Changes in surgical mortality during COVID-19 pandemic by patients' race, ethnicity and socioeconomic status among US older adults: a quasi-experimental event study model.

OBJECTIVES: To examine changes in the 30-day surgical mortality rate after common surgical procedures during the COVID-19 pandemic and investigate whether its impact varies by urgency of surgery or patient race, ethnicity and socioeconomic status. DESIGN: We used a quasi-experimental event study design to examine the effect of the COVID-19 pandemic on surgical mortality rate, using patients who received the same procedure in the prepandemic years (2016-2019) as the control, adjusting for patient characteristics and hospital fixed effects (effectively comparing patients treated at the same hospital). We conducted stratified analyses by procedure urgency, patient race, ethnicity and socioeconomic status (dual-Medicaid status and median household income). SETTING: Acute care hospitals in the USA. PARTICIPANTS: Medicare fee-for-service beneficiaries aged 65-99 years who underwent one of 14 common surgical procedures from 1 January 2016 to 31 December 2020. MAIN OUTCOME MEASURES: 30-day postoperative mortality rate. RESULTS: Our sample included 3 620 689 patients. Surgical mortality was higher during the pandemic, with peak mortality observed in April 2020 (adjusted risk difference (aRD) +0.95 percentage points (pp); 95% CI +0.76 to +1.26 pp; p<0.001) and mortality remained elevated through 2020. The effect of the pandemic on mortality was larger for non-elective (vs elective) procedures (April 2020: aRD +0.44 pp (+0.16 to +0.72 pp); p=0.002 for elective; aRD +1.65 pp (+1.00, +2.30 pp); p<0.001 for non-elective). We found no evidence that the pandemic mortality varied by patients' race and ethnicity (p for interaction=0.29), or socioeconomic status (p for interaction=0.49). CONCLUSIONS: 30-day surgical mortality during the COVID-19 pandemic peaked in April 2020 and remained elevated until the end of the year. The influence of the pandemic on surgical mortality did not vary by patient race and ethnicity or socioeconomic status, indicating that once patients were able to access care and undergo surgery, surgical mortality was similar across groups.

Dual antiplatelet management in the perioperative period: updated and expanded systematic review.

BACKGROUND: Antiplatelet agents are central in the management of vascular disease. The use of dual antiplatelet therapy (DAPT) for the management of thromboembolic complications must be weighed against bleeding risk in the perioperative setting. This balance is critical in patients undergoing cardiac or non-cardiac surgery. The management of patients on DAPT for any indication (including stents) is not clear and there is limited evidence to guide decision-making. This review summarizes current evidence since 2015 regarding the occurrence of major adverse events associated with continuing, suspending, or varying DAPT in the perioperative period. METHODS: A research librarian searched PubMed and Cochrane from November 30, 2015 to May 17, 2022, for relevant terms regarding adult patients on DAPT for any reason undergoing surgery, with a perioperative variation in DAPT strategy. Outcomes of interest included the occurrence of major adverse cardiac events, major adverse limb events, all-cause death, major bleeding, and reoperation. We considered withdrawal or discontinuation of DAPT as stopping either aspirin or a P2Y12 inhibitor or both agents; continuation of DAPT indicates that both drugs were given in the specified timeframe. RESULTS: Eighteen observational studies met the inclusion criteria. No RCTs were identified, and no studies were judged to be at low risk of bias. Twelve studies reported on CABG. Withholding DAPT therapy for more than 2 days was associated with less blood loss and a slight trend favoring less transfusion and surgical re-exploration. Among five observational CABG studies, there were no statistically significant differences in patient death across DAPT management strategies. Few studies reported cardiac outcomes. The remaining studies, which were about procedures other than exclusively CABG, demonstrated mixed findings with respect to DAPT strategy, bleeding, and ischemic outcomes. CONCLUSION: The evidence base on the benefits and risks of different perioperative DAPT strategies for patients with stents is extremely limited. The strongest signal, which was still judged as low certainty evidence, is that suspension of DAPT for greater than 2 days prior to CABG surgery is associated with less bleeding, transfusions, and re-explorations. Different DAPT strategies' association with other outcomes of interest, such as MACE, remains uncertain. SYSTEMATIC REVIEW REGISTRATION: A preregistered protocol for this review can be found on the PROSPERO International Prospective Register of systematic reviews ( http://www.crd.york.ac.uk/PROSPERO/ ; registration number: CRD42022371032).

Inequities in surgical outcomes by race and sex in the United States: retrospective cohort study.

