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1.
Obstet Gynecol ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31503160

RESUMO

OBJECTIVE: To evaluate the effects of shared decision making using a simple decision aid for opioid prescribing after hysterectomy. METHODS: We conducted a prospective quality initiative study including all patients undergoing hysterectomy for benign, nonobstetric indications between March 1, 2018, and July 31, 2018, at our academic institution. Using a visual decision aid, patients received uniform education regarding postoperative pain management. They were then educated on the department's guidelines regarding the maximum number of tablets recommended per prescription and the mean number of opioid tablets used by a similar cohort of patients in a previously published study at our institution. Patients were then asked to choose their desired number of tablets to receive on discharge. Structured telephone interviews were conducted 14 days after surgery. The primary outcome was total opioids prescribed before compared with after implementation of the decision aid. Secondary outcomes included opioid consumption, patient satisfaction, and refill requests after intervention implementation. RESULTS: Of 170 eligible patients, 159 (93.5%) used the decision aid (one patient who used the decision aid was subsequently excluded from the analysis owing to significant perioperative complications), including 110 (69.6%) laparoscopic, 40 (25.3%) vaginal, and eight (5.3%) abdominal hysterectomies. Telephone surveys were completed for 89.2% (n=141) of participants. Student's t-test showed that patients who participated in the decision aid (post-decision aid cohort) were discharged with significantly fewer oral morphine equivalents than patients who underwent hysterectomy before implementation of the decision aid (pre-decision aid cohort) (92±35 vs 160±81, P<.01), with no significant change in the number of requested refills (9.5% [n=15] vs 5.7% [n=14], P=.15). In the post-decision aid cohort, 76.6% of patients (n=121) chose fewer tablets than the guideline-allotted maximum. Approximately 76% of patients (n=102) reported having leftover tablets. CONCLUSION: This quality improvement initiative illustrates that a simple decision aid can result in a significant decrease in opioid prescribing without compromising patient satisfaction or postoperative pain management.

2.
Ann Surg ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31389832

RESUMO

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.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31393537

RESUMO

Importance: Practice guidelines recommend nonopioid medications in children after tonsillectomy, but to date, studies have not used recent national data to assess perioperative opioid prescribing patterns or the factors associated with these patterns in this population. Closing this knowledge gap may help in assessing whether such prescribing and prescription duration could be safely reduced. Objective: To assess national perioperative opioid prescribing patterns, clinical and demographic factors associated with these patterns, and association between these patterns and complications in children after tonsillectomy compared with children not using opioids. Design, Setting, and Participants: This cohort analysis used the 2016 to 2017 claims data from the database of a large national private insurer in the United States. Opioid-naive children aged 1 to 18 years with a claims code for tonsillectomy with or without adenoidectomy between April 1, 2016, and December 15, 2017, were identified (n = 22 567) and screened against the exclusion criteria. The final sample included 15 793 children. Main Outcomes/Measures: The percentage of children with 1 or more perioperative fills (prescription drug claims for opioids between 7 days before to 1 day after tonsillectomy) was calculated, along with the duration of perioperative prescriptions (days supplied). Linear regression was used to identify the demographic and clinical factors associated with the duration of perioperative opioid prescriptions. Logistic regression was used to assess the association between having 1 or more perioperative fills and their duration and the risk of return visits 2 to 14 days after tonsillectomy for pain or dehydration, secondary hemorrhage, and constipation compared with children not using opioids. Results: Among 15 793 children, the mean (SD) age was 7.8 (4.2) years, 12 807 (81.1%) were younger than 12 years, 2986 (18.9%) were between 12 and 18 years of age, and 8289 (52.6%) were female. In total, 9411 (59.6%) children had 1 or more perioperative fills, and the median (25th-75th percentile) duration was 8 (6-10) days; 6382 had not perioperative fills. The probability of having 1 or more perioperative fills and the duration of prescription varied across US census divisions. Having 1 or more perioperative fills was not associated with return visits for pain or dehydration (adjusted odds ratio [AOR], 1.13; 95% CI, 0.95-1.34) or secondary hemorrhage (AOR, 0.90; 95% CI, 0.73-1.10) compared with children not using opioids, but it was associated with increased risk of return visits for constipation (AOR, 2.02; 95% CI, 1.24-3.28). Duration was not associated with return visits for complications. Conclusions and Relevance: These findings suggest that reducing perioperative opioid prescribing and the duration of perioperative opioid prescriptions may be possible without increasing the risk of these complications.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31411333

RESUMO

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.

