Anterior Wall Success at 1 Year After Vaginal Uterosacral Ligament Suspension and Sacral Colpopexy.

OBJECTIVES: The primary objective was to evaluate 1-year anterior wall anatomic success rates for vaginal uterosacral ligament suspension (USLS) and minimally invasive sacral colpopexy (SCP) using delayed-absorbable suture. Secondary objectives included assessment of apical success, mesh or suture exposure, and postoperative quality of life (QoL) measures 12 months after surgery. METHODS: This was a retrospective cohort study including women who underwent a hysterectomy with concomitant USLS or SCP with delayed-absorbable suture from January 2011 to December 2015 with 1-year follow-up. Successful anterior vaginal wall support was defined as Ba of less than 0. Successful apical support was defined as no apical descent (point C) greater than one half of the total vaginal length. In addition, 1-year QoL questionnaires were measured postoperatively. RESULTS: A total of 282 women were identified. Sixty-two women (31 vaginal USLS and 31 SCP) met inclusion criteria. Demographics were similar between groups except for a higher body mass index in the USLS group (27.5 ± 5.6 kg/m vs 24.1 ± 3.3 kg/m, P < 0.05). Preoperative POP-Q was mostly stage II and III. At 1-year, anatomic success rates for the anterior compartment were 66.7% versus 90.3% for USLS and SCP groups, respectively (P = 0.02). There was no significant difference in apical success (P = 1.00) or QoL scores between groups at 1 year. CONCLUSIONS: Anatomic success rates at 1 year using delayed-absorbable suture were better for SCP when using the anterior wall as a measure of success, but there were no significant differences in apical success rates, mesh or suture exposure, and QoL measures between groups.

Impact of shift duration on alertness among air-medical emergency care clinician shift workers.

BACKGROUND: Greater than half of Emergency Medical Services (EMS) shift workers report fatigue at work and most work long duration shifts. We sought to compare the alertness level of EMS shift workers by shift duration. METHODS: We used a multi-site, 14-day prospective observational cohort study design of EMS clinician shift workers at four air-medical EMS organizations. The primary outcome was behavioral alertness as measured by psychomotor vigilance tests (PVT) at the start and end of shifts. We stratified shifts by duration (< 24 h and 24 h), night versus day, and examined the impact of intra-shift napping on PVT performance. RESULTS: One hundred and twelve individuals participated. The distribution of shifts <24 h and 24 h with complete data were 54% and 46%, respectively. We detected no differences in PVT performance measures stratified by shift duration (P > 0.05). Performance for selected PVT measures (lapses and false starts) was worse on night shifts compared to day shifts (P < 0.05). Performance also worsened with decreasing time between waking from a nap and the end of shift PVT assessment. CONCLUSIONS: Deficits in performance in the air-medical setting may be greatest during night shifts and proximal to waking from an intra-shift nap. Future research should examine alertness and performance throughout air-medical shifts, as well as investigate the timing and duration of intra-shift naps on outcomes.

Risk of donor demise after laser therapy for twin-twin transfusion when complicated by growth discordance and abnormal umbilical artery Doppler findings.

OBJECTIVE: To investigate the natural course of abnormal umbilical artery Doppler (UAD) findings in donor fetuses after laser surgery and the prognostic significance of resolution, persistence, or new onset UAD abnormalities with and without the presence of preoperative growth discordance. STUDY DESIGN: Retrospective cohort study of all monochorionic-diamniotic multi-fetal gestations diagnosed with twin-twin transfusion syndrome (TTTS) undergoing laser surgery at a single large metropolitan referral center from 2010-2016. The estimated fetal weight was measured preoperatively and the UAD were measured both pre- and postoperatively (median = 8 days). Patients were grouped according to the presence of abnormal UAD with or without growth discordance pre- and postoperatively. Risk ratios (RR) were calculated for each group for risk of intrauterine fetal demise compared to the pre- and postoperative normal UAD groups as the referents. RESULTS: There were eighty-one women who met inclusion criteria throughout the study period. Forty-three (53.1%) patients had abnormal donor twin UAD preoperatively and 33 (40.7%) were diagnosed with growth discordance. However, 13 (44.8%) had normalization of the UAD postoperatively (median = 8 days) with a similar rate of donor fetal demise as the non-discordant preoperative normal UAD group (7.7% versus 10.3%, p = .79). Abnormal preoperative UAD was associated with an increased risk of donor demise (RR 3.6, CI 1.1-12.1), which was further elevated in the presence of growth discordance (RR 5.2, CI 1.7-16.3). The greatest risk for donor demise was seen if the UAD remained abnormal postoperatively with concomitant growth discordance (RR 10.3, CI 2.5-41.6). CONCLUSIONS: Preoperative abnormal donor UAD is a significant risk for donor demise post-laser therapy for TTTS. Persistent postoperative abnormal UAD with concomitant growth discordance confers the greatest risk for donor demise. However, resolution of abnormal UAD has a similar rate of donor demise when compared to patients with normal UAD preoperatively.

