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Abstract Opioid prescription records in existing electronic health record (EHR) databases are a potentially useful, high-fidelity data source for opioid use-related risk phenotyping in genetic analyses. Prescriptions for codeine derived from EHR records were used as targeting traits by screening 16 million patient-level medication records. Genome-wide association analyses were then conducted to identify genomic loci and candidate genes associated with different count patterns of codeine prescriptions. Both low- and high-prescription counts were captured by developing 8 types of phenotypes with selected ranges of prescription numbers to reflect potentially different levels of opioid risk severity. We identified one significant locus associated with low-count codeine prescriptions (1, 2 or 3 prescriptions), while up to 7 loci were identified for higher counts (≥ 4, ≥ 5, ≥6, or ≥ 7 prescriptions), with a strong overlap across different thresholds. We identified 9 significant genomic loci with all-count phenotype. Further, using the polygenic risk approach, we identified a significant correlation (Tau = 0.67, p = 0.01) between an externally derived polygenic risk score for opioid use disorder and numbers of codeine prescriptions. As a proof-of-concept study, our research provides a novel and generalizable phenotyping pipeline for the genomic study of opioid-related risk traits.

Abstract Background Supplemental oxygen (SO) potentiates opioid-induced respiratory depression (OIRD) in experiments on healthy volunteers. Our objective was to examine the relationship between SO and OIRD in patients on surgical units. Methods This post-hoc analysis utilized a portion of the observational PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) trial dataset (202 patients, two trial sites), which involved blinded continuous pulse oximetry and capnography monitoring of postsurgical patients on surgical units. OIRD incidence was determined for patients receiving room air (RA), intermittent SO, or continuous SO. Generalized estimating equation (GEE) models, with a Poisson distribution, a log-link function and time of exposure as offset, were used to compare the incidence of OIRD when patients were receiving SO vs RA. Results Within the analysis cohort, 74 patients were always on RA, 88 on intermittent and 40 on continuous SO. Compared with when on RA, when receiving SO patients had a higher risk for all OIRD episodes (incidence rate ratio [IRR] 2.7, 95% confidence interval [CI] 1.4–5.1), apnea episodes (IRR 2.8, 95% CI 1.5–5.2), and bradypnea episodes (IRR 3.0, 95% CI 1.2–7.9). Patients with high or intermediate PRODIGY scores had higher IRRs of OIRD episodes when receiving SO, compared with RA (IRR 4.5, 95% CI 2.2–9.6 and IRR 2.3, 95% CI 1.1–4.9, for high and intermediate scores, respectively). Conclusions Despite oxygen desaturation events not differing between SO and RA, SO may clinically promote OIRD. Clinicians should be aware that postoperative patients receiving SO therapy remain at increased risk for apnea and bradypnea. Trial registration Clinicaltrials.gov: NCT02811302, registered June 23, 2016.

Background:. No study has contextualized the excess mortality attributable to racial and ethnic disparities in surgical outcomes. Further, not much effort has been made to quantify the effort needed to eliminate these disparities. Objective:. We examined the current trends in mortality attributable to racial or ethnic disparities in the US postsurgical population. We then identified the target for mortality reduction that would be necessary to eliminate these disparities by 2030. Methods:. We performed a population-based study of 1,512,974 high-risk surgical procedures among adults (18–64 years) performed across US hospitals between 2000 and 2020. Results:. Between 2000 and 2020, the risk-adjusted mortality rates declined for all groups. Nonetheless, Black patients were more likely to die following surgery (adjusted relative risk 1.42; 95% CI, 1.39–1.46) driven by higher Black mortality in the northeast (1.60; 95% CI, 1.52–1.68), as well as the West (1.53; 95% CI, 1.43–1.62). Similarly, mortality risk remained consistently higher for Hispanics compared with White patients (1.21; 95% CI, 1.19–1.24), driven by higher mortality in the West (1.26; 95% CI, 1.21–1.31). Overall, 8364 fewer deaths are required for Black patients to experience mortality on the same scale as White patients. Similar figures for Hispanic patients are 4388. To eliminate the disparity between Black and White patients by 2030, we need a 2.7% annualized reduction in the projected mortality among Black patients. For Hispanics, the annualized reduction needed is 0.8%. Conclusions:. Our data provides a framework for incorporating population and health systems measures for eliminating disparity in surgical mortality within the next decade.

