opioids than prescribed, it was deemed appropriate to increase monitoring, inappropriate to taper opioids, and of uncertain appropriateness to increase the patient's opioids or transition to buprenorphine/naloxone. For a patient with a urine drug test positive for non-prescribed benzodiazepines, regardless of prognosis, it was deemed appropriate to increase monitoring, inappropriate to taper opioids and prescribe buprenorphine/naloxone. Conclusions and Relevance:The findings of this qualitative study provide urgently needed consensus-based guidance for clinicians and highlight critical research and policy gaps. 10.1001/jamaoncol.2022.2191
Balancing opioid analgesia with the risk of nonmedical opioid use in patients with cancer. Arthur Joseph,Bruera Eduardo Nature reviews. Clinical oncology The current opioid crisis has brought renewed attention and scrutiny to opioid prescriptions. When patients receiving opioid therapy for pain engage in nonmedical opioid use (NMOU) or diversion, untoward consequences can occur. New evidence suggests that patients with cancer might be at a higher risk of NMOU than was previously thought, but clinical evidence still supports the use of opioid analgesics as the gold standard to treat cancer-related pain, creating a dilemma in patient management. Clinicians are encouraged to adopt a universal precautions approach to patients with cancer receiving opioids, which includes screening all patients; discussing the risks, benefits, adverse effects and alternatives of opioid therapy; and providing education on safe use, storage and disposal. Use of urine drug tests, prescription drug monitoring programmes and close observation of behaviours related to opioid use help to ensure treatment adherence, detect NMOU and support therapeutic decision-making. These measures can optimize the risk-benefit ratio while supporting safe opioid use. In this Review, we examine the role of opioids in cancer pain, the risk of substance use disorder and methods to achieve the right balance between the two in order to ensure safe opioid use. 10.1038/s41571-018-0143-7
Automatic Detection of Pain from Facial Expressions: A Survey. Hassan Teena,Seus Dominik,Wollenberg Johannes,Weitz Katharina,Kunz Miriam,Lautenbacher Stefan,Garbas Jens-Uwe,Schmid Ute IEEE transactions on pattern analysis and machine intelligence Pain sensation is essential for survival, since it draws attention to physical threat to the body. Pain assessment is usually done through self-reports. However, self-assessment of pain is not available in the case of noncommunicative patients, and therefore, observer reports should be relied upon. Observer reports of pain could be prone to errors due to subjective biases of observers. Moreover, continuous monitoring by humans is impractical. Therefore, automatic pain detection technology could be deployed to assist human caregivers and complement their service, thereby improving the quality of pain management, especially for noncommunicative patients. Facial expressions are a reliable indicator of pain, and are used in all observer-based pain assessment tools. Following the advancements in automatic facial expression analysis, computer vision researchers have tried to use this technology for developing approaches for automatically detecting pain from facial expressions. This paper surveys the literature published in this field over the past decade, categorizes it, and identifies future research directions. The survey covers the pain datasets used in the reviewed literature, the learning tasks targeted by the approaches, the features extracted from images and image sequences to represent pain-related information, and finally, the machine learning methods used. 10.1109/TPAMI.2019.2958341
Chronic back pain with possible prescription opioid misuse. Alford Daniel P JAMA IMPORTANCE:Data on the effectiveness and safety of long-term opioid therapy for chronic pain are limited. Opioid adherence monitoring includes urine drug testing. Determining whether a patient's opioid prescription should be discontinued after an unexpected urine test result can be clinically complex. OBJECTIVE:To review safe opioid prescribing practices and appropriate interpretation and management of unexpected urine drug test results. EVIDENCE REVIEW:Systematic reviews of the effectiveness and safety of long-term opioid therapy for chronic noncancer pain. Clinical management recommendations are derived from clinical guidelines generated by several professional medical organizations including the American Pain Society, the American Academy of Pain Medicine, and the Federation of State Medical Boards. FINDINGS:Informed consent and patient-prescriber agreements are important strategies to ensure that patients understand treatment goals and potential opioid risks. Monitoring for benefit and opioid misuse is accomplished by having frequent face-to-face assessments, performing urine drug tests, monitoring pill counts, and reviewing prescription drug monitoring program data, when available. CONCLUSIONS AND RELEVANCE:The underlying causes for worrisome behaviors such as urine drug test results that are negative for the prescribed opioid should be fully investigated. Subsequent opioid prescriptions should be based on the revised risk and benefit assessment. 10.1001/jama.2013.522
Biomarkers and Imaging in Chest Pain: The Iceberg Beneath the Waterline. Chinnaiyan Kavitha,Januzzi James L Journal of the American College of Cardiology 10.1016/j.jacc.2021.08.004
Composite Pain Biomarker Signatures for Objective Assessment and Effective Treatment. Tracey Irene,Woolf Clifford J,Andrews Nick A Neuron Pain is a subjective sensory experience that can, mostly, be reported but cannot be directly measured or quantified. Nevertheless, a suite of biomarkers related to mechanisms, neural activity, and susceptibility offer the possibility-especially when used in combination-to produce objective pain-related indicators with the specificity and sensitivity required for diagnosis and for evaluation of risk of developing pain and of analgesic efficacy. Such composite biomarkers will also provide improved understanding of pain pathophysiology. 10.1016/j.neuron.2019.02.019
CDC Guideline for Prescribing Opioids for Chronic Pain--United States, 2016. JAMA IMPORTANCE:Primary care clinicians find managing chronic pain challenging. Evidence of long-term efficacy of opioids for chronic pain is limited. Opioid use is associated with serious risks, including opioid use disorder and overdose. OBJECTIVE:To provide recommendations about opioid prescribing for primary care clinicians treating adult patients with chronic pain outside of active cancer treatment, palliative care, and end-of-life care. PROCESS:The Centers for Disease Control and Prevention (CDC) updated a 2014 systematic review on effectiveness and risks of opioids and conducted a supplemental review on benefits and harms, values and preferences, and costs. CDC used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to assess evidence type and determine the recommendation category. EVIDENCE SYNTHESIS:Evidence consisted of observational studies or randomized clinical trials with notable limitations, characterized as low quality using GRADE methodology. Meta-analysis was not attempted due to the limited number of studies, variability in study designs and clinical heterogeneity, and methodological shortcomings of studies. No study evaluated long-term (≥1 year) benefit of opioids for chronic pain. Opioids were associated with increased risks, including opioid use disorder, overdose, and death, with dose-dependent effects. RECOMMENDATIONS:There are 12 recommendations. Of primary importance, nonopioid therapy is preferred for treatment of chronic pain. Opioids