A brief overview of pilot studies and their sample size justification.

Pilot studies, when properly designed and implemented, are an important tool that provide critical information for the development and potential success of a subsequent, larger trial. In fact, these small-scale studies are commonly used to assess the feasibility of whether a larger trial should be initiated. A popular investigator question is whether a pilot study requires a formal statistical power calculation. In general, the answer is "no"; however, the sample size needs to be justified on the basis of the goal of the pilot study.

Novel cross-linked polysaccharide-polyelectrolyte hemostatic foam improves survival compared to CombatGauze in swine femoral artery hemorrhage model.

BACKGROUND: Uncontrolled hemorrhage is the leading cause of preventable death in combat and civilian trauma. Efficacious hemostatic agents in junctional hemorrhage can quell blood loss and improve survival. We hypothesized that a novel hemostatic foam of starch and chitosan would improve hemostasis, and thereby increase survival in a swine femoral artery hemorrhage model when compared with CombatGauze (CG). METHODS: A novel hemostatic foam of starch and chitosan was created and modified during the study period. Thirty pigs (four excluded) were assigned to treatment using either foam version 1 (FV1, n = 9) or 2 (FV2, n = 8), or (n = 9) in a standard swine femoral artery hemorrhage model. Animals were observed for 150 minutes. Outcomes assessed included hemostasis, survival, posttreatment blood loss, IV fluid volume, and hemodynamic and laboratory trends. RESULTS: Hemostasis prior to 150 minutes was similar with 44.4%, 77.8%, and 50% of swine treated with CG, FV1 and FV2, respectively (Kaplan-Meyer and log-rank test [KM-LR] p > 0.05). Survival to 150 minutes was improved in swine treated with FV1 (100%) compared with CG (55.6%) (KM-LR p = 0.02). Survival was similar between FV1 and FV2 (75%) (KM-LR p > 0.05), and between CG and FV2 (KM-LR p > 0.05). Using mixed model for longitudinal data, mean arterial pressure decreased significantly in CG- and FV2-treated swine, while there was no significant change in mean arterial pressure in FV1-treated swine. Trends in lactic acid, hematocrit, platelets, INR, and thrombelastography were more favorable for FV1 compared with CG. CONCLUSION: In this preclinical study of junctional hemorrhage, survival was improved in swine treated with version 1 of a novel chitosan/starch foam compared with CG. Trends in hemodynamics and laboratory data were also more favorable in the FV1-treated swine. This novel hemostatic foam may be an effective alternative to current hemostatic agents.

Liberal vs. restricted opioid prescribing following midurethral sling dataset.

Postoperative opioid prescribing has historically lacked information critical to balancing the pain control needs of the individual patient with our professional responsibility to judiciously prescribe these high-risk medications. This data evaluates pain control, satisfaction with pain control, and opioid utilization among patients undergoing isolated mid-urethral sling (MUS) randomized to one of two different opioid prescribing regimens. This study was registered on clinicaltrials.gov (NCT04277975). Women undergoing isolated MUS by a Female Pelvic Medicine and Reconstructive Surgery physician at a Penn State Health hospital from June 1, 2020 to November 22, 2021 were offered enrollment into this prospective, randomized, open-label, non-inferiority clinical trial. Participants gave informed consent and were enrolled by a member of the study team. Allocation was concealed to patient and study personnel until randomization on the day of surgery. Preoperatively, all participants completed baseline demographic and pain surveys including CSI-9, PCS, and Likert pain score (scale 0-10). Participants were randomized to either receive a standard prescription of ten 5 mg tablets oxycodone provided preoperatively (standard) or opioid prescription provided only upon patient request postoperatively (restricted). Randomization was performed by the study team surgeon using the REDCap randomization module on the day of surgery. Following MUS, subjects completed a daily diary for 1 week, i.e., postoperative day (POD) 0 through 7. Within the dairy, subjects provided the following information: average daily pain score, opioid use and amount of opioid utilized, other forms of pain management, satisfaction with pain control, perception of the amount of opioid prescribed, and need for pain management hospital/clinic visits. The online Prescription Drug Monitoring Program (PDMP) was queried for all patients to determine if prescriptions for opioids were filled during the postoperative period. The primary outcome was average postoperative day 1 pain score and an a priori determined margin of non-inferiority was set at 2 points. Secondary outcomes included whether subject filled an opioid prescription (indicated by the online PDMP), opioid use (yes/no), satisfaction with pain control (on a scale of 1= "much worse" to 5= "much better" than expected), and how subjects felt about the amount of opioid prescribed (on a scale of 1="prescribed far more" to 3="prescribed the right amount" to 5="prescribed far less" opioid than needed). 82 participants underwent isolated MUS placement and met inclusion criteria; 40 were randomized to the standard arm and 42 to the restricted group. Within this manuscript, we detail the data obtained from this randomized clinical trial and the methods utilized.