Abstract Background The surge of critically ill patients due to the coronavirus disease-2019 (COVID-19) overwhelmed critical care capacity in areas of northern Italy. Anesthesia machines have been used as alternatives to traditional ICU mechanical ventilators. However, the outcomes for patients with COVID-19 respiratory failure cared for with Anesthesia Machines is currently unknow. We hypothesized that COVID-19 patients receiving care with Anesthesia Machines would have worse outcomes compared to standard practice. Methods We designed a retrospective study of patients admitted with a confirmed COVID-19 diagnosis at a large tertiary urban hospital in northern Italy. Two care units were included: a 27-bed standard ICU and a 15-bed temporary unit emergently opened in an operating room setting. Intubated patients assigned to Anesthesia Machines (AM group) were compared to a control cohort treated with standard mechanical ventilators (ICU-VENT group). Outcomes were assessed at 60-day follow-up. A multivariable Cox regression analysis of risk factors between survivors and non-survivors was conducted to determine the adjusted risk of death for patients assigned to AM group. Results Complete daily data from 89 mechanically ventilated patients consecutively admitted to the two units were analyzed. Seventeen patients were included in the AM group, whereas 72 were in the ICU-VENT group. Disease severity and intensity of treatment were comparable between the two groups. The 60-day mortality was significantly higher in the AM group compared to the ICU-vent group (12/17 vs. 27/72, 70.6% vs. 37.5%, respectively, p = 0.016). Allocation to AM group was associated with a significantly increased risk of death after adjusting for covariates (HR 4.05, 95% CI: 1.75–9.33, p = 0.001). Several incidents and complications were reported with Anesthesia Machine care, raising safety concerns. Conclusions Our results support the hypothesis that care associated with the use of Anesthesia Machines is inadequate to provide long-term critical care to patients with COVID-19. Added safety risks must be considered if no other option is available to treat severely ill patients during the ongoing pandemic. Clinical trial number Not applicable.

Purpose: Does surgical approach (minimally invasive vs. open) and type (radical vs. partial nephrectomy) affects opioid use and workplace absenteeism. Materials and Methods: Retrospective multivariable regression analysis of 2,646 opioid-naïve patients between 18 and 64 undergoing radical or partial nephrectomy via either a minimally invasive vs. open approach for kidney cancer in the United States between 2012 and 2017 drawn from the IBM Watson Health Database was performed. Outcomes included: (1) opioid use in opioid-naïve patients as measured by opioid prescriptions in the post-operative setting at early, intermediate and prolonged time periods and (2) workplace absenteeism after surgery. Results: Patients undergoing minimally invasive surgery had a lower odds of opioid use in the early and intermediate post-operative periods (early: odds ratio [OR], 0.77; 95% confidence interval [CI], 0.62–0.97; p=0.02, intermediate: OR, 0.60; 95% CI, 0.48–0.75; p

Abstract Background This Consensus Statement introduces a standardized framework, in a checklist format, to support future development and reporting of TDABC studies in healthcare, and to encourage their reproducibility. Additionally, it establishes the first formal networking of TDABC researchers through the creation of the TDABC in Healthcare Consortium. Methods A consensus group of researchers reviewed the most relevant TDABC studies available in Medline and Scopus databases to identify the initial elements of the checklist. Using a Focus Group process, each element received a recommendation regarding where in the scientific article section it should be placed and whether the element was required or suggested. A questionnaire was circulated with expert researchers in the field to provide additional recommendations regarding the content of the checklist and the strength of recommendation for each included element. Results The TDABC standardized framework includes 32 elements, provides recommendations where in the scientific article to include each element, and comments on the strength of each recommendation. All 32 elements were validated, with 21 elements classified as mandatory and 11 as suggested but not mandatory. Conclusions This is the first standardized framework to support the development and reporting of TDABC research in healthcare and to stablish a community of experts in TDABC methodology. We expect that it can contribute to scale strategies that would result in cost-savings outcomes and in value-oriented strategies that can be adopted in healthcare systems and institutions.

