Association of Physician Management Companies and Private Equity Investment With Commercial Health Care Prices Paid to Anesthesia Practitioners.

IMPORTANCE: Physician management companies (PMCs), often backed by private equity (PE), are increasingly providing staffing and management services to health care facilities, yet little is known of their influence on prices. OBJECTIVE: To study changes in prices paid to practitioners (anesthesiologists and certified registered nurse anesthetists) before and after an outpatient facility contracted with a PMC. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used difference-in-differences methods to compare price changes before and after a facility contracted with a PMC with facilities that did not and to compare differences between PMCs with and without PE investment. Commercial claims data (2012-2017) from 3 large national insurers in the Health Care Cost Institute database were combined with a novel data set of PMC facility contracts to identify prices paid to anesthesia practitioners in hospital outpatient departments and ambulatory surgery centers. The cohort included 2992 facilities that never contracted with a PMC and 672 facilities that contracted with a PMC between 2012 and 2017, collectively representing 2 255 933 anesthesia claims. EXPOSURES: Temporal variation in facility-level exposure to PMC contracts for anesthesia services. MAIN OUTCOMES AND MEASURES: Main outcomes were (1) allowed amounts and the unit price (allowed amounts standardized per unit of service) paid to anesthesia practitioners; and (2) the probability that a practitioner was out of network. RESULTS: From before to after the PMC contract period, allowed amounts increased by 16.5% (+$116.39; 95% CI, $76.11 to $156.67; P < .001), and the unit price increased by 18.7% (+$18.79; 95% CI, $12.73 to $24.84; P < .001) in PMC facilities relative to non-PMC facilities. Results did not show evidence that anesthesia practitioners were moved out of network (+2.25; 95% CI, -2.56 to 7.06; P < .36). In subsample analyses, PMCs without PE investment increased allowed amounts by 12.9% (+$89.88; 95% CI, $42.07 to $137.69; P < .001), while PE-backed PMCs (representing half of the PMCs in the sample) increased allowed amounts by 26.0% ($187.06; 95% CI, $133.59 to $240.52; P < .001). Similar price increases were observed for unit prices. CONCLUSIONS AND RELEVANCE: In this cohort study, prices paid to anesthesia practitioners increased after hospital outpatient departments and ambulatory surgery centers contracted with a PMC and were substantially higher if the PMC received PE investment. This research provides insights into the role of corporate ownership in health care relevant to policy makers, payers, practitioners, and patients.

Quality Assurance and Quality Improvement in the Labor and Delivery Setting.

Quality assurance (QA) is the maintenance of a desired level of quality, whereas quality improvement (QI) is the continuous process of creating systems to make things better. Implementation science promotes the systematic uptake of best practices. Bundles are a structured list of best practices whereas toolkits provide the necessary details, rationale, and implementation materials, such as sample policies and protocols. Metrics that can guide care on the labor and delivery (L&D) floor may be related to team structure (obstetric, multidisciplinary, anesthetic), processes (patient monitoring, team effects), and outcomes (postpartum hemorrhage, venous thromboembolism). Multiple anesthetic quality metrics have been proposed, including the mode of anesthesia for cesarean delivery.

Association of Surprise-Billing Legislation with Prices Paid to In-Network and Out-of-Network Anesthesiologists in California, Florida, and New York: An Economic Analysis.

