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Introduction: Helicopter Emergency Medical Services (HEMS) is integrated into modern emergency medical services because of its suggested mortality benefit in certain patient populations, it is an expensive resource and appropriate use/feasibility in low- to middle income countries (LMIC) is highly debated. To maximise benefit, correct patient selection in HEMS is paramount. To achieve this, current practices first need to be described. The study aims to describe a population of patients utilising HEMS in South Africa, in terms of flight data, patient demographics, provisional diagnosis, as well as clinical characteristics and interventions. Methods: A retrospective flight- and patient-chart review were conducted, extracting clinical and mission data of a single aeromedical operator in South Africa, over a 12-month period (July 2017 – June 2018) in Gauteng, Free State, Mpumalanga and North-West provinces. Results: A total of 916 cases were included (203 primary cases, 713 interfacility transport (IFT) cases). Most patients transported were male (n=548, 59.8%) and suffered blunt trauma (n=379, 41.4%). Medical pathology (n=247, 27%) and neonatal transfers (n=184, 20.1%) follows. Flights occurred mainly in daylight hours (n=729, 79.6%) with median mission times of 1-hour 53 minutes (primary missions), and 3 hours 10 minutes (IFT missions). Median on-scene times were 26 minutes (primary missions) and 55 minutes (IFT missions). Almost half were transported with an endotracheal tube (n=428, 46.7%), with a large number receiving no respiratory support (n=414, 45.2%). No patients received fibrinolysis, defibrillation, cardioversion or cardiac pacing. Intravenous fluid therapy (n=867, 94.7%) was almost universal, with common administration of sedation (n=430, 46.9%) and analgesia (n=329, 35.9%). Conclusion: Apart from the lack of universal call-out criteria and response to the high burden of trauma, HEMS seem to fulfil an important critical care transport role. It seems that cardiac pathologies are under-represented in this study and might have an important implication for crew training requirements.

Background: Waveform capnography has proven to be of great value in the provision of safe patient care especially in the intubated patient. Although seldom available, or used in African contexts, capnography has become standard practice in well-resourced out-of-hospital services for confirmation of intubation, and optimization of resuscitation and ventilation. To date there has been little research into the knowledge of out-of-hospital staff, both local and internationally, utilising capnography. This study describes the knowledge of paramedics who use waveform capnography in the out-of-hospital environment. Methods: A cohort of advanced life support qualified paramedics in a private ambulance service in South Africa undertook a web-based survey around their background, training and use of capnography. Participants’ knowledge was assessed by exploring their interpretation of waveform capnography and establishing attitudes pertaining to training and constraints of availability of capnography. Results: Seventy eight paramedics responded, and most (91%) indicated they were likely to use capnography when the tool was available. The majority of training in capnography had been during their primary qualification (85%). Most participants indicated that they would like further training (91%). Use of capnography for confirmation of endotracheal tube placement and quality of compressions during cardiopulmonary resuscitation was well understood (correct in 94% and 84% respectively), while more complicated knowledge such as waveform changes during ventilation (66%) and the effect of hypovolaemia (48%) on capnography were lacking. Conclusion: Paramedics report using waveform capnography extensively when it is available in the South African out-of-hospital environment. Although the knowledge around capnography and its usage was found to be good in most areas, more complicated scenarios exposed flaws in the knowledge of many paramedics and suggest the need for improved and ongoing training, as well as incorporation into curricula as the field develops across the continent. Keywords: Waveform capnography, Paramedics, Emergency medical services, South Africa

Introduction: Out-of-Hospital Cardiac Arrest (OHCA) is a time-sensitive emergency requiring prompt identification and emergency care to reduce morbidity and mortality. The first step in managing OHCA is rapid identification by the emergency dispatch centre. Identification of these patients remains challenging in South Africa due to multiple languages and widely differing levels of education. This study aimed to identify the key descriptors (words and phrases) of OHCA used by callers in the Western Cape when contacting the provincial Emergency Medical Services' emergency call centre. Methodology: Computer-aided dispatch data with a corresponding “patient unresponsive” incident type were drawn for a 12-month period (January–December 2018). Corresponding patient care records were extracted to verify OHCA. The original voice recordings between the caller and emergency call taker at the time of the emergency were extracted and transcribed verbatim. Transcriptions were subjected to inductive, qualitative content analysis to the manifest level. Descriptors of OHCA in isiXhosa, English and Afrikaans calls were coded, categorised, and quantified. Results: A total of 729 confirmed OHCA cases were identified, of which 38 (5.2%) Afrikaans, 24 (3.3%) isiXhosa and a random sample of 50 (6.8%) English calls were transcribed. Following content analysis, five distinct categories were identified. The most prevalent categories were descriptors related to ill health (medical history and suspected diagnosis; 35.5%), level of consciousness (unresponsive; 18.6%) and cardiac activity (pulselessness and suspected death; 17.2%). Conclusion: The vast majority of callers within the Western Cape province of South Africa use consistent descriptors across languages when requesting an ambulance for OHCA. Future studies should focus on the development and validation of OHCA recognition algorithms, based on these findings.

Objectives While prospective epidemiological data for out-of-hospital cardiac arrest (OHCA) exists in many high-income settings, there is a dearth of such data for the African continent. The aim of this study was to describe OHCA in the Cape Town metropole, South Africa.Design Observational study with a retrospective descriptive design.Setting Cape Town metropole, Western Cape province, South Africa.Participants All patients with OHCA for the period 1 January 2018–31 December 2018 were extracted from public and private emergency medical services (EMS) and described.Outcome measures Description of patients with OHCA in terms of demographics, treatment and short-term outcome.Results A total of 929 patients with OHCA received an EMS response in the Cape Town metropole, corresponding to an annual prevalence of 23.2 per 100 000 persons. Most patients were adult (n=885; 96.5%) and male (n=526; 56.6%) with a median (IQR) age of 63 (26) years. The majority of cardiac arrests occurred in private residences (n=740; 79.7%) and presented with asystole (n=322; 34.6%). EMS resuscitation was only attempted in 7.4% (n=69) of cases and return of spontaneous circulation (ROSC) occurred in 1.3% (n=13) of cases. Almost all patients (n=909; 97.8%) were declared dead on the scene.Conclusion To our knowledge, this was the largest study investigating OHCA ever undertaken in Africa. We found that while the incidence of OHCA in Cape Town was similar to the literature, resuscitation is attempted in very few patients and ROSC-rates are negligible. This may be as a consequence of protracted response times, poor patient prognosis or an underdeveloped and under-resourced Chain of Survival in low- to middle-income countries, like South Africa. The development of contextual guidelines given resources and disease burden is essential.

