Collagen-ß-cyclodextrin hydrogels for advanced wound dressings: super-swelling, antibacterial action, inflammation modulation, and controlled drug release.

A key strategy in enhancing the efficacy of collagen-based hydrogels involves incorporating polysaccharides, which have shown great promise for wound healing. In this study, semi-interpenetrating polymeric network (semi-IPN) hydrogels comprised of collagen (Col) with the macrocyclic oligosaccharide ß-cyclodextrin (ß-CD) (20-80 wt.%) were synthesised. Fourier-transform infrared (FTIR) spectroscopy confirmed the successful fabrication of these Col/ß-CD hydrogels, evidenced by the presence of characteristic absorption bands, including the urea bond band at ∼1740 cm-1, related with collagen crosslinking. Higher ß-CD content was associated with increased crosslinking, higher swelling, and faster gelation. The ß-CD content directly influenced the morphology and semi-crystallinity. All Col/ß-CD hydrogels displayed superabsorbent properties, enhanced thermal stability, and exhibited slow degradation rates. Mechanical properties were significantly improved with contents higher than ß-CD 40 wt.%. These hydrogels inhibited the growth of Escherichia coli bacteria and facilitated the controlled release of agents, such as malachite green, methylene blue, and ketorolac. The chemical composition of the Col/ß-CD hydrogels did not induce cytotoxic effects on monocytes and fibroblast cells. Instead, they actively promoted cellular metabolic activity, encouraging cell growth and proliferation. Moreover, cell signalling modulation was observed, leading to changes in the expression of TNF-α and IL-10 cytokines. In summary, the results of this research indicate that these novel hydrogels possess multifunctional characteristics, including biocompatibility, super-swelling capacity, good thermal, hydrolytic, and enzymatic degradation resistance, antibacterial activity, inflammation modulation, and the ability to be used for controlled delivery of therapeutic agents, indicating high potential for application in advanced wound dressings.

The experience of pregnant women and their families who were infected with covid-19 before vaccination: A qualitative approach within a multicenter study in Brazil.

BACKGROUND: Pregnant and postpartum women infected by COVID-19 are at increased risk of adverse outcomes, including negative effects on their mental health. Brazilian maternal mortality rate due to COVID-19 is 2.5 times higher than overall mortality rates. This study aimed to understand how pregnant/postpartum women experienced the COVID-19 suspicion/investigation or confirmed infection in different Brazilian cities, the pandemic's consequences to women and their families, and their needs to improve maternal health services during public health emergencies. METHODS: We conducted a qualitative study with 27 women with COVID-19 and 6 of their family members, as part of a multicenter study among 15 maternity hospitals in Brazil. We applied in-depth interviews through telephone calls when women received the diagnostic or had a suspect infection and after 60 days. Another semi-structured interview was applied to their close family members. The interviews were considered through thematic analysis. RESULTS: From the thematic content analysis three major themes emerged from the first and second interviews: (Cucinotta and Vanelli, 2020) assistance received by the woman and newborn in the medical services; (World Health Organization (WHO) 2021) stigma/fear of contamination from health workers and from family and friends reported by the women; (Allotey et al., 2020) the COVID-19 pandemic impact. CONCLUSION: Before the availability of the COVID-19 vaccine, pregnant women experienced fear of death, hospitalization, quarantine, loss of family members, and financial repercussions, resulting in physical, psychological, and socioeconomic impacts on these women's lives.

Surviving maternal sepsis: Clinical, laboratory, and treatment features.

OBJECTIVE: To describe clinical, laboratory, and antibiotic treatment characteristics in pregnant or recently pregnant women diagnosed with maternal sepsis. METHODS: A retrospective cohort study was conducted in a Brazilian tertiary hospital from March 2014 until February 2018. The hospital implemented a Sepsis Protocol, based on the Brazilian Ministry of Health recommendation. All women who were pregnant or recently pregnant (up to 42 days postpartum), and who presented with suspected sepsis were included. Unconfirmed infections were excluded. Three hundred sixty-five women were included and divided into three groups according to sepsis severity (SEPSIS-2): sepsis, severe sepsis, and septic shock. Clinical, laboratory, and management characteristics were described and compared. RESULTS: Pregnancy-related and respiratory tract infections were the greater causes of maternal sepsis, and the urinary tract was the major cause of septic shock. We found almost total compliance with blood culture sample collection, and samples were positive in 10.8% of the cases, and in 41% of septic shock patients. Escherichia coli was the most common pathogen found and it was resistant to third-generation cephalosporins in none of the blood cultures and 3.3% of the urine cultures. Using the AWaRe (Access, Watch and Reserve) classification groups of antibiotics, Access and Watch antibiotics were used in virtually all women. We did not find any fatal maternal outcomes. CONCLUSION: Maternal sepsis is seldom the result of resistant microorganisms in this setting and the use of Access group antibiotics is widely possible. Health professionals' awareness of and institutional policies for maternal sepsis are crucial to its adequate treatment and better outcomes.