Importance: Several states have passed surprise-billing legislation to protect patients from unanticipated out-of-network medical bills, yet little is known about how state laws influence out-of-network prices and whether spillovers exist to in-network prices. Objective: To identify any changes in prices paid to out-of-network anesthesiologists at in-network facilities and to in-network anesthesiologists before and after states passed surprise-billing legislation. Design, Setting, and Participants: This retrospective economic analysis used difference-in-differences methods to compare price changes before and after the passage of legislation in California, Florida, and New York, which passed comprehensive surprise-billing legislation between January 1, 2014, and December 31, 2017, to 45 states that did not. Commercial claims data from the Health Care Cost Institute were used to identify prices paid to anesthesiologists in hospital outpatient departments and ambulatory surgery centers. The final analytic sample comprised 2 713 913 anesthesia claims across the 3 treated states and the 45 control states. Exposures: Temporal and state-level variation in exposure to surprise-billing legislation. Main Outcomes and Measures: The unit price (allowed amounts standardized per unit of service) paid to out-of-network anesthesiologists at in-network facilities and to in-network anesthesiologists. Results: This retrospective economic analysis of 2 713 913 anesthesia claims found that after surprise-billing laws were passed in 3 states, the unit price paid to out-of-network anesthesiologists at in-network facilities decreased significantly in 2 of them: California, -$12.71 (95% CI, -$25.70 to -$0.27; P = .05) and Florida, -$35.67 (95% CI, -$46.27 to -$25.07; P < .001). In New York, a decline in the overall out-of-network price was not statistically significant (-$7.91; 95% CI, -$17.48 to -$1.68; P = .10); however, by the fourth quarter of 2017, the decline was -$41.28 (95% CI, -$70.24 to -$12.33; P = .01). In-network prices decreased in California by -$10.68 (95% CI, -$12.70 to -$8.66; P < .001); in Florida, -$3.18 (95% CI, -$5.17 to -$1.19; P = .002); and in New York, -$8.05 (95% CI, -$11.46 to -$4.64; P < .001). Conclusions and Relevance: This retrospective study found that prices paid to in-network and out-of-network anesthesiologists in hospital outpatient departments and ambulatory surgery centers decreased after the introduction of surprise-billing legislation, providing early insights into how prices may change under the federal No Surprises Act and in states that have recently passed their own legislation.

Patient-Reported Pain and Opioid Use After Ambulatory Head and Neck Surgery.

OBJECTIVE: The main objective of this study was to quantify daily pain and opioid use in patients after hemithyroidectomy and cervical lymph node biopsy (CLNB). The secondary objective was to identify factors associated with decreased pain and opioid use. STUDY DESIGN: Prospective cohort study from June 2017 to February 2019. Patients were given paper surveys to record daily postoperative opioid use and maximal pain on a visual analog scale. SETTING: Single institution (NewYork-Presbyterian/Weill Cornell Medical Center). METHODS: All adult patients undergoing hemithyroidectomy and CLNB by a single surgeon were consecutively selected for participation. Patients recorded daily pain and opioid analgesic use over a 2-week postoperative period. RESULTS: Of 33 patients enrolled, 29 (87.9%) returned a survey. Thirteen underwent CLNB, and 16 underwent hemithyroidectomy. Pain resolved after both procedures by the end of the 2-week period. CLNB patients used a median (interquartile range) of 15.0 (0-41.2) morphine milligram equivalents (MME), and 95% used 70 or fewer MME. Hemithyroidectomy patients used a median of 8.2 (4.5-13.9) MME, and 95% used 30 or fewer MME. Use of nonopioid analgesics was associated with a statistically significant decrease in pain (56.1 vs 171 visual analog scale, 95% confidence interval [CI] of Δ = [12.0 to 217.8]) and opioid use (12.2 vs 48.8 MME, 95% CI of Δ = [5.0 to 68.1 MME]) in CLNB but not in hemithyroidectomy. CONCLUSION: Patients have low pain and opioid requirements after hemithyroidectomy and CLNB. Head and neck surgeons should evaluate their opioid-prescribing patterns for opportunities to safely decrease postoperative prescriptions.

The Society for Obstetric Anesthesia and Perinatology Coronavirus Disease 2019 Registry: An Analysis of Outcomes Among Pregnant Women Delivering During the Initial Severe Acute Respiratory Syndrome Coronavirus-2 Outbreak in the United States.

