The impact of different strategies for modeling associations between medications at low doses and health outcomes: a simulation study and practical application to postpartum opioid use.

Pharmacoepidemiological studies commonly examine the association between drug dose and adverse health outcomes. In situations where no safe dose exists, the choice of modeling strategy can lead to identification of an apparent safe low dose range in the presence of a non-linear relationship or due to the modeling strategy forcing a linear relationship through a dose of 0. We conducted a simulation study to assess the performance of several regression approaches to model the drug dose-response curve at low doses in a setting where no safe range exists, including the use of a (1) linear dose term, (2) categorical dose term, and (3) natural cubic spline terms. Additionally, we introduce and apply an expansion of prior work related to modeling dose-response curves at low and infrequently used doses in the setting of no safe dose ("spike-at-zero" and "slab-and-spline"). Furthermore, we demonstrate and empirically assess the use of these regression strategies in a practical scenario examining the association between the dose of the initial postpartum opioid prescribed after vaginal delivery and the subsequent total dose of opioids prescribed in the entire postpartum period among a cohort of opioid-naïve women with a vaginal delivery enrolled in a State Medicaid program (2007-2014).

Walk before you run: Feasibility challenges and lessons learned from the PROCLAIM study, a multicenter randomized controlled trial of misoprostol for prevention of recurrent Clostridioides difficile during COVID-19.

We analyzed our challenging experience with a randomized controlled trial of misoprostol for prevention of recurrent C. difficile. Despite careful prescreening and thoughtful protocol modifications to facilitate enrollment, we closed the study early after enrolling just 7 participants over 3 years. We share lessons learned, noting the importance of feasibility studies, inclusion of biomarker outcomes, and dissemination of such findings to inform future research design and implementation successes.

Risk of Death at 1 Year Following Postpartum Opioid Exposure.

OBJECTIVE: Opioids are commonly prescribed to women for acute pain following childbirth. Postpartum prescription opioid exposure is associated with adverse opioid-related morbidities but the association with all-cause mortality is not well studied. This study aimed to examine the association between postpartum opioid prescription fills and the 1-year risk of all-cause mortality among women with live births. METHODS: In a retrospective cohort study of live births among women enrolled in Tennessee Medicaid (TennCare) between 2007 and 2015, we compared women who filled two or more postpartum outpatient opioid prescriptions (up to 41 days of postdelivery discharge) to women who filled one or fewer opioid prescription. Women were followed from day 42 postdelivery discharge through 365 days of follow-up or date of death. Deaths were identified using linked death certificates (2007-2016). We used Cox's proportional hazard regression and inverse probability of treatment weights to compare time to death between exposure groups while adjusting for relevant confounders. We also examined effect modification by delivery route, race, opioid use disorder, use of benzodiazepines, and mental health condition diagnosis. RESULTS: Among 264,135 eligible births, 216,762 (82.1%) had one or fewer maternal postpartum opioid fills and 47,373 (17.9%) had two or more fills. There were 182 deaths during follow-up. The mortality rate was higher in women with two or more fills (120.5 per 100,000 person-years) than in those with one or fewer (57.7 per 100,000 person-years). The risk of maternal death remained higher in participants exposed to two or more opioid fills after accounting for relevant covariates using inverse probability of treatment weighting (adjusted hazard ratio: 1.46 [95% confidence interval: 1.01, 2.09]). Findings from stratified analyses were consistent with main findings. CONCLUSION: Filling two or more opioid prescriptions during the postpartum period was associated with a significant increase in 1-year risk of death among new mothers. KEY POINTS: · Opioid prescribing in the postpartum period is common.. · Prior studies show that >1 postnatal opioid fill is associated with adverse opioid-related events.. · > 1 opioid fill within 42 days of delivery was associated with an increase in 1-year risk of death..

Enhanced rates of detection and treatment of depression and anxiety disorders among adult patients with epilepsy using automated EMR-based screening.

