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Please note: These are preprints and have not been peer reviewed. Data may be preliminary. Preprints should not be relied on to guide medical practice or health-related decisions. News media reporting on preprints should stress that the research should not yet be considered conclusive.
The COVID-19 Epidemic in Madagascar: clinical description and laboratory results of t...
Rindra Randremanana
Soa-Fy Andriamandimby

Rindra Randremanana

and 29 more

January 17, 2021
Background: Following the first detection of SARS-CoV-2 in passengers arriving from Europe on 19 March 2020, Madagascar took several mitigation measures to limit the spread of the virus in the country. Methods: Nasopharyngeal and/or oropharyngeal swabs were collected from travellers to Madagascar, suspected SARS-CoV-2 cases, and contact of confirmed cases. Swabs were tested at the national reference laboratory using real-time RT-PVR. Data collected from patients were entered in an electronic database for subsequent statistical analysis. All distribution of laboratory confirmed cases were mapped and six genomes of viruses were fully sequenced. Results: Overall, 26,415 individuals were tested for SARS-CoV-2 between 18 March and 18 September 2020, of whom 21.0% (5,553/26,145) returned positive. Among laboratory-confirmed SARS-CoV-2 positive patients, the median age was 39 years (CI95%: 28-52), and 56.6% (3,311/5,553) were asymptomatic at the time of sampling. The probability of testing positive increased with age with the highest adjusted odds ratio of 2.2 [95% CI: 1.9-2.5] for individuals aged 49 years and more. Viral strains sequenced belong to clades 19A, 20A, and 20B in favour of several independent introduction of viruses. Conclusions. Our study describes the first wave of the COVID-19 in Madagascar. Despite early strategies in place Madagascar could not avoid the introduction and spread of the virus. More studies are needed to estimate the true burden of disease and make public health recommendations for a better preparation to another wave.
SIR epidemiological model with ratio-dependent incidence: influence of preventive vac...
Uday Kumar
PARTHA MANDAL

Uday Kumar

and 4 more

January 17, 2021
In this paper, we study an SIR epidemic model with ratio dependent incident rate function. We explore the impact of vaccination and treatment on the transmission dynamics of the disease. The treatment control strategies depend on the availability of maximal treatment capacity: treatment rate is constant when the number of infected individuals is greater than the maximal capacity of treatment and proportional to the number of infected individuals when the number of infected individuals is less than the maximal capacity of treatment. The existence and stability of the endemic equilibria are governed by the basic reproduction number and treatment control strategies. By carrying out rigorous mathematical analysis and numerical evaluations, it has been shown that (1) the sufficiently large value of the preventive vaccination rate can control the spread of disease, (2) a threshold level of the psychological (or inhibitory) effects in the incidence rate function is enough to decrease the infective population. Model system also undergoes a transcritical and a saddle-node bifurcation with respect to disease contact rate. In the presence of treatment strategies, system have multiple endemic equilibria and undergoes a backward bifurcation. The number of infected individuals decreases with respect to maximal treatment capacity and disease dies out from the system for large capacity of the treatment when constant treatment strategy is applied. Further, it is also found that the spread of disease can be suppressed by increasing treatment rate. Sensitivity analysis shows that the transmission and treatment rates are most sensitive parameters on the model system.
A SARS-CoV-2 overview for people in a hurry
Sylvester Jian Ming Lim

Sylvester Jian Ming Lim

and 1 more

January 15, 2021
SARS-CoV-2 is the etiologic agent of the current COVID-19 pandemic which has wreaked unprecedented economic and healthcare calamity. It is a deadly virus belonging to the Coronaviridae family, with high sequence similarity to the 2003 SARS epidemic coronavirus. The global race to produce vaccines to stem the disease-as well as the public health urgency-has spurred tremendous growth in the litany of literature which attempts to uncover the enigma of this deadly virus. Amidst this evergrowing list of literature , this paper seeks to concisely elaborate on key progresses made in the understanding of SARS-CoV-2 in the realms of its life cycle, epidemiology, methods for detection, and vaccine research into an easily assimilable paper for readers.
Incidence, characteristic and risk factors of drug-induced liver injury in hospitaliz...
Xianghao Kong
Daihong Guo

