Factors affecting turnaround time of SARS-CoV-2 sequencing for inpatient infection prevention and control decision making: analysis of data from the COG-UK HOCI study.

BACKGROUND: Barriers to rapid return of sequencing results can affect the utility of sequence data for infection prevention and control decisions. AIM: To undertake a mixed-methods analysis to identify challenges that sites faced in achieving a rapid turnaround time (TAT) in the COVID-19 Genomics UK Hospital-Onset COVID-19 Infection (COG-UK HOCI) study. METHODS: For the quantitative analysis, timepoints relating to different stages of the sequencing process were extracted from both the COG-UK HOCI study dataset and surveys of study sites. Qualitative data relating to the barriers and facilitators to achieving rapid TATs were included from thematic analysis. FINDINGS: The overall TAT, from sample collection to receipt of sequence report by infection control teams, varied between sites (median 5.1 days, range 3.0-29.0 days). Most variation was seen between reporting of a positive COVID-19 polymerase chain reaction (PCR) result to sequence report generation (median 4.0 days, range 2.3-27.0 days). On deeper analysis, most of this variability was accounted for by differences in the delay between the COVID-19 PCR result and arrival of the sample at the sequencing laboratory (median 20.8 h, range 16.0-88.7 h). Qualitative analyses suggest that closer proximity of sequencing laboratories to diagnostic laboratories, increased staff flexibility and regular transport times facilitated a shorter TAT. CONCLUSION: Integration of pathogen sequencing into diagnostic laboratories may help to improve sequencing TAT to allow sequence data to be of tangible value to infection control practice. Adding a quality control step upstream to increase capacity further down the workflow may also optimize TAT if lower quality samples are removed at an earlier stage.

Evaluating the cost implications of integrating SARS-CoV-2 genome sequencing for infection prevention and control investigation of nosocomial transmission within hospitals.

BACKGROUND: The COG-UK hospital-onset COVID-19 infection (HOCI) trial evaluated the impact of SARS-CoV-2 whole-genome sequencing (WGS) on acute infection, prevention, and control (IPC) investigation of nosocomial transmission within hospitals. AIM: To estimate the cost implications of using the information from the sequencing reporting tool (SRT), used to determine likelihood of nosocomial infection in IPC practice. METHODS: A micro-costing approach for SARS-CoV-2 WGS was conducted. Data on IPC management resource use and costs were collected from interviews with IPC teams from 14 participating sites and used to assign cost estimates for IPC activities as collected in the trial. Activities included IPC-specific actions following a suspicion of healthcare-associated infection (HAI) or outbreak, as well as changes to practice following the return of data via SRT. FINDINGS: The mean per-sample costs of SARS-CoV-2 sequencing were estimated at £77.10 for rapid and £66.94 for longer turnaround phases. Over the three-month interventional phases, the total management costs of IPC-defined HAIs and outbreak events across the sites were estimated at £225,070 and £416,447, respectively. The main cost drivers were bed-days lost due to ward closures because of outbreaks, followed by outbreak meetings and bed-days lost due to cohorting contacts. Actioning SRTs, the cost of HAIs increased by £5,178 due to unidentified cases and the cost of outbreaks decreased by £11,246 as SRTs excluded hospital outbreaks. CONCLUSION: Although SARS-CoV-2 WGS adds to the total IPC management cost, additional information provided could balance out the additional cost, depending on identified design improvements and effective deployment.

Vaginal birth after Cesarean rates are declining rapidly in the rural state of Maine.

OBJECTIVE: The American College of Obstetricians and Gynecologists (ACOG) revised its practice bulletin on vaginal birth after Cesarean (VBAC) in October 1998 and July 1999 to require the presence of a surgeon, anesthesiologist and operating personnel throughout the trial of labor for patients with prior Cesarean. This study measures the change in VBAC rates from 1998 to 2001 and examines possible reasons for this change. STUDY DESIGN: We examined birth certificate and hospital data in the State of Maine from 1998 to 2001. Hospital-specific rates for primary Cesareans, total Cesareans, repeat Cesareans and vaginal deliveries after previous Cesarean were obtained. Additionally, we surveyed current obstetric-care providers in Maine regarding reasons for change in VBAC rates at their institutions. RESULTS: VBAC rates declined by over 50% from 30.1 to 13.1%. The total Cesarean rate climbed from 19.4 to 24.0%. The most commonly reported reason for decrease in VBAC varied depending on whether a practitioner's hospital met ACOG guidelines. CONCLUSION: A marked decline in VBAC occurred after the change in ACOG vaginal birth after Cesarean policy. Multiple factors have contributed to this decline, including patients refusing VBAC after counseling and inability of institutions to meet ACOG guidelines.