OBJECTIVE: Depression and anxiety disorders are common among patients with epilepsy (PWE). These comorbidities have been shown to influence prognosis and may have a greater impact on quality of life than seizure control. Despite guideline recommendations and expert consensus to regularly screen for and treat both conditions, there is evidence that they are underdiagnosed and undertreated. Our goal was to test a novel screening method to determine if it would increase the rate of detecting and treating depression and anxiety disorders among PWE. METHOD: The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and the Brief Epilepsy Anxiety Survey Instrument (brEASI) were selected as validated screening instruments for depression and anxiety disorders, respectively. They were sent via an electronic medical record-linked patient portal to all patients of four epileptologists 48 h prior to their clinic appointment. We evaluated whether this increased the rate of detecting and treating depression and anxiety disorders relative to a historical control group. RESULTS: A total of 563 patients were included of whom 351 were sent the screening instruments. 62.7% of patients completed the screening instruments of whom 47.7% screened positive for either depression only (16.4%), anxiety disorders only (5.5%) or both (25.9%); a statistically significant increase relative to the control group. There was also a significantly increased proportion of patients for whom treatment was initiated for depression (p < 0.01), anxiety disorders (p < 0.01), or both (p < 0.01). CONCLUSIONS: We identified an easily applicable and efficient means of enhancing detection and treatment rates for depression and anxiety disorders among PWE in a busy clinic setting.

Appropriate patient selection facilitates safe discharge from the PACU after laparoscopic ventral hernia repair: an analysis of the AHSQC database.

BACKGROUND: The postoperative management of patients undergoing laparoscopic ventral hernia repair (VHR) remains relatively unknown. The purpose of our study was to determine if patient and hernia-specific factors could be used to predict the likelihood of hospital admission following laparoscopic VHR using the Americas Hernia Society Quality Collaborative (AHSQC) database. METHODS: All patients who underwent elective, laparoscopic VHR with mesh placement from October 2015 through April 2019 were identified within the AHSQC database. Patients without clean wounds, those with chronic liver disease, and those without 30-day follow-up data were excluded from our analysis. Patient and hernia-specific variables were compared between patients who were discharged from the post-anesthesia care unit (PACU) and patients who required hospital admission. Comparisons were also made between the two groups with respect to 30-day morbidity and mortality events. RESULTS: A total of 1609 patients met inclusion criteria; 901 (56%) patients were discharged from the PACU. The proportion of patients discharged from the PACU increased with each subsequent year. Several patient comorbidities and hernia-specific factors were found to be associated with postoperative hospital admission, including older age, repair of a recurrent hernia, a larger hernia width, longer operative time, drain placement, and use of mechanical bowel preparation. Patients who required hospital admission were more likely than those discharged from the PACU to be readmitted to the hospital within 30 days (4% vs. 2%, respectively) and to experience a 30-day morbidity event (18% vs. 8%, respectively). CONCLUSIONS: Patient- and hernia-specific factors can be used to identify patients who can be safely discharged from the PACU following laparoscopic VHR. Additional studies are needed to determine if appropriate patient selection for discharge from the PACU leads to decreased healthcare costs for laparoscopic VHR over the long-term.

Heller myotomy versus Heller myotomy with Dor fundoplication for achalasia: long-term symptomatic follow-up of a prospective randomized controlled trial.

BACKGROUND: Our prior randomized controlled trial of Heller myotomy alone versus Heller plus Dor fundoplication for achalasia from 2000 to 2004 demonstrated comparable postoperative resolution of dysphagia but less gastroesophageal reflux after Heller plus Dor. Patient-reported outcomes are needed to determine whether the findings are sustained long-term. METHODS: We actively engaged participants from the prior randomized cohort, making up to six contact attempts per person using telephone, mail, and electronic messaging. We collected patient-reported measures of dysphagia and gastroesophageal reflux using the Dysphagia Score and the Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQL) instrument. Patient-reported re-interventions for dysphagia were verified by obtaining longitudinal medical records. RESULTS: Among living participants, 27/41 (66%) were contacted and all completed the follow-up study at a mean of 11.8 years postoperatively. Median Dysphagia Scores and GERD-HRQL scores were slightly worse for Heller than Heller plus Dor but were not statistically different (6 vs 3, p = 0.08 for dysphagia, 15 vs 13, p = 0.25 for reflux). Five patients in the Heller group and 6 in Heller plus Dor underwent re-intervention for dysphagia with most occurring more than five years postoperatively. One patient in each group underwent redo Heller myotomy and subsequent esophagectomy. Nearly all patients (96%) would undergo operation again. CONCLUSIONS: Long-term patient-reported outcomes after Heller alone and Heller plus Dor for achalasia are comparable, providing support for either procedure.