Xianghao Kong

and 4 more

January 12, 2021
Abstract: Aims: The diagnosis of drug-induced liver injury (DILI) is relatively complex, involving a wide variety of drugs. The purpose of this study is to use algorithms to quickly screen DILI patients, count incidence rates and find risk factors. Methods: The Adverse Drug Events Active Surveillance and Assessment System-2 was used to extract the data of hospitalized patients in 2019 according to the set standards, then the RUCAM was used to evaluate patients who meet the standards. A retrospective case-control study was conducted according to suspected drugs, length of hospital stay, height and weight matched controls, and logistic regression was used to find risk factors. Results: Among the 156,570 hospitalized patients, 480 patients (499 cases) of DILI were confirmed, and the incidence of DILI was 0.32%. Anti-infective agents, antineoplastic agents, non-steroidal anti-inflammatory drugs (NASIDs) were the major category of causative drugs causing DILI, and the highest incidence of DILI caused by agent of voriconazole. The latency period and hospital stay of patients with cholestasis was relatively long. Patients with hyperlipidemia (AOR: 1.884), cardiovascular disease (AOR: 1.465), pre-existing liver disease (AOR: 1.827) and surgical history (AOR: 1.312) were likely to be risk factors for DILI. Conclusions: The incidence of DILI in hospitalized patients was uncommon (0.32%), and its pathogenic drugs were widely distributed. LiverTox’s information could assist in the diagnosis of DILI. The incidence of DILI in many drugs was seriously underestimated. It is recommended to focus on patients with hyperlipidemia, cardiovascular disease, pre-existing liver disease, and surgical history.
Attributable factors for the rising caesarean delivery rate over three decades: an ob...
Bradley de Vries
Rhett Morton

Bradley de Vries

and 6 more

January 07, 2021
Objective: Caesarean delivery rates continue to rise globally the reasons for which are poorly understood. We aimed to characterize attributable factors for increasing caesarean delivery rates over a 30-year period within our health network. Design: Observational cohort study. Setting: Two hospitals (large tertiary referral hospital and metropolitan hospital) in Sydney, Australia, across two time periods: 1989-1999 and 2009-2016, between which the caesarean delivery rate increased from 19% to 30%. Participants: All women who had a caesarean delivery after 24 weeks gestation Methods: Data were analysed using multiple imputation and robust Poisson regression to estimate the changes in the caesarean delivery rate attributable to maternal and clinical factors. Main outcome measures: Caesarean delivery. Results: Fifty-six percent of the increase in the rate of caesarean delivery was attributed to changes in the distribution of maternal factors including maternal age, body mass index, parity and history of previous caesarean delivery. When changes in the obstetric management of multiple gestation, malpresentation and preterm singleton birth were considered, 66% of the increase in caesarean rate was explained. When pre-labour caesarean deliveries for maternal choice, suspected fetal compromise, previous pregnancy issues and suspected large fetus were excluded, 78% of the increase was explained. Conclusions: Most of the steep rise in the caesarean delivery rate from 19% to 30% is attributable to changes in maternal demographic and clinical factors.
Functional Bowel Disorders in Patients with Brugada Syndrome and Drug-Induced Type 1...
Anil Sarica
Serhat Bor

Anil Sarica

and 6 more

December 30, 2020
Introduction: Irritable bowel syndrome (IBS) is one of the most widely recognized functional bowel disorders (FBDs) with a genetic component. SCN5A gene and SCN1B loci have been identified in population-based IBS cohorts and proposed to have a mechanistic role in the pathophysiology of IBS. These same genes have been associated with Brugada syndrome (BrS). The present study examines the hypothesis that these two inherited syndromes are linked. Methods and Results: Prevalence of FBDs over a 12 months period were compared between probands with BrS/drug-induced type 1 Brugada pattern (DI-Type1 BrP) (n=148) and a control group (n=124) matched for age, female sex, presence of arrhythmia and co-morbid conditions. SCN5A/SCN1B genes were screened in 88 patients. Prevalence of IBS was 25% in patients with BrS/DI-Type1 BrP and 8.1% in the control group (p=2.34×10−4). On stepwise logistic regression analysis, presence of current and/or history of migraine (OR of 2.75; 95% CI: 1.08 to 6.98; p=0.033) was a predictor of underlying BrS/DI-Type1 BrP among patients with FBDs. We identified 8 putative SCN5A/SCN1B variants in 7 (12.3%) patients with BrS/DI-Type1 BrP and 1 (3.2%) patient in control group. Five out of 8 (62.5%) patients with SCN5A/SCN1B variants had FBDs. Conclusion: IBS is a common co-morbidity in patients with BrS/DI-Type1 BrP. Presence of current and/or history of migraine is a predictor of underlying BrS/DI-Type1 BrP among patients with FBDs. Frequent co-existence of IBS and BrS/DI-Type1 BrP necessitates cautious use of certain drugs among the therapeutic options for IBS that are known to exacerbate the Brugada phenotype.
Development and internal validation of a model predicting severe maternal morbidity u...
Natalie Dayan
Gabriel Shapirio

