Reasons for Preoperative Opioid Use Are Associated with Persistent Use following Surgery Among Patients Undergoing Total Knee and Hip Arthroplasty.

OBJECTIVE: Most studies on preoperative opioid use only describe whether or not patients use opioids without characterizing reasons for use. Knowing why patients use opioids can help inform perioperative opioid management. The objective of this study was to explore pain specific reasons for preoperative opioid use prior to total hip and knee arthroplasty (THA and TKA) and their association with persistent use. METHODS: This is a prospective study of 197 patients undergoing THA (n = 99) or TKA (n = 98) enrolled in the Analgesic Outcomes Study between December 2015 and November 2018. All participants reported preoperative opioid use. RESULTS: Reasons for preoperative opioid use were categorized as surgical site pain only (81 [41.1%]); pain in other body areas only (22 [11.2%]); and combined pain (94 [47.7%]). Compared to patients taking opioids for surgical site pain, those with combined reasons for use had 1.24 (P = .40) and 2.28 (P = .16) greater odds of persistent use at 3 and 6 months postoperatively, adjusting for relevant covariates. CONCLUSIONS: This study provides novel insights into the heterogeneity of reasons for presurgical opioid use in patients undergoing a THA or TKA. One key take away is that not all preoperative opioid use is the same and many patients are taking opioids preoperatively for more than just pain at the surgical site. Combined reasons for use was associated with long-term use, suggesting nonsurgical pain, in part, drives persistent opioid use after surgery. Future directions in perioperative care should focus on pain and non-pain reasons for presurgical opioid use to create tailored postoperative opioid weaning plans.

Patient Factors Associated With Opioid Consumption in the Month Following Major Surgery.

OBJECTIVE: The aim of this study was to determine preoperative patient characteristics associated with postoperative outpatient opioid use and assess the frequency of postoperative opioid overprescribing. SUMMARY BACKGROUND DATA: Although characteristics associated with inpatient opioid use have been described, data regarding patient factors associated with opioid use after discharge are lacking. This hampers the development of individualized approaches to postoperative prescribing. METHODS: We included opioid-naïve patients undergoing hysterectomy, thoracic surgery, and total knee and hip arthroplasty in a single-center prospective observational cohort study. Preoperative phenotyping included self-report measures to assess pain severity, fibromyalgia survey criteria score, pain catastrophizing, depression, anxiety, functional status, fatigue, and sleep disturbance. Our primary outcome measure was self-reported total opioid use in oral morphine equivalents. We constructed multivariable linear-regression models predicting opioids consumed in the first month following surgery. RESULTS: We enrolled 1181 patients; 1001 had complete primary outcome data and 913 had complete phenotype data. Younger age, non-white race, lack of a college degree, higher anxiety, greater sleep disturbance, heavy alcohol use, current tobacco use, and larger initial opioid prescription size were significantly associated with increased opioid consumption. Median total oral morphine equivalents prescribed was 600 mg (equivalent to one hundred twenty 5-mg hydrocodone pills), whereas median opioid consumption was 188 mg (38 pills). CONCLUSIONS: In this prospective cohort of opioid-naïve patients undergoing major surgery, we found a number of characteristics associated with greater opioid use in the first month after surgery. Future studies should address the use of non-opioid medications and behavioral therapies in the perioperative period for these higher risk patients.

Perioperative cannabis use: a longitudinal study of associated clinical characteristics and surgical outcomes.

