Early Convalescent Plasma for High-Risk Outpatients with Covid-19.

BACKGROUND: Early administration of convalescent plasma obtained from blood donors who have recovered from coronavirus disease 2019 (Covid-19) may prevent disease progression in acutely ill, high-risk patients with Covid-19. METHODS: In this randomized, multicenter, single-blind trial, we assigned patients who were being treated in an emergency department for Covid-19 symptoms to receive either one unit of convalescent plasma with a high titer of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or placebo. All the patients were either 50 years of age or older or had one or more risk factors for disease progression. In addition, all the patients presented to the emergency department within 7 days after symptom onset and were in stable condition for outpatient management. The primary outcome was disease progression within 15 days after randomization, which was a composite of hospital admission for any reason, seeking emergency or urgent care, or death without hospitalization. Secondary outcomes included the worst severity of illness on an 8-category ordinal scale, hospital-free days within 30 days after randomization, and death from any cause. RESULTS: A total of 511 patients were enrolled in the trial (257 in the convalescent-plasma group and 254 in the placebo group). The median age of the patients was 54 years; the median symptom duration was 4 days. In the donor plasma samples, the median titer of SARS-CoV-2 neutralizing antibodies was 1:641. Disease progression occurred in 77 patients (30.0%) in the convalescent-plasma group and in 81 patients (31.9%) in the placebo group (risk difference, 1.9 percentage points; 95% credible interval, -6.0 to 9.8; posterior probability of superiority of convalescent plasma, 0.68). Five patients in the plasma group and 1 patient in the placebo group died. Outcomes regarding worst illness severity and hospital-free days were similar in the two groups. CONCLUSIONS: The administration of Covid-19 convalescent plasma to high-risk outpatients within 1 week after the onset of symptoms of Covid-19 did not prevent disease progression. (SIREN-C3PO ClinicalTrials.gov number, NCT04355767.).

Customizing CAT Administration of the PROMIS Misuse of Prescription Pain Medication Item Bank for Patients with Chronic Pain.

OBJECTIVE: The 22-item PROMIS®-Rx Pain Medication Misuse item bank (Bank-22) imposes a high response burden. This study aimed to characterize the performance of the Bank-22 in a computer adaptive testing (CAT) setting based on varied stopping rules. METHODS: The 22 items were administered to 288 patients. We performed a CAT simulation using default stopping rules (CATPROMIS). In 5 other simulations, a "best health" response rule was added to decrease response burden. This rule stopped CAT administration when a participant selected "never" to a specified number of initial Bank-22 items (2-6 in this study, designated CATAlt2-Alt6). The Bank-22 and 7-item short form (SF-7) scores were compared to scores based on CATPROMIS, and the 5 CAT variations. RESULTS: Bank-22 scores correlated highly with the SF-7 and CATPROMIS, Alt5, Alt6 scores (r=0.87-0.95) and moderately with CATAlt2- Alt4 scores (r=0.63-0.74). In all CAT conditions, the greatest differences with Bank-22 scores were at the lower end of misuse T-scores. The smallest differences with Bank-22 and CATPROMIS scores were observed with CATAlt5 and CATAlt6. Compared to the SF-7, CATAlt5 and CATAlt6 reduced overall response burden by about 42%. Finally, the correlations between PROMIS-Rx Misuse and Anxiety T-scores remained relatively unchanged across the conditions (r=0.31-0.43, Ps < .001). CONCLUSIONS: Applying a stopping rule based on number of initial "best health" responses reduced response burden for respondents with lower levels of misuse. The tradeoff was less measurement precision for those individuals, which could be an acceptable tradeoff when the chief concern is in discriminating higher levels of misuse.

Consensus practice guidelines on interventions for cervical spine (facet) joint pain from a multispecialty international working group.

