The Association between Sickle Cell Disease and Postpartum Severe Maternal Morbidity.

OBJECTIVE: To compare the risk of severe maternal morbidity (SMM) from the delivery admission to 42 days' postdischarge among persons with sickle cell disease (SCD) to those without SCD. STUDY DESIGN: This retrospective cohort study included deliveries ≥20 weeks' gestation at an urban safety net hospital in Atlanta, GA from 2011 to 2019. The exposure was SCD diagnosis. The outcome was a composite of SMM from the delivery admission to 42 days' postdischarge. SMM indicators as defined by the Centers for Disease Control and Prevention were identified using the International Classification of Diseases, Ninth and Tenth Revisions (ICD-9/10) codes; transfusion of blood products and sickle cell crisis were excluded. RESULTS: Of N = 17,354 delivery admissions, n = 92 (0.53%) had SCD. Persons with SCD versus without SCD had an increased risk of composite SMM (15.22 vs. 2.29%, p < 0.001), acute renal failure (6.52 vs. 0.71%, p < 0.001), acute respiratory distress syndrome (4.35 vs. 0.17%, p < 0.001), puerperal cerebrovascular disorders (3.26 vs. 0.10%, p < 0.001), sepsis (4.35 vs. 0.42%, p < 0.01), air and thrombotic embolism (5.43 vs. 0.10%, p < 0.001), and ventilation (2.17 vs. 0.09%, p < 0.01). Ultimately, those with SCD had an approximately 6-fold higher incidence risk ratio of SMM, which remained after adjustment for confounders (adjusted incidence risk ratio [aIRR]: 5.96, 95% confidence interval [CI]: 3.4-9.19, p < 0.001). Persons with SCD in active vaso-occlusive crisis at the delivery admission had an approximately 9-fold higher risk of SMM up to 42 days' postdischarge compared with those with SCD not in crisis at the delivery admission (incidence: 25.71 vs. 8.77%, p < 0.05; aIRR: 8.92, 95% CI: 4.5-10.04, p < 0.05). Among those with SCD, SMM at the delivery admission was primarily related to renal and cerebrovascular events, whereas most postpartum SMM was related to respiratory events or sepsis. CONCLUSION: SCD is significantly associated with an increased risk of SMM during the delivery admission and through 42 days' postdischarge. Active crisis at delivery further increases the risk of SMM. KEY POINTS: · Sickle cell disease was associated with an approximately 6-fold increased risk of SMM.. · Active vaso-occlusive crisis at delivery was associated with an approximately 9-fold increased risk of SMM.. · 48% of SMM events in persons with SCD occurred postpartum and were respiratory- or sepsis-related..

Cutaneous Permeation of a Percutaneously Applied Glucocorticoid Using Plant-Based Anionic Phospholipids in Hydrogenated Vegetable Oil: A Preliminary Study.

Purpose: It is important that, when corticosteroids are used therapeutically, concentrations be reduced as much as possible to mitigate potential adverse events and side effects. This preliminary study compares the permeation for the delivery of a corticosteroid in a 1% hydrocortisone-supplemented topical cream containing anionic polar phospholipids (APP) in hydrogenated vegetable oil (triglyceride) versus a market-leading 1% hydrocortisone in a mineral hydrocarbon-based skin cream. Methods: Using the Franz diffusion cell method with cadaveric skin, the permeation of a 1% hydrocortisone-supplemented cream containing APP (test preparation) was compared with a commercially available 1% hydrocortisone cream (control preparation). The principal APP in the test preparation were phosphatidylinositol, phosphatidylserine and phosphatidylglycerol. Permeation was determined at 4 and 8 h time intervals. Results: The permeation values for the 1% hydrocortisone supplemental APP cream (test preparation) were comparatively very high 1180 ng/cm2 at 4 h and 2173 ng/cm2 at 8 h, in contrast to the 1% hydrocortisone cream (control preparation) values of 13 ng/cm2 at 4 h and 98 ng/cm2 at 8 h. Permeation of skin cream increased significantly from 0 to 4 and 8 h, when comparing the APP test preparation with the control preparation (p < 0.001). This translates, respectively, into the 90-fold greater and a 20-fold greater penetration of the test preparation APP cream over the 1% hydrocortisone cream at 4 h and 8 h time points. Conclusions: This preliminary study demonstrates the enhanced permeation of 1% hydrocortisone when applied topically to the skin in an APP skin cream vehicle. This enhanced permeation suggests the potential use of APP technology to deliver therapeutically effective hydrocortisone treatment to the skin at markedly reduced concentrations of steroid. As such, APP technology may offer an improved approach to the treatment of dermatoses associated with inflammatory diseases and conditions requiring prolonged topical corticosteroid therapy.