Aetiology and use of antibiotics in pregnancy-related infections: results of the WHO Global Maternal Sepsis Study (GLOSS), 1-week inception cohort.

BACKGROUND: Pregnancy-related infections are important contributors to maternal sepsis and mortality. We aimed to describe clinical, microbiological characteristics and use of antibiotics by source of infection and country income, among hospitalized women with suspected or confirmed pregnancy-related infections. METHODS: We used data from WHO Global Maternal Sepsis Study (GLOSS) on maternal infections in hospitalized women, in 52 low-middle- and high-income countries conducted between November 28th and December 4th, 2017, to describe the frequencies and medians of maternal demographic, obstetric, and clinical characteristics and outcomes, methods of infection diagnosis and causative pathogens, of single source pregnancy-related infection, other than breast, and initial use of therapeutic antibiotics. We included 1456 women. RESULTS: We found infections of the genital (n = 745/1456, 51.2%) and the urinary tracts (UTI) (n = 531/1456, 36.5%) to be the most frequent. UTI (n = 339/531, 63.8%) and post-caesarean skin and soft tissue infections (SSTI) (n = 99/180, 55.0%) were the sources with more culture samples taken and microbiological confirmations. Escherichia coli was the major uropathogen (n = 103/118, 87.3%) and Staphylococcus aureus (n = 21/44, 47.7%) was the commonest pathogen in SSTI. For 13.1% (n = 191) of women, antibiotics were not prescribed on the same day of infection suspicion. Cephalosporins (n = 283/531, 53.3%) were the commonest antibiotic class prescribed for UTI, while metronidazole (n = 303/925, 32.8%) was the most prescribed for all other sources. Ceftriaxone with metronidazole was the commonest combination for the genital tract (n = 98/745, 13.2%) and SSTI (n = 22/180, 12.2%). Metronidazole (n = 137/235, 58.3%) was the most prescribed antibiotic in low-income countries while cephalosporins and co-amoxiclav (n = 129/186, 69.4%) were more commonly prescribed in high-income countries. CONCLUSIONS: Differences in antibiotics used across countries could be due to availability, local guidelines, prescribing culture, cost, and access to microbiology laboratory, despite having found similar sources and pathogens as previous studies. Better dissemination of recommendations in line with antimicrobial stewardship programmes might improve antibiotic prescription.

The effect of body mass index on maternal and perinatal outcomes in COVID-19 infection during pregnancy and postpartum: Secondary analysis from the REBRACO cohort study.

OBJECTIVES: To compare maternal and perinatal outcomes among women with obesity, overweight, and normal body mass index, associated with COVID-19 infection during pregnancy and postpartum. METHOD: Prospective Cohort Study, within the REBRACO (Brazilian Network of COVID-19 in Pregnancy) multicenter initiative. Confirmed positive cases of SARS-CoV-2 were included, and women categorized into three groups according to their pre-pregnancy BMI: obesity (BMI ≥ 30), overweight (BMI <30 but >25), and normal BMI. Sociodemographic, clinical, and obstetric characteristics and different maternal and perinatal outcomes were compared, and a multiple regression analysis was performed to investigate factors independently associated with adverse maternal and perinatal outcomes. RESULTS: Two hundred eighty-nine women positive for SARS-CoV-2 infection were considered, and 202 had available data on maternal BMI for the current analysis. Overall, 72 (35.6%)obese, 68 (33.6%) overweight, and 60 (29.7%) normal BMI. Obesity was associated with increased adverse clinical outcomes including sepsis (P = 0.02), acute respiratory distress syndrome (P = 0.002), and the need for mechanical ventilation (P = 0.044). Considering perinatal outcomes, a multiple regression model confirmed obesity as an independent factor associated with adverse results (adjusted odds ratio 3.73, 95% CI 1.54-9.08). CONCLUSION: Obesity and overweight were associated with worse clinical outcomes, severe/critical COVID-19, and adverse perinatal outcomes.

Role of biomarkers (sFlt-1/PlGF) in cases of COVID-19 for distinguishing preeclampsia and guiding clinical management.