BACKGROUND: Early reports associating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection with adverse pregnancy outcomes were biased by including only women with severe disease without controls. The Society for Obstetric Anesthesia and Perinatology (SOAP) coronavirus disease 2019 (COVID-19) registry was created to compare peripartum outcomes and anesthetic utilization in women with and without SARS-CoV-2 infection delivering at institutions with widespread testing. METHODS: Deliveries from 14 US medical centers, from March 19 to May 31, 2020, were included. Peripartum infection was defined as a positive SARS-CoV-2 polymerase chain reaction test within 14 days of delivery. Consecutive SARS-CoV-2-infected patients with randomly selected control patients were sampled (1:2 ratio) with controls delivering during the same day without a positive test. Outcomes were obstetric (eg, delivery mode, hypertensive disorders of pregnancy, and delivery <37 weeks), an adverse neonatal outcome composite measure (primary), and anesthetic utilization (eg, neuraxial labor analgesia and anesthesia). Outcomes were analyzed using generalized estimating equations to account for clustering within centers. Sensitivity analyses compared symptomatic and asymptomatic patients to controls. RESULTS: One thousand four hundred fifty four peripartum women were included: 490 with SARS-CoV-2 infection (176 [35.9%] symptomatic) and 964 were controls. SARS-CoV-2 patients were slightly younger, more likely nonnulliparous, nonwhite, and Hispanic than controls. They were more likely to have diabetes, obesity, or cardiac disease and less likely to have autoimmune disease. After adjustment for confounders, individuals experiencing SARS-CoV-2 infection exhibited an increased risk for delivery <37 weeks of gestation compared to controls, 73 (14.8%) vs 98 (10.2%) (adjusted odds ratio [aOR], 1.47; 95% confidence interval [CI], 1.03-2.09). Effect estimates for other obstetric outcomes and the neonatal composite outcome measure were not meaningfully different between SARS-CoV-2 patients versus controls. In sensitivity analyses, compared to controls, symptomatic SARS-CoV-2 patients exhibited increases in cesarean delivery (aOR, 1.57; 95% CI, 1.09-2.27), postpartum length of stay (aOR, 1.89; 95% CI, 1.18-2.60), and delivery <37 weeks of gestation (aOR, 2.08; 95% CI, 1.29-3.36). These adverse outcomes were not found in asymptomatic women versus controls. SARS-CoV-2 patients (asymptomatic and symptomatic) were less likely to receive neuraxial labor analgesia (aOR, 0.52; 95% CI, 0.35-0.75) and more likely to receive general anesthesia for cesarean delivery (aOR, 3.69; 95% CI, 1.40-9.74) due to maternal respiratory failure. CONCLUSIONS: In this large, multicenter US cohort study of women with and without peripartum SARS-CoV-2 infection, differences in obstetric and neonatal outcomes seem to be mostly driven by symptomatic patients. Lower utilization of neuraxial analgesia in laboring patients with asymptomatic or symptomatic infection compared to patients without infection requires further investigation.

Core temperature monitoring during cesarean delivery under spinal anesthesia: a quality improvement descriptive study.

Aim: To analyze intraoperative temperature change over time following spinal anesthesia for cesarean delivery using temperature enabled Foley catheters. Materials & methods: 512 records of women who underwent scheduled cesarean deliveries were retrospectively identified from January 1, 2018 through September 9, 2018 using our anesthesia information management system. Results: Median minimum temperature at min 1 following foley insertion was 35.24°C (interquartile range: 1.43), with an average of 12 minutes until temperature equilibration at median maximum temperature of 36.54°C (interquartile range 0.39). Temperature dropped to a nadir of 35.9°C at the 45 min mark, reflecting an average 0.64°C decline in temperature. Conclusion: Bladder temperature is a useful surrogate for core temperature and offers a practical solution to continuous temperature monitoring in awake patients.

RRP7A links primary microcephaly to dysfunction of ribosome biogenesis, resorption of primary cilia, and neurogenesis.