Genome-Scale Phylogeny and Evolutionary Analysis of Ross River Virus Reveals Periodic Sweeps of Lineage Dominance in Western Australia, 1977-2014.

Ross River virus (RRV), an alphavirus of the Togaviridae family, is the most medically significant mosquito-borne virus of Australia. Past RRV phylogenetic and evolutionary analyses have been based on partial genome analyses only. Three geographically distinct RRV lineages, the Eastern, the Western, and the supposedly extinct North-Eastern lineage, were classified previously. We sought to expand on past phylogenies through robust genome-scale phylogeny to better understand RRV genetic diversity and evolutionary dynamics. We analyzed 106 RRV complete coding sequences, which included 13 genomes available on NCBI and 94 novel sequences derived for this study, sampled throughout Western Australia (1977-2014) and during the substantial Pacific Islands RRV epidemic (1979-1980). Our final data set comprised isolates sampled over 59 years (1959-2018) from a range of locations. Four distinct genotypes were defined, with the newly described genotype 4 (G4) found to be the contemporary lineage circulating in Western Australia. The prior geographical classification of RRV lineages was not supported by our findings, with evidence of geographical and temporal cocirculation of distinct genetic groups. Bayesian Markov chain Monte Carlo (MCMC) analysis revealed that RRV lineages diverged from a common ancestor approximately 94 years ago, with distinct lineages emerging roughly every 10 years over the past 50 years in periodic bursts of genetic diversity. Our study has enabled a more robust analysis of RRV evolutionary history and resolved greater genetic diversity that had been previously defined by partial E2 gene analysis.IMPORTANCE Ross River virus (RRV) causes the most common mosquito-borne infection in Australia and causes a significant burden of suffering to infected individuals as well as being a large burden to the Australian economy. The genetic diversity of RRV and its evolutionary history have so far only been studied using partial E2 gene analysis with a limited number of isolates. Robust whole-genome analysis has not yet been conducted. This study generated 94 novel near-whole-genome sequences to investigate the evolutionary history of RRV to better understand its genetic diversity through comprehensive whole-genome phylogeny. A better understanding of RRV genetic diversity will enable better diagnostics, surveillance, and potential future vaccine design.

Corneal absorption of glycerylphosphorylcholine.

This study documents the absorption of glycerylphosphorylcholine (GPC) into corneas ex vivo. Corneas in quadruplicate were incubated in preservation medium containing 30 mM GPC, which is used as a reference marker. The GPC reference marker is used to calibrate 31P nuclear magnetic resonance (NMR) spectral chemical-shift positions for identification of phosphatic metabolites and to calculate intracorneal pH in intact tissues ex vivo. Following baseline NMR ex vivo analysis, corneas were stored in eye bank chambers in preservation medium containing 30 mM GPC at 4 °C overnight for 8 h. After returning to room temperature, NMR analysis was repeated on the same corneas in fresh GPC-free preservation medium. NMR analysis also was performed on the 30 mM GPC preservation medium alone from the eye bank chambers for detection of the GPC signal. The elevated GPC signal unexpectedly persisted in corneas incubated at 4 °C overnight even though GPC was not present in the fresh GPC-free preservation medium. In fact, the concentration of GPC in the intact cornea was many times higher than that found in the cornea endogenously. The levels of phosphatic metabolites and the energy modulus, after subtracting the spectral contribution of the 30 mM exogenous GPC, as well as the intracorneal pH remained unchanged from pre-refrigeration analyses. Corneas also retained transparency through the time-course of this study irrespective of temperature or change in temperature. The GPC signal in the NMR analysis of the preservation medium from the eye bank chambers was nearly undetectable. GPC was unexpectedly absorbed into the corneal tissue without detectable metabolic or physical toxicity. The intracorneal uptake of GPC at reduced temperatures parallels the increase in GPC that occurs naturally in muscle tissue in animals during wintering periods and the very high concentration of GPC in sperm, a cryogenically compatible cell, suggestive of a potential role for GPC in cryopreservation.