6.
Genet Epidemiol ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31433078

RESUMO

The power of genetic association analyses can be increased by jointly meta-analyzing multiple correlated phenotypes. Here, we develop a meta-analysis framework, Meta-MultiSKAT, that uses summary statistics to test for association between multiple continuous phenotypes and variants in a region of interest. Our approach models the heterogeneity of effects between studies through a kernel matrix and performs a variance component test for association. Using a genotype kernel, our approach can test for rare-variants and the combined effects of both common and rare-variants. To achieve robust power, within Meta-MultiSKAT, we developed fast and accurate omnibus tests combining different models of genetic effects, functional genomic annotations, multiple correlated phenotypes, and heterogeneity across studies. In addition, Meta-MultiSKAT accommodates situations where studies do not share exactly the same set of phenotypes or have differing correlation patterns among the phenotypes. Simulation studies confirm that Meta-MultiSKAT can maintain the type-I error rate at the exome-wide level of 2.5 × 10-6 . Further simulations under different models of association show that Meta-MultiSKAT can improve the power of detection from 23% to 38% on average over single phenotype-based meta-analysis approaches. We demonstrate the utility and improved power of Meta-MultiSKAT in the meta-analyses of four white blood cell subtype traits from the Michigan Genomics Initiative (MGI) and SardiNIA studies.

8.
Genet Epidemiol ; 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31452258

RESUMO

Array genotyping is a cost-effective and widely used tool that enables assessment of up to millions of genetic markers in hundreds of thousands of individuals. Genotyping array data are typically highly accurate but sensitive to mixing of DNA samples from multiple individuals before or during genotyping. Contaminated samples can lead to genotyping errors and consequently cause false positive signals or reduce power of association analyses. Here, we propose a new method to identify contaminated samples and the sources of contamination within a genotyping batch. Through analysis of array intensity and genotype data from intentionally mixed samples and 22,366 samples of the Michigan Genomics Initiative, an ongoing biobank-based study, we show that our method can reliably estimate contamination. We also show that identifying sources of contamination can implicate problematic sample processing steps and guide process improvements. Compared to existing methods, our approach can estimate the proportion of contaminating DNA more accurately, eliminate the need for external databases of allele frequencies, and provide contamination estimates that are more robust to the ancestral origin of the contaminating sample.

9.
Ann Thorac Surg ; 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31447051

RESUMO

BACKGROUND: New persistent opioid use occurs in 3% to 14% of patients after elective surgery, but is poorly described after cardiothoracic surgery. We examined the association of prescription size with new persistent opioid use after cardiothoracic surgery. METHODS: Opioid-naive Medicare patients undergoing cardiothoracic surgery between 2009 and 2015 were identified. Patients who filled an opioid prescription between 30 days before surgery and 14 days after discharge and with continuous Medicare enrollment 12 months before and 6 months after surgery were selected (n = 24,549). New persistent use was defined as continued prescription fills 91 to 180 days after surgery. Prescription size was reported in oral morphine equivalents. Multivariable regression was performed for risk adjustment, and new persistent use rate was estimated. RESULTS: Patient age was 71 ± 8 years, 9222 (38%) were female, and 20,898 (85%) were white. Overall new persistent use was 12.8% (3153 of 24,549), and declined yearly from 17% in 2009 to 7.1% in 2015 (P < .001). Prescription size, preoperative prescription fills, black race, gastrointestinal complications, disability status, open lung resection, dual eligibility (Medicare and Medicaid), drug and substance abuse, female sex, tobacco use, high comorbidity, pain disorders, longer hospital stay, and younger age were associated with new persistent use. Adjusted new persistent use was 19.6% (95% confidence interval, 18.7% to 20.4%) among patients prescribed more than 450 oral morphine equivalents, compared with 10.4% (95% confidence interval, 9.9% to 10.8%) among those prescribed 200 oral morphine equivalents or less (P < .001). CONCLUSIONS: Size and timing of perioperative opioid prescriptions were the strongest predictors of new persistent opioid use after cardiothoracic surgery. Modifiable risk factors such as prescription size should be targeted to reduce new persistent use.