should be used only when benefits for pain and function are expected to outweigh risks. Before starting opioids, clinicians should establish treatment goals with patients and consider how opioids will be discontinued if benefits do not outweigh risks. When opioids are used, clinicians should prescribe the lowest effective dosage, carefully reassess benefits and risks when considering increasing dosage to 50 morphine milligram equivalents or more per day, and avoid concurrent opioids and benzodiazepines whenever possible. Clinicians should evaluate benefits and harms of continued opioid therapy with patients every 3 months or more frequently and review prescription drug monitoring program data, when available, for high-risk combinations or dosages. For patients with opioid use disorder, clinicians should offer or arrange evidence-based treatment, such as medication-assisted treatment with buprenorphine or methadone. CONCLUSIONS AND RELEVANCE:The guideline is intended to improve communication about benefits and risks of opioids for chronic pain, improve safety and effectiveness of pain treatment, and reduce risks associated with long-term opioid therapy. 10.1001/jama.2016.1464
Chronobiology and anaesthesia. Chassard Dominique,Duflo Frederic,de Queiroz Siqueira Mathilde,Allaouchiche Bernard,Boselli Emmanuel Current opinion in anaesthesiology PURPOSE OF REVIEW:It has been shown that biological rhythms influence the pharmacology and effects of anaesthetic agents such as local anaesthetics, hypnotics and muscle relaxants. This review discusses the latest findings and their consequences for anaesthesiological practice. RECENTS FINDINGS: Opioids and new local anaesthetics exhibit circadian changes when they are injected into spinal or epidural spaces for labour pain analgesia. Other studies have demonstrated that propofol and ketamine have maximal duration of action when they are injected during a period of rest in animals (at night in humans). It has been also shown that propofol can perturb the central circadian pacemaker and so cause a phase-shifted advance in effect on activity in rats. SUMMARY:Although studies are lacking for most newer anaesthetic agents used in humans, recent findings emphasize once again that chronobiology should be considered in studies of anaesthetic drugs. Circadian rhythms should be considered in pharmacokinetic and pharmacodynamic analyses so that proper research protocols can be designed. The implications of chronobiology for the practice of clinical anaesthesia are probably of lesser importance because of the use of patient-controlled devices for pain management, monitoring of muscle paralysis and depth of anaesthesia monitors. 10.1097/ACO.0b013e328136c55e
Opioids in chronic non-cancer pain. Chan Bob Kwok Bun,Tam Lee Ka,Wat Chun Yin,Chung Yu Fai,Tsui Siu Lun,Cheung Chi Wai Expert opinion on pharmacotherapy INTRODUCTION:The use of chronic opioid therapy for chronic non-cancer pain is growing and is now accepted as an effective treatment modality. AREAS COVERED:Although there are guidelines and reviews for chronic opioid therapy for chronic non-cancer pain patients, physicians may still have concerns and be reluctant to prescribe strong opioids for chronic non-cancer pain. Common issues and concerns when prescribing opioid for chronic pain management are reviewed and discussed. The literature search was done using Medline with key words 'chronic non-cancer pain', 'chronic opioid therapy', 'effectiveness', 'opioid tolerance', 'opioid-induced hyperalgesia', 'adverse effect', 'opioid dependency', 'addiction', 'monitoring', 'opioid contract' and various combinations with these key words. Studies from 1990 - 2010 have been included. This article helps readers to update, clarify and understand the common concerns when using opioid for chronic non-cancer pain. Clinical effectiveness and adverse effects with chronic opioid therapy, opioid tolerance and opioid-induced hyperalgesia, opioid dependency and addiction, monitoring during chronic opioid use, and opioid contact are discussed in detailed. EXPERT OPINION:Not much strongly positive data supports the long-term use of opioids for pain relief, and the evidence for an improvement in functional activity is inconclusive. With careful selection of patients, meticulous prescription and monitoring protocol, chronic non-cancer pain patients who are likely to benefit from potent opioids should not be prevented from obtaining this treatment. 10.1517/14656566.2011.536335
Pain Management in Chronic Pancreatitis: Summary of Clinical Practice, Current Challenges and Potential Contribution of the M-ANNHEIM Classification. Schneider Alexander,Hirth Michael Drugs Abdominal pain, diarrhea with weight loss, and endocrine insufficiency represent the dominant symptoms of chronic pancreatitis (CP). High intensity of pain and constant pain have been shown to reduce quality of life in CP and may result in disability and increased health resource utilization. Various basic challenges and unanswered questions still exist regarding the treatment of pain in CP. Recently, limited evidence has been gained that early surgery for painful disease might be associated with better treatment results. Thus, timing of pancreatic surgery in painful disease represents a major issue that needs to be clarified in future studies. In this context, surveillance of patients is necessary in clinical practice. It appears that a generally accepted classification of the disease represents a major requirement for inter-institutional comparison of data with future progress in clinical research. Among recently proposed classification systems, the M-ANNHEIM classification system of CP with its recently presented M-ANNHEIM Surgery Score might be a useful tool to picture the course of the disease and to monitor treatment results. Future research is required to clarify the possible role of this system in the management of pain in CP. In the present article, we provide an overview of current status, challenges, and unanswered questions in the treatment of pain in CP, and we demonstrate the potential benefits of the M-ANNHEIM classification system in the management of painful CP. 10.1007/s40265-021-01472-7
Moderate and deep procedural sedation-the role of proper monitoring and safe techniques in clinical practice. Manzi Joseph E,Jones Mark R,Cornett Elyse M,Kaye Alan D Current opinion in anaesthesiology PURPOSE OF REVIEW:Interventional pain management procedures provide significant improvement to patient quality of life and functionality. In-office procedures are becoming an increasingly more common site of pain management intervention for patients with minimal risk of harm. RECENT FINDINGS:Moderate and deep sedation techniques can be used in patients with high anxiety, complex pharmacotherapy, or a low pain threshold. Proper guidance and oversight by an attending anesthesiologist, in addition to appropriate monitoring, are key. Epidural steroid injection complications rates have been cited at 2.4%, with the most common complications noted as persistent pain and flushing. SUMMARY:Serious complication errors can be avoided with proper supervision and monitoring. The adherence to published societal recommendations and guidelines for indications of when to use moderate to deep sedation techniques, and appropriate supervision and monitoring methods, can avoid errors in interventional pain management procedures. 10.1097/ACO.0000000000001011
