Characterization of Moderate and Severe Asthma Exacerbations in the CAPTAIN Study.

BACKGROUND: Limited data exist on the relative impact of moderate and severe exacerbations on asthma control and impairment. OBJECTIVE: To explore data from the CAPTAIN trial to evaluate the relationship between first moderate or severe exacerbation and changes in lung function, symptoms, physical activity limitation scores, and short-acting ß2-agonist (SABA) usage to determine the clinical relevance of moderate events. METHODS: CAPTAIN was a phase IIIA 24- to 52-week, multicenter, international, randomized controlled trial evaluating efficacy and safety of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI in patients with uncontrolled asthma on inhaled corticosteroid/long-acting ß2-agonist. Outcomes reported include first postrandomization exacerbation event by severity (wk 1-52), frequency and duration of moderate and severe exacerbations, and time course of changes over ± 14-day peri-exacerbation period for lung function, symptoms, limitations, and SABA use. RESULTS: Of the intent-to-treat population (n = 2,436), 550 patients (23%) continued to 52 weeks. There were 529 moderate and 546 severe exacerbations. Lung function changes were similar, but symptom, physical activity limitation scores, and SABA use were higher, for severe versus moderate exacerbations. Lung function decline preceded increases in symptom, physical activity limitation scores, and SABA use, irrespective of exacerbation severity. Lung function variables, limitation scores, and SABA use returned to pre-exacerbation baseline after approximately 8 to 12 days for both exacerbation severities. CONCLUSIONS: Whereas severe events were associated with greater impact on symptoms, physical activity limitations, and SABA use, onset and time to resolution were generally similar for moderate and severe events. Both exacerbation severities represent clinically important deteriorations comprising clinical and functional changes.

NAxtra magnetic nanoparticles for low-cost, efficient isolation of mammalian DNA and RNA.

A cost-effective, viral nucleic acid (NA) isolation kit based on NAxtra magnetic nanoparticles was developed at the Norwegian University of Science and Technology in response to the shortage of commercial kits for isolation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA during the coronavirus disease 2019 (COVID-19) pandemic. This method showed comparable sensitivity to available kits at significantly reduced cost, making its application for other biological sources an intriguing prospect. Thus, based on this low-cost nucleic acid extraction technology, we developed a simple, low- and high-throughput, efficient method for isolation of high-integrity total NA, DNA and RNA from mammalian cell lines (monolayer) and organoids (3D-cultures). The extracted NA are compatible with downstream applications including (RT-)qPCR and next-generation sequencing. When automated, NA isolation can be performed in 14 min for up to 96 samples, yielding similar quantities to available kits.

The psychopathic hospital.

A new psychiatric institution emerged in the late nineteenth and early twentieth centuries: the psychopathic hospital. This institution represented a significant development in the history of psychiatry, as it marked the profession's reorientation from asylum-based to hospital-based care, and in this way presaged the deinstitutionalization movement that would begin half a century later. Psychopathic hospitals were also an important marker of psychiatry's efforts to redefine its professional boundaries and respond to its vociferous critics. This entailed both a rapprochement with general medicine in an effort to assert its scientific bona fides and a redefinition of its scope of practice to absorb non-certifiable 'borderland' cases in order both to emphasize non-coercive treatment and to enlarge the profession's boundaries.

The role of Medical Officers of Health in Civil Defence and how they influenced modern emergency medical practice.

OBJECTIVES: The article will examine the role of the Medical Officer of Health within United Kingdom Local Authorities in the period preceding the Second World War, the war itself, the residual impact of their work on emergency medical and public health practice and lessons that can be learned to improve. STUDY DESIGN: The article uses archival and secondary source analysis of documents related to the work of the Medical Officer of Health, their staff, and associated organisations. METHODS AND RESULTS: The Medical Officer of Health performed a key role in the Civil Defence of the United Kingdom, ensuring that the victims of aerial bombardment were treated quickly. They also worked to ensure the public health of the population was maintained, especially those covering areas receiving evacuees, and worked to improve conditions within deep shelters and other areas with displaced individuals. CONCLUSIONS: The work of the Medical Officer of Health created the forerunner of modern emergency medical practice in the United Kingdom, often through local innovation, and embedded the work on health promotion and protection fulfilled by Directors of Public Health.

