Association of preoperative opioid use and postoperative complications following breast reconstruction.

BACKGROUND: Previous studies in orthopedics and general surgery have linked negative patient outcomes with preoperative opioid use. In this study, we investigated the association of preoperative opioid use on breast reconstruction outcomes and quality of life (QoL). METHODS: We reviewed our prospective registry of patients who underwent breast reconstruction for documented preoperative opioid use. Postoperative complications were recorded at 60 days after the first reconstructive surgery and 60 days after the final staged reconstruction. We used a logistic regression model to assess the association between opioid use and postoperative complications, controlling for smoking, age, laterality, BMI, comorbidities, radiation, and previous breast surgery; linear regression to analyze RAND36 scores to evaluate the impact of preoperative opioid use on postoperative QoL, controlling for the same factors; and Pearson chi-squared test to assess factors that may be associated with opioid use. RESULTS: Of the 354 patients eligible for inclusion, 29 (8.2%) were prescribed preoperative opioids. There were no differences in opioid use by race, BMI, comorbidities, previous breast surgery, or laterality. Preoperative opioids were associated with increased odds of postoperative complications within 60 days after the first reconstructive surgery (OR: 6.28; 95% CI: 1.69-23.4; p = 0.006) and within 60 days after the final staged reconstruction (OR: 8.38; 95% CI: 1.17-59.4; p = 0.03). Among patients using opioids preoperatively, the RAND36 physical and mental scores decreased but were not statistically significant. CONCLUSION: We found that preoperative opioid use is associated with increased odds of postoperative complications among patients who underwent breast reconstruction and may contribute to clinically significant declines in postoperative QoL.

Improving understanding of disease control implementation research through a mooc with participants from low- and middle-income countries: Evaluating participant reactions and learning.

The Special Programme for Research and Training in Tropical Diseases developed a massive open online course (MOOC) on implementation research with a focus on infectious diseases of poverty (IDPs) to reinforce the explanation of implementation research concepts through real case studies. The target MOOC participant group included public health officers, researchers and students. By reshaping institutions and building resilience in communities and systems, implementation research will allow progress towards universal health coverage and sustainable development goals. This study evaluates learners' knowledge in implementation research after completing the MOOC using anonymous exit survey responses. Of the almost 4000 enrolled in the two sessions of the MOOC in 2018, about 30% completed all five modules and the assessments, and were awarded certificates. The majority of the participants were early to mid-career professionals, under the age of 40, and from low- and middle-income countries. They were slightly more likely to be men (56%) with a Bachelor or a Master's degree. Participants were public health researchers (45%), public health officers (11%) or students (11%). On completion of the course, an exit survey revealed that 80.9% of respondents indicated significant improvement to strong and very strong implementation research knowledge. This evaluation clearly shows the usefulness of the MOOC on implementation research for reaching out to field researchers and public health practitioners who are facing problems in the implementation of control programmes in low- and middle-income countries.

Adverse Effects Associated with Patient-Controlled Analgesia with Ketamine Combined with Opioids and Ketamine Infusion with PCA Bolus in Postoperative Spine Patients: A Retrospective Review.