BACKGROUND: Despite increases in cannabis use generally and for pain management, data regarding cannabis use in patients undergoing surgery are lacking. This study examined the prevalence of cannabis use among patients undergoing elective surgery and explored differences in clinical characteristics and surgical outcomes between cannabis users and non-cannabis users. METHODS: This prospective study included 1335 adults undergoing elective surgery. Participants completed self-report questionnaires preoperative and at 3-month and 6-month postsurgery to assess clinical characteristics and surgical outcomes. RESULTS: Overall, 5.9% (n=79) of patients reported cannabis use (53.2% medical, 19.0% recreational and 25.3% medical and recreational). On the day of surgery, cannabis users reported worse pain, more centralized pain symptoms, greater functional impairment, higher fatigue, greater sleep disturbances and more symptoms of anxiety and depression versus non-cannabis users (all p<0.01). Additionally, a larger proportion of cannabis users reported opioid (27.9%) and benzodiazepine use (19.0%) compared with non-cannabis users (17.5% and 9.2%, respectively). At 3 and 6 months, cannabis users continued to report worse clinical symptoms; however, both groups showed improvement across most domains (p≤0.05). At 6 months, the groups did not differ on surgical outcomes, including surgical site pain (p=0.93) or treatment efficacy (p=0.88). CONCLUSIONS: Cannabis use is relatively low in this surgical population, yet cannabis users have higher clinical pain, poorer scores on quality of life indicators, and higher opioid use before and after surgery. Cannabis users reported similar surgical outcomes, suggesting that cannabis use did not impede recovery.

Opioid Fills for Lumbar Facet Radiofrequency Ablation Associated with New Persistent Opioid Use.

BACKGROUND: Zygapophyseal (facet) joint interventions are the second most common interventional procedure in pain medicine. Opioid exposure after surgery is a significant risk factor for chronic opioid use. The aim of this study was to determine the incidence of new persistent use of opioids after lumbar facet radiofrequency ablation and to assess the effect of postprocedural opioid prescribing on the development of new persistent opioid use. METHODS: The authors conducted a retrospective cohort study using claims from the Clinformatics Data Mart Database (OptumInsight, USA) to identify opioid-naïve patients between 18 and 64 yr old who had lumbar radiofrequency ablation. Patients who had either subsequent radiofrequency ablation 15 to 180 days or subsequent surgery within 180 days after the primary procedure were excluded from the analysis. The primary outcome was new persistent opioid use, defined as opioid prescription fulfillment within the 8 to 90 and 91 to 180 day periods after radiofrequency ablation. The authors then assessed patient-level risk factors for new persistent opioid use. RESULTS: A total of 2,887 patients met the inclusion criteria. Of those patients, 2,277 (78.9%) had radiofrequency ablation without a perioperative opioid fill, and 610 (21.1%) patients had the procedure with a perioperative opioid fill. The unadjusted rate of new persistent opioid use was 5.6% (34 patients) in the group with a perioperative opioid fill versus 2.8% (63 patients) for those without an opioid fill. Periprocedural opioid prescription fill was independently associated with increased odds of new persistent use (adjusted odds ratio, 2.35; 95% CI, 1.51 to 3.66; P < 0.001). CONCLUSIONS: Periprocedural opioid use after lumbar radiofrequency ablation was associated with new persistent use in previously opioid-naïve patients, suggesting that new exposure to opioids is an independent risk factor for persistent use in patients having radiofrequency ablation for chronic back pain. Opioid prescribing after radiofrequency ablation should be reevaluated and likely discontinued in this population.

Prescribing and Consumption of Opioids After Primary, Unilateral Total Hip and Knee Arthroplasty in Opioid-Naive Patients.

BACKGROUND: This cohort study was designed to determine the discrepancy between the quantity of opioid prescribed vs that which was consumed after total knee arthroplasty (TKA) and total hip arthroplasty (THA) in opioid-naive patients. METHODS: Seven hundred twenty-three opioid-naive patients (426 TKAs and 297 THAs) from 7 hospitals in Michigan were contacted within 3 months of their surgery. Opioid prescribing and self-reported consumption was calculated in oral morphine equivalents (OMEs). Secondary outcomes included opioid refill in the first 90 days, pain in the first 7 days post-operatively, and satisfaction with pain care. RESULTS: For TKA, the mean prescribing was 632 mg OME (±229), and the mean consumption was 416 mg (±279). For THA, the mean prescribing was 584 mg OME (±335), and the mean consumption was 285 mg (±301). There were no associations between the amount of opioid prescribed and the likelihood of refill, post-operative pain, or satisfaction with pain control. The amount of opioid prescribed was associated with increased consumption, such that each increase of 1 pill was associated with approximately an additional half pill consumed after adjusting for other covariates. Moreover, 48.2% felt that they received "More" or "Much more" opioid than they needed. CONCLUSION: We recommend no more than 50 tablets of 5 mg oxycodone or its equivalent after TKA and 30 tablets after THA. Although dose reductions in other surgeries have not resulted in harm, continued assessment is needed to ensure that there are no unintended effects of opioid reduction, including worsened pain, decreased satisfaction, emergency department visits, or hospital readmissions. LEVEL OF EVIDENCE: Level III; Retrospective, cohort study.