Introduction: Helicopter Emergency Medical Services (HEMS) exists to supplement the operations of ground-based emergency care providers, mainly in high acuity cases. One of the important procedures frequently carried out by HEMS personnel is endotracheal intubation. Several HEMS providers exist in South Africa, with a mix of advanced life support personnel, however intubation success rates and adverse events have not been described in any local HEMS operation. Methods: This was a retrospective chart review of intubation-related data collected by a HEMS operation based in Johannesburg over a 16-month period. First-pass and overall success rates were described, in addition to perceived airway difficulty, adverse events and other data. Results: Of the 49 cases recorded in the study period, one was excluded leaving 48 cases for analysis. Most cases (n = 34, 71%) involved young male trauma patients who were intubated with rapid sequence intubation. The first pass success rate was 79% (n = 38) with an overall success rate of 98% (n = 47). At least one factor suggesting airway difficulty was present in 29% (n = 14) of cases, with most perceived airway difficulty related to the high prevalence of trauma cases. At least one adverse event occurred in 27% (n = 13) of cases with hypoxaemia, hypotension and bradycardia most prevalent. Discussion: In this small sample of South African HEMS intubation cases, we found overall and first-pass success rates comparable to those reported in similar contexts. Keywords: Helicopter Emergency Medical Services, Endotracheal intubation, Airway management, Prehospital care

Background We aimed to determine the relationship between ruptured abdominal aortic aneurysm (AA) and serum concentrations of lipids and apolipoproteins. [ABSTRACT FROM PUBLISHER]

Introduction: It is difficult to initiate clinical quality improvement projects through continuous education in the prehospital environment due to the very nature of their mobile workplace and unpredictable presence in a specific location. This study reviews the impact of an online learning platform and the effect it had on the clinical quality of care offered to patients with traumatic brain injury (TBI) during Helicopter Emergency Medical Services (HEMS) operations. Methods: A prospective improvement project was initiated to improve the clinical care for patients with TBI. A clinical monitoring tool, based on the prehospital care guidelines of the Brain Trauma Foundation was designed to assess the clinical quality of TBI patient care. The clinical indicators measured included initial Glasgow Coma Score, motor function, pupil size and reactivity, hypotension, hypoxaemia, carbon dioxide levels, temperature control, and patient position. A four month baseline monitoring was completed to determine the level of adherence to the guidelines, and subsequently an online, free access lecture series was presented to the HEMS operational staff. The clinical monitoring tool was applied during this time and afterwards to review adherence to guidelines. Results: A total of 71 cases of TBI were seen during the period of assessment and 64.8% of HEMS crew participated in the online training programme. A change in the average adherence to the clinical guidelines improved from 66.9% to 75.7% (p = 0.033) from the baseline monitoring period, to the period immediately after the online training. Conclusion: Free and open online learning platforms can be implemented at little to no cost and can be accessed anywhere. This initiative has shown benefit in ensuring best care for critically ill TBI HEMS patients.

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Esophageal perforation (EP) can be a diagnostic challenge. Computed tomography (CT) and CT esophagography (CTE) are often used to rule out EP in the emergency setting with promising diagnostic performance, but the standard of care remains fluoroscopic esophagography (FE). We assess the diagnostic performance of CT and CTE when interpreted by expert and generalist radiologists and created an imaging workflow guide., Methods: Retrospective study of patients presenting with suspected EP. Two expert radiologists independently reviewed blinded CT/CTE studies, recorded CT findings, and assigned an esophageal injury grade. We also collected initial (general radiologist) CT findings and interpretation and FE diagnoses. We assessed inter-reader reliability and diagnostic performance., Results: EP was diagnosed in 46/139 (33%) encounters. The most common CT/CTE findings in EP were esophageal wall thickening (46/46, 100%), pneumomediastinum (42/46, 91%), and mediastinal stranding (39/46, 85%). CT and CTE sensitivity for detecting EP was 89% and 89% for expert radiologists, respectively, and 79% and 82% for general radiologists, compared with 46% for FE. Inter-reader agreement for detecting EP by CT and CTE was kappa 0.35 and 0.42 (both p < .001) between expert and generalist radiologists. We present radiographic images for key CT/CTE findings and a suggested workflow for the evaluation of possible EP., Conclusion: CT and CTE are more sensitive than FE for EP in the emergency setting. Due to the rarity of EP and current wide variability in imaging interpretation, an imaging workflow and injury grading system based on esophageal and mediastinal CT findings are offered to help guide management., (© 2023. The Author(s), under exclusive licence to American Society of Emergency Radiology (ASER).)

Background: Total knee arthroplasty (TKA) is a commonly performed procedure to alleviate pain and improve functional limitations caused by end-stage joint damage. Effective management of postoperative pain following TKA is crucial to the prevention of complications and enhancement of recovery. Adductor canal blocks (ACB) with conventional bupivacaine (CB) provide adequate analgesia after TKA, but carry a risk of rebound pain following block resolution. Liposomal bupivacaine (LB) is an extended-release local anesthetic that can provide up to 72 h of pain relief. The objective of this study was to compare postoperative outcomes between ACBs using LB and CB after TKA., Methods: This single institution, prospective, randomized, clinical trial enrolled patients scheduled for TKA. Participants were randomized to receive ACB with either LB or CB. Pain scores up to 72 h postoperatively were assessed as the primary outcome. Opioid consumption and length of stay were evaluated as secondary outcomes., Results: A total of 80 patients were enrolled. Demographic and clinical characteristics were similar between the two groups. LB group showed significantly lower cumulative opioid use during the 72 h evaluated (P = 0.016). There were no differences in pain scores or length of stay between the groups., Conclusion: The study demonstrated that LB ACBs led to significantly lower opioid consumption in the days following TKA without affecting pain scores or length of stay. This finding has important implications for improving postoperative outcomes and reducing opioid use in TKA patients. Previous studies have reported inconsistent results regarding the benefits of LB, highlighting the need for further research., Trial Registration: This project was retrospectively registered with clinicaltrials.gov ( NCT05635916 ) on 2 December 2022., (© 2024. The Author(s).)

The number of patients maintained on buprenorphine is steadily increasing. To date, no study has reported buprenorphine management practices for these patients during critical illness, nor its relationship with supplemental full-agonist opioid administration during their hospital stay. In this single-center retrospective study, we have explored the incidence of buprenorphine continuation during critical illness among patients receiving buprenorphine for the treatment of opioid use disorder. Additionally, we investigated the relationship between nonbuprenorphine opioid exposure and buprenorphine administration during the intensive care unit (ICU) and post-ICU phases of care. Our study included adults maintained on buprenorphine for opioid use disorder admitted to the ICU between December 1, 2014, and May 31, 2019. Nonbuprenorphine, full agonist opioid doses were converted to fentanyl equivalents (FEs). Fifty-one (44%) patients received buprenorphine during the ICU phase of care, with an average dose of 8 (8-12) mg/day. During the post-ICU phase of care, 68 (62%) received buprenorphine, with an average dose of 10 (7-14) mg/day. Lack of mechanical ventilation and acetaminophen use were also associated with buprenorphine use. Full agonist opioid use was more frequent on days when buprenorphine was not given (odds ratio [OR], 6.2 [95% CI, 2.3-16.4]; P < .001). Additionally, the average cumulative dose of opioids given on nonbuprenorphine administration days was significantly higher both in the ICU (OR, 1803 [95% CI, 1271-2553] vs OR, 327 [95% CI, 152-708] FEs/day; P < 0.001) and after ICU discharge (OR, 1476 [95% CI, 962-2265] vs OR, 238 [95% CI, 150-377] FEs/day; P < .001). Given these findings, buprenorphine continuation during critical illness should be considered, as it is associated with significantly decreased full agonist opioid use., (© 2023, The American College of Clinical Pharmacology.)