OBJECTIVE: To assess inequities in mortality by race and sex for eight common surgical procedures (elective and non-elective) across specialties in the United States. DESIGN: Retrospective cohort study. SETTING: US, 2016-18. PARTICIPANTS: 1 868 036 Black and White Medicare beneficiaries aged 65-99 years undergoing one of eight common surgeries: repair of abdominal aortic aneurysm, appendectomy, cholecystectomy, colectomy, coronary artery bypass surgery, hip replacement, knee replacement, and lung resection. MAIN OUTCOME MEASURE: The main outcome measure was 30 day mortality, defined as death during hospital admission or within 30 days of the surgical procedure. RESULTS: Postoperative mortality overall was higher in Black men (1698 deaths, adjusted mortality rate 3.05%, 95% confidence interval 2.85% to 3.24%) compared with White men (21 833 deaths, 2.69%, 2.65% to 2.73%), White women (21 847 deaths, 2.38%, 2.35% to 2.41%), and Black women (1631 deaths, 2.18%, 2.04% to 2.31%), after adjusting for potential confounders. A similar pattern was found for elective surgeries, with Black men showing a higher adjusted mortality (393 deaths, 1.30%, 1.14% to 1.46%) compared with White men (5650 deaths, 0.85%, 0.83% to 0.88%), White women (4615 deaths, 0.82%, 0.80% to 0.84%), and Black women (359 deaths, 0.79%, 0.70% to 0.88%). This 0.45 percentage point difference implies that mortality after elective procedures was 50% higher in Black men compared with White men. For non-elective surgeries, however, mortality did not differ between Black men and White men (1305 deaths, 6.69%, 6.26% to 7.11%; and 16 183 deaths, 7.03%, 6.92% to 7.14%, respectively), although mortality was lower for White women and Black women (17 232 deaths, 6.12%, 6.02% to 6.21%; and 1272 deaths, 5.29%, 4.93% to 5.64%, respectively). These differences in mortality appeared within seven days after surgery and persisted for up to 60 days after surgery. CONCLUSIONS: Postoperative mortality overall was higher among Black men compared with White men, White women, and Black women. These findings highlight the need to understand better the unique challenges Black men who require surgery face.

Dopamine D2 receptors bidirectionally regulate striatal enkephalin expression: Implications for cocaine reward.

Low dopamine D2 receptor (D2R) availability in the striatum can predispose for cocaine abuse; though how low striatal D2Rs facilitate cocaine reward is unclear. Overexpression of D2Rs in striatal neurons or activation of D2Rs by acute cocaine suppresses striatal Penk mRNA. Conversely, low D2Rs in D2-striatal neurons increases striatal Penk mRNA and enkephalin peptide tone, an endogenous mu-opioid agonist. In brain slices, met-enkephalin and inhibition of enkephalin catabolism suppresses intra-striatal GABA transmission. Pairing cocaine with intra-accumbens met-enkephalin during place conditioning facilitates acquisition of preference, while mu-opioid receptor antagonist blocks preference in wild-type mice. We propose that heightened striatal enkephalin potentiates cocaine reward by suppressing intra-striatal GABA to enhance striatal output. Surprisingly, a mu-opioid receptor antagonist does not block cocaine preference in mice with low striatal D2Rs, implicating other opioid receptors. The bidirectional regulation of enkephalin by D2R activity and cocaine offers insights into mechanisms underlying the vulnerability for cocaine abuse.

Evaluation of Opioid Prescription and Consumption Habits Following Endovascular Aortic Aneurysm Repair.

BACKGROUND: There has been a dramatic rise in opioid-related deaths over the past decade. Most of the reduction strategies have focused on outpatient use; however, recent studies have demonstrated an association between inpatient opioid use and consumption following discharge across a variety of surgical procedures. The objective of this study is to evaluate the association of inpatient use of opioids as well as the consumption of opioids after discharge following endovascular aortic aneurysm repair (EVAR). METHODS: A prospectively maintained database was reviewed for cases between 2015 and 2018. Patients were included in the study if they underwent an elective EVAR, had an intensive care unit stay less than 1 day and total length of stay less than 3 days. Patients were contacted to participate in a survey of opioid use if they received a prescription at discharge. The primary outcome was percent of prescribed opioids consumed following discharge. Multivariate analyses were performed to determine predictors of receiving an opioid prescription. RESULTS: One hundred seventy-one patients were included in the analysis; 95% patients were white and 85% male. 59% of patients responded to the survey. Seventy-one (42%) received an opioid prescription at discharge. Patients that received a discharge prescription tended to be younger (71 vs. 75 years, P = 0.005) and more likely to have received opioids while in the hospital (79% vs. 45%, P < 0.001). Additionally, patients who received opioids at discharge received a significantly greater amount of milligram oral morphine equivalents (OME) while in the hospital (27.76 ± 38.91 vs. 10.05 ±29.43, P < 0.001). Multivariate analysis demonstrated age, estimated blood loss (EBL), and OME per day to be significant inpatient predictors of requiring an outpatient opioid prescription. Open femoral access (27%) was not a predictor of opioid prescription at discharge. A total of 1185 pills were prescribed (29.6 ± 2.06 per patient), but only 208 pills consumed (5.2 ± 1.27 per patient). Around 82% of total pills prescribed were not consumed. CONCLUSIONS: This study evaluates inpatient opioid use and postdischarge consumption following EVAR. These data identify key factors associated with receiving an opioid prescription at discharge and demonstrate that patients consume far fewer opioids than prescribed. These findings provide insight as to which patients may not require an outpatient prescription following EVAR, leading to potential practice-changing opioid reduction strategies.

Postdischarge Opioid Use after Lower Extremity Bypass Surgery.