Natalie Dayan

and 8 more

December 27, 2020
Objective: To improve the prediction of maternal end-organ injury or death using routinely-collected variables from the pre-pregnancy and the early pregnancy period. Design: Population-based cohort study using linked administrative health data. Setting: Ontario, Canada, April 1, 2006 to March 31, 2014. Sample: Women aged 18-60 years with a livebirth or stillbirth, of which one birth was randomly selected per woman. Methods and main outcome measures: We constructed a CPM for the primary composite outcome of any maternal end-organ injury or death, arising between 20 weeks’ gestation and 42 days after the birth hospital discharge date. Our CPM included variables collected from 12 months before estimated conception until 19 weeks’ gestation. We developed a separate CPM for parous women to allow for the inclusion of factors from previous pregnancy(ies). Results: Of 634,290 women, 1969 experienced the primary composite outcome (3.1 per 1000). Predictive factors in the main CPM included maternal world region of origin, chronic medical conditions, parity, and obstetrical/perinatal issues – with moderate model discrimination (C-statistic 0.68, 95% CI 0.66-0.69). Among 333,435 parous women, the C-statistic was 0.71 (0.69-0.73) in the model using variables from the current (index) pregnancy as well as pre-pregnancy predictors and variables from any previous pregnancy. Conclusions: A combination of factors ascertained early in pregnancy through a basic medical history help to identify women at risk for severe morbidity, who may benefit from targeted preventive and surveillance strategies including appropriate specialty-based antenatal care pathways. Further refinement of this model would enable clinical use.
Pleuropulmonary Blastoma: A Single-center Case Series of 7 Patients
M Masood Sidiqi
Ling  Xu

M Masood Sidiqi

and 3 more

December 20, 2020
Introduction Pleuropulmonary blastoma (PPB) is an aggressive primary neoplasm of pleuropulmonary mesenchyme occurring in children. Given its rarity, the International Pleuropulmonary Blastoma Registry (IPPBR) was established in 1988 to collect and assess data on PPB worldwide. We assessed the clinical characteristics, histopathology, genetic studies, management, and treatment outcomes of patients with PPB in our institution, and compared with the published literature. Materials and Methods We retrospectively reviewed the medical records of all PPB cases diagnosed at Princess Margaret Hospital for Children in Western Australia over a period of 26 years (1990-2016). Results Seven children (4 boys and 3 girls) were treated for PPB at a mean age of 11.5 months (ranges 1 month to 3.55 years). Histopathology showed type I PPB in five, type II in one, and type III in one. All seven patients underwent thoracotomy/lobectomy of the corresponding site. One patient required additional bladder resection for coexisting rhabdomyosarcoma. One patient was found to be positive for DICER1 gene mutation. Six patients received adjuvant chemotherapy with vincristine, adriamycin, cyclophosphamide (VAC) regime, with the mean duration of treatment for five patients being 9.4 months excluding one patient who deceased without completion of chemotherapy. During a mean follow-up time of 9 years, the overall survival rate for this cohort was 85.7% (6/7). Conclusions Our results are similar to those reported in the literature. It is crucial for clinicians to consider PPB in the evaluation of patients presenting with a cystic lung abnormality, especially in cases with DICER1 mutation or a strong family history of unusual cancers.
EDITORIAL: The Many Challenges to the Field of Pediatric Pulmonology Posed by Pediatr...
George Mallory
Steven Abman

George Mallory

and 1 more

December 12, 2020
Pulmonary hypertension represents an increasingly important group of pediatric patients which commonly come to the attention, if not the primary care of pediatric pulmonologists around the world. There have been major advances in diagnosis and therapy over the past 25 years. To address potential gaps in knowledge, the authors were invited by the Editor of Pediatric Pulmonology to organize a series of manuscripts in a special supplement of the journal. Our authors include pulmonologists, pharmacists, intensivists, mid-level practitioners, neonatologists and cardiologists. We believe that this issue will be of great interest to most of the readership community that the Journal addresses.
Coronavirus antibody screening identifies children with mild to moderate courses of P...
Otto  Laub
Georg Leipold