Centrifugal or Roller Blood Pumps for Neonatal Venovenous Extracorporeal Membrane Oxygenation: Extracorporeal Life Support Organization Database Comparison of Mortality and Morbidity.

OBJECTIVES: To investigate outcomes associated with conventional roller or centrifugal pumps during neonatal venovenous extracorporeal membrane oxygenation (ECMO). Our primary hypothesis is that in comparison with conventional roller-pump support, centrifugal pump use is associated with greater odds of survival. Our secondary hypothesis is that centrifugal pump use is associated with lesser odds of complications. DESIGN: Retrospective cohort identified using the Extracorporeal Life Support Organization (ELSO) registry 2016 to 2020 dataset. SETTING: All ECMO centers reporting to the ELSO registry. PATIENTS: All neonates (≤ 28 d) supported with venovenous ECMO and cannulated via right internal jugular vein using dual-lumen venovenous cannulas and polymethyl pentene membrane oxygenators. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 612 neonates (centrifugal, n = 340; conventional roller, n = 272) were included in the analysis. Using a multivariable logistic regression model, centrifugal pump use-as opposed to roller pump use-was associated with lesser odds of survival (odds ratio [OR], 0.53; 95% CI, 0.33-0.84; p < 0.008). Thrombosis and clots in the circuit components were also associated with lesser odds of survival (OR, 0.28; 95% CI, 0.16-0.60; p < 0.001). We failed to show that hemolysis was an independent variable for survival (OR, 0.60; 95% CI, 0.31-1.19; p = 0.14). The primary diagnosis of neonatal aspiration/meconium aspiration is associated with more than seven-fold greater odds of survival (OR, 7.57; 95% CI, 4.02-15.74; p < 0.001). CONCLUSIONS: Contrary to our hypotheses, conventional roller pump use was associated with greater odds of survival. While thrombosis and clots in circuit components were independent variables for lesser odds of survival, further research is needed better to understand the use of centrifugal pumps in neonatal practice.

Oil-based or saline contrast for sono-hysterosalpingography in infertile women: a pilot randomized controlled double blind trial.

Objective: To determine the feasibility, safety, and outcomes of an oil-based, iodinated contrast using office-based, ultrasound-imaged hysterosalpingography in women with infertility. Design: Randomized Controlled Double Blind Clinical Trial. Setting: Academic health center. Interventions: Tubal flushing with oil-based contrast medium (Lipiodol UF) versus saline. Main Outcome Measures: Ongoing pregnancy rate, pain, quality of life, and thyroid function. Results: Forty-eight patients (24 in each group) were analyzed. The groups were well-matched at baseline. Ongoing pregnancy was noted in 17% (4/24) of the oil-contrast group versus 37% (9/24) in the saline group. Saline group patients more frequently initiated infertility therapy in the six-month follow-up period (saline, 67% vs. oil, 33%), and no serious adverse events in either group. There were no differences in pain from the procedure between groups. There were no differences in thyroid function tests postprocedure between groups, but within the oil-contrast group, there was a slight increase in thyroid-stimulating hormone (post vs. preratio of geometric means: 1.18; 95% confidence interval [CI], 1.02-1.38) and decrease in Free T4 (postdifference vs. predifference in means: 0.08 ng/dL; 95% CI, -0.14 to -0.01). Immediately after the test, the physicians correctly guessed 79% of oil and 71% of saline randomization assignments, whereas patients correctly guessed 63% of oil and 38% of saline. Conclusions: This pilot study demonstrates the safety and feasibility of giving an oil-based contrast medium during ultrasound-imaged hysterosalpingography. Pregnancies were seen after oil-based administration, and this contrast is associated with minor thyroid function impairment.

