ABSTRACT Objectives Anecdotal evidence suggests that oropharyngeal squamous cell carcinoma (OPSCC) should be suspected in patients presenting with symptoms of peritonsillar abscess (PTA) or cellulitis (PTC). The aim of this study was to estimate the prevalence of OPSCC in patients presenting with symptoms of PTA/PTC. Method, Setting and Participants We retrospectively identified all adults with a coded diagnosis of PTA or PTC who presented between 2012-2016 inclusive, across six ENT units in ——–. Records were compared to that of the centralised regional head and neck cancer database. The clinical records of a subset of patients were reviewed for the purposes of data validation. Results A total of 1975 patients with PTA/PTC were identified. Three patients were subsequently diagnosed with OPSCC. None of the three actually had an objective underlying diagnosis of PTA/PTC on the same side. The prevalence of OPSCC in patients admitted with symptoms of PTA/PTC was 0.15%, or approximately 1:650 admissions. The records of 510 patients who presented over a one-year period (2016) were reviewed in even greater detail. There were 298 patients with PTA (59.4%), 151 with PTC (29.1%) and 61 had an alternative diagnosis (11.9%). High risk features (age ≥40, tonsillar asymmetry or tonsillar lesion) were present in 106 patients (24%). Urgent follow up was expedited for 77 patients (73%). Conclusion This study estimates the risk of OPSCC in patients with peritonsillar symptoms. The prevalence is low, even in a region with a relatively heavy disease burden. Clinicians should, however, retain a high level of suspicion in patients with persistent symptoms.

Approval of direct-acting oral anticoagulants (DOACs) for stroke prevention in atrial fibrillation (AF) was an important milestone, providing widened treatment choices along with the possibility for inter-drug switching after initiation. In addition to improved utilisation of oral anticoagulants (OACs) for stroke prevention, reports of switching among OACs are growing in the literature. Switching may influence clinical outcomes, healthcare costs and patient satisfaction. This review aimed to summarise the current literature on the pattern of OAC switching in patients with AF, including reasons for switching and clinical consequences following switching. We included articles published after 2013, following the introduction of apixaban; searched on June 27, 2020 from PubMed, Scopus and Embase. The review found that switching among OACs was common in clinical practice, significantly varying with the type of OAC. Studies reporting the reason for switching and clinical outcomes were comparatively limited. The reasons were often related to safety issues, poor anticoagulation control and ease of use. Factors that can increase the risk of bleeding and stroke were found to be associated with switching from vitamin K antagonists, but less for DOAC switching. Findings regarding bleeding outcomes following switching were inconsistent, possibly confounded with the type of OAC, reasons for switching and switching protocol. Despite the limited number of studies included and their relatively short follow-up periods, our review revealed that switching had minimal impact on stroke and other related thrombotic outcomes. Further prospective studies are needed to better understand possible reasons for switching and its influence on clinical outcomes.

Objective: To determine the association between treatment of persistent BV in pregnancy and risk for spontaneous preterm birth (sPTB). Design: The retrospective data from IBM® MarketScan® Commercial Database was analyzed. Setting: United States outpatient data. Population or Sample: Women aged 12–55 years with a singleton gestation. Methods: Women were linked to an outpatient medications database and medications taken during the pregnancy were analyzed. Treatment of BV in pregnancy was defined as a diagnosis of BV and treatment with Metronidazole and/or Clindamycin, and persistent treatment of BV was defined as BV in more than 1 trimester or BV requiring more than 1 antibiotic prescription. Odds ratios were calculated comparing sPTB in those with BV and persistent BV to women without BV in pregnancy. Survival analysis using Kaplan-Meier curves for the gestational age at delivery was also performed. Main outcome measures: sPTB Results: Among a cohort of 2,538,606 women, 216,611 had an associated ICD-9 or ICD-10 code for diagnosis of BV alone, and 63,817 had BV and were treated with either metronidazole and/or clindamycin. The sPTB rate among women treated with BV was 7.5% compared with 5.7% for women without BV who did not receive antibiotics. Relative to those without BV in pregnancy, odds ratios for sPTB were highest in those treated for BV in both the first and second trimester (1.66 [95% CI 1.52, 1.81]) or those with 3 or more prescriptions in pregnancy (1.48 [95% CI 1.35, 1.63]. Conclusions: Treatment of persistent BV is associated with increased sPTB risk.