Top down or bottom up? An observational investigation of improvement in fibromyalgia symptoms following hip and knee replacement.

OBJECTIVES: Many patients with osteoarthritis have comorbid symptoms of FM, but it is unknown how these symptoms respond to surgical procedures that address nociceptive input in the periphery, such as total joint replacement. Here we explore differences in clinical characteristics between patients whose FM symptoms do and do not improve following total hip or knee replacement. METHODS: Participants were 150 patients undergoing knee or hip replacement who had a minimum FM survey score of 4 or greater prior to surgery. The top tertile of patients experiencing the most improvement in FM symptoms at month 6 were categorized as 'Improve' (n = 48) while the bottom two tertiles were categorized as 'Worsen/Same' (n = 102). Baseline symptom characteristics were compared between groups, as well as improvement in overall pain severity, surgical pain severity and physical function at 6 months. RESULTS: The Worsen/Same group had higher levels of fatigue, depression and surgical site pain at baseline (all P < 0.05). Additionally, they improved less on overall pain severity and physical functioning 6 months after surgery (both P < 0.05). CONCLUSION: Most patients derive significant benefit in improvement of comorbid FM symptoms following total joint replacement, but a substantial proportion do not. Understanding the neurobiological basis for these different trajectories may help inform clinical judgment and improve patient care.

Heritability of the Fibromyalgia Phenotype Varies by Age.

OBJECTIVE: Many studies suggest a strong familial component to fibromyalgia (FM). However, those studies have nearly all been confined to individuals with primary FM, i.e., FM without any other accompanying disorder. The current 2011 and 2016 criteria for diagnosing FM construct a score using a combination of the number of painful body sites and the severity of somatic symptoms (FM score). This study was undertaken to estimate the genetic heritability of the FM score across sex and age groups to identify subgroups of individuals with greater heritability, which may help in the design of future genetic studies. METHODS: We collected data on 26,749 individuals of European ancestry undergoing elective surgery at the University of Michigan (Michigan Genomics Initiative study). We estimated the single-nucleotide polymorphism-based heritability of FM score by age and sex categories using genome-wide association study data and a linear mixed-effects model. RESULTS: Overall, the FM score had an estimated heritability of 13.9% (SE 2.9%) (P = 1.6 × 10-7 ). Estimated FM score heritability was highest in individuals ≤50 years of age (23.5%; SE 7.9%) (P = 3.0 ×10-4 ) and lowest in individuals >60 years of age (7.5%; SE 8.1%) (P = 0.41). These patterns remained the same when we analyzed FM as a case-control phenotype. Even though women had an ~30% higher average FM score than men across age categories, FM score heritability did not differ significantly by sex. CONCLUSION: Younger individuals appear to have a much stronger genetic component to the FM score than older individuals. Older individuals may be more likely to have what was previously called "secondary FM." Regardless of the cause, these results have implications for future genetic studies of FM and associated conditions.

Sepsis Induces Prolonged Epigenetic Modifications in Bone Marrow and Peripheral Macrophages Impairing Inflammation and Wound Healing.

