Community Surveillance of Respiratory Viruses Among Families in the Utah Better Identification of Germs-Longitudinal Viral Epidemiology (BIG-LoVE) Study.

BACKGROUND: This study: (1) describes the viral etiology of respiratory illness by prospectively collecting weekly symptom diaries and nasal swabs from families for 1 year, (2) analyzed data by reported symptoms, virus, age, and family composition, and (3) evaluated the duration of virus detection. METHODS: Twenty-six households (108 individuals) provided concurrent symptom and nasal swab data for 4166 person-weeks. The FilmArray polymerase chain reaction (PCR) platform (BioFire Diagnostics, LLC) was used to detect 16 respiratory viruses. Viral illnesses were defined as ≥1 consecutive weeks with the same virus detected with symptoms reported in ≥1 week. RESULTS: Participants reported symptoms in 23% and a virus was detected in 26% of person-weeks. Children younger than 5 years reported symptoms more often and were more likely to have a virus detected than older participants (odds ratio [OR] 2.47, 95% confidence interval [CI], 2.08-2.94 and OR 3.96, 95% CI, 3.35-4.70, respectively). Compared with single person households, individuals living with children experienced 3 additional weeks of virus detection. There were 783 viral detection episodes; 440 (56%) associated with symptoms. Coronaviruses, human metapneumovirus, and influenza A detections were usually symptomatic; bocavirus and rhinovirus detections were often asymptomatic. The mean duration of PCR detection was ≤2 weeks for all viruses and detections of ≥3 weeks occurred in 16% of episodes. Younger children had longer durations of PCR detection. CONCLUSIONS: Viral detection is often asymptomatic and occasionally prolonged, especially for bocavirus and rhinovirus. In clinical settings, the interpretation of positive PCR tests, particularly in young children and those who live with them, may be confounded.

All that wheezes is not asthma: A cautionary case study of shortness of breath in pregnancy.

BACKGROUND: Shortness of breath is a common physiological pregnancy presentation, secondary to both hormonal and mechanical effects. Its pathological causes are common (asthma exacerbation or infection); new-onset cardiac pathology is rarely considered. CASE: JC, a 39-year old G4P2T1, presented at 34 weeks' gestation with shortness of breath unrelieved by salbutamol. History included asthma, poly-drug abuse and smoking. Initial presentation was consistent with asthma exacerbation and she was treated as such. There was deterioration of symptoms and on re-examination raised jugular venous pressure was noted with bibasal lung crepitations and cardiac systolic murmur. Echocardiogram showed severe cardiomyopathy (left ventricular ejection fraction 20%). JC was commenced on diuretics, digoxin and fluid restricted. Labour was induced at 35 weeks' gestation, with birth of a healthy female infant (BW 2475 g) by elective assisted vaginal delivery. Cardiac function improved in subsequent weeks, confirming peripartum cardiomyopathy. CONCLUSION: Peripartum cardiomyopathy affects 1 in 2500-4000 live births. Over 90% of women regain normal cardiac function postpartum with optimal medical management. Peripartum cardiomyopathy presents a diagnostic conundrum as its primary symptoms mimic not only those of normal pregnancy but also a number of other, more common conditions. It is important to consider cardiac causes of shortness of breath initially, and vital to revisit an initial non-cardiac shortness of breath diagnosis if there is no sustained improvement with treatment. In this case, asthma history and initial wheeze on examination impeded correct diagnosis; however, the situation was re-evaluated and correct diagnosis made when the patient's shortness of breath deteriorated. Subsequent multidisciplinary management and birth in an appropriate setting facilitated the best outcome for both mother and baby.

Improving VBAC rates: the combined impact of two management strategies.