Objectives: Pneumothorax (PTX) in newborns is a life-threatening condition associated with high morbidity and mortality especially in premature infants. The frequency of PTX in neonates at different gestational ages (GA) and its impact on neonatal mortality have not been quantified. We aimed to determine: 1) the prevalence of PTX in neonates at different GA from ≤24 weeks to ≥37 weeks, 2) the impact of PTX on mortality per GA, and 3) the impact of PTX on the length of stay (LOS) per GA. Methods: The national Kids’ Inpatient Database (KID) for the years of 2006 to 2012 were used. We included all infants admitted to the hospital with a documented GA and ICD9 code of pneumothorax. Bivariate and multivariate analyses were conducted and odds ratios (OR) were calculated. Results: A total of 10 625 036 infants were included; of them 3665 infants (0.034 %) had a diagnosis of PTX, with highest prevalence at ≤24 weeks GA (0.67%), and lowest at term (0.02%). The overall mortality rate of patients with PTX was 8.8%, and greater in preterm (16.3%) vs. term infants (2.7%). The association of mortality with PTX was greatest at GA of 29−32 weeks (OR = 8.55 (95% CI: 6.56−11.13). Infants who survived until discharge had a median of 2–12 days longer length of stay depending on GA category. Conclusions: The prevalence of PTX peaks in infants <24 weeks, however its impact on mortality is greatest at 29-32 weeks. PTX is associated with longer length of stay in survivors.

Background: Pharmacological pain management options can relieve women’s pain during labour and birth. Trials of these interventions have used a wide variety of outcomes, complicating meaningful comparisons of their effects. Consensus about key outcomes would facilitate the development of a core outcome set to assess the effectiveness of labour pain management. Objective: To identify all outcomes used in studies of pharmacological pain management interventions during labour and birth. Design: A review of systematic reviews and their included randomised controlled trials was undertaken. Search Strategy: Cochrane CENTRAL was searched to identify all Cochrane systematic reviews describing pharmacological pain management options for labour and birth. Search terms included “pain management”, “labour” and variants, with no limits on year of publication or language. Selection Criteria: Cochrane reviews and randomised controlled trials contained within these reviews were included, provided they compared a pharmacological intervention with other pain management options, placebo or no treatment. Data Collection and Analysis: All outcomes reported by reviews or trials were extracted and tabulated, with frequencies of individual outcomes reported. Main Results: Nine Cochrane reviews and 227 unique trials were included. In total, 148 unique outcomes were identified and categorised into maternal, fetal, neonatal, child, health service, provider’s perspective, or economic outcome domains. Conclusions: Outcomes of pharmacological pain management interventions during labour and birth vary widely between trials. The standardisation of trial outcomes would permit more meaningful comparison between studies. Funding: No external funding was provided. Keywords: Labour and birth; pain management; pharmacological interventions; systematic review

Background-The SARS-CoV-2/ Covid-19 pandemic is still going on and globally healthcare