Managing Cancer Pain in Patients with Opioid and Substance Use Disorders. Edwards Tonya,Foster Toya,Brant Jeannine M Seminars in oncology nursing OBJECTIVE:To discuss the assessment and management of pain in patients with substance use disorders. DATA SOURCES:Peer-reviewed articles, book chapters, internet sources. CONCLUSION:Patients should be routinely assessed for SUDs. Pain management should be stratified according to patient risk. An interdisciplinary approach is essential. IMPLICATIONS FOR NURSING PRACTICE:Oncology nurses should be aware of assessment approaches to screen and monitor patients with SUDs. Oncology nurses are an essential part of the interdisciplinary team when monitoring patients with SUDs. 10.1016/j.soncn.2019.04.009
[Does NoL monitoring affect opioid consumption during da Vinci prostatectomy?] Die Anaesthesiologie BACKGROUND:Administration of opioids to suppress pain plays a major role in modern anesthesia. Measuring depth of hypnosis and neuromuscular recovery are already well established, and devices for pain monitoring are available. Nonetheless pain monitoring is rare in clinical practice. Recently, the pain monitoring device PMD200 (Medasense Biometrics™ , Israel) was introduced. It non-invasively measures heart rate, heart rate variability, skin resistance, resistance variability, temperature and movement to calculate a nociception level (NoL) index. The NoL index range starts at zero, which is equivalent to being painless, and goes up to a value of 100. The validity and reliability of NoL monitoring is the content of current studies. OBJECTIVE:We tested the hypothesis if the use of the PMD200 significantly reduces opioid consumption during da Vinci prostatectomy. MATERIAL AND METHODS:A total of 50 male patients were included in this randomized, single blinded study. Exclusion criteria were arrhythmia because the pain monitoring device requires a sinus rhythm for reliable results. Patients received a weight-adjusted sufentanil bolus (0.3 µg/kg ideal body weight) during induction of anesthesia. Additionally, they received 10 µg of sufentanil before skin incision. Both groups received total intravenous anesthesia with propofol and continuous muscle relaxation through cis-atracurium. In the control group (CONT; n = 26), a standardized sufentanil bolus of 10 µg were administered by common criteria (heart rate/blood pressure increase, lacrimation, gut feeling) at the anesthesiologist's discretion. In the intervention group (INT; n = 24), patients received the standardized sufentanil bolus when the NoL index was above 25 for 2 min, which corresponds to the manufacturer's recommendation. The NoL index and bolus administrations were recorded for every patient. In the control group, the display of the pain monitor showing the NoL index was not visible for the anesthesiologist. Postoperatively, pain/nausea scores and piritramide consumption were taken every 10 min for 1h in the recovery room. None of the patients had prior chronic pain with long-term use of painkillers. Statistics were done using Mann-Whitney U‑test, Kolmogorov-Smirnov test and Levene test. RESULTS:Sufentanil bolus administrations, normalized for duration of surgery, were not significantly lower in the intervention group (p = 0.065). We noticed a significant difference in variation of opioid administrations (p = 0.033). Sufentanil boluses per hour in the INT were normally distributed (p = 0.2), whereas in CONT they were not (p = 0.003). Postoperative data like nausea, opioid consumption and pain scale showed no differences between groups. CONCLUSION:The use of PMD200 did not significantly reduce cumulative opioid consumption. Following on we must reject the initial hypothesis. The difference in sufentanil bolus variances may point to an individualized antinociceptive therapy when NoL monitoring is used. We suppose patients with high opioid demands are detected and patients with low opioid demands did not receive unnecessary opioids. This assumption is only true if the PMD200 measures the entity pain. Further studies with more participants during surgery with higher tissue damage could lead to more convincing data and conclusions. 10.1007/s00101-022-01126-7
A Review of Automated Pain Assessment in Infants: Features, Classification Tasks, and Databases. Zamzmi Ghada,Kasturi Rangachar,Goldgof Dmitry,Zhi Ruicong,Ashmeade Terri,Sun Yu IEEE reviews in biomedical engineering Bedside caregivers assess infants' pain at constant intervals by observing specific behavioral and physiological signs of pain. This standard has two main limitations. The first limitation is the intermittent assessment of pain, which might lead to missing pain when the infants are left unattended. Second, it is inconsistent since it depends on the observer's subjective judgment and differs between observers. Intermittent and inconsistent assessment can induce poor treatment and, therefore, cause serious long-term consequences. To mitigate these limitations, the current standard can be augmented by an automated system that monitors infants continuously and provides quantitative and consistent assessment of pain. Several automated methods have been introduced to assess infants' pain automatically based on analysis of behavioral or physiological pain indicators. This paper comprehensively reviews the automated approaches (i.e., approaches to feature extraction) for analyzing infants' pain and the current efforts in automatic pain recognition. In addition, it reviews the databases available to the research community and discusses the current limitations of the automated pain assessment. 10.1109/RBME.2017.2777907
Monitoring of analgesia level during general anesthesia in children. Current opinion in anaesthesiology PURPOSE OF REVIEW:Monitoring of intraoperative nociception has made substantial progress in adult anesthesia during the last 10 years. Several monitors have been validated and their use has been associated with intraoperative or postoperative benefits in the adult population. In pediatric anesthesia, less data are available. However, several recent publications have assessed the performance of nociception monitors in children, and investigated their potential benefits in this context. This review will describe the main validated intraoperative nociception monitors, summarize adult findings and describe the available pediatric data. RECENT FINDINGS:Six intraoperative nociception indices were included in this review. Among them, four have shown promising results in children: Surgical Pleth Index (GE-Healthcare, Helsinki, Finland), Analgesia-Nociception Index (Mdoloris Medical Systems, Loos, France), Newborn-Infant Parasympathetic Evaluation (Mdoloris Medical Systems), and Pupillometry (IDMED, Marseille, France). The relevance of Skin Conductance (MedStorm innovations, AS, Oslo, Norway) under general anesthesia could not be established. Finally, the Nociception Level (Medasense, Ramat Gan, Israel) still requires to be investigated in children. SUMMARY:To date, four monitors may provide a relevant assessment of intraoperative nociception in children. However, the potential clinical benefits associated with their use to guide analgesia remain to be demonstrated. 10.1097/ACO.0000000000001141
Heterogeneity of chronic pain. Vellucci Renato Clinical drug investigation Chronic pain is a widespread public health issue that has many effects on physical, emotional and cognitive functions. An estimated 10-55% of all adults are thought to have chronic pain. Chronic pain is a multifactorial condition, caused by the complex interplay of nociceptive, neuropathic or mixed pathogenic mechanisms. Chronic pain is associated with specific and non-specific medical conditions such as cancer, HIV/AIDS, rheumatoid arthritis, fibromyalgia, osteoarthritis, low back pain or spinal stenosis and is broadly categorized as cancer pain and non-cancer pain. Evaluation of chronic pain requires a clear understanding of the nature of the pain and its underlying pathophysiology. Adequate assessment of pain, using validated tools, is an essential prerequisite of successful pain management. Unidimensional scales are useful for the measurement of pain intensity, while multidimensional scales measure both pain intensity and the extent to which pain interferes with life activity and emotional functioning. Patients should be reassessed and followed up in order to monitor progress and measure improvements in pain. 10.2165/11630030-000000000-00000