BACKGROUND: The past two decades have witnessed a surge in the use of cervical spine joint procedures including joint injections, nerve blocks and radiofrequency ablation to treat chronic neck pain, yet many aspects of the procedures remain controversial. METHODS: In August 2020, the American Society of Regional Anesthesia and Pain Medicine and the American Academy of Pain Medicine approved and charged the Cervical Joint Working Group to develop neck pain guidelines. Eighteen stakeholder societies were identified, and formal request-for-participation and member nomination letters were sent to those organizations. Participating entities selected panel members and an ad hoc steering committee selected preliminary questions, which were then revised by the full committee. Each question was assigned to a module composed of 4-5 members, who worked with the Subcommittee Lead and the Committee Chairs on preliminary versions, which were sent to the full committee after revisions. We used a modified Delphi method whereby the questions were sent to the committee en bloc and comments were returned in a non-blinded fashion to the Chairs, who incorporated the comments and sent out revised versions until consensus was reached. Before commencing, it was agreed that a recommendation would be noted with >50% agreement among committee members, but a consensus recommendation would require ≥75% agreement. RESULTS: Twenty questions were selected, with 100% consensus achieved in committee on 17 topics. Among participating organizations, 14 of 15 that voted approved or supported the guidelines en bloc, with 14 questions being approved with no dissensions or abstentions. Specific questions addressed included the value of clinical presentation and imaging in selecting patients for procedures, whether conservative treatment should be used before injections, whether imaging is necessary for blocks, diagnostic and prognostic value of medial branch blocks and intra-articular joint injections, the effects of sedation and injectate volume on validity, whether facet blocks have therapeutic value, what the ideal cut-off value is for designating a block as positive, how many blocks should be performed before radiofrequency ablation, the orientation of electrodes, whether larger lesions translate into higher success rates, whether stimulation should be used before radiofrequency ablation, how best to mitigate complication risks, if different standards should be applied to clinical practice and trials, and the indications for repeating radiofrequency ablation. CONCLUSIONS: Cervical medial branch radiofrequency ablation may provide benefit to well-selected individuals, with medial branch blocks being more predictive than intra-articular injections. More stringent selection criteria are likely to improve denervation outcomes, but at the expense of false-negatives (ie, lower overall success rate). Clinical trials should be tailored based on objectives, and selection criteria for some may be more stringent than what is ideal in clinical practice.

Peripheral Nerve Stimulation for Occipital Neuralgia.

BACKGROUND: Chronic headaches are the second most prevalent disease and second most common cause for years lived with disability worldwide. Occipital neuralgia can cause headaches or be present in addition to other more prevalent causes of headache. If these headaches fail to respond to conservative and pharmacological therapy, physicians proceed to more invasive treatments, starting with infiltration of the greater occipital nerve with local anesthetic with or without corticosteroids, followed by nerve ablation or stimulation. Occipital nerve stimulation gained more popularity as the technology improved and more pain physicians received training on interventional procedures. METHODS: In this manuscript, we are presenting our experience with ultrasound-guided implant of occipital nerve stimulators using peripheral nerve stimulator systems. After confirming appropriateness of treatment by a successful occipital nerve block (i.e., resulting in >50% relief in patients' pain intensity), we implanted five stimulator systems in three patients (two bilateral). RESULTS: We followed these patients for an average of eight months, and the average pain reduction was ∼50%. We did not observe any adverse events during or immediately after surgery. One patient developed an adverse reaction to the adhesive of the battery transmitter, but it was not severe enough to stop her from using the stimulator. CONCLUSIONS: Considering the ease of implant and minimal side effects, implant of peripheral nerve stimulators to stimulate the occipital nerve is a promising treatment modality for patients with chronic headache who present with features of occipital neuralgia. However, wider use of this treatment modality is subject to further studies.

Peripheral Nerve Stimulation for Pudendal Neuralgia: A Technical Note.