Background: The purpose of this study was to compare the clinical outcomes of adults with uncomplicated streptococcal bacteremia who received either oral (PO) step-down or continued intravenous (IV) therapy., Methods: This was a retrospective, single-center, cohort study, including adults admitted with Streptococcal bloodstream infection between January 1, 2013, and December 31, 2020. Only patients with uncomplicated Streptococcal bloodstream infections were included. Patients who transitioned to PO therapy within 5 days from bacteremia onset were compared to patients receiving continued IV therapy. The primary outcome was clinical failure, defined by either 90-day hospital readmission or mortality. Secondary outcomes included hospital length of stay (LOS) and antibiotic-related adverse events (AAEs)., Results: Of the 264 patients included, 42% were transitioned to PO therapy. Group B Streptococcus (22.7%) was the most common isolate. The most common sources of infection were skin and soft tissue (35%) and pulmonary (25%). Intensive care unit (ICU) stay was more common in the continued IV therapy group (22.2%) than in the PO step-down group (5.4%). The frequency of clinical failure was similar in the IV and PO groups (24.2% vs. 18.0%, P=0.23). The IV group had longer hospital LOS (median, [interquartile range (IQR)]) compared with the PO group (7 [5-13.5] vs. 4 [3-5] days, P<0.001). The incidence of AAEs was similar in the IV and PO groups (1.3% vs. 1.8%, P=0.74)., Conclusion: Oral antibiotic step-down therapy may be appropriate for the treatment of uncomplicated Streptococcal bacteremia, with consideration of factors such as patient comorbidities, type of infection, source control and clinical progress., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Introduction: An increasing number of individuals are taking buprenorphine for management of opioid use disorder (OUD). Pain control can be challenging when these patients develop acute pain requiring supplemental analgesia. Buprenorphine's pharmacokinetic profile can render supplemental opioid-based analgesia ineffective. There is limited guidance on the optimal management of buprenorphine when acute pain is anticipated. Although there is growing acceptance that the risk of OUD relapse with buprenorphine discontinuation overshadows the risks of increased opioid utilization and difficult pain control with buprenorphine continuation, perioperative courses comparing buprenorphine dose reduction and full dose buprenorphine continuation have yet to be investigated. Here, we describe the protocol for our randomized controlled, prospective trial investigating the effect of buprenorphine continuation compared to buprenorphine dose reduction on pain control, post-operative opioid use, and OUD symptom management in patients on buprenorphine scheduled for elective surgery., Methods and Analysis: This is a single institution, randomized trial that aims to enroll 80 adults using 12 mg buprenorphine or greater for treatment of OUD, scheduled for elective surgery. Participants will be randomly assigned to receive 8mg of buprenorphine on the day of surgery onwards until postsurgical pain subsides or to have their buprenorphine formulation continued at full dose perioperatively. Primary outcome will be a clinically significant difference in pain scores 24 hours following surgery. Secondary outcomes will be opioid consumption at 24, 48, and 72 hours postoperatively, opioid dispensing up to 30 days following surgery, changes in mood and withdrawal symptoms, opioid cravings, relapse of opioid misuse, and continued use of buprenorphine treatment postoperatively., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To compare maternal and perinatal outcomes in pregnancies with transient and persistent idiopathic polyhydramnios to those with normal amniotic fluid volume., Methods: This retrospective cohort study included subjects delivering a singleton pregnancy between January 1, 2015, and June 30, 2020, with sonography ≥26 weeks' gestation demonstrating transient or persistent idiopathic polyhydramnios (amniotic fluid index [AFI] ≥24.0 cm) or normal AFI (referent group). The primary maternal outcome was a composite of spontaneous preterm delivery <37 weeks, cesarean delivery for malpresentation, abnormal labor progress, or nonreassuring fetal status, operative vaginal delivery, hemorrhage requiring transfusion, and umbilical cord prolapse. The primary perinatal outcome was a composite of birthweight >4500 g, fetal or neonatal death, 5-minute Apgar score <7, and neonatal intensive care unit admission for >24 hours., Results: Patients with transient polyhydramnios (n = 259) exhibited maternal outcomes similar to those of the referent group (n = 435) but had significantly increased odds for the primary perinatal outcome (odds ratio [OR] 1.70, 95% confidence interval [CI] 1.15-2.53; P = .008) and for birthweight ≥4500 g (OR 8.70, 95% CI 1.89-40.0; P = .005). Persistent polyhydramnios (n = 176) was significantly associated with both the primary maternal (OR 1.93, 95% CI 1.27-2.95, P = .002) and primary perinatal outcome (OR 2.15, 95% CI 1.40-3.30; P < .001), and individually with cesarean delivery for abnormal labor (OR 3.22, 95% CI 1.55-6.68; P = .002) and birthweight ≥4500 g (OR 8.97, 95% CI 1.84-43.6; P = .007)., Conclusions: Transient idiopathic polyhydramnios does not impact maternal outcomes but is associated with increased odds of newborn birthweight >4500 g. Persistent polyhydramnios is associated with both adverse maternal and perinatal outcomes., (© 2022 American Institute of Ultrasound in Medicine.)

Cystic fibrosis (CF) may predispose patients to urinary stone disease (USD), but reported prevalence of USD in patients with CF in previous small studies is variable. To date, analysis of risk factors for USD within the CF population has been limited. We studied 29,396 patients in the Cystic Fibrosis Foundation Patient Registry to calculate age and sex-stratified prevalence of USD. For adult patients, we examined age and multivariable-adjusted cross-sectional associations between demographic and clinical factors, CFTR mutation class, and prevalent USD. Prevalence of USD was 0.4% (95% CI 0.3-0.5%) under age 18 years, 3.1% (2.7-3.6%) at 18-24 years, 6.4% (5.8-7.1%) at 25-34 years, 7.5% (6.5-8.5%) at 35-44 years, and 6.7% (5.8-7.8%) at 45 years and older. Prevalence for women was higher than men at younger (< 45 years) but not older ages (P value for interaction < 0.0005). Multivariable odds of prevalent USD were significantly increased for severe CFTR mutations, OR 1.53 (1.14-2.06), diabetes, OR 1.24 (1.03-1.50), hypertension, OR 1.58 (1.29-1.93), and chronic macrolide therapy, OR 1.27 (1.07-1.52). BMI was not associated with USD. USD prevalence in CF is similar to that in the general population. With the exception of BMI, known risk factors for USD in the general population also appear to be important for patients with CF. We identified several novel associations in CF patients, including greater prevalence of USD in individuals with severe CFTR mutations and among young women., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Purpose: Despite its availability for more than 70 years, many details concerning methadone remain contentious, such as the dosing equivalents for intravenous and enteral administration. A scoping review was performed to evaluate whether existing literature on methadone bioavailability in human subjects support the current recommendation that an equivalent enteral dose is twice the intravenous dose., Methods: A librarian-assisted search of the PubMed and EMBASE databases identified all English-language articles with the terms methadone and bioavailability and/or conversion in the title or abstract published from inception though December 2019. A manual search of references was also performed to identify any additional articles. Studies were included in a scoping review if they were published in English and evaluated methadone bioavailability in human subjects., Results: Among 65 publications initially identified, 6 studies involving a total of 50 patients were included in the review. Bioavailability data for healthy volunteers and patients with opioid use disorder, metastatic cancer, chronic pain from malignant or nonmalignant disease were available for analysis. The pooled mean (95% confidence interval) bioavailability (F) was 85.4% (75.2%-95.6%), with heterogeneity (I2) of 0. In the 4 studies that provided individual patient-level data, F was >50% in 40 of 42 patient measurements (95.2%) and ≥75% in 33 of 42 patient measurements (78.6%)., Conclusion: Available evidence suggests the bioavailability of methadone is generally more than 75%, there is limited evidence for the currently recommended 1:2 ratio (intravenous:enteral), and a more appropriate dosing ratio may be 1:1.3. This scoping review underscores the need for further research to establish an effective and safe ratio when converting between intravenous and enteral dosing formulations of methadone., (© American Society of Health-System Pharmacists 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: This study assessed the use, tolerability, and safety of anticoagulation via direct oral anticoagulants or warfarin in medical and psychiatric inpatients receiving ECT., Methods: This retrospective cohort study included 32 patients who received ECT while on either a direct oral anticoagulant (9) or warfarin (23) and spanned 247 encounters at Maine Medical Center between December 2012 and December 2018. Data are presented descriptively and analyzed using SPSS version 25 and Microsoft Excel version 2016., Results: Among the 247 ECT patient encounters, there were few major adverse effects of ECT in this medically complex population. These adverse effects included headache during 4 encounters (1.6%), respiratory distress during 2 encounters (0.8%) and a cardiovascular event during 1 encounter (0.4%). One patient (3.1%) who was receiving concurrent rivaroxaban and venlafaxine experienced gastrointestinal bleeding that was determined to be unrelated to ECT. One patient on fluoxetine and warfarin experienced hemoptysis thought to be secondary to epistaxis. No other major bleeding or clotting event occurred during an ECT session nor for the duration of the hospitalization., Discussion: Direct oral anticoagulants and warfarin appear safe in the treatment of patients with atrial fibrillation or acute venous thromboembolism who are receiving concomitant ECT. Prospective studies are needed to confirm these findings., Competing Interests: Disclosures: This work was supported in part by the Northern New England Clinical and Translational Research grant U54GM115516., (© 2021 CPNP. The Mental Health Clinician is a publication of the College of Psychiatric and Neurologic Pharmacists.)