Assessment of salivary cortisol concentrations for procedural pain monitoring in newborns. Journal of perinatal medicine OBJECTIVES:The study aimed to evaluate the usefulness of salivary cortisol (SC) for the assessment of procedural pain intensity in preterm and term newborns. METHODS:Three groups of neonates (term, 37-41 weeks; moderate to late preterm, 32-36; and very preterm, <32) hospitalized in neonatal intensive care unit were assessed for the study. Response to nappy change, lung ultrasound (LUS), and blood sampling was analyzed. The intensity of pain was evaluated using continuous heart rate and blood oxygen saturation (SpO) monitoring, Neonatal Infant Pain Scale (NIPS), and SC concentrations. Saliva samples were collected before and 20 min after the procedure's end. RESULTS:Seventy-one infants were examined: 30 term, 21 moderate to late preterm, and 20 very preterm. SC has increased significantly in response to nappy change only in very preterm newborns (2.13 ng/mL [1.55-3.68] vs. 2.84 ng/mL [1.93-9.06], p = 0.01). LUS did not affect concentrations of SC in any group. Significant increase in SC was observed after blood sampling in term and very preterm infants (2.2 ng/mL [1.45-2.92] vs. 4.29 ng/mL [3.88-5.73], p = 0.002, and 1.88 ng/mL [1.47-4.13] vs. 5.3 ng/mL [3.42-8.02], p = 0.002, respectively). A significant correlation between values of SC increase and NIPS scores was found (Spearman's rank correlation coefficient [r] = 0.31, p = 0.001). CONCLUSIONS:We observed the increase in SC concentrations in response to painful stimulus. The presence of a correlation between NIPS scores and SC increase suggests that SC can be used as an objective parameter to assess pain in neonates. 10.1515/jpm-2022-0320
Wearable Respiratory Monitoring and Feedback for Chronic Pain in Adult Survivors of Childhood Cancer: A Feasibility Randomized Controlled Trial From the Childhood Cancer Survivor Study. Alberts Nicole M,Leisenring Wendy M,Flynn Jessica S,Whitton Jillian,Gibson Todd M,Jibb Lindsay,McDonald Aaron,Ford James,Moraveji Neema,Dear Blake F,Krull Kevin R,Robison Leslie L,Stinson Jennifer N,Armstrong Gregory T JCO clinical cancer informatics PURPOSE:Approximately 40% of childhood cancer survivors experience chronic pain, with many also reporting pain-related disability. Given associations established in the general population among respiration, anxiety, and pain, continuous tracking and feedback of respiration may help survivors manage pain. METHODS:A feasibility, nonblinded, randomized controlled trial (RCT) comparing wearable respiratory monitoring with a control group examined feasibility, acceptability, and preliminary efficacy among survivors of childhood cancer with chronic pain who were ≥ 18 years of age, able to speak and read English, lived in the United States, and had access to a smartphone and the Internet. The primary outcomes were pain interference, pain severity, anxiety, negative affect, and perceived stress. The intervention group (n = 32) received a wearable respiratory monitor, used the device, and completed an in-application breathing exercise daily for 30 days. The control group (n = 33) received psychoeducation after completion of the study. RESULTS:Almost all participants in the intervention group (n = 31 of 32) and control group (n = 32 of 33) completed the study. Of those who completed the intervention, 90.3% wore the device for ≥ 50% of the trial. Posttreatment improvement for negative affect (Cohen = 0.59; 95% CI, 0.09 to 1.10) was significantly greater in the intervention group compared with the control group. A follow-up study (n = 24) examined acceptability and feasibility of a second-generation device among those who completed the RCT. Most survivors (81.0%) wore the device daily during the trial and 85.7% reported satisfaction with the device and the application. CONCLUSION:The results of this pilot study support the acceptability and feasibility of wearable respiratory monitoring among survivors of childhood cancer. Larger randomized trials are needed to assess efficacy and maintenance of this intervention for chronic pain. 10.1200/CCI.20.00070
Neurophysiological evaluation of pain. Bromm B,Lorenz J Electroencephalography and clinical neurophysiology Neurophysiological techniques for the evaluation of pain in humans have made important advances in the last decade. A number of features of neuroanatomy and physiology of nociception qualifies pain as a multidimensional phenomenon which is rather unique among the sensory systems and which poses a number of technical and procedural requirements for its appropriate diagnostic assessment. Various stimulation techniques to induce defined pain in humans and used in combination with the methodology of evoked electrical brain potentials and magnetic fields are presented. Most recent knowledge gathered from scalp topography and dipole source analysis of pain-relevant evoked potentials and fields is discussed. Particular emphasis is put upon laser-evoked potentials and their application for diagnosis, pathophysiological description and monitoring of patients with neurological disorders and abnormal pain states. Future perspectives in this growing field of research are discussed briefly. 10.1016/s0013-4694(98)00075-3
Pain monitor: reality or fantasy in ambulatory patients. Farhang Borzoo,Mathews Donald M Current opinion in anaesthesiology PURPOSE OF REVIEW:In an unconscious patient, there can be significant challenges to monitoring nociception and proper dosing of analgesic medications. The traditional measures of intraoperative nociception have poor sensitivity and specificity with little predictive value in postoperative outcomes such as postoperative pain, opioid-induced side effects, length of stay or incidence of opioid use disorder. To date, several monitoring modalities are in development to establish objective measures of the balance between nociception and analgesia with the goal of guiding anesthesiologists and improve patient outcomes. In this review, some of the most promising monitoring modalities are discussed with the most recent findings. RECENT FINDINGS:Multiple modalities are beginning to demonstrate utility compared with traditional care. Most, but not all, of these studies show decreased intraoperative opioid use and some show lower pain scores and opioid requirements in the postanesthesia care unit. SUMMARY:Recent evidence points to promising efficacy for these monitoring modalities; however, this field is in its infancy. More investigation is required to demonstrate differences in outcome compared with traditional care, and these differences need to be of sufficient import to achieve widespread adoption. 10.1097/ACO.0000000000000797
[Pain among children with cerebral palsy]. Rastoden Ema,Brown Annemette,Pedersen Charlotte Reinhardt Ugeskrift for laeger Although children diagnosed with cerebral palsy have a number of pain triggers (directly from the cerebral palsy, from sequelae and iatrogenic), pain is underdiagnosed. The gap between research and clinical practice is well-known as this group of patients demand special knowledge regarding monitoring of pain. This article presents various pain-monitoring methods. Combining different methods may improve pain assessment and thereby improve quality of life for children with cerebral palsy.