Objective: To assess the general population’s knowledge regarding the utility and availability of tools to diagnosis endometriosis, with focus on ultrasound. Design: An international cross-sectional online survey study was performed between August and October 2019. Setting and Population: 5301 respondents, representing 73 countries. Methods: 23 questions survey focused on knowledge of endometriosis diagnosis distributed globally via patient- and community-endometriosis groups using social media. Main outcomes and measures: Descriptive data of the knowledge of diagnostic tools for diagnosing endometriosis, including details about diagnosis using ultrasound. Results: 84.0% of respondents had been previously diagnosed with endometriosis, 71.5% of which were diagnosed at the time of surgery. Ultrasound and MRI were the methods of diagnosis in 6.5% and 1.8%, respectively. 91.8%, 28.8%, and 16.6% of respondents believed surgery, ultrasound and MRI could diagnose endometriosis, respectively (more than one answer allowed). In those diagnosed by surgery, 21.7% knew about ultrasound as a diagnosis method compared to 51.5% knowing in those diagnosed non-surgically (p<0.001). 14.7%, 31.1%, and 18.2% stated superficial, ovarian, and deep endometriosis could be diagnosed with ultrasound (32.9% stated they did not know which phenotypes of endometriosis could be diagnosed). 58.4% of respondents do not believe they could access an advanced ultrasound in their region. Conclusions: There are significant gaps in the understanding of diagnosing endometriosis using non-surgical tools in this study population.

A document by Lara Lemon, written on Authorea.

Objective The My Baby’s Movements (MBM) trial aimed to evaluate the impact on stillbirth rates of a multifaceted awareness package (MBM intervention). Design Stepped-wedge cluster-randomised controlled trial. Setting Twenty-seven maternity hospitals in Australia and New Zealand. Population Women with a singleton pregnancy without major fetal anomaly ≥28 weeks’ gestation from August 2016-May 2019. Methods The MBM intervention was implemented at randomly assigned time points with sequential introduction into 8 clusters of 3-5 hospitals at four-monthly intervals. The stillbirth rate was compared in the control and intervention periods. Generalised linear mixed models controlled for calendar time, clustering, and hospital effects. Outcome Measures Stillbirth at ≥28 weeks’ gestation. Results There were 304,853 births with 290,219 meeting inclusion criteria: 150,079 in control and 140,140 in intervention periods. The stillbirth rate during the intervention was lower than the control period (2.2/1000 births versus 2.4, odds ratio [OR] 0.91, 95% Confidence Intervals [CI] 0.78-1.06, p=0.22). The decrease was larger across calendar time with 2.7/1000 in the first 18 months versus 2.0/1000 in the last 18 months (OR 0.74; 95% CI 0.63-0.86; p≤0.01). Following adjustment, stillbirth rates between the control and intervention periods were not significantly different: (aOR 1.18, 95% CI 0.93-1.50; p=0.18). No increase in secondary outcomes, including obstetric intervention or adverse neonatal outcome, was evident. Conclusion The MBM intervention did not reduce stillbirths beyond the downward trend over time, suggesting hospitals may have implemented best practice in DFM management outside their randomisation schedule. The role of interventions for raising awareness of DFM remains unclear

Increase of allergic conditions has occurred at the same pace with the Great Accleration, which stands for the rapid growth rate of human activities upon Earth from 1950s. Changes of environment and lifestyle along with escalating urbanization, are acknowledged as the main underlying causes. Secondary (tertiary) prevention for better disease control has advanced considerably with innovations for oral immunotherapy and effective treatment of inflammation with corticosteroids, calcineurin inhibitors and biologic medications. Patients are less disabled than before. However, primary prevention has remained a dilemma. Factors predicting allergy and asthma risk have proven complex: risk factors increase the risk while protective factors counteract them. Interaction of human body with environmental biodiversity with micro-organisms and biogenic compounds as well as the central role of epigenetic adaptation in immune homeostasis have given new insight. Allergic diseases are good indicators of the twisted relation to environment. In various non-communicable diseases, the protective mode of the immune system indicates low-grade inflammation without apparent cause. Giving microbes, pro- and prebiotics, has shown some promise in prevention and treatment. The real-world public health programme in Finland (2008-2018) emphasized nature relatedness and protective factors for immunological resilience, instead of avoidance. The nationwide action mitigated the allergy burden, but in the lack of controls, primary preventive effect remains to be proven. The first results of controlled biodiversity interventions are promising. In the fastly urbanizing world, new approaches are called for allergy prevention, which also has a major cost saving potential.