Objective: There has been increasing use of ketamine at subanesthetic doses as an adjunct to opioids in perioperative pain management. There are several known adverse drug effects (ADEs) associated with ketamine. However, the incidence of ADEs with ketamine infusions with patient-controlled analgesia (PCA) boluses compared with combined opioid and ketamine PCAs is not well described. The objectives of this study were to compare the incidence and type of ADEs in postoperative spine surgery patients on ketamine infusions with as-needed PCA boluses to patients on combined opioid and ketamine PCAs. Methods: The medical records of patients who underwent spine surgery between March 2016 and March 2020 who were postoperatively treated with a ketamine infusion and as-needed PCA boluses and parenteral opioids or treated with a combined opioid and ketamine PCA were reviewed. Perioperative information including patient characteristics and preoperative morphine equivalent daily dose (MEDD) were collected. Patient charts were reviewed for ADEs including psychological and neurological side effects, nausea, and new-onset tachycardia. Results: A total of 315 patients met the inclusion criteria and were included in the final analysis. Of these patients, 121 experienced at least one ADE (38%). Sixteen of the 68 ketamine infusion with PCA bolus patients (24%), 77 of the 203 hydromorphone and ketamine patients (38%), and 28 of the 44 morphine and ketamine patients (64%) experienced an ADE [p<0.01]. In patients with preoperative MEDD ≤ 90, nausea was the only ADE that differed significantly among the three groups. Conclusion: This retrospective analysis suggests that postoperative spine patients treated with a ketamine infusion with as-needed PCA boluses and parenteral opioids were associated with fewer ADEs when compared to an intravenous combined opioid and ketamine PCA. In patients with preoperative MEDD ≤ 90, nausea with and without emesis was the only ADE that showed statistically significant difference amongst the three groups.

Estimates of Probabilities of Successful Development of Pain Medications: An Analysis of Pharmaceutical Clinical Development Programs from 2000 to 2020.

BACKGROUND: The authors estimate the probability of successful development and duration of clinical trials for medications to treat neuropathic and nociceptive pain. The authors also consider the effect of the perceived abuse potential of the medication on these variables. METHODS: This study uses the Citeline database to compute the probabilities of success, duration, and survivorship of pain medication development programs between January 1, 2000, and June 30, 2020, conditioned on the phase, type of pain (nociceptive vs. neuropathic), and the abuse potential of the medication. RESULTS: The overall probability of successful development of all pain medications from phase 1 to approval is 10.4% (standard error, 1.5%). Medications to treat nociceptive and neuropathic pain have a probability of successful development of 13.3% (standard error, 2.3%) and 7.1% (standard error, 1.9%), respectively. The probability of successful development of medications with high abuse potential and low abuse potential are 27.8% (standard error, 4.6%) and 4.7% (standard error, 1.2%), respectively. The most common period for attrition is between phase 3 and approval. CONCLUSIONS: The authors' data suggest that the unique attributes of pain medications, such as their abuse potential and intended pathology, can influence the probability of successful development and duration of development.

Evaluating results of the implementation research MOOC using Kirkpatrick's four-level model: a cross-sectional mixed-methods study.

INTRODUCTION: An implementation research (IR) massive open online course (MOOC) was developed by the Special Programme for Research and Training in Tropical Diseases, to address the scarcity of training in low-income and middle-income countries in the field of IR. The Kirkpatrick model was used to evaluate the IR MOOC as it is widely applied for evaluation of training and educational programmes. The Kirkpatrick model evaluates training programmes on four levels: reaction, learning, behaviour and results. This paper addresses the impact of the IR MOOC on participants' professional practice. METHODS: Findings are based on analysis of survey and interview data collected 1.5-2 years after the conclusion of the two 2018 IR MOOC offerings. Of the 3858 MOC participants, 748 responded to the anonymous online survey and seven of these respondents were interviewed. All data are self-reported. RESULTS: The IR MOOC was successful in enhancing the professional practice of participants and for their organisations. Over 40% reported modifying or implementing changes in their professional work. Respondents reported that participation in the MOOC had improved their ability to conduct IR, enhanced their professional profiles and increased their opportunities for collaboration, research and job promotion. Respondents stated that the MOOC had improved their work quality and productivity, and allowed them to contribute to research, initiate and develop professional collaborations and train others in IR. Respondents reported an increase in applying for grants and scholarships and presenting and publishing work on IR after participating in the MOOC. Barriers applying the knowledge gained from the IR MOOC were experienced, for example, due to a lack of funding and lack of support from colleagues, managers and organisations. CONCLUSION: Participants perceived that the IR MOOC was successful in its aims of delivering medium-term and long-term results in relation to their own and their organisations' professional outcomes.

Infectious Complications of Dorsal Root Ganglion Stimulation: A Systematic Review and Pooled Analysis of Incidence.

