Pregnancy and COVID-19: pharmacologic considerations.

In this review, we summarize evidence regarding the use of routine and investigational pharmacologic interventions for pregnant and lactating patients with coronavirus disease 2019 (COVID-19). Antenatal corticosteroids may be used routinely for fetal lung maturation between 24 and 34 weeks' gestation, but decisions in those with critical illness and those < 24 or > 34 weeks' gestation should be made on a case-by-case basis. Magnesium sulfate may be used for seizure prophylaxis and fetal neuroprotection, albeit cautiously in those with hypoxia and renal compromise. There are no contraindications to using low-dose aspirin to prevent placenta-mediated pregnancy complications when indicated. An algorithm for thromboprophylaxis in pregnant patients with COVID-19 is presented, which considers disease severity, timing of delivery in relation to disease onset, inpatient vs outpatient status, underlying comorbidities and contraindications to the use of anticoagulation. Nitrous oxide may be administered for labor analgesia while using appropriate personal protective equipment. Intravenous remifentanil patient-controlled analgesia should be used with caution in patients with respiratory depression. Liberal use of neuraxial labor analgesia may reduce the need for emergency general anesthesia which results in aerosolization. Short courses of non-steroidal anti-inflammatory drugs can be administered for postpartum analgesia, but opioids should be used with caution due to the risk of respiratory depression. For mechanically ventilated pregnant patients, neuromuscular blockade should be used for the shortest duration possible and reversal agents should be available on hand if delivery is imminent. To date, dexamethasone is the only proven and recommended experimental treatment for pregnant patients with COVID-19 who are mechanically ventilated or who require supplemental oxygen. Although hydroxycholoroquine, lopinavir/ritonavir and remdesivir may be used during pregnancy and lactation within the context of clinical trials, data from non-pregnant populations have not shown benefit. The role of monoclonal antibodies (tocilizumab), immunomodulators (tacrolimus), interferon, inhaled nitric oxide and convalescent plasma in pregnancy and lactation needs further evaluation. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Postnatal demoralisation among women admitted to a hospital mother-baby unit: validation of a psychometric measure.

Demoralisation is a psychological state characterised by experiences of distress and sadness, helplessness, subjective incompetence and hopelessness, in the context of a stressful situation. Experiences of demoralisation may be particularly relevant to women who have recently given birth, who can feel incompetent, isolated and helpless. The psychometric properties of the Demoralisation Scale among women in the postnatal period participating in a clinical program were examined. Women admitted with their infants to a hospital mother-baby unit in Australia for five nights were recruited consecutively (N = 209) and assessed at admission and discharge. The Demoralisation Scale was perceived as relevant and exhibited high reliability, acceptable construct validity and good sensitivity to change. The mean demoralisation score was high (M = 30.9, SD = 15.5) and associated with negative experiences of motherhood and functional impairment, independent of depression and anxiety symptoms. Mean demoralisation decreased significantly after program completion (M = 18.4, SD = 12.4). More participants showed a significant improvement in demoralisation (57.5 %) than in depression (34.8 %) and anxiety (9.8 %) symptoms. Demoralisation can provide a useful framework for understanding and measuring the experiences of women participating in postnatal clinical programs and in directing treatment towards helping women to acquire the necessary caregiving skills and increasing parental efficacy. The Demoralisation Scale is a useful clinical tool for assessing intervention effects.

Mothers' perceptions of primary health-care providers: thematic analysis of responses to open-ended survey questions.

General practitioners and maternal, child and family health nurses have a central role in postpartum primary health care for women and their infants. Positive client-provider relationships are particularly important for women experiencing mental health problems or unsettled infant behaviour. However, little is known about their experiences of postnatal primary health care. The study aimed to describe views of postnatal primary health care among women completing a residential early parenting programme and to identify potential strategies to enhance provider-patient interactions. Participants (n=138) were women admitted with their infants to a private or a public early parenting service in Melbourne, Australia. Women completed a detailed self-report survey, including open-ended questions about experiences of primary health-care services, and a structured psychiatric interview to diagnose anxiety and depression. Survey responses were analysed thematically. Womens' experiences of primary health care were influenced by their perceptions of provider competence and the quality of interactions. While similar positive characteristics of doctor and nurse care were valued, medical and nursing practices were judged in different ways. Women described GPs who listened, understood and were thorough as providing good care, and maternal, child and family health nurses were valued for providing support, advice and encouragement. Threats to therapeutic relationships with doctors included feeling rushed during consultations, believing that GPs were not mental health-care providers and the clinician not being 'good' with the infant; with nurses, problems included feeling judged or given advice that was inconsistent or lacked an evidence-base. Postpartum primary health care will be improved by unhurried consultations, empathic recognition, encouragement, evidence-informed guidance and absence of criticism.