OBJECTIVES: To analyze soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factors (PlGF) concentrations and their ratio in pregnant and postpartum women with suspected COVID-19, and further investigate conditions associated with an increased ratio (sFlt-1/PlGF > 38), including preeclampsia (PE) and severe acute respiratory syndrome (SARS). STUDY DESIGN: The present study is a secondary analysis of a prospective cohort. Blood samples were collected at time of COVID-19 investigation and the serum measurements of sFlt-1 and PlGF were performed. Clinical background, SARS-CoV-2 infection characteristics, maternal and perinatal outcomes were further analyzed. MAIN OUTCOME MEASURES: Serum measurements of sFlt-1 and PlGF; obstetrics and clinical outcomes. RESULTS: A total of 97 SARS-CoV-2 unvaccinated women with suspected infection were considered, 76 were COVID-19 positive cases and 21 COVID-19 negative. Among COVID-19 positive cases, 09 presented with SARS and 11 were diagnosed with PE, of which 6 had SARS-CoV-2 infection in first and second trimester (04 with sFlt-1/PlGF ≥ 38) and 05 with PE and COVID-19 diagnosed at the same time, during third trimester (03 with sFlt-1/PlGF ≥ 38). Five presented with PE with severe features. sFlt-1/PlGF ratio was significantly higher in the COVID-19 positive/PE positive group compared to COVID-19 positive/PE negative group (p-value = 0.005), with no increase in cases complicated by SARS. CONCLUSIONS: sFlt-1/PlGF ratio could be a useful tool for differential diagnosis and adequate counseling among cases of COVID-19 and PE, especially if severe disease. COVID-19 early in pregnancy could potentially be a risk factor for PE later during gestation.

The COVID-19 pandemic in Brazilian pregnant and postpartum women: results from the REBRACO prospective cohort study.

Brazil presented a very high number of maternal deaths and evident delays in healthcare. We aimed at evaluating the characteristics of SARS-CoV-2 infection and associated outcomes in the obstetric population. We conducted a prospective cohort study in 15 Brazilian centers including symptomatic pregnant or postpartum women with suspected COVID-19 from Feb/2020 to Feb/2021. Women were followed from suspected infection until the end of pregnancy. We analyzed maternal characteristics and pregnancy outcomes associated with confirmed COVID-19 infection and SARS, determining unadjusted risk ratios. In total, 729 symptomatic women with suspected COVID-19 were initially included. Among those investigated for COVID-19, 51.3% (n = 289) were confirmed COVID-19 and 48% (n = 270) were negative. Initially (before May 15th), only 52.9% of the suspected cases were tested and it was the period with the highest proportion of ICU admission and maternal deaths. Non-white ethnicity (RR 1.78 [1.04-3.04]), primary schooling or less (RR 2.16 [1.21-3.87]), being overweight (RR 4.34 [1.04-19.01]) or obese (RR 6.55 [1.57-27.37]), having public prenatal care (RR 2.16 [1.01-4.68]), planned pregnancies (RR 2.09 [1.15-3.78]), onset of infection in postpartum period (RR 6.00 [1.37-26.26]), chronic hypertension (RR 2.15 [1.37-4.10]), pre-existing diabetes (RR 3.20 [1.37-7.46]), asthma (RR 2.22 [1.14-4.34]), and anaemia (RR 3.15 [1.14-8.71]) were associated with higher risk for SARS. The availability of tests and maternal outcomes varied throughout the pandemic period of the study; the beginning was the most challenging period, with worse outcomes. Socially vulnerable, postpartum and previously ill women were more likely to present SARS related to COVID-19.

Preeclampsia among women with COVID-19 during pregnancy and its impact on maternal and perinatal outcomes: Results from a national multicenter study on COVID in Brazil, the REBRACO initiative.

OBJECTIVE: To evaluate the prevalence of preeclampsia among cases of COVID-19 infection during pregnancy and the association between both conditions, in a multicenter cohort of Brazilian women with respiratory symptoms. STUDY DESIGN: Ancillary analysis of the Brazilian Network of COVID-19 in Obstetrics (REBRACO) study. We performed a nested case-control analysis selecting all women with COVID-19 and compared outcomes between women with and without PE. MAIN OUTCOMES: Maternal, gestational, and clinical characteristics and perinatal outcomes. MEASURES: Prevalence ratio (PR) and its 95%CI for each of the predictors and outcomes. RESULTS: A total of 203 women were included: 21 (10.3%) in PE group and 182 (89.7%) in non-PE group. Preeclampsia was not different among women with and without COVID-19 (10.3% vs 13.1%, p-value = 0.41), neither complication such as eclampsia and HELLP syndrome. Chronic hypertension (33.4%) (p < 0.01) and obesity (60.0%) (p = 0.03) were the most frequent comorbidities in PE group, and they were significantly more frequent in this group. Women with PE had more cesarean section (RR 5.54 [1.33 - 23.14]) and their neonates were more frequently admitted to neonatal intensive care unit (PR 2.46[1.06 - 5.69]), most likely due to preterm-birth-related complications. CONCLUSION: The prevalence of PE among women with COVID-19 infection during pregnancy was around 10%; women with COVID-19 and a history of chronic hypertension or obesity are more likely to have preeclampsia. Cesarean section is increased among women with PE and COVID-19, with increased rates of neonatal admission to intensive care units, mostly due to prematurity.