BACKGROUND: Caesarean section rates in Australia have risen to >30%, with repeat caesarean delivery the most common indication. One method of reducing caesarean delivery rates is to increase rates of vaginal birth after caesarean section (VBAC). AIMS: To determine the combined effect of two management strategies on the rates of successful VBAC in women experiencing their first pregnancy following primary caesarean section. METHODS: Prospective cohort study from May 2009 to October 2010 at a metropolitan Australian teaching hospital. The strategies studied were (i) allocating responsibility for VBAC candidates attempting labour to the hospital's three high-risk obstetric consultants and (ii) implementing a next birth after caesarean (NBAC) antenatal clinic designed to counsel and support women deciding on mode of birth for their next pregnancy after a primary caesarean section. Data were collected from Obstetrix, a NBAC logbook and medical records of 396 eligible women who gave birth during the study period. RESULTS: Overall VBAC rates improved from 17.2% in 2006 prior to implementation of the combined strategies, to 27.0% over the studied period (P < 0.001). Of those women who desired and attempted a VBAC, the success rate was 64.4%. Regression analysis identified an increased likelihood of attempted vaginal birth where malpresentation was the indication for previous caesarean, while Eastern Asian ethnicity was associated with increased likelihood of choosing repeat caesarean. CONCLUSIONS: A dedicated NBAC clinic and more consistent approach to labour management can help improve VBAC rates. Further targeted counselling towards women with previous malpresentation and/or East Asian descent may further improve VBAC attempt rates.

Incidence of venous thromboembolism in the setting of hematopoietic cell transplantation.

The underlying risk of venous thromboembolism (VTE) is unclear in patients undergoing hematopoietic cell transplantation (HCT). As such, these patients should still be considered at risk for development of VTE due to factors such as their underlying malignancy and the marked inflammatory state that develops from treatment. The purpose of this study was to characterize the incidence of VTE in patients undergoing HCT. Retrospective chart review of patients from the Indiana University Stem Cell Transplant Unit treated between January 1, 2008, and May 24, 2011. Patients were older than 18 years and had undergone HCT. The primary objective was to analyze the incidence of VTE in patients undergoing autologous HCT versus allogeneic HCT. Secondary objectives included documentation of VTE treatment strategies and time to occurrence of VTE. Of the 567 patients who underwent autologous HCT, 14 developed VTE (2.5%), whereas 5 of the 180 patients who underwent allogeneic HCT developed VTE (2.8%; P = 1.000). The median time to development of VTE from admission for HCT was 12 days in the autologous HCT arm versus 19 days in the allogeneic HCT arm (P = 0.610). The most commonly used VTE treatment strategy was enoxaparin (12 out of 19 VTEs). This study illustrates that VTE does occur rarely in patients who have undergone HCT. The optimal treatment regimen in this population requires further evaluation. Until a reliable protocol for treatment and evidence for risk factors are established, providers should be vigilant for occurrence of VTE in these patients.

Spontaneous septostomy in monochorionic diamniotic twins resulting in cord entanglement and fetal demise.

Monoamniotic twins are known to be at risk of cord entanglement, and have an elevated perinatal morbidity and mortality associated with this. We present a case of cord entanglement in a monochorionic diamniotic (MCDA) twin pregnancy thought to be due to spontaneous septostomy. Unfortunately the cord entanglement was detected postpartum, and ultimately resulted in the demise of one of the twins. Literature review reveals this as a recognised, albeit rare, phenomena.

Molecular genetics and impact of residual in vitro phenylalanine hydroxylase activity on tetrahydrobiopterin responsiveness in Turkish PKU population.

BACKGROUND: The prevalence of phenylalanine hydroxylase (PAH)-deficient phenylketonuria (PKU) in Turkey is high (1 in 6500 births), but data concerning the genotype distribution and impact of the genotype on tetrahydrobiopterin (BH(4)) therapy are scarce. OBJECTIVE: To characterize the phenotypic and genotypic variability in the Turkish PKU population and to correlate it with physiological response to BH(4) challenge. METHODS: We genotyped 588 hyperphenylalaninemic patients and performed a BH(4) loading test (20mg/kg bw) in 462 patients. Residual PAH activity of mutant proteins was calculated from available in vitro expression data. Data were tabulated in the BIOPKU database (www.biopku.org). RESULTS: Eighty-eight mutations were observed, the most common missense mutations being the splice variant c.1066-11G>A (24.6%). Twenty novel mutations were detected (11 missense, 4 splice-site, and 5 deletion/insertions). Two mutations were observed in 540/588 patients (91.8%) but in 9 patients atypical genotypes with >2 mutations were found (8 with p.R155H in cis with another variant) and in 19 patients mutations were found in BH(4)-metabolizing genes. The most common genotype was c.1066-11G>A/c.1066-11G>A (15.5%). Approximately 22% of patients responded to BH(4) challenge. A substantial in vitro residual activity (average >25% of the wild-type enzyme) was associated with response to BH(4). In homozygous genotypes (n=206), both severity of the phenotype (r=0.83) and residual PAH activity (r=0.85) correlate with BH(4) responsiveness. CONCLUSION: Together with the BH(4) challenge, these data enable the genotype-based classification of BH(4) responsiveness and document importance of residual PAH activity. This first report of a large-scale genotype assessment in a population of Turkish PKU patients also documents a high prevalence (47%) of the severe classic phenotype.