BACKGROUND: Pudendal neuropathy is a chronic, disabling form of perineal pain that involves the pudendal nerve, a mixed somatic and autonomic nerve that originates from sacral nerve roots. Peripheral nerve stimulation of the pudendal nerve can be useful to decrease symptom burden in patients who have failed initial conservative treatment modalities. METHODS: In this manuscript, we describe an approach to the placement of a peripheral nerve stimulator for the treatment of pudendal neuralgia. We present a case of complex pelvic neuropathy and review the factors that lead to successful placement. Technical aspects of stimulator placement and ultrasound landmarks are reviewed. RESULTS: A lateral to medial approach with ultrasound guidance at the level of the ischial spine is likely to facilitate proper lead placement along the course of the pudendal nerve. Aftercare and adherence to postimplant activity restrictions-particularly avoiding use of the extremes of hip flexion and extension for four weeks-lead to the absence of lead migration. CONCLUSIONS: Pudendal nerve stimulation is an emerging technique for neuromodulation of refractory pudendal neuralgia. Ultrasound-guided pudendal nerve stimulation is a viable technique for neuromodulation of pudendal neuralgia. Optimization of patient selection, ultrasound guidance, and proper adherence to postimplant activity restrictions may be helpful for long-term therapeutic success.

Clinical Profiles of Concurrent Cannabis Use in Chronic Pain: A CHOIR Study.

OBJECTIVE: Despite evidence of the analgesic benefits of cannabis, there remains a relative scarcity of research on the short- and long-term effects of cannabis use in individuals with chronic pain. DESIGN: The current study is a secondary analysis of clinical data from the Collaborative Health Outcomes Information Registry (CHOIR). SETTING: Data were drawn from a cohort of patients of a multidisciplinary tertiary care pain clinic. SUBJECTS: The study sample consisted of data from 7,026 new patient visits from CHOIR; of these, 1,668 patients with a follow-up time point within 180 days were included in a longitudinal analysis. METHODS: Clinical data were analyzed to characterize cross-sectional differences in pain and indicators of psychological and physical function according to self-reported, concurrent cannabis use. Additionally, a propensity score-weighted longitudinal analysis was conducted, examining cannabis use as a predictor of changes in clinical variables across time. RESULTS: Cross-sectional analyses suggested significantly poorer sleep and significantly higher intensities of pain, emotional distress, and physical and social dysfunction in patients reporting ongoing cannabis use; however, these differences were relatively small in magnitude. However, no differences between cannabis users and nonusers in terms of longitudinal changes in clinical variables were noted. DISCUSSION: Our results are among the first to examine concurrent cannabis use as a prognostic variable regarding trajectories of pain-related variables in tertiary care. Future studies may benefit from examining the effect of cannabis initiation, concurrent medication use, and specific aspects of cannabis use (dose, duration of use, or cannabis type) on clinical outcomes.

Evaluation of the Preliminary Validity of Misuse of Prescription Pain Medication Items from the Patient-Reported Outcomes Measurement Information System (PROMIS)®.

OBJECTIVE: The National Institutes of Health's Patient-Reported Outcomes Measurement Information System (PROMIS)® includes an item bank for measuring misuse of prescription pain medication (PROMIS-Rx Misuse). The bank was developed and its validity evaluated in samples of community-dwelling adults and patients in addiction treatment programs. The goal of the current study was to investigate the validity of the item bank among patients with mixed-etiology chronic pain conditions. METHOD: A consecutive sample of 288 patients who presented for initial medical evaluations at a tertiary pain clinic completed questionnaires using the open-source Collaborative Health Outcomes Information Registry. Participants were predominantly middle-aged (M [SD] = 51.6 [15.5] years), female (62.2%), and white/non-Hispanic (51.7%). Validity was evaluated by estimating the association between PROMIS-Rx Misuse scores and scores on other measures and testing the ability of scores to distinguish among risk factor subgroups expected to have different levels of prescription pain medicine misuse (known groups analyses). RESULTS: Overall, score associations with other measures were as expected and scores effectively distinguished among patients with and without relevant risk factors. CONCLUSION: The study results supported the preliminary validity of PROMIS-Rx Misuse item bank scores for the assessment of prescription opioid misuse in patients visiting an outpatient pain clinic.

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Perioperative Opioid Minimization in Opioid-Naïve Patients.