A document by Ian Sinha, written on Authorea.

Background: A series of repeated questionnaire surveys among 8- and 9-year-old schoolchildren in the city of Patras, Greece, demonstrated a continuous rise in the prevalence of wheeze/asthma from 1978 to 2003, with a plateau between 2003 and 2008. We further investigated wheeze/asthma trends within the same environment during the last decade. Methods: Two further identical cross-sectional surveys were conducted in 2013 (N=2554) and 2018 (N=2648). Physician-diagnosed wheeze and asthma were analysed separately and in relation to their occurrence (recent-onset: solely within the last two years; non-current: prior to the last two years; persistent: both before and within the last two years). In addition, in 2018, spirometry was performed in participants reporting relevant symptoms and in a random sample of healthy controls. Results: The prevalence of current wheeze/asthma declined from 6.9% in 2008 to 5.2% in 2013 and 4.3% in 2018. The persistent and non-current wheeze/asthma groups (both including children with symptoms at preschool age) followed this overall trend, while the prevalence of recent-onset wheeze/asthma remained unchanged. Persistent and non-current wheezers were also more frequently diagnosed with asthma, in contrast to those with recent-onset wheeze. Children with recent-onset wheeze/asthma and a considerable fraction of those with persistent symptoms had lower lung function. Conclusions: The prevalence of childhood wheeze/asthma has declined significantly during the last decade in Greece. Our analysis suggests that the reversing trend is most likely attributed to changing asthma perceptions among physicians and/or parents, especially in the case of preschool children with troublesome respiratory symptoms.

Objectives: This study investigated the relationship between viral load and the incidence and recovery of olfactory and gustatory dysfunction (OD and GD), incidence of respiratory and gastrointestinal symptoms in COVID-19 patients. Design: A Retrospective Cohort Study. Setting and Participants: In total 599 outpatients’ cases polymerase chain reaction (PCR)–confirmed COVID-19-positive patients in Golestan province were included in the study. Main Outcome Measures: The incidence of OD, GD, their severity and the time of recovery was determined. The association of these variables with cycle threshold (CT) values of SARS-CoV-2 polymerase chain reaction was assessed. Results: The mean age of patients was 38.27 ± 13.62 years. The incidence of general symptoms included myalgia 70.1%, headache 51.8%, fever 47.7%, and dyspnea 21.4%. 41.9% of patients had gastrointestinal symptoms, including abdominal pain 26.5%, diarrhea 25.2%, nausea 20.5%, and vomiting 12.9%. 12.2% of patients had comorbidity. The trimester recovery rates of OD and GD were 93.94% and 94.74%, respectively. The mean recovery time of OD and GD was 14.56±13.37 and 13.8±3.77 days, respectively. The mean CT value in all patients was 27.45±4.55. There were significant associations between CT value with headache (P=0.04), GD (P=0.002) and OD (P=0.001). Conclusions: The intensity and the recovery of OD and GD in Covid-19 patients may be affected by initial viral load. Unlike to respiratory and gastrointestinal symptoms, the OD and GD were associated with lower viral load. Therefore, it may be recommended to use these clinical symptoms as an indicator in the initial screening of patients during pandemics.

