Self-swabbing versus assisted swabbing for viral detection by qRT-PCR: the experience from SARS-CoV-2 based on a meta-analysis of six prospectively designed evaluations conducted in a UK setting.

PURPOSE: In April 2020, the UK Government implemented NHS Test and Trace to provide SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (qRT-PCR) testing for the public, with nose-and-throat swabbing for samples performed by trained staff. Self-swabbing (SS) would allow rapid scale-up of testing capacity and access. Six studies were undertaken to determine whether SS was as effective for detecting SARS-CoV-2 as swabbing performed by trained staff. METHODS: Six prospective studies were conducted between April-October 2020, using six swab/media combinations. Differences between assisted swabbing (AS) and SS were evaluated for concordance, positivity, sensitivity, cycle threshold (Ct) values and void rates. Statistical analysis was performed using 95% confidence intervals (CIs), paired t-tests and model-based methods. RESULTS: Overall, 3,253 individuals were recruited (median age 37 years, 49% female), with 2,933 having valid paired qRT-PCR results. Pooled concordance rate was 98% (95% CI: 96%, 99%). Positivity rate differences for SS (8.1%) and AS (8.4%) and differences in pooled sensitivities between SS (86%; 95% CI: 78%, 92%) and AS (91%; 95% CI: 78%, 96%) were nonsignificant. Both types of swabbing led to pooled void rates below 2% and strongly correlated Ct values. Age, sex and previous swabbing experience did not have a significant impact on concordance or sensitivity. CONCLUSION: The UK adopted a policy to promote self-testing for SARS-CoV-2 based on data demonstrating equivalence of SS versus AS. Positive outcomes with SS are likely generalisable to testing for other respiratory pathogens, and we consider self-sampling and self-testing essential for future pandemic preparedness.

Defining cases of asthma, eczema and allergic rhinitis using electronic health records in the Born in Bradford birth cohort.

Key Messages • In electronic health records, the accuracy of diagnostic codes to define outcomes can be uncertain • The accuracy can vary in different settings, doctors and practices, even with validated codes • We recommend definitions combining codes previously described and other codes available in the records.

Evidence for causal associations between prenatal and postnatal antibiotic exposure and asthma in children, England.

BACKGROUND: Higher risks of asthma have been observed in children with prenatal exposure to antibiotics and during early life compared with those who have not. However, the causality of such associations is unclear. OBJECTIVE: To assess whether exposure to antibiotics in early life had a causal effect in increasing the risk of asthma in children diagnosed at 5-8 years of life, and the impact in the target population. METHODS: Data were from electronic health records and questionnaires for children and their mothers in the Born in Bradford birth cohort. Exposure variables were prescriptions of systemic antibiotics to the mother during pregnancy (prenatal) and to the children at 0-24 months of life (postnatal). We assessed the association in 12,476 children with several approaches to deal with different sources of bias (triangulation): the interactions with mother's ethnicity, mode of delivery, and between prenatal and postnatal exposures; dose-response; and estimated the population attributable risk. RESULTS: There was an association between prenatal exposure at 7-27 days before the child's birth and asthma (adjusted OR = 1.40; 1.05, 1.87), but no association with the negative control exposure (before pregnancy) (adjusted OR = 0.99 (0.88, 1.12)). For postnatal exposure, the adjusted OR was 2.00 (1.71, 2.34), and for sibling analysis, it was 1.99 (1.00, 3.93). For postnatal exposure, the risk of asthma increased with the number of prescriptions. The observed effect of both exposures was lower among children with mothers of Pakistani ethnicity, but inconclusive (p > .25). The interaction between prenatal and postnatal exposures was also inconclusive (p = .287). The population attributable risk of postnatal exposure for asthma was 4.6% (0.1% for prenatal). CONCLUSIONS: We conclude that the associations between both late-pregnancy prenatal exposure to antibiotics and postnatal exposure to antibiotics and an increased risk of asthma are plausible and consistent with a causal effect.

Dissociation between skin test reactivity and anti-aeroallergen IgE: Determinants among urban Brazilian children.