Otto Laub

and 20 more

December 12, 2020
Background: Children are affected rather mildly by the acute phase of COVID-19, but predominantly in children and youths, the potentially severe and life threatening pediatric multiorgan immune syndrome (PMIS) occurs later on. To identify children at risk early on, we searched for antibodies against SARS-CoV-2 and searched for early and mild symptoms of PMIS in those with high levels of antibodies. Methods: In a cross-sectional design, children aged 1-17 were recruited through primary care pediatricians for the study (a), if they had an appointment for a regular health check-up or (b), or if parents and children volunteered to participate in the study. Two antibody tests were performed in parallel and children with antibody levels >97th percentile (in the commercially available test) were screened for signs and symptoms of PMIS and SARS-CoV-2 neutralization tests were performed. Results: We identified antibodies against SARS-CoV-2 in 162 of 2832 eligible children (5.7%) between June and July 2020 in three, in part strongly affected regions of Bavaria. Approximately 60% of antibody positive children showed high levels of antibodies. In those who participated in the follow up screening, 30% showed some mild and minor symptoms similar to Kawasaki disease and in three children, cardiac and neuropsychological symptoms were identified. Symptoms correlated with high levels of non-neutralizing and concomitantly low levels of neutralizing antibodies and lower neutralizing capacity. Conclusions: Children exposed to SARS-CoV-2 should be screened for antibodies and those children with positive antibody responses should undergo a stepwise assessment for late COVID-19 effects.
Environmental factors prediction in preterm birth using comparison between logistic r...
Rakesh Saroj
Madhu Anand

Rakesh Saroj

and 2 more

December 02, 2020
Objective The main objective of this paper is to compare the performance of logistic regression and decision tree classification methods and to find the significant environment determinants that causes pre-term birth. Design, setting and population Between 2017 to 2018, 90 pregnant females underwent birth outcome followed by research staff at our institutions, out of those 50 are full-term and 40 are preterm births in this study. Method Before and after feature selection logistic regression and decision tree classifier model has been compared in this dataset and to evaluate the model accuracy. Main outcome measures Preforming the accuracy of machine learning classification model and important factors on pre-term birth. Results: Using chi-square test and find the Area of residence and GSH, MDA, α-HCH, total HCH and total DDT are responsible for the preterm birth. Using the multiple logistic regression, pre term birth was associated with MDA and α-HCH (95% CI 0.04 to 0.48 and 95% CI 0.82 to 0.97). The logistic and decision tree model comparison result shows that logistic regression is better in terms of metrics (precision = 0.92, F1-score = 0.96 and AUROC = 0.97), while decision tree performs the poor (precision = 0.75, F1-score = 0.86 and AUROC = 0.87). Conclusions The logistic regression is accurate model to predict the pre-term as compare to decision tree method. The variables like α-HCH , total HCH and MDA (Malondialdehyde) are the most influential factors for preterm birth.
A Structural Equation Model of Social Support, Stress and Depression in Pregnant Wome...
Yi Liang
Shengfeng Dong

Yi Liang

and 4 more

December 01, 2020
Objective: To investigate the connections among social support, stress, and depression. Design: Cross-sectional study. Setting: Guizhou Province in China. Population or Sample: An aggregate of 1,056 expectant ladies, had finished our questionnaire during pregnancy from March to April in 2020. Methods: The Edinburgh prenatal sadness scale, an independent pressure scale, and social support scale evaluated the downturn, stress, and social support of pregnant people during the pestilence. An auxiliary condition model was utilized to examine the immediate and aberrant connection between social support and prenatal misery. Main Outcome Measures: Incidence of depression. Results: During the pandemic time, 73.01% of pregnant ladies experienced prenatal misery. The model is suitable (chi-square = 11.96, CFI = 0.97, RMSEA = 0.07, RMR = 0.03). The auxiliary condition model indicated that the immediate pathway of social support to depression was critical (normalized pathway coefficient = - 0.34), and the aberrant pathway of stress to depression via social support was additionally huge (normalized pathway coefficient = 0.50). Stress partially intercedes the connection between social support and depression. Conclusion: Our discoveries posit that social support is related to an expanded danger of depression. Stress is decidedly corresponding to depression and assumes an interceding position between social support and stress. Thusly, directed mediation ought to be completed to lessen the depression of pregnant ladies and improve their psychological wellness status. Keywords: stress, depression, social support, structural equation model
An ultrasound study of the prevalence of endometriosis in women attending for early p...
Elisabeth Bean
Joel Naflalin