Abstract Background The rise in deaths attributed to opioid drugs has become a major public health problem in the United States and in the world. Minimally invasive surgery (MIS) is associated with a faster postoperative recovery and our aim was to investigate if the use of MIS was associated with lower odds of prolonged opioid prescriptions after major procedures. Methods Retrospective study using the IBM Watson Health Marketscan® Commerical Claims and Encounters Database investigating opioid-naïve cancer patients aged 18–64 who underwent open versus MIS radical prostatectomy (RP), partial colectomy (PC) or hysterectomy (HYS) from 2012 to 2017. Propensity weighted logistic regression analyses were used to estimate the independent effect of surgical approach on prolonged opioid prescriptions, defined as prescriptions within 91–180 days of surgery. Results Overall, 6838 patients underwent RP (MIS 85.5%), 4480 patients underwent PC (MIS 61.6%) and 1620 patients underwent HYS (MIS 41.8%). Approximately 70–80% of all patients had perioperative opioid prescriptions. In the weighted model, patients undergoing MIS were significantly less likely to have prolonged opioid prescriptions in all three surgery types (Odds Ratio [OR] 0.737, 95% Confidence Interval [CI] 0.595–0.914, p = 0.006; OR 0.728, 95% CI 0.600–0.882, p = 0.001; OR 0.655, 95% CI 0.466–0.920, p = 0.015, respectively). Conclusion The use of the MIS was associated with lower odds of prolonged opioid prescription in all procedures examined. While additional studies such as clinical trials are needed for further confirmation, our findings need to be considered for patient counseling as postoperative differences between approaches do exist.

Abstract Purpose of Review This is a comprehensive literature review of the available evidence and techniques of foot injections for chronic pain conditions. It briefly describes common foot chronic pain syndromes and then reviews available injection techniques for each of these syndromes, weighing the available evidence and comparing the available approaches. Recent Findings Foot and ankle pain affects 20% of the population over 50 and significantly impairs mobility and ability to participate in activities of daily living (ADLs), as well as increases fall risk. It is commonly treated with costly surgery, at times with questionable efficacy. Injection therapy is challenging when the etiology is anatomical or compressive. Morton’s neuroma is a budging of the interdigital nerve. Steroid, alcohol, and capsaicin injections provide some benefit, but it is short lived. Hyaluronic acid (HA) injection provided long-term relief and could prove to be a viable treatment option. Achilles tendinopathy (AT) is most likely secondary to repeat tendon stress—platelet-rich-plasma (PRP) and prolotherapy have been trialed for this condition, but more evidence is required to show efficacy. Similar injections were trials for plantar fasciitis and achieved only short-term relief; however, some evidence suggests that PRP injections reduce the frequency of required therapy. Tarsal tunnel syndrome, a compressive neuropathy carries a risk of permanent neural injury if left untreated. Injection therapy can provide a bridge to surgery; however, surgical decompression remains the definitive therapy. When the etiology is inflammatory, steroid injection is more likely to provide benefit. This has been shown in several studies for gout, as well as osteoarthritis of the foot and ankle and treatment-refractory rheumatoid arthritis. HA showed similar benefit, possibly due to anti-inflammatory effects. Stem cell injections may provide the additional benefit of structure restoration. Summary Chronic foot pain is common in the general population and has significant associated morbidity and disability. Traditionally treated with surgery, these are costly and only somewhat effective. Injections provide an effective alternative financially and some evidence exists that they are effective in pain alleviation. However, current evidence is limited and the benefit described from injection therapy has been short-lived in most cases. Further studies in larger populations are required to evaluate the long-term effects of these treatments.