Maternal autonomy and prenatal harm.

This paper offers an account of why prenatal harms seem particularly objectionable. It identifies structural similarities between key cases of prenatal harm and the recently characterized "all-or-nothing" problem from Joe Horton. According to the account defended by the paper, a willingness to parent incurs a duty to protect the fetus from harm. This implication provides independent support for so-called "voluntarist" or "intentionalist" accounts of parental role obligations, according to which, roughly, a mother's autonomous choice to parent a child suffices for having the obligations distinctive of parenthood toward the child.

Message framing and COVID-19 vaccine acceptance among millennials in South India.

Vaccine hesitancy and refusal remain a major concern for healthcare professionals and policymakers. Hence, it is necessary to ascertain the underlying factors that promote or hinder the uptake of vaccines. Authorities and policy makers are experimenting with vaccine promotion messages to communities using loss and gain-framed messages. However, the effectiveness of message framing in influencing the intention to be vaccinated is unclear. Based on the Theory of Planned Behaviour (TPB), this study analysed the impact of individual attitude towards COVID-19 vaccination, direct and indirect social norms, perceived behavioural control and perceived threat towards South Indian millennials' intention to get vaccinated. The study also assessed the effect of framing vaccine communication messages with gain and loss framing. Data was collected from 228 Millennials from South India during the COVID-19 pandemic from September to October 2021 and analysed using PLS path modelling and Necessary Condition Analysis (NCA). The findings reveal that attitudes towards vaccination, perceived threat and indirect social norms positively impact millennials' intention to take up vaccines in both message frames. Further, independent sample t-test between the framing groups indicate that negative (loss framed message) leads to higher vaccination intention compared to positive (gain framed message). A loss-framed message is thus recommended for message framing to promote vaccine uptake among millennials. These findings provide useful information in understanding the impact of message framing on behavioural intentions, especially in the context of vaccine uptake intentions of Millennials in South India.

Gym-Goers' Self-Identification with Physically Attractive Fitness Trainers and Intention to Exercise.

Gym-goers often socially compare themselves with their trainers as they strive to look as attractive as their fitness trainers. The aim of this study was to better understand this phenomenon in the fitness industry. Relying on social comparison theory and social identity theory, self-identification with a physically attractive fitness trainer was posited to have a strong mediating effect on the relationship between appearance motive, weight management motive and gym-goers' intention to exercise. The moderation effects of gym-goers' age and gender in the direct relationships between appearance motive, weight management motive and exercise intention were also examined. The primary outcome of this study revealed that gym-goers who were influenced by appearance and weight management motives are more likely to identify with physically attractive fitness trainers. Additionally, gender significantly moderates the relationships between appearance motive, weight management motive and exercise intention. Appearance and weight management motives are the primary factors that influence the exercise intention of female gym-goers as compared to their male counterparts. This study sheds new insights into understanding the influence of the physical attractiveness of fitness trainers and its impact on gym-goers' exercise intentions via self and social identification process.

Food Innovation Adoption and Organic Food Consumerism-A Cross National Study between Malaysia and Hungary.

In order to meet the rising global demand for food and to ensure food security in line with the United Nation's Sustainable Development Goal 2, technological advances have been introduced in the food production industry. The organic food industry has benefitted from advances in food technology and innovation. However, there remains skepticism regarding organic foods on the part of consumers, specifically on consumers' acceptance of food innovation technologies used in the production of organic foods. This study measured factors that influence consumers' food innovation adoption and subsequently their intention to purchase organic foods. We compared the organic foods purchase behavior of Malaysian and Hungarian consumers to examine differences between Asian and European consumers. The findings show food innovation adoption as the most crucial predictor for the intention to purchase organic foods in Hungary, while social lifestyle factor was the most influential in Malaysia. Other factors such as environmental concerns and health consciousness were also examined in relation to food innovation adoption and organic food consumerism. This paper discusses differences between European and Asian organic foods consumers and provides recommendations for stakeholders.

Efficacy and safety of once-daily single-inhaler triple therapy (FF/UMEC/VI) versus FF/VI in patients with inadequately controlled asthma (CAPTAIN): a double-blind, randomised, phase 3A trial.