Comparison of the CIPHER prognostic model with the existing scores in predicting severe maternal outcomes during intensive care unit admission.

OBJECTIVE: To compare the performance of the Collaborative Integrated Pregnancy High-Dependency Estimate of Risk (CIPHER) model in predicting maternal death and near-miss morbidity (Severe Maternal Outcome [SMO]) with the Sequential Organ Failure Assessment (SOFA), the Acute Physiology and Chronic Health Evaluation (APACHE) II, and the Simplified Acute Physiology Score (SAPS) III scores. METHODS: A retrospective and a prospective study was conducted at two centers in Brazil. For each score, area under curve (AUC) was used and score calibration was assessed using the Hosmer-Lemeshow statistic (H-L) test and the standardized mortality ratio (SMR). RESULTS: A cohort of 590 women was analyzed. A SMO was observed in 216 (36.6%) women. Of these, 13 (2.2%) were maternal deaths and 203 (34.4%) met one or more maternal near-miss criteria. The CIPHER model did not show significant diagnostic ability (AUC 0.52) and consequently its calibration was poor (H-L P < 0.05). The SAPS III had the best performance (AUC 0.77, H-L P > 0.05 and SMR 0.85). CONCLUSION: The performance of the CIPHER model was lower compared to the other scores. Since the CIPHER model is not ready for clinical use, the SAPS III score should be considered for the prediction of SMO.

Prognostic Value of an Estimate-of-Risk Model in Critically Ill Obstetric Patients in Brazil.

OBJECTIVE: To externally validate the CIPHER (Collaborative Integrated Pregnancy High-Dependency Estimate of Risk) prognostic model for pregnant and postpartum women admitted to the intensive care unit. METHODS: A retrospective and a prospective validation study were conducted at two reference centers in Brazil. A composite outcome was defined as maternal death or need for prolonged organ support (more than 7 days) or acute lifesaving intervention. To evaluate the performance of the CIPHER model, a receiver operating characteristic curve was used and score calibration was assessed by the Hosmer-Lemeshow test. We conducted a descriptive analysis comparing the results of the current study with the results of the model development study. RESULTS: A total of 590 women were included. The composite outcome was observed in 90 (15.2%) women. Of these, 13 (2.2%) were maternal deaths and 77 (13%) required one or more component of organ support or lifesaving intervention. The CIPHER model's area under the curve (AOC) did not show significant predictive ability (AOC 0.53, 95% CI 0.46-0.60), and consequently its calibration was poor (Hosmer-Lemeshow test P<.05). CONCLUSION: The CIPHER model for prediction of mortality and need for interventions in critically ill obstetric patients did not perform well in our Brazilian population. Different predictors of morbidity and mortality may need to be used for patients receiving care in public hospitals in low- and middle-income countries.

Brazilian network of COVID-19 during pregnancy (REBRACO: a multicentre study protocol).

INTRODUCTION: The aim of this study was to evaluate the clinical, epidemiological and laboratory aspects of SARS-CoV-2 infection during pregnancy and postpartum in 16 maternity hospitals. METHODS AND ANALYSIS: A prospective multicentre study, with five axes. First, the prevalence of SARS-CoV-2 infection among women admitted for childbirth will be described in a cross-sectional study. Second, maternal and perinatal outcomes will be assessed in a prospective cohort study including pregnant or postpartum women with suspected COVID-19. Third, a cohort of positive COVID-19 cases with sampling of a variety of biological material. Histopathological and viral analysis of biological maternal and neonatal samples will be performed, and the assessment of nutritional variables to evaluate the association between vitamin D and severity of infection. Fourth, a monitoring and evaluation committee to collect relevant healthcare information and plan actions in centres facing the pandemic. Furthermore, qualitative studies will be performed to study pregnant women, their families and health professionals. Fifth, an ecological study will monitor the number of live births, stillbirths and other outcomes to explore any trend among the periods before, during and after the pandemic. Data will systematically be collected in an electronic platform following standardised operational procedures. For quantitative study components, an appropriate statistical approach will be used for each analysis. For qualitative data, in-depth interviews recorded in audio will be transcribed, checking the text obtained with the recording. Subsequently, thematic analysis with the aid of the NVivo programme will be performed. ETHICS AND DISSEMINATION: Ethical approval was obtained (letters of approval numbers 4.047.168, 4.179.679 and 4.083.988). All women will be fully informed to sign the consent form before enrolment in the study. Findings will be disseminated through peer-reviewed journals and scientific conferences.