10.
Reg Anesth Pain Med ; 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31278203

RESUMO

INTRODUCTION: We hypothesized that patients with complex regional pain syndrome (CRPS) would describe a more negative pain phenotype including higher pain severity, more neuropathic pain descriptors, more centralized pain symptoms, poorer physical function, and more affective distress when compared with patients with neuropathic pain of the extremities not meeting CRPS criteria. MATERIALS AND METHODS: This was a retrospective cross-sectional study conducted at a tertiary pain center. The sample included 212 patients who met Budapest Criteria for CRPS and 175 patients with neuropathic pain of the extremities who did not meet criteria. All patients completed a packet of questionnaires before their initial visit containing validated outcome measures assessing pain severity, pain interference, physical functioning, depression, anxiety, and catastrophizing. RESULTS: Patients with CRPS reported higher physical disability (p=0.022) and more neuropathic pain symptoms (p=0.002) than patients not meeting CRPS criteria, but the groups did not otherwise differ significantly. There were no significant differences in pain severity or affective distress, despite power analyses suggesting the ability to detect small to medium effect sizes (d=0.29; w=0.14). Subanalyses of differences in neuropathic pain symptoms revealed that patients with CRPS, compared with patients not meeting CRPS criteria, were more likely to report pain with light touch (p=0.003), sudden pain attacks (p=0.003), pain with cold or heat (p=0.002), sensation of numbness (p=0.042), and pain with slight pressure (p=0.018). DISCUSSION: Counter to our hypothesis, the present study suggests that patients with CRPS do not have a worse clinical phenotype compared with patients not meeting CRPS criteria, with the exception of higher physical disability and more neuropathic pain symptoms. This corresponds to recent evidence that patients with CRPS are similar to other patient populations with chronic pain.

11.
Surgery ; 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31303324

RESUMO

BACKGROUND: Persistent opioid use is common after surgical procedures, and postoperative opioid prescribing often transitions from surgeons to primary care physicians in the months after surgery. It is unknown how surgeons currently transition these patients or the preferred approach to successful coordination of care. This qualitative study aimed to describe transitions of care for postoperative opioid prescribing and identify barriers and facilitators of ideal transitions for potential intervention targets. METHODS: We conducted a qualitative study of surgeons and primary care physicians at a large academic healthcare system using a semi-structured interview guide. Transcripts were independently coded using the Theoretical Domains Framework to identify underlying determinants of physician behaviors. We mapped dominant themes to the Behavior Change Wheel to propose potential interventions targeting these behaiors. RESULTS: Physicians were interviewed between July 2017 and December 2017 beyond thematic saturation (n = 20). Surgeons report passive transitions to primary care physicians after ruling out surgical complications, and these patients often bounce back to the surgeon when primary care physicians are uncertain of the cause of ongoing pain. Ideal practices were identified as setting preoperative expectations and engaging in active transition for postoperative opioid prescribing. We identified 3 behavioral targets for multidisciplinary intervention: knowledge (guidelines for coordination of care), barriers (utilizing support staff for active transition), and professional role (incentive for multidisciplinary collaboration). CONCLUSION: This qualitative study identifies potential interventions aimed at changing physician behaviors regarding transitions of care for postoperative opioid prescribing. Implementation of these interventions could improve coordination of care for patients with persistent postoperative opioid use.

13.
Surgery ; 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31349994

RESUMO

BACKGROUND: Although new persistent opioid use and high-risk prescribing have been recognized as important postoperative complications among younger patients (18-64 years of age), little is known about the incidence for postoperative opioid use among older patients (>65 years of age). METHODS: We analyzed a 20% national sample of Medicare Part D claims among beneficiaries >65 years of age who underwent a major or minor surgical procedure between January 1, 2009, and June 30, 2015. We identified patients without an opioid prescription fill in the year before surgery and examined their perioperative and 6-month postoperative opioid prescription fills to examine the incidence of new persistent opioid use and high-risk prescribing. RESULTS: We identified 81,839 opioid naïve patients who underwent surgery and filled an opioid prescription perioperatively. Overall, 9.8% developed new persistent opioid use. Risk factors for new persistent opioid use included major surgery (adjusted odds ratio [aOR] 1.24, 95% confidence interval [CI] 1.17-1.31), more comorbid conditions (aOR 1.71, 95% CI 1.58-1.84), mood disorders (aOR 1.16, 95% CI 1.09-1.24), suicide or self-harm (aOR 1.60, 95% CI 1.05-2.44), substance abuse disorders (aOR 1.38, 95% CI 1.20-1.59), filling an opioid prescription before surgery (aOR 1.67, 95% CI 1.58-1.77), higher amounts of opioids filled (aOR 1.44, 95% CI 1.37-1.52), black race (aOR 1.23, 95% CI 1.12-1.36), and Medicaid eligibility (aOR 1.45, 95% CI 1.35-1.55). CONCLUSION: About 10% of Medicare beneficiaries who were previously opioid naïve continue to fill opioids past 3 months after surgery. In addition to comorbidities and mental health conditions, new persistent opioid use is associated with surgery type, preoperative opioid fill, high-risk prescribing practices, and sociodemographic factors.