Context: Testosterone (T) or estradiol (E2) are administered to suppress gonadal function in female-to-male (FTM) and male-to-female (MTF) transgender patients. How often sex steroids cause adequate suppression without GnRH agonist (GnRHa) or progestin therapy has not been reported., Objectives: (1) To determine how often T and E2 therapy alone can effectively suppress gonadal function in MTF and FTM transgender patients, and (2) to determine the frequency and range of serum E2 levels above the normal male range in FTM patients receiving T therapy., Design: Retrospective cohort study., Setting: Outpatient reproductive endocrinology clinic at an academic medical center., Patients: A total of 65 FTM and 33 MTF patients were included who were > 18 years of age and not receiving progestin or GnRHa therapy., Intervention: Female-to-male patients were receiving T through injections or gel. Male-to-female patients were receiving oral or subcutaneous E2., Main Outcome Measurements: In FTM patients the indicator of ovary suppression was amenorrhea. In MTF patients, the indicator of testes suppression was T levels <50 ng/dL., Results: Median serum total T level for FTM patients was 712 ng/dL (range, 370-1164 ng/dL). On T therapy alone, 90.8% of patients achieved amenorrhea and 49.2% of patients had serum E2 levels above the normal range for women. For MTF patients, the median serum E2 level was 129.2 pg/mL (range, 75-197 pg/mL). On E2 therapy alone, 84.8% of MTF patients had adequate suppression of testicular function., Conclusions: Testosterone and E2 therapy are usually effective without progestin or GnRHa therapy to suppress gonadal function in transgender patients. Progestin and/or GnRHa therapy should only be initiated in those patients who do not have adequate gonadal suppression on optimized doses of T or E2 alone., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The value of positive follow-up blood cultures (FUBCs) in streptococcal bacteremia has not been well defined. Therefore, we explored the frequency of and risk factors for positive FUBC in a retrospective cohort of patients with streptococcal bacteremia., Methods: Adults ≥18 years of age, admitted with at least 1 positive blood culture for Streptococcus spp between 2013 and 2018 followed by at least 1 FUBC, were potentially eligible. Positive FUBCs were defined as cultures positive for the same streptococcal species drawn >24 hours after the index culture. We excluded patients with polymicrobial bacteremia. We compared the characteristics of patients with and without a positive FUBC., Results: In our single-center cohort, we identified 590 patients with streptococcal bacteremia, and 314 patients met inclusion criteria. Ten patients had FUBC with Streptococcus spp (3.2%), 4 (1.3%) had a contaminant identified, and 3 (1.0%) had a new pathogen isolated. Endocarditis (5 of 10 [50.0%] vs 35 of 304 [11.5%]), epidural abscess (2 of 10 [20%] vs 4 of 304 [1.3%]), and discitis or vertebral osteomyelitis (3 of 10 [30.0%] vs 14 of 304 [4.6%]) were associated with positive FUBC. Patients with positive FUBC had a longer median length of stay (12.9 vs 7.1 days, P  = .004) and longer duration of antibiotic treatment (14.9 vs 43.2 days, P  = .03)., Conclusions: Follow-up blood cultures among patients with streptococcal BSI are rarely positive. Clinicians could consider limiting follow-up blood cultures in patients at low risk for deep-seated streptococcal infections, persistent bacteremia, or endovascular infection., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: We sought to study potential diagnostic criteria for marginal placental cord insertions as determined by associations with obstetric outcomes., Methods: This single-center retrospective cohort investigation included singleton gestations delivering from January 1, 2012, to December 31, 2016, and having a standard or detailed fetal ultrasound examination from 18 weeks to 21 weeks 6 days. Cord insertion-to-placental edge distances were used to create a referent comparison group and 3 patient groups: greater than 3.0 cm (comparison); greater than 2.0 to 3.0 cm (group 1); greater than 1.0 to 2.0 cm (group 2); and 1.0 cm or less (group 3). The primary outcome consisted of any one of spontaneous delivery before 37 weeks, fetal growth restriction, oligohydramnios, placental abruption, or intrauterine fetal demise., Results: The numbers of participants and mean distances ± SDs for the comparison group and groups 1 to 3, respectively, were 628 and 4.68 ± 1.17 cm, 106 and 2.52 ± 0.26 cm, 131 and 1.60 ± 0.29 cm, and 77 and 0.36 ± 0.37 cm, respectively. The primary outcome was significantly associated only with cord insertion-to-placental edge distances of 1.0 cm or less (adjusted odds ratio, 3.05; 95% confidence interval, 1.73-5.38)., Conclusions: Marginal cord insertions may be diagnosed when the cord insertion-to-placental edge distance is 1.0 cm or less., (© 2019 by the American Institute of Ultrasound in Medicine.)

Background: Healthcare workers experience a disproportionately high frequency of workplace assaults. Incidents involving firearms are of particular concern., Objective: To provide detailed characterizations of recent hospital shootings to better inform prevention and mitigation strategies., Methods: Quantitative content analysis of reports involving hospital shootings resulting in casualties derived from web searches for each year from 2012-2016. Data were abstracted independently by two investigators, with differences resolved by consensus. Data were compared between subgroups by chi-square test, Fisher's exact test, or Kruskal-Wallis test, as appropriate., Results: Eighty-eight shootings occurred in 86 hospitals resulting in 121 firearms-related casualties, including 54 victims and 67 perpetrators. Case fatality rates were 55.6% (n = 30) and 70.1% (n = 47), respectively. The most frequent sites involved were the emergency department, (n = 27, 30.3%), patient room (n = 19, 21.3%), and parking lot (n = 13, 14.6%). Grudge (n = 17, 19.3%), suicide (n = 14, 15.9%), and mental instability (n = 13, 14.8%) were the most common explanations for these shootings. Four inadvertent discharges occurred and were more likely to involve a female perpetrator (p = 0.03). Shootings were most frequent during summer (p = 0.03) and winter (p = 0.04)., Conclusions: Out study findings on location and seasonal patterns can guide the development or improvement of prevention and mitigations strategies for hospital shootings.