Identifying sequence variants in the human mitochondrial genome using high-resolution melt (HRM) profiling.

Identifying mitochondrial DNA (mtDNA) sequence variants in human diseases is complicated. Many pathological mutations are heteroplasmic, with the mutant allele represented at highly variable percentages. High-resolution melt (HRM or HRMA) profiling was applied to comprehensive assessment of the mitochondrial genome and targeted assessment of recognized pathological mutations. The assay panel providing comprehensive coverage of the mitochondrial genome utilizes 36 overlapping fragments (301-658 bp) that employ a common PCR protocol. The comprehensive assay identified heteroplasmic mutation in 33 out of 33 patient specimens tested. Allele fraction among the specimens ranged from 1 to 100%. The comprehensive assay panel was also used to assess 125 mtDNA specimens from healthy donors, which identified 431 unique sequence variants. Utilizing the comprehensive mtDNA panel, the mitochondrial genome of a patient specimen may be assessed in less than 1 day using a single 384-well plate or two 96-well plates. Specific assays were used to identify the myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) mutation m.3243A>G, myoclonus epilepsy, ragged red fibers (MERRF) mutation m.8344A>G, and m.1555A>G associated with aminoglycoside hearing loss. These assays employ a calibrated, amplicon-based strategy that is exceedingly simple in design, utilization, and interpretation, yet provides sensitivity to detect variants at and below 10% heteroplasmy. Turnaround time for the genotyping tests is about 1 hr.

Misoprostol to induce labour: a review of its use in a NSW hospital.

BACKGROUND: Induction of labour (IOL) is a common procedure in maternity care. Misoprostol is a prostaglandin E(1) analogue that is effective, cheap and easily stored but not licensed for this use in Australia. Despite evidence supporting the use of misoprostol for IOL, few Australian maternity units use it. AIMS: To review the outcomes of women who received vaginal misoprostol for IOL. METHODS: A retrospective review of all births induced with vaginal misoprostol from July 1998 to October 2005 at one hospital in New South Wales. Women who had an IOL for multiple pregnancy, known fetal death or congenital abnormality were excluded. RESULTS: In total, 1998 women with a normal, viable, single fetus received vaginal misoprostol for IOL. More than half (57%) of women did not require augmentation during labour. More than one third (37%) had epidural analgesia, 25% had an emergency Caesarean section, 7% had a post-partum haemorrhage and 16% of babies were admitted to the special care nursery. Uterine rupture occurred in two women, one of whom had a history of uterine surgery. There were two neonatal deaths, both because of Group B Streptococcus infection. CONCLUSIONS: In this cohort of women, misoprostol was an effective and safe agent to induce labour. Recent legal concerns at this hospital make its future use in normal clinical practice unlikely.

Use of the Atad catheter for the induction of labour in women who have had a previous Caesarean section--a case series.

Abstract The induction of labour of women with an unfavourable cervix who have had a previous Caesarean section, is challenging. Eight women who had a Caesarean section in a previous pregnancy had labour induced with an Atad catheter. Six out of eight women achieved labour, and two out of these six women had a vaginal delivery. An Atad catheter is an option for women needing induction of labour with an unfavourable cervix who have had a Caesarean section previously and are motivated to have a vaginal delivery.