BACKGROUND AND OBJECTIVES: Dorsal root ganglion stimulation (DRGS) is a newer form of neuromodulation that targets the dorsal root ganglion. DRGS has superior efficacy in complex regional pain syndrome compared to spinal cord stimulation (SCS) and may have efficacy in other forms of chronic pain. While decades of safety data are available for SCS, there is less available safety information for DRGS. The objectives of this systematic review and pooled analysis of incidence are to determine the overall incidence of DRGS infections, incidence at each stage (trial vs implant vs revision), infection characteristics, and outcomes. MATERIALS AND METHODS: A comprehensive search of databases from January 1980 to January 2021 was conducted. RESULTS: Ten studies met inclusion criteria. Eight studies reported patients with trial data (n = 291), ten studies reported patients with implant data (n = 250), and seven studies reported data with revisions (n = 26). The pooled incidence of trial infections was 1.03% (95% CI 0.35-2.99%), implant infections was 4.80% (95% CI 2.77-8.20%), revision infections was 3.85% (95% CI 0.20-21.59%), and overall infections was 2.82% (95% CI 1.62-4.54%). There was a statistically significant difference in infection rates between the trial, implant, and revision stages, X2 (2, N = 567) = 8.9839, p = 0.01. CONCLUSIONS: This is the first systematic review and pooled analysis that followed PRISMA guidelines to report infectious complications of DRGS by stage (trial vs implant vs revision). DRGS trial appears to be low risk for infection but that risk is significantly increased with DRGS implant. Our findings highlight the need for further study of infectious complications, their risks, and optimal prophylaxis.

Changes in Patient Satisfaction Scores During the Early COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has caused a rapid and widespread application of telemedicine services in the outpatient setting. Prior to COVID-19, patient satisfaction was measured with Consumer Assessment of Healthcare Providers and Systems (CAHPS) Clinician & Group Survey (CG-CAHPS) and was then measured with the Press Ganey telemedicine survey. Both surveys ask about a patient's likelihood to recommend a particular medical practice, which is a useful, but imperfect, surrogate for overall satisfaction. The purpose of this analysis was to identify any changes in patient satisfaction scores with the implementation of telemedicine services. A retrospective analysis of our institution's experience during the early months of the COVID-19 pandemic compared to the months immediately prior to the pandemic was conducted. The percent of patients with a "Top box" response to survey questions regarding their likelihood to recommend a medical practice were compared. A total of 14 430 CG-CAHPS results collected in November 2019 through February 2020 were compared to 22 009 telemedicine survey results collected between March and May 2020. In general, most medical specialties incorporated telemedicine but suffered a decrease in their patient's likelihood to recommend a medical practice during the first few months of the pandemic. However, the magnitude of this decrease was variable by medical specialty. Physical medicine and rehabilitation and pain medicine had relatively poor scores prior to the pandemic which did not statistically change. Oncology was the sole medical specialty that continued to have unchanged high patient satisfaction scores. These data provide insights for the refinement of telemedicine.

Implementation research training for learners in low- and middle-income countries: evaluating behaviour change after participating in a massive open online course.

