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Global research priorities for COVID-19 in maternal, reproductive and child health: Results of an international survey
(2021)
Melanie Etti
;
Jackeline Alger
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Sofía P. Salas
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Robin Saggers
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Tanusha Ramdin
<jats:sec id="sec001"> <jats:title>Background</jats:title> <jats:p>The World Health Organization’s “<jats:italic>Coordinated Global Research Roadmap</jats:italic>: <jats:italic>2019 Novel Coronavirus</jats:italic>” outlined the need for research that focuses on the impact of COVID-19 on pregnant women and children. More than one year after the first reported case significant knowledge gaps remain, highlighting the need for a coordinated approach. To address this need, the Maternal, Newborn and Child Health Working Group (MNCH WG) of the COVID-19 Clinical Research Coalition conducted an international survey to identify global research priorities for COVID-19 in maternal, reproductive and child health.</jats:p> </jats:sec> <jats:sec id="sec002"> <jats:title>Method</jats:title> <jats:p>This project was undertaken using a modified Delphi method. An electronic questionnaire was disseminated to clinicians and researchers in three different languages (English, French and Spanish) via MNCH WG affiliated networks. Respondents were asked to select the five most urgent research priorities among a list of 17 identified by the MNCH WG. Analysis of questionnaire data was undertaken to identify key similarities and differences among respondents according to questionnaire language, location and specialty. Following elimination of the seven lowest ranking priorities, the questionnaire was recirculated to the original pool of respondents. Thematic analysis of final questionnaire data was undertaken by the MNCH WG from which four priority research themes emerged.</jats:p> </jats:sec> <jats:sec id="sec003"> <jats:title>Results</jats:title> <jats:p>Questionnaire 1 was completed by 225 respondents from 29 countries. Questionnaire 2 was returned by 49 respondents. The four priority research themes which emerged from the analysis were 1) access to healthcare during the COVID-19 pandemic, 2) the direct and 3) indirect effects of COVID-19 on pregnant and breastfeeding women and children and 4) the transmission of COVID-19 and protection from infection.</jats:p> </jats:sec> <jats:sec id="sec004"> <jats:title>Conclusion</jats:title> <jats:p>The results of these questionnaires indicated a high level of concordance among continents and specialties regarding priority research themes. This prioritized list of research uncertainties, developed to specifically highlight the most urgent clinical needs as perceived by healthcare professionals and researchers, could help funding organizations and researchers to answer the most pressing questions for clinicians and public health professionals during the pandemic. It is hoped that these identified priority research themes can help focus the discussion regarding the allocation of limited resources to enhance COVID-19 research in MNCH globally.</jats:p> </jats:sec>
3Scopus© Citations 8
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Breaking the breach in Latin America: A pilot study of mechanical thrombectomy in the public healthcare system in Chile
(2020)
Rodrigo Rivera
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Cristian Amudio
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Enzo Brunetti
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Pascual Catalan
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Juan Gabriel Sordo
<jats:sec><jats:title>Background</jats:title><jats:p> Mechanical Thrombectomy (MT) is the standard of care for treatment of large vessel occlusion stroke. Until the beginning of 2020 MT was not funded nor widely implemented at the public healthcare level in Chile. </jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p> To describe the results of a pilot program created to provide access to public MT in Santiago - Chile. </jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p> Analysis from a prospectively collected database of MT cases performed between September 2017 and September 2019 in one center. A stroke network was developed with a single MT capable stroke center and five primary stroke centers. The primary efficacy endpoint was the rate of functional independence (mRS 0-2) at 90 days. Successful reperfusion was defined as 2 b-3 according to the thrombolysis in cerebral infarction scale. Safety outcomes include the rates of symptomatic intracranial hemorrhage and 90-day mortality. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> A total of 100 patients were treated over the study period. Their mean age was 62.8 ± 11.8 years and median baseline National Institute of Health Stroke Scale (NIHSS) measurement was 17. Seventy-seven percent of the patients received intra venous thrombolysis. Successful reperfusion was achieved in 95% of the cases. NIHSS at 24 hours showed a median drop of 7 points from baseline (p < 0.00001) and 50% of the follow-up patients were functionally independent at 90 days. Symptomatic Intracerebral hemorrhage occurred in 5% of the patients and 90-day all case mortality was 11%. </jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p> We demonstrated the feasibility of a publicly funded MT program in Chile, with similar results as other international randomized control trials. </jats:p></jats:sec>