Perinatal outcomes among births to women with infection during pregnancy.

OBJECTIVE: This study is part of the Global Maternal Sepsis Study (GLOSS). It aimed to estimate neonatal near-miss (NNM) and perinatal death frequency and maternal risk factors among births to women with infection during pregnancy in low-income and middle-income countries (LMIC). DESIGN: We conducted a 1-week inception hospital-based cohort study. SETTING: The study was carried out in 408 hospitals in 43 LMIC of all the WHO regions in 2017. PATIENTS: We included women with suspected or confirmed infection during pregnancy with at least 28 weeks of gestational age up to day-7 after birth. All babies born to those women were followed from birth until the seventh day after childbirth. Perinatal outcomes were considered at the end of the follow-up. MAIN OUTCOME MEASURES: Perinatal outcomes were (i) babies alive without severe complication, (ii) NNM and (iii) perinatal death (stillbirth and early neonatal death). RESULTS: 1219 births were analysed. Among them, 25.9% (n=316) and 10.1% (n=123) were NNM and perinatal deaths, respectively. After adjustment, maternal pre-existing medical condition (adjusted odds ratios (aOR)=1.5; 95% CI 1.1 to 2.0) and maternal infection suspected or diagnosed during labour (aOR=1.9; 95% CI 1.2 to 3.2) were the independent risk factors of NNM. Maternal pre-existing medical condition (aOR=1.7; 95% CI 1.0 to 2.8), infection-related severe maternal outcome (aOR=3.8; 95% CI 2.0 to 7.1), mother's infection suspected or diagnosed within 24 hours after childbirth (aOR=2.2; 95% CI 1.0 to 4.7) and vaginal birth (aOR=1.8; 95% CI 1.1 to 2.9) were independently associated with increased odds of perinatal death. CONCLUSIONS: Overall, one-third of births were adverse perinatal outcomes. Pre-existing maternal medical conditions and severe infection-related maternal outcomes were the main risk factors of adverse perinatal outcomes.

Amyloid Aggregation of Streptococcus mutans Cnm Influences Its Collagen-Binding Activity.

The cnm gene, coding for the glycosylated collagen- and laminin-binding surface adhesin Cnm, is found in the genomes of approximately 20% of Streptococcus mutans clinical isolates and is associated with systemic infections and increased caries risk. Other surface-associated collagen-binding proteins of S. mutans, such as P1 and WapA, have been demonstrated to form an amyloid quaternary structure with functional implications within biofilms. In silico analysis predicted that the ß-sheet-rich N-terminal collagen-binding domain (CBD) of Cnm has a propensity for amyloid aggregation, whereas the threonine-rich C-terminal domain was predicted to be disorganized. In this study, thioflavin-T fluorescence and electron microscopy were used to show that Cnm forms amyloids in either its native glycosylated or recombinant nonglycosylated form and that the CBD of Cnm is the main amyloidogenic unit of Cnm. We then performed a series of in vitro, ex vivo, and in vivo assays to characterize the amylogenic properties of Cnm. In addition, Congo red birefringence indicated that Cnm is a major amyloidogenic protein of S. mutans biofilms. Competitive binding assays using collagen-coated microtiter plates and dental roots, a substrate rich in collagen, revealed that Cnm monomers inhibit S. mutans binding to collagenous substrates, whereas Cnm amyloid aggregates lose this property. Thus, while Cnm contributes to recognition and initial binding of S. mutans to collagen-rich surfaces, amyloid formation by Cnm might act as a negative regulatory mechanism to modulate collagen-binding activity within S. mutans biofilms and warrants further investigation. IMPORTANCE Streptococcus mutans is a keystone pathogen that promotes caries by acidifying the dental biofilm milieu. The collagen- and laminin-binding glycoprotein Cnm is a virulence factor of S. mutans. Expression of Cnm by S. mutans is hypothesized to contribute to niche expansion, allowing colonization of multiple sites in the body, including collagen-rich surfaces such as dentin and heart valves. Here, we suggest that Cnm function might be modulated by its aggregation status. As a monomer, its primary function is to promote attachment to collagenous substrates via its collagen-binding domain (CBD). However, in later stages of biofilm maturation, the same CBD of Cnm could self-assemble into amyloid fibrils, losing the ability to bind to collagen and likely becoming a component of the biofilm matrix. Our findings shed light on the role of functional amyloids in S. mutans pathobiology and ecology.

Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice.

Zika virus (ZIKV) has the ability to cross placental and brain barriers, causing congenital malformations in neonates and neurological disorders in adults. However, the pathogenic mechanisms of ZIKV-induced neurological complications in adults and congenital malformations are still not fully understood. Gas6 is a soluble TAM receptor ligand able to promote flavivirus internalization and downregulation of immune responses. Here we demonstrate that there is a correlation between ZIKV neurological complications with higher Gas6 levels and the downregulation of genes associated with anti-viral response, as type I IFN due to Socs1 upregulation. Also, Gas6 gamma-carboxylation is essential for ZIKV invasion and replication in monocytes, the main source of this protein, which was inhibited by warfarin. Conversely, Gas6 facilitates ZIKV replication in adult immunocompetent mice and enabled susceptibility to transplacental infection. Our data indicate that ZIKV promotes the upregulation of its ligand Gas6, which contributes to viral infectivity and drives the development of severe adverse outcomes during ZIKV infection.

Facing the COVID-19 pandemic inside maternities in Brazil: A mixed-method study within the REBRACO initiative.

INTRODUCTION: COVID-19 pandemic posed major challenges in obstetric health care services. Preparedness, development, and implementation of new protocols were part of the needed response. This study aims to describe the strategies implemented and the perspectives of health managers on the challenges to face the pandemic in 16 different maternity hospitals that comprise a multicenter study in Brazil, called REBRACO (Brazilian network of COVID-19 during pregnancy). METHODS: Mixed-method study, with quantitative and qualitative approaches. Quantitative data on the infrastructure of the units, maternal and perinatal health indicators, modifications on staff and human resources, from January to July/2020. Also, information on total number of cases, and availability for COVID-19 testing. A qualitative study by purposeful and saturation sampling was undertaken with healthcare managers, to understand perspectives on local challenges in facing the pandemic. RESULTS: Most maternities early implemented their contingency plan. REBRACO centers reported 338 confirmed COVID-19 cases among pregnant and post-partum women up to July 2020. There were 29 maternal deaths and 15 (51.8%) attributed to COVID-19. All maternities performed relocation of beds designated to labor ward, most (75%) acquired mechanical ventilators, only the minority (25%) installed new negative air pressure rooms. Considering human resources, around 40% hired extra health professionals and increased weekly workload and the majority (68.7%) also suspended annual leaves. Only one center implemented universal screening for childbirth and 6 (37.5%) implemented COVID-19 testing for all suspected cases, while around 60% of the centers only tested moderate/severe cases with hospital admission. Qualitative results showed that main challenges experienced were related to the fear of the virus, concerns about reliability of evidence and lack of resources, with a clear need for mental health support among health professionals. CONCLUSION: Study findings suggest that maternities of the REBRACO initiative underwent major changes in facing the pandemic, with limitations on testing, difficulties in infrastructure and human resources. Leadership, continuous training, implementation of evidence-based protocols and collaborative initiatives are key to transpose the fear of the virus and ascertain adequate healthcare inside maternities, especially in low and middle-income settings. Policy makers need to address the specificities in considering reproductive health and childbirth during the COVID-19 pandemic and prioritize research and timely testing availability.

Maternal outcomes and risk factors for COVID-19 severity among pregnant women.

Pregnant women may be at higher risk of severe complications associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may lead to obstetrical complications. We performed a case control study comparing pregnant women with severe coronavirus disease 19 (cases) to pregnant women with a milder form (controls) enrolled in the COVI-Preg international registry cohort between March 24 and July 26, 2020. Risk factors for severity, obstetrical and immediate neonatal outcomes were assessed. A total of 926 pregnant women with a positive test for SARS-CoV-2 were included, among which 92 (9.9%) presented with severe COVID-19 disease. Risk factors for severe maternal outcomes were pulmonary comorbidities [aOR 4.3, 95% CI 1.9-9.5], hypertensive disorders [aOR 2.7, 95% CI 1.0-7.0] and diabetes [aOR2.2, 95% CI 1.1-4.5]. Pregnant women with severe maternal outcomes were at higher risk of caesarean section [70.7% (n = 53/75)], preterm delivery [62.7% (n = 32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n = 31/75)]. In this study, several risk factors for developing severe complications of SARS-CoV-2 infection among pregnant women were identified including pulmonary comorbidities, hypertensive disorders and diabetes. Obstetrical and neonatal outcomes appear to be influenced by the severity of maternal disease.