BACKGROUND: The dissociation between specific IgE and skin prick test reactivity to aeroallergens, a common finding in populations living in low and middle-income countries, has important implications for the diagnosis and treatment of allergic diseases. Few studies have investigated the determinants of this dissociation. In the present study, we explored potential factors explaining this dissociation in children living in an urban area of Northeast Brazil, focusing in particular on factors associated with poor hygiene. METHODS: Of 1445 children from low income communities, investigated for risk factors of allergies, we studied 481 with specific IgE antibodies to any of Blomia tropicalis, Dermatophagoides pteronyssinus, Periplaneta americana and Blatella germanica allergens. Data on demographic, environmental and social exposures were collected by questionnaire; serum IgG and stool examinations were done to detect current or past infections with viral, bacterial, protozoan and intestinal helminth pathogens. We measured atopy by skin prick testing (SPT) and specific IgE (sIgE) to aerollergens in serum (by ImmunoCAP). SIgE reactivity to B. tropicalis extract depleted of carbohydrates was measured by an in-house ELISA. Total IgE was measured by in house capture ELISA. SNPs were typed using Illumina Omni 2.5. RESULTS: Negative skin prick tests in the presence of specific IgE antibodies were frequent. Factors independently associated with a reduced frequency of positive skin prick tests were large number of siblings, the presence of IgG to herpes simplex virus, Ascaris lumbricoides and Trichuris trichiura infections, living in neighborhoods with infrequent garbage collection, presence of rodents and cats in the household and sIgE reactivity to glycosylated B. tropicalis allergens. Also, SNP on IGHE (rs61737468) was negatively associated with SPT reactivity. CONCLUSIONS: A variety of factors were found to be associated with decreased frequency of SPT such as unhygienic living conditions, infections, total IgE, IgE response to glycosylated allergens and genetic polymorphisms, indicating that multiple mechanisms may be involved. Our data, showing that exposures to an unhygienic environment and childhood infections modulate immediate allergen skin test reactivity, provide support for the "hygiene hypothesis".

The effect of thiamine deficiency on inflammation, oxidative stress and cellular migration in an experimental model of sepsis.

BACKGROUND: Sepsis is a prevalent condition in critically ill patients and may be associated with thiamine deficiency (TD). The aim of this study was to evaluate the effect of TD on inflammation, oxidative stress and cellular recruitment in a sepsis model. METHODS: The experimental sepsis model, cecal ligation and puncture (CLP), was utilized on mice in comparison with a sham procedure. The following four groups were compared against each other: SHAM with AIN93G complete chow, SHAM with thiamine deficient (TD) chow, CLP with AIN93G complete chow, and CLP with TD chow. Thiamine pyrophosphate (TPP) blood concentrations were determined, and blood and peritoneal fluid were evaluated for differences in TNF-alpha, IL-1, IL-6, KC and MCP-1/CCL2 levels. In addition, the levels of 4-HNE adducts in liver proteins were evaluated by Western Blot. RESULTS: The mean TPP blood concentration from the mice fed with the complete chow was 303.3 ± 42.6 nmol/L, and TD occurred within 10 days. TNF-α and MCP-1 concentrations in the peritoneal fluid were significantly greater in the CLP with TD chow group when compared with the other groups. The blood IL-1ß level, however, was lower in the CLP with TD chow group. Liver 4-HNE levels were highest in the TD chow groups. Blood mononuclear cell numbers, as well as peritoneal total leukocyte, mononuclear cell and neutrophil numbers were greater in the CLP with TD chow group. Peritoneal bacterial colony forming units (CFU) were significantly lower in the CLP with TD chow group. CONCLUSION: TD was associated with greater bacterial clearance, oxidative stress and inflammatory response changes.

Does BCG revaccination protect against the development of asthma?

