Global Perspectives on the Management of Primary Progressive Aphasia.

Speech-language therapists/pathologists (SLT/Ps) are key professionals in the management and treatment of primary progressive aphasia (PPA), however, there are gaps in education and training within the discipline, with implications for skills, confidence, and clinical decision-making. This survey aimed to explore the areas of need amongst SLT/Ps working with people living with PPA (PwPPA) internationally to upskill the current and future workforce working with progressive communication disorders. One hundred eighty-five SLT/Ps from 27 countries who work with PwPPA participated in an anonymous online survey about their educational and clinical experiences, clinical decision-making, and self-reported areas of need when working with this population. Best practice principles for SLT/Ps working with PwPPA were used to frame the latter two sections of this survey. Only 40.7% of respondents indicated that their university education prepared them for their current work with PwPPA. Competency areas of "Knowing people deeply," "Practical issues," "Connectedness," and "Preventing disasters" were identified as the basic areas of priority and need. Respondents identified instructional online courses (92.5%), sample tools and activities for interventions (64.8%), and concrete training on providing care for advanced stages and end of life (58.3%) as central areas of need in their current work. This is the first international survey to comprehensively explore the perspectives of SLT/Ps working with PwPPA. Based on survey outcomes, there is a pressing need to enhance current educational and ongoing training opportunities to better promote the well-being of PwPPA and their families, and to ensure appropriate preparation of the current and future SLT/P workforce.

Machine learning on cardiotocography data to classify fetal outcomes: A scoping review.

INTRODUCTION: Uterine contractions during labour constrict maternal blood flow and oxygen delivery to the developing baby, causing transient hypoxia. While most babies are physiologically adapted to withstand such intrapartum hypoxia, those exposed to severe hypoxia or with poor physiological reserves may experience neurological injury or death during labour. Cardiotocography (CTG) monitoring was developed to identify babies at risk of hypoxia by detecting changes in fetal heart rate (FHR) patterns. CTG monitoring is in widespread use in intrapartum care for the detection of fetal hypoxia, but the clinical utility is limited by a relatively poor positive predictive value (PPV) of an abnormal CTG and significant inter and intra observer variability in CTG interpretation. Clinical risk and human factors may impact the quality of CTG interpretation. Misclassification of CTG traces may lead to both under-treatment (with the risk of fetal injury or death) or over-treatment (which may include unnecessary operative interventions that put both mother and baby at risk of complications). Machine learning (ML) has been applied to this problem since early 2000 and has shown potential to predict fetal hypoxia more accurately than visual interpretation of CTG alone. To consider how these tools might be translated for clinical practice, we conducted a review of ML techniques already applied to CTG classification and identified research gaps requiring investigation in order to progress towards clinical implementation. MATERIALS AND METHOD: We used identified keywords to search databases for relevant publications on PubMed, EMBASE and IEEE Xplore. We used Preferred Reporting Items for Systematic Review and Meta-Analysis for Scoping Reviews (PRISMA-ScR). Title, abstract and full text were screened according to the inclusion criteria. RESULTS: We included 36 studies that used signal processing and ML techniques to classify CTG. Most studies used an open-access CTG database and predominantly used fetal metabolic acidosis as the benchmark for hypoxia with varying pH levels. Various methods were used to process and extract CTG signals and several ML algorithms were used to classify CTG. We identified significant concerns over the practicality of using varying pH levels as the CTG classification benchmark. Furthermore, studies needed to be more generalised as most used the same database with a low number of subjects for an ML study. CONCLUSION: ML studies demonstrate potential in predicting fetal hypoxia from CTG. However, more diverse datasets, standardisation of hypoxia benchmarks and enhancement of algorithms and features are needed for future clinical implementation.

Machine Learning to Classify Cardiotocography for Fetal Hypoxia Detection.