BACKGROUND: Opioid overprescription for acute postoperative pain is an inadvertent contributor to the opioid epidemic via pill diversion and misuse. In response, the surgical community advocates for evidence-based postoperative opioid prescribing guidelines. The objective of this study is to evaluate patient-reported opioid consumption after lower extremity bypass surgery. METHODS: We conducted a retrospective review of a prospectively maintained database of infrainguinal bypass operations from 2016 to 2019. For patients receiving an opioid prescription at discharge, a telephone survey was administered questioning the percentage of pills used. Exclusion criteria included chronic opioid use and reoperations or amputations within 30 days. The primary outcome was the difference in opioids prescribed versus opioids consumed. RESULTS: Forty-nine patients met inclusion criteria. Forty-one (84%) were prescribed opioids at discharge, and 27 (65.9%) completed the survey. The average age was 65.8 ± 7.7 years; 29.6% were women. Oxycodone immediate-release was most commonly prescribed (78%). On average, patients received 318 ± 156 morphine milligram equivalent. A total of 940 opioid pills were prescribed (36.0 ± 11.3 per patient), but only 37% were consumed. This difference resulted in 568 unused pills. CONCLUSIONS: This is the first study to specifically evaluate opioid use in a strictly lower extremity bypass population. Over 60% of pills were unused, which poses significant societal risk for misuse. Our findings contribute to knowledge of operation-specific opioid use, which may shape practice recommendations and reduce opioid overprescription after vascular surgery.

Alcohol operant self-administration: Investigating how alcohol-seeking behaviors predict drinking in mice using two operant approaches.

Alcohol operant self-administration paradigms are critical tools for studying the neural circuits implicated in both alcohol-seeking and consummatory behaviors and for understanding the neural basis underlying alcohol-use disorders. In this study, we investigate the predictive value of two operant models of oral alcohol self-administration in mice, one in which alcohol is delivered into a cup following nose-poke responses with no accurate measurement of consumed alcohol solution, and another paradigm that provides access to alcohol via a sipper tube following lever presses and where lick rate and consumed alcohol volume can be measured. The goal was to identify a paradigm where operant behaviors such as lever presses and nose pokes, as well as other tracked behavior such as licks and head entries, can be used to reliably predict blood alcohol concentration (BAC). All mice were first exposed to alcohol in the home cage using the "drinking in the dark" (DID) procedure for 3 weeks and then were trained in alcohol self-administration using either of the operant paradigms for several weeks. Even without sucrose fading or food pre-training, mice acquired alcohol self-administration with both paradigms. However, neither lever press nor nose-poke rates were good predictors of alcohol intake or BAC. Only the lick rate and consumed alcohol were consistently and significantly correlated with BAC. Using this paradigm that accurately measures alcohol intake, unsupervised cluster analysis revealed three groups of mice: high-drinking (43%), low-drinking (37%), and non-drinking mice (20%). High-drinking mice showed faster acquisition of operant responding and achieved higher BACs than low-drinking mice. Lick rate and volume consumed varied with the alcohol concentration made available only for high- and low-drinking mice, but not for non-drinking mice. In addition, high- and low-drinking mice showed similar patterns during extinction and significant cue-induced reinstatement of seeking. Only high-drinking mice showed insensitivity to quinine adulteration, indicating a willingness to drink alcohol despite pairing with aversive stimuli. Thus, this study shows that relying on active presses is not an accurate determination of drinking behavior in mice. Only paradigms that allow for accurate measurements of consumed alcohol and/or lick rate are valid models of operant alcohol self-administration, where compulsive-like drinking could be accurately determined based on changes in alcohol intake when paired with bitter-tasting stimuli.

Multigenerational effects of fetal-neonatal iron deficiency on hippocampal BDNF signaling.

Fetal-neonatal iron deficiency induces adult learning impairments concomitant with changes in expression of key genes underlying hippocampal learning and memory in spite of neonatal iron replenishment. Notably, expression of brain-derived neurotrophic factor (BDNF), a gene critical for neuronal maturation and synaptic plasticity, is lowered both acutely and in adulthood following early-life iron deficiency. Although the mechanism behind its long-term downregulation remains unclear, epigenetic modification in BDNF, as seen in other models of early-life adversity, may play a role. Given that early iron deficiency occurs during critical periods in both hippocampal and gonadal development, we hypothesized that the iron-sufficient offspring (F2 IS) of formerly iron-deficient (F1 FID) rats would show a similar suppression of the BDNF gene as their parents. We compared hippocampal mRNA levels of BDNF and functionally related genes among F1 IS, F1 ID, and F2 IS male rats at postnatal day (P) 15 and P65 using RT-qPCR. As expected, the F1 ID group showed a downregulation of BDNF and associated genes acutely at P15 and chronically at P65. However, the F2 IS group showed an upregulation of these genes at P15, returning to control levels at P65. These results demonstrate that adverse effects of early iron deficiency on hippocampal gene expression observed in the F1 are not present in the F2 generation, suggesting differential effects of nutritionally induced epigenetic programing during the critical periods of hippocampal and gonadal development.