Elisabeth Bean

and 5 more

December 01, 2020
Objective To assess the prevalence of endometriosis using pelvic ultrasound examination in women attending for early pregnancy care Design Prospective observational study. Setting A dedicated early pregnancy unit. Population We included 1341 consecutive women who attended for an early pregnancy assessment and had transvaginal ultrasound scans performed by a single clinician. Methods In addition to the presence of endometriosis on ultrasound scan, we collected data on patient demographics and concurrent gynaecological conditions. Data analysis was performed using logistic regression and multivariate analysis. Main outcome measures The prevalence of endometriosis in addition to possible associations with demographic and clinical variables. Results The prevalence of endometriosis in women attending the early pregnancy unit was 4.9% (95% CI 3.8 – 6.2); In 33/66 (50%, 95% CI 37.9 – 62.1) women with endometriosis, this was a new diagnosis made for the first time during their early pregnancy scan. The presence of endometriosis was strongly associated with congenital uterine anomalies (p < 0.001; OR 5.69, 95% CI 2.17 – 14.9) and uterine fibroids (p = 0.004; OR 2.37, 95% CI 1.31, 4.28). Conclusions Endometriosis is present in nearly 5% of women attending for early pregnancy assessment. In half of the women with endometriosis, the diagnosis was made for the first time during pregnancy. We propose that ultrasound may be a useful tool for the detection of endometriosis and to identify pregnant women who may benefit from specialist antenatal care. Funding No funding was obtained for this work. Keywords Endometriosis, Prevalence, Pregnancy, Ultrasonography
Impact of early life geohelminths on wheeze, asthma, and atopy in Ecuadorian children...
Philip Cooper
Irina Chis Ster

Philip Cooper

and 8 more

December 01, 2020
Background: Early-life exposures to geohelminths may protect against the development of wheeze/asthma and atopy. Objective: Study effect of maternal geohelminths and infections in children during the first 5 years of life on atopy, wheeze/asthma, and airways reactivity/inflammation at 8 years. Methods: Birth cohort of 2,404 neonates followed to 8 years in rural Ecuador. Data on wheeze/asthma were collected by questionnaire and atopy by skin prick test (SPT) reactivity to 9 allergens. We measured airways reactivity to bronchodilator, fractional exhaled nitric oxide (FeNO), and nasal eosinophilia. Stool samples were examined for geohelminths by microscopy. Results: 1,933 (80.4%) children were evaluated at 8 years. Geohelminths were detected in 45.8% of mothers and in 45.5% of children to 5 years. Frequencies of outcomes at 8 years were: wheeze (6.6%), asthma between 5 and 8 years (7.9%), SPT (14.7%), airways reactivity (10%), and elevated FeNO (10.3%) and nasal eosinophilia (9.2%). Any maternal geohelminth was associated with reduced prevalence of SPT (OR 0.72). Childhood T. trichiura infections were associated with reduced wheeze (OR 0.57) but greater parasite burdens with A. lumbricoides were associated with increased wheeze (OR 2.83) and asthma (OR 2.60). Associations between maternal geohelminths and wheeze/asthma were modified by atopy. Parasite-specific effects on wheeze/asthma and airways reactivity and inflammation were observed in non-atopic children. Conclusions: Our data provide novel evidence for persistent effects of in utero geohelminth exposures on childhood atopy but highlight the complex nature of the relationship between geohelminths and the airways. Registered as an observational study (ISRCTN41239086).
Asthma is not a risk factor for the severity of SARS-CoV-2 infection in the Mexican p...
Jaime Morales-Romero
Martín Bedolla-Barajas