Scopus© Citations 10 4
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Structural brain abnormalities in schizophrenia in adverse environments: examining the effect of poverty and violence in six Latin American cities
(2020)
Nicolas A. Crossley
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Andre Zugman
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Francisco Reyes-Madrigal
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Leticia S. Czepielewski
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Mariana N. Castro
<jats:title>Summary</jats:title><jats:sec id="S0007125020001439_sec_a1"><jats:title>Background</jats:title><jats:p>Social and environmental factors such as poverty or violence modulate the risk and course of schizophrenia. However, how they affect the brain in patients with psychosis remains unclear.</jats:p></jats:sec><jats:sec id="S0007125020001439_sec_a2"><jats:title>Aims</jats:title><jats:p>We studied how environmental factors are related to brain structure in patients with schizophrenia and controls in Latin America, where these factors are large and unequally distributed.</jats:p></jats:sec><jats:sec id="S0007125020001439_sec_a3" sec-type="methods"><jats:title>Method</jats:title><jats:p>This is a multicentre study of magnetic resonance imaging in patients with schizophrenia and controls from six Latin American cities. Total and voxel-level grey matter volumes, and their relationship with neighbourhood characteristics such as average income and homicide rates, were analysed with a general linear model.</jats:p></jats:sec><jats:sec id="S0007125020001439_sec_a4" sec-type="results"><jats:title>Results</jats:title><jats:p>A total of 334 patients with schizophrenia and 262 controls were included. Income was differentially related to total grey matter volume in both groups (<jats:italic>P</jats:italic> = 0.006). Controls showed a positive correlation between total grey matter volume and income (<jats:italic>R</jats:italic> = 0.14, <jats:italic>P</jats:italic> = 0.02). Surprisingly, this relationship was not present in patients with schizophrenia (<jats:italic>R</jats:italic> = −0.076, <jats:italic>P</jats:italic> = 0.17). Voxel-level analysis confirmed that this interaction was widespread across the cortex. After adjusting for global brain changes, income was positively related to prefrontal cortex volumes only in controls. Conversely, the hippocampus in patients with schizophrenia, but not in controls, was relatively larger in affluent environments. There was no significant correlation between environmental violence and brain structure.</jats:p></jats:sec><jats:sec id="S0007125020001439_sec_a5" sec-type="conclusions"><jats:title>Conclusions</jats:title><jats:p>Our results highlight the interplay between environment, particularly poverty, and individual characteristics in psychosis. This is particularly important for harsh environments such as low- and middle-income countries, where potentially less brain vulnerability (less grey matter loss) is sufficient to become unwell in adverse (poor) environments.</jats:p></jats:sec>
Scopus© Citations 10 1
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Could Subtle Obstetrical Brachial Plexus Palsy Be Related to Unilateral B Glenoid Osteoarthritis?
(2021)
Alexandre Lädermann
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Hugo Bothorel
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Philippe Collin
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Bassem Elhassan
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Luc Favard
<jats:p>Background: Several factors associated with B glenoid are also linked with obstetrical brachial plexus palsy (OBPP). The purpose of this observational study was to determine the incidence of OBPP risk factors in type B patients. Methods: A cohort of 154 patients (68% men, 187 shoulders) aged 63 ± 17 years with type B glenoids completed a questionnaire comprising history of perinatal characteristics related to OBPP. A literature review was performed following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) to estimate the incidence of OBPP risk factors in the general population. Results: Twenty-seven patients (18%) reported one or more perinatal OBPP risk factors, including shoulder dystocia (n = 4, 2.6%), macrosomia >4 kg (n = 5, 3.2%), breech delivery (n = 6, 3.9%), fetal distress (n = 8, 5.2%), maternal diabetes (n = 2, 1.3%), clavicular fracture (n = 2, 1.3%), and forceps delivery (n = 4, 2.6%). The comparison with the recent literature suggested that most perinatal OBPP risk factors were within the normal range, although the incidence of shoulder dystocia, forceps and vaginal breech deliveries exceeded the average rates. Conclusion: Perinatal factors related to OBPP did not occur in a higher frequency in patients with Walch type B OA compared to the general population, although some of them were in the high normal range.</jats:p>
Scopus© Citations 3 20
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Seroprevalence of Natural and Acquired Immunity against the SARS-CoV-2 Virus in a Population Cohort from Two Chilean Cities, 2020–2022
(2023)
Loreto Núñez-Franz
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Muriel Ramírez-Santana
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RUBILAR RAMIREZ, PAOLA