Fetal atrial septal aneurysm. Prenatal diagnosis by ultrasonography.

OBJECTIVE: To assess prenatal diagnosis by ultrasonography in five cases of fetal atrial septal aneurysm. STUDY DESIGN: Five cases of fetal atrial septal aneurysm were diagnosed prenatally by ultrasound. Postpartum fetal cardiac echocardiography was performed in three of five infants from the first to the fourth day of life. The medical records of the five cases were reviewed and analyzed after delivery. RESULTS: Echocardiograms confirmed atrial septal aneurysm in two of the three neonates. One of the two infants was also found to have a patent foramen ovale, and the other infant had patent duct arteriosis in addition to a patent foramen ovale. Two had fetal cardiac arrythmias that resolved after birth. CONCLUSION: Atrial septal aneurysm in fetuses may be a natural transition in spontaneous closure of the associated patent foramen ovale or septal defect. The same phenomenon has been found in children and infants. Due to the uniqueness of the fetal circulation, atrial septal aneurysm may predispose to fetal arrythmias.

Prenatal diagnosis of fetal bladder and cloacal exstrophy by ultrasound. A report of three cases.

BACKGROUND: Bladder and cloacal exstrophy can be diagnosed with prenatal ultrasound. CASES: Three cases of bladder and cloacal exstrophy were diagnosed prenatally by ultrasound and confirmed at birth. The ultrasound findings were a soft tissue mass in the lower abdominal wall (which appeared larger and more heterogeneous in cloacal exstrophy than in bladder exstrophy), absent bladder, malformation of the external genitalia and normal kidneys along with normal amniotic fluid volume. CONCLUSION: Prenatal diagnosis of these defects will allow appropriate referrals prior to birth.

Hepatic vascular calcification: an early second trimester sonographic feature of idiopathic infantile arterial calcinosis.

Prenatal sonographic diagnosis of idiopathic infantile arterial calcinosis has been limited to the third trimester. We report a monozygotic twin gestation for which an 18-week ultrasound detected the unique finding of hepatic vascular calcification as the earliest feature of the disorder. In contrast to previous reports, second-trimester ultrasound may permit timely diagnosis of idiopathic infantile arterial calcinosis.

Bilateral inferior petrosal sinus corticotropin sampling with corticotropin-releasing hormone stimulation in a pregnant patient with Cushing's syndrome.

A patient was diagnosed with Cushing's syndrome during her first pregnancy. Bilateral simultaneous inferior petrosal sinus corticotropin sampling with corticotropin-releasing hormone stimulation was performed before transphenoidal pituitary adenomectomy, with successful localization of the pituitary adenoma. Her Cushing's syndrome was controlled postoperatively with resolution of hypertension. This case report demonstrates that the procedure of bilateral simultaneous inferior petrosal venous corticotropin sampling can be safely performed during pregnancy.

Fetal cardiac effects of oral ritodrine tocolysis.

The beta-sympathomimetic oral tocolytic ritodrine can cause maternal tachycardia and hypotension, and may cross the placenta. A new echocardiographic technique has been developed to explore fetal and placental ritodrine effects. Values in 76 healthy historic controls were compared to 18 studies in 16 patients performed while receiving stable oral ritodrine therapy, measured both at baseline and 30 minutes after a dose. Data collected included maternal pulse and blood pressure (BP), fetal cerebral and umbilical Doppler waveforms, and fetal heart rate. A new index of fetal myocardial contractility, combined ventricular shortening fraction, was derived from two-dimensionally directed M-mode. Maternal pulse and BP, fetal heart rate and heart size, and all Doppler indices were normal, without demonstrable dose-response effects. In the control subjects, combined ventricular shortening fraction fell with increasing gestational age (combined ventricular shortening fraction = -0.27 estimated gestational age + 49; r = 0.27; P < or = 0.02; standard error of the estimate, 11%). However, combined ventricular shortening fraction in ritodrine patients was abnormally decreased in 72% of cases. The mean index in normal subjects was 43 +/- 5%, but in ritodrine patients it was only 31%. We conclude that a history of premature labor or oral ritodrine, or both, is associated with reduced shortening fraction. Since there was no change in placental resistance, cerebral hypoxia, fetal heart rate, or heart size (preload), then low shortening fraction may be due to increased fetal systemic vascular resistance (BP) or decreased myocardial contractility.