BACKGROUND: Implementation research (IR) can play a critical role in the delivery of disease control interventions, particularly in low- and middle-income countries (LMICs). The growing demand for IR training has led to the development of a range of training programmes and university courses, the majority of which can not be accessed by learners in LMICs. This article reports on the evaluation of the massive open online course (MOOC) developed by the Special Programme for Research and Training in Tropical Diseases hosted by WHO on the topic of IR with a focus on infectious diseases of poverty. This study followed the Kirkpatrick Model to evaluate training programmes with a specific focus on post-training changes in behaviour. METHODS: MOOC participants were invited to take part in an anonymous online survey examining their knowledge of IR and how they applied it in their professional practice approximately 1-1.5 years after completing their course. The survey contained 43 open-ended, multiple choice and Likert-type questions. Descriptive statistics were calculated for the quantitative data and responses to the open-ended questions were thematically coded. RESULTS: A total of 748 MOOC participants responded to the survey. The demographic profile of the survey respondents aligned with that of the MOOC participants, with nearly 70% of respondents originating from Africa. Responses to the quantitative and open-ended survey questions revealed that respondents' knowledge of IR had improved to a large extent as a result of the MOOC, and that they used the knowledge and skills gained in their professional lives frequently and had consequently changed their professional behaviour. Respondents most often cited the problem-solving aspect of IR as a substantial area of behavioral change influenced by participating in the MOOC. CONCLUSIONS: These findings indicate that the MOOC was successful in targeting learners from LMICs, in strengthening their IR knowledge and contributing to their ability to apply it in their professional practice. The utility of MOOCs for providing IR training to learners in LMICs, where implementation challenges are encountered often, makes this platform an ideal standalone learning tool or one that could be combined with other training formats.

Pilot randomized active-placebo-controlled trial of low-dose ketamine for the treatment of multiple sclerosis-related fatigue.

BACKGROUND: Fatigue is the most common symptom of MS and has no effective pharmacotherapy. OBJECTIVE: To determine the tolerability, safety, and efficacy of low-dose ketamine infusion for MS-related fatigue. METHODS: In this double-blind, randomized, active-placebo-controlled trial, 18 subjects with multiple sclerosis (MS) and reported fatigue received a single intravenous infusion of ketamine (0.5 mg/kg) or midazolam (0.05 mg/kg). The primary outcome was change in Daily Fatigue Severity (DFS) for 7 days following the infusion. Secondary outcomes included Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS) measured up to day 28 post-infusion. We analyzed changes in all outcomes using mixed-effect models. RESULTS: In total, 18 participants were enrolled; 67% participants received ketamine. Side effects of ketamine were transient. No change in the DFS was observed after 7 days (-0.10 point; 95% confidence interval (CI): -0.32, 0.12; p = 0.40). We observed a trend in reduced FSS scores at 1 week (-5.2 points; 95% CI: -10.4, 0.14; p = 0.06) and a clinically and statistically significant reduction in MFIS score at day 28 (-13.5 point; 95% CI: -25.0, -1.98; p = 0.04). CONCLUSIONS: Ketamine infusions were safe and well-tolerated. While no change in DFS after 7 days was observed, secondary analyses suggest a benefit of ketamine infusion for reduction of longer term fatigue severity in people with MS.

Incorporating operational research in programmes funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria in four sub-Saharan African countries.

BACKGROUND: The current study builds upon a previous situation analysis of the extent to which grants from the Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund) are being utilized to support operational research and implementation research (OR/IR) activities in recipient countries. The objective of this follow-up study was to identify approaches and pathways to implement an OR component into grants to the Global Fund, in four sub-Saharan African countries. Special focus was given to the Structured Operational Research and Training IniTiative (SORT IT). METHODS: The conceptual framework was based on an analysis to identify elements supporting and blocking the integration of OR, called force field analysis, and a behavioural change assessment covering aspects such as opportunity, motivation, capability and triggers to do the integration. Data were collected through online surveys and stakeholder interviews both via telephone/online conference tools and in person in four countries with a high burden of malaria and tuberculosis. These countries were Ghana, Sierra Leone, the United Republic of Tanzania and Zimbabwe. The stakeholders included programme managers, implementation partners, representatives from international organisations, academic and governmental research institutions and other individuals involved in the countries' needs assessment and National Strategic Plan development. RESULTS: We identified opportunities to integrate OR into the countries' programmes during the funding process, the country's needs assessment being the most important one, including the need of OR-related capacity. Both the force field analysis and the behavioural change assessment showed that the necessary elements to integrate OR were present in the countries. Motivation, capability and efficiency were found to be a managerial value omnipresent across stakeholders. However, those elements were influenced by the tendency to favour tangible assets over any abstract ones, such as increasing organisational capacity in OR. CONCLUSIONS: In each of the countries assessed, there is potential to integrating OR into the programmes supported by the Global Fund. However, given the relative lack of OR-related capacity and skills encountered, a capacity strengthening tool, such as SORT IT, would be of benefit helping to identify and carry forward OR activities sustainably.