Abstract Introduction Cosmetic breast surgery is commonly performed in the United States; 520,000 procedures of the total 1.8 million cosmetic surgical procedures performed in 2018 were breast related. Postoperative chronic pain, defined as lasting 3 or more months, has been reported in a wide variety of breast surgical procedures including breast augmentation, reduction mammaplasty, mastectomy, and mastectomy with reconstruction. Patient characteristics associated with the development of postoperative chronic pain following cosmetic breast surgery include a younger age, larger BMI, smaller height, postoperative hyperesthesia, and elevated baseline depression, anxiety, and catastrophizing scores. The anatomical distribution of chronic pain following breast augmentation procedures is dependent upon incision site placement; pectoral and intercostal nerves have been implicated. The purpose of this review is to provide an update on the current literature addressing the pathophysiology, clinical presentation, and treatment of patients presenting with chronic postoperative pain following cosmetic breast surgery. Methods A comprehensive literature review was performed in MEDLINE, PubMed, and Cochrane databases from 1996 to 2019 using the terms “cosmetic surgery”, “breast surgery”, “postoperative pain”, and “chronic pain”. Results Cosmetic breast surgery can have a similar presentation as post-mastectomy pain syndrome and thus have overlapping diagnostic criteria. Seven domains are identified for a diagnosis of PBSPS: Pain after breast surgery, neuropathic in nature, at least a moderate intensity of pain, as defined as within the middle one-third of the selected pain scale, pain for at least 6 months, symptoms occurring for 12 or more hours a day for a minimum of 4 days each week, pain in at least one of the following sites: breast, chest wall, axilla, or arm on the affected side, pain exacerbated by movement. Patient risk factors and surgical risk factors may influence the development of chronic post-cosmetic surgery breast pain. Improved perioperative analgesia including preoperative regional nerve anesthesia and postoperative catheter infusion have been shown to improve chronic postoperative pain outcomes. Conclusions The present review provides a discussion of clinical presentation, pathophysiology, and treatment and preventative strategies for chronic breast pain following cosmetic surgery. This review provides evidence from multiple randomized controlled trials (RCTs) and systematic reviews of efficacy and effectiveness. While chronic postoperative breast pain remains challenging to treat, various preventative strategies have been described to improve postoperative pain outcomes.

Optimization of pain assessment and treatment is an active area of research in healthcare. The purpose of this research is to create an objective pain intensity estimation system based on multimodal sensing signals through experimental studies. Twenty eight healthy subjects were recruited at Northeastern University. Nine physiological modalities were utilized in this research, namely facial expressions (FE), electroencephalography (EEG), eye movement (EM), skin conductance (SC), and blood volume pulse (BVP), electromyography (EMG), respiration rate (RR), skin temperature (ST), blood pressure (BP). Statistical analysis and machine learning algorithms were deployed to analyze the physiological data. FE, EEG, SC, BVP, and BP proved to be able to detect different pain states from healthy subjects. Multi-modalities proved to be promising in detecting different levels of painful states. A decision-level multi-modal fusion also proved to be efficient and accurate in classifying painful states.

**Background:** Innovative methodologies to redesign care delivery are being applied to increase value in health care, including the creation of enhanced recovery pathways (ERPs) for surgical patients. However, there is a lack of standardized methods to evaluate ERP implementation costs. **Objectives:** This Recommendations Statement aims to introduce a standardized framework to guide the economic evaluation of ERP care-design initiatives, using the Time-Driven Activity-Based Costing (TDABC) methodology. **Methods:** We provide recommendations on using the proposed framework to support the decision-making processes that incorporate ERPs. Since ERPs are usually composed of activities distributed throughout the patient care pathway, the framework can demonstrate how the TDABC may be a valuable method to evaluate the incremental costs of protocol implementation. Our recommendations are based on the review of available literature and expert opinions of the members of the TDABC in Healthcare Consortium. **Results:** The ERP framework, composed of 11 steps, was created describing how the techniques and methods can be applied to evaluate the economic impact of an ERP and guide health-care leaders to optimize the decision-making process of incorporating ERPs into health-care settings. Finally, six recommendations are introduced to demonstrate that using the suggested framework could increase value in ERP care-design initiatives by reducing variability in care delivery, educating multidisciplinary teams about value in health, and increasing transparency when managing surgical pathways. **Conclusions:** Our proposed standardized framework can guide decisions and support measuring improvements in value achieved by incorporating the perioperative redesign protocols.