Objectives: To evaluate perinatal outcomes in singleton and twin pregnancies with pathologically confirmed velamentous cord insertion without vasa previa., Methods: This retrospective case-control study included all nonanomalous singleton and twin pregnancies with pathologically confirmed velamentous cord insertion delivered in a single institution between January 1, 2005, and July 1, 2015, and having an ultrasound examination by maternal-fetal medicine. For each case, the next 2 consecutive deliveries matched for gestational age at delivery ± 1 week and, in twins, amnionicity and chorionicity served as controls. Primary outcomes included surgical delivery for a nonreassuring intrapartum fetal heart rate tracing, umbilical arterial cord pH of less than 7.2, 5-minute Apgar score of less than 7, birth weight below the 10th percentile, neonatal intensive care unit admission, fetal or neonatal death, and cord avulsion necessitating manual placental extraction., Results: Outcomes were available for 53 singletons with 103 matched controls and 33 twin pregnancies with 65 matched controls. In singletons, velamentous cord insertion was associated with cord pH of less than 7.2 (odds ratio [OR] 3.5; 95% confidence interval [CI], 1.1-11.2; P = .039), 5-minute Apgar score of less than 7 (OR, 5.3; 95% CI, 0.99-28.1; P = .045), and cord avulsion requiring manual placental extraction (7.5% versus 0%; P = .012). Associations were suggested with increased surgical delivery for a nonreassuring intrapartum fetal heart rate tracing (OR, 2.4; 95% CI, 0.9-6.9; P = .14), birth weight below the 10th percentile (OR, 2.1; 95% CI, 0.8-5.9; P = .21), and fetal or neonatal death (3.8% versus 0%; P = .11). Velamentous cord insertions were also associated with placental abruption in singletons (7.5% versus 0%; P = .013). Among twins, velamentous cord insertion was associated with fetal or neonatal death (9.1% versus 0%; P = .036)., Conclusions: Isolated confirmed velamentous cord insertion is associated with adverse perinatal outcomes in singleton and twin gestations., (© 2017 by the American Institute of Ultrasound in Medicine.)

Objective: Lower extremity bypass (LEB) operations have high rates of surgical site infections (SSI). Phenylephrine is a commonly used vasoconstrictor which may reduce skin blood flow and increase the likelihood of SSI in these patients. We studied the potential effect of phenylephrine infusion during LEB surgery on SSI., Methods: LEB cases and their demographic data were identified through the Vascular Quality Initiative registry. SSI in this population was identified using the hospital epidemiology surveillance database. Phenylephrine use in this population was identified through chart review., Results: We identified 699 patients who underwent LEB; 82 (11.7%) developed an SSI, and 244 of 698 (35.0%) were treated with phenylephrine infusion. In bivariate analysis, higher body mass index (28.8 kg/m 2 vs 27.3 kg/m 2 ; P = .034), diabetes (14.6% vs 9.4%; P = .035), hypertension (12.6% vs 4.7%; P = .038), groin incision (13.2 vs 5.4%; P = .013) and longer procedure times (17.1% for >220 minutes and 8.9% for ≤220 minutes; P = .003) were associated with higher rates of SSI. Whereas phenylephrine infusion exhibited a trend toward a higher rate (14.8% vs 9.9%; P = .057). In the logistic regression model, diabetes (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.0-3.2; P = .032), total procedure time (OR, 1.85; 95% CI, 1.1-3.1; P = .026) and vertical groin incision (OR, 2.6; 95% CI, 1.1-6.5; P = .035) were independent predictors of increased SSI rates, whereas body mass index (OR, 1.04; 95% CI, 0.99-1.08; P = .09), hypertension (OR, 2.5; 95% CI, 0.6-10.9; P = .22), and phenylephrine infusion (OR, 1.08; 95% CI, 0.63-1.85; P = .78) were not independent predictors of increased SSI rates., Conclusions: Phenylephrine infusion did not increase the risk of SSI in patients who underwent LEB., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Oral and injected steroids are used commonly in the treatment of cervical radicular pain despite a paucity of data demonstrating their efficacy. The purpose of this study is to assess whether the response to orally administered steroids among patients with acute cervical radicular pain who develop recurrent pain is associated with their subsequent response to cervical epidural steroid injections., Methods: Patients referred to our center were evaluated and then referred for cervical epidural steroid injections at the clinical discretion of the provider; those who met inclusion criteria were offered participation in the study. After the injection was administered, patients were contacted by telephone and asked to complete the Brief Pain Inventory Short Form at one week, one month, three months, and six months postinjection., Results: Pain reduction after cervical steroid injection was not significantly different between 49 patients who reported pain reduction with a prior course of oral steroids and 22 patients who reported no pain reduction. Average pain scores decreased over six months (P < 0.001) among 72 patients treated with epidural steroid injection for cervical radicular pain. Of the 55 who provided baseline and six-month data, 14 (25.5%) reported complete relief at six months and 20 (36.4%) reported decreased pain., Conclusions: Patients can be reassured that they may experience pain reduction after a cervical epidural steroid injection even if oral steroid therapy was not effective. The majority of patients treated for cervical radicular pain with epidural steroid injection have reduced or absent pain for at least six months after treatment., (© 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Several studies have now reported associations between gestational diabetes mellitus (GDM) and low free thyroxine (fT4) during the second and third trimesters, but not in the first trimester. The present study further examines relationships between low fT4, maternal weight, and GDM among women in the FaSTER (First and Second Trimester Evaluation of Risk) trial, in an effort to determine the extent to which thyroid hormones might contribute to causality. The FaSTER cohort includes 9351 singleton, euthyroid women; 272 of these women were subsequently classified as having GDM. Thyrotropin (TSH), fT4, and thyroid antibodies were measured at 11-14 weeks' gestation (first trimester) and 15-18.9 weeks' gestation (second trimester). An earlier report of this cohort documented an inverse relationship between fT4 in the second trimester and maternal weight. In the current analysis, women with GDM were significantly older (32 vs. 28 years) and weighed more (75 vs. 64.5 kg). Maternal weight and age (but not TSH) were significantly associated univariately with fT4 (dependent variable), in the order listed. Second trimester fT4 odds ratios (OR) for GDM were 2.06 [95% CI 1.37-3.09] (unadjusted); and 1.89 [95% CI 1.26-2.84] (adjusted). First trimester odds ratios were not significant: OR 1.45 [95%CI 0.97-2.16] (unadjusted) and 1.11 [95% CI 0.74-1.62] (adjusted). The second trimester fT4/GDM relationship thus appeared to strengthen as gestation progressed. In FaSTER, high maternal weight was associated with both low fT4 and a higher GDM rate in the second trimester. Peripheral deiodinase activity is known to increase with high caloric intake (represented by high weight). We speculate that weight-related low fT4 (the metabolically inactive prohormone) is a marker for deiodinase activity, serving as a substrate for conversion of fT4 to free triiodothyronine (fT3), the active hormone responsible for glucose-related metabolic activity.

Context: Lower birth weight has been reported in conjunction with high maternal free T4 (FT4) in euthyroid pregnancies, raising concerns for suboptimal outcomes., Objective: The objective of the study was to explore the relationships between high maternal FT4 and pregnancy complications in euthyroid women and to further examine the relationships among maternal size, FT4, and birth weight., Design: This was an observational multicenter cohort study., Setting: The study was conducted at prenatal clinics., Study Subjects: A total of 9209 euthyroid women with singleton pregnancies participated in the study., Interventions: There were no interventions., Main Outcome Measures: Relationships between second-trimester high maternal FT4 and pregnancy/delivery complications and, among FT4, maternal weight and birth weight were measured., Results: Women in the highest FT4 quintile are younger and weigh less than women in quintiles 1-4; gestational diabetes and preeclampsia occur less often (P = < .001, P < .001, P < .001, and P = .05, respectively). Lowest median birth weight occurs among women in the highest FT4 quintile (P = < .001), but deliveries less than 37 weeks' gestation are not increased. Labor/delivery complications do not differ by FT4 quintile. Restricting analyses to maternal weight-adjusted small-for-gestational-age deliveries yields similar results, except for preeclampsia. In the highest maternal weight decile, adjusted median birth weight is 266 g higher (8.3%) than in the lowest weight decile; adjusted median FT4 is 0.91 pmol/L lower (6.8%). Among women in the highest FT4 decile, adjusted median birth weight is 46 g lower (1.3%) than in the lowest FT4 decile. All three relationships are statistically significant (P < .001, P < .001, and P = .004, respectively)., Conclusions: Lower median birth weight among euthyroid women with high FT4 is not associated with adverse pregnancy outcomes. Further investigation is indicated to determine how the variations in thyroid hormone concentration influence birth weight.