OBJECTIVE: Sepsis represents an acute life-threatening disorder resulting from a dysregulated host response. For patients who survive sepsis, there remains long-term consequences, including impaired inflammation, as a result of profound immunosuppression. The mechanisms involved in this long-lasting deficient immune response are poorly defined. Approach and Results: Sepsis was induced using the murine model of cecal ligation and puncture. Following a full recovery period from sepsis physiology, mice were subjected to our wound healing model and wound macrophages (CD11b+, CD3-, CD19-, Ly6G-) were sorted. Post-sepsis mice demonstrated impaired wound healing and decreased reepithelization in comparison to controls. Further, post-sepsis bone marrow-derived macrophages and wound macrophages exhibited decreased expression of inflammatory cytokines vital for wound repair (IL [interleukin]-1ß, IL-12, and IL-23). To evaluate if decreased inflammatory gene expression was secondary to epigenetic modification, we conducted chromatin immunoprecipitation on post-sepsis bone marrow-derived macrophages and wound macrophages. This demonstrated decreased expression of Mll1, an epigenetic enzyme, and impaired histone 3 lysine 4 trimethylation (activation mark) at NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells)-binding sites on inflammatory gene promoters in bone marrow-derived macrophages and wound macrophages from postcecal ligation and puncture mice. Bone marrow transplantation studies demonstrated epigenetic modifications initiate in bone marrow progenitor/stem cells following sepsis resulting in lasting impairment in peripheral macrophage function. Importantly, human peripheral blood leukocytes from post-septic patients demonstrate a significant reduction in MLL1 compared with nonseptic controls. CONCLUSIONS: These data demonstrate that severe sepsis induces stable mixed-lineage leukemia 1-mediated epigenetic modifications in the bone marrow, which are passed to peripheral macrophages resulting in impaired macrophage function and deficient wound healing persisting long after sepsis recovery.

Exploring various polygenic risk scores for skin cancer in the phenomes of the Michigan genomics initiative and the UK Biobank with a visual catalog: PRSWeb.

Polygenic risk scores (PRS) are designed to serve as single summary measures that are easy to construct, condensing information from a large number of genetic variants associated with a disease. They have been used for stratification and prediction of disease risk. The primary focus of this paper is to demonstrate how we can combine PRS and electronic health records data to better understand the shared and unique genetic architecture and etiology of disease subtypes that may be both related and heterogeneous. PRS construction strategies often depend on the purpose of the study, the available data/summary estimates, and the underlying genetic architecture of a disease. We consider several choices for constructing a PRS using data obtained from various publicly-available sources including the UK Biobank and evaluate their abilities to predict not just the primary phenotype but also secondary phenotypes derived from electronic health records (EHR). This study was conducted using data from 30,702 unrelated, genotyped patients of recent European descent from the Michigan Genomics Initiative (MGI), a longitudinal biorepository effort within Michigan Medicine. We examine the three most common skin cancer subtypes in the USA: basal cell carcinoma, cutaneous squamous cell carcinoma, and melanoma. Using these PRS for various skin cancer subtypes, we conduct a phenome-wide association study (PheWAS) within the MGI data to evaluate PRS associations with secondary traits. PheWAS results are then replicated using population-based UK Biobank data and compared across various PRS construction methods. We develop an accompanying visual catalog called PRSweb that provides detailed PheWAS results and allows users to directly compare different PRS construction methods.

Medial branch radiofrequency ablation outcomes in patients with centralized pain.

BACKGROUND AND OBJECTIVES: We hypothesized that patients with characteristics of centralized pain (fibromyalgia (FM)-like phenotype) would be less likely to respond to radiofrequency ablation (RFA), which may explain some of the failures of this peripherally directed therapy. METHODS: We conducted a prospective, observational study of patients undergoing RFA using a number of validated self-report measures of pain, mood and function. The 2011 Fibromyalgia Survey Criteria were used to assess for symptoms of centralized pain and was the primary predictor of interest. We constructed multivariable linear regression models to evaluate covariates independently associated with change in pain 3 months after RFA. RESULTS: 141 patients scheduled for medial branch blocks were enrolled in the study; 55 underwent RFA (51 with complete 3 months' follow-up). Patients with higher FM scores had less improvement in overall body pain; however, this was not statistically significant (adjusted mean change in pain FM+0.41, FM-1.11, p=0.396). In a secondary analysis, the FM score was not associated with change in back pain (p=0.720), with both groups improving equally. This cohort also reported significant improvement in anxiety, physical function, catastrophizing, and sleep disturbance at 3 months after RFA. CONCLUSIONS: Although patients with high baseline centralized pain exhibited less improvement in overall pain, this trend was not statistically significant, possibly due to insufficient power. The same trend was not seen with change in spine pain with both groups improving equally. Centralized pain patients may have less improvement in overall pain but may have equal improvement in their site-specific pain levels after localized interventions.