Content and Quality of Mobile Apps for the Monitoring of Musculoskeletal or Neuropathic Pain in Australia: Systematic Evaluation. JMIR mHealth and uHealth Background:Mobile apps offer a potential mechanism for people with persistent pain to monitor pain levels conveniently within their own environment and for clinicians to remotely monitor their patients' pain. However, the quality of currently available apps and the usefulness of included features from a clinical perspective are not known. Objective:The aim of this study was to examine the content and quality of currently available smartphone apps designed for monitoring the intensity or presence of musculoskeletal or neuropathic pain. Methods:A systematic search was performed in the Australian Apple and Google Play stores. Apps were included if they were designed to monitor the intensity or presence of musculoskeletal or neuropathic pain and were available in the English language within the Australian app stores. Data pertaining to the intended use of the app and clinical population were extracted by using a custom-designed data extraction form, and app quality was assessed by using the 23-item Mobile App Rating Scale. Results:Of the 2190 apps screened, 49 met the inclusion criteria. Apps were primarily designed for adult users (36/49, 73%) with nonspecific musculoskeletal or neuropathic pain conditions, arthritis, and joint pain. All apps monitored pain intensity, with almost half (23/49, 47%) also specifying pain location. Overall, the mean quality scores from the Mobile App Rating Scale ranged from 1.5 to 4.4 (out of 5.0). Between 20% (10/49) and 22% (11/49) of apps involved clinicians, consumers, or both in their development, and 20% (10/49) had published literature related to the development or use of the app in clinical scenarios. Although 71% (35/49) had data sharing features, only 5 apps enabled client-clinician communication through the app. Conclusions:The overall quality of mobile apps that are currently available for monitoring pain intensity is acceptable. Presently, mobile apps for remote pain monitoring lack functionality for clinicians to view data between consults. Both users and clinicians should be aware of the limitations of these apps and make informed choices in using or recommending apps that best suit the clinical need. 10.2196/46881
Heterogeneity of chronic pain. Vellucci Renato Clinical drug investigation Chronic pain is a widespread public health issue that has many effects on physical, emotional and cognitive functions. An estimated 10-55% of all adults are thought to have chronic pain. Chronic pain is a multifactorial condition, caused by the complex interplay of nociceptive, neuropathic or mixed pathogenic mechanisms. Chronic pain is associated with specific and non-specific medical conditions such as cancer, HIV/AIDS, rheumatoid arthritis, fibromyalgia, osteoarthritis, low back pain or spinal stenosis and is broadly categorized as cancer pain and non-cancer pain. Evaluation of chronic pain requires a clear understanding of the nature of the pain and its underlying pathophysiology. Adequate assessment of pain, using validated tools, is an essential prerequisite of successful pain management. Unidimensional scales are useful for the measurement of pain intensity, while multidimensional scales measure both pain intensity and the extent to which pain interferes with life activity and emotional functioning. Patients should be reassessed and followed up in order to monitor progress and measure improvements in pain. 10.2165/11630030-000000000-00000
A form to report pain assessment and monitoring in the oncology clinical record: a Delphi process. Future oncology (London, England) Treatment of cancer pain remains suboptimal worldwide. In Italy, a law requires that pain be regularly assessed and reported in both medical and nursing records. To provide a homogeneous form to get exhaustive clinical information in the clinical report according to Italian legislation. A board, including oncologists and pain therapists, designed a form to report the pain characteristics of cancer patients in Italy in clinical records. The form was voted on through a Delphi process among directors of 18 clinical oncology specialization schools in Italy to obtain agreement on its content. A form useful for collecting and reporting comprehensive and homogeneous information on pain among oncologists in Italy was produced. The development of common strategies for pain management can be improved by using this tool. 10.2217/fon-2022-1109
IoT-Based Remote Pain Monitoring System: From Device to Cloud Platform. Yang Geng,Jiang Mingzhe,Ouyang Wei,Ji Guangchao,Xie Haibo,Rahmani Amir M,Liljeberg Pasi,Tenhunen Hannu IEEE journal of biomedical and health informatics Facial expressions are among behavioral signs of pain that can be employed as an entry point to develop an automatic human pain assessment tool. Such a tool can be an alternative to the self-report method and particularly serve patients who are unable to self-report like patients in the intensive care unit and minors. In this paper, a wearable device with a biosensing facial mask is proposed to monitor pain intensity of a patient by utilizing facial surface electromyogram (sEMG). The wearable device works as a wireless sensor node and is integrated into an Internet of Things (IoT) system for remote pain monitoring. In the sensor node, up to eight channels of sEMG can be each sampled at 1000 Hz, to cover its full frequency range, and transmitted to the cloud server via the gateway in real time. In addition, both low energy consumption and wearing comfort are considered throughout the wearable device design for long-term monitoring. To remotely illustrate real-time pain data to caregivers, a mobile web application is developed for real-time streaming of high-volume sEMG data, digital signal processing, interpreting, and visualization. The cloud platform in the system acts as a bridge between the sensor node and web browser, managing wireless communication between the server and the web application. In summary, this study proposes a scalable IoT system for real-time biopotential monitoring and a wearable solution for automatic pain assessment via facial expressions. 10.1109/JBHI.2017.2776351