Background: This hypothesis generating study explores second trimester maternal body mass index (BMI) during pregnancy and offspring neurocognitive development., Methods: Mothers and offspring served as controls in two earlier studies: 101 children at age two years and 118 children at age eight years., Results: Frequency of maternal BMI ≥30 kg/m 2 increased from 10% in 1987-1990 to 30% in 2004-2006 ( P < 0.001); the socioeconomic gradient became more pronounced. At age two, one or more BSID-III (Bayley Scales of Infant Development, 3rd Edition) scores <85 were more frequent with higher maternal BMI ( P = 0.029); regression analysis suggested an inverse relationship between language scores and BMI ( P = 0.054). Among eight-year-olds, one or more WISC-III (Wechsler Intelligence Scale for Children, 3rd edition) scores <85 increased with maternal BMI ( P = 0.017); regression analysis showed an inverse relationship between performance subscale IQ score and BMI ( P = 0.023)., Conclusion: Second trimester maternal obesity may be an independent risk factor for some aspects of children's neurocognitive development. Further study is indicated.

Background: Among euthyroid pregnant women in a large clinical trial, free thyroxine (FT4) measurements below the 2.5th centile were associated with a 17 lb higher weight (2.9 kg/m(2)) than in the overall study population. We explore this relationship further., Methods: Among 9351 women with second trimester thyrotropin (TSH) measurements between 1st and 98th centiles, we examine: (i) the weight/FT4 relationship; (ii) percentages of women in three weight categories at each FT4 decile; (iii) FT4 concentrations in three weight categories at each TSH decile; and (iv) impact of adjusting FT4 for weight--in the reference group and in 190 additional women with elevated TSH measurements., Results: FT4 values decrease steadily as weight increases (p<0.0001 by ANOVA) among women in the reference group (TSH 0.05-3.8 IU/L). TSH follows no consistent pattern with weight. When stratified into weight tertiles, 48% of women at the lowest FT4 decile are heavy; the percentage decreases steadily to 22% at the highest FT4 decile. Median FT4 is lowest in heaviest women regardless of the TSH level. In the reference group, weight adjustment reduces overall variance by 2.9%. Fewer FT4 measurements are at either extreme (below the 5th FT4 centile: 4.8% before adjustment, 4.7% after adjustment; above the 95th FT4 centile: 5.0% and 4.7%, respectively). Adjustment places more light weight women and fewer heavy women below the 5th FT4 centile; the converse above the 95th centile. Between TSH 3.8 and 5 IU/L, the FT4 percentage below the 5th FT4 centile is not elevated (3.8% before adjustment, 3.1% after adjustment). Percentage of FT4 values above the 95th centile, however, is lower (1.5% before adjustment, 0.8% after adjustment). Above TSH 5 IU/L, 25% of women have FT4 values below the 5th FT4 centile; weight adjustment raises this to 30%; no FT4 values remain above the 95th FT4 centile., Conclusions: During early pregnancy, TSH values are not associated with weight, unlike nonpregnant adults. Lower average FT4 values among heavy women at all TSH deciles partially explain interindividual differences in FT4 reference ranges. The continuous reciprocal relationship between weight and FT4 explains lower FT4 with higher weight. Weight adjustment refines FT4 interpretation.

Context: Lower neurocognitive development scores at age 2 yr have been reported in association with euthyroid hypothyroxinemia during early pregnancy., Objective: The objective of this study was to further explore this association with euthyroid hypothyroxinemia during early pregnancy., Design: This was an observational, nested case-control study., Setting: The study was conducted at physician offices and prenatal clinics throughout Maine., Study Subjects: Between May 2004 and March 2006, TSH was measured in 5734 women in conjunction with second-trimester Down syndrome screening. After completion of pregnancy, free T(4) was measured in stored second-trimester sera from euthyroid women (TSH 0.1-3.5 mIU/ml; n = 5560). Women with free T(4) at the third centile or less (n = 99) were matched with women whose free T(4) was at the 10th to the 90th centile (n = 99)., Interventions: There were no interventions., Main Outcome Measure: Bayley Scales of Infant Development (BSID III) were administered to the 198 offspring at age 2 yr. Scores for cognitive, language, and motor development were compared between matched pairs of offspring from the two groups before and after correcting for relevant variables., Results: Unadjusted BSID-III scores (cognitive, language, and motor) were lower by about 3% at age 2 yr among offspring of 98 hypothyroxinemic women (cases), reaching borderline significance for cognitive and motor scores. After adjustment for gestational age, the child's age at testing, maternal weight, and education, all differences diminished and became nonsignificant. Scores less than 85 were more frequent among case children but did not reach statistical significance (P = 0.14)., Conclusions: Isolated hypothyroxinemia during the second trimester is not associated with significantly lower BSID-III scores at age 2 yr, compared with scores for offspring of matched euthyroxinemic women.

Background: Anti-extractable nuclear antigen antibodies (anti-ENA) have diagnostic significance in systemic rheumatic disease (SRD)., Methods: Anti-ENA were tested in 1685/30,196 sera that were submitted sequentially for antinuclear antibody (ANA) testing. Frequency was stratified by ANA titer and pattern, by referral source, by submitted diagnosis and by patient age and sex., Results: Anti-ENA frequency increased with ANA titer (7.3% at < 32%-43.3% at ≥ 1024). Anti-histone (11.6%) and anti-SSA/SSB (13.9%) were the most frequent finding with a homo\xadgeneous pattern; anti-SSA/SSB (39.7%) and anti-RNP/anti-Sm (37.7%) were the most frequent finding with a speckled pattern. Sera with speckled, multiple and homogenous ANA patterns accounted for 92.6% of positive anti-ENA findings. At ANA titer ≥ 256, 29.2% of these sera were tested for anti-ENA, of which 41.2% were positive; frequency was higher with an accompanying diagnosis of SRD (53.5% vs. 36.5%, p < 0.004 by χ2-test) but not with referral by rheumatologists (43.5% vs. 35.9%) and did not differ by patient age or sex., Conclusions: Reflexive anti-ENA testing may be helpful among sera with ANA titer ≥ 256 and homogeneous, speckled or multiple patterns, irrespective of referral source or accompanying diagnosis. Further work is needed to evaluate the clinical impact of this protocol.

Background: We examined the relationship between antinuclear antibody (ANA) data and the presence of anti-double stranded DNA antibodies (anti-dsDNA)., Methods: De-identified demographic, ANA and anti-dsDNA data were available for 30,196 individuals aged ≥ 20 years, whose sera were submitted sequentially to our laboratory. When multiple sera were received for the same subject, data from the earliest sample were used. Anti-dsDNA frequency was stratified by ANA titer and pattern, sample referral source, and by the patient's age, gender, and diagnosis., Results: For sera with ANA titer ≥ 256 and an accompanying diagnosis of systemic lupus erythematosus, anti-dsDNA frequency was 53.7%, 35.3%, and 37.5% for homogeneous, speckled, or multiple ANA patterns, respectively. Among remaining sera with ANA titer ≥ 256, anti-dsDNA frequency was highest for the homogeneous pattern (15.9%). Anti-dsDNA frequency was three-fold higher among sera submitted by rheumatologists compared with other providers. However, its relative distribution by ANA pattern and titer was similar between these groups. Patient age and gender had no significant effect on anti-dsDNA frequency after ANA data were taken into account., Conclusions: ANA pattern and titer, together with the diagnosis submitted with the serum sample, can be used to guide decisions for reflexive anti-dsDNA testing in a clinical laboratory setting.