BACKGROUND: Despite inhaled corticosteroid plus long-acting ß2-agonist (ICS/LABA) therapy, 30-50% of patients with moderate or severe asthma remain inadequately controlled. We investigated the safety and efficacy of single-inhaler fluticasone furoate plus umeclidinium plus vilanterol (FF/UMEC/VI) compared with FF/VI. METHODS: In this double-blind, randomised, parallel-group, phase 3A study (Clinical Study in Asthma Patients Receiving Triple Therapy in a Single Inhaler [CAPTAIN]), participants were recruited from 416 hospitals and primary care centres across 15 countries. Participants were eligible if they were aged 18 years or older, with inadequately controlled asthma (Asthma Control Questionnaire [ACQ]-6 score of ≥1·5) despite ICS/LABA, a documented health-care contact or a documented temporary change in asthma therapy for treatment of acute asthma symptoms in the year before screening, pre-bronchodilator FEV1 between 30% and less than 85% of predicted normal value, and reversibility (defined as an increase in FEV1 of ≥12% and ≥200 mL in the 20-60 min after four inhalations of albuterol or salbutamol) at screening. Participants were randomly assigned (1:1:1:1:1:1), via central based randomisation stratified by pre-study ICS dose at study entry, to once-daily FF/VI (100/25 µg or 200/25 µg) or FF/UMEC/VI (100/31·25/25 µg, 100/62·5/25 µg, 200/31·25/25 µg, or 200/62·5/25 µg) administered via Ellipta dry powder inhaler (Glaxo Operations UK, Hertfordshire, UK). Patients, investigators, and the funder were masked to treatment allocation. Endpoints assessed in the intention-to-treat population were change from baseline in clinic trough FEV1 at week 24 (primary) and annualised moderate and/or severe asthma exacerbation rate (key secondary). Other secondary endpoints were change from baseline in clinic FEV1 at 3 h post-dose, St George's Respiratory Questionnaire (SGRQ) total score, and ACQ-7 total score, all at week 24. Change from baseline in Evaluating Respiratory Symptoms in Asthma total score at weeks 21-24 was also a secondary endpoint but is not reported here. Exploratory analyses of biomarkers of type 2 airway inflammation on treatment response were also done. This study is registered with ClinicalTrials.gov, NCT02924688, and is now complete. FINDINGS: Between Dec 16, 2016, and Aug 31, 2018, 5185 patients were screened and 2439 were recruited and randomly assigned to FF/VI (100/25 µg n=407; 200/25 µg n=406) or FF/UMEC/VI (100/31·25/25 µg n=405; 100/62·5/25 µg n=406; 200/31·25/25 µg n=404; 200/62·5/25 µg n=408), with three patients randomly assigned in error and not included in analyses. In the intention-to-treat population, 922 (38%) patients were men, the mean age was 53·2 years (SD 13·1) and body-mass index was 29·4 (6·6). Baseline demographics were generally similar across all treatment groups. The least squares mean improvement in FEV1 change from baseline for FF/UMEC/VI 100/62·5/25 µg versus FF/VI 100/25 µg was 110 mL (95% CI 66-153; p<0·0001) and for 200/62·5/25 µg versus 200/25 µg was 92 mL (49-135; p<0·0001). Adding UMEC 31·25 µg to FF/VI produced similar improvements (FF/UMEC/VI 100/31·25/25 µg vs FF/VI 100/25 µg: 96 mL [52-139; p<0·0001]; and 200/31·25/25 µg vs 200/25 µg: 82 mL [39-125; p=0·0002]). These results were supported by the analysis of clinic FEV1 at 3 h post-dose. Non-significant reductions in moderate and/or severe exacerbation rates were observed for FF/UMEC 62·5 µg/VI versus FF/VI (pooled analysis), with rates lower in FF 200 µg-containing versus FF 100 µg-containing treatment groups. All pooled treatment groups demonstrated mean improvements (decreases) in SGRQ total score at week 24 compared with baseline in excess of the minimal clinically important difference of 4 points; however, there were no differences between treatment groups. For mean change from baseline to week 24 in asthma control questionnaire-7 score, improvements (decreases) exceeding the minimal clinically important difference of 0·5 points were observed in all pooled treatment groups. Adding UMEC to FF/VI resulted in small, dose-related improvements compared with FF/VI (pooled analysis: FF/UMEC 31·25 µg/VI versus FF/VI, -0·06 (95% CI -0·12 to 0·01; p=0·094) FF/UMEC 62·5 µg/VI versus FF/VI, -0·09 (-0·16 to -0·02, p=0·0084). By contrast with adding UMEC, the effects of higher dose FF on clinic trough FEV1 and annualised moderate and/or severe exacerbation rate were increased in patients with higher baseline blood eosinophil count and exhaled nitric oxide. Occurrence of adverse events was similar across treatment groups (patients with at least one event ranged from 210 [52%] to 258 [63%]), with the most commonly reported adverse events being nasopharyngitis (51 [13%]-63 [15%]), headache (19 [5%]-36 [9%]), and upper respiratory tract infection (13 [3%]-24 [6%]). The incidence of serious adverse events was similar across all groups (range 18 [4%]-25 [6%)). Three deaths occurred, of which one was considered to be related to study drug (pulmonary embolism in a patient in the FF/UMEC/VI 100/31·25/25 µg group). INTERPRETATION: In patients with uncontrolled moderate or severe asthma on ICS/LABA, adding UMEC improved lung function but did not lead to a significant reduction in moderate and/or severe exacerbations. For such patients, single-inhaler FF/UMEC/VI is an effective treatment option with a favourable risk-benefit profile. Higher dose FF primarily reduced the rate of exacerbations, particularly in patients with raised biomarkers of type 2 airway inflammation. Further confirmatory studies into the differentiating effect of type 2 inflammatory biomarkers on treatment outcomes in asthma are required to build on these exploratory findings and further guide clinical practice. FUNDING: GSK.