The effects of pulsatile versus nonpulsatile flow on cerebral pulsatility index, mean flow velocity at the middle cerebral artery, regional cerebral oxygen saturation, cerebral gaseous microemboli counts, and short-term clinical outcomes in patients undergoing congenital heart surgery.

Objective: The objective of this retrospective review was to evaluate whether or not pulsatile flow improves cerebral hemodynamics and clinical outcomes in pediatric congenital cardiac surgery patients. Methods: This retrospective study included 284 pediatric patients undergoing congenital cardiac surgery with cardiopulmonary bypass support utilizing nonpulsatile (n = 152) or pulsatile (n = 132) flow. Intraoperative cerebral gaseous microemboli counts, pulsatility index, and mean blood flow velocity at the right middle cerebral artery were assessed using transcranial Doppler ultrasound. Clinical outcomes were compared between groups. Results: Patient demographics and cardiopulmonary bypass characteristics between groups were similar. Although the pulsatility index during aortic crossclamping was consistently higher in the pulsatile group (P < .05), a significant degree of pulsatility was also observed in the nonpulsatile group. No significant differences in mean cerebral blood flow velocity, regional cerebral oxygen saturation, or gaseous microemboli counts were observed between the perfusion modality groups. Clinical outcomes, including intubation duration, intensive care unit and hospital length of stay, and mortality within 180 days were similar between groups. Conclusions: Although the pulsatility index was greater in the pulsatile group, other measures of intraoperative cerebral perfusion and short-term outcomes were similar to the nonpulsatile group. These findings suggest that while pulsatile perfusion represents a safe modality for cardiopulmonary bypass support, its use may not translate into detectably superior clinical outcomes.

Enhanced recovery for cesarean delivery leads to no difference in length of stay, decreased opioid use and lower infection rates.

OBJECTIVE: The primary objective of this study was to report surgical outcomes for cesarean delivery (CD) patients following the implementation of an Enhanced Recovery after Surgery (ERAS) pathway based on the ERAS Society recommendations. The primary outcome for which the study was powered was the length of stay (LOS). METHODS: This IRB-approved cohort study was conducted at a single tertiary-care labor and delivery unit and utilized a pre-post intervention design. Our ERAS for CD protocol was designed using the ERAS Society recommendations and implemented globally for every patient admitted to the labor and delivery unit including both scheduled and unscheduled cases. The study was designed to have at least 85% power to detect a 6-h difference in length of stay (LOS) between the pre-intervention and post-intervention cohorts, assuming a standard deviation of 18 h. A total of 339 records were included for data analysis, 170 in the pre-intervention cohort and 169 in the post-intervention cohort. To assess the difference between groups with respect to the primary outcome of LOS, linear regression was used with and without adjusting for covariates. Differences in dichotomous secondary outcomes were assessed using binary logistic regression. Differences in continuous secondary outcomes were assessed via a two-sample t-test or Wilcoxon rank sum test. Individual components of protocol adherence were compared using chi-square tests. RESULTS: Mean LOS was 80.5 ± 22.9 h and 82.3 ± 28.0 h, pre- and post-intervention respectively. There was no difference in LOS between the 2 cohorts (difference of means = 1.8 h; 95% confidence interval (CI): (-3.7, 7.3); p = .51). Cesarean procedure infection decreased from 11.8% pre-intervention to 5.3% post-intervention, corresponding to a 58% decrease in odds of cesarean procedure infection (odds ratio (OR)=0.42; 95% CI: (0.19, 0.96); p = .04). Inpatient opioid use also significantly decreased in the post-intervention cohort with a median MME per 12 h-period of 5.1 (25th percentile = 2.2, 75th percentile = 7.8) pre-intervention and 3.3 (25th percentile = 1.0, 75th percentile = 7.6) post-intervention (p = .04). CONCLUSION: The results of this study support the implementation of an ERAS for CD protocol based on ERAS Society recommendations as evidenced by the statistically significant decrease observed in both procedure-related infection rates and inpatient opioid use. We did not find a significant difference in LOS, which leaves room for further investigation into factors that impact LOS after CD.

Exclusion of Reproductive-aged Women in COVID-19 Vaccination and Clinical Trials.