Objective: Estimate steroid sulfatase deficiency (STSD) prevalence among California's racial/ethnic groups using data from a previous study focused on prenatal detection of Smith-Lemli-Opitz syndrome (SLOS). SLOS and STSD both have low maternal serum unconjugated estriol (uE3) levels., Methods: Prevalence was estimated using three steps: listing clinically identified cases; modeling STSD frequency at three uE3 intervals using diagnostic urine steroid measurements; applying this model to determine frequency in pregnancies not providing urine., Results: Overall, 2151 of 777 088 pregnancies (0.28%) were screen positive; 1379 of these were explained and excluded. Fifty-four cases were diagnosed clinically among 707 remaining pregnancies with a male fetus. Urine steroid testing identified 74 additional STSD cases: 66 (89.2%) at uE3 values < 0.15 MoM, 8 (10.8%) at 0.15-0.20 MoM, and 0 (0%) at > 0.20 MoM. Modeling estimated 107.5 STSD cases among 370 pregnancies without urine samples. In males, STSD prevalence was highest among non-Hispanic Whites (1:1230) compared to Hispanics (1:1620) and Asians (1:1790), but differences were not significant. No STSD pregnancies were found among 65 screen positive Black women., Conclusion: The overall prevalence estimate of 1:1500 males is consistent with published estimates and is reasonable for counseling, except among Black pregnancies where no reliable estimate could be made., ((c) 2010 John Wiley & Sons, Ltd.)

Objective: To document the performance of second trimester maternal urine and serum steroid measurements for detecting fetal steroid sulfatase deficiency (STSD)., Methods: We studied detection rate and false positive rate (DR, FPR) of analytes in maternal urine [combinations of 16alpha-OH-dehydroepiandrosterone sulfate (16alpha-OH-DHEAS), 11beta-hydroxyandrosterone, total estriol] and serum [combinations of 16alpha-OH-DHEAS, 11beta-hydroxyandrosterone, total estriol, unconjugated estriol (uE3)]. Samples were obtained from pregnancies which were screen positive for Smith-Lemli-Opitz syndrome (SLOS)., Results: Among 1 079 301 pregnancies, 3083 (0.29%) were screen positive for SLOS. Urine and/or serum samples were available from 917 viable pregnancies with known gender. We assigned likelihood ratios (LRs) to steroid measurements from male fetuses with known STSD and unaffected female fetuses. An LR > or = 100 was present in urine from 84 of 86 STSD pregnancies (98% DR, 95% CI 92-99), along with 0 of 198 pregnancies with normal female fetuses (0.0% FPR, CI 0-1.9). LRs were > or = 100 in 4 of 129 female fetuses with major abnormalities (3% FPR). In maternal serum, steroid measurements performed less effectively, achieving a 71% DR for STSD at a 1.6% FPR., Conclusion: Maternal urine steroid measurements are effective for detecting STSD, including those with point mutations and those with full deletions.

Objectives: To evaluate whether obesity is associated with changes in pro-inflammatory and immunomodulatory cytokines in pregnancy., Methods: We performed a cross-sectional study using maternal serum from the early second trimester to examine biomarkers associated with inflammation in relation to maternal body mass index (n=80 total)., Results: Leptin and high sensitivity C-reactive protein were significantly different between groups and increased with increasing body mass index. MCP-1 was significantly increased in the morbidly obese mothers. Interleukin-2 exhibited a U-shaped relationship with body mass index; transforming growth factor-beta1 demonstrated a nonsignificant negative trend with body mass index; and the levels of hepatocyte growth factor and tumor necrosis factor-alpha did not differ appreciably between groups., Conclusions: Maternal obesity in pregnancy is associated with changes in cytokines, protein hormones and acute phase proteins in the second trimester, with an increase in MCP-1 in the morbid obesity category, and an increase in Leptin and hsCRP with increasing BMI category.

In a large multi-center trial involving prenatal screening for Smith-Lemli-Opitz syndrome (SLOS), we evaluated maternal urine and serum steroid analysis as a non-invasive diagnostic alternative to amniotic fluid sterol analysis. Candidate steroid ratios included: 7-dehydropregnanetriol/pregnanetriol (7-PT/PT), 8-dehydropregnanetriol/PT (8-PT/PT), the sum of these two (7 + 8-PT/PT), and dehydroestriol/estriol (DHE3/E3). Results are presented from 19 SLOS pregnancies, and 732 reference pregnancies that were screen positive for SLOS but negative on testing in amniotic fluid. Steroid ratios are expressed as multiples of the 75th centile (MoS), rather than multiples of the median, as most reference measurements were undetectable. All four urine ratios were available in 12 SLOS pregnancies; the median 7-PT/PT MoS was 94, with no overlap between affected and reference pregnancies in the second trimester. The separation between these groups increased by 27% per week. The other three ratios performed similarly in urine, with (7 + 8)-PT/PT ratios being marginally superior, due to fewer high reference outliers. All four steroid ratios in urine were diagnostic for SLOS between 14 and 22 weeks' gestation. In six SLOS pregnancies in which all serum analytes were measured, the median 7-PT/PT MoS was 71, and there was slight overlap in the second trimester. The separation increased by 28% per week. Steroid ratios in serum were less definitive than in urine but might be useful in certain circumstances, at 14 weeks gestation or later. Urine testing performance prior to 14 weeks gestation appears promising, but reference data are sparse., ((c) 2007 Wiley-Liss, Inc.)

Objective: Determine the relationship between positive screening interpretations for Smith-Lemli-Opitz syndrome (SLOS) and other fetal abnormalities, to aid counseling and diagnostic activities., Methods: An SLOS screening algorithm was incorporated into California's second-trimester screening program for Down syndrome and open neural tube defects (ONTDs). Between 2002 and 2004, 777 088 pregnant women were given an SLOS risk interpretation, using alpha-fetoprotein (AFP), unconjugated estriol (uE3), and human chorionic gonadotrophin (hCG) measurements. Outcomes were obtained in 98.8% of screen-positive pregnancies., Results: SLOS screen positives, alone or in combination with screen positives for other fetal disorders (Down syndrome, trisomy 18, ONTD), were associated with a high risk for fetal pathology. Type and frequency of chromosomal or anatomic abnormalities (or fetal death) varied according to screen-positive combination. Among 2018 screen-positive pregnancies, 644 fetal deaths were identified. Among the 1374 viable pregnancies, 519 were screen positive for SLOS alone; two SLOS cases and 51 other serious abnormalities were identified (14 aneuploidies; 37 anatomic). The remaining 855 were also screen positive for at least one other disorder; two SLOS cases and 327 other abnormalities were identified (180 aneuploidies; 157 anatomic)., Conclusion: For screening programs implementing the SLOS algorithm, the present data may be useful for counseling and to guide diagnostic studies.

Movement of body water from compartment to compartment during any time period is attributable to forces active within and upon each space. The result of these forces leads to transfer of water between intravascular and extravascular compartments, as well as shifts between extracellular and intracellular spaces. The importance of these shifts and of the associated mechanism was described by Ernest Starling in 1896 in very much the same manner as it is viewed today. The end result of fluid transfer and its physiological and laboratory consequences has not been fully appreciated. Despite awareness that fluid shifts can affect laboratory analytical results, little recent investigation has addressed the problem in the routine clinical laboratory. Thus, the potential for significant misinterpretation remains. For example, it is known that individual laboratory test values can vary widely, depending on many factors including the subject's posture during and immediately before phlebotomy, leading to significant changes in the interpretation of blood analyte values. Furthermore, a variety of ubiquitous environmental effects have additional impact on fluid distribution and thus on test values. In other words, patient hydration status is a major pre-analytical variable that needs to be addressed by the clinical laboratory. The need to adjust data for patient hydration status is especially important in the case of colloid analytes for which the dynamic range includes a narrow "gray zone" where hydration changes of a few percentage points can change the clinical implications. The crucial importance of this adjustment is underscored by the fact that neither the testing laboratory nor the clinician are aware of this unseen circumstance and are thus compelled to work with data that do not necessarily reflect the clinical situation.