Primary microcephaly (MCPH) is characterized by reduced brain size and intellectual disability. The exact pathophysiological mechanism underlying MCPH remains to be elucidated, but dysfunction of neuronal progenitors in the developing neocortex plays a major role. We identified a homozygous missense mutation (p.W155C) in Ribosomal RNA Processing 7 Homolog A, RRP7A, segregating with MCPH in a consanguineous family with 10 affected individuals. RRP7A is highly expressed in neural stem cells in developing human forebrain, and targeted mutation of Rrp7a leads to defects in neurogenesis and proliferation in a mouse stem cell model. RRP7A localizes to centrosomes, cilia and nucleoli, and patient-derived fibroblasts display defects in ribosomal RNA processing, primary cilia resorption, and cell cycle progression. Analysis of zebrafish embryos supported that the patient mutation in RRP7A causes reduced brain size, impaired neurogenesis and cell proliferation, and defective ribosomal RNA processing. These findings provide novel insight into human brain development and MCPH.

Pain and Opioid Analgesic Use After Otorhinolaryngologic Surgery.

OBJECTIVE: To quantify pain and opioid use after otorhinolaryngologic surgery. To determine the effect of patient and surgical factors on primary outcomes. STUDY DESIGN: Prospective cohort. SETTING: Tertiary academic hospital. SUBJECTS AND METHODS: Patients undergoing elective otorhinolaryngologic surgery were prospectively enrolled. Patients completed demographic surveys and psychometric questionnaires assessing attitudes toward pain and baseline anxiety and depression before surgery. After surgery, patients documented peak pain levels (0-100 mm, visual analog scale) and daily prescription and nonprescription analgesic requirements over a 2-week period. Average daily and cumulative pain and opioid use were calculated and compared among patient cohorts stratified by procedure and preoperative factors. RESULTS: A total of 134 patients were enrolled. Total tonsillectomy was associated with significantly higher pain scores and opioid consumption, as compared to all other procedures. There was moderate correlation between average cumulative pain and opioid use. Older patients required significantly fewer doses of opioids. There was no effect of sex, marital status, or education level on postoperative pain or opioid use. Psychometric instrument scores and chronic pain or analgesic use were not associated with significant differences in pain or opioid requirements. Most patients were prescribed substantially more opioids than they actually required. CONCLUSION: Postoperative pain following elective otorhinolaryngologic surgery decreases dramatically within the first week and requires only few days of opioid analgesia, with the exception of tonsillectomy. Almost all patients required fewer than 15 doses of opioids.

The effect of intravenous dexamethasone on postoperative nausea and vomiting after Cesarean delivery with intrathecal morphine: a randomized-controlled trial.

PURPOSE: Intrathecal morphine administered during spinal anesthesia for Cesarean delivery is associated with a high incidence of postoperative nausea and vomiting (PONV). Small studies performed to date provide conflicting evidence on the effectiveness of dexamethasone as prophylaxis in this setting, raising the possibility that efficacy may be linked to dose timing. This study hypothesized that intravenous dexamethasone given prior to intrathecal morphine during spinal anesthesia may reduce the incidence of PONV. METHODS: In this double-blind, placebo-controlled trial, 108 patients undergoing Cesarean delivery were randomized to receive 8 mg dexamethasone or placebo prior to spinal anesthesia that included 0.2 mg intrathecal morphine. Outcomes were assessed on postanesthesia care unit arrival, as well as at postoperative hours one, three, six, 24, and 48. The primary outcome was the total number of subjects experiencing PONV during the study period of 48 hr postpartum. Secondary outcomes included severity of pain via the numeric rating scale pain score, and the use of rescue antiemetics and analgesics. RESULTS: No significant difference in the number of patients experiencing PONV was found between the treatment (n = 44, 80.0%) and control groups (n = 45, 84.9%) (difference -4.9%; 95% confidence interval, -19.2 to 9.4; P = 0.50), nor for median numeric rating scale pain scores (P = 0.24), total consumption of rescue antiemetics (P = 0.40), or opioid analgesics (P = 0.26). CONCLUSIONS: This trial does not support the use of dexamethasone prior to intrathecal morphine for PONV prophylaxis in Cesarean delivery. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01734161); registered 27 November, 2012.