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Macarena Said
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VIAL COX, MARIA CECILIA
<jats:p>Background: Chile has achieved the highest coverage for vaccines against the SARS-CoV-2 virus worldwide. Objective: To assess the progression of immunity (natural and acquired by vaccine) in a cohort from two Chilean cities. Methods: Individuals (n = 386) who participated in three phases of population-based serial prevalence studies were included (2020–2021 and 2022). Presence of SARS-CoV-2 antibodies was measured in serum. Data including time of vaccination and type of vaccine received were analysed with descriptive statistics. Results: Seroprevalence was 3.6% in the first round and increased to 96.9% in the second and 98.7% in the third. In the third round, 75% of individuals who had received the basal full scheme were seropositive at 180 days or more since their last dose; 98% of individuals who received one booster dose were seropositive at 180 days or more, and 100% participants who received two boosters were seropositive, regardless of time since their last dose. Participants receiving mRNA vaccines had higher seroprevalence rates over time. Conclusions: The high vaccination coverage in Chile enabled the population to maintain high levels of antibodies. Vaccination boosters are essential to maintain immunity over time, which also depends on the type of vaccine administered.</jats:p>
1Scopus© Citations 12
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Association between spontaneous internal carotid artery dissection and perivascular adipose tissue attenuation on computed tomography angiography
(2023)
Kevin Cheng
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Andrew Lin
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STECHER GUZMAN, XIMENA PATRICIA
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Tomas Bernstein
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Paulo Zuñiga
<jats:sec><jats:title>Background:</jats:title><jats:p> Spontaneous cervical artery dissection (sCAD) is a leading cause of ischemic stroke in young patients. Studies using high-resolution magnetic resonance imaging and positron emission tomography have suggested vessel wall inflammation to be a pathogenic factor in sCAD. Computed tomography (CT) attenuation of perivascular adipose tissue (PVAT) is an established non-invasive imaging biomarker of inflammation in coronary arteries, with higher attenuation values reflecting a greater degree of vascular inflammation. </jats:p></jats:sec><jats:sec><jats:title>Objectives:</jats:title><jats:p> We evaluate the CT attenuation of PVAT surrounding the internal carotid artery (PVAT<jats:sub>carotid</jats:sub>) with and without spontaneous dissection. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> Single-center prospective observational study of 56 consecutive patients with CT-verified spontaneous dissection of the internal carotid artery (ICA). Of these patients, six underwent follow-up computed tomography angiography (CTA). Twenty-two patients who underwent CTA for acute neurological symptoms but did not have dissection formed the control group. Using semi-automated research software, PVAT<jats:sub>carotid</jats:sub> was measured as the mean Hounsfield unit (HU) attenuation of adipose tissue within a defined volume of interest surrounding the ICA. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> PVAT<jats:sub>carotid</jats:sub> was significantly higher around dissected ICA compared with non-dissected contralateral ICA in the same patients (−58.7 ± 10.2 vs −68.9 ± 8.1 HU, p < 0.0001) and ICA of patients without dissection (−58.7 ± 10.2 vs −69.3 ± 9.3 HU, p < 0.0001). After a median follow-up of 89 days, there was a significant reduction in PVAT<jats:sub>carotid</jats:sub> around dissected ICA (−57.5 ± 13.4 to −74.3 ± 10.5 HU, p < 0.05), while no change was observed around non-dissected contralateral ICA (−71.0 ± 4.4 to −74.1 ± 4.1 HU, p = 0.19). ICA dissection was an independent predictor of PVAT<jats:sub>carotid</jats:sub> following multivariable adjustment for age and the presence of ICA occlusion. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> PVAT<jats:sub>carotid</jats:sub> is elevated in the presence of sCAD and may decrease following the acute event. </jats:p></jats:sec>
3 1Scopus© Citations 5
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Clinical characteristics, microbiology and outcomes of a cohort of patients treated with ceftolozane/tazobactam in acute care inpatient facilities, Houston, Texas, USA
(2022)
Truc T Tran
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Nicolo L Cabrera
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Anne J Gonzales-Luna
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Travis J Carlson
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Faris Alnezary