Jaime Morales-Romero

and 1 more

November 30, 2020
Background. Asthma does not seem to confer a risk for developing a disease caused by 2019 novel coronavirus (COVID-19). The aim of this study was to assess the association between asthma and severity of COVID-19 in the Mexican population. Methods. In a cross-sectional study, we analyzed the data of the population in Mexico who underwent a test to detect COVID-19 from February 27 to June 21, 2020. The primary outcomes were hospitalization, pneumonia, endotracheal intubation, and death related to COVID-19 in patients with asthma. Results. Asthma was associated with a lower risk of hospitalization (OR = 0.71, 95% CI 0.66 to 0.76), lower risk of pneumonia (OR = 0.75, 95% CI 0.69 to 0.81), and lower risk of endotracheal intubation (OR = 0.79, 95% CI 0.63 to 0.98). In addition, asthma decreased the risk of dying from COVID-19 (OR = 0.73, 95% CI 0.65 to 0.82). In a subgroup analysis, the same trend was observed in patients who required hospitalization (OR = 0.79, 95% CI 0.69 to 0.90); while in non-hospitalized patients, associations were inconsistent according to the covariates introduced to the models. There was no association between asthma and death in patients admitted to the intensive care unit (ICU); however, in hospitalized patients who did not require ICU management, asthma significantly reduced the risk of dying. Conclusion. Our results suggest that compared to patients without asthma, patients with asthma are less likely to require hospitalization, develop pneumonia, be intubated endotracheally, or die from COVID-19.
End to secondary care services for otitis externa?
Michael Mather
Hassan Mohammed

Michael Mather

and 2 more

November 25, 2020
Introduction: Referrals for OE have increased but the reasons for this remain unclear. We characterise referrals to inform primary secondary care interface improvements. Methods: Questionnaire study from dedicated consultant-led research clinic for OE referrals. Results: 62 patients responded; 63% female, mean age 54 years. One was excluded (not OE). Most had multiple primary care visits before referral (average 4 GP; 2 practice nurse). 60% had received oral antibiotics (16% multiple classes). 18% had never had ear drops. 39% were not advised to keep ears dry. 21% had dermatitis; 13% contact allergy, 30% systemic allergy, 5% diabetes. <10% had narrow canals. 36% had active discharge but <7% needed a wick. Conclusion: OE occurs most commonly in women - often with associated risk factors. Lifestyle advice and ototopical drops are frequently overlooked; instead often inappropriately treated with oral antibiotics. Most ear were anatomically normal and community aural care clinics may have a role in reducing referrals.
The Molecular Epidemiology and Clinical Phylogenetics of Rhinoviruses among Paediatri...
Dillon   Adam
Xin Chen

Dillon Adam

and 5 more

November 23, 2020
Background Rhinoviruses (RV) represent the most common aetiological agent of all acute respiratory tract infections across all age groups and a significant burden of disease among children. Recent studies have shown that RV-A and RV-C species are associated with varying degrees of disease severity and clinical symptoms. Methods In this study, we uncovered potential associations between RV species and subtypes, and clinical disease severity using a matched dataset of 52 RV isolates sampled from children (<18 years) in Sydney, Australia between 2006 and 2009 using epidemiological and phylogenetic methods. Results We found that RV-C was significantly more likely to be isolated from paediatric cases under two years of age compared to RV-A, although no significant differences in recorded symptoms were observed. Significant phylogenetic-trait associations between age and the VP4/VP2 capsid protein phylogeny suggests age-specific variations in infectivity among subtypes might also be possible. Conclusions This study adds to the growing body of epidemiological evidence concerning RV. Improving surveillance and testing for RV, including routine whole genome sequencing may improve our understanding of the varied diseashe outcomes of RV species and subtypes. Future studies could aim to identify specific genetic markers associated with age-specific infectivity of RV which could inform treatment practices and public health surveillance of RV.
Outcomes and Clinical Relevance of a 16-Gene Pharmacogenetic Panel Test for Medicatio...
David Niedrig
Ali Rahmany