Initial fluid resuscitation following adjusted body weight dosing is associated with improved mortality in obese patients with suspected septic shock.

OBJECTIVE: The optimal initial fluid resuscitation strategy for obese patients with septic shock is unknown. We evaluated fluid resuscitation strategies across BMI groups. MATERIALS AND METHODS: Retrospective analysis of 4157 patients in a multicenter activation pathway for treatment of septic shock between 2014 and 2016. RESULTS: 1293 (31.3%) patients were obese (BMI≥30). Overall, higher BMI was associated with lower mortality, however this survival advantage was eliminated in adjusted analyses. Patients with higher BMI received significantly less fluid per kilogram at 3h than did patients with lower BMI (p≤0.001). In obese patients, fluid given at 3h mimicked a dosing strategy based on actual body weight (ABW) in 780 (72.2%), adjusted body weight (AdjBW) in 95 (8.8%), and ideal body weight (IBW) in 205 (19.0%). After adjusting for condition- and treatment-related variables, dosing based on AdjBW was associated with improved mortality compared to ABW (OR 0.45; 95% CI [0.19, 1.07]) and IBW (OR 0.29; 95% CI [0.11,0.74]). CONCLUSIONS: Using AdjBW to calculate initial fluid resuscitation volume for obese patients with suspected shock may improve outcomes compared to other weight-based dosing strategies. The optimal fluid dosing strategy for obese patients should be a focus of future prospective research.

Hospital Differences Drive Antibiotic Delays for Black Patients Compared With White Patients With Suspected Septic Shock.

OBJECTIVE: Evaluate racial disparities in sepsis processes of care. DESIGN: Observational cohort study. SETTING: Nine hospitals in the Southeastern United States between 2014 and 2016. PATIENTS: Two thousand two hundred twenty-one white and 707 black patients treated in the emergency department through "code sepsis" pathway for suspected septic shock. MEASUREMENTS AND MAIN RESULTS: Black patients were less likely to receive timely antibiotics than were white patients using multiple definitions (1 hr from code sepsis activation [odds ratio, 0.57; 95% CI, [0.44-0.74]; 85.6% vs. 91.2%; p < 0.0001]; 1 hr from triage [odds ratio, 0.83; 95% CI, [0.69-1.00]; 28.0% vs. 31.8%; p = 0.06]; 3 hr from triage [odds ratio, 0.71; 95% CI, [0.57-0.88]; 80.1% vs. 85.0%; p = 0.002]). Focusing on antibiotic administration within 1 hour of triage, these differences were enhanced after adjusting for patient-level factors (adjusted odds ratio, 0.80; 95% CI, [0.66-0.96]; p = 0.02), but attenuated after adjusting for hospital-level differences (adjusted odds ratio, 0.90; 95% CI, [0.81-1.01]; p = 0.07). Black and white patients did not differ on other sepsis quality indicators or adjusted mortality. CONCLUSIONS: Black patients appear to be less likely than white patients to receive timely antibiotic therapy for sepsis. These differences were largely explained by variation in care among hospitals, such that hospitals that disproportionately treat black patients were less likely to provide timely antibiotic therapy overall. There were no differences between races in other sepsis quality measures or adjusted mortality.

Randomized Controlled Feasibility Trial of Intranasal Ketamine Compared to Intranasal Fentanyl for Analgesia in Children with Suspected Extremity Fractures.