Magician's Corner: 7. Using Convolutional Neural Networks to Reduce Noise in Medical Images.

This article shows how to train a convolutional neural network to reduce noise in CT images, although the principles apply to medical and nonmedical images; authors also explore mathematical and visually weighted loss functions to adjust the appearance.

A phase IIb, randomised, parallel-group study: the efficacy, safety and tolerability of once-daily umeclidinium in patients with asthma receiving inhaled corticosteroids.

BACKGROUND: Patients with asthma uncontrolled on inhaled corticosteroids may benefit from umeclidinium (UMEC), a long-acting muscarinic antagonist. METHODS: This Phase IIb, double-blind study included patients with reversible, uncontrolled/partially-controlled asthma for ≥6 months, receiving ≥100 mcg/day fluticasone propionate (or equivalent) for ≥12 weeks. Following a 2-week run-in on open-label fluticasone furoate (FF) 100 mcg, patients were randomised (1:1:1) to receive UMEC 31.25 mcg, UMEC 62.5 mcg or placebo on top of FF 100 mcg once-daily for 24 weeks. As-needed salbutamol was provided. Primary and secondary endpoints were change from baseline in clinic trough forced expiratory volume in 1 s (FEV1) and clinic FEV1 3 h post-dose, respectively, at Week 24. Other endpoints included change from baseline in home daily spirometry (trough FEV1, evening FEV1, morning [pre-dose] and evening peak expiratory flow) over 24 weeks. Safety was assessed throughout the study. RESULTS: The intent-to-treat population comprised 421 patients (UMEC 31.25 mcg: n =139, UMEC 62.5 mcg: n =139, placebo: n =143). UMEC 31.25 mcg and 62.5 mcg demonstrated significantly greater improvements from baseline in clinic trough FEV1 at Week 24 (difference [95% CI]: 0.176 L [0.092, 0.260; p<0.001] and 0.184 L [0.101, 0.268; p<0.001], respectively), clinic FEV1 3 h post-dose at Week 24 (0.190 L [0.100, 0.279; p<0.001] and 0.198 L [0.109, 0.287; p<0.001], respectively) and mean change from baseline in daily home spirometry over 24 weeks versus placebo. No new safety signals were identified. CONCLUSIONS: UMEC is a highly effective bronchodilator that leads to improved lung function when administered as a single bronchodilator on top of FF in subjects with fully reversible, uncontrolled/partially-controlled moderate asthma. These data support a favourable benefit/risk profile for UMEC (31.25 mcg and 62.5 mcg). TRIAL REGISTRATION: GSK study ID: 205832; Clinicaltrials.gov ID: NCT03012061.