Impact of the occupational environment of a submerged submarine on cardiometabolic health of Royal Navy submariners.

OBJECTIVE: To determine the effect of prolonged exposure to a submarine environment on biomarkers of cardiometabolic risk in Royal Navy (RN) submariners. METHODS: Serum lipids (cholesterol (C), triglyceride (TG), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), non-HDL-C), glucose, insulin and anthropometrics were compared within three RN submarine crews before and after submerged patrols of 12 or 6 weeks, and with a crew that remained ashore (SUB-HOME). Dietary intake and activity patterns were self-reported during each patrol. Differences were assessed in crew characteristics using one-way analysis of variance and in serum lipids using paired t-tests. RESULTS: Postpatrol, the mean body weight of submerged crews decreased (-1.4±4.2 kg, p=0.0001), but increased in SUB-HOME (1.9±1.8 kg, p=0.0001). Modest improvements in serum lipids (mean individual change (mmol/L); C=-0.3±0.7, p=0.0001; TG=-0.3±0.7, p=0.0001; HDL-C=-0.1±0.3, p=0.0001; non-HDL-C=-0.2±0.6, p=0.012), glucose (-0.2±0.5, p=0.0001) and insulin (-1.5±4.6 mU/L, p=0.001) were observed in submerged crews. Changes in serum lipids were positively associated with changes in body weight within crews combined. Energy intake was maintained during submerged patrols but was lower compared with non-submerged (11 139±2792 vs. 9617±2466 kJ, p=0.001; 11 062±2775 vs. 9632±2682 kJ, p=0.003). CONCLUSIONS: The environment of a submerged submarine produced no adverse effects on serum biomarkers of cardiometabolic risk in crew. Conversely, modest improvements in these biomarkers were associated with a decrease in body weight.

Adverse perinatal outcomes are more frequent in pregnancies with a low fetal fraction result on noninvasive prenatal testing.

OBJECTIVE: This study aimed to assess risk of an adverse perinatal outcome for women with a low fetal fraction (LFF) result on noninvasive prenatal testing (NIPT). STUDY DESIGN: A retrospective cohort study whereby women with an LFF result were compared with women who had a sufficient fetal fraction (SFF) result on NIPT. Inclusion criteria were singleton pregnancies with quantification of fetal fraction and pregnancy outcome information. Primary outcome was a composite of any of the following: miscarriage, fetal demise, neonatal death, preterm birth, pregnancy-associated hypertensive disorder, placental abruption, and low birth weight. RESULTS: Three hundred forty-eight (94%) women had an SFF result, and 22 (6%) women had an LFF result. The mean gestational age at the time of NIPT was comparable for both groups. Women with an LFF result were more likely to be African American (86% vs 52%; p = 0.007) and have a higher body mass index (BMI) (mean BMI = 37 kg/m(2) vs BMI = 29 kg/m(2) ; p ≤ 0.001) than women with an SFF result. The composite outcome was significantly more common in the LFF group (59.1% vs 29%; p = 0.003). After adjusting for race and BMI, LFF remained independently associated with adverse perinatal outcome with adjusted odds ratio = 2.5 (95% confidence interval 1.01-6.2; p = 0.049). CONCLUSIONS: Women with an LFF result have an increased likelihood of an adverse pregnancy outcome.

Fetal Implications of Diagnostic Radiation Exposure During Pregnancy: Evidence-based Recommendations.