INTRODUCTION: We analyzed the exclusion of pregnant and breastfeeding individuals and those capable of pregnancy in COVID-19 vaccine and clinical treatment trials. METHODS: Inclusion and exclusion criteria were extracted from all listed COVID-19 vaccine and treatment clinical trials from May 1, 2020, to October 31, 2020, using the U.S. National Library of Medicine database. We report rates of rates of exclusion for pregnant and lactating individuals and requirements for contraception for pregnancy-capable participants in COVID-19 vaccine and treatment clinical trials. The analysis included the association between clinical trial exclusion and vaccine and treatment type, study location, sponsor, and phase. RESULTS: Pregnant and lactating individuals were explicitly excluded from most COVID-19 vaccine and treatment clinical trials. Of the 90 vaccine trials, 88 (97.8%) excluded pregnant individuals, 73 (81.1%) excluded lactating individuals, and 56 (62.2%) required contraception use. Of the 495 treatment trials, 350 (70.7%) excluded pregnant individuals, 269 (54.3%) excluded lactating individuals, and 91 (18.4%) required contraception use. Although vaccine type was not associated with pregnancy exclusion, it was associated with lactation exclusion (p = .01) and contraception requirement (p < .001). Treatment type was associated with pregnancy exclusion, lactation exclusion, and contraception requirement (all p < .001). CONCLUSIONS: COVID-19 vaccination and treatment clinical trials mirrored historical trends restricting participation owing to pregnancy, lactation, and contraception nonuse, despite known safety profiles. People of childbearing potential should be considered for and afforded the same opportunity as males to make informed decisions on study participation, particularly in the setting of a global pandemic.

Dedicated Psychiatry Clinic for Inflammatory Bowel Disease Patients Has a Positive Impact on Depression Scores.

Background: Psychiatric disorders, including anxiety and depression, are significantly more common in patients with inflammatory bowel disease (IBD). We established an integrated psychiatry clinic for IBD patients at our tertiary center IBD clinic to provide patients with critical, but frequently unavailable, coordinated mental health services. We undertook this study to evaluate the impact of this service on psychiatric outcomes, quality of life, and symptom experience. Methods: We performed a longitudinal prospective study comparing patients who had been cared for at our integrated IBD-psychiatry clinic to those who had not. We abstracted demographic and clinical information as well as contemporaneous responses to validated surveys. Results: Thirty-six patients cared for in the IBD psychiatry clinic were compared to a control cohort of 35 IBD patients. There was a significant reduction in the Hospital Anxiety and Depression Scale (HADS) depression score over time in the study cohort (p = 0.001), though not in the HADS anxiety score. When compared to the control group, the study cohort showed a significant reduction in the HADS depression score. No significant differences were observed in the Harvey-Bradshaw Index, Simple Clinical Colitis Activity Index, or Short IBD Questionnaire. Conclusions: This is the first study to evaluate the impact of an integrated psychiatry clinic for IBD patients. Unlike their control counterparts, individuals treated in this clinic had a significant reduction in the mean HADS depression score. Larger scale studies are necessary to verify these findings. However, this study suggests that use of an integrated psychiatry IBD clinic model can result in improvement in mental health outcomes, even in the absence of significant changes in IBD activity.

Biomechanical Comparison of Fiber Tape Device Versus Transarticular Screws for Ligamentous Lisfranc Injury in a Cadaveric Model.