14.
Ann Surg ; 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31290756

RESUMO

MINI: This study sought to examine if early care-coordination between a patient's surgeon and usual prescriber of long-term opioid therapy could mitigate high-risk opioid prescribing following surgery. In this national cohort, 74.3% of chronic opioid users were exposed to episodes of high risk prescribing following surgery. Having a usual preoperative opioid prescriber and visiting this prescriber within 30 days after surgery was associated with decreased odds of having multiple prescribers in the postoperative period. OBJECTIVE: To describe if patients with chronic opioid use with a consistent usual prescriber (UP) prior to surgery and if early return to that UP (<30 d) would be associated with fewer high risk prescribing events in the postoperative period. SUMMARY BACKGROUND DATA: Over 10 million people each year are prescribed opioids for chronic pain. There is little evidence regarding coordination of opioid management and best practices for patients on long-term opioid therapy patients following surgery. METHODS: The study design is a retrospective cohort study. We identified 5749 commercially insured patients aged 18 to 64 with chronic opioid use who underwent elective surgery between January 2008 and March 2015. The predictors were presence of a UP and early return (<30 d from surgery) to a UP. The primary outcome was new high-risk opioid prescribing in the 90-day postoperative period (multiple prescribers, overlapping opioid and/or benzodiazepine prescriptions, new long acting opioid prescriptions, or new dose escalations to > 100 mg OME). RESULTS: In this cohort, 73.8% of patients were exposed to high risk prescribing postoperatively. Overall, 10% of patients did not have a UP preoperatively, and were more likely to have prescriptions from multiple prescribers (OR 2.23 95% CI 1.75-2.83) and new long acting opioid prescriptions (OR 1.69, 95% CI 1.05-2.71). Among patients with a UP, earlier return was associated with decreased odds of receiving prescriptions from multiple prescribers (OR 0.80, 95% CI 0.68-0.95). CONCLUSION: Patients without a UP prior to surgery are more likely to be exposed to high-risk opioid prescribing following surgery. Among patients who have a UP, early return visits may enhance care coordination with fewer prescribers.