Strengthening the core health research capacity of national health systems helps build country resilience to epidemics: a cross-sectional survey.

Background:  TDR, The Special Programme for Research and Training hosted at the World Health Organization, has long supported Low- and Middle-Income Countries in strengthening research capacity through three training programmes: the Postgraduate Training Scheme (PGTS), the Clinical Research and Development Fellowship (CRDF), and the Structured Operational Research Training InitiaTive (SORT IT). In the advent of the COVID-19 pandemic, we assessed whether those trained through these programmes were involved in the COVID-19 response and if so, in which area(s) of the emergency response they were applying their skills. Methods: From the records for each training programme, we identified the individuals who had completed training during the relevant timespan of each programme: 1999-2018 for the CRDF scheme, 2015-2020 for PGTS, and 2009-2019 for SORT-IT. Between March and April 2020, we sent trainees an online questionnaire by e-mail. Results: Out of 1254 trained, 1143 could be contacted and 699 responded to the survey. Of the latter, 411 were involved with the COVID-19 response, of whom 315 (77%) were applying their acquired skills in 85 countries. With some overlap between programmes, 84% of those trained through CRDF were applying their skills in 27 countries, 91% of those trained through PGTS were applying their skills in 19 countries, and through SORT IT, this was 73% in 62 countries.  Skills were being applied in various areas of the emergency response, including: emergency preparedness, situation analysis/surveillance, infection control and clinical management, data generation, mitigating the effect of COVID on the health system, and research.  Depending on the type of training programme, 26-74% were involved in implementation, operational or clinical research. Conclusion: Research training programmes build research capacity and equip health workers with transferable core competencies and skillsets prior to epidemics. This becomes invaluable in building health system resilience at a time of pandemics.

Anti-nerve growth factor antibodies for the treatment of low back pain.

INTRODUCTION: The treatment of chronic low back pain (cLBP) often involves multimodal pharmacologic and non-pharmacologic strategies. There remain shortcomings with these tools with regards to both effect size and side effects. AREAS COVERED: In an effort to better address cLBP, anti-nerve growth factor (NGF) monoclonal antibodies (mAbs) are nearing marketing approval. This class of medications has been primarily evaluated for osteoarthritis, but are being examined at higher doses for use in cLBP. We review the efficacy of this class in treating LBP as well as their potential side effects based on nine phase II or III published clinical trials. Five trials evaluated Tanezumab and four trials evaluated Fasinumab, with seven trials evaluating nonspecific LBP, one evaluating sciatica related cLBP, and one evaluating vertebral fracture related cLBP. EXPERT OPINION: The results of available clinical trials indicate modest effectiveness with regard to reduction of pain in the low back, and improved functionality, compared to placebo in keeping with the effect size of other pharmacologic treatment modalities. Rapidly progressive osteoarthritis was infrequently reported. However, the continued observation of this serious side effects warrants careful patient selection and balancing the risks and benefits of anti-NGF mAbs in treating cLBP.

Workplace Violence in the Setting of Pain Management.