Cancer Survivorship: Defining the Incidence of Incisional Hernia After Resection for Intra-Abdominal Malignancy.

BACKGROUND: Cancer survivorship focuses largely on improving quality of life. We aimed to determine the rate of ventral incisional hernia (VIH) formation after cancer resection, with implications for survivorship. METHODS: Patients without prior VIH who underwent abdominal malignancy resections at a tertiary center were followed up to 2 years. Patients with a viewable preoperative computed tomography (CT) scan and CT within 2 years postoperatively were included. Primary outcome was postoperative VIH on CT, reviewed by a panel of surgeons uninvolved with the original operation. Factors associated with VIH were determined using Cox proportional hazards regression. RESULTS: 1847 CTs were reviewed among 491 patients (59 % men), with inter-rater reliability 0.85 for the panel. Mean age was 60 ± 12 years; mean follow-up time 13 ± 8 months. VIH occurred in 41 % and differed across diagnoses: urologic/gynecologic (30 %), colorectal (53 %), and all others (56 %) (p < 0.001). Factors associated with VIH (adjusting for stage, age, adjuvant therapy, smoking, and steroid use) included: incision location [flank (ref), midline, hazard ratio (HR) 6.89 (95 %CI 2.43-19.57); periumbilical, HR 6.24 (95 %CI 1.84-21.22); subcostal, HR 4.55 (95 %CI 1.51-13.70)], cancer type [urologic/gynecologic (ref), other {gastrointestinal, pancreatic, hepatobiliary, retroperitoneal, and others} HR 1.86 (95 %CI 1.26-2.73)], laparoscopic-assisted operation [laparoscopic (ref), HR 2.68 (95 %CI 1.44-4.98)], surgical site infection [HR 1.60 (95 %CI 1.08-2.37)], and body mass index [HR 1.06 (95 %CI 1.03-1.08)]. CONCLUSIONS: The rate of VIH after abdominal cancer operations is high. VIH may impact cancer survivorship with pain and need for additional operations. Further studies assessing the impact on QOL and prevention efforts are needed.

The use of an extracorporeal membrane oxygenation anticoagulation laboratory protocol is associated with decreased blood product use, decreased hemorrhagic complications, and increased circuit life.

OBJECTIVES: To determine if a comprehensive extracorporeal membrane oxygenation anticoagulation monitoring protocol results in fewer hemorrhagic complications, reduced blood product usage, and increased circuit life. DESIGN: In September 2011, we augmented our standard extracorporeal membrane oxygenation laboratory protocol to include anti-factor Xa assays, thromboelastography, and antithrombin measurements. We performed a retrospective chart review to determine outcomes for patients placed on extracorporeal membrane oxygenation prior to and after the initiation of our anticoagulation laboratory protocol. SETTING: Tertiary care, academic children's hospital. PATIENTS: All patients who were placed on extracorporeal membrane oxygenation at our institution from January 1, 2007, to September 30, 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 261 extracorporeal membrane oxygenation runs before the initiation of the protocol and 105 extracorporeal membrane oxygenation runs after the initiation of the protocol. There were no major changes to our extracorporeal membrane oxygenation circuit or changes to our transfusion threshold during the study period. The indication for extracorporeal membrane oxygenation, age, and severity of illness of the patients were similar before and after protocol initiation. Median blood product usage for packed RBCs, fresh frozen plasma, platelets, and cryoprecipitate decreased significantly after protocol initiation. The occurrence of cannula site bleeding decreased from 22% to 12% (p = 0.04), and surgical site bleeding decreased from 38% to 25% (p = 0.02). Median extracorporeal membrane oxygenation circuit life increased from 3.6 to 4.3 days (p = 0.02). A trend toward increased patient survival was noted, but it did not reach statistical significance. CONCLUSIONS: We demonstrate an association between an extracorporeal membrane oxygenation anticoagulation laboratory protocol using anti-factor Xa assays, thromboelastography, and antithrombin measurements and a decrease in blood product transfusion, a decrease in hemorrhagic complications, and an increase in circuit life. To our knowledge, this is the first study to demonstrate clinical benefit associated with the use of these laboratory values for patients on extracorporeal membrane oxygenation.