Background: Smith-Lemli-Opitz syndrome (SLOS) is a rare hereditary disorder of cholesterol metabolism. We examine the feasibility of identifying SLOS as a part of a routine prenatal screening and evaluate diagnostic testing in maternal urine (or serum), in addition to amniotic fluid., Methods: Our SLOS risk algorithm utilized three Down syndrome screening markers (estimated 62% detection rate; 0.3% screen-positive rate). Fifteen North American prenatal screening programs implemented this algorithm., Results: SLOS risk was assigned to 1 079 301 pregnancies; 3083 were screen-positive (0.29%). Explanations were found for 1174, including 914 existing fetal deaths. Among the remaining pregnancies, 739 were screen-positive only for SLOS; 1170 were also screen-positive for other fetal disorders. Five of six SLOS pregnancies (83%) were screen-positive. All six had sonographic findings, were biochemically confirmed, and were terminated. Maternal urine steroid measurements were confirmatory in four cases tested. Second-trimester prevalence among Caucasians was 1 in 101 000 (1 in 130 000 overall; no cases in other racial groups). Among 739 pregnancies screen-positive only for SLOS, two cases were identified; another 69 had major fetal abnormalities., Conclusions: Although SLOS occurred less often than previously reported, many other major abnormalities were detected. Implementing the algorithm as an adjunct to Down syndrome screening may be feasible.

Background: There are currently no guidelines concerning additional laboratory testing for specific autoantibodies among anti-nuclear antibody-negative sera with an anti-cytoplasmic staining pattern identified by indirect immunofluorescence assay. Moreover, few data are available that address this laboratory situation., Methods: We performed specific autoantibody assays in 200 sera with an anti-nuclear antibody titer < or =1:32 and a cytoplasmic titer (undefined staining pattern) of > or =1:64, identified sequentially in the course of routine anti-nuclear antibody testing., Results: A total of 85 sera (42.5%) were positive in one (n=57) or more (n=28) of the specific autoantibody tests performed. Autoantibodies identified were antimitochondrial (15%), antimicrosomal (13%), anti-neutrophil cytoplasmic (10%), anti-smooth muscle (6%), anti-parietal cell (4%), and extractable nuclear antigen (8.5%, including histones, SSA, SSB, Sm, Jo-1 or Scl-70). A positive result in one or more of these assays was more frequent at anti-cytoplasmic titers > or =1:1024 (77.8%) than at titers of 1:64-1:128 (7%) (chi2=25.3, p<0.001)., Conclusions: The present data demonstrate that undefined anti-cytoplasmic staining in anti-nuclear antibody-negative sera is associated with, although not necessarily caused by, a high frequency and wide range of specific autoantibodies. Further work is needed before specific recommendations can be made concerning follow-up in subjects with this laboratory finding.

The two serum apolipoproteins in the highest concentrations, apolipoprotein (apo) AI and apolipoprotein B, and the apolipoprotein B/AI ratio are measured to assess clinical risk for atherosclerotic heart and peripheral vascular diseases. The study is based on a cohort of over 37,000 Caucasian individuals from northern New England measured in one laboratory by immunonephelometry using standardized reference materials. All samples received for protein analyses were accepted provided adequate identifying information was available. Laboratory and demographic information was entered into a single database for subsequent study. Our results show that for males without evidence of inflammation, values of apo AI change little through life. For females, however, values gradually increase until about 60 years of age then fall somewhat thereafter. Among adults, females have higher apo AI values on average, than males. Apo B values change significantly through life, increasing after the end of the second decade to a peak during the sixth decade, then falling thereafter. In the past, concern has been expressed that apo AI is an acute phase reactant (APR), thus complicating cardiovascular risk assessment. The effects of an APR (C-reactive protein >or=10 mg/L) on apo AI, but not on apo B, are measurable for both sexes, most noticeably beyond the age of 60 years in males and females. When values were expressed as age- and gender-specific multiples of the median (MoMs), the resulting distributions fit a log-Gaussian distribution well over a broad range. The size of the relatively homogenous cohort, by a standardized approach, provides a firm basis for comparison to preexisting reference intervals and for establishing a clinically useful and current reference interval for the three main apolipoprotein values.

In this 11th article in a series, reference values of serum levels alpha(2)-macroglobulin alpha(2)M) are examined. The study is based on a cohort of 40,420 Caucasian individuals from northern New England that were tested in our laboratory between 1994 and 2000. Measurements were standardized against Certified Reference Material (CRM 470)/Reference Preparation for Proteins in Human Serum (RPPHS) and the results analyzed using a previously described statistical approach. Individuals with unequivocal laboratory evidence of inflammation (C-reactive protein >10 mg/L) were excluded in one leg of the study and included in the other, confirming that alpha(2)M does not respond to acute phase drive in man. Nephrotic syndrome, diabetes mellitus, and chronic liver disease have significant effect on levels of alpha(2)M. Dramatic changes occur during life with males higher from birth to age 12, females thereafter have higher values until the ninth decade. When values were expressed as multiples of the age- and gender-specific median levels, the resulting distributions fitted a log-Gaussian distribution well over a broad range. When patient data are normalized in this manner, the distribution parameters can be used to assign a centile corresponding to an individual's measurement thus simplifying interpretation., (Copyright 2004 Wiley-Liss, Inc.)

The two serum proteins of the complement cascade in the highest concentrations, C3 and C4, respond to various conditions in much the same manner as do other positive acute-phase proteins. A major difference is that they are relatively sluggish in response to cytokine drive, requiring several days rather than hours to be detectably elevated by serial measurements. As with other acute-phase proteins, there are many processes that up- or down-regulate synthesis, including infection or inflammation, hepatic failure, and immune-complex formation. Clinicians may find it difficult to distinguish among these processes, because they often occur simultaneously. The situation is further complicated by genetic polymorphism, with rare instances of markedly reduced synthesis and circulating levels, and consequent vulnerability to infection. C3 and C4 are measured for clinical purposes to help define certain rheumatic and immunologically mediated renal diseases. Interpreting the measured blood levels of these two components requires one to consider the intensity of the inflammatory drive, the timing of the suspected clinical process, the production of complement-consuming immune complexes, and the possible existence of benign circumstances. In this fifth article in a series, reference ranges for serum levels of two complement proteins (C3 and C4) are examined. The study is based on a cohort of over 55,000 Caucasian individuals from northern New England, who were tested in our laboratory in 1994-1999. Measurements were standardized against certified reference material (CRM) 470/reference preparation for proteins in human serum (RPPHS), and analyzed using a previously described statistical approach. Individuals with unequivocal laboratory evidence of inflammation (C-reactive protein of 10 mg/L or higher) were excluded. Our results show that the levels of C3 and C4 change little during life and between the sexes, except that they increase slightly and then fall after age 20 in males and at about age 45 in females. When values were expressed as multiples of the age- and gender-specific median levels, the resulting distributions fitted a log-Gaussian distribution well over a broad range. When patient data are normalized in this manner, the distribution parameters can be used to assign a centile corresponding to an individual's measurement, thus simplifying interpretation., (Copyright 2004 Wiley-Liss, Inc.)