In the context of the opioid crisis, increased attention has been placed on the risk of violence in outpatient pain medicine clinics. The primary objective of this study was to determine the prevalence and characteristics of workplace violence in a mixed group of clinicians (ie, practicing physicians, resident and fellow physicians in training, nurse practitioners, physician assistants, psychologists) participating in a workplace violence education session at a national pain conference held March 6 through March 10, 2019. A published survey instrument developed to assess workplace violence among pain management clinicians was offered to all 70 attendees, and 58 (82.9%) completed the survey. The mean age of respondents was 47.5 years, and 23 of 56 (41.1%) were female. Of the 58 respondents, 48 (82.8%) reported calling security at least once in the past year, and 39 of 57 (68.4%) reported being threatened with bodily harm. Among those threatened (multiple responses possible per respondent), 41 of 78 responses (52.6%) reported verbal threats, 11 of 78 (14.1%) reported being threatened with an object, and 11 of 78 (14.1%) reported threats of physical violence. Of 59 reponses, 15 (25.6%) endorsed carrying a weapon or using protective equipment. When asked about the clinical context of threats, 37 of 77 responses (48.1%) cited opioid management, 9 (11.7%) cited Workers' Compensation, 6 (7.8%) cited disability request, and 4 (5.2%) cited litigation related to an automobile accident. The observations from this survey suggest that clinicians practicing pain medicine experience workplace violence and threats of violence on a frequent basis. It is imperative for clinicians to acknowledge the risk of workplace violence and to recognize high-risk clinical scenarios. Future research should be directed toward developing and implementing data-driven risk mitigation strategies aimed at reducing the rate of workplace violence in outpatient pain clinics.

Emerging concepts on the use of ketamine for chronic pain.

Introduction: The use of ketamine infusions for chronic pain has surged, with utilization exceeding the proliferation of knowledge. A proposed mechanism for the long-term benefit in chronic pain is that ketamine may alter the affective-motivational component of pain.Areas covered: In this review, we discuss the classification and various dimensions of pain, and explore the effects of ketamine on different pain categories and components. The relationship between ketamine's action at the NMDA receptor, the development of chronic pain, and the its possible role in preventing the persistence of pain are examined. We also summarize animal models evaluating the antinociceptive effects of ketamine and risk mitigation strategies of ketamine-associated side effects.Expert opinion: Although ketamine exerts most of its analgesic effects via the NMDA receptor, recent evidence suggests that other receptors such as AMPA, and active metabolites such as nor-ketamine, may also play a role in pain relief and alleviation of depression. Data from clinical studies performed in patients with chronic pain and depression, and the observation that ketamine's analgesic benefits outlast its effects on quantitative sensory testing, suggest that the enduring effects on chronic pain may be predominantly due ketamine's ability to modulate the affective-motivational dimension of pain.

Survey of Spinal Cord Stimulation Hardware Currently Available for the Treatment of Chronic Pain in the United States.

Background: The number of spinal cord stimulator (SCS) units sold in the United States (US) for the treatment of chronic pain has increased with a corresponding expansion in the number of different SCS platforms available. Each marketed stimulator has several unique features, indications, and limitations, which distinguish one from the other and makes the selection of appropriate hardware possible for optimal patient care. There are an even greater number of similar and overlapping features between SCS. Measures: We used market analysis techniques to survey the currently available SCS technology. We then reviewed published device specifications and manuals for comparison of features. Outcomes: As of 2020, there are nine commonly used SCS platforms made by four manufacturers including four SCS units from Abbott, three from Boston Scientific, and one each from Medtronic and Nevro. Conclusions: A working understanding of each SCS product's nuances is needed for selecting the most appropriate device with which to manage chronic pain patients. Here we present a brief survey of currently available SCS hardware in the US and the features that make each product unique.

The effect of patient satisfaction scores on physician job satisfaction and burnout.

Physician burnout is recognized as reversible with the potential to negatively influence quality of care and patient outcomes. The study objective was to evaluate associations between patient satisfaction scores (PSS) and physicians' perceptions of job satisfaction and burnout via a physician survey. Eighty two out of 107 report PSS are institutionally tracked, with 23/107 and 39/107 reporting PSS utilization in financial compensation or performance review, respectively. Fifty four out of 107, report pressure to emphasize PSS; 63/107, report PSS having negative effect on job satisfaction; 31/107 considered leaving their job or career due to PSS and 84/107 report PSS contribute to burnout. In the cohort of physicians treating patients with spine pain who responded to this survey, PSS are associated with decreased job satisfaction and increased burnout.