Contemporary prevalence of pretreatment urinary, sexual, hormonal, and bowel dysfunction: Defining the population at risk for harms of prostate cancer treatment.

BACKGROUND: The authors investigated the prevalence of pretreatment urinary, sexual, hormonal, and bowel dysfunction in a contemporary, population-based prostate cancer cohort. They also explored the associations between baseline function and age, comorbidity, and timing of baseline survey completion with respect to treatment. METHODS: The Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study is a population-based, prospective cohort study that enrolled 3691 men with incident prostate cancer during 2011 and 2012. Pretreatment function was ascertained using the Expanded Prostate Cancer Index-26 (EPIC-26). Data were stratified by age, comorbidity, and timing of baseline survey completion with respect to treatment. Unadjusted and multivariable linear regression analyses were performed to evaluate the relations between exposures and pretreatment function. RESULTS: After applying exclusion criteria, the study cohort comprised 3072 men. A strikingly high proportion of men reported inability to obtain erections satisfactory for intercourse (45%) and some degree of urinary incontinence (17%) at baseline. Sexual function was particularly age-sensitive, with patients aged ≤60 years reporting summary scores in excess of 30 points higher than patients aged ≥75 years (P < .001). Compared with the healthiest men, highly comorbid patients reported less favorable function in each domain, including urinary incontinence (summary score, 89.5 vs 74.1; P < .001) and sexual function (summary score, 70.8 vs 32.9; P < .001). Although statistically significant differences in summary scores were identified between patients who completed the baseline questionnaire before treatment (52%) versus after treatment (48%), the absolute differences were small (range, 1-3 points). CONCLUSIONS: Patients with newly diagnosed prostate cancer exhibit a wide distribution of pretreatment function. The current data may be used to redefine the population "at risk" for treatment-related harms.

Defining intraoperative hypothermia in ventral hernia repair.

BACKGROUND: Intraoperative normothermia, a single measurement of core body temperature≥36°C, is an important quality metric outlined by the World Health Organization for the reduction of surgical site infections (SSIs). Hypothermia has been linked to SSI in colorectal and trauma patients, but the effect in ventral hernia repair (VHR) is unknown. MATERIALS AND METHODS: Patients who underwent VHR at a single institution between 2005 and 2012 were included. Temperature data were matched with National Surgical Quality Improvement Program SSI data. Novel definitions of hypothermia were explored: patient temperature nadir, percentage of time spent at the nadir, mean temperature, and time spent <36°C. Multivariable regression models were performed. RESULTS: Five hundred fifty-three patients were included with temperature recorded every 8-15 min. Mean temperature nadir was 35.7°C (±1.3°C [standard deviation]) and was not associated with SSI (odds ratio [OR], 0.938; 95% confidence interval, 0.778-1.131). The percentage of readings spent at the nadir was 31% (±31%) and was not predictive of SSI (OR, 1.471; 95% CI, 0.983-2.203). As mean temperature increased, the risk of SSI increased (OR, 1.115; 95% CI, 0.559-2.225). Percentage of temperature readings<36°C was 29% (±38%) and was not associated with SSI (OR, 1.062; 95% CI, 0.628-1.796). In all models, body mass index, smoking, and length of surgery were predictive of SSI. CONCLUSIONS: Our results demonstrate no association between temperature and SSI in VHR. Efforts to reduce SSI should focus on factors such as smoking cessation, weight loss, and length of surgery. Our study suggests that maintenance of perioperative normothermia may only decrease SSIs in certain at-risk populations.