The purpose of this article is to review the fetal and long-term implications of diagnostic radiation exposure during pregnancy. Evidence-based recommendations for radiologic imaging modalities utilizing exposure of diagnostic radiation during pregnancy, including conventional screen-film mammography, digital mammography, tomosynthesis, and contrast-enhanced mammography are described.

Perinatal outcomes in HIV positive pregnant women with concomitant sexually transmitted infections.

OBJECTIVE: To evaluate whether HIV infected pregnant women with concomitant sexually transmitted infection (STIs) are at increased risk of adverse perinatal and neonatal outcomes. METHODS: We conducted a cohort study of HIV positive women who delivered at an inner-city hospital in Atlanta, Georgia, from 2003 to 2013. Demographics, presence of concomitant STIs, prenatal care information, and maternal and neonatal outcomes were collected. The outcomes examined were the association of the presence of concomitant STIs on the risk of preterm birth (PTB), postpartum hemorrhage, chorioamnionitis, preeclampsia, intrauterine growth restriction, small for gestational age, low Apgar scores, and neonatal intensive care admission. Multiple logistic regression was performed to adjust for potential confounders. RESULTS: HIV positive pregnant women with concomitant STIs had an increased risk of spontaneous PTB (odds ratio (OR) 2.11, 95% confidence interval [CI] 1.12-3.97). After adjusting for a history of preterm birth, maternal age, and low CD4+ count at prenatal care entry the association between concomitant STIs and spontaneous PTB persisted (adjusted OR 1.96, 95% CI 1.01-3.78). CONCLUSIONS: HIV infected pregnant women with concomitant STIs relative to HIV positive pregnant women without a concomitant STI are at increased risk of spontaneous PTB.

Rainfall and sentinel chicken seroconversions predict human cases of Murray Valley encephalitis in the north of Western Australia.

BACKGROUND: Murray Valley encephalitis virus (MVEV) is a flavivirus that occurs in Australia and New Guinea. While clinical cases are uncommon, MVEV can cause severe encephalitis with high mortality. Sentinel chicken surveillance is used at many sites around Australia to provide an early warning system for risk of human infection in areas that have low population density and geographical remoteness. MVEV in Western Australia occurs in areas of low population density and geographical remoteness, resulting in logistical challenges with surveillance systems and few human cases. While epidemiological data has suggested an association between rainfall and MVEV activity in outbreak years, it has not been quantified, and the association between rainfall and sporadic cases is less clear. In this study we analysed 22 years of sentinel chicken and human case data from Western Australia in order to evaluate the effectiveness of sentinel chicken surveillance for MVEV and assess the association between rainfall and MVEV activity. METHODS: Sentinel chicken seroconversion, human case and rainfall data from the Kimberley and Pilbara regions of Western Australia from 1990 to 2011 were analysed using negative binomial regression. Sentinel chicken seroconversion and human cases were used as dependent variables in the model. The model was then tested against sentinel chicken and rainfall data from 2012 and 2013. RESULTS: Sentinel chicken seroconversion preceded all human cases except two in March 1993. Rainfall in the prior three months was significantly associated with both sentinel chicken seroconversion and human cases across the regions of interest. Sentinel chicken seroconversion was also predictive of human cases in the models. The model predicted sentinel chicken seroconversion in the Kimberley but not in the Pilbara, where seroconversions early in 2012 were not predicted. The latter may be due to localised MVEV activity in isolated foci at dams, which do not reflect broader virus activity in the region. CONCLUSIONS: We showed that rainfall and sentinel chickens provide a useful early warning of MVEV risk to humans across endemic and epidemic areas, and that a combination of the two indicators improves the ability to assess MVEV risk and inform risk management measures.

Ross River virus infection surveillance in the Greater Perth Metropolitan area--has there been an increase in cases in the winter months?