RAD in the realm of next-generation sequencing technologies.

The first North American RAD Sequencing and Genomics Symposium, sponsored by Floragenex (http://www.floragenex.com/radmeeting/), took place in Portland, Oregon (USA) on 19 April 2011. This symposium was convened to promote and discuss the use of restriction-site-associated DNA (RAD) sequencing technologies. RAD sequencing is one of several strategies recently developed to increase the power of data generated via short-read sequencing technologies by reducing their complexity (Baird et al. 2008; Huang et al. 2009; Andolfatto et al. 2011; Elshire et al. 2011). RAD sequencing, as a form of genotyping by sequencing, has been effectively applied in genetic mapping and quantitative trait loci (QTL) analyses in a range of organisms including nonmodel, genetically highly heterogeneous organisms (Table 1; Baird et al. 2008; Baxter et al. 2011; Chutimanitsakun et al. 2011; Pfender et al. 2011). RAD sequencing has recently found applications in phylogeography (Emerson et al. 2010) and population genomics (Hohenlohe et al. 2010). Considering the diversity of talks presented during this meeting, more developments are to be expected in the very near future.

Breastfeeding after assisted conception: a prospective cohort study.

AIM: The aims were to investigate the prevalence of breastfeeding after conception with assisted reproductive technology (ART) and identify risk factors for breastfeeding duration <6 weeks and cessation of breastfeeding before the baby is 8 months old. METHODS: A consecutive cohort of women who had conceived at one of two ART centres in Melbourne, Australia, was recruited in early pregnancy. The women completed telephone interviews and postal questionnaires in pregnancy and 3, 8 and 18 months after the birth. RESULTS: Of 239 eligible women, 183 (77%) agreed to take part. Participants were more likely than the general population of childbearing Australian women to initiate breastfeeding (89% vs 83.3%, p=0.05) but by 3 months, a smaller proportion was breastfeeding exclusively (46% vs 57.3%, p=0.004). The proportions not providing any breast milk at 6 weeks and 8 months were 23% and 57%, respectively. More anxiety in late pregnancy and sub-optimal breastfeeding advice predicted breastfeeding duration <6 weeks and breastfeeding cessation before 8 months. CONCLUSION: The predictors of less favourable breastfeeding outcomes after ART identified may be modifiable. Antenatal strategies to reduce anxiety in pregnancy and postnatal strategies to ensure consistent breastfeeding advice may improve breastfeeding outcomes among women who give birth after ART.

Early post-partum adjustment and admission to parenting services in Victoria, Australia after assisted conception.

BACKGROUND: Higher rates of admission to residential early parenting services (REPSs) after assisted conception compared with spontaneous conception have been reported. The aim of this study was to characterize early post-partum psychological functioning and the rate of, and risks factors for, admission to REPSs in women conceiving with assisted reproductive technology (ART) in Australia. METHODS: A consecutive cohort of women who had conceived through ART was recruited systematically in early pregnancy. At 3 months post-partum, participants completed postal questionnaires which included a new measure of the degree of difficulty involved in conceiving, the Burden of Infertility and Treatment (BIT) scale. RESULTS: Of 166 women who participated, 8% had already been admitted to a REPS within 3 months, which is a higher rate compared with other women in the first 12 months (5%). Compared with community samples of new mothers, there was no difference in rate of depression. A higher proportion reported dysregulated infant behaviours (P < 0.0001) and a smaller proportion was breast feeding exclusively (P < 0.0001). Greater difficulty conceiving (higher BIT score) was associated with lower maternal confidence. CONCLUSIONS: Clinical care of the increasing group of women who conceive with ART should include explicit assessment of early post-partum psychological functioning and early intervention if difficulties in managing infant behaviour are reported.

Women's experiences of childbirth and post-natal healthcare after assisted conception.

BACKGROUND: The proportion of women who give birth after assisted reproduction technology (ART) treatment is increasing. To date, little is known about their experience of childbirth. One of the aims of this study was to investigate the experience of childbirth and the post-natal healthcare after ART. METHODS: A prospective, longitudinal study of a systematically recruited consecutive cohort of women who had conceived with ART in Melbourne, Australia, in 2001 was investigated using telephone interviews and self-report questionnaires. The experience of birth was explored 3 months post-partum. RESULTS: One hundred and sixty-six women who had conceived through ART participated. Compared with other Australian women, participants were more likely to have a Caesarean birth (51% versus 25%, P < 0.0001). Women who had a Caesarean birth were less likely to report having had an active say about the management of the birth (P < 0.01) and to have held their baby at birth (P < 0.0001) and more likely to report disappointment with the birth event (P < 0.0001), severe post-natal pain (P = 0.02) and needing a lot of help or advice with infant feeding (P = 0.001) than those who had a vaginal birth. CONCLUSIONS: After ART, there are highly elevated rates of operative birth which appear to influence early post-natal adjustment.