Prevalence of Preoperative Opioid Use and Characteristics Associated With Opioid Use Among Patients Presenting for Surgery.

Importance: Patterns of preoperative opioid use are not well characterized across different surgical services, and studies in this patient population have lacked important self-reported data of pain and affect. Objectives: To assess the prevalence of preoperative opioid use and the characteristics of these patients in a broadly representative surgical cohort. Design, Setting, and Participants: Cross-sectional, observational study of patients undergoing surgery at a tertiary care academic medical center. Data were collected as a part of large prospective institutional research registries from March 1, 2010, through April 30, 2016. Exposures: Preoperative patient and procedural characteristics, including prospectively assessed self-reported pain and functional measures. Main Outcomes and Measures: Patient-reported opioid use before surgery. Results: Of the total 34 186 patients recruited (54.2% women; mean [SD] age, 53.1 [16.1] years), preoperative opioid use was reported in 7894 (23.1%). The most common opioids used were hydrocodone bitartrate (4685 [59.4%]), tramadol hydrochloride (1677 [21.2%]), and oxycodone hydrochloride (1442 [18.3%]). Age of 31 to 40 years (adjusted odds ratio [aOR], 1.26; 95% CI, 1.10-1.45), tobacco use (former use aOR, 1.32 [95% CI, 1.22-1.42]; current use aOR, 1.62 [95% CI, 1.48-1.78]), illicit drug use (aOR, 1.74; 95% CI, 1.16-2.60), higher pain severity (aOR, 1.33; 95% CI, 1.31-1.35), depression (aOR, 1.22; 95% CI, 1.12-1.33), higher Fibromyalgia Survey scores (aOR, 1.06, 95% CI, 1.05-1.07), lower life satisfaction (aOR, 0.95, 95% CI, 0.93-0.96), and more medical comorbidities (American Society of Anesthesiology score aOR, 1.47 [95% CI, 1.37-1.58]; Charlson Comorbidity Index aOR, 1.29 [95% CI, 1.18-1.41]) were all independently associated with preoperative opioid use. Preoperative opioid use was most commonly reported by patients undergoing orthopedic (226 [65.1%]) and neurosurgical spinal (596 [55.1%]) procedures and least common among patients undergoing thoracic procedures (244 [15.7%]). After adjusting for patient characteristics, the patients undergoing lower extremity procedures were most likely to report preoperative opioid use (aOR, 3.61; 95% CI, 2.81-4.64), as well as those undergoing pelvic (excluding hip) (aOR, 3.09; 95% CI, 1.88-5.08), upper extremity (aOR, 3.07; 95% CI, 2.12-4.45), and spinal or spinal cord (aOR, 2.68; 95% CI, 2.15-3.32) procedures, with the group undergoing intrathoracic surgery as the reference group. Conclusions and Relevance: In this large study of preoperative opioid use that includes patient-reported outcome measures, more than 1 in 4 patients presenting for surgery reported opioid use. These data provide important insights into this complicated patient population that would appear to help guide future preoperative optimization and perioperative opioid-weaning interventions.

Association of Polygenic Risk Scores for Multiple Cancers in a Phenome-wide Study: Results from The Michigan Genomics Initiative.