An increase in off-season (June to September) Ross River virus (RRV) notifications from the greater Perth metropolitan area was observed from 2006 to 2009. We investigated the increase to determine whether it is likely to have reflected a true increase in off-season cases. A single positive RRV IgM test result is sufficient for RRV notification but where follow-up testing was performed, the positive predictive value of an IgM test where IgG was negative was very low in the off-season and also in the season when using the only commercially available test kit. The increase in off-season notifications was not associated with an increase in off-season testing. Some Perth laboratories use more stringent notification criteria than the nationally agreed RRV case definition, and the geographical distribution of samples tested varies between laboratories. Our findings make a strong case to change the nationally agreed case definition for RRV to not accept a single IgM positive test result as laboratory definitive evidence where the IgG is negative. Our study also identified a range of challenges in interpreting changes in seasonal patterns and geographical distribution of RRV. Any such observed changes should be investigated through further data analysis and/or mosquito trapping and testing in order to assess validity.

The use of narcotics and street drugs during pregnancy.

All prenatal care providers should offer routine voluntary substance use screening to all patients. Parturients who screen positive for illicit substances require a multidisciplinary team approach to drug rehabilitation and prenatal care. This review will examine the pharmacological properties and the neonatal consequences of the use of opioids and amphetamines. Substance-abusing parturients typically abuse multiple substances simultaneously and have other comorbidities including psychosocial instability and mental illness. These comorbidities must be effectively addressed to achieve optimal health outcomes for both mother and infant.

Comparison of pregnancies between perinatally and sexually HIV-infected women: an observational study at an urban hospital.

As perinatally HIV-infected (PHIV) women reach reproductive age, there is an increasing number who become pregnant. This is a retrospective cohort study of HIV-infected women who delivered from June 2007 to July 2012 at our institution. Maternal demographics, HIV characteristics, and obstetric and neonatal outcomes were compared. 20 PHIV and 80 SHIV pregnancies were reviewed. The groups had similar CD4+ counts, prevalence of AIDS, and use of antiretrovirals (ARV) at initiation of obstetrical care. PHIV women were significantly more likely to be younger, have a detectable viral load (35% versus 74%, P < 0.01), and have HIV-genotype resistance (40% versus 12%, P < 0.01) than the SHIV women. The median gestational age at delivery (38 weeks) and rates of obstetrical and neonatal complications were similar between the groups. While the overall rate of cesarean delivery (CD) was similar, the rates for CD due to HIV were higher in the PHIV group (64% versus 22%, P < 0.01). There was one case (5.3%) of mother-to-child transmission in the PHIV group versus two cases (2.6%) in the SHIV group. In our population, PHIV pregnant women have a higher rate of HIV-genotype resistance and higher rate of detectable viral load leading to a higher rate of CD secondary to HIV.

Association of Sickle Cell Disease With Severe Maternal Morbidity.

OBJECTIVE: To evaluate the association between sickle cell disease (SCD) and severe maternal morbidity (SMM) in a contemporary cohort of deliveries by non-Hispanic Black people. METHODS: We retrospectively examined SMM by using electronic health record data on deliveries by non-Hispanic Black patients between 2011 and 2020 at a single tertiary, public institution. Sickle cell disease was identified during the delivery admission by using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes. The primary outcome, SMM at delivery hospitalization, was ascertained using ICD-9-CM and ICD-10-CM codes and excluded sickle cell crisis as an indicator of SMM. We also constructed a secondary measure of SMM that excluded deliveries in which blood transfusion was the only indication of SMM. Poisson regression models were used to estimate risk ratios (RRs) and 95% CIs for the associations between SCD and SMM (overall and for individual indicators). Multivariable models adjusted for age, parity, insurance type, chronic conditions (chronic hypertension, diabetes mellitus, obesity), and multiple gestation. RESULTS: Among 17,493 deliveries by non-Hispanic Black patients during the study period, 132 (0.8%) had a diagnosis of SCD. Of those patients, 87 (65.9%, 95% CI 57.2-73.9) with SCD and 2,035 (11.7%), 95% CI 11.2-12.2) without SCD had SMM. Sickle cell disease was associated with increased risk of SMM (87 vs 2,035, adjusted risk ratio [aRR] 5.4, 95% CI 4.6-6.3) and nontransfusion SMM (51 vs 1,057, aRR 6.0, 95% CI 4.6-8.0). Effect estimates were highest for cardiac arrest (3 vs 14, RR 28.2, 95% CI 3.8-209.3), air and thrombotic embolism (14 vs 72, RR 25.6, 95% CI 12.0-54.6), and puerperal cerebrovascular disorders (10 vs 53, RR 24.8, 95% CI 10.2-60.5). CONCLUSION: Sickle cell disease was associated with a more than fivefold increased risk of SMM during the delivery hospitalization. Our data suggest cardiovascular morbidity as the driving major risk. The identification and monitoring of cardiovascular pathology in patients with SCD before and during pregnancy may reduce SMM.