Fetal hypoxia can cause damaging consequences on babies' such as stillbirth and cerebral palsy. Cardiotocography (CTG) has been used to detect intrapartum fetal hypoxia during labor. It is a non-invasive machine that measures the fetal heart rate and uterine contractions. Visual CTG suffers inconsistencies in interpretations among clinicians that can delay interventions. Machine learning (ML) showed potential in classifying abnormal CTG, allowing automatic interpretation. In the absence of a gold standard, researchers used various surrogate biomarkers to classify CTG, where some were clinically irrelevant. We proposed using Apgar scores as the surrogate benchmark of babies' ability to recover from birth. Apgar scores measure newborns' ability to recover from active uterine contraction, which measures appearance, pulse, grimace, activity and respiration. The higher the Apgar score, the healthier the baby is.We employ signal processing methods to pre-process and extract validated features of 552 raw CTG. We also included CTG-specific characteristics as outlined in the NICE guidelines. We employed ML techniques using 22 features and measured performances between ML classifiers. While we found that ML can distinguish CTG with low Apgar scores, results for the lowest Apgar scores, which are rare in the dataset we used, would benefit from more CTG data for better performance. We need an external dataset to validate our model for generalizability to ensure that it does not overfit a specific population.Clinical Relevance- This study demonstrated the potential of using a clinically relevant benchmark for classifying CTG to allow automatic early detection of hypoxia to reduce decision-making time in maternity units.

Ambient air pollution and maternal cardiovascular health in pregnancy.

In this review, we summarise the current epidemiological and experimental evidence on the association of ambient (outdoor) air pollution exposure and maternal cardiovascular health during pregnancy. This topic is of utmost clinical and public health importance as pregnant women represent a potentially susceptible group due to the delicate balance of the feto-placental circulation, rapid fetal development and tremendous physiological adaptations to the maternal cardiorespiratory system during pregnancy.Several meta-analyses including up to 4 245 170 participants provide robust evidence that air pollutants, including particulate matter, nitrogen oxides and others, have adverse effects on the development of hypertensive disorders of pregnancy, gestational diabetes mellitus and cardiovascular events during labour. Potential underlying biological mechanisms include oxidative stress with subsequent endothelial dysfunction and vascular inflammation, ß-cell dysfunction and epigenetic changes. Endothelial dysfunction can lead to hypertension by impairing vasodilatation and promoting vasoconstriction. Air pollution and the consequent oxidative stress can additionally accelerate ß-cell dysfunction, which in turn triggers insulin resistance leading to gestational diabetes mellitus. Epigenetic changes in placental and mitochondrial DNA following air pollution exposures can lead to altered gene expression and contribute to placental dysfunction and induction of hypertensive disorders of pregnancy.The maternal and fetal consequences of such cardiovascular and cardiometabolic disease during pregnancy can be serious and long lasting, including preterm birth, increased risk of type 2 diabetes mellitus or cardiovascular disease later in life. Acceleration of efforts to reduce air pollution is therefore urgently needed to realise the full health benefits for pregnant mothers and their children.

Systematic review and meta-analysis of the effectiveness and perinatal outcomes of COVID-19 vaccination in pregnancy.

Safety and effectiveness of COVID-19 vaccines during pregnancy is a particular concern affecting vaccination uptake by this vulnerable group. Here we evaluated evidence from 23 studies including 117,552 COVID-19 vaccinated pregnant people, almost exclusively with mRNA vaccines. We show that the effectiveness of mRNA vaccination against RT-PCR confirmed SARS-CoV-2 infection 7 days after second dose was 89·5% (95% CI 69·0-96·4%, 18,828 vaccinated pregnant people, I2 = 73·9%). The risk of stillbirth was significantly lower in the vaccinated cohort by 15% (pooled OR 0·85; 95% CI 0·73-0·99, 66,067 vaccinated vs. 424,624 unvaccinated, I2 = 93·9%). There was no evidence of a higher risk of adverse outcomes including miscarriage, earlier gestation at birth, placental abruption, pulmonary embolism, postpartum haemorrhage, maternal death, intensive care unit admission, lower birthweight Z-score, or neonatal intensive care unit admission (p > 0.05 for all). COVID-19 mRNA vaccination in pregnancy appears to be safe and is associated with a reduction in stillbirth.

Applicability of the GAIA Maternal and Neonatal Outcome Case Definitions for the Evaluation of Adverse Events Following Vaccination in Pregnancy in High-income Countries.