Treatment of maternal mood disorder and infant behaviour disturbance in an Australian private mothercraft unit: a follow-up study.

Australia has a system of residential parentcraft services which offer brief admissions to mothers experiencing difficulties with infant care and postnatal mood disturbance. Most of these are state-funded public access services. In 1996 a comparable but differentiated service was opened in the private sector. Masada Private Hospital Mother Baby Unit accommodates five mother-infant pairs who are admitted to a five-night structured residential program. Care is provided by a multidisciplinary team comprising a paediatrician, general practitioner, clinical psychologist and specialist nurses. Complex maternal mood disorders as measured on standardised psychometric instruments include depression, anxiety and severe occupational fatigue. Their babies are unsettled, cry for prolonged periods, wake frequently at night and do not sleep well during the day. Many have feeding difficulties. The treatment program comprises both individualised training in infant care and settling strategies and psycho-educational groups offered in a supportive non-judgemental setting. One month post-discharge maternal mood is significantly improved and infant behaviour more manageable compared with functioning on admission.

Self-referencing intensity measurements based on square-wave gated phase-modulation fluorimetry.

An adaptation of square-wave gated phase-modulation (GPM) fluorimetry allows for self-referenced intensity measurements without the complexity of dual excitation or dual emission wavelengths. This AC technique utilizes square-wave excitation, gated detection, a reference emitter, and a sensor molecule. The theory and experimental data demonstrating the effectiveness and advantages of the adapted GPM scheme are presented. One component must have an extremely short lifetime relative to the other. Both components are affected identically by changes in intensity of the excitation source, but the sensor intensity also depends on the concentration of the analyte. The fluctuations of the excitation source and any optical transmission changes are eliminated by ratioing the sensor emission to the reference emission. As the concentration of the analyte changes, the corresponding sensor intensity changes can be quantified through several schemes including digitization of the signal and digital integration or AC methods. To measure pH, digital methods are used with Na3[Tb(dpa)3] (dpa = 2,6-pyridinedicarboxylic acid) as the long-lived reference molecule and fluorescein as the short-lived sensor molecule. Measurements from the adapted GPM scheme are directly compared to conventional ratiometric measurements. Good agreement between the data collection methods is demonstrated through the apparent pKa. For the adapted GPM measurements, conventional measurements, and a global fit the apparent pKa values agree within less than 2%. A key element of the adapted GPM method is its insensitivity to fluctuations in the source intensity. For a roughly 8-fold change in the excitation intensity, the signal ratio changes by less than 3%.

Elimination of fluorescence and scattering backgrounds in luminescence lifetime measurements using gated-phase fluorometry.

A new gated form of phase fluorometry for measuring lifetimes is presented. The technique uses a square-wave excitation and gates the detector on only during the off period of the excitation. Using a long-lived sample, this eliminates or reduces errors from scattered light and short-lived fluorescences. Using a square-wave modulated excitation source with a 50% duty cycle, traditional data treatment can be used after, at most, a simple pi/2 phase adjustment. A combination of theory and experimental results demonstrates the validity of this new gated method and its utility for eliminating or reducing background. The results are precise, accurate, eliminate scattering errors, and greatly reduce errors due to short-lived fluorescence impurities. Errors from fluorescence bleed-through into the detection period or a slow excitation source turn off can be mitigated by using an offset time prior to gating the detector on.

Early warming of tropical South America at the last glacial-interglacial transition.

Glaciation in the humid tropical Andes is a sensitive indicator of mean annual temperature. Here, we present sedimentological data from lakes beyond the glacial limit in the tropical Andes indicating that deglaciation from the Last Glacial Maximum led substantial warming at high northern latitudes. Deglaciation from glacial maximum positions at Lake Titicaca, Peru/Bolivia (16 degrees S), and Lake Junin, Peru (11 degrees S), occurred 22,000 to 19,500 calendar years before the present, several thousand years before the Bølling-Allerød warming of the Northern Hemisphere and deglaciation of the Sierra Nevada, United States (36.5 degrees to 38 degrees N). The tropical Andes deglaciated while climatic conditions remained regionally wet, which reflects the dominant control of mean annual temperature on tropical glaciation.