Objectives: To assess the effectiveness of dimethyl fumarate (DMF) on annual rate of relapse (ARR) and disability progression in multiple sclerosis (MS) compared to injectable immunomodulators (IMM), teriflunomide (TERI) and fingolimob (FTY), in real life setting. Methods: A population-based cohort study was conducted using data of the French nationwide claims database, SNDS. All patients initiating IMM, TERI, FTY or DMF between July 1, 2015 and December 12, 2017, with 4.5 years of database history and 1 to 3.5 years of follow-up were included in this study. DMF patients were 1:1 matched to IMM, TERI or FTY using a high dimensional Propensity Score. Negative binomial regression and a logistic regression models were used to estimate the relative risk (RR ± [95% CI]) of ARR and the Odds Ratio (OR ± [95% CI]) of disability progression, respectively. Results: Overall, 9 304 subjects were identified: 29.0% initiated DMF, 33.2% TERI, 5.6% FTY and 32.2% an IMM. The matched cohorts consisted of 1779 DMF- IMM, patients, 1679 DMF-TERI patients, and 376 DMF-FTY patients. DMF significantly reduced ARR compared to IMM (RR 0.72 [0.61 - 0.86]) and TERI (0.81 [0.68 - 0.96]) and did not show any significant difference when compared with FTY The risk of the progression of MS specific disability was not significantly different for any matched cohorts. Interpretation: DMF is associated with lower risk of relapse for patients with RRMS than other first-line RRMS agents (TERI and IIM).

Objective: To estimate the causal impact of small for gestational age (SGA) births on caesarean delivery, with and without trial of labour (TOL); and to quantify how much of the association is mediated through gestational age at delivery. Design: Cross-sectional analysis. Setting: Para 2 women who delivered non-anomalous, singleton live births from 22-44 weeks’ gestation in the US (2015-2018). Main outcomes and measures: Caesarean delivery with and without TOL. The exposure was SGA births (sex-specific birthweight <5th and <3rd percentiles for gestational age), and AGA births (10-89th percentile). We performed causal mediation analysis to determine the impact of gestational age at delivery (22-33, 34-36, 37-38, 39-40 and ≥41 weeks) as intermediate. Results: Of the 3,755,798 subjects, compared to AGA (29.6%), caesarean risks were higher for SGA <5th (34.3%) and SGA <3rd (36.4%) percentiles. For SGA <5th percentile, the adjusted excess risk of caesarean delivery without TOL had a “U” shaped association, with increased risk at preterm gestations, nadir at 39-40 weeks, and increased thereafter. The decomposition analysis revealed the driver of this excess risk was SGA births. The risk of caesarean delivery with TOL was highest <34 weeks’ gestation and was primarily an interaction effect. As gestation advanced, SGA births contributed proportionately greater to the risk. Associations were stronger for SGA <3rd percentile. Conclusions: Exposure to SGA drives high rates of prelabour caesareans and contributes to high risks of caesarean deliveries after TOL at >41 weeks gestation; a different mechanism drives high rates of caesareans after TOL at preterm gestations.

Research data derived from observational studies are accumulating quickly in the field of allergy and immunology and a large amount of observational studies are published every year. The aim of the present study was to evaluate the adherence to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist by papers published in the three European Academy of Allergy and Clinical Immunology journals, during the period 2009-2018. To this end, we conducted a bibliographic study of up to eight randomly selected papers per year per Journal. Our literature search resulted in 223 papers. Among those, 80, 80 and 63 records were from Pediatric Allergy and Immunology, Allergy and Clinical and Translational Allergy, respectively; the latter was published only from 2011 on. Prospective, case-control, and cross-sectional designs were described in 88, 43, and 92 papers, respectively. Full reporting of all STROBE items was present in 47.4%, 45.6%, and 41.2% for the cohort, cross-sectional, and case-control studies, respectively. Generally, no time trend in adherence of reporting STROBE items was observed, apart from reporting funding, which increased from 60% in 2009/2010 to more than 90% in 2018. We identified a cluster of STROBE items with low proportions of full reporting constituted by the items on reporting study design in the title and methods, variables types along with their measurement/assessment, bias and confounding, study size, and grouping of variables. It appears that the STROBE checklist is a suitable tool in observational allergy epidemiology. However, adherence to the STROBE checklist appeared suboptimal.