Effect of photoaging on skin test response to histamine independent of chronologic age.

BACKGROUND: Skin prick-puncture test responses to histamine on the upper back and forearms in older individuals are frequently small or absent but are often present or larger when repeated on the lower back. OBJECTIVE: To determine whether photoaging or natural aging causes a smaller response to a prick-puncture skin test. METHODS: Prick-puncture skin tests to histamine were performed on sun-exposed and sun-protected areas in younger (n = 61, aged 20-50 years) and older (n = 63, aged 60-87 years) adult volunteers. The skin was scored for photoaging by physical examination, and coloration was measured by a colorimeter. RESULTS: Large variation of photoaging occurred within age groups. Histamine wheals and flare were not different between the 2 age groups, but those adults with the greatest photoaging had smaller histamine wheals and flare on the upper back, with a trend for smaller flares on the volar aspect of the forearms and lower back. There was marked variability in response to histamine within individual adults, depending on the locale of the tests. CONCLUSION: Photoaging, but not age alone, is associated with a smaller response to histamine in sun-exposed areas. Before prick-puncture skin tests are performed, the skin should be examined for sun damage, and a sun-protected area should be selected; in vitro allergy testing may be substituted if there is no sun-protected skin area.

Social Vulnerability and Initiation of Pharmacotherapy for Gestational Diabetes Mellitus in a Medicaid Population.

OBJECTIVE: Our study examines the association between social vulnerability index (SVI) and pharmacotherapy initiation for gestational diabetes mellitus (GDM). METHODS: We studied a retrospective cohort of pregnant patients with GDM, enrolled in Tennessee Medicaid, who gave birth between 2007 and 2019. Enrollment files were linked to birth and death certificates, state hospitalization registries, and pharmacy claims. SVI, measured at the community level and determined by residential census tract, ranged from 0 to 100 (low to high vulnerability). Multivariable logistic regression assessed the association between SVI and the odds of initiating the most common pharmacotherapies for GDM-insulin, glyburide, or metformin-and adjusted for relevant covariates. SVI was modeled with restricted cubic splines to account for nonlinear associations, using the median Tennessee SVI as a reference. Secondary analysis assessed associations with the SVI subthemes. RESULTS: Among 33,291 patients with GDM, 21.7% (7,209) initiated pharmacotherapy during pregnancy. Patients from areas with higher SVI were more likely to be non-Hispanic Black with higher body mass index, whereas those with lower SVI were more likely to be nulliparous. Multivariable modeling demonstrated a complex nonlinear association between SVI and GDM pharmacotherapy initiation, relative to the reference. Higher SVI was associated with elevated odds of GDM pharmacotherapy initiation (e.g., odds ratio 1.11 [95% confidence interval 1.02-1.22] for SVI 80) and low to medium SVI had variable nonsignificant associations with GDM pharmacotherapy initiation, relative to the reference (lower odds of initiation for values 25-50, higher odds of initiation for values < 25). Secondary analysis demonstrated a nonlinear association between subtheme 3 and the odds of GDM pharmacotherapy initiation. CONCLUSION: Social vulnerability is associated with initiation of pharmacotherapy for GDM, highlighting the possible role of social determinants of health in achieving glycemic control.

Maternal Opioid Use Disorder and the Risk of Postneonatal Infant Mortality.