Oligohydramnios: a prospective study of fetal, neonatal and maternal outcomes in low-middle income countries.

BACKGROUND: Oligohydramnios is a condition of abnormally low amniotic fluid volume that has been associated with poor pregnancy outcomes. To date, the prevalence of this condition and its outcomes has not been well described in low and low-middle income countries (LMIC) where ultrasound use to diagnose this condition in pregnancy is limited. As part of a prospective trial of ultrasound at antenatal care in LMICs, we sought to evaluate the incidence of and the adverse maternal, fetal and neonatal outcomes associated with oligohydramnios. METHODS: We included data in this report from all pregnant women in community settings in Guatemala, Pakistan, Zambia and the Democratic Republic of Congo (DRC) who received a third trimester ultrasound as part of the First Look Study, a randomized trial to assess the value of ultrasound at antenatal care. Using these data, we conducted a planned secondary analysis to compare pregnancy outcomes of women with to those without oligohydramnios. Oligohydramnios was defined as measurement of an Amniotic Fluid Index less than 5 cm in at least one ultrasound in the third trimester. The outcomes assessed included maternal morbidity and fetal and neonatal mortality, preterm birth and low-birthweight. We used pairwise site comparisons with Tukey-Kramer adjustment and multivariable logistic models using general estimating equations to account for the correlation of outcomes within cluster. RESULTS: Of 12,940 women enrolled in the clusters in Guatemala, Pakistan, Zambia and the DRC in the First Look Study who had a third trimester ultrasound examination, 87 women were diagnosed with oligohydramnios, equivalent to 0.7% of those studied. Prevalence of detected oligohydramnios varied among study sites; from the lowest of 0.2% in Zambia and the DRC to the highest of 1.5% in Pakistan. Women diagnosed with oligohydramnios had higher rates of hemorrhage, fetal malposition, and cesarean delivery than women without oligohydramnios. We also found unfavorable fetal and neonatal outcomes associated with oligohydramnios including stillbirths (OR 5.16, 95%CI 2.07, 12.85), neonatal deaths < 28 days (OR 3.18, 95% CI 1.18, 8.57), low birth weight (OR 2.10, 95% CI 1.44, 3.07) and preterm births (OR 2.73, 95%CI 1.76, 4.23). The mean birth weight was 162 g less (95% CI -288.6, - 35.9) with oligohydramnios. CONCLUSIONS: Oligohydramnos was associated with worse neonatal, fetal and maternal outcomes in LMIC. Further research is needed to assess effective interventions to diagnose and ultimately to reduce poor outcomes in these settings. TRIAL REGISTRATION: NCT01990625.

Serious Asthma Outcomes and Asthma Exacerbations with Maintenance on Inhaled Corticosteroid (Mometasone Furoate)/Long-Acting Beta Agonist (Formoterol) Combination Compared to Step Down to Mometasone Monotherapy.

BACKGROUND: Because of historical safety concerns with the use of long-acting ß-agonists (LABA) in asthma, step-down from inhaled corticosteroid (ICS)/LABA combination therapy to ICS monotherapy is recommended once asthma control is achieved. OBJECTIVE: To evaluate the benefit/risk question about whether patients with asthma who achieve disease control on fixed-dose ICS/LABA combination therapy, such as mometasone furoate/formoterol fumarate (MF/F), should continue with this therapy or be stepped down to ICS monotherapy, such as MF. METHODS: Using data from 8447 clinically stable patients with persistent asthma in the Safety Pharma Investigation of Respiratory Outcomes trial who had been receiving a stable dose of ICS/LABA for ≥4 weeks, this post hoc analysis evaluated the risk of serious asthma outcomes (SAOs) (adjudicated hospitalization, intubation, or death) and asthma exacerbation (AEX) (composite of hospitalizations ≥24 hours, emergency visits <24 hours requiring systemic corticosteroid, or systemic corticosteroid for ≥3 consecutive days) in participants randomized to remain on ICS/LABA (MF/F) or step down to ICS (MF) for 26 weeks. RESULTS: There was no significant difference in SAO risk among patients maintained on ICS/LABA with MF/F compared with those who stepped down from ICS/LABA to MF (hazard ratio [HR], 1.03 [95% confidence interval (CI): 0.61, 1.75], P = .913). The risk of AEX was significantly lower in patients maintained on ICS/LABA with MF/F compared with those who stepped down from ICS/LABA to MF (HR, 0.87 [95% CI: 0.78, 0.98], P = .020). CONCLUSIONS: In this post hoc analysis of a large clinical trial dataset, maintenance on ICS/LABA with MF/F is not associated with an increased risk of SAOs and also significantly reduces the risk of AEX compared with step-down from ICS/LABA to MF.