Health systems are stewards of patient electronic health record (EHR) data with extraordinarily rich depth and breadth, reflecting thousands of diagnoses and exposures. Measures of genomic variation integrated with EHRs offer a potential strategy to accurately stratify patients for risk profiling and discover new relationships between diagnoses and genomes. The objective of this study was to evaluate whether polygenic risk scores (PRS) for common cancers are associated with multiple phenotypes in a phenome-wide association study (PheWAS) conducted in 28,260 unrelated, genotyped patients of recent European ancestry who consented to participate in the Michigan Genomics Initiative, a longitudinal biorepository effort within Michigan Medicine. PRS for 12 cancer traits were calculated using summary statistics from the NHGRI-EBI catalog. A total of 1,711 synthetic case-control studies was used for PheWAS analyses. There were 13,490 (47.7%) patients with at least one cancer diagnosis in this study sample. PRS exhibited strong association for several cancer traits they were designed for, including female breast cancer, prostate cancer, melanoma, basal cell carcinoma, squamous cell carcinoma, and thyroid cancer. Phenome-wide significant associations were observed between PRS and many non-cancer diagnoses. To differentiate PRS associations driven by the primary trait from associations arising through shared genetic risk profiles, the idea of "exclusion PRS PheWAS" was introduced. Further analysis of temporal order of the diagnoses improved our understanding of these secondary associations. This comprehensive PheWAS used PRS instead of a single variant.

Association Between the 2011 Fibromyalgia Survey Criteria and Multisite Pain Sensitivity in Knee Osteoarthritis.

OBJECTIVES: The present study evaluated the relationship between the 2011 American College of Rheumatology fibromyalgia (FM) survey criteria and quantitative sensory testing (QST). MATERIALS AND METHODS: Patients with knee osteoarthritis scheduled to undergo knee arthroplasty completed the FM survey criteria and self-report measures assessing clinical symptoms. Patients also underwent a battery of QST procedures at the surgical knee and remote body sites, including pressure algometry, conditioned pain modulation, and temporal summation. All assessments were completed before surgery. FM survey criteria were used to calculate a continuous FM score indicating FM severity. RESULTS: A total of 129 patients were analyzed. Of these, 52.7% were female, 93.8% were Caucasian, and 3.8% met the FM survey criteria for FM classification. Mean age for females (63.6 y) and males (64.7 y) was similar. Females and males differed significantly in nearly every outcome, including FM severity, clinical pain, anxiety, depression, and pressure pain sensitivity. In females, FM scores significantly correlated with pressure pain sensitivity, but not conditioned pain modulation or temporal summation, such that increased sensitivity was associated with greater FM severity at all body sites examined. In addition, as FM scores increased, the association between pain sensitivity at the surgical knee and pain sensitivity at remote body sites also increased. No relationship between FM score and QST was observed in males. DISCUSSION: We demonstrated an association between diffuse hyperalgesia as measured by QST and FM severity in females with knee osteoarthritis. These results suggest that the FM survey criteria may represent a marker of pain centralization in females with potential utility in clinical decision making.

Changes in Anxiety and Depression Are Mediated by Changes in Pain Severity in Patients Undergoing Lower-Extremity Total Joint Arthroplasty.

BACKGROUND: Depression and anxiety are common comorbidities in chronic pain including osteoarthritis patients undergoing total joint arthroplasty (TJA). What is not clear is whether psychiatric comorbidity precedes the manifestation of painful states or represents a reaction to living with chronic pain and associated functional impairment. The objective of this research was to explore whether decreases in depressive and anxiety symptoms after lower-extremity TJA could be due to postsurgical reductions in pain. METHODS: We conducted a secondary analysis of data from 1448 TJA patients enrolled in the Analgesics Outcome Study. Patients completed measures of pain intensity, functional status, and depressive and anxiety symptoms preoperatively and at 3 and 6 months postoperatively. Data were analyzed using a structural equation modeling approach. RESULTS: We found that improvement in pain and physical function from baseline to 6 months postoperatively was associated with improvement in depression and anxiety symptoms. We also found that a change in overall body pain at 3 months after surgery significantly mediated changes in both the depression and anxiety scores at 6 months after surgery even when controlling for age, sex, baseline body pain, education, opioid use, and type of surgery. CONCLUSIONS: Presurgical affective symptoms not only have an effect on change in postsurgical pain, whereby lower preoperative scores on depression and anxiety were associated with lower postsurgical pain, but also postsurgical decreases in pain were associated with lower levels of depression and anxiety after surgery. Taking these points into consideration may prove useful in working toward better outcomes for TJA.