Responsible, Safe, and Effective Prescription of Opioids for Chronic Non-Cancer Pain: American Society of Interventional Pain Physicians (ASIPP) Guidelines. Manchikanti Laxmaiah,Kaye Adam M,Knezevic Nebojsa Nick,McAnally Heath,Slavin Konstantin,Trescot Andrea M,Blank Susan,Pampati Vidyasagar,Abdi Salahadin,Grider Jay S,Kaye Alan D,Manchikanti Kavita N,Cordner Harold,Gharibo Christopher G,Harned Michael E,Albers Sheri L,Atluri Sairam,Aydin Steve M,Bakshi Sanjay,Barkin Robert L,Benyamin Ramsin M,Boswell Mark V,Buenaventura Ricardo M,Calodney Aaron K,Cedeno David L,Datta Sukdeb,Deer Timothy R,Fellows Bert,Galan Vincent,Grami Vahid,Hansen Hans,Helm Ii Standiford,Justiz Rafael,Koyyalagunta Dhanalakshmi,Malla Yogesh,Navani Annu,Nouri Kent H,Pasupuleti Ramarao,Sehgal Nalini,Silverman Sanford M,Simopoulos Thomas T,Singh Vijay,Solanki Daneshvari R,Staats Peter S,Vallejo Ricardo,Wargo Bradley W,Watanabe Arthur,Hirsch Joshua A Pain physician BACKGROUND:Opioid use, abuse, and adverse consequences, including death, have escalated at an alarming rate since the 1990s. In an attempt to control opioid abuse, numerous regulations and guidelines for responsible opioid prescribing have been developed by various organizations. However, the US opioid epidemic is continuing and drug dose deaths tripled during 1999 to 2015. Recent data show a continuing increase in deaths due to natural and semisynthetic opioids, a decline in methadone deaths, and an explosive increase in the rates of deaths involving other opioids, specifically heroin and illicit synthetic fentanyl. Contrary to scientific evidence of efficacy and negative recommendations, a significant proportion of physicians and patients (92%) believe that opioids reduce pain and a smaller proportion (57%) report better quality of life. In preparation of the current guidelines, we have focused on the means to reduce the abuse and diversion of opioids without jeopardizing access for those patients suffering from non-cancer pain who have an appropriate medical indication for opioid use. OBJECTIVES:To provide guidance for the prescription of opioids for the management of chronic non-cancer pain, to develop a consistent philosophy among the many diverse groups with an interest in opioid use as to how appropriately prescribe opioids, to improve the treatment of chronic non-cancer pain and to reduce the likelihood of drug abuse and diversion. These guidelines are intended to provide a systematic and standardized approach to this complex and difficult arena of practice, while recognizing that every clinical situation is unique. METHODS:The methodology utilized included the development of objectives and key questions. The methodology also utilized trustworthy standards, appropriate disclosures of conflicts of interest, as well as a panel of experts from various specialties and groups. The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed, with a best evidence synthesis of the available literature, and utilized grading for recommendation as described by the Agency for Healthcare Research and Quality (AHRQ).Summary of Recommendations:i. Initial Steps of Opioid Therapy 1. Comprehensive assessment and documentation. (Evidence: Level I; Strength of Recommendation: Strong) 2. Screening for opioid abuse to identify opioid abusers. (Evidence: Level II-III; Strength of Recommendation: Moderate) 3. Utilization of prescription drug monitoring programs (PDMPs). (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 4. Utilization of urine drug testing (UDT). (Evidence: Level II; Strength of Recommendation: Moderate) 5. Establish appropriate physical diagnosis and psychological diagnosis if available. (Evidence: Level I; Strength of Recommendation: Strong) 6. Consider appropriate imaging, physical diagnosis, and psychological status to collaborate with subjective complaints. (Evidence: Level III; Strength of Recommendation: Moderate) 7. Establish medical necessity based on average moderate to severe (≥ 4 on a scale of 0 - 10) pain and/or disability. (Evidence: Level II; Strength of Recommendation: Moderate) 8. Stratify patients based on risk. (Evidence: Level I-II; Strength of Recommendation: Moderate) 9. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. (Evidence: Level I-II; Strength of Recommendation: Moderate) 10. Obtain a robust opioid agreement, which is followed by all parties. (Evidence: Level III; Strength of Recommendation: Moderate)ii. Assessment of Effectiveness of Long-Term Opioid Therapy 11. Initiate opioid therapy with low dose, short-acting drugs, with appropriate monitoring. (Evidence: Level II; Strength of Recommendation: Moderate) 12. Consider up to 40 morphine milligram equivalent (MME) as low dose, 41 to 90 MME as a moderate dose, and greater than 91 MME as high dose. (Evidence: Level II; Strength of Recommendation: Moderate) 13. Avoid long-acting opioids for the initiation of opioid therapy. (Evidence: Level I; Strength of Recommendation: Strong) 14. Recommend methadone only for use after failure of other opioid therapy and only by clinicians with specific training in its risks and uses, within FDA recommended doses. (Evidence: Level I; Strength of Recommendation: Strong) 15. Understand and educate the patients of the effectiveness and adverse consequences. (Evidence: Level I; Strength of Recommendation: Strong) 16. Similar effectiveness for long-acting and short-acting opioids with increased adverse consequences of long-acting opioids. (Evidence: Level I-II; Strength of recommendation: Moderate to strong) 17. Periodically assess pain relief and/or functional status improvement of ≥ 30% without adverse consequences. (Evidence: Level II; Strength of recommendation: Moderate) 18. Recommend long-acting or high dose opioids only in specific circumstances with severe intractable pain. (Evidence: Level I; Strength of Recommendation: Strong)iii. Monitoring for Adherence and Side Effects 19. Monitor for adherence, abuse, and noncompliance by UDT and PDMPs. (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 20. Monitor patients on methadone with an electrocardiogram periodically. (Evidence: Level I; Strength of Recommendation: Strong). 21. Monitor for side effects including constipation and manage them appropriately, including discontinuation of opioids when indicated. (Evidence: Level I; Strength of Recommendation: Strong)iv. Final Phase 22. May continue with monitoring with continued medical necessity, with appropriate outcomes. (Evidence: Level I-II; Strength of Recommendation: Moderate) 23. Discontinue opioid therapy for lack of response, adverse consequences, and abuse with rehabilitation. (Evidence: Level III; Strength of Recommendation: Moderate) CONCLUSIONS: These guidelines were developed based on comprehensive review of the literature, consensus among the panelists, in consonance with patient preferences, shared decision-making, and practice patterns with limited evidence, based on randomized controlled trials (RCTs) to improve pain and function in chronic non-cancer pain on a long-term basis. Consequently, chronic opioid therapy should be provided only to patients with proven medical necessity and stability with improvement in pain and function, independently or in conjunction with other modalities of treatments in low doses with appropriate adherence monitoring and understanding of adverse events.Key words: Chronic pain, persistent pain, non-cancer pain, controlled substances, substance abuse, prescription drug abuse, dependency, opioids, prescription monitoring, drug testing, adherence monitoring, diversionDisclaimer: The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."