David Niedrig

and 8 more

November 23, 2020
Background and Purpose: There is an increasing number of evidence-based indications for pharmacogenetic (PGx) tests and a growing demand for PGx screening. We aimed to evaluate clinical relevance of a 16-gene panel test for PGx-guided pharmacotherapy. Experimental Approach: Observational cohort study of subjects tested with a PGx panel for variants of ABCB1, COMT, CYP1A2, CYP2B6, CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, CYP4F2, DPYD, OPRM1, POR, SLCO1B1, TPMT and VKORC1. Specialized clinical pharmacology consultations with PGx-guided pharmacotherapy management were supported by the PGx expert system SONOGEN XP. Study outcomes were PGx-based changes and recommendations regarding current and potential future medication. Key Results: PGx-testing was triggered by specific drug-gene pairs in 102 subjects, whereas screening was performed in 33. Based on PHARMGKB expert guidelines the 16-gene panel identified at least one “actionable” variant relevant for current or potential future medication in all 135 (100%) tested patients. Drugs that triggered PGx-testing were clopidogrel in 60, tamoxifen in 15, polypsychopharmacotherapy in 9, opioids in 7, and other in 11 patients. Among those, PGx variants resulted in clinical recommendations to change PGx-triggering drugs in 33 (32.4 %), and other current pharmacotherapy in 23 (22.5%). Conclusion and Implications: The 16-gene PGx panel detected clinically relevant variants in a high proportion of tested patients, and SONOGEN XP supported their interpretation based on latest evidence. Additional costs of panel vs. single gene tests are moderate, and the efficiency of PGx panel testing challenges traditional cost-benefit calculations for single drug-gene pairs. However, PGx-guided pharmacotherapy requires specialized consultations with interdisciplinary collaborations.
Teenage pregnancy as a risk factor for placental abruption: Findings from the prospec...
Hyo Kyozuka
Tsuyoshi Murata

Hyo Kyozuka

and 13 more

November 16, 2020
Objective: To examine the effect of maternal age on placental abruption Design: Prospective cohort study Setting: Fifteen regional centers across Japan Population: We identified 94,410 Japanese women (93,994 without placental abruption and 416 with placental abruption) who were recruited in the Japan Environment and Children’s study between January 2011 and March 2014. Methods: Multiple regression models were used to identify whether maternal age (<20 years, 20–24 years, 25–29 years, 30–34 years, and ≥ 35 years) is a risk factor for placental abruption. The analyses were conducted while considering history of placental abruption, assisted reproductive technology, number of previous deliveries, smoking during pregnancy, body mass index before pregnancy, chronic hypertension, and uterine myoma as confounding factors. Main outcome measures: Maternal age as a risk factor for placental abruption Results: Besides advanced maternal age (≥35 years; adjusted odds ratio [aOR]: 1.7, 95% confidence interval [CI]: 1.1–2.5), teenage pregnancy was also a risk factor for placental abruption (aOR: 2.8, 95% CI: 1.2–6.5) when maternal age of 20–24 years was set as a reference. Conclusions: In the Japanese general population, besides advanced maternal age, teenage pregnancy was also a strong risk factor for placental abruption. The maternal age in Japan is changing since recent decades. Therefore, it is important for obstetric care providers to provide proper counseling to young women based on the up-to-date evidences. Funding: The Japan Environment and Children’s Study was funded by the Ministry of the Environment, Japan
EVALI versus MIS-C, one more overlapping diagnosis to consider
Diego Cruz-Vidal
Eric Mull

Diego Cruz-Vidal

and 7 more

November 12, 2020
We describe six teenagers presenting with fever and severe abdominal symptoms admitted with concerns for multisystem inflammatory syndrome in children (MIS-C). Laboratory evaluation revealed elevated markers of inflammation, lymphopenia, and increased d-dimers. Imaging studies revealed multifocal airspace disease and ground-glass opacities. SARS-CoV-2 PCR and serologies were negative. All patients reported a history of vaping, prompting E-cigarette, or vaping, product use-associated lung injury (EVALI) diagnosis. MIS-C has overlapping clinical and laboratory features highlighting the added challenge of diagnosing EVALI during the COVID-19 pandemic.
Towards a new epidemiological definition of chronic rhinitis: prevalence of nasal com...
Klementina Avdeeva
S. Reitsma

Klementina Avdeeva

and 2 more

November 12, 2020
Background: Chronic rhinitis (CR) is currently defined as at least two nasal symptoms present for at least 1 hour per day for more than 12 weeks per year. Such definition lacks evidence-based foundation. Depending on the most troublesome symptom, CR patients are often divided into ‘runners’ and ‘blockers’, although the evidence supporting such subdivision is limited. The aim of the current study was to define CR, and to estimate its prevalence and the prevalence of the ‘runners’ and ‘blockers’ subtypes. Methods: Cross-sectional, questionnaire-based study in a random sample of participants representing the general population of the Netherlands. Results: The questionnaire was sent to 5000 residents; the response rate was 27%. CR was defined as at least 1 nasal complaint present for more than 3 weeks per year. The prevalence of CR in the general population was 40%. Participants who were excluded by the former CR definition (i.e. nasal complaints present for less than 1 hour per day, only one complaint, duration of complaints for 3-12 weeks per year) were shown to have a significantly higher VAS compared to the control group. The larger part of CR group was represented by non-allergic rhinitis (NAR): 70% vs 30%. There were 25% ‘Blockers’ and 22% ‘Runners’ in the CR group, whereas more than a half of the CR group could be classified in neither of these subgroups. Conclusion: Based on our data, we propose a new definition of CR: at least one nasal complaint present for at least 3 weeks per year.
COVID-19 in Childhood: Transmission, Clinical Presentation, Complications and Risk Fa...
Melissa Siebach
Giovanni Piedimonte