BACKGROUND: The preferred method of fixation and surgical treatment for ligamentous Lisfranc injuries is controversial. Transarticular screws, bridge plating, fusion, and flexible fixation have been described, yet none have demonstrated superiority. Furthermore, screw fixation and plating often require secondary surgery to remove implants, leading surgeons to seek alternative fixation methods. PURPOSE: To compare transarticular screws and a fiber tape construct under a spectrum of biomechanical loads by evaluating the diastasis at 3 joints in the Lisfranc complex. STUDY DESIGN: Controlled laboratory study. METHODS: Eight matched pairs of fresh, previously frozen lower extremity cadaveric specimens were fixed with either 2 cannulated transarticular crossed screws or a fiber tape construct with a supplemental intercuneiform limb. The diastasis between bones was measured at 3 midfoot joints in the Lisfranc complex: the Lisfranc articulation, the second tarsometatarsal joint, and the intercuneiform joint. Measurements were obtained for the preinjured, injured, and fixation conditions under static loading at 50% donor body weight. Specimens then underwent cyclic loading performed at 1 Hz and 100 cycles, based on 100-N stepwise increases in ground-reaction force from 100 to 2000 N, to simulate postoperative loading from the partial weightbearing stage to high-energy activities. Failure of fixation was defined as diastasis ≥2 mm at the Lisfranc articulation (second metatarsal-medial cuneiform joint). RESULTS: There were no significant differences in diastasis detected at the Lisfranc articulation or the intercuneiform joint throughout all loading cycles between groups. All specimens endured loading up to 50% body weight + 1400 N. Up to and including this stage, there were 2 failures in the cannulated transarticular crossed-screw group and none in the fiber tape group. CONCLUSION: The fiber tape construct with a supplemental intercuneiform limb, which does not require later removal, may provide comparable biomechanical stability to cannulated transarticular crossed screws, even at higher loads. CLINICAL RELEVANCE: Ligamentous Lisfranc injuries are common among athletes. Therefore, biomechanical evaluations are necessary to determine stable constructs that can limit the time to return to play. This study compares the biomechanical stability of 2 methods of fixation for ligamentous injury through a wide spectrum of loading, including those experienced by athletes.

The Association Between Adverse Childhood Experiences and Postpartum Depression.

Objective: Adverse childhood experiences (ACEs) are linked to worsening overall health outcomes and psychological diagnoses. Routine screening, particularly in patients with postpartum depression (PPD), would identify patients who could benefit from interventions to prevent the perpetuation of ACEs and establish a system of preventative care to mitigate the risks of adverse health outcomes associated with high ACE scores. The purpose of this study is to explore the link between ACEs and PPD to advocate for the use of the ACE questionnaire as a routine screening tool in all pregnant patients diagnosed with PPD. We hypothesize that a cohort of patients with PPD will be more likely to have high-risk ACE scores than the general female population. Study Design: Our IRB approved, retrospective cohort study identified all patients diagnosed with PPD at an academic medical center between January 2015 and December 2019. The subjects were identified using retrospective chart review. Subjects were recruited via telephone and asked to complete an ACE questionnaire. Questionnaires were sent via RedCap. ACE scores were calculated, categorized as 0, 1, 2, 3, or 4 or more ACEs, and compared to the prevalence in the original Kaiser-CDC ACE study female cohort using a chi-square goodness-of-fit test. Results: There were 132/251 surveys completed (53% response rate). In our PPD population, 19.3% had 0 ACEs, 17.0% had 1 ACE, 13.1% had 2 ACEs, 16.5% had 3 ACEs, and 34.1% had 4 or more ACEs. These percentages were significantly different from the Kaiser-CDC ACE Study percentages of 34.5, 24.5, 15.5, 10.3, and 15.2%, respectively (p < 0.001). Conclusion: Our unique study showed that women with PPD are more likely to have high-risk ACE scores than the general female population. This finding has important implications in regards to counseling, intervening to prevent perpetual ACEs, and establishing important provider-patient relationships for life-long preventative care.Non-gendered language is used when possible throughout. However, the wording from studies cited in this paper was preserved.

Multiple Laser Doppler Flowmetry Probes Increase the Reproducibility of Skin Blood Flow Measurements.

Cutaneous microcirculatory perfusion is commonly measured using laser Doppler flowmetry (LDF) probes, which provide a continuous, non-invasive quantification of skin blood flow (SkBF). However, inhomogeneities in the skin's microvasculature density contribute to a decrease in reproducibility whenever an LDF probe is removed and replaced, as is the case during pre- and post-intervention or between-day measurements. Therefore, this study aimed to determine whether increasing the total number of individual LDF probes in a localized area improves the reproducibility of the measurement. Seven laser Doppler probes were secured in a custom-made acrylic holder designed to attach to the skin's surface easily. SkBF, local skin temperature (Tsk), and blood pressure (BP) were assessed in 11 participants (6 M, 5 F, 42 ± 15 years). SkBF and Tsk were measured from the dorsal forearm (arm trial) for 5 min. Next, the multi-laser device was moved to the lateral side of the calf (leg trial), and measurements were obtained for 5 min. Each arm and leg trial was cyclically repeated three times, and all trials were separated by intermissions lasting 10-15 min. The average SkBF and the cutaneous vascular conductance (CVC) from all possible LDF probe combinations were not statistically different across the three arm and leg trials. Two-way mixed-effects models with absolute agreement were used to compute the intraclass correlation coefficient (ICC) for CVC, and the minimum ICC increased with the addition of LDF probes. The ICC of the average CVC from seven LDF probes was 0.96 between the arm trials and 0.91 between the leg trials, which suggests that there is excellent reliability and little difference between trials following the removal and replacement of the device. Moreover, all individual ICC values from ≥3 LDF probe combinations were greater than 0.70 (i.e., good reliability). These data suggest that SkBF measurements with multiple laser Doppler probes in a custom-made holder have excellent reproducibility after replacing the probes within the same participant. Therefore, this application could provide more reproducible assessments between repeated measurements (e.g., before and after exercise or clinical procedures) where the LDF probes must be removed and replaced within the same location.