Background: The study assessed whether pre-existing cognitive impairment (CI) prior to elective total knee arthroplasty (TKA) is associated with worse postoperative outcomes such as delirium, in-hospital medical complications, 30-day mortality, hospital length of stay and non-home discharge. Methods: A retrospective database analysis from the NSQIP Geriatric Surgery Pilot Project was used. There was an initial cohort of 6350 patients undergoing elective TKA, 104 patients with CI were propensity score matched to 104 patients without CI. Results: Analysis demonstrated a significantly increased incidence of post-operative delirium (POD) in the cohort with pre-op CI (p = < .001), a worsened functional status (p = < .001) and increased nonhome discharge postoperatively compared to the group without CI (p = 0.029). Other post-operative outcomes included 30-day mortality of 0% in both groups, and low rate of complications such as infection (2.88% vs 0.96%), pneumonia (1.92% vs 0%), failure to wean (0.96% vs 0%), and reintubation (0.96% vs 0%). Some other differences between the CI group and non-CI group, although not statistically significant, included increased rate of transfusion (10.58% vs 6.73%), and sepsis (1.92% vs 0%). The length of stay was increased in the non-CI group (4.28% vs 2.32%, p = 0.122). Conclusion: CI in patients undergoing TKA is associated with an increased risk of POD, worsened postoperative functional status, and discharge to non-home facility.

Introduction: Based upon the Third National Health and Nutrition Examination Survey data, iron deficiency anemia is the cause of at least 20% of cases of anemia in adults over the age of 65. This is especially relevant in patients undergoing major orthopedic surgery as substantial perioperative blood loss is possible, leading to a high rate of allogeneic blood transfusion in total hip replacements, total knee replacements, and hip fracture repairs. Significance: The results of this systematic review may be of interest to clinicians and hospital administrators evaluating the clinical efficacy and cost effectiveness of intravenous (IV) iron administration prior to major orthopedic surgery. Materials and Methods: The original studies considered for this review included patients who were over 18 years of age, undergoing major orthopedic surgery, and who received an IV iron treatment in the preoperative setting. A total of 1083 articles were identified and reviewed. After removing duplicates, 1031 publications were screened, and 105 full-text studies were assessed for eligibility. A total of 98 were excluded and 7 articles remained which met the criteria for this review. The primary outcome examined in the included studies was the allogeneic blood transfusion rate. The secondary areas of interest were changes in serum hemoglobin, morbidity and mortality, length of stay, and cost effectiveness. Results: This systematic review found little evidence that IV iron therapy is effective at reducing transfusion in patients undergoing major orthopedic surgery. Conclusions: We do not recommend preoperative IV iron therapy for all patients scheduled for major orthopedic surgery.

Introduction: Opioid-related adverse drug events (ORADEs) are an increasingly recognized complication associated with the common prescription of opioids after orthopedic surgery. In this study, we attempted to understand how potential ORADEs following hip replacement surgery in older patients affected hospital length of stay, hospital revenue, and their association with specific risk factors and clinically relevant diseases occurring during hospitalization. Methods: We conducted a retrospective study using the Centers for Medicare and Medicaid Services Administrative Database to analyze Medicare discharges after hip replacement surgery to identify potential ORADEs. The impact of potential ORADEs on mean hospital length of stay (LOS) and hospital revenue was analyzed. Results: The potential ORADE rate in patients who underwent hip replacement surgery was 8.6%. The mean LOS for discharges with a potential ORADE was 1.41 days longer than that for discharges without an ORADE. The mean hospital revenue per day with a potential ORADE was US$1708 less than without an ORADE. Potential ORADEs were also found to be strongly associated with poor patient outcomes such as pneumonia, septicemia, and shock. Discussion: Potential ORADEs in hip replacement surgery in older patients are associated with longer hospitalizations, decreased hospital revenue per day, certain patient risk factors, and clinically relevant diseases occurring during hospitalizations. Our finding of an association between potential ORADEs and decreased hospital revenue per day may be attributed to the management of these adverse events, as a patient may need to undergo additional testing, may need additional treatment regimens, and may need a higher level of care. Conclusion: By reducing the use of opioids and employing a multimodal analgesic approach, we may improve patient care, decrease hospital lengths of stay, and increase hospital revenue