microRNA-451a prevents activation of matrix metalloproteinases 2 and 9 in human cardiomyocytes during pathological stress stimulation.

Matrix metalloproteinases (MMP) are important for cardiac remodeling. Recently, microRNA (miR)-451a has been found to inhibit the expression of both MMP-2 and MMP-9 in human malignancies, but its role in cardiomyocytes has not been explored. We hypothesized that miR-451a modulates MMP-2 and MMP-9 levels in human cardiomyocytes. The role of miR-451a on regulation of MMP-2 and MMP-9 was evaluated in two separate pathological models using Cor.4U human inducible pluripotent stem cell-derived cardiomyocytes (hiPS-CMs): 1) endothelin-1 (ET-1), and 2) 48-h hypoxia (1% O2). Both models were transfected with synthetic miR-451a mimics or scramble control. Expression of both mRNA and miR was determined by quantitative real-time polymerase chain reaction and protein activity by (MMP-2/9) activity assay. Bioinformatic analyses were performed using Targetscan 7.1 and STRING 10.5. hiPS-CMs stimulated by hypoxia increased both MMP-2 and MMP-9 expression levels compared with normoxia (P < 0.05), whereas ET-1 stimulation only increased the MMP-9 level compared with vehicle controls (P < 0.05). miR-451a mimics prevented the increase of MMP-2 and MMP-9 expression in both models. Protein activity of MMP-2 and MMP-9 was confirmed to be lower following treatment with miR-451a mimic compared with scramble-controls. Six of 28 predicted gene transcripts of miR-451a were linked to MMP-2 and MMP-9; Macrophage migration inhibitory factor (MIF) was the only predicted target of miR-451a that was increased by ET-1 and hypoxia and reduced following miR-451a mimic transfection. miR-451a prevent the increase of MMP-2 and MMP-9 in human cardiomyocytes during pathological stress. The modulation by miR-451a on MMP-2 and MMP-9 is caused by MIF.

Polyhydramnios among women in a cluster-randomized trial of ultrasound during prenatal care within five low and low-middle income countries: a secondary analysis of the first look study.

BACKGROUND: In many low and low-middle income countries, the incidence of polyhydramnios is unknown, in part because ultrasound technology is not routinely used. Our objective was to report the incidence of polyhydramnios in five low and low-middle income countries, to determine maternal characteristics associated with polyhydramnios, and report pregnancy and neonatal outcomes. METHODS: We performed a secondary analysis of the First Look Study, a multi-national, cluster-randomized trial of ultrasound during prenatal care. We evaluated all women enrolled from Guatemala, Pakistan, Zambia, Kenya and the Democratic Republic of Congo (DRC) who received an examination by prenatal ultrasound. We used pairwise site comparisons with Tukey-Kramer adjustment and multivariable logistic models with general estimating equations to control for cluster-level effects. The diagnosis of polyhydramnios was confrimed by an U.S. based radiologist in a majority of cases (62%). RESULTS: We identified 305/18,640 (1.6%) cases of polyhydramnios. 229 (75%) cases were from the DRC, with an incidence of 10%. A higher percentage of women with polyhydramnios experienced obstructed labor (7% vs 4%) and fetal malposition (4% vs 2%). Neonatal death was more common when polyhydramnios was present (OR 2.43; CI 1.15, 5.13). CONCLUSIONS: Polyhydramnios occured in these low and low-middle income countries at a rate similar to high-income contries except in the DRC where the incidence was 10%. Polyhydramnios was associated with obstructed labor, fetal malposition, and neonatal death. TRIAL REGISTRATION: NCT01990625 , November 21, 2013.