Surgical care episodes place opioid-naïve patients at risk for transitioning to new persistent postoperative opioid use. With one of the central principles being the application of multimodal pain interventions to reduce the reliance on opioid-based medications, enhanced recovery pathways provide a framework that decreases perioperative opioid use. The fourth Perioperative Quality Initiative brought together a group of international experts representing anesthesiology, surgery, and nursing with the objective of providing consensus recommendations on this important topic. Fourth Perioperative Quality Initiative was a consensus-building conference designed around a modified Delphi process in which the group alternately convened for plenary discussion sessions in between small group discussions. The process included several iterative steps including a literature review of the topics, building consensus around the important questions related to the topic, and sequential steps of content building and refinement until agreement was achieved and a consensus document was produced. During the fourth Perioperative Quality Initiative conference and thereafter as a writing group, reference applicability to the topic was discussed in any area where there was disagreement. For this manuscript, the questions answered included (1) What are the potential strategies for preventing persistent postoperative opioid use? (2) Is opioid-free anesthesia and analgesia feasible and appropriate for routine operations? and (3) Is opioid-free (intraoperative) anesthesia associated with equivalent or superior outcomes compared to an opioid minimization in the perioperative period? We will discuss the relevant literature for each questions, emphasize what we do not know, and prioritize the areas for future research.

Predictors of Daily Pain Medication Use in Individuals with Recurrent Back Pain.

PURPOSE: A key component to chronic pain management regimens is the use of analgesic medications. Psychological factors, such as mood states, may also affect the use of pain medications for individuals with chronic pain, but few observational studies have examined how these factors may predict pain medication use at the daily level. METHODS: Daily assessments from 104 individuals with back pain were used to examine fluctuations in daily pain intensity, mood, sleep quality, and physical activity as predictors of the likelihood of pain medication (opioid and non-opioid) use and levels of medication use on the same day. RESULTS: Pain intensity and mood ratings significantly predicted whether participants used pain medication on the same day, while only pain intensity predicted whether participants used more medication than usual. Further, current opioid users were more likely to increase the amount of their medication use on days of higher pain. DISCUSSION: This article identifies fluctuations in daily pain intensity and mood as salient predictors of daily pain medication use in individuals with recurrent back pain. The current study is among the first to highlight both pain and mood states as predictors of daily pain medication use in individuals with back pain, though future studies may expand on these findings through the use of higher-resolution daily medication use variables.

Chronic Opioid Use After Surgery: Implications for Perioperative Management in the Face of the Opioid Epidemic.

Physicians, policymakers, and researchers are increasingly focused on finding ways to decrease opioid use and overdose in the United States both of which have sharply increased over the past decade. While many efforts are focused on the management of chronic pain, the use of opioids in surgical patients presents a particularly challenging problem requiring clinicians to balance 2 competing interests: managing acute pain in the immediate postoperative period and minimizing the risks of persistent opioid use after the surgery. Finding ways to minimize this risk is particularly salient in light of a growing literature suggesting that postsurgical patients are at increased risk for chronic opioid use. The perioperative care team, including surgeons and anesthesiologists, is poised to develop clinical- and systems-based interventions aimed at providing pain relief in the immediate postoperative period while also reducing the risks of opioid use longer term. In this paper, we discuss the consequences of chronic opioid use after surgery and present an analysis of the extent to which surgery has been associated with chronic opioid use. We follow with a discussion of the risk factors that are associated with chronic opioid use after surgery and proceed with an analysis of the extent to which opioid-sparing perioperative interventions (eg, nerve blockade) have been shown to reduce the risk of chronic opioid use after surgery. We then conclude with a discussion of future research directions.

Pain Duration and Resolution following Surgery: An Inception Cohort Study.