Different classes of antibiotics given to women routinely for preventing infection at caesarean section.

BACKGROUND: Caesarean section increases the risk of postpartum infection for women and prophylactic antibiotics have been shown to reduce the incidence; however, there are adverse effects. It is important to identify the most effective class of antibiotics to use and those with the least adverse effects.  OBJECTIVES: To determine, from the best available evidence, the balance of benefits and harms between different classes of antibiotic given prophylactically to women undergoing caesarean section, considering their effectiveness in reducing infectious complications for women and adverse effects on both mother and infant. SEARCH METHODS: For this 2020 update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (2 December 2019), and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing different classes of prophylactic antibiotics given to women undergoing caesarean section.  RCTs published in abstract form were also included. We excluded trials that compared drugs with placebo or drugs within a specific class; these are assessed in other Cochrane Reviews. We excluded quasi-RCTs and cross-over trials. Cluster-RCTs were eligible for inclusion but none were identified. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 39 studies, with 33 providing data (8073 women). Thirty-two studies (7690 women) contributing data administered antibiotics systemically, while one study (383 women) used lavage and was analysed separately. We identified three main comparisons that addressed clinically important questions on antibiotics at caesarean section (all systemic administration), but we only found studies for one comparison, 'antistaphylococcal cephalosporins (1st and 2nd generation) versus broad spectrum penicillins plus betalactamase inhibitors'.   We found no studies for the following comparisons: 'antistaphylococcal cephalosporins (1st and 2nd generation) versus lincosamides' and 'antistaphylococcal cephalosporins (1st and 2nd generation) versus lincosamides plus aminoglycosides'. Twenty-seven studies (22 provided data) included comparisons of cephalosporins (only) versus penicillins (only). However for this update, we only pooled data relating to different sub-classes of penicillins and cephalosporins where they are known to have similar spectra of action against agents likely to cause infection at caesarean section. Eight trials, providing data on 1540 women, reported on our main comparison, 'antistaphylococcal cephalosporins (1st and 2nd generation) versus broad spectrum penicillins plus betalactamase inhibitors'. We found data on four other comparisons of cephalosporins (only) versus penicillins (only) using systemic administration: antistaphylococcal cephalosporins (1st and 2nd generation) versus non-antistaphylococcal penicillins (natural and broad spectrum) (9 studies, 3093 women); minimally antistaphylococcal cephalosporins (3rd generation) versus non-antistaphylococcal penicillins (natural and broad spectrum) (4 studies, 854 women); minimally antistaphylococcal cephalosporins (3rd generation) versus broad spectrum penicillins plus betalactamase inhibitors (2 studies, 865 women); and minimally antistaphylococcal cephalosporins (3rd generation) versus broad spectrum and antistaphylococcal penicillins (1 study, 200 women). For other comparisons of different classes of antibiotics, only a small number of trials provided data for each comparison, and in all but one case data were not pooled. For all comparisons, there was a lack of good quality data and important outcomes often included few women. Three of the studies that contributed data were undertaken with drug company funding, one was funded by the hospital, and for all other studies the funding source was not reported. Most of the studies were at unclear risk of selection bias, reporting bias and other biases, partly due to the inclusion of many older trials where trial reports did not provide sufficient methodological information. We undertook GRADE assessment on the only main comparison reported by the included studies, antistaphylococcal cephalosporins (1st and 2nd generation) versus broad spectrum penicillins plus betalactamase inhibitors, and the certainty ranged from low to very low, mostly due to concerns about risk of bias, wide confidence intervals (CI), and few events. In terms of the primary outcomes for our main comparison of 'antistaphylococcal cephalosporins (1st and 2nd generation) versus broad spectrum penicillins plus betalactamase inhibitors': only one small study reported sepsis, and there were too few events to identify clear differences between the drugs (risk ratio (RR) 2.37, 95% CI 0.10 to 56.41, 1 study, 75 women, very low-certainty evidence). There may be little or no difference between these antibiotics in preventing endometritis (RR 1.10; 95% CI 0.76 to 1.60, 7 studies, 1161 women; low-certainty evidence). None of the included studies reported on infant sepsis or infant oral thrush. For our secondary outcomes, we found there may be little or no difference between interventions for maternal fever (RR 1.07, 95% CI 0.65 to 1.75, 3 studies, 678 women; low-certainty evidence). We are uncertain of the effects on maternal: wound infection (RR 0.78, 95% CI 0.32 to 1.90, 4 studies, 543 women), urinary tract infection (average RR 0.64, 95% CI 0.11 to 3.73, 4 studies, 496 women), composite adverse effects (RR 0.96, 95% CI 0.09 to 10.50, 2 studies, 468 women), and skin rash (RR 1.08, 95% CI 0.28 to 4.1, 3 studies, 591 women) (all very low certainty evidence). Although maternal allergic reactions were reported by two studies, there were no events. There were no infant outcomes reported in the included studies. For the other comparisons, the results for most outcomes had wide CIs, few studies and few women included. None of the included trials reported on longer-term maternal outcomes, or on any infant outcomes. AUTHORS' CONCLUSIONS: Based on the best currently available evidence, 'antistaphylococcal cephalosporins' and 'broad spectrum penicillins plus betalactamase inhibitors' may have similar efficacy at caesarean section when considering immediate postoperative infection, although we did not have clear evidence for several important outcomes. Most trials administered antibiotics at or after cord clamping, or post-operatively, so results may have limited applicability to current practice which generally favours administration prior to skin incision. We have no data on any infant outcomes, nor on late infections (up to 30 days) in the mother; these are important gaps in the evidence that warrant further research. Antimicrobial resistance is very important but more appropriately investigated by other trial designs.