BACKGROUND: The Brighton Collaboration Global Alignment of Immunization Safety in Pregnancy (GAIA) project developed case definitions for the assessment of adverse events in mothers and infants following maternal immunization. This study evaluated the applicability of these definitions to data collected in routine clinical care and research trial records across 7 sites in high-resource settings. METHODS: Data collection forms were designed and used to retrospectively abstract the key elements of the GAIA definitions from records for 5 neonatal and 5 maternal outcomes, as well as gestational age. Level of diagnostic certainty was assessed by the data abstractor and an independent clinician, and then verified by Automated Brighton Case logic. The ability to assign a level of diagnostic certainty for each outcome and the positive predictive value (PPV) for their respective ICD-10 codes were evaluated. RESULTS: Data from 1248 case records were abstracted: 624 neonatal and 622 maternal. Neonatal outcomes were most likely to be assessable and assigned by the level of diagnostic certainty. PPV for preterm birth, low birth weight, small for gestational age and respiratory distress were all above 75%. Maternal outcomes for preeclampsia and fetal growth restriction showed PPV over 80%. However, microcephaly (neonatal outcome) and dysfunctional labor (maternal outcome) were often nonassessable, with low PPVs. CONCLUSIONS: The applicability of GAIA case definitions to retrospectively ascertain and classify maternal and neonatal outcomes was variable among sites in high-resource settings. The implementation of the case definitions is largely dependent on the type and quality of documentation in clinical and research records in both high- and low-resource settings. While designed for use in the prospective evaluation of maternal vaccine safety, the GAIA case definitions would likely need to be specifically adapted for observational studies using alternative sources of data, linking various data sources and allowing flexibility in the ascertainment of the elements and levels of certainty of the case definition.

Global changes in maternity care provision during the COVID-19 pandemic: A systematic review and meta-analysis.

BACKGROUND: The COVID-19 pandemic has had a profound impact on healthcare systems globally, with a worrying increase in adverse maternal and foetal outcomes. We aimed to assess the changes in maternity healthcare provision and healthcare-seeking by pregnant women during the COVID-19 pandemic. METHODS: We performed a systematic review and meta-analysis of studies of the effects of the pandemic on provision of, access to and attendance at maternity services (CRD42020211753). We searched MEDLINE and Embase in accordance with PRISMA guidelines from January 1st, 2020 to April 17th 2021 for controlled observational studies and research letters reporting primary data comparing maternity healthcare-seeking and healthcare delivery during compared to before the COVID-19 pandemic. Case reports and series, systematic literature reviews, and pre-print studies were excluded. Meta-analysis was performed on comparable outcomes that were reported in two or more studies. Data were combined using random-effects meta-analysis, using risk ratios (RR) or incidence rate ratios (IRR) with 95% confidence intervals (CI). FINDINGS: Of 4743 citations identified, 56 were included in the systematic review, and 21 in the meta-analysis. We identified a significant decrease in the number of antenatal clinic visits (IRR 0614, 95% CI 0486-0776, P<00001, I2=54.6%) and unscheduled care visits (IRR 0741, 95% CI 0602-0911, P = 00046, I2=00%) per week, and an increase in virtual or remote antenatal care (IRR 4656 95% CI 7762-2794, P<00001, I2=90.6%) and hospitalisation of unscheduled attendees (RR 1214, 95% CI 1118-1319, P<00001, I2=00%). There was a decrease in the use of GA for category 1 Caesarean sections (CS) (RR 0529, 95% CI 0407-0690, P<00001, I2=00%). There was no significant change in intrapartum epidural use (P = 00896) or the use of GA for elective CS (P = 079). INTERPRETATION: Reduced maternity healthcare-seeking and healthcare provision during the COVID-19 pandemic has been global, and must be considered as potentially contributing to worsening of pregnancy outcomes observed during the pandemic.

Development of a core outcome set for interventions to prevent stillbirth.