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Ceftolozane/tazobactam is a β-lactam/β-lactamase inhibitor combination with activity against a variety of Gram-negative bacteria, including MDR Pseudomonas aeruginosa. This agent is approved for hospital-acquired and ventilator-associated bacterial pneumonia. However, most real-world outcome data come from small observational cohorts. Thus, we sought to evaluate the utilization of ceftolozane/tazobactam at multiple tertiary hospitals in Houston, TX, USA.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>We conducted a multicentre retrospective study of patients receiving at least 48 h of ceftolozane/tazobactam therapy from January 2016 through to September 2019 at two hospital systems in Houston. Demographic, clinical and microbiological data were collected, including the infecting bacterial isolate, when available. The primary outcome was composite clinical success at hospital discharge. Secondary outcomes included in-hospital mortality and clinical disposition at 14 and 30 days post ceftolozane/tazobactam initiation. Multivariable logistic regression analysis was used to identify predictors of the primary outcome and mortality. Recovered isolates were tested for susceptibility to ceftolozane/tazobactam and underwent WGS.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>A total of 263 patients were enrolled, and composite clinical success was achieved in 185 patients (70.3%). Severity of illness was the most consistent predictor of clinical success. Combination therapy with ceftolozane/tazobactam and another Gram-negative-active agent was associated with reduced odds of clinical success (OR 0.32, 95% CI 0.16–0.63). Resistance to ceftolozane/tazobactam was noted in 15.4% of isolates available for WGS; mutations in ampC and ftsI were common but did not cluster with a particular ST.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Clinical success rate among this patient cohort treated with ceftolozane/tazobactam was similar compared with previous experiences. Ceftolozane/tazobactam remains an alternative agent for treatment of susceptible isolates of P. aeruginosa.</jats:p> </jats:sec>
Scopus© Citations 3 2
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Inborn errors of OAS–RNase L in SARS-CoV-2–related multisystem inflammatory syndrome in children
(2023)
Danyel Lee
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Jérémie Le Pen
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Ahmad Yatim
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Beihua Dong
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Yann Aquino
<jats:p> Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of <jats:italic>OAS1</jats:italic> , <jats:italic>OAS2</jats:italic> , or <jats:italic>RNASEL</jats:italic> in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)–sensing OAS1 and OAS2 generate 2′-5′-linked oligoadenylates (2-5A) that activate the single-stranded RNA–degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L–deficient cells. Cytokine production in RNase L–deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS–RNase L deficiencies in these patients unleash the production of SARS-CoV-2–triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C. </jats:p>
11Scopus© Citations 137
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Dysconnectivity in Schizophrenia Revisited: Abnormal Temporal Organization of Dynamic Functional Connectivity in Patients With a First Episode of Psychosis
(2022)
Juan P Ramirez-Mahaluf
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Ángeles Tepper
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Luz Maria Alliende
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Carlos Mena
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Carmen Paz Castañeda
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background and Hypothesis</jats:title> <jats:p>Abnormal functional connectivity between brain regions is a consistent finding in schizophrenia, including functional magnetic resonance imaging (fMRI) studies. Recent studies have highlighted that connectivity changes in time in healthy subjects. We here examined the temporal changes in functional connectivity in patients with a first episode of psychosis (FEP). Specifically, we analyzed the temporal order in which whole-brain organization states were visited.</jats:p> </jats:sec> <jats:sec> <jats:title>Study Design</jats:title> <jats:p>Two case-control studies, including in each sample a subgroup scanned a second time after treatment. Chilean sample included 79 patients with a FEP and 83 healthy controls. Mexican sample included 21 antipsychotic-naïve FEP patients and 15 healthy controls. Characteristics of the temporal trajectories between whole-brain functional connectivity meta-states were examined via resting-state functional MRI using elements of network science. We compared the cohorts of cases and controls and explored their differences as well as potential associations with symptoms, cognition, and antipsychotic medication doses.</jats:p> </jats:sec> <jats:sec> <jats:title>Study Results</jats:title> <jats:p>We found that the temporal sequence in which patients’ brain dynamics visited the different states was more redundant and segregated. Patients were less flexible than controls in changing their network in time from different configurations, and explored the whole landscape of possible states in a less efficient way. These changes were related to the dose of antipsychotics the patients were receiving. We replicated the relationship with antipsychotic medication in the antipsychotic-naïve FEP sample scanned before and after treatment.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>We conclude that psychosis is related to a temporal disorganization of the brain’s dynamic functional connectivity, and this is associated with antipsychotic medication use.</jats:p> </jats:sec>
Scopus© Citations 17 1

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