Objective: To estimate the association between chronic hypertension and perinatal mortality and evaluate the extent to which this risk is impacted by preterm delivery. Design: Cross-sectional analysis. Setting: US, 2015-2018. Population: Singleton births from 20-44 weeks’ gestation. Main outcomes and measures: We derived the risk of perinatal mortality in relation to chronic hypertension from fitting log-linear Poisson models with robust variance. Risk ratios (RR) and 95% confidence intervals (CI) were estimated after adjusting for confounders. The impact of misclassifications and unmeasured confounding biases were assessed. Causal mediation analysis was performed to quantify the impact of preterm delivery on the association. Results: Of the 15,090,678 singleton births, perinatal mortality was 22.5 per 1000 births in chronic hypertensive pregnancies compared to 8.2 per 1000 births in normotensive pregnancies (adjusted RR 2.05, 95% CI 2.00, 2.10). Corrections for exposure misclassification and unmeasured confounding biases substantially increased the risk estimate. Although, causal mediation analysis revealed that most of the effect of chronic hypertension on perinatal mortality was mediated through preterm delivery, the perinatal mortality rates were highest at early term, term, and late term gestations, suggesting that a planned early term delivery at 37-386/7 weeks may optimally balance risk in these pregnancies. Additionally, 87% (95% CI 84, 90) of perinatal deaths could be eliminated if preterm deliveries, as a result of chronic hypertension were prevented. Conclusions: Chronic hypertensive pregnancies are associated with increased risk for perinatal mortality. Planned early term delivery and targeting modifiable risk factors for chronic hypertension may reduce perinatal mortality rates.

Proposals for SARS-CoV-2 virus vaccination priorities in the UK and in many other countries are heavily influenced by epidemiological models, which use outcome measures such as deaths or hospitalisation. Limiting the values under consideration to those attributable to the direct effects of infection has the advantage of simplifying the models and the process of decision-making. However, the consequences of the pandemic extend beyond outcomes directly attributable to SARS-CoV-2 infection. The alternative to vaccination (in addition the threat of illness and death) is restrictions on educational and work opportunities, access to services, recreational activities, affiliations and relationships with others, freedom of movement (including escaping abusive relationships), and other determinants of human experience. Capability theory gives emphasis to the freedoms that individuals have to express themselves (in doings and beings). Restrictions on freedoms restrict our capabilities. Capability theory has been used to provide a framework for the evaluation and comparison of international development approaches and in the evaluation of public health policy. There is a clustering of disadvantages associated with this pandemic that adds to pre-existing inequalities. Much of the disadvantage engendered in the SARS-CoV-2 pandemic is left out when public health policy is based on a limited range of metrics. Acknowledging the impact of policy across the range of human freedoms at both a national and international level has the potential to improve policy, facilitate the mitigation of direct and indirect adverse consequences, and improve public confidence in vaccine deployment strategies.

Objective: To investigate the association between maternal apolipoprotein A-1 (ApoA-1), apolipoprotein B (ApoB), ApoB/ApoA-1ratio and preterm birth (PTB). Design: Observational survey. Setting: Guangdong Women and Children Hospital, China Samples: 5986 pregnant women. Method: Data were extracted from the information system of Guangdong Women and Children Hospital. Maternal serum ApoB, ApoA-1 and ApoB/ApoA-1 ratio were categorized into tertiles. Logistic regression models were performed to evaluate the odds ratios and 95% confidence intervals for PTB. Main outcome measures: PTB (gestational age < 37 weeks) Results: Of the study participants, the rate of preterm birth was 5.7% (n= 344). Compare with individuals in the lowest tertile, the adjusted ORs of PTB was 1.41 (95% CI: 1.07-1.87) for individuals in the highest tertile of ApoB and 1.35 (95% CI: 1.03-1.78) for those in the highest tertile of ApoB/ApoA-1. The association of ApoB/ApoA-1 and PTB was more relevant among women with pre-pregnancy BMI ≤ 24 kg/m2, age at delivery ≥ 35 years or those who were multiparous. Conclusions: Elevated maternal ApoB level and ApoB/ApoA-1 ratio during mid-pregnancy were related to increased risk of PTB. Monitoring serum apolipoprotein levels may help to prevent preterm birth. Funding: The study was funded by grants 2019FYH003 from Chinese Center for Disease Control and Prevention. Keywords: Apolipoprotein A-1, Apolipoprotein B, Apolipoprotein B/Apolipoprotein A-1, Preterm birth Tweetable abstract：Maternal mid-pregnancy ApoB level and ApoB/ApoA-1 ratio were associated with PTB.