OBJECTIVE: Preoperative determinants of pain duration following surgery are poorly understood. We identified preoperative predictors of prolonged pain after surgery in a mixed surgical cohort. METHODS: We conducted a prospective longitudinal study of patients undergoing mastectomy, lumpectomy, thoracotomy, total knee replacement, or total hip replacement. We measured preoperative psychological distress and substance use, and then measured pain and opioid use after surgery until patients reported the cessation of both opioid consumption and pain. The primary endpoint was time to opioid cessation, and those results have been previously reported. Here, we report preoperative determinants of time to pain resolution following surgery in Cox proportional hazards regression. RESULTS: Between January 2007 and April 2009, we enrolled 107 of 134 consecutively approached patients undergoing the aforementioned surgical procedures. In the final multivariate model, preoperative self-perceived risk of addiction predicted more prolonged pain. Unexpectedly, anxiety sensitivity predicted more rapid pain resolution after surgery. Each one-point increase (on a four point scale) of self-perceived risk of addiction was associated with a 38% (95% CI 3-61) reduction in the rate of pain resolution (P = 0.04). Furthermore, higher anxiety sensitivity was associated with an 89% (95% CI 23-190) increased rate of pain resolution (P = 0.004). CONCLUSIONS: Greater preoperative self-perceived risk of addiction, and lower anxiety sensitivity predicted a slower rate of pain resolution following surgery. Each of these factors was a better predictor of pain duration than preoperative depressive symptoms, post-traumatic stress disorder symptoms, past substance use, fear of pain, gender, age, preoperative pain, or preoperative opioid use.

Self-loathing aspects of depression reduce postoperative opioid cessation rate.

OBJECTIVE: We previously reported that increased preoperative Beck Depression Inventory II (BDI-II) scores were associated with a 47% (95% CI 24%-64%) reduction in the rate of opioid cessation following surgery. We aimed to identify the underlying factors of the BDI-II (affective/cognitive vs somatic) associated with a decreased rate of opioid cessation after surgery. METHODS: We conducted a secondary analysis of the data from a previously reported prospective, longitudinal, observational study of opioid use after five distinct surgical procedures (total hip replacement, total knee replacement, thoracotomy, mastectomy, and lumpectomy) in 107 patients. The primary endpoint was time to opioid cessation. After exploratory factor analysis of the BDI-II, mean summary scores were calculated for each identified factor. These scores were evaluated as predictors of time to opioid cessation using Cox proportional hazards regression. RESULTS: The exploratory factor analysis produced three factors (self-loathing symptoms, motivational symptoms, emotional symptoms). All three factors were significant predictors in univariate analysis. Of the three identified factors of the BDI-II, only preoperative self-loathing symptoms (past failure, guilty feelings, self-dislike, self-criticalness, suicidal thoughts, worthlessness) independently predicted a significant decrease in opioid cessation rate after surgery in the multivariate analysis (HR 0.86, 95% CI 0.75-0.99, P value 0.037). CONCLUSIONS: Our results identify a set of negative cognitions predicting prolonged time to postoperative opioid cessation. Somatic symptoms captured by the BDI-II were not primarily responsible for the association between preoperative BDI-II scores and postoperative prolonged opioid use.

Long-Term Epidural Patching Outcomes and Predictors of Benefit in Patients With Suspected CSF Leak Nonconforming to ICHD-3 Criteria.

BACKGROUND AND OBJECTIVES: Spinal CSF leaks lead to spontaneous intracranial hypotension (SIH). While International Classification of Headache Disorders, Third Edition (ICHD-3) criteria necessitate imaging confirmation or low opening pressure (OP) for SIH diagnosis, their sensitivity may be limited. We offered epidural blood patches (EBPs) to patients with symptoms suggestive of SIH, with and without a documented low OP or confirmed leak on imaging. This study evaluates the efficacy of this strategy. METHODS: We conducted a prospective cohort study with a nested case-control design including all patients who presented to a tertiary headache clinic with clinical symptoms of SIH who completed study measures both before and after receiving an EBP between August 2016 and November 2018. RESULTS: The mean duration of symptoms was 8.7 ± 8.1 years. Of 85 patients assessed, 69 did not meet ICHD-3 criteria for SIH. At an average of 521 days after the initial EBP, this ICHD-3-negative subgroup experienced significant improvements in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Physical Health score of +3.3 (95% CI 1.5-5.1), PROMIS Global Mental Health score of +1.8 (95% CI 0.0-3.5), Headache Impact Test (HIT)-6 head pain score of -3.8 (95% CI -5.7 to -1.8), Neck Disability Index of -4.8 (95% CI -9.0 to -0.6) and PROMIS Fatigue of -2.3 (95% CI -4.1 to -0.6). Fifty-four percent of ICHD-3-negative patients achieved clinically meaningful improvements in PROMIS Global Physical Health and 45% in HIT-6 scores. Pain relief following lying flat prior to treatment was strongly associated with sustained clinically meaningful improvement in global physical health at an average of 521 days (odds ratio 1.39, 95% CI 1.1-1.79; p < 0.003). ICHD-3-positive patients showed high rates of response and previously unreported, treatable levels of fatigue and cognitive deficits. DISCUSSION: Patients who did not conform to the ICHD-3 criteria for SIH showed moderate rates of sustained, clinically meaningful improvements in global physical health, global mental health, neck pain, fatigue, and head pain after EBP therapy. Pre-treatment improvement in head pain when flat was associated with later, sustained improvement after EBP therapy among patients who did not meet the ICHD-3 criteria. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that epidural blood patch is an effective treatment of suspected CSF leak not conforming to ICHD-3 criteria for SIH.