A randomized trial of standard vs restricted opioid prescribing following midurethral sling.

BACKGROUND: Postoperative opioid prescribing has historically lacked information crucial to balancing the pain control needs of the individual patient with our professional responsibility to judiciously prescribe these high-risk medications. OBJECTIVE: This study aimed to evaluate pain control, satisfaction with pain control, and opioid use among patients undergoing isolated midurethral sling randomized to 1 of 2 different opioid-prescribing regimens. STUDY DESIGN: Patients who underwent isolated midurethral sling placement from June 1, 2020, to November 22, 2021, were offered enrollment into this prospective, randomized, open-label, noninferiority clinical trial. Participants were randomized to receive either a standard prescription of ten 5-mg oxycodone tablets provided preoperatively (standard) or an opioid prescription provided only during patient request postoperatively (restricted). Preoperatively, all participants completed baseline demographic and pain surveys, including the 9-Question Central Sensitization Index, Pain Catastrophizing Scale, and Likert pain score (scale 0-10). The participants completed daily surveys for 1 week after surgery to determine the average daily pain score, number of opioids used, other forms of pain management, satisfaction with pain control, perception of the number of opioids prescribed, and need to return to care for pain management. The online Prescription Drug Monitoring Program was used to determine opioid filling in the postoperative period. The primary outcome was average postoperative day 1 pain score, and an a priori determined margin of noninferiority was set at 2 points. RESULTS: Overall, 82 patients underwent isolated midurethral sling placement and met the inclusion criteria: 40 were randomized to the standard arm, and 42 were randomized to the restricted group. Concerning the primary outcome of average postoperative day 1 pain score, the restricted arm (mean pain score, 3.9±2.4) was noninferior to the standard arm (mean pain score, 3.7±2.7; difference in means, 0.23; 95% confidence interval, -∞ to 1.34). Of note, 23 participants (57.5%) in the standard arm vs 8 participants (19.0%) in the restricted arm filled an opioid prescription (P<.001). Moreover, 18 of 82 participants (22.0%) used opioids during the 7-day postoperative period, with 10 (25.0%) in the standard arm and 8 (19.0%) in the restricted arm using opioids (P=.52). Of participants using opioids, the average number of tablets used was 3.4±2.3, and only 3 participants used ≥5 tablets. On a scale of 1="prescribed far more opioids than needed" to 5="prescribed far less opioids than needed," the means were 1.9±1.0 in the standard arm and 2.7±1.0 in the restricted arm (P<.001). CONCLUSION: Restricted opioid prescription was noninferior to standard opioid prescription in the setting of pain control and satisfaction with pain control after isolated midurethral placement. Participants in the restricted arm filled fewer opioid prescriptions than participants in the standard arm. On average, only 3.4 tablets were used by those that filled prescriptions in both groups. Restrictive opioid-prescribing practices may reduce unused opioids in the community while achieving similar pain control.

A Randomized Clinical Trial of Perfusion Modalities in Pediatric Congenital Heart Surgery Patients.