Abstract Background: Habitual snoring (HS), a prominent symptom of sleep-disordered breathing , is important to also consider the associated, multidimensional risk factors for HS in children. Aim: To identify risk factors for HS in children. Methods: A cross-sectional survey was performed in Chengdu. Children aged 2–14 years from four districts were randomly chosen to participate.Questionnaires were voluntarily completed by the children’s guardians. Results: The survey included 926 boys and 622 girls, who were an average of 7.11 5.25 years old. The sample included 463 habitual snorers (30.38%), 683 occasional snorers (44.82%), and 402 non-snorers (26.38%). HS was found in 51.84% of preschool children and 26.6% of school children.Among the HS group, 31.3% had a maternal education of a college degree or higher and 86.6%had an immediate family member who snores. Breastfeeding duration among the HS group was significantly less than among the occasional snoring and non-snoring groups. History of symptoms of allergic rhinitis, rhinosinusitis, tonsillitis, and pneumonia/bronchitis in the past six months were associated with HS. Likewise, maternal smoking during pregnancy, maternal exposure to secondhand smoke during pregnancy , and child exposure to secondhand smoke were also associated with HS. Conclusion: The prevalence of HS was higher in preschool children. Having a mother with more education, a family history of snoring, a shorter period of breastfeeding, upper respiratory tract inflammation, and passive smoking are important risk factors for HS.

Higher risk of allergies at 4-6 years of age after systemic antibiotics in the first week of life To the editor,In humans, the first 100 days appear to be a ”critical window” of colonization during which microbial communities shape immune maturation.1,2. The use of antibiotics early in life may disrupt the normal maturation process leading to adverse health outcomes such as atopic disorders 1,3-5. The effects of antibiotic exposure immediately in the first week of life have rarely been investigated, nor the differences between treatment of 2-3 days and a prolonged treatment of 5-7 days. In the INCA study, a prospective birth cohort study of 151 infants receiving broad-spectrum antibiotics in their first week of life (AB+), and 285 healthy controls (AB-), we previously showed that antibiotic treatment in the first week of life was associated with an increased risk of wheezing, infantile colic and a trend towards more allergic sensitization in the first year of life6. The aim of this follow-up study in 418 eligible children was to determine if antibiotic treatment in the first week of life in term-born children was associated with an increase in atopic disorders at 4-6 years of age, using ISAAC questionnaires filled out by parents, ICPC codes derived from general physicians, and pharmaceutical records from local pharmacies. Detailed information regarding the subjects and methods is described in the online Appendix.In total, 341 of 418 (82%) questionnaires were filled out (114 AB+ and 227 AB-), Parental reported allergy was significantly higher in AB+ vs AB- children (23% vs 11% respectively, p=0.003) as was doctor-diagnosed allergy (12% vs 4% respectively, p=0.008). Confirmed food allergies were more common in AB+ children compared with AB- children (10 vs. 4% respectively, p=0.03). After correcting for sex, age, daycare attendance, family atopy, and parental level of education, parental-reported allergy was clearly associated with antibiotics use in the first week of life (aOR 2.40 [95%CI 1.22-4.72, p=0.01]). Additional adjustment for treatment duration showed that only 5-7 and not 2-3 days AB treatment was associated with a higher risk of parental reported allergy (aOR 2.85 [95%CI 1.37-5.91, p=0.005]). More importantly, this effect was independent of exposure to acid-suppressive drugs or additional antibiotics in the first two years of life (36% and 35% in AB- and AB+ group, respectively). The prevalence of eczema, wheezing/asthma, or allergic rhinitis was not different between AB+ and AB- children (Table 2).These results suggest that very early exposure to AB in the first week of life has a higher impact on microbiota and immune development than when administered later in childhood. It also emphasizes the need for judicious use of AB in neonates, especially prolonged treatment of 5-7 days. Moreover, our findings accentuate the need for finding strategies to modify microbiome development after AB exposure to minimize aberrant immune development.Strengths of this study are the prospective design, the high response rate (82%), and the combined information collected from doctors and pharmacists, contributing to the reliability of the reported results, which allowed us to distinguish between the effect of antibiotics within and after the first week of life. A limitation of the study is the 4-6-year follow-up, which may have been too short for diagnosing asthma and allergic rhinitis.In conclusion, the risk of having an allergy at 4-6 years of age increased nearly 3-fold in children after antibiotic treatment for 5-7 days in their first week of life, independent of later AB treatment. These long-term adverse health effects of neonatal antibiotic use emphasize the need to implement AB stewardship programs to avoid AB overuse and reduce the duration of AB treatment where possible in the first week of life.