Single BCG vaccination has been considered as a protective factor against asthma. However the effect of a second dose of BCG on the prevalence rate of asthma and asthma-allergic rhinitis-eczema comorbidity has not been studied exclusively among adolescents. In this ISAAC protocol-based cross sectional study we assessed the association between one single versus two doses of BCG among 2213 individuals aged 13-14 years old. We found no association between BCG revaccination and asthma, associated (OR = 0.68, 95% CI, 0.37-1.25) or not to allergic rhinitis and/or atopic eczema (OR = 1.07, 95% CI, 0.84-1.36).

A community study of factors related to poorly controlled asthma among Brazilian urban children.

BACKGROUND: Asthma constitutes a serious public health problem in many regions of the world, including the city of Salvador, State of Bahia-Brazil. The purpose of this study was to analyse the factors associated with poor asthma control. METHODOLOGY/PRINCIPAL FINDINGS: Two definitions were used for asthma: 1) wheezing in the last 12 months; 2) wheezing in the last 12 months plus other asthma symptoms or asthma diagnosis ever. The definition of poorly controlled asthma was: at least one reported hospitalisation due to asthma and/or high frequency of symptoms, in the last year. Children with poorly controlled asthma (N = 187/374) were compared with wheezing children with controlled asthma regarding age, gender, atopy, parental asthma, rhinitis, eczema, exposure to second hand tobacco smoke, presence of moulds, pets and pests in the house, helminth infections and body mass index. Crude and logistic regression adjusted odds ratios were used as measures of association. There was a higher proportion of poorly controlled asthma among children with eczema (OR = 1.55; 95% CI 1.02; 2.37). The strength of the association was greater among children with eczema and rhinitis (42.6%, 53.4% and 57.7%, respectively, in children who had no rhinitis nor eczema, had only one of those, and had both (p = 0.02 for trend test). The presence of mould in the houses was inversely associated with poorly controlled asthma (OR = 0.54; 95% CI 0.34; 0.87). CONCLUSIONS/SIGNIFICANCE: Our results indicate an association between eczema and poor asthma control in this environment, but emphasize the role of various other individual and environmental factors as determinants of poor control.

Involvement of methicillin-susceptible Staphylococcus aureus related to sequence type 25 and harboring pvl genes in a case of carotid cavernous fistula after community-associated sepsis.

Staphylococcus aureus encoding Panton-Valentine leukocidin (PVL) genes has become the cause of life-threatening infections. We describe a case of carotid cavernous fistula after bacteremia in a 12-year-old male, caused by a methicillin-susceptible S. aureus isolate carrying the pvl, fnbA, and ebpS genes and related to sequence type 25 (ST25). The patient's condition was complicated by pleural empyema and osteomyelitis in the right femur. The patient was discharged in good clinical condition after 160 days of hospitalization.

Distribution of bupivacaine enantiomers and lidocaine and its metabolite in the placental intervillous space and in the different maternal and fetal compartments in term pregnant women.

The aim of this study is to determine the concentrations of lidocaine and its metabolite, monoethylglycine xylidide (MEGX), and of the enantiomers of bupivacaine in maternal and fetal compartments. Ten healthy pregnant women were submitted to epidural anesthesia. Drug concentrations were determined in the maternal vein, fetal umbilical artery and vein, and the placental intervillous space. The highest concentrations of the bupivacaine enantiomers lidocaine and of lidocaine and of its MEGX metabolite were detected in maternal plasma and in the placental intervillous space. The placental transfer was 33% for the (+)-(R)-bupivacaine enantiomer and 31% for the (-)-(S)-bupivacaine enantiomer. For lidocaine and its MEGX metabolite, respective placental transfers were 60% and 43%. Lidocaine concentration in the fetal umbilical vein was 1.46 times higher than in the fetal umbilical artery. The highest concentrations of lidocaine and its metabolite and of the enantiomers of bupivacaine were detected in the placental intervillous space. The higher lidocaine concentrations in the fetal umbilical vein than in the fetal umbilical artery suggest that there was tissue uptake of the drug or drug metabolization by the fetus.

Seroprevalence and potential risk factors for Helicobacter pylori infection in Brazilian children.