Pain management in the 21st century: utilization of pharmacogenomics and therapeutic drug monitoring. Jannetto Paul J,Bratanow Nancy C Expert opinion on drug metabolism & toxicology INTRODUCTION:Anesthesiologists and pain management physicians recognize that the key to clinical success is the ability to effectively control pain and related symptoms in patients without causing excess side effects from prescribed medications. The use of opioids for pain management is broadly accepted by regulatory bodies, professional organizations (i.e., the WHO) and physicians, as is the wide range of patient responses to these medications. Pharmacogenomics and therapeutic drug monitoring are two underutilized tools which can be implemented to best predict and monitor which opioid and dose may be the most appropriate for an individual patient. AREAS COVERED:This review summarizes and discusses evidence for the use of genetic analysis to guide the selection and modification of opioid therapy along with the use of therapeutic drug monitoring to objectively check therapeutic outcomes and compliance. The reader will gain an understanding of the most notable genetic polymorphisms that can affect a patient's response to commonly prescribed opioids, along with the clinical benefits of genotyping and performing therapeutic drug monitoring. EXPERT OPINION:In the end, the authors strongly believe that objective tools such as pharmacogenomics and therapeutic drug monitoring provide added benefit (minimizing adverse effects, while maximizing efficacy) and will ultimately advance the practice of pain management by incorporating these tools into the standard of care. 10.1517/17425255.2011.565051
Risk factors of non-specific neck pain and low back pain in computer-using office workers in China: a cross-sectional study. Ye Sunyue,Jing Qinglei,Wei Chen,Lu Jie BMJ open OBJECTIVES:Several studies have found that inappropriate workstations are associated with musculoskeletal disorders. The present cross-sectional study aimed to identify the risk factors of non-specific neck pain (NP) and low back pain (LBP) among computer-using workers. DESIGN:Observational study with a cross-sectional sample. SETTING:This study surveyed 15 companies in Zhejiang province, China. PARTICIPANTS:After excluding participants with missing variables, 417 office workers, including 163 men and 254 women, were analyzed. OUTCOME MEASURES:Demographic information was collected by self-report. The standard Northwick Park Neck Pain Questionnaire and Oswestry Low Back Pain Disability Index, along with other relevant questions, were used to assess the presence of potential occupational risk factors and the perceived levels of pain. Multinomial logistic regression analysis, adjusted for age, sex, body mass index, education, marital status and neck/low back injury, was performed to identify significant risk factors. RESULTS:Compared with low-level NP, the computer location (monitor not in front of the operator, but on the right or left side) was associated with ORs of 2.6 and 2.9 for medium- and high-level NP, respectively. For LBP, the computer location (monitor not in front) was associated with an OR of 3.2 for high-level pain, as compared with low-level pain, in females. Significant associations were also observed between the office temperature and LBP (OR 5.4 for high vs low), and between office work duration ≥5 years and NP in female office workers (OR 2.7 for medium vs low). CONCLUSIONS:Not having the computer monitor located in front of the operator was found to be an important risk factor for NP and LBP in computer-using female workers. This information may not only enable the development of potential preventive strategies but may also provide new insights for designing appropriate workstations. 10.1136/bmjopen-2016-014914
[Monitoring of pain, nociception, and analgesia under general anesthesia: Relevance, current scientific status, and clinical practice]. von Dincklage F Der Anaesthesist BACKGROUND:To avoid negative effects of painful stimuli under general anesthesia, an adequate analgesia is needed. Since both overdosing and underdosing of analgesics may lead to negative consequences, an optimal dosing is crucial, requiring a continuous monitoring of the balance between the ongoing nociception and the level of analgesia. METHODS:This review describes current methods for the monitoring of nociception and analgesia as well as their inherent differences. RESULTS:Monitors of nociception register organic responses that are triggered through painful stimuli and therefore allow the detection of phases of excessive nociception during inadequate analgesia. In contrast, monitors of analgesia register nociception-specific organic responses that are triggered through test stimuli and allow a preemptive adaption of the level of analgesia, before a painful clinical stimulus is applied, but require the application of test stimuli. Preliminary proof-of-concept studies were able to demonstrate the potential of the here described methods; however, an effect on the clinical outcome of patients has not yet been shown for either of the two types of monitoring. CONCLUSIONS:For the routine application of monitors of nociception and analgesia in daily clinical practice, large clinical studies are necessary, proving a positive outcome effect. Without reliable parameters for nociception and analgesia it was hitherto impossible to perform such studies. The progress made in recent years generates optimism that in the not too distant future the currently available methods to monitor nociception and analgesia might improve to a level of reliability to allow them to be used to investigate the clinical outcome relevance of nociception and analgesia. 10.1007/s00101-015-0080-0
Remote Pain Monitoring Using Fog Computing for e-Healthcare: An Efficient Architecture. Hassan Syed Rizwan,Ahmad Ishtiaq,Ahmad Shafiq,Alfaify Abdullah,Shafiq Muhammad Sensors (Basel, Switzerland) The integration of medical signal processing capabilities and advanced sensors into Internet of Things (IoT) devices plays a key role in providing comfort and convenience to human lives. As the number of patients is increasing gradually, providing healthcare facilities to each patient, particularly to the patients located in remote regions, not only has become challenging but also results in several issues, such as: (i) increase in workload on paramedics, (ii) wastage of time, and (iii) accommodation of patients. Therefore, the design of smart healthcare systems has become an important area of research to overcome these above-mentioned issues. Several healthcare applications have been designed using wireless sensor networks (WSNs), cloud computing, and fog computing. Most of the e-healthcare applications are designed using the cloud computing paradigm. Cloud-based architecture introduces high latency while processing huge amounts of data, thus restricting the large-scale implementation of latency-sensitive e-healthcare applications. Fog computing architecture offers processing and storage resources near to the edge of the network, thus, designing e-healthcare applications using the fog computing paradigm is of interest to meet the low latency requirement of such applications. Patients that are minors or are in intensive care units (ICUs) are unable to self-report their pain conditions. The remote healthcare monitoring applications deploy IoT devices with bio-sensors capable of sensing surface electromyogram (sEMG) and electrocardiogram (ECG) signals to monitor the pain condition of such patients. In this article, fog computing architecture is proposed for deploying a remote pain monitoring system. The key motivation for adopting the fog paradigm in our proposed approach is to reduce latency and network consumption. To validate the effectiveness of the proposed approach in minimizing delay and network utilization, simulations were carried out in iFogSim and the results were compared with the cloud-based systems. The results of the simulations carried out in this research indicate that a reduction in both latency and network consumption can be achieved by adopting the proposed approach for implementing a remote pain monitoring system. 10.3390/s20226574
Depth of Anesthesia and Nociception Monitoring: Current State and Vision For 2050. Anesthesia and analgesia Anesthesia objectives have evolved into combining hypnosis, amnesia, analgesia, paralysis, and suppression of the sympathetic autonomic nervous system. Technological improvements have led to new monitoring strategies, aimed at translating a qualitative physiological state into quantitative metrics, but the optimal strategies for depth of anesthesia (DoA) and analgesia monitoring continue to stimulate debate. Historically, DoA monitoring used patient's movement as a surrogate of awareness. Pharmacokinetic models and metrics, including minimum alveolar concentration for inhaled anesthetics and target-controlled infusion models for intravenous anesthesia, provided further insights to clinicians, but electroencephalography and its derivatives (processed EEG; pEEG) offer the potential for personalization of anesthesia care. Current studies appear to affirm that pEEG monitoring decreases the quantity of anesthetics administered, diminishes postanesthesia care unit duration, and may reduce the occurrence of postoperative delirium (notwithstanding the difficulties of defining this condition). Major trials are underway to further elucidate the impact on postoperative cognitive dysfunction. In this manuscript, we discuss the Bispectral (BIS) index, Narcotrend monitor, Patient State Index, entropy-based monitoring, and Neurosense monitor, as well as middle latency evoked auditory potential, before exploring how these technologies could evolve in the upcoming years. In contrast to developments in pEEG monitors, nociception monitors remain by comparison underdeveloped and underutilized. Just as with anesthetic agents, excessive analgesia can lead to harmful side effects, whereas inadequate analgesia is associated with increased stress response, poorer hemodynamic conditions and coagulation, metabolic, and immune system dysregulation. Broadly, 3 distinct monitoring strategies have emerged: motor reflex, central nervous system, and autonomic nervous system monitoring. Generally, nociceptive monitors outperform basic clinical vital sign monitoring in reducing perioperative opioid use. This manuscript describes pupillometry, surgical pleth index, analgesia nociception index, and nociception level index, and suggest how future developments could impact their use. The final section of this review explores the profound implications of future monitoring technologies on anesthesiology practice and envisages 3 transformative scenarios: helping in creation of an optimal analgesic drug, the advent of bidirectional neuron-microelectronic interfaces, and the synergistic combination of hypnosis and virtual reality. 10.1213/ANE.0000000000006860