Use of ultrasound and mHealth to improve perinatal outcomes in low and middle income countries.

The explosion of mobile health and portable obstetric ultrasound interventions in low- and middle-income countries (LMIC) reflects the optimism that technology can help reduce persistently high rates of maternal and neonatal mortality and morbidity in these settings. While these technology-driven interventions have had success in improving aspects of antenatal and perinatal care, they have not clearly demonstrated reductions in mortality. The expanding synergy between mobile health (mHealth) and ultrasound technology shows promise to enhance care, but it will likely take combining these technological advances with system-wide approaches that also address referral patterns and infrastructure barriers to improve outcomes.

Including ultrasound scans in antenatal care in low-resource settings: Considering the complementarity of obstetric ultrasound screening and maternity waiting homes in strengthening referral systems in low-resource, rural settings.

Recent World Health Organization (WHO) antenatal care recommendations include an ultrasound scan as a part of routine antenatal care. The First Look Study, referenced in the WHO recommendation, subsequently shows that the routine use of ultrasound during antenatal care in rural, low-income settings did not improve maternal, fetal or neonatal mortality, nor did it increase women's use of antenatal care or the rate of hospital births. This article reviews the First Look Study, reconsidering the assumptions upon which it was built in light of these results, a supplemental descriptive study of interviews with patients and sonographers that participated in the First Look study intervention, and a review of the literature. Two themes surface from this review. The first is that focused emphasis on building the pregnancy risk screening skills of rural primary health care personnel may not lead to adaptations in referral hospital processes that could benefit the patient accordingly. The second is that agency to improve the quality of patient reception at referral hospitals may need to be manufactured for obstetric ultrasound screening, or remote pregnancy risk screening more generally, to have the desired impact. Stemming from the literature, this article goes on to examine the potential for complementarity between obstetric ultrasound screening and another approach encouraged by the WHO, the maternity waiting home. Each approach may address existing shortcomings in how the other is currently understood. This paper concludes by proposing a path toward developing and testing such a hybrid approach.

Serious asthma events with mometasone furoate plus formoterol compared with mometasone furoate.

BACKGROUND: The safety of long-acting ß-agonists added to inhaled corticosteroids for the treatment of persistent asthma has been controversial. OBJECTIVE: We sought to determine whether administering formoterol in combination with mometasone furoate increases the risk of serious asthma outcomes (SAOs) compared with mometasone furoate alone. This clinical trial is registered as NCT01471340. METHODS: We conducted a 26-week, randomized, double-blind trial in adolescent and adult patients (≥12 years) with persistent asthma in 35 countries with the primary objective of evaluating whether mometasone furoate-formoterol increases the risk of SAOs (adjudicated hospitalization, intubation, or death) compared with mometasone furoate alone. The key efficacy end point was asthma exacerbation (composite of hospitalization of ≥24 hours, emergency department visits of <24 hours requiring systemic corticosteroids, or use of systemic corticosteroids for ≥3 consecutive days). RESULTS: Among 11,729 patients (mometasone furoate-formoterol, n = 5,868; mometasone furoate, n = 5,861), a total of 81 SAOs, all asthma-related hospitalizations, were observed in 71 patients: 45 events from 39 patients receiving mometasone furoate-formoterol and 36 events from 32 patients receiving mometasone furoate. The hazard ratio for the first SAO in the mometasone furoate-formoterol versus mometasone furoate group was 1.22 (95% CI, 0.76-1.94; P = .411). Asthma exacerbation occurred in 1,487 patients: 708 receiving mometasone furoate-formoterol and 779 receiving mometasone furoate. The hazard ratio for the first asthma exacerbation in the mometasone furoate-formoterol versus mometasone furoate group was 0.89 (95% CI, 0.80-0.98; P = .021). CONCLUSIONS: The addition of formoterol to mometasone furoate maintenance therapy did not increase the risk of serious asthma-related events and reduced the risk of asthma exacerbation.