OBJECTIVES: We compared the tolerability and efficacy of intranasal subdissociative ketamine to intranasal fentanyl for analgesia of children with acute traumatic pain and investigated the feasibility of a larger noninferiority trial that could investigate the potential opioid-sparing effects of intranasal ketamine. METHODS: This randomized controlled trial compared 1 mg/kg intranasal ketamine to 1.5 µg/kg intranasal fentanyl in children 4 to 17 years old with acute pain from suspected isolated extremity fractures presenting to an urban Level II pediatric trauma center from December 2015 to November 2016. Patients, parents, treating physicians, and outcome assessors were blinded to group allocation. The primary outcome, a tolerability measure, was the frequency of cumulative side effects and adverse events within 60 minutes of drug administration. The secondary outcomes included the difference in mean pain score reduction at 20 minutes, the proportion of patients achieving a clinically significant reduction in pain in 20 minutes, total dose of opioid pain medication in morphine equivalents/kg/hour (excluding study drug) required during the emergency department (ED) stay, and the feasibility of enrolling children presenting to the ED in acute pain into a randomized trial conducted under U.S. regulations. All patients were monitored until 6 hours after their last dose of study drug or until admission to the hospital ward or operating room. RESULTS: Of 629 patients screened, 87 received the study drug and 82 had complete data for the primary outcome (41 patients in each group). The median (interquartile range) age was 8 (6-11) years and 62% were male. Baseline pain scores were similar among patients randomized to receive ketamine (73 ± 26) and fentanyl (69 ± 26; mean difference [95% CI] = 4 [-7 to 15]). The cumulative number of side effects was 2.2 times higher in the ketamine group, but there were no serious adverse events and no patients in either group required intervention. The most common side effects of ketamine were bad taste in the mouth (37; 90.2%), dizziness (30; 73.2%), and sleepiness (19; 46.3%). The most common side effects of fentanyl were sleepiness (15; 36.6%), bad taste in the mouth (9; 22%), and itchy nose (9; 22%). No patients experienced respiratory side effects. At 20 minutes, the mean pain scale score reduction was 44 ± 36 for ketamine and 35 ± 29 for fentanyl (mean difference = 9 [95% CI = -4 to 23]). Procedural sedation with ketamine occurred in 28 ketamine patients (65%) and 25 fentanyl patients (57%) prior to completing the study. CONCLUSIONS: Intranasal ketamine was associated with more minor side effects than intranasal fentanyl. Pain relief at 20 minutes was similar between groups. Our data support the feasibility of a larger, noninferiority trial to more rigorously evaluate the safety, efficacy, and potential opioid-sparing benefits of intranasal ketamine analgesia for children with acute pain.

Antifungal use in immunocompetent, critically ill patients with pneumonia does not improve clinical outcomes.

PURPOSE: To determine if treating bronchoalveolar lavage (BAL) culture-positive patients with antifungal therapy impacted mortality compared to not treating due to presumed colonization. METHODS: We conducted a retrospective study of immunocompetent, critically ill adult patients from 2010 to 2014. Patients with a BAL culture-positive for Candida or unspeciated yeast and a clinical suspicion of pneumonia were included. The treatment group received an antifungal agent for at least 5 days, and the control group received either no antifungal therapy or an antifungal agent for less than 48 h. Recruitment occurred in a 2:1 ratio of untreated versus treated patients. RESULTS: Seventy-five patients were included. In-hospital mortality was similar between treated and untreated groups (24% vs. 26%, P = 0.85). Length of stay and duration of mechanical ventilation also did not differ between the two groups. CONCLUSION: We did not observe a difference in mortality or clinical outcomes in patients treated with antifungal agents. Presumptive antifungal therapy for BAL-positive Candida or yeast in immunocompetent patients did not result in improved clinical outcomes.

Evaluation of a New Vancomycin Dosing Protocol in Morbidly Obese Patients.

BACKGROUND: Optimal dosing of vancomycin in morbidly obese patients (>100 kg and at least 140% of their ideal body weight) has not been determined. Conventional dosing strategies have led to the observation of supratherapeutic trough concentrations (>20 mcg/mL). OBJECTIVE: To evaluate the effectiveness of a new vancomycin dosing protocol in morbidly obese patients in achieving therapeutic trough concentrations between 10 and 20 mcg/mL and to determine patient-specific factors influencing the trough concentration attained. METHODOLOGY: A single-center, retrospective chart review included morbidly obese adult patients with a pharmacy-to-dose vancomycin consult and at least 1 trough concentration obtained at steady state. Patients were excluded if they had a creatinine clearance (CrCl) less than 35 mL/min or unstable renal function, were not dosed according to the revised protocol, or received vancomycin prior to initiation of the protocol. RESULTS: Of the 48 patients included, 17 (35.4%) achieved a therapeutic vancomycin trough concentration. Subtherapeutic concentrations (<10 mcg/mL) were observed in 27 patients (56.3%) and supratherapeutic concentrations were observed in 4 (8.3%) patients. Age less than 45 years and CrCl greater than 100 mL/min were associated with subtherapeutic trough concentrations. CONCLUSION: This study demonstrates that the revised vancomycin dosing protocol led to the attainment of therapeutic trough concentrations in 35.4% of patients. The majority had subtherapeutic concentrations, which increases the risk of treatment failures and resistance. Further study is needed to determine the optimal dosing strategy in this patient population.