Identifying and monitoring pain in farm animals: a review. Prunier A,Mounier L,Le Neindre P,Leterrier C,Mormède P,Paulmier V,Prunet P,Terlouw C,Guatteo R Animal : an international journal of animal bioscience One important objective for animal welfare is to maintain animals free from pain, injury or disease. Therefore, detecting and evaluating the intensity of animal pain is crucial. As animals cannot directly communicate their feelings, it is necessary to identify sensitive and specific indicators that can be easily used. The aim of the present paper is to review relevant indicators to assess pain in several farm species. The term pain is used for mammals, birds and fish, even though the abilities of the various species to experience the emotional component of pain may be different. Numerous behavioural changes are associated with pain and many of them could be used on farms to assess the degree of pain being experienced by an animal. Pain, as a stressor, is associated with variations in the hypothalamic-pituitary-adrenal axis as well as in the sympathetic and immune systems that can be used to identify the presence of pain rapidly after it started. However, most of these measures need sophisticated equipment for their assessment. Therefore, they are mainly adapted to experimental situations. Injuries and other lesional indicators give information on the sources of pain and are convenient to use in all types of situations. Histopathological analyses can identify sources of pain in experimental studies. When pronounced and/or long lasting, the pain-induced behavioural and physiological changes can decrease production performance. Some indicators are very specific and sensitive to pain, whereas others are more generally related to stressful situations. The latter can be used to indicate that animals are suffering from something, which may be pain. Overall, this literature review shows that several indicators exist to assess pain in mammals, a few in birds and very few in fish. Even if in some cases, a single indicator, usually a behavioural indicator, may be sufficient to detect pain, combining various types of indicators increases sensitivity and specificity of pain assessment. Research is needed to build and validate new indicators and to develop systems of pain assessment adapted to each type of situation and each species. 10.1017/S1751731112002406
Surgical pleth index monitoring in perioperative pain management: usefulness and limitations. Korean journal of anesthesiology Surgical pleth index (SPI) monitoring is a representative, objective nociception-monitoring device that measures nociception using photoplethysmographic signals. It is easy to apply to patients and the numerical calculation formula is intuitively easy to understand; therefore, its clinical interpretation is simple. Several studies have demonstrated its efficacy and utility. Compared with hemodynamic parameters, the SPI can detect the degree of nociception during surgery under general anesthesia with greater accuracy, and therefore can provide better guidance for the administration of various opioids, including remifentanil, fentanyl, and sufentanil. Indeed, SPI-guided analgesia is associated with lower intraoperative opioid consumption, faster patient recovery, and comparable or lower levels of postoperative pain and rates of adverse events compared with conventional analgesia. In addition, SPI monitoring allows for the degree of postoperative pain and analgesic requirements to be predicted through the SPI values immediately before patient arousal. However, because patient age, effective circulating volume, position, concomitant medication and anesthetic regimen and level of consciousness may be confounding factors in SPI monitoring, clinicians must be careful when interpreting SPI values. In addition, as SPI values can differ depending on anesthetic and analgesic regimens and the underlying disease, an awareness of the effects of these variables with an understanding of the advantages and disadvantages of SPI monitoring compared to other nociception monitoring devices is essential. Therefore, this review aimed to help clinicians perform optimal SPI-guided analgesia and to assist with the establishment of future research designs through clarifying current usefulness and limitations of SPI monitoring in perioperative pain management. 10.4097/kja.23158
Objective monitoring of nociception: a review of current commercial solutions. Ledowski Thomas British journal of anaesthesia Nociception, in contrast to pain, is not a subjective feeling, but the physiological encoding and processing of nociceptive stimuli. However, monitoring nociception remains a challenge in attempts to lower the incidence of acute postoperative pain and the move towards a more automated approach to analgesia and anaesthesia. To date, several commercialised devices promise a more accurate reflection of nociception than the traditionally used vital signs, blood pressure and heart rate. This narrative review presents an overview of existing technologies and commercially available devices, and offers a perspective for future research. Although firm conclusions about individual methods may be premature, none currently appears to offer a sufficiently broad applicability. Furthermore, there is currently no firm evidence for any clinically relevant influence of such devices on patient outcome. However, the available monitors have significantly aided the understanding of underlying mechanisms and identification of potential pitfalls. 10.1016/j.bja.2019.03.024
Understanding Monitoring Technologies for Adults With Pain: Systematic Literature Review. Journal of medical Internet research BACKGROUND:Monitoring of patients may decrease treatment costs and improve quality of care. Pain is the most common health problem that people seek help for in hospitals. Therefore, monitoring patients with pain may have significant impact in improving treatment. Several studies have studied factors affecting pain; however, no previous study has reviewed the contextual information that a monitoring system may capture to characterize a patient's situation. OBJECTIVE:The objective of this study was to conduct a systematic review to (1) determine what types of technologies have been used to monitor adults with pain, and (2) construct a model of the context information that may be used to implement apps and devices aimed at monitoring adults with pain. METHODS:A literature search (2005-2015) was conducted in electronic databases pertaining to medical and computer science literature (PubMed, Science Direct, ACM Digital Library, and IEEE Xplore) using a defined search string. Article selection was done through a process of removing duplicates, analyzing title and abstract, and then reviewing the full text of the article. RESULTS:In the final analysis, 87 articles were included and 53 of them (61%) used technologies to collect contextual information. A total of 49 types of context information were found and a five-dimension (activity, identity, wellness, environment, physiological) model of context information to monitor adults with pain was proposed, expanding on a previous model. Most technological interfaces for pain monitoring were wearable, possibly because they can be used in more realistic contexts. Few studies focused on older adults, creating a relevant avenue of research on how to create devices for users that may have impaired cognitive skills or low digital literacy. CONCLUSIONS:The design of monitoring devices and interfaces for adults with pain must deal with the challenge of selecting relevant contextual information to understand the user's situation, and not overburdening or inconveniencing users with information requests. A model of contextual information may be used by researchers to choose possible contextual information that may be monitored during studies on adults with pain. 10.2196/jmir.7279
[Monitoring pain intensity during general anaesthesia]. Bjørn Maria,Andersen Claus Ugeskrift for laeger This review summarises the knowledge of pain monitoring during surgery in Denmark. General anaesthesia consists of hypnosis, relaxation and analgesia. The first two can be objectively monitored, but analgesia is traditionally evalu-ated by the anaesthesiologist. Several monitors for as-sessing pain exist, and all types of pain monitoring are superior to traditional evaluation and seem to have several advantages but are still not used routinely in Denmark. The nociception level monitor is multimodal and incorporates movement, heart rate, heart rate variability, pulse plethysmography, skin temperature and galvanic skin response. It has been validated, but further research is needed.