Introduction: To evaluate the body of evidence on the predictive value of preoperative cognitive impairment on in-hospital, short-term, and midterm postoperative outcomes for elderly patients undergoing total knee arthroplasty (TKA). Significance: With an aging population, an increasing percentage of the U.S. patient population will be living with cognitive impairment. There is currently no systematic review that assesses postoperative outcomes of patients with mild cognitive impairment (MCI) or preexisting diagnosis of dementia while undergoing elective primary TKA. Results: A database search between January 1, 1997, and November 1, 2017 in EMBASE, MEDLINE, and PubMed was conducted to identify articles that compared postoperative outcomes after TKA between patients aged 60 years with and without cognitive impairment. Cognitive impairment included preexisting diagnosis of dementia or MCI identified during preoperative assessment. Eligible articles were selected using dual reviewer and third-party arbitrator. The quality of the studies was evaluated using the Newcastle-Ottawa Scale. The strength of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. A total of 6163 abstracts were screened. Only 11 full text articles met inclusion criteria, including 1 case–control, 5 prospective cohort, and 5 retrospective cohort studies. Two studies were of poor quality. Overall, there is moderate strength of evidence for increased risk of postoperative delirium, increased length of stay, and discharge to health-care facility among patients with preoperative MCI or preexisting dementia. The body of evidence is weak for other outcomes of interest including mortality, functionality and complications while in-hospital and in the short- and midterm. Conclusion: This review highlights the need for additional good quality studies to provide more information about MCI and dementia as risk factors in primary TKA.

Purpose: Emergency hip surgery generally has worse outcomes than elective hip surgery, even when adjusted for patient and surgical factors. Do-not-resuscitate (DNR) status patients are typically at higher perioperative risk and undergo a narrow range of surgical procedures. We aimed to compare the outcomes after hip surgery of differing degrees of urgency in this cohort. Materials and Methods: Using National Surgical Quality Improvement Program (NSQIP) data, we conducted univariate and multivariate analyses comparing outcomes of DNR status patients after emergency and nonemergency hip surgery (2007-2013). We conducted a subanalysis of mortality in elective versus nonelective cases (elective variable introduced from 2011). Results: Of 668 hip surgery cases in DNR status patients, 210 (31.4%) were emergency and 458 (68.8%) were nonemergency. There were no significant associations between emergency and nonemergency surgery regarding patient demographics, comorbidities, functional capacity, anesthesia type, or operative duration. There was no significant difference in the 30-day postoperative mortality between emergency (21.4%) and nonemergency (16.4%) or between elective (19.6%) and nonelective (18.3%) hip fracture surgeries performed in patients with preexisting DNR status. Morbidity patterns in emergency vs nonemergency cases demonstrated no significant differences, with the commonest 3 complications being transfusion (21.0% and 21.4%, respectively), urinary tract infection (9.5% and 7.9%, respectively), and pneumonia (both at 5.2%). The 30-day home discharge rates were low at 4.7% and 5.6%, respectively. Multivariate analysis demonstrated no significant associations between emergency and nonemergency surgery for mortality, discharge destination, length of stay or complications, except perioperative myocardial infarction (3.7% vs 1.3%, P < .04). Conclusion: For patients with DNR status, both emergent and non-emergent hip surgery carries high mortality, greatly exceeding rates predicted for that patient by American College of Surgeons NSQIP risk calculators. Morbidity rates and patterns for patients with DNR status are also similar in emergency and nonemergency groups. These data may be useful in discussing risk and obtaining adequately informed consent in DNR patients undergoing hip surgery.

Objectives. The propofol infusion syndrome (PRIS), a rare, often fatal, condition of unknown etiology, is defined by development of lipemic serum, metabolic acidosis, rhabdomyolysis, hepatomegaly, cardiac arrhythmias, and acute renal failure. Methods. To identify risk factors for and biomarkers of PRIS, a retrospective chart review of all possible PRIS cases during a 1-year period was conducted at a level 1 trauma hospital in ICU patients over 18 years of age receiving continuous propofol infusions for ≥3 days. Additional study inclusion criteria included vasopressor support and monitoring of serum triglycerides and creatinine. Results. Seventy-two patients, 61 males (84.7%) and 11 females (15.3%), satisfied study inclusion criteria; and of these, 3 males met the study definition for PRIS, with 1 case fatality. PRIS incidence was 4.1% with a case-fatality rate of 33%. The mean duration of propofol infusion was 6.96 days. A positive linear correlation was observed between increasing triglyceride levels and infusion duration, but no correlation was observed between increasing creatinine levels and infusion duration. Conclusions. Risk factors for PRIS were confirmed as high dose infusions over prolonged periods. Increasing triglyceride levels may serve as reliable biomarkers of impending PRIS, if confirmed in future investigations with larger sample sizes.