RéSUMé: OBJECTIF: La morphine intrathécale administrée au cours de la rachianesthésie pour un accouchement par césarienne est associée à une forte incidence de nausées et vomissements postopératoires (PONV). Les petites études menées à ce jour ont fourni des données probantes contradictoires sur l'efficacité de la prophylaxie par dexaméthasone dans ce contexte, soulevant la possibilité que son efficacité soit liée au moment de l'administration. Les auteurs de cette étude ont fait l'hypothèse que la dexaméthasone intraveineuse administrée avant la morphine intrathécale au cours d'une rachianesthésie pouvait réduire l'incidence des PONV. MéTHODES: Dans cette étude en double insu, contrôlée contre placebo, 108 patientes subissant un accouchement par césarienne ont été randomisées pour recevoir 8 mg de dexaméthasone ou un placebo avant une rachianesthésie qui incluait 0,2 mg de morphine intrathécale. Les résultats ont été évalués à l'arrivée dans l'unité de soins post anesthésie ainsi qu'à 1, 3, 6, 24 et 48 heures postopératoires. Le critère d'évaluation principal était le nombre de patientes éprouvant des PONV au cours de la période d'étude de 48 heures post-partum. Les critères d'évaluation secondaires étaient, notamment, la sévérité de la douleur établie par le score de douleur sur une échelle d'évaluation numérique, et le recours aux antiémétiques et analgésiques de secours. RéSULTATS: Aucune différence significative n'a été constatée sur le nombre de patientes éprouvant des PONV entre le groupe recevant le traitement (n = 44; 80,0 %) et le groupe contrôle (n = 45; 84,9 %) (différence -4,9 %; intervalle de confiance à 95 % : -19,2 % à 9,4%; P = 0,50). Il n'y a pas eu non plus de différences dans les scores de douleur avec l'échelle d'évaluation numérique (P = 0,24) et la consommation totale de médicaments de secours, antiémétiques (P = 0,40) ou narcotiques (P = 0,26). CONCLUSIONS: Cette étude ne soutient pas l'utilisation de dexaméthasone avant l'administration de morphine intrathécale pour la prophylaxie des PONV dans l'accouchement par césarienne. ENREGISTREMENT DE L'ESSAI CLINIQUE: www.clinicaltrials.gov (NCT01734161); enregistré le 27 novembre 2012.

Prioritizing Patient Safety Efforts in Office Practice Settings.

OBJECTIVES: Outpatient care settings face unique risks of adverse events and medico-legal liability, often worsened by inconsistent processes and fragmented care. Health systems are increasingly providing integrated care that includes outpatient care, but models of how to systematically target medico-legal risk in office practices are largely absent. Innovative and scalable efforts are needed to guide large health systems in their approach to outpatient safety. METHODS: A malpractice consortium consisting of five large health care delivery systems identified that its ambulatory care cases (including office practices, outpatient hospital settings, and emergency departments) account for 30% to 35% of annual medical malpractice costs, and missed or delayed diagnoses account for approximately 50% of office practice liability risk. To further understand risks and opportunities in office-based practices, a team of patient safety and loss prevention professionals conducted site visits to seven outpatient-affiliated sites of the five health systems from January to March 2016 and interviewed several key informant members of physician, nursing, and administrative leadership. RESULTS: We identified eight common patient safety risk domains based on analysis of eight sets of group interviews. Risk domains were then prioritized by members of the consortium leadership using scoring criteria that we developed based on existing risk assessment and prioritization approaches. The method helped identify communication and follow-up of diagnostic test results in the outpatient setting as the single most important risk area to target improvement efforts. CONCLUSIONS: A targeted approach to identify a single high-risk area led to development of dedicated teams to conduct local patient safety improvement projects at the affiliated health systems and for sharing lessons learned. Similar efforts elsewhere could lead to safety improvements in office practices at other large health systems.