AIMS: To develop a core outcome set for trials investigating interventions to prevent stillbirth. MATERIALS & METHODS: Outcomes identified from a systematic literature review and semi-structured interviews with parents in Australia and the UK were entered into a two-round online Delphi survey and focus group/consensus meetings. RESULTS: A core outcome set containing 11 outcomes in two categories. Five outcomes were related to the mother; fetal loss, onset of and mode of delivery, maternal mortality or near miss, psychological and social impact on the women, women's knowledge. Six outcomes were related to the baby; timing of stillbirth, neonatal mortality, gestational age at delivery, birthweight, congenital anomaly, NICU/SCBU or other higher-level neonatal care length of stay. CONCLUSIONS: Implementation and dissemination of this core outcome set in future trials will contribute towards coordinated outcome reporting and advancing usefulness of research to guide clinical practice.

Effects of the COVID-19 pandemic on maternal and perinatal outcomes: a systematic review and meta-analysis.

BACKGROUND: The COVID-19 pandemic has had a profound impact on health-care systems and potentially on pregnancy outcomes, but no systematic synthesis of evidence of this effect has been undertaken. We aimed to assess the collective evidence on the effects on maternal, fetal, and neonatal outcomes of the pandemic. METHODS: We did a systematic review and meta-analysis of studies on the effects of the pandemic on maternal, fetal, and neonatal outcomes. We searched MEDLINE and Embase in accordance with PRISMA guidelines, from Jan 1, 2020, to Jan 8, 2021, for case-control studies, cohort studies, and brief reports comparing maternal and perinatal mortality, maternal morbidity, pregnancy complications, and intrapartum and neonatal outcomes before and during the pandemic. We also planned to record any additional maternal and offspring outcomes identified. Studies of solely SARS-CoV-2-infected pregnant individuals, as well as case reports, studies without comparison groups, narrative or systematic literature reviews, preprints, and studies reporting on overlapping populations were excluded. Quantitative meta-analysis was done for an outcome when more than one study presented relevant data. Random-effects estimate of the pooled odds ratio (OR) of each outcome were generated with use of the Mantel-Haenszel method. This review was registered with PROSPERO (CRD42020211753). FINDINGS: The search identified 3592 citations, of which 40 studies were included. We identified significant increases in stillbirth (pooled OR 1·28 [95% CI 1·07-1·54]; I2=63%; 12 studies, 168 295 pregnancies during and 198 993 before the pandemic) and maternal death (1·37 [1·22-1·53; I2=0%, two studies [both from low-income and middle-income countries], 1 237 018 and 2 224 859 pregnancies) during versus before the pandemic. Preterm births before 37 weeks' gestation were not significantly changed overall (0·94 [0·87-1·02]; I2=75%; 15 studies, 170 640 and 656 423 pregnancies) but were decreased in high-income countries (0·91 [0·84-0·99]; I2=63%; 12 studies, 159 987 and 635 118 pregnancies), where spontaneous preterm birth was also decreased (0·81 [0·67-0·97]; two studies, 4204 and 6818 pregnancies). Mean Edinburgh Postnatal Depression Scale scores were higher, indicating poorer mental health, during versus before the pandemic (pooled mean difference 0·42 [95% CI 0·02-0·81; three studies, 2330 and 6517 pregnancies). Surgically managed ectopic pregnancies were increased during the pandemic (OR 5·81 [2·16-15·6]; I2=26%; three studies, 37 and 272 pregnancies). No overall significant effects were identified for other outcomes included in the quantitative analysis: maternal gestational diabetes; hypertensive disorders of pregnancy; preterm birth before 34 weeks', 32 weeks', or 28 weeks' gestation; iatrogenic preterm birth; labour induction; modes of delivery (spontaneous vaginal delivery, caesarean section, or instrumental delivery); post-partum haemorrhage; neonatal death; low birthweight (<2500 g); neonatal intensive care unit admission; or Apgar score less than 7 at 5 min. INTERPRETATION: Global maternal and fetal outcomes have worsened during the COVID-19 pandemic, with an increase in maternal deaths, stillbirth, ruptured ectopic pregnancies, and maternal depression. Some outcomes show considerable disparity between high-resource and low-resource settings. There is an urgent need to prioritise safe, accessible, and equitable maternity care within the strategic response to this pandemic and in future health crises. FUNDING: None.

Ultrasound screening for complications in twin pregnancy.