Importance: The risk of serious long-term outcomes for infants born to individuals with opioid use disorder (OUD) is not fully characterized, nor is it well understood whether risks are modified by infant diagnosis of neonatal opioid withdrawal syndrome (NOWS). Objective: To characterize the risk of postneonatal infant mortality among infants with a NOWS diagnosis or born to individuals with OUD. Design, Setting, and Participants: The study team conducted a retrospective cohort study of 390 075 infants born from 2007 through 2018 to mothers who were enrolled in Tennessee Medicaid from 183 days prior to delivery through 28 days post partum (baseline). Maternal and infant baseline characteristics were measured using administrative claims and birth certificates, and infants were followed up from day 29 post partum through day 365 or death. Deaths were identified using linked death certificates through 2019. These data were analyzed from February 10, 2022, through March 3, 2023. Exposure: Infant exposures included birth to an individual with OUD or postnatal diagnosis of NOWS. The study team defined a pregnant individual's OUD status (maternal OUD) as having OUD diagnosis or a maintenance medication prescription fill during baseline; this study defined NOWS as having NOWS diagnosis up to day 28. Groups were categorized by exposures as maternal OUD with NOWS (OUD positive/NOWS positive), maternal OUD without NOWS (OUD positive/NOWS negative), no documented maternal OUD with NOWS (OUD negative/NOWS positive), and no documented maternal OUD or NOWS (OUD negative/NOWS negative, unexposed). Main Outcome and Measures: The outcome was postneonatal infant death, confirmed by death certificates. Cox proportional hazards models were used, adjusting for baseline maternal and infant characteristics, to estimate adjusted hazard ratios (aHRs) and 95% CIs for the association between maternal OUD or NOWS diagnosis with postneonatal death. Results: Pregnant individuals in the cohort had a mean (SD) age of 24.5 (5.2) years; 51% of infants were male. The study team observed 1317 postneonatal infant deaths and incidence rates of 3.47 (OUD negative/NOWS negative, 375 718), 8.41 (OUD positive/NOWS positive, 4922); 8.95 (OUD positive/NOWS negative, 7196), and 9.25 (OUD negative/NOWS positive, 2239) per 1000 person-years. After adjustment, the risk of postneonatal death was elevated for all groups, relative to the unexposed: OUD positive/NOWS positive (aHR, 1.54; 95% CI, 1.07-2.21), OUD positive/NOWS negative (aHR, 1.62; 95% CI, 1.21-2.17), and OUD negative/NOWS positive (aHR, 1.64; 95% CI, 1.02-2.65). Conclusions and Relevance: Infants born to individuals with OUD or with a NOWS diagnosis had an increased risk of postneonatal infant mortality. Future work is necessary to create and evaluate supportive interventions for individuals with OUD during and after pregnancy to reduce adverse outcomes.

Robotic Enhanced-View Totally Extraperitoneal vs Intraperitoneal Onlay Mesh Evaluation: 1-Year Exploratory Outcomes of the REVEAL Randomized Clinical Trial.

BACKGROUND: Patients with small- to medium-sized ventral hernias randomized to robotic enhanced-view totally extraperitoneal (eTEP) or robotic intraperitoneal onlay mesh (rIPOM) previously demonstrated comparable 30-day patient-reported outcomes. Here we report 1-year exploratory outcomes for this multi-center, patient-blinded randomized clinical trial. STUDY DESIGN: Patients with midline ventral hernias 7 cm wide or less undergoing mesh repair were randomized to robotic eTEP or rIPOM. Planned exploratory outcomes at 1 year include pain intensity (using the Patient-Reported Outcomes Measurement Information System [PROMIS 3a]), Hernia-Related Quality of Life Survey (HerQLes) scores, pragmatic hernia recurrence, and reoperation. RESULTS: One hundred randomized patients (51 eTEP, 49 rIPOM) reached a median 12-month follow-up (interquartile range 11 to 13) with 7% lost. After regression analysis adjusting for baseline scores, there was no difference in postoperative pain intensity at 1-year for eTEP compared with rIPOM (odds ratio [OR] 2.1 [95% CI 0.85 to 5.1]; p = 0.11). HerQLes scores were 15 points lower on average (ie less improved) at 1 year after eTEP repairs compared with rIPOM, a difference maintained after regression analysis (OR 0.31 [95% CI 0.15 to 0.67]; p = 0.003). Pragmatic hernia recurrence was 12.2% (6 of 49) for eTEP and 15.9% (7 of 44) for rIPOM (p = 0.834). In the first year, 2 eTEP and 1 rIPOM patients required reoperations related to their index repair (p = 0.82). CONCLUSIONS: Exploratory analyses showed similar outcomes at 1 year in regard to pain, hernia recurrence, and reoperation. Abdominal wall quality of life at 1 year appears to favor rIPOM, and the possibility that an eTEP dissection is less advantageous in that regard should be the subject of future investigation.