Number of Remaining Teeth and Its Association with Educational Level in Chilean Adults: Data from the National Health Survey 2016-2017.

INTRODUCTION: Several population studies have addressed oral health inequalities. Edentulism, functional dentition, and number of remaining teeth have been associated with different socioeconomic level measurements. The aim of this study was to evaluate the association between educational level and tooth loss in the Chilean population aged 15 years and above, based on the 2016-2017 National Health Survey (ENS 2016-2017). Material and Methods. The sample for this cross-sectional study comprised 5473 subjects. The main independent variable was educational level (LEL: low, MEL: medium, and HEL: high). To measure tooth loss, we considered the variables number of remaining teeth, edentulism, and functional dentition. We used logistic regressions to assess the condition of dentition according to the subject's EL. As to the number of teeth variable, linear regressions were conducted. The analyses were carried out considering the complex sampling design in SPSS 24.0. RESULTS: When comparing LEL subjects with HEL subjects, the adjusted difference in number of remaining teeth was 3.11 for the maxilla and 1.72 for the mandible. An individual with LEL had a 7.51 [3.50-16.10] and 6.06 [2.68-13.68] times higher risk of upper edentulism and lower edentulism than a HEL individual, respectively. Regarding functional dentition, the adjusted OR in HEL subjects was 13.33 [8.02-22.15] and in MEL subjects was 2.81 [2.03-3.87], compared to LEL results. CONCLUSIONS: LEL was associated with a significant tooth loss in the Chilean population. Subjects with LEL obtained a lower mean of number of remaining teeth and higher prevalence of edentulism and nonfunctional dentition.

Quality of medicines for life-threatening pregnancy complications in low- and middle-income countries: A systematic review.

BACKGROUND: There are concerns about the quality of medicines available in low- and middle-income countries (LMIC) to manage hemorrhage, pre-eclampsia/eclampsia and sepsis. We aimed to identify, critically appraise, and synthesize the findings of studies on the quality of these three types of medicines available in LMIC. METHODS: This systematic review searched Medline, EMBASE and LILACS (from inception to 25 May 2020) for studies on the quality of selected medicines available in LMIC that provided at least the amount of active pharmaceutical ingredient. We contacted study authors for additional information. We excluded simulation studies. We used the MEDQUARG tool to assess study quality. The main outcome was the prevalence of failed samples. FINDINGS: We identified 9699 unique citations and included 34 studies (3159 samples from 40 countries) in the review. Most studies (65%) had low quality (scores <6/12). Overall, 48.9% of 1890 uterotonic samples (19 studies) failed quality tests; failures rates were 75% for ergometrine and nearly 40% each for oxytocin and misoprostol. The overall prevalence of failed injectable antibiotics (1090 samples, 18 studies) was 13.4%, ranging from 2.9% for injectable metronidazole (34 samples, 3 studies) to 16.0% for cefazolin (449 samples, 2 studies). The prevalence of low quality magnesium sulphate (179 samples, 2 studies) was 3.4%. We did not find any studies on the quality of carbetocin, tranexamic acid, or clindamycin. CONCLUSIONS: There is a widespread problem with the quality of medicines used to manage life-threatening maternal conditions in LMIC. This can be a contributing factor to high maternal mortality rates in these regions.