Current interventions to promote safe and appropriate pain management.

PURPOSE: Describe patient-, clinician-, system-, and community-level interventions for pain management developed and employed by 9 healthcare systems across the United States and report on lessons learned from the implementation of these interventions. SUMMARY: The high cost associated with pain coupled with the frequent use of opioid analgesics as primary treatment options has made novel pain management strategies a necessity. Interventions that target multiple levels within healthcare are needed to help combat the opioid epidemic and improve strategies to manage chronic pain. Patient-level interventions implemented ranged from traditional paper-based educational tools to videos, digital applications, and peer networks. Clinician-level interventions focused on providing education, ensuring proper follow-up care, and establishing multidisciplinary teams that included prescribers, pharmacists, nurses, and other healthcare professionals. System- and community-level interventions included metric tracking and analytics, electronic health record tools, lockbox distribution for safe storage, medication return bins for removal of opioids, risk assessment tool utilization, and improved access to reversal agents. CONCLUSION: Strategies to better manage pain can be implemented within health systems at multiple levels and on many fronts; however, these changes are most effective when accepted and widely used by the population for which they are targeted.

Impact of anesthesiologist's fellowship status on the risk of general anesthesia for unplanned cesarean delivery.

BACKGROUND: Neuraxial analgesia is preferred over general anesthesia for cesarean delivery (CD), particularly in the presence of a labor epidural catheter. We hypothesize that care by a non-obstetric anesthesiologist as compared to care by an obstetric anesthesiologist is associated with a higher risk for use of general anesthesia for CD for patients with a preexisting labor epidural catheter. METHODS: To determine whether fellowship status of the covering anesthesiologist was a risk factor for general anesthesia, we retrospectively investigated the rate of general anesthesia use in patients with epidural catheters placed for labor analgesia who subsequently required CD. To standardize the practice environment under which these cases occurred, we examined only cases which occurred during coverage by the call team on nights, weekends, and holidays. RESULTS: There were 1820 cases in which a patient had epidural labor analgesia followed by a CD. Nine hundred and twelve cases were covered by an obstetric anesthesiologist and 908 cases were covered by a non-obstetric anesthesiologist. General anesthesia was used in only 16 of these cases. General anesthesia was more likely to be performed by non-obstetric fellowship trained anesthesiologists (1.54% or 14/908 compared to 0.22% or 2/912; P = 0.002). CONCLUSIONS: This investigation suggests that the presence of an obstetric fellowship-trained anesthesiologist may be a predictor of decreased rate of general anesthesia use in patients with preexisting indwelling labor epidural catheters.

Postoperative pain and analgesic requirements after septoplasty and rhinoplasty.

OBJECTIVES/HYPOTHESIS: To assess and define the level of pain after rhinoplasty and septoplasty and to better define the strength and quantity of postoperative opioids needed. STUDY DESIGN: Prospective outcomes research. METHODS: Two groups of patients were enrolled. One group underwent septoplasty with/without turbinate reduction and the other group underwent functional and/or cosmetic rhinoplasty (with/without septoplasty). Patients completed a 15-day log (daily, beginning on the day of surgery) to record the analgesics used and the daily maximal level of pain using a visual analog scale. Level of pain, number of days of moderate or severe pain, total number of opioid pills used, and total morphine milligram equivalents (MMEs) of opioid used were assessed. RESULTS: Pain after septoplasty and rhinoplasty was generally mild. Average pain was moderate through postoperative day (POD) 2 after rhinoplasty and only on POD 0 after septoplasty. There was no statistically significant difference between the two groups in terms of number of opioid tablets consumed or total MMEs used. Patients undergoing rhinoplasty consumed more acetaminophen than septoplasty-only patients (7471 ± 1009 vs. 2781 ± 585, P = .0112). Ninety percent of patients would have received adequate analgesia with as few as 11 opioid tablets. All patients had excess opioid at the end of the study period. CONCLUSIONS: Both septoplasty and rhinoplasty are associated with mostly mild pain, and postoperative opioid requirements are quite low. Surgeons can reliably reduce opioid prescription after septoplasty and rhinoplasty to as few as 11 tablets. Reducing opioid prescribing will not adversely affect the patient but will reduce the availability of opioids for misuse or diversion. LEVEL OF EVIDENCE: 2c Laryngoscope, 129:2020-2025, 2019.