Measurement of fetal nasal width by ultrasonography.

OBJECTIVE: This study was designed to determine the range of normal fetal nasal width by ultrasonography, which may be beneficial for detection of trisomy 21 and other chromosomal abnormalities. We hypothesize that a wide, saddle-shaped nose, which is one of the clinical neonatal anatomic features of trisomy 21, can be diagnosed prenatally. STUDY DESIGN: Fetal nasal width diameter was measured on 782 normal white fetuses by ultrasonography. Gestational ages ranged from 13.8 to 40.4 weeks. Mean and SD of fetal width diameter was calculated weekly by gestational age to establish normal values. RESULTS: The fetal nasal width increased as a function of gestational age, showing a polynomial curve during pregnancy (r = 0.912, p = 0.002). With use of mean +/- 1 SD as a cutoff value, the results showed a sensitivity of 80% with a specificity of 67% and a positive predictive value of 2.2% with a negative predictive value of 99.7% for the diagnosis of trisomy 21. CONCLUSION: The fetal nasal width diameter may be used as a biometric measurement and may be useful to identify trisomy 21 or other chromosomal abnormalities in conjunction with other already defined parameters used in a genetic ultrasonographic screen.

Highly abnormal maternal inhibin and beta-human chorionic gonadotropin levels along with severe HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome at 17 weeks' gestation with triploidy.

A 17-week pregnancy complicated by severe hypertension is reported. The fetus had multiple anomalies and was found to have triploidy. Assay of maternal serum markers for trisomy 21 revealed elevated levels of inhibin (137.51 multiples of the median) and human chorionic gonadotropin (41.51 multiples of the median).

Prenatal diagnosis of nonmosaic trisomy 9 and related ultrasound findings at 11.7 weeks.

Trisomy 9 is a relatively rare chromosomal abnormality. There have been no reports of first trimester ultrasound findings associated with mosaic or nonmosaic trisomy 9 in the literature. A case of nonmosaic trisomy 9 diagnosed prenatally with ultrasound findings at 11.7 weeks gestation is presented along with associated abnormal ultrasound findings.

Successful planned pregnancy following endometrial ablation with the YAG laser.

In selected patients who previously have undergone YAG laser ablation of the endometrium and who have demonstrated normal intrauterine architecture, pregnancy as a planned event may be a reasonable and safe option.

Estimation of fetal weight: mean value from multiple formulas.

Mean fetal weight value from multiple formulas was compared to fetal weight from single formulas. Data were collected on 975 fetuses who had estimation of fetal weight by ultrasonography within 1 week before birth. Improvement in estimation of fetal weight occurred using either the mean value of multiple formulas or the Hadlock BPD/FL/AC, in comparison to fetal volume, BPD/AC, or FL/AC. BPD/FL/AC appeared to provide the best estimate of true weight in terms of overall accuracy and in terms of not showing a trend in either overestimating or underestimating true weight.

Normal midtrimester (17-20 weeks) genetic sonogram decreases amniocentesis rate in a high-risk population.

OBJECTIVE: To evaluate a screening protocol using advanced maternal age, triple-marker screening, and genetic sonography. METHODS: We compared adverse chromosomal outcomes of pregnancy in 1556 women referred for increased risk of aneuploidy because of either advanced maternal age or triple-marker test results. Patients were counseled about the results of the triple-marker test and subsequent sonography, which led to a patient decision of whether to pursue amniocentesis. Fetal measurements and structural abnormalities were compared with chromosomal findings. When patients elected amniocentesis, karyotypes were obtained. RESULTS: Genetic sonography reduced the rate of amniocentesis by 61% overall and by 40% when compared with an alpha-fetoprotein profile alone. The sensitivity of sonography combined with the triple-marker screen for the detection of trisomy 21 was 87% compared with 91% for the triple-marker screen alone. CONCLUSIONS: This study confirmed that sonographic findings in a targeted population, in combination with other risk markers (advanced maternal age and triple-marker screening), can be used to assess the risk of aneuploidy. Biometry provides additional information for assessing the risk of aneuploidy. Combining advanced maternal age, serum triple-marker screening, and sonographic screening may provide better risk prediction for use in clinical counseling.