BACKGROUND: Helicobacter pylori infection has been proved to be of great relevance to public health in unindustrialized countries, especially in low socioeconomic groups. Poor hygiene, deficient sanitation, and crowded conditions have been reported as risk factors for this infection. In this work, we investigated whether social and demographic characteristics were associated with anti-H. pylori IgG antibodies in 1104 children aged 4-11 years old from Salvador, a large city located in northeastern Brazil. METHODS: Standardized questionnaires were used to obtain social, demographic, and environmental data for the studied population in two periods of time (from 1997 to 2003 and in 2005). Anti-H. pylori IgG antibodies were assessed by indirect enzyme-linked immunosorbent assay in 2005. RESULTS: Anti-H. pylori IgG antibody was present in 28.7% of the children. Among the studied variables, the following were positively associated with the presence of anti-H. pylori antibodies in multivariable analyses: age above 8 years old (OR = 1.72, 95% CI = 1.23-2.40), a larger sibling number (OR = 1.66, 95% CI = 1.26-2.18), nursery attendance (OR = 1.49, 95% CI = 1.04-2.12), location of the house at an unpaved street (OR = 2.03, 95% CI = 1.44-2.87) and absence of a flush toilet (OR = 1.32, 95% CI = 1.00-1.74). CONCLUSION: Our data show that H. pylori infection in children from a major Brazilian city is associated with variables indicative of a crowded environment and deficient sanitation/habitation conditions, leading to the conclusion that improvements in hygiene and social conditions may protect children against this infection.

Asthma cases in childhood attributed to atopy in tropical area in Brazil.

OBJECTIVE: This study aimed to explore the association between asthma and atopy in a cohort of children living in a large urban center in Brazil. Atopy was defined by the presence of allergen-specific IgE in serum or by a positive skin prick test. METHODS: In a sample of 1 445 Brazilian children, the association between the prevalence of asthma, skin prick test positivity, and allergen-specific IgE in serum was investigated. RESULTS: The prevalence of asthma was 22.6%. The presence of serum allergen-specific IgE was frequent in asthmatics and nonasthmatics, and the prevalence of asthma increased only with levels of allergen-specific IgE > 3.5 kilounits/L. The proportion of asthma attributable to atopy was estimated to be 24.5% when atopy was defined by the presence of allergen-specific IgE. With a given level of specific IgE, no association between skin test reactivity and asthma was observed. Skin prick tests were less sensitive than specific IgE for detection of atopy. CONCLUSIONS: Most asthma cases in an urban underprivileged setting in Brazil were not attributable to atopy. This observation has important implications for understanding the risk factors for the asthma epidemic in Latin America.

Distribution of fentanyl in the placental intervillous space and in the different maternal and fetal compartments in term pregnant women.

BACKGROUND: Fentanyl is used in obstetrical practice to promote analgesia and anesthesia during labor and in cesarean delivery, with rapid and short-term effects. OBJECTIVE: To determine fentanyl concentrations in maternal plasma, in the placental intervillous space, and in the umbilical artery and vein in term pregnant women. PATIENTS AND METHODS: Ten healthy pregnant women underwent epidural anesthesia with fentanyl plus bupivacaine and lidocaine, and fentanyl concentrations were determined in the various maternal and fetal compartments, including the placental intervillous space, which has not been previously studied in the literature. RESULTS: The ratios of fentanyl concentrations in the various maternal and fetal compartments revealed an 86% rate of placental fentanyl transfer. The highest fentanyl concentrations were detected in the placental intervillous space, being 2.19 times higher than in maternal plasma, 2.8 times higher than in the umbilical vein and 3.6 times higher than in the umbilical artery, with no significant differences between the umbilical vein and artery, demonstrating that there was no drug uptake by fetal tissues nor metabolism of the drug by the fetus despite the high rates of placental transfer. CONCLUSION: The present study demonstrated that the placental intervillous space acted as a site of fentanyl deposit, a fact that may be explained by two hypotheses: (1) the blood collected from the placental intervillous space is arterial and, according to some investigators, the arterial plasma concentrations of the drugs administered to patients undergoing epidural anesthesia are higher than the venous concentrations, and (2) a possible role of P-glycoprotein (P-gp).