BACKGROUND: The objective of this randomized clinical trial was to investigate the effects of perfusion modalities on cerebral hemodynamics, vital organ injury, quantified by the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) Score, and clinical outcomes in risk-stratified congenital cardiac surgery patients. METHODS: This randomized clinical trial included 159 consecutive congenital cardiac surgery patients in whom pulsatile (n = 83) or nonpulsatile (n = 76) perfusion was used. Cerebral hemodynamics were assessed using transcranial Doppler ultrasound. Multiple organ injury was quantified using the PELOD-2 score at 24, 48, and 72 hours. Clinical outcomes, including intubation time, intensive care unit length of stay (LOS), hospital LOS, and mortality, were also evaluated. RESULTS: The Pulsatility Index at the middle cerebral artery and in the arterial line during aortic cross-clamping was consistently better maintained in the pulsatile group. Demographics and cardiopulmonary bypass characteristics were similar between the 2 groups. While risk stratification with The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) Mortality Categories was similar between the groups, Mortality Categories 1 to 3 demonstrated more patients than Mortality Categories 4 and 5. There were no differences in clinical outcomes between the groups. The PELOD-2 scores showed a progressive improvement from 24 hours to 72 hours, but the results were not statistically different between the groups. CONCLUSIONS: The Pulsatillity Index for the pulsatile group demonstrated a more physiologic pattern compared with the nonpulsatile group. While pulsatile perfusion did not increase plasma-free hemoglobin levels or microemboli delivery, it also did not demonstrate any improvements in clinical outcomes or PELOD-2 scores, suggesting that while pulsatile perfusion is a safe method, it not a "magic bullet" for congenital cardiac operations.

Opioid use after cesarean: a cohort study comparing combined versus separate oxycodone and acetaminophen regimens.

OBJECTIVE: To determine whether an inpatient post-cesarean analgesic regimen which separated oxycodone and acetaminophen resulted in less inpatient opioid use, when compared to a regimen using combination medications containing both acetaminophen and oxycodone in a cohort including patients of all gestational ages, acuity levels, and modes of operative anesthesia. METHODS: This is a retrospective cohort study which was conducted at a single tertiary care center Labor and Delivery unit. Data were collected via retrospective chart review, and a total of 170 records were examined with a final N = 150. Inclusion criteria were all patients over the age of 18, and >23.0 weeks gestational age, who had a singleton or twin cesarean delivery regardless of their mode of operative anesthesia and whether or not they received intrathecal opioid at time of delivery. Exclusion criteria were pregnancies of higher-level multiples (triplets or greater), prolonged intensive care unit (ICU) stay, and patients who received both combination oxycodone-acetaminophen and separately administered oxycodone. For analysis patients were classified into two groups: the "Combined Medication" group representing patients who received combination oxycodone-acetaminophen medication only (n = 83) and the "Separate Medication" group representing patients who received oxycodone and acetaminophen separately (n = 67). Differences between the groups with respect to opioid use and acetaminophen use were assessed. RESULTS: The primary outcome was inpatient opioid medication use per 12-h period in intravenous morphine mg equivalents (MME). Patients received an average of 4.6 ± 3.5 MME IV morphine per 12 h in the Separate Medication group and 5.7 ± 3.7 MME IV morphine per 12 h in the Combined Medication group. When controlled for several covariates, the Separate Medication group took significantly fewer MME per 12-h period (mean difference = -1.2, 95% CI: (-2.3, -0.1), p = .04). There was no appreciable difference in acetaminophen utilization between groups. CONCLUSIONS: An analgesic regimen where oxycodone is ordered separately from acetaminophen is associated with reduced inpatient opioid medication use in patients of all gestational ages, acuity levels, and modes of operative anesthesia.

Opioid Prescribing and Utilization Following Isolated Mid-Urethral Sling.

INTRODUCTION: Overprescribing by providers is a leading contributor to the opioid crisis. Despite available information regarding the role that physician prescribing plays in the community availability of opioids, guidelines for the management of acute pain remain sparse. This project aims to evaluate opioid prescribing, opioid usage patterns, and postoperative pain control in patients undergoing isolated mid-urethral sling (MUS) placement. METHODS: Patients who underwent isolated MUS placement from March 19, 2019 through March 19, 2020 were contacted by telephone in May 2020 and asked a series of questions examining opioid usage, postoperative pain, what they did with unused opioids, and whether they had received education on disposal techniques. A chart review was utilized to determine the amount of opioid prescribed, the presence of any operative complications, and medical and demographic characteristics of subjects. RESULTS: A total of 53 subjects met inclusion criteria, of which 31 participated in a phone interview. Of the 53 subjects, 54.7% received a postoperative opioid prescription, and all but two of these subjects filled their prescription. Of the interviewed subjects, only 66.6% who filled a prescription reported using opioids Fifty percent (n=6) of patients that required oxycodone reported use of four tablets (30 morphine milligram equivalents (MMEs)) or less and used for 1-2 days postoperatively. No patient reported using opioids beyond five days. Only 22.2% reported receiving instruction on opioid disposal, and 16.7% returned unused opioids to a disposal center. 87.1% of subjects rated postoperative pain as "better" or "much better" than expected. CONCLUSION: Patients undergoing isolated MUS placement require limited amounts of postoperative opioids, if any are needed at all, to achieve satisfactory pain control. Excess prescribed opioids, along with inadequate patient education on proper disposal techniques, may contribute towards opioids that are at risk of diversion for nonmedical use.