Melissa Siebach

and 2 more

November 11, 2020
Children less than 18 years of age account for an estimated 500,000 to 1.5 million global SARS-CoV-2 cases. Lower prevalence of COVID-19 among children, in addition to higher numbers of mild and asymptomatic cases, continues to provide challenges in determining appropriate prevention and treatment courses. Here, we summarize the current evidence on the transmission, clinical presentation, complications and risk factors in regards to SARS-CoV-2 in children and highlight crucial gaps in knowledge going forward. Based on current evidence, children are rarely the primary source of secondary transmission in the household or in child care and school settings and are more likely to contract the virus from an adult household member. Higher transmission rates are observed in older children (10-19 years old) compared to younger children (<10 years old). While increasing incidence of COVID-19 in neonates raises the suspicion of vertical transmission, it is unlikely that breast milk is a vehicle for transmission from mother to infant. The vast majority of clinical cases of COVID-19 in children are mild, but there are rare cases that have developed complications such as multisystem inflammatory syndrome in children (MIS-C), which often presents with severe cardiac symptoms requiring intensive care. Childhood obesity is associated with a higher risk of infection and a more severe clinical presentation. Although immediate mortality rates among children are low, long-term respiratory and developmental implications of the disease remain unknown in this young and vulnerable population.
Lipids and lipoproteins in plasma from early pregnancy to postpartum and associations...
Christin Waage
Ibrahimu Mdala

Christin Waage

and 8 more

November 11, 2020
Objective To describe ethnic differences in plasma lipid levels and their changes during pregnancy to postpartum. Design Population-based cohort study Setting Primary antenatal care, Eastern Oslo, Norway Population or Sample Healthy pregnant women, 59% with ethnic minority background (n=806). Methods Fasting lipid levels were measured at gestational week (GW) 15, 28 and 14 weeks postpartum. We performed linear regression models and linear mixed models to explore the total effect of ethnicity on lipids, adjusting for GW or week postpartum, age and education. Main Outcome Measures Levels of triglycerides, HDL-, LDL- and total cholesterol. Results At GW 15, triglyceride levels were lower in women of African origin (1.03 mmol/mol (95% CI: 0.90, 1.16)) and higher in women of South Asian (1.42 mmol/mol (1.35, 1.49)) and East Asian origin (1.58 mmol/mol (1.43, 1.73)) compared with Western Europeans (1.26 mmol/mol (1.20, 1.32)). Women of Asian and African origin had a smaller increase in triglycerides, LDL and total cholesterol from GW 15 to 28. At GW 28 LDL-cholesterol levels were lowest among East Asians at (3.03 mmol/mol (2.72, 3.34)) compared with Western Europeans (3.62 mmol/mol (3.50, 3.74)). Triglyceride and HDL-cholesterol levels were lower postpartum than in early pregnancy in all groups, but LDL-cholesterol levels were higher, except in Africans. South and East Asian women had lower HDL-cholesterol and higher triglycerides postpartum, while African women had lower triglyceride levels than Western Europeans. Conclusion We found significant differences in lipid levels and changes during pregnancy and the early postpartum period related to ethnic origin.
Impact of the COVID-19 Pandemic on Pediatric Cystic Fibrosis Pulmonary Exacerbations
Shreya Patel
Misty Thompson

Shreya Patel

and 4 more

November 09, 2020
To assess the impact of COVID-19 restrictions on cystic fibrosis (CF) pulmonary exacerbations (PEx) we performed a retrospective review of PEx events at our CF Center and compared the rate of PEx in 2019 vs 2020. Restrictions on social interaction due to the COVID-19 pandemic were associated with a lower rate of PEx at our pediatric CF Center, suggesting that these restrictions also reduced exposure to other respiratory viral infection in children with CF.
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