Stereoselective analysis of labetalol in human plasma by LC-MS/MS: application to pharmacokinetics.

Labetalol is clinically available as a mixture of two racemates (four stereoisomers). The stereoisomer (R,R) has as main activity the beta1-antagonism and the stereoisomer (S,R) is highly selective for the alpha1 adrenoceptor and is responsible for most of the alpha-blocker activity. In the present investigation, a method for the analysis of labetalol stereoisomers in human plasma was developed and applied to pharmacokinetic studies. Plasma samples (0.5 ml) were extracted with methyl tert-butyl ether at pH 9.5. The four labetalol stereoisomers were analyzed by LC-MS/MS on a Chirobiotic V column using a mobile phase consisting of methanol, acetic acid, and diethylamine, with a recovery of more than 90% for all four. The quantitation limit was 0.5 ng/ml and linearity was observed at 250 ng/ml plasma for each stereoisomer. Studies of precision and accuracy presented coefficients of variation and percentage inaccuracy of less than 15%, indicating that the method is precise and accurate. The method was applied to the study of the kinetic disposition of labetalol over a period of 12 h after oral administration of a single 100 mg dose to a hypertensive pregnant woman. The clinical study revealed stereoselectivity in the pharmacokinetics of labetalol, with a lower plasma proportion for the active stereoisomers (R,R)-labetalol and (S,R)-labetalol. The stereoselectivity observed after oral administration is due to the hepatic metabolism and the first pass effect, with an AUC(R,R)/AUC(S,S) ratio of 0.5.

Minor psychiatric disorders in mothers and asthma in children.

OBJECTIVE: Recent studies have shown that asthma represents a major health issue not only in children of developed countries but also in urban centers in some middle-income countries. Brazil has one of the highest prevalences of asthma worldwide. Recently, interest has grown in the relationship between psychosocial factors and asthma. This article examines the relationship between maternal mental disorders and the prevalence of asthma in low-income children from an inner city area of Salvador in the state of Bahia, Brazil, and is part of the SCAALA program (Social Change, Allergy and Asthma in Latin America). PATIENTS AND METHODS: A total of 1,087 children between the ages of 5 and 12 were investigated, together with their mothers. The mothers' mental health was evaluated using the SRQ-20, an instrument for the psychiatric screening of minor psychiatric disorders (depression, anxiety and somatic complaints). The prevalence of asthma was investigated using the ISAAC survey, a standardized, validated questionnaire for asthma and other allergic diseases. Cases were defined as asthma if the patient reported having had wheezing in the previous 12 months in addition to at least one of the following: having asthma, wheezing while exercising, waking during the night because of wheezing, or having had at least four episodes of wheezing in the previous 12 months. Atopy was defined as a positive skin prick test to allergens. RESULTS AND CONCLUSION: The presence of minor psychiatric disorders in the mothers was significantly associated with the presence of asthma in the children, and this association was consistent with all forms of asthma, irrespective of whether it was atopic or nonatopic. Future studies should be carried out to further investigate this association and the potential biological mechanisms involved. Programs for asthma control should include strategies for stress reduction and psychological support for the families of asthmatic children.

Pharmacokinetics of lidocaine and its metabolite in peridural anesthesia administered to pregnant women with gestational diabetes mellitus.

BACKGROUND: Peridural blockade with lidocaine, bupivacaine, and fentanyl is an anesthetic procedure extensively used in obstetrics, justifying the pharmacokinetic study of these drugs during labor. OBJECTIVE: To investigate the influence of the physiopathological changes of gestational diabetes mellitus (GDM) on the pharmacokinetics of lidocaine and its metabolite monoethylglycinexylidide (MEGX) in pregnant women subjected to peridural anesthesia. PATIENTS AND METHODS: Ten normal pregnant women (group 1) and six pregnant women with GDM (group 2) were studied, all of them at term. The patients received 200 mg 2% lidocaine hydrochloride without a vasoconstrictor by the peridural locoregional route. Maternal blood samples were collected at predetermined times for the analysis of lidocaine and MEGX by chromatography and pharmacokinetic analysis. RESULTS: The median pharmacokinetic parameters of lidocaine for groups 1 and 2 (P

Cardiac alterations in furosemide-treated thiamine-deprived rats.