Opioid analgesic use and patient-reported pain outcomes after rhinologic surgery.

BACKGROUND: Opioid-based analgesics are routinely prescribed after elective rhinologic surgery. Balancing appropriate pain management while avoiding overprescription necessitates an evidence-based approach. METHODS: Patients undergoing elective rhinologic surgery, including endoscopic sinus surgery (ESS), septoplasty, or ESS with septoplasty, were prospectively enrolled. Patients completed demographic and psychometric questionnaires assessing attitudes toward pain, baseline anxiety, and depression before surgery. Postoperatively, patients documented peak pain levels (0-100 visual analog scale) and daily prescription and nonprescription medication requirements over a 2-week period. RESULTS: Of the 42 patients enrolled, 15 underwent ESS, 14 septoplasty, and 13 ESS with septoplasty. Five patients (11.9%) reported a history of chronic pain before surgery. Patients were given a median of 30 opioid pain pills after surgery: acetaminophen with codeine 325/30 mg (10 patients) or oxycodone with acetaminophen 5/325 mg (32 patients). Patients had a median of 27 pills left over at the end of the study period. Median peak pain levels for all procedures were 22 (range, 0-94) on day 0, 26.5 (range, 0-86) on day 1, 8.5 (range, 0-85) on day 3, and 3 (range, 0-52) on day 7. Median opioid requirements measured in morphine milligram equivalents (MME) over those same days were 6.0, 4.1, 0, and 0, respectively. CONCLUSION: Postoperative pain after elective rhinologic surgery appears to peak over the first 3 days and decreases rapidly afterward. Most patients require a few doses of opioid analgesics. Opioid requirements and pain levels did not vary based on surgeon, type and extent of surgery, and demographic factors. Judicious prescribing of opioid medication after rhinologic surgery represents a practical opportunity for rhinologists and otolaryngologists to reduce opioid overprescription and abuse.

A novel mutation in CDK5RAP2 gene causes primary microcephaly with speech impairment and sparse eyebrows in a consanguineous Pakistani family.

CDK5RAP2 gene encodes a centrosomal protein, highly expressed in fetal brain and essentially indispensable for its normal development, as biallelic mutations in it lead to primary microcephaly (MCPH). Despite being known as MCPH linked gene for more than a decade, the phenotypic spectrum of CDK5RAP2 mutations is still under explored as only eleven families have been reported worldwide. Here, we analyzed a consanguineous Pakistani MCPH family, characterized by moderate to severe intellectual disability, speech impairment, moderately short stature and sparse eyebrows. Whole exome sequencing of the proband identified a 2bp duplication in exon 34 of CDK5RAP2 that causes frame-shift, leading to a premature stop codon. The resultant transcript is resistant to nonsense mediated decay, suggesting that the mutation leads to a truncated protein lacking C-terminal domains; CDK5R1, and Cnn motif 2 (CM2), required for its localization to centrosome and Golgi Apparatus. Clinical variability observed in the family highlights the importance of further detailed clinical description of patients with CDK5RAP2 mutations.