Survival of Mannheimia (Pasteurella) haemolytica in tracheobronchial washings of sheep and cattle.

The growth, morphology and long-term survival of a representative isolate of Mannheimia haemolytica serotypes A1 and A2 were monitored in ovine and bovine tracheobronchial washings. Both strains survived for at least 244 days in ovine tracheobronchial washings and 156 days in bovine tracheobronchial washings. The addition of fresh washings at these times prompted an increase for serotype A2 but no change in viability for serotype A1 in ovine tracheobronchial washings and an increase for both serotypes in bovine tracheobronchial washings. When growth and survival was compared using tracheobronchial washings from ruminant and non-ruminant species there was a trend towards longer survival in ruminant fluids.Long-term survival was associated with temporary or permanent change from normal size colonies to 'micro-colonies' on sheep blood agar. Subculture allowed reversion to normal colony morphology. Analysis showed these micro-colonies to consist of chains of elongated bacteria. M. haemolytica serotype A2 was more robust in its ability to withstand nutrient deprivation for long periods of time. These survival mechanisms may have important implications for pathogenesis.

The history of South American tropical precipitation for the past 25,000 years.

Long sediment cores recovered from the deep portions of Lake Titicaca are used to reconstruct the precipitation history of tropical South America for the past 25,000 years. Lake Titicaca was a deep, fresh, and continuously overflowing lake during the last glacial stage, from before 25,000 to 15,000 calibrated years before the present (cal yr B.P.), signifying that during the last glacial maximum (LGM), the Altiplano of Bolivia and Peru and much of the Amazon basin were wetter than today. The LGM in this part of the Andes is dated at 21,000 cal yr B.P., approximately coincident with the global LGM. Maximum aridity and lowest lake level occurred in the early and middle Holocene (8000 to 5500 cal yr B.P.) during a time of low summer insolation. Today, rising levels of Lake Titicaca and wet conditions in Amazonia are correlated with anomalously cold sea-surface temperatures in the northern equatorial Atlantic. Likewise, during the deglacial and Holocene periods, there were several millennial-scale wet phases on the Altiplano and in Amazonia that coincided with anomalously cold periods in the equatorial and high-latitude North Atlantic, such as the Younger Dryas.

Adherence of ovine and human Bordetella parapertussis to continuous cell lines and ovine tracheal organ culture.

The adherence of ovine and human isolates of Bordetella parapertussis to ovine and human continuous culture cell lines and to ovine tracheal organ culture was compared. Adherence to non-ciliated respiratory continuous culture cells did not reveal any host-specificity of the isolates. In contrast, adherence of ovine B. parapertussis strains to ciliated ovine tracheal organ culture was significantly greater than that of human strains. These results indicate that tracheal organ culture is a useful tool for studying host-specific adherence of B. parapertussis and suggest that adherence of B. parapertussis to ciliated epithelia is species-specific making it unlikely that the transfer of B. parapertussis between humans and sheep will result in an infection.

Divergent activity and function of superoxide dismutases in Pasteurella haemolytica serotypes A1 and A2 and Pasteurella trehalosi serotype T10.

Representative strains of Pasteurella haemolytica serotypes A1 and A2 and Pasteurella trehalosi serotype T10 were examined for the presence of superoxide dismutase. Visualisation of superoxide dismutase enzyme activity on polyacrylamide gels, and specific inhibition with potassium cyanide verified a copper/zinc (Cu/Zn) superoxide dismutase only in serotype A2 whereas serotypes A1 and T10 showed other superoxide dismutase activity. Using a simple freeze-thaw method the cellular location of superoxide dismutase enzyme activity was determined in all three serotypes. In serotypes A1 and A2 but not T10 superoxide dismutases were located in the periplasm. The viability of serotypes A2 and T10 cells in the presence of exogenous superoxide was unchanged over a 30 min period, whereas serotype A1 cells declined in viability between 15 and 30 min. Purified immunoglobulin from sheep convalescent serum did not reduce superoxide dismutase activity in the serotypes in an in vitro assay. The presence of this enzyme within the pasteurellae suggests a supportive role in the virulence of this major pathogen of ruminants.

Occurrence of [copper, zinc]-cofactored superoxide dismutase in Pasteurella haemolytica and its serotype distribution.