Influence of Intrinsic and Lifestyle Factors on the Development of IgE Sensitization.

BACKGROUND: IgE sensitization is a prerequisite for the development of allergic symptoms. The investigation of factors influencing the development of IgE is therefore crucial for understanding the onset of allergic diseases. METHODS: This epidemiological study investigated personal, intrinsic, and lifestyle factors in a nonselected cohort of 501 Austrian adolescents (aged 12-21 years). IgE levels to 112 allergen molecules were analyzed in the serum of participants using the ImmunoCAP ISAC®. Allergic sensitization, IgE levels to single allergens, and ISAC score sums were correlated with results obtained from a questionnaire. RESULTS: In this adolescent cohort, male participants showed a higher sensitization frequency (56.8%) compared to females (50.9%) and significantly increased IgE levels to profilins. Underweight subjects demonstrated a stronger IgE sensitization. Family size inversely correlated with IgE levels to PR-10 allergens, and predominately paternal allergies were a predictive factor for IgE sensitization in the children. Vaccination, breastfeeding, and delivery mode showed no influence, while a highly protective effect was observed for growing up on a farm. Of all of the investigated lifestyle factors, only smoking significantly influenced the risk for IgE development. Participants with moderate frequencies of colds showed increased sensitization levels. CONCLUSION: A hereditary predisposition and lifestyle factors such as a farming environment, smoking, family size, body weight, or frequency of colds significantly influenced the development of allergen-specific IgE in this cohort of adolescents.

Pressure sensitivity and phenotypic changes in patients with suspected opioid-induced hyperalgesia being withdrawn from full mu agonists.

OBJECTIVES: To assess changes in phenotype and pressure sensitivity in patients with suspected opioid-induced-hyperalgesia (OIH) after transitioning to buprenorphine. METHODS: Twenty patients with suspected OIH were enrolled to transition to buprenorphine therapy. Patients completed validated self-report measures at baseline and at 1, 4, 8 weeks, and 6 months after initiation of buprenorphine along with quantitative sensory testing including measures of pressure pain threshold, pain tolerance and Pain 50 (a pain intensity rating). RESULTS: 20 patients were enrolled, 17 were treated with buprenorphine and 11 completed all assessment points. We found that after transitioning to buprenorphine, patients on higher opioid doses (≥100mg oral morphine equivalents) had significant improvements for some measures including decreased pain severity and fibromyalgia survey scores, fewer neuropathic pain features, less catastrophizing, fewer depressive symptoms, and improved functioning 1-week after transitioning to buprenorphine with an eventual return back to baseline. Although not statistically significant, patients on high dose opioids (≥100mg OME) also showed a trend of decreased pressure sensitivity 1-week after transitioning to buprenorphine with a gradual return back to baseline. CONCLUSIONS: Our study is the first to look at pressure pain sensitivity in patients who were taking opioids and transitioned to buprenorphine. These results suggest that the patients most likely to benefit from buprenorphine therapy are those on higher doses. In addition, the eventual return back to baseline on measures of pain phenotype and pressure sensitivity suggests that buprenorphine may over time result in a return of the hyperalgesic effects of a full mu agonist.

New Persistent Opioid Use After Minor and Major Surgical Procedures in US Adults.