The Impact of a High-risk Psychosocial Assessment on Outcomes After Durable Mechanical Circulatory Support.

Patient adherence is vital to the success of durable mechanical circulatory support (MCS), and the pre-MCS assessment of adherence by the multidisciplinary advanced heart failure team is a critical component of the evaluation. We assessed the impact of a high-risk psychosocial assessment before durable MCS implantations on post-MCS outcomes. Between January 2010 and April 2018, 319 patients underwent durable MCS at our center. We excluded those who died or were transplanted before discharge. The remaining 203 patients were grouped by pre-MCS psychosocial assessment: high-risk (26; 12.8%) versus acceptable risk (177; 87.2%). We compared clinical characteristics, nonadherence, and outcomes between groups. High-risk patients were younger (48 vs. 56; p = 0.006) and more often on extracorporeal membrane oxygenation at durable MCS placement (26.9% vs. 9.0%; p = 0.007). These patients had a higher incidence of post-MCS nonadherence including missed clinic appointments, incorrect medication administration, and use of alcohol and illicit drugs. After a mean follow-up of 15.3 months, 100% of high-risk patients had unplanned hospitalizations compared with 76.8% of acceptable-risk patients. Per year, high-risk patients had a median of 2.9 hospitalizations per year vs. 1.2 hospitalizations per year in acceptable-risk patients. While not significant, there were more driveline infections over the follow-up period in high-risk patients (27% vs. 14.7%), deaths (27% vs. 18%), and fewer heart transplants (53.8% vs. 63.8%).The pre-MCS psychosocial assessment is associated with post-MCS evidence of nonadherence and unplanned hospitalizations. Attention to pre-MCS assessment of psychosocial risk factors is essential to optimize durable MCS outcomes.

Executive Summary and Call to Action: Maternal Mortality Summit at National Medical Association Meeting, July 28, 2019 in Honolulu, Hawaii Obstetrics and Gynecology Section of the National Medical Association.

Non-Hispanic black women are 3-4 fold more likely to experience a maternal death than white women in the US, a health disparity that has been persistent for the past 50 years. The complete explanation for this disparity is unknown, but awareness of factors contributing to this disparity is key in addressing it. To address the emerging public health issue of the high rate of maternal mortality in African American women, NMA leaders in obstetrics and gynecology and women's health care, family planning, and reproductive health gathered for the "Black Maternal Mortality Summit." The Summit was held in conjunction with the 117th Annual Convention and Scientific Assembly of the NMA. Reducing maternal mortality will take a multifaceted approach. It was the goal of this summit and writing group that this workshop and executive summary with recommendations will be a call to action to establish the will for developing and implementing developed guidelines and protocols to reduce maternal mortality among vulnerable patient populations.

Corneal Cryopreservation Using Glycerylphosphorylcholine-Enriched Medium.