The morbidity and mortality of patients with fungal infections before and during extracorporeal membrane oxygenation support.

OBJECTIVE: To evaluate the prevalence of fungal infections (both pre-cannulation and post-cannulation) while on extracorporeal membrane oxygenation support and the associated morbidity and mortality. DESIGN: Retrospective cohort study. PATIENT AND METHODS: The Extracorporeal Life Support Organization database is an international voluntary registry of clinical data for patients placed on extracorporeal membrane oxygenation. The database was queried for all patients on extracorporeal membrane oxygenation from 1997 to 2009. Patient and extracorporeal membrane oxygenation data collected included age, support type, length of support, infection status and organism code, discharge status, complications, and component failures. Outcomes of interest were mortality, extracorporeal membrane oxygenation-related patient complications, and mechanical component failures. RESULTS: From 1997 to 2009, there were 21,073 patients' extracorporeal membrane oxygenation runs analyzed of which 12,933 were in the neonatal group (0-30 days), 6,073 were in the pediatric group (31 days to <18 yrs old), and 2,067 were in the adult group (≥18 yrs). The prevalence of fungal infection during extracorporeal membrane oxygenation varied by age group and timing of infection and ranged from 0.04% to 5%. Fungal infections pre-extracorporeal membrane oxygenation and on-extracorporeal membrane oxygenation conferred a statistically significant higher relative risk of mortality for all age groups and varied by support type and timing of infection. Extracorporeal membrane oxygenation-related complications and component failures were not statistically significantly affected by infection status. CONCLUSIONS: Fungal infection before or during extracorporeal membrane oxygenation increases the odds of mortality and the magnitude of this effect is dependent upon age-group and timing of infection. This increased mortality was not the result of increased patient or mechanical complications during extracorporeal membrane oxygenation. For patients with fungal infections pre-extracorporeal membrane oxygenation, 82%-89% demonstrated presumed clearance during extracorporeal membrane oxygenation. Although the risk of mortality increased with fungal infections, it does not appear that fungal infection before or during extracorporeal membrane oxygenation is a contraindication to initiation or continuation of support.

Association of high ventilator pressures with the development of chronic pulmonary hypertension in congenital diaphragmatic hernia patients requiring ECMO.

PURPOSE: Congenital diaphragmatic hernia (CDH) patients requiring extracorporeal membrane oxygenation (ECMO) were examined to determine, if aspects of their complex ventilatory management were associated with the development of chronic pulmonary hypertension (cPH). METHODS: CDH patients requiring ECMO from 1992 to 2007 were retrospectively reviewed. cPH was defined as pulmonary hypertension at 3 months of age. Demographic and clinical variables including peak ventilatory pressures (PVP) and mean airway pressures (MAP) were tabulated. RESULTS: 10/31 (32 %) patients developed cPH. Gestational age, birth weight, inborn status, CDH side and liver position were not different between cPH and non-cPH patients. Pre-ECMO, both groups required statistically similar ventilatory support, though there was a trend toward higher oxygenation index and higher PVP for cPH patients. While ECMO duration was similar between groups, cPH patients required significantly higher PVP (30.0 vs. 25.0 cmH(2)O, p = 0.01) and MAP (11.5 vs. 9.0 cmH(2)O, p = 0.02) for ECMO decannulation. Post-ECMO, maximum PVP (50.0 vs. 26.0 cmH(2)O, p < 0.001), MAP (18.1 vs. 12.0, p = 0.001), HFV requirement (90 vs. 10 %, p < 0.001), and ventilator time (35.7 vs. 20 days, p < 0.001) increased significantly for cPH patients. CONCLUSION: Not until after ECMO decannulation do we see clinical differences separating patients who ultimately develop cPH. Although the degree of pulmonary hypoplasia may ultimately dictate ECMO decannulation criteria, perhaps greater physiologic optimization before decannulation could decrease the incidence of cPH.