Mutation of the Planar Cell Polarity Gene VANGL1 in Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Mutation analysis of a candidate disease gene in a cohort of patients with moderate to severe Adolescent idiopathic scoliosis (AIS). OBJECTIVE: To investigate if damaging mutations in the planar cell polarity gene VANGL1 could be identified in AIS patients. SUMMARY OF BACKGROUND DATA: AIS is a spinal deformity which occurs in 1% to 3% of the population. The cause of AIS is often unknown, but genetic factors are important in the etiology. Rare variants in genes encoding regulators of WNT/planar cell polarity (PCP) signaling were recently identified in AIS patients. METHODS: We analyzed the coding region of the VANGL1 gene for mutations using Sanger sequencing in 157 unrelated patients with moderate to severe AIS. The frequency of mutations in the patient cohort was compared with their frequency in a large cohort of controls. Functional effect of mutations were predicted in silico and analyzed in vitro by transfection of normal and mutant recombinant VANGL1 protein in Madin-Darby Canine Kidney (MDCK) cells. Cellular localization of recombinant proteins was analyzed by immunofluorescence microscopy analysis. RESULTS: In the patient cohort, we identified two rare missense mutations in VANGL1, encoding a receptor involved in WNT/PCP signaling. The mutations, p.I136N and p.F440 V, are very rare in the normal population. Both mutations are predicted to be damaging, and to affect evolutionary conserved amino acid residues of VANGL1. Functional analysis in MDCK cells showed that the mutations abolished the normal translocation of VANGL1 to the cell membrane. CONCLUSION: Our data support that mutations in genes involved in WNT/PCP signaling may be associated with AIS, but replication in other patient cohorts and further analysis of the role of WNT/PCP signaling in AIS is needed. LEVEL OF EVIDENCE: 4.

Neonatal and Maternal Temperature Regulation During and After Delivery.

An important goal of obstetric anesthesia is to provide for the safety and comfort of the mother as well as to optimize physiologic outcomes for the neonate. Markers of neonatal physiologic outcome include cord umbilical artery pH and Apgar scores. Neonatal temperature has often been overlooked by anesthesiologists as an important physiologic outcome measure, but it may be significantly affected by operating room conditions and obstetric anesthesia technique at cesarean delivery. There is a dose-dependent increase in mortality with decreasing body temperature as well as an increased likelihood for more severe early respiratory distress. Multiple neonate-focused strategies have been shown to decrease the incidence of neonatal hypothermia. Because fetal temperature is affected by maternal temperature, strategies to mitigate maternal hypothermia at the time of delivery may also be important in preventing neonatal hypothermia. This focused review will examine the importance of neonatal temperature and discuss its relationship to maternal temperature as well as strategies for maintaining neonatal normothermia after delivery.

Characterization of a novel missense mutation in the prodomain of GDF5, which underlies brachydactyly type C and mild Grebe type chondrodysplasia in a large Pakistani family.

All TGF-beta family members have a prodomain that is important for secretion. Lack of secretion of a TGF-beta family member GDF5 is known to underlie some skeletal abnormalities, such as brachydactyly type C that is characterized by a huge and unexplained phenotypic variability. To search for potential phenotypic modifiers regulating secretion of GDF5, we compared cells overexpressing wild type (Wt) GDF5 and GDF5 with a novel mutation in the prodomain identified in a large Pakistani family with Brachydactyly type C and mild Grebe type chondrodyslplasia (c527T>C; p.Leu176Pro). Initial in vitro expression studies revealed that the p.Leu176Pro mutant (Mut) GDF5 was not secreted outside the cells. We subsequently showed that GDF5 was capable of forming a complex with latent transforming growth factor binding proteins, LTBP1 and LTBP2. Furthermore, secretion of LTBP1 and LTBP2 was severely impaired in cells expressing the Mut-GDF5 compared to Wt-GDF5. Finally, we demonstrated that secretion of Wt-GDF5 was inhibited by the Mut-GDF5, but only when LTBP (LTBP1 or LTBP2) was co-expressed. Based on these findings, we suggest a novel model, where the dosage of secretory co-factors or stabilizing proteins like LTBP1 and LTBP2 in the microenvironment may affect the extent of GDF5 secretion and thereby function as modifiers in phenotypes caused by GDF5 mutations.