The cross-hemispheric nigrostriatal pathway prevents the expression of levodopa-induced dyskinesias.

Parkinson's disease (PD) is a neurodegenerative movement disorder that is routinely treated with levodopa. Unfortunately, long-term dopamine replacement therapy using levodopa leads to levodopa-induced dyskinesias (LID), a significant and disabling side-effect. Clinical findings indicate that LID typically only occurs following the progression of PD motor symptoms from the unilateral (Hoehn and Yahr (HY) Stage I) to the bilateral stage (HY Stage II). This suggests the presence of some compensatory interhemispheric mechanisms that delay the occurrence of LID. We therefore investigated the role of interhemispheric connections of the nigrostriatal pathway on LID expression in a rat model of PD. The striatum of one hemisphere of rats was first injected with a retrograde tracer to label the ipsi- and cross-hemispheric nigrostriatal pathways. Rats were then split into groups and unilaterally lesioned in the striatum or medial forebrain bundle of the tracer-injected hemisphere to induce varying levels of hemiparkinsonism. Finally, rats were treated with levodopa and tested for the expression of LID. Distinct subsets emerged from rats that underwent the same lesioning paradigm based on LID. Strikingly, non-dyskinetic rats had significant sparing of their cross-hemispheric nigrostriatal pathway projecting from the unlesioned hemisphere. In contrast, dyskinetic rats only had a small proportion of this cross-hemispheric nigrostriatal pathway survive lesioning. Crucially, both non-dyskinetic and dyskinetic rats had nearly identical levels of ipsi-hemispheric nigrostriatal pathway survival and parkinsonian motor deficits. Our data suggest that the survival of the cross-hemispheric nigrostriatal pathway plays a crucial role in preventing the expression of LID and represents a potentially novel target to halt the progression of this devastating side-effect of a common anti-PD therapeutic.

Sensory Stimulation Threshold: A Viable Tool to Improve the Outcome of Lumbar Facet Radiofrequency Denervation?

BACKGROUND: Sensory stimulation threshold (SST) has been used as a surrogate marker to target a nerve branch for radiofrequency (RF) denervation; however, the validity of SST as a prognostic marker is still under debate. OBJECTIVE: To assess whether lower SST values correlate with better outcomes of radiofrequency denervation for facetogenic low back pain. DESIGN: Prospective cohort study. PATIENTS: Sixty-seven patients who underwent radiofrequency denervation for low back pain. METHODS: Correlations, between the average percentage of pain relief from diagnostic medial branch block (MBB) and RF denervation procedure outcome, and between SST and RF denervation procedure outcome, were analyzed using Spearman correlation coefficient (rs ). Wilcoxon rank sum test was performed to assess whether magnitude and duration of pain relief following RF denervation differed by the levels of SST (<0.5 and ≥0.5) or pain relief (<80% and ≥80%) from diagnostic MBB. RESULTS: There was a positive correlation between pain relief after diagnostic MBB and pain relief 2 weeks after denervation (rs 0.31, 95% CI 0.08 to 0.51, p < 0.01), but not between pain relief after MBB and pain relief 6 months after denervation, nor pain relief duration after denervation. There was a negative correlation between SST and pain relief 6 months after denervation (rs -0.41, 95% CI -0.59 to -0.18, p < 0.001). There was also a negative correlation between SST and pain relief duration after denervation (rs -0.33, 95% CI -0.53 to -0.09, p < 0.01). CONCLUSION: SST is a viable measurement with which to guide needle placement during RF denervation for lumbar facet pain, and enhances pain relief outcomes.