Cortistatin is endogenous to the human intervertebral disc and exerts in vitro mitogenic effects on annulus cells and a downregulatory effect on TNF-α expression.

BACKGROUND CONTEXT: Cortistatin (CST) is a recently discovered cyclic neuropeptide with biologic anti-inflammatory properties relevant to disc degeneration. PURPOSE: To test whether CST is present in the disc tissue, whether its expression is influenced by tumor necrosis factor-α (TNF-α), and whether it influences cell proliferation. STUDY DESIGN: Institutional review board-approved study using immunohistochemistry on human disc tissue, in vitro annulus cultures to determine the effect of CST on cell proliferation, and the effect of TNF-α on CST gene expression. PATIENT SAMPLE: Discs from 12 subjects used for immunohistochemistry, four annulus specimens used for cell culture with proinflammatory cytokines, and 11 used for cell proliferation analyses. OUTCOME MEASURES: Immunohistochemical localization of CST, gene expression of CST, and cell proliferation analyses. METHODS: Immunohistochemistry localized CST in disc tissue. Microarray analysis measured CST gene expression. Human annulus cells were exposed to CST for proliferation tests or cultured for the effect of TNF-α on CST expression. Standard statistical analyses were performed. RESULTS: Immunohistochemistry identified CST in outer annulus, inner annulus, and nucleus tissue. Annulus cells exposed to TNF-α revealed significantly lower CST expression (p=.013). Exposure to CST significantly increased proliferation. Quantitative real-time polymerase chain reaction also confirmed expression of CST in vitro. CONCLUSIONS: Data provide the first evidence that CST is present in the human disc. Addition of CST significantly increased cell proliferation. Cortistatin expression was significantly downregulated by TNF-α exposure in vitro. Findings suggest possible in vivo reduction of the anti-inflammatory actions of CST because of elevated proinflammatory cytokines during degenerating disc.

Obstetric and gynecologic challenges in women with Ehlers-Danlos syndrome.

OBJECTIVE: To determine how often women with Ehlers-Danlos syndrome experience obstetric and gynecologic issues both compared with the general population and within the three most common subtypes of Ehlers-Danlos syndrome. METHODS: An anonymous, prospective, online questionnaire in English was posted to the Ehlers-Danlos National Foundation web site (http://ednf.org). RESULTS: Of the 1,769 of those who completed the survey, 1,225 reported a typed diagnosis of Ehlers-Danlos syndrome. Further stratification to the three most common types and reproductive-aged women (n=775) allowed conclusions to be made about differences in rates of obstetric complications and gynecologic dysfunction compared with the general population and between types of Ehlers-Danlos syndrome. Rates of obstetric outcomes for women who reported at least one pregnancy included term pregnancy in 69.7%, preterm birth in 25.2%, spontaneous abortion in 57.2%, and ectopic pregnancy in 5.1%. Infertility was reported by 44.1% of survey respondents. Normal menstrual cycles were reported by only 32.8% with intermenstrual bleeding occurring in 18.6%. Heavy menstrual bleeding was reported by 32.9% survey participants. Gynecologic pain reported included dysmenorrhea by 92.5% and dyspareunia by 77.0%. CONCLUSION: There is a much greater prevalence of obstetric and gynecologic issues reported by women with Ehlers-Danlos syndrome than in the general population. Additionally, rates differed significantly among the three most common types of Ehlers-Danlos syndrome with vascular type having the highest rates of adverse pregnancy outcomes and menstrual abnormalities. Physician providers should be aware of these challenges and should counsel patients with Ehlers-Danlos syndrome about relevant options and risks.