In the decades since the introduction of ultrasound into routine obstetric practice, the advantages of ultrasound have moved beyond the simple ability to identify multiple pregnancies antenatally to the possibility of screening them for fetal anomalies, pre-eclampsia, preterm birth, and the complications specific to monochorionic pregnancies. Screening studies have often excluded twins because physiological differences impact on the validity and sensitivity of the screening tests in routine use in singletons, and therefore, the evidence of screening performance in multiple pregnancy lags behind the evidence from singleton pregnancies. In general, most pregnancy complications are more common in twin pregnancy, but screening tests are less accurate or well validated. In this review article we present the current state of the evidence and avenues for future research relating to the use of ultrasound and screening for complications in twin pregnancies, including the monochorionicity-related pathologies, such as twin-twin transfusion syndrome, selective growth restriction, twin anaemia-polycythaemia sequence and twin reversed arterial perfusion sequence.

Twin pregnancy complicated by selective growth restriction.

PURPOSE OF REVIEW: Selective intrauterine growth restriction (sIUGR) in twin pregnancies presents a complex management problem for the fetal medicine specialist. This review summarizes what is currently known about sIUGR pathophysiology, particularly in monochorionic pregnancies and looks at the results of early trials of fetal intervention in high-risk sIUGR pregnancies. RECENT FINDINGS: sIUGR in monochorionic pregnancies is due to unequal placental sharing, but the clinical outcome is determined by the characteristics of the placental vascular anastomoses. Classification of monochorionic sIUGR by umbilical artery Doppler allows interventions to be targeted at high-risk subgroups. The overall survival after diagnosis of early-onset Type II/III sIUGR is similar after the management with cord occlusion and selective laser photocoagulation of connecting vessels. SUMMARY: Fetal interventions have been shown to be feasible and of potential benefit in early-onset sIUGR in a monochorionic twin pregnancy. Cord occlusion or selective laser photocoagulation of connecting vessels may be offered as an alternative to expectant management or preterm delivery in early-onset severe cases after careful discussion with the parents. Randomized controlled trial evidence is required to make a definitive judgment and to determine the impact of fetal intervention on the neurological outcomes.

Current best practice in the management of hypertensive disorders in pregnancy.

Preeclampsia is a potentially serious complication of pregnancy with increasing significance worldwide. Preeclampsia is the cause of 9%-26% of global maternal mortality and a significant proportion of preterm delivery, and maternal and neonatal morbidity. Incidence is increasing in keeping with the increase in obesity, maternal age, and women with medical comorbidities entering pregnancy. Recent developments in the understanding of the pathophysiology of preeclampsia have opened new avenues for prevention, screening, and management of this condition. In addition it is known that preeclampsia is a risk factor for cardiovascular disease in both the mother and the child and presents an opportunity for early preventative measures. New tools for early detection, prevention, and management of preeclampsia have the potential to revolutionize practice in the coming years. This review presents the current best practice in diagnosis and management of preeclampsia and the hypertensive disorders of pregnancy.

Evolution of Stage 1 Twin-to-Twin Transfusion Syndrome (TTTS): Systematic Review and Meta-Analysis.

OBJECTIVES: The natural history of stage 1 Twin-to-twin transfusion syndrome (TTTS) remains unclear and its optimal management is yet to be established. The main aims of this meta-analysis were to quantify the incidence of progression in stage 1 TTTS and to ascertain survival in these pregnancies. METHODS: MEDLINE, EMBASE, and The Cochrane Library were searched. Reference lists within each article were hand-searched for additional reports. The outcomes included incidence of progression and survival in stage 1 TTTS. Randomized controlled trials, cohort and case-control studies were included. Case reports, studies including three or fewer cases of stage 1 TTTS, and editorials were excluded. Proportion meta-analysis was used for analysis (Registration number: CRD42016036190). RESULTS: The search yielded 3,085 citations; 18 studies were included in the review (172 pregnancies to assess progression and 433 pregnancies to assess the survival). The pooled incidence of progression in stage 1 TTTS was 27% [95% CI 16-39%]. The pooled overall survival, double survival and at least one survival in the pregnancies managed expectantly were 79% [95% CI 62-92%], 70% [95% CI 54-84%] and 87% [95% CI 69-98%], respectively. In those undergoing amnioreduction, the corresponding figures were 77% [95% CI 68-85%], 67% [95% CI 57-76%] and 86% [95% CI 76-94%], respectively. The survival rates were 68% [95% CI 54-81%], 54% [95% CI 36-72%], and 81% [95% CI 69-90%], when laser surgery was performed. CONCLUSIONS: The optimal initial management of stage 1 TTTS remains in equipoise. The ongoing randomized trial comparing immediate laser surgery versus conservative management should provide a definitive answer.