Predicting the probability of 90-day survival of elderly patients with bladder cancer treated with radical cystectomy.

PURPOSE: Despite the increased morbidity and mortality of radical cystectomy in elderly individuals with bladder cancer numerous studies show that surgery can provide a survival benefit. We sought to better identify patients at substantial risk for postoperative mortality. MATERIALS AND METHODS: We evaluated 220 consecutive patients 75 years old or older treated with radical cystectomy for bladder cancer at a single institution from 2000 to 2008. The analytical cohort comprised 169 patients with complete preoperative data available. A Cox proportional hazards model was used to determine the value of precystectomy clinical information to predict 90-day survival after radical cystectomy. Results were used to create a nomogram predicting the probability of 90-day survival after radical cystectomy. The model was then subjected to 200 bootstrap resamples for internal validation. RESULTS: Of the 220 patients 28 (12.7%) died within 90 days of surgery. Older age (HR 2.30, 95% CI 1.22-4.32) and lower preoperative albumin (HR 2.50, 95% CI 1.40-4.45) were significant predictors of 90-day mortality. We developed a nomogram based on patient age, clinical stage, Charlson comorbidity index and albumin to predict the likelihood of 90-day mortality with 75% accuracy. Internal validation showed a bootstrap adjusted concordance index of 71%. CONCLUSIONS: We developed a nomogram that provides individualized risk estimations to predict the probability of 90-day mortality, potentially enhancing preoperative counseling and providing clinicians with an added tool to individualize treatment decisions in this challenging patient population. These data suggest that albumin is a strong predictor of postoperative mortality and show the importance of assessing this variable before surgery.

Risk Factors for Surgical Site Occurrence or Infection and Recurrence After Incisional Hernia Repair in Abdominal Transplant Population.

PURPOSE: To investigate risk factors for hernia recurrence, surgical site occurrence/infection (SSO/I) and those requiring procedural intervention (SSOPI) after incisional hernia repair (IHR) following abdominal transplantation. METHODS: Patients undergoing IHR following abdominal transplant were retrospectively identified in the Americas Hernia Society Quality Collaborative database. Primary outcome measures were SSO/I, SSOPI and hernia recurrence. RESULTS: There was a total of 166 patients. Seventeen patients (10%) had an SSO/I at 30 days. Overall complication rate was 26%, and there was 1 mortality (1%). Composite recurrence rate was 28% (21/75) over 2 years. In univariate analysis, history of diabetes (DM), body mass index (BMI) >35 kg/m2, and history of open abdomen were associated with SSO/I (P < .05). Immunosuppression had a negative correlation with SSO/Is and SSOPIs. BMI >35 kg/m2 was associated with 180-day recurrence, whereas history of hypertension remained significant for recurrence at 2 years (P < .05). CONCLUSION: History of an open abdomen, DM, and obesity are risk factors for SSO/I, and obesity and hypertension are associated with short-term and long-term recurrence after IHR following abdominal organ transplantation. Immunosuppression had negative correlation with SSO/I. However, long-term outcomes and those related to immunosuppression should be interpreted cautiously in view of the small sample size and low follow-up rates. Baseline comorbidities seem to be the main drive for hernia outcomes for transplant population, similar to the general population. Larger cohorts and longer follow-up are necessary to delineate preventable risk factors for SSO/Is and hernia recurrences after organ transplantation.