Clinical study of a micro-implantable pulse generator for the treatment of peripheral neuropathic pain: 3-month and 6-month results from the COMFORT-randomised controlled trial.

BACKGROUND: We report the results from the first large, postmarket, multicentre, randomised controlled trial (RCT) evaluating peripheral nerve stimulation (PNS) for the treatment of chronic peripheral pain with a micro-implantable pulse generator (micro-IPG). METHODS: Subjects meeting eligibility were randomised (2:1) to either the active arm receiving PNS and conventional medical management (CMM) or the control arm receiving CMM alone. Treatments were limited to the following areas: lower back, shoulder, knee and foot/ankle. RESULTS: At 6 months, the active arm achieved an 88% responder rate with a 70% average reduction in pain. At the 3-month primary endpoint, the active arm achieved an 84% responder rate with an average pain reduction of 67% compared with the control arm, which achieved a 3% responder rate with an average pain reduction of 6%. Both responder rate and pain reduction in the active arm were significantly better than in the control arm (p<0.001). A majority of patient-reported outcomes also reached statistical significance. There have been no reports of pocket pain and no serious adverse device effects. 81% of subjects found the external wearable component of the PNS system to be comfortable. CONCLUSIONS: This study successfully reached its primary endpoint-the active arm achieved a statistically significant superior responder rate as compared with the control arm at 3 months. These RCT results demonstrated that PNS, with this micro-IPG, is efficacious and safe. This ongoing study will follow subjects for 3 years, the results of which will be reported as they become available.

Diagnosis and Treatment of Spontaneous Intracranial Hypotension: Role of Epidural Blood Patching.

Purpose of Review: This review focuses on the challenges of diagnosing and treating spontaneous intracranial hypotension (SIH), a condition caused by spinal CSF leakage. It emphasizes the need for increased awareness and advocates for early and thoughtful use of empirical epidural blood patches (EBPs) in suspected cases. Recent Findings: SIH diagnosis is hindered by variable symptoms and inconsistent imaging results, including normal brain MRI and unreliable spinal opening pressures. It is crucial to consider SIH in differential diagnoses, especially in patients with connective tissue disorders. Early EBP intervention is shown to improve outcomes. Summary: SIH remains underdiagnosed and undertreated, requiring heightened awareness and understanding. This review promotes proactive EBP use in managing suspected SIH and calls for continued research to advance diagnostic and treatment methods, emphasizing the need for innovative imaging techniques for accurate diagnosis and timely intervention.

Perioperative interventions to reduce chronic postsurgical pain.

Approximately 10% of patients following a variety of surgeries develop chronic postsurgical pain. Reducing chronic postoperative pain is especially important to reconstructive surgeons because common operations such as breast and limb reconstruction have even higher risk for developing chronic postsurgical pain. Animal studies of posttraumatic nerve injury pain demonstrate that there is a critical time frame before and immediately after nerve injury in which specific interventions can reduce the incidence and intensity of chronic neuropathic pain behaviors-so called "preventative analgesia." In animal models, perineural local anesthetic, systemic intravenous local anesthetic, perineural clonidine, systemic gabapentin, systemic tricyclic antidepressants, and minocycline have each been shown to reduce pain behaviors days to weeks after treatment. The translation of this work to humans also suggests that brief perioperative interventions may protect patients from developing new chronic postsurgical pain. Recent clinical trial data show that there is an opportunity during the perioperative period to dramatically reduce the incidence and severity of chronic postsurgical pain. The surgeon, working with the anesthesiologist, has the ability to modify both early and chronic postoperative pain by implementing an evidence-based preventative analgesia plan.