Abnormal Middle Cerebral Artery Doppler Associates with Spontaneous Preterm Birth in Normally Grown Fetuses.

OBJECTIVE: Our aim was to evaluate whether Doppler changes in the fetal middle cerebral (MCA) and umbilical arteries (UA) suggesting fetal hypoxemia precede the onset of spontaneous preterm birth (PTB). METHODS: We studied 2,340 appropriate-for-gestational-age singleton pregnancies that had MCA and UA pulsatility indices (PI) recorded at 28-32 weeks. Values including the cerebroplacental ratio (CPR) were converted into multiples of the median and evaluated according to both gestational age at the onset of labor and the interval between ultrasound and labor. ROC analysis was used to calculate the ability in the prediction of spontaneous PTB before 32, 34 and 37 weeks' gestation. RESULTS: While no correlations were observed for the UA PI and CPR, lower MCA PI values were associated with an earlier onset of labor (p < 0.001) and a shorter ultrasound-labor interval (p = 0.028). The ROC analysis at different gestational ages and intervals to labor indicated that MCA PI values were poorly predictive of spontaneous PTB (all areas under the curve <0.7). CONCLUSIONS: Low MCA PI values at 28-32 weeks are associated with subsequent spontaneous PTB, indicating that fetal hypoxemia unrelated with placental disease might be implicated in the onset of labor. This association, however, is unlikely to be useful in the prediction of PTB.

Modelling for the robust design of layered resonators for ultrasonic particle manipulation.

Several approaches have been described for the manipulation of particles within an ultrasonic field. Of those based on standing waves, devices in which the critical dimension of the resonant chamber is less than a wavelength are particularly well suited to microfluidic, or "lab on a chip" applications. These might include pre-processing or fractionation of samples prior to analysis, formation of monolayers for cell interaction studies, or the enhancement of biosensor detection capability. The small size of microfluidic resonators typically places tight tolerances on the positioning of the acoustic node, and such systems are required to have high transduction efficiencies, for reasons of power availability and temperature stability. Further, the expense of many microfabrication methods precludes an iterative experimental approach to their development. Hence, the ability to design sub-wavelength resonators that are efficient, robust and have the appropriate acoustic energy distribution is extremely important. This paper discusses one-dimensional modelling used in the design of ultrasonic resonators for particle manipulation and gives example of their uses to predict and explain resonator behaviour. Particular difficulties in designing quarter wave systems are highlighted, and modelling is used to explain observed trends and predict performance of such resonators, including their performance with different coupling layer materials.

Spore and micro-particle capture on an immunosensor surface in an ultrasound standing wave system.

The capture of Bacillus subtilis var. niger spores on an antibody-coated surface can be enhanced when that coated surface acts as an acoustic reflector in a quarter wavelength ultrasonic (3 MHz) standing wave resonator. Immunocapture in such a resonator has been characterised here for both spores and 1 microm diameter biotinylated fluorescent microparticles. A mean spatial acoustic pressure amplitude of 460 kPa and a frequency of 2.82 MHz gave high capture efficiencies. It was shown that capture was critically dependent on reflector thickness. The time dependence of particle deposition on a reflector in a batch system was broadly consistent with a calculated time of 35 s to bring 95% of particles to the coated surface. A suspension flow rate of 0.1 ml/min and a reflector thickness of 1.01 mm gave optimal capture in a 2 min assay. The enhancement of particle detection compared with the control (no ultrasound) situation was x 70. The system detects a total of five particles in 15 fields of view in a 2 min assay when the suspending phase concentration was 10(4) particles/ml. A general expression for the dependence of minimum concentration detectable on; number of fields examined, sample volume flowing through the chamber and assay time shows that, for a practical combination of these variables, the threshold detection concentration can be two orders of magnitude lower.