BACKGROUND: Chronic administration of furosemide may induce thiamine deficiency and cause or aggravate myocardial dysfunction. METHODS AND RESULTS: Wistar rats were divided into four groups according to food and treatment: (1) thiamine standard chow with intraperitoneal furosemide administration; (2) thiamine standard chow with intraperitoneal saline administration; (3) thiamine-deficient chow with intraperitoneal furosemide administration; and (4) thiamine-deficient chow with intraperitoneal saline administration. Thiamine status was evaluated by high-performance liquid chromatography determination in plasma, erythrocytes, and myocardium, and by erythrocyte transketolase activity and the thiamine pyrophosphate effect to recover transketolase activity. Left ventricular mass index, intramyocardial arteries-to-cardiomyocyte ratio, cardiomyocyte cross-sectional area, and cardiomyocyte nuclei number were estimated. Myocardial structure was also studied by transmission electronic microscopy. Group 3 showed significantly lower blood and myocardial thiamine levels, which was not observed in group 1. Left ventricular mass index, cardiomyocyte cross-sectional area, and intramyocardial arteries-to-cardiomyocyte ratio were smaller in thiamine-deficient and furosemide-treated rats. However, no significant variation was found in the number of cardiomyocyte nuclei among the groups. Transmission electronic microscopy showed mitochondrial alterations in the thiamine-deficient groups. CONCLUSION: The present results indicate that furosemide administration is not the primary cause of thiamine deficiency in rats with adequate thiamine intake. Furosemide aggravates thiamine deficiency only in situations associated with insufficient thiamine intake, causing cardiac structural alterations, such as myocardial fiber hypotrophy, poor microvascularization, and mitochondrial degeneration.

Ecological study of socio-economic indicators and prevalence of asthma in schoolchildren in urban Brazil.

BACKGROUND: There is evidence of higher prevalence of asthma in populations of lower socio-economic status in affluent societies, and the prevalence of asthma is also very high in some Latin American countries, where societies are characterized by a marked inequality in wealth. This study aimed to examine the relationship between estimates of asthma prevalence based on surveys conducted in children in Brazilian cities and health and socioeconomic indicators measured at the population level in the same cities. METHODS: We searched the literature in the medical databases and in the annals of scientific meeting, retrieving population-based surveys of asthma that were conducted in Brazil using the methodology defined by the International Study of Asthma and Allergies in Childhood. We performed separate analyses for the age groups 6-7 years and 13-14 years. We examined the association between asthma prevalence rates and eleven health and socio-economic indicators by visual inspection and using linear regression models weighed by the inverse of the variance of each survey. RESULTS: Six health and socioeconomic variables showed a clear pattern of association with asthma. The prevalence of asthma increased with poorer sanitation and with higher infant mortality at birth and at survey year, GINI index and external mortality. In contrast, asthma prevalence decreased with higher illiteracy rates. CONCLUSION: The prevalence of asthma in urban areas of Brazil, a middle income country, appears to be higher in cities with more marked poverty or inequality.

Determination of pindolol enantiomers in amniotic fluid and breast milk by high-performance liquid chromatography: applications to pharmacokinetics in pregnant and lactating women.

A method for the determination of pindolol enantiomers in amniotic fluid and breast milk was developed, validated, and applied to the investigation of six pregnant women treated with rac-pindolol (10 mg/12 h). Biological samples were extracted with tert-methyl-butyl ether, and the pindolol enantiomers were resolved on a Chiralpak AD column. Amniotic fluid/plasma and milk/plasma concentrations ratios ranged from 0.4 to 4.5 and from 0.6 to 3.7, respectively, for (+)-R-pindolol and from 0.5 to 3.5 and from 1.1 to 2.8, respectively, for (-)-S-pindolol. Preliminary data suggest that amniotic fluid and breast milk are routes of fetal exposure to pindolol enantiomers.