PURPOSE: To determine the effects of prolonged cryopreservation at subzero-degree temperatures on corneal transparency and histology after treatment with preservation medium containing the phosphodiester glycerylphosphorylcholine (GPC). METHODS: Rabbit corneas (n = 30) were immersed for 3 hours in K-Sol preservation medium containing 30 mM GPC. Three groups with 6 corneas each were refrigerated at -8°C for 2 weeks and liquid nitrogen temperature for 2 and 6 weeks, respectively. Two groups with 6 corneas each immersed in K-Sol preservation medium only were refrigerated at -8°C for 2 weeks and liquid nitrogen temperature for 6 weeks, respectively. Postthawing corneal transparency was measured on a grading scale after which corneas were prepared for and analyzed by light and transmission electron microscopy. RESULTS: All 3 groups of corneas preserved with GPC maintained a greater degree of corneal transparency compared with corneas preserved without GPC. The number of corneas retaining epithelial and endothelial layers increased in all groups where corneas were preserved in medium containing GPC, in contrast to corneas preserved in medium without GPC. Cytoplasmic vacuolization or nuclear damage was greater in corneas preserved without GPC. Similar findings were found in corneas stored at -8°C and liquid nitrogen temperatures. CONCLUSIONS: This study demonstrates a cryoprotective effect of corneas preserved in K-Sol containing the phosphodiester GPC at subzero-degree temperatures. In corneas immersed in preservation medium containing GPC, a higher degree of transparency is maintained and a lesser degree of histopathologic changes is observed with storage at both -8°C and in liquid nitrogen.

Implementation of a Postpartum Hemorrhage Safety Bundle at an Urban Safety-Net Hospital.

Background Postpartum hemorrhage (PPH) is a leading cause of preventable maternal morbidity and mortality. Standardized response to obstetric hemorrhage is associated with significant improvement in maternal outcomes, yet implementation can be challenging. Objective The primary objective is to describe the methodology for program implementation of the Alliance for Innovation on Maternal Health Safety Bundle on PPH at an urban safety-net hospital. Methods Over an 18-month period, interventions geared toward (1) risk assessment and stratification, (2) hemorrhage identification and management, (3) team communication and simulation, and (4) debriefs and case review were implemented. Hemorrhage risk assessment stratification rates were tracked overtime as an early measure of bundle compliance. Results Hemorrhage risk assessment stratification rates improved to >90% during bundle implementation. Conclusion Keys to implementation included multidisciplinary stakeholder commitment, stepwise and iterative approach, and parallel systems for monitoring and evaluation Implementation of a PPH safety bundle is feasible in a resource-constrained setting.

The Diversity and Distribution of Viruses Associated with Culex annulirostris Mosquitoes from the Kimberley Region of Western Australia.

Metagenomics revealed an impressive breadth of previously unrecognized viruses. Here, we report the virome of the Culex annulirostris Skuse mosquito, an important vector of pathogenic arboviruses in Australia. Mosquitoes were collected from three sites in the Kimberley region of Western Australia. Unbiased high-throughput sequencing (HTS) revealed the presence of 16 novel viral sequences that share less than 90% identity with known viruses. None were closely related to pathogenic arboviruses. Viruses were distributed unevenly across sites, indicating a heterogeneous Cx. annulirostris virome. Polymerase chain reaction assays confirmed HTS data and identified marked variation between the virus prevalence identified at each site.

Phylogenetic and Timescale Analysis of Barmah Forest Virus as Inferred from Genome Sequence Analysis.

Barmah Forest virus (BFV) is a medically important mosquito-borne alphavirus endemic to Australia. Symptomatic disease can be a major cause of morbidity, associated with fever, rash, and debilitating arthralgia. BFV disease is similar to that caused by Ross River virus (RRV), the other major Australian alphavirus. Currently, just four BFV whole-genome sequences are available with no genome-scale phylogeny in existence to robustly characterise genetic diversity. Thirty novel genome sequences were derived for this study, for a final 34-taxon dataset sampled over a 44 year period. Three distinct BFV genotypes were characterised (G1-3) that have circulated in Australia and Papua New Guinea (PNG). Evidence of spatio-temporal co-circulation of G2 and G3 within regions of Australia was noted, including in the South West region of Western Australia (WA) during the first reported disease outbreaks in the state's history. Compared with RRV, the BFV population appeared more stable with less frequent emergence of novel lineages. Preliminary in vitro assessment of RRV and BFV replication kinetics found that RRV replicates at a significantly faster rate and to a higher, more persistent titre compared with BFV, perhaps indicating mosquitoes may be infectious with RRV for longer than with BFV. This investigation resolved a greater diversity of BFV, and a greater understanding of the evolutionary dynamics and history was attained.