16.
J Manag Care Spec Pharm ; 25(9): 973-983, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31313621

RESUMO

BACKGROUND: The treatment of postsurgical pain with prescription opioids has been associated with persistent opioid use and increased health care utilization and costs. OBJECTIVE: To compare the health care burden between opioid-naive adult patients who were prescribed opioids after a major surgery and opioidnaive adult patients who were not prescribed opioids. METHODS: Administrative claims data from the IBM Watson Health MarketScan Research Databases for 2010-2016 were used. Opioid-naive adult patients who underwent major inpatient or outpatient surgery and who had at least 1 year of continuous enrollment before and after the index surgery date were eligible for inclusion. Cohorts were defined based on an opioid pharmacy claim between 7 days before index surgery and 1 year after index surgery (opioid use during surgery and inpatient use were not available). To ensure an opioid-naive population, patients with opioid claims between 365 and 8 days before surgery were excluded. Acute medical outcomes, opioid utilization, health care utilization, and costs were measured during the post-index period (index surgery hospitalization and day of index outpatient surgery not included). Predicted costs were estimated from multivariable log-linked gamma-generalized linear models. RESULTS: The final sample consisted of 1,174,905 opioid-naive patients with an inpatient surgery (73% commercial, 20% Medicare, 7% Medicaid) and 2,930,216 opioid-naive patients with an outpatient surgery (74% commercial, 23% Medicare, and 3% Medicaid). Opioid use after discharge was common among all 3 payer types but was less common among Medicare patients (63% inpatient/43% outpatient) than patients with commercial (80% inpatient/75% outpatient) or Medicaid insurance (86% inpatient/81% outpatient). Across all 3 payers, opioid users were younger, were more likely to be female, and had a higher preoperative comorbidity burden than nonopioid users. In unadjusted analyses, opioid users tended to have more hospitalizations, emergency department visits, and pharmacy claims. Adjusted predicted 1-year post-period total health care costs were significantly higher (P< 0.001) for opioid users than nonopioid users for commercial insurance (inpatient: $22,209 vs. $14,439; outpatient: $13,897 vs. $8,825), Medicare (inpatient: $31,721 vs. $26,761; outpatient: $24,529 vs. $15,225), and Medicaid (inpatient: $13,512 vs. $9,204; outpatient: $11,975 vs. $8,212). CONCLUSIONS: Filling an outpatient opioid prescription (vs. no opioid prescription) in the 1 year after inpatient or outpatient surgery was associated with increased health care utilization and costs across all payers. DISCLOSURES: Funding for this study was provided by Heron Therapeutics, which participated in analysis and interpretation of data, drafting, reviewing, and approving the publication. All authors contributed to the development of the publication and maintained control over the final content. Brummett is a paid consultant for Heron Therapeutics and Recro Pharma and reports receipt of research funding from MDHHS (Sub K Michigan Open), NIDA (Centralized Pain Opioid Non-Responsiveness R01 DA038261-05), NIH0DHHS-US-16 PAF 07628 (R01 NR017096-05), NIH-DHHS (P50 AR070600-05 CORT), NIH-DHHS-US (K23 DA038718-04), NIH-DHHS-US-16-PAF06270 (R01 HD088712-05), NIH-DHHS-US-17-PAF02680 (R01 DA042859-05), and UM Michigan Genomics Initiative and holding a patent for peripheral perineural dexmedetomidine. Oderda is a paid consultant for Heron Therapeutics. Pawasauskas is a paid consultant to Heron Therapeutics and Mallinckrodt Pharmaceuticals. England and Evans-Shields are employees of Heron Therapeutics. Kong, Lew, Zimmerman, and Henriques are employees of IBM Watson Health, which was compensated by Heron Therapeutics for conducting this research. Portions of this work were presented as a poster at the AMCP Managed Care and Specialty Pharmacy Annual Meeting 2019; March 25-28, 2019; San Diego, CA.

17.
Ann Surg ; 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31188218

RESUMO

: Surgeons universally overprescribe opioids even in surgeries that are minimally invasive. Despite some drops in opioid prescribing nationally, surgeons and dentists have not changed their prescribing habits. Opioid guidelines are inherently flawed by the anchoring heuristic and efforts should center on decreasing exposures to opioids through a physician-lead response. No-opioid minimally invasive surgery should be the goal rather than the exception.

18.
PLoS Genet ; 15(6): e1008202, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31194742

RESUMO

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.

19.
Circ Genom Precis Med ; 12(6): e002476, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31211624

RESUMO

BACKGROUND: Thoracic aortic dissection is an emergent life-threatening condition. Routine screening for genetic variants causing thoracic aortic dissection is not currently performed for patients or family members. METHODS: We performed whole exome sequencing of 240 patients with thoracic aortic dissection (n=235) or rupture (n=5) and 258 controls matched for age, sex, and ancestry. Blinded to case-control status, we annotated variants in 11 genes for pathogenicity. RESULTS: Twenty-four pathogenic variants in 6 genes (COL3A1, FBN1, LOX, PRKG1, SMAD3, and TGFBR2) were identified in 26 individuals, representing 10.8% of aortic cases and 0% of controls. Among dissection cases, we compared those with pathogenic variants to those without and found that pathogenic variant carriers had significantly earlier onset of dissection (41 versus 57 years), higher rates of root aneurysm (54% versus 30%), less hypertension (15% versus 57%), lower rates of smoking (19% versus 45%), and greater incidence of aortic disease in family members. Multivariable logistic regression showed that pathogenic variant carrier status was significantly associated with age <50 (odds ratio [OR], 5.5; 95% CI, 1.6-19.7), no history of hypertension (OR, 5.6; 95% CI, 1.4-22.3), and family history of aortic disease (mother: OR, 5.7; 95% CI, 1.4-22.3, siblings: OR, 5.1; 95% CI, 1.1-23.9, children: OR, 6.0; 95% CI, 1.4-26.7). CONCLUSIONS: Clinical genetic testing of known hereditary thoracic aortic dissection genes should be considered in patients with a thoracic aortic dissection, followed by cascade screening of family members, especially in patients with age-of-onset <50 years, family history of thoracic aortic disease, and no history of hypertension.

20.
Reg Anesth Pain Med ; 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31048494

RESUMO

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.

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