Respiratory syncytial virus (RSV) infection is the leading cause of bronchiolitis among infants <12 months old. It is widely known that coinfections between RSV and other viruses can worsen the clinical picture of affected patients. To evaluate the severity of clinical pictures of bronchiolitis in the 2019-2020 winter season, we performed a retrospective study of our third-level Pediatric Emergency Department (ED) admission charts. From February 2 to March 9, 2020 (start date of the Italian lockdown), we observed a peak of patients with a clinical picture of bronchiolitis requiring oxygen therapy of 55.1%, compared with 18% and 14.5% during the same period in 2017-2018 and 2018-2019, respectively (p<0.0001), without other clinically significant differences between the groups. Several authors hypothesized that SARS-CoV2 was present in northern Italy some weeks be-fore the first confirmed case. We suggest that one of the causes of this unexpected severe bronchiolitis peak may be a SARS-CoV2 - RSV coinfection in a period when SARS-CoV2 was already circulating in north-ern Italy. Given the lack of real-time polymerase chain reaction (RT-PCR) tests for SARS-CoV2 at that time, our suggestion remains a hypothesis.

Known knowns, unknown unknowns and everything in-between

Background Hypothyroxinemia, i.e. Low free T4 with normal TSH level, which overlaps, to a great extent, with the laboratory criteria of central hypothyroidism, could be easily neglected, if attention is paid only to patients with elevated TSH. We aimed to assess the association between mirtazapine use and hypothyroxinemia in patients affected by major depressive disorder. Methods We conducted a retrospective cohort study in the Second Affiliated Hospital of Xinxiang Medical University between January 2016 and December 2018. Patients affected by major depression disorder and admitted to the hospital for treatment during the study period and had thyroid tests at admission and after treatment were included. Patients with abnormal thyroid function at baseline or received mood stabilizers or quetiapine during hospitalization were excluded. Mirtazapine use was the exposure measure, and hypothyroxinemia was as the primary outcome of this study. Log-binomial model was used to estimate the association between mirtazapine use and hypothyroxinemia, after adjusting for potential confounding factors. Results A total of 220 eligible patients were included in the final analysis. Of them, 88 used mirtazapine. The incidence of hypothyroxinemia in patients who used mirtazapine was higher (37.5%) than those patients who did not use (19.7%). The relative risk of developing hypothyroxinemia was 1.64 (95% confidence interval: 1.31-1.78) for mirtazapine use, after adjusting for confounding factors. Conclusion Mirtazapine use was associated with the risk of developing hypothyroxinemia. Clinicians should be aware that hypothyroxinemia may be neglected in patients treated by mirtazapine due to attention paid only to those with elevated TSH.