Postoperative opioid prescribing patients with diabetes: Opportunities for personalized pain management.

BACKGROUND: Opioids are commonly prescribed for postoperative pain, but may lead to prolonged use and addiction. Diabetes impairs nerve function, complicates pain management, and makes opioid prescribing particularly challenging. METHODS: This retrospective observational study included a cohort of postoperative patients from a multisite academic health system to assess the relationship between diabetes, pain, and prolonged opioid use (POU), 2008-2019. POU was defined as a new opioid prescription 3-6 months after discharge. The odds that a patient had POU was assessed using multivariate logistic regression controlling for patient factors (e.g., demographic and clinical factors, as well as prior pain and opiate use). FINDINGS: A total of 43,654 patients were included, 12.4% with diabetes. Patients with diabetes had higher preoperative pain scores (2.1 vs 1.9, p<0.001) and lower opioid naïve rates (58.7% vs 68.6%, p<0.001). Following surgery, patients with diabetes had higher rates of POU (17.7% vs 12.7%, p<0.001) despite receiving similar opioid prescriptions at discharge. Patients with Type I diabetes were more likely to have POU compared to other patients (Odds Ratio [OR]: 2.22; 95% Confidence Interval [CI]:1.69-2.90 and OR:1.44, CI: 1.33-1.56, respectively). INTERPRETATION: In conclusion, surgical patients with diabetes are at increased risk for POU even after controlling for likely covariates, yet they receive similar postoperative opiate therapy. The results suggest a more tailored approach to diabetic postoperative pain management is warranted.

Preoperative Versus Perioperative Risk Factors for Delayed Pain and Opioid Cessation After Total Joint Arthroplasty: A Prospective Cohort Study.

INTRODUCTION: The evolution of pre- versus postoperative risk factors remains unknown in the development of persistent postoperative pain and opioid use. We identified preoperative versus comprehensive perioperative models of delayed pain and opioid cessation after total joint arthroplasty including time-varying postoperative changes in emotional distress. We hypothesized that time-varying longitudinal measures of postoperative psychological distress, as well as pre- and postoperative use of opioids would be the most significant risk factors for both outcomes. METHODS: A prospective cohort of 188 patients undergoing total hip or knee arthroplasty at Stanford Hospital completed baseline pain, opioid use, and emotional distress assessments. After surgery, a modified Brief Pain Inventory was assessed daily for 3 months, weekly thereafter up to 6 months, and monthly thereafter up to 1 year. Emotional distress and pain catastrophizing were assessed weekly to 6 months, then monthly thereafter. Stepwise multivariate time-varying Cox regression modeled preoperative variables alone, followed by all perioperative variables (before and after surgery) with time to postoperative opioid and pain cessation. RESULTS: The median time to opioid and pain cessation was 54 and 152 days, respectively. Preoperative total daily oral morphine equivalent use (hazard ratio-HR 0.97; 95% confidence interval-CI 0.96-0.98) was significantly associated with delayed postoperative opioid cessation in the perioperative model. In contrast, time-varying postoperative factors: elevated PROMIS (Patient-Reported Outcomes Measurement Information System) depression scores (HR 0.92; 95% CI 0.87-0.98), and higher Pain Catastrophizing Scale scores (HR 0.85; 95% CI 0.75-0.97) were independently associated with delayed postoperative pain resolution in the perioperative model. CONCLUSIONS: These findings highlight preoperative opioid use as a key determinant of delayed postoperative opioid cessation, while postoperative elevations in depressive symptoms and pain catastrophizing are associated with persistent pain after total joint arthroplasty providing the rationale for continued risk stratification before and after surgery to identify patients at highest risk for these distinct outcomes. Interventions targeting these perioperative risk factors may prevent prolonged postoperative pain and opioid use.