Fifty-two ovine strains of Pasteurella haemolytica and P. trehalosi representing serotypes 1-16 were examined for the presence of [copper, zinc]superoxide dismutase DNA sequences. This was done using a combination of polymerase chain reaction with degenerate primers based on the sequence of the [Cu,Zn]superoxide dismutase gene (sodC) in related species and Southern hybridization using a fragment of sodC from P. haemolytica A2 serotype as a probe. Both detection methods identified a fragment of the sodC gene in 9/9 strains of P. haemolytica serotype 2 examined and in 5/8 strains of serotype 7. No evidence of this gene was found in any other serotype of P. haemolytica or in any P. trehalosi serotype. Comparison of DNA sequence showed near identity between sodC from the A2 and A7 serotypes of P. haemolytica and substantial similarity (70%) to sodC previously sequenced in P. multocida, Haemophilus parainfluenzae and H. influenzae. Analysis by gel electrophoresis of the superoxide dismutase activity present in cell lysates showed that one or more superoxide dismutase is present in all serotypes. However, cyanide-inhibitable activity, corresponding to [Cu,Zn]superoxide dismutase, was detected only in those strains of serotypes A2 and A7 which showed evidence of the sodC gene fragment.

Multidisciplinary teamwork--myth or reality?

The provision and delivery of health care has become increasingly complex in recent years due to technological innovation in medicine and increasing client expectations. The challenge for health care workers is to meet the purchasers' demands, one option may be to shift working practices from a functionalist approach to one of multidisciplinary teamwork. This paper explores one example of multidisciplinary teamwork and examines the processes which enhance and those that limit collaboration.

[Lys(B28), Pro(B29)]-human insulin: effect of injection time on postprandial glycemia.

BACKGROUND: [Lys(B28), Pro(B29)]-human insulin (lispro) is an insulin analogue with a reduced capacity for self-association and faster absorption from subcutaneous injection sites. We hypothesized that administration of lispro closer to a meal would result in better glucose control than that achieved with regular insulin. METHODS: This trial used a randomized crossover design that consisted of a period of metabolic stabilization lasting 9 days followed by an evaluation period lasting 5 days. The patients received weight-maintenance diets, and insulin doses were adjusted as needed. Calorie intake, insulin dose, and activities were kept constant once the evaluation period began. During the evaluation period, we varied the time between insulin injection and mealtime and assessed glucose control. RESULTS: During the evaluation period, the lowest mean glucose concentrations were 117.9 mg/dl for lispro and 119.8 mg/dl (p = 0.817) for regular insulin. To obtain these, we gave lispro, on average, 22.5 minutes before meals and regular insulin 63.8 minutes before meals (p = 0.006). A similar pattern was evident throughout the glucose control parameters. The exception was mean amplitude of glucose excursion, which was lower after lispro (59 versus 75 mg/dl; p = 0.007) compared with regular insulin. CONCLUSIONS: We achieved equal or slightly better glucose control, as reflected by mean amplitude of glucose excursion, with insulin lispro given much closer to meal time than that achieved with regular insulin. As a result of these findings, we propose that a rapidly absorbed analogue of insulin is capable of achieving better control of postprandial glucose at a more convenient injection time.

Local and systemic phentolamine antagonism of norepinephrine-induced hand vein constriction.

The dorsal hand vein distention technique has been used to study the effects of alpha-adrenergic receptor antagonists on alpha-agonist-induced venoconstriction. Using this technique, we investigated the dose-effect relationships between different intravenous routes of phentolamine (an alpha-antagonist) administration on norepinephrine (an alpha-agonist)-induced hand vein constriction. Hand vein studies were done on healthy men; each man was studied on up to four occasions. On one occasion for each man, graded doses of phentolamine were infused into a hand vein preconstricted (submaximally) with norepinephrine. The dose of phentolamine producing a half maximal response (ED50) for reversal of venoconstriction, and the maximal reversal were calculated. On the other three occasions (randomly allocated) for each man, graded doses of norepinephrine were infused into a hand vein before and during intravenous infusions of (1) control (vehicle solutions); (2) systemic (other arm vein) phentolamine; and (3) local (hand vein) phentolamine. Systemic and local phentolamine dose ratios (ED50 of norepinephrine during phentolamine, divided by ED50 of norepinephrine before phentolamine; divided by the control dose ratio) were calculated. These studies show that phentolamine (administered directly into a preconstricted hand vein) can completely reverse norepinephrine-induced venoconstriction. Phentolamine, administered by either local or systemic intravenous infusion, induces a significant rightward shift (approximately 10-fold) in responsiveness to norepinephrine-induced venoconstriction. To achieve comparable degrees of alpha-antagonism, however, systemic phentolamine must be administered intravenously at a dose approximately 3,000-fold higher than that of local phentolamine.(ABSTRACT TRUNCATED AT 250 WORDS)