Importance: Despite increased focus on reducing opioid prescribing for long-term pain, little is known regarding the incidence and risk factors for persistent opioid use after surgery. Objective: To determine the incidence of new persistent opioid use after minor and major surgical procedures. Design, Setting, and Participants: Using a nationwide insurance claims data set from 2013 to 2014, we identified US adults aged 18 to 64 years without opioid use in the year prior to surgery (ie, no opioid prescription fulfillments from 12 months to 1 month prior to the procedure). For patients filling a perioperative opioid prescription, we calculated the incidence of persistent opioid use for more than 90 days among opioid-naive patients after both minor surgical procedures (ie, varicose vein removal, laparoscopic cholecystectomy, laparoscopic appendectomy, hemorrhoidectomy, thyroidectomy, transurethral prostate surgery, parathyroidectomy, and carpal tunnel) and major surgical procedures (ie, ventral incisional hernia repair, colectomy, reflux surgery, bariatric surgery, and hysterectomy). We then assessed data for patient-level predictors of persistent opioid use. Main Outcomes and Measures: The primary outcome was defined a priori prior to data extraction. The primary outcome was new persistent opioid use, which was defined as an opioid prescription fulfillment between 90 and 180 days after the surgical procedure. Results: A total of 36 177 patients met the inclusion criteria, with 29 068 (80.3%) receiving minor surgical procedures and 7109 (19.7%) receiving major procedures. The cohort had a mean (SD) age of 44.6 (11.9) years and was predominately female (23 913 [66.1%]) and white (26 091 [72.1%]). The rates of new persistent opioid use were similar between the 2 groups, ranging from 5.9% to 6.5%. By comparison, the incidence in the nonoperative control cohort was only 0.4%. Risk factors independently associated with new persistent opioid use included preoperative tobacco use (adjusted odds ratio [aOR], 1.35; 95% CI, 1.21-1.49), alcohol and substance abuse disorders (aOR, 1.34; 95% CI, 1.05-1.72), mood disorders (aOR, 1.15; 95% CI, 1.01-1.30), anxiety (aOR, 1.25; 95% CI, 1.10-1.42), and preoperative pain disorders (back pain: aOR, 1.57; 95% CI, 1.42-1.75; neck pain: aOR, 1.22; 95% CI, 1.07-1.39; arthritis: aOR, 1.56; 95% CI, 1.40-1.73; and centralized pain: aOR, 1.39; 95% CI, 1.26-1.54). Conclusions and Relevance: New persistent opioid use after surgery is common and is not significantly different between minor and major surgical procedures but rather associated with behavioral and pain disorders. This suggests its use is not due to surgical pain but addressable patient-level predictors. New persistent opioid use represents a common but previously underappreciated surgical complication that warrants increased awareness.

Exposure to Indoor Allergens in Different Residential Settings and Its Influence on IgE Sensitization in a Geographically Confined Austrian Cohort.

BACKGROUND: Exposure to indoor allergens is crucial for IgE sensitization and development of allergic symptoms. Residential settings influence the allergen amount in house dust and hence allergic sensitization. Within this study, we investigated allergen exposure and molecule-based IgE levels in a geographically confined region and evaluated the impact of housing, pets and cleaning. METHODS: 501 adolescents from Salzburg, Austria participated in this cross-sectional study. House dust samples were examined regarding major mite, cat, dog, and mold allergens using a multiplex assay. Serum samples of participants were analyzed for specific IgE to Der p 1, Der p 2, Fel d 1, Can f 1 and Alt a 1 using the multiplex array ImmunoCAP ISAC. Information on allergies, living areas, dwelling form (house, flat, farm), pets, and household cleanliness were obtained by a questionnaire. RESULTS: In investigated house dust samples, the concentration of cat allergen was highest while the prevalence of mold allergens was very low. Participants showed IgE sensitization to Der p 1 (13.2%), Der p 2 (18.2%), Fel d 1 (14.4%), Can f 1 (2.4%) and Alt a 1 (2.0%). In alpine regions, lower mite allergen concentrations were detected which correlated with reduced IgE levels. A trend for increased sensitization prevalence from rural to alpine to urban regions was noted. Living on farms resulted in lower sensitization prevalence to mite and cat allergens, even though exposure to mites was significantly elevated. The presence of cats was associated with a lower sensitization rate and IgE levels to cat and mite allergens, and less frequent allergic diseases. Cleaning did not impact allergen concentrations, while IgE reactivity to mites and allergic diseases were more pronounced when living in cleaner homes. CONCLUSION: Allergen exposure to indoor allergens was influenced by setting of homes. Living in a farm environment and having a cat at home showed a protective effect for IgE sensitization and allergies. This cross-sectional study in combination with hereditary and lifestyle factors enables development of risk schemes for a more efficient management and potential prevention of allergic diseases.