The pandemic characteristics of 2019-nCoV: case-control study for severity and geographic locations for 2019-nCoV epidemics worldwide.

Using available official data we found 248 epidemics curves caused worldwide by the 2019-nCoV in the period December 2019-March 31st 2020. The analysis of this material allowed two main observations: 1) it is possible to describe the main geographical pathway of the diffusion of the virus in different directions. This strongly suggests a unique point of origin of the pandemics in Wuhan, China, from where it spread in many different directions. 2) of the 74 epidemics which were characterized by at least 1000 cases, 65 (90%) were located in the geographic region of the world delimitated by 52-30 degrees latitude North. Viceversa 110 (60%) of the 176 epidemics with less than 1000 cases were located outside the cited geographical world region. These results suggest considerations on the pandemic characteristics of 2019-nCoV.

[Many doubts about the relationship between cases of microcephaly and Zika virus in Brazil]. / I molti dubbi sul rapporto tra casi di microcefalia e infezione da virus Zika in Brasile.

During the last few years, Zika virus rapidly spread across Central and South America and in the last months has spread also across Southern States of USA. As the epidemic began in Brazil, an increase of microcephaly cases was registered, causing concern and inducing the World Health Organization to raise an alarm. Certainly, the Zika virus, as many other viruses, has the capacity to induce severe cerebral lesions in foetuses of women infected during the first months of pregnancy. Moreover, more than 80% of cases of craniostenosys that verisimilarly took place in Brazil from September 2015 up to now were registered in few states of North- Eastern Brazil, where peaks of this malformation were registered several years before the appearance of Zika virus. In addition, in none of the 60 Countries where Zika virus is epidemiologically active an increase of the incidence of microcephaly has been reported. This paper intends to analyse some doubts concerning the link between Zika virus and the epidemic of craniostenosys.

Is asthma caused by atopy (positive skin prick tests)? Epidemiologic evidence suggests a negative answer.

In this paper we shortly discuss epidemiological data on the relationship between asthma and atopy according to recent personal and literature epidemiological publications. The coexistence in several subjects of asthma (and of other "atopic" diseases) and IgE hyperproduction generated the dogma that these two biological conditions are mainly genetic in origin and are linked by a strong casual relationship. In the last decades atopy increased at 5-10 % annual rate and at present atopy prevalence, although variable in different countries, reaches somewhere the prevalence of more than 60 %. Similarly, asthma prevalence increased in the last decades, especially so in western and English speaking countries, reaching in certain countries prevalence values higher than 40 %. For these reasons, although certainly dependent on a genetic predisposition, atopy and asthma can nowadays be considered to be largely determined by environmental factors. Moreover, the analysis of epidemiological data derived from studies conducted worldwide, showed that the prevalence of the two conditions were clearly not correlated so that in certain countries with a 50-60% prevalence of atopy asthma prevalence is lower than 2-6 %, while in other countries asthma prevalence is double than atopy prevalence. Further, in countries with high atopy, the prevalence this conditions is high both in asthmatics and in normal subjects and in the places where asthma prevalence reaches high levels this condition is high both in atopic and non atopic people. In conclusion, epidemiological data show that environmental factors affecting asthma prevalence are different from those affecting atopy prevalence and that subjects bearing one of the two conditions don't show any preferential tendency to develop the other one. From aetiological and pathogenetic point of view asthma and atopy appear to be independent conditions We therefore believe that the association between asthma and atopy demonstrated in almost all the "population studies" (atopy prevalence has always been found 20-30 % higher in asthmatics than in non asthmatic subjects) doesn't prove the existence of a "causal" relationship between the two conditions: this could be a kind of association without causative meaning as is the association between blond hair and blue eyes which in no way can be considered a prove that one of the two conditions is the cause of the other.

Reproducibility of food atopy patch tests over time in the general child population.

BACKGROUND: The atopy patch test (APT) is no longer an experimental method; it is increasingly being used as a standard diagnostic tool for the characterization of patients with aeroallergen- and food-triggered disorders. Some technical aspects of this test still remain to be answered. We aimed to study the reproducibility of this test over time in the general child population. METHODS: In a general population of 118 children, we investigated the reproducibility of duplicate APTs with four food allergens in their native form, which were repeated at set intervals from the first test: 7 days (group 1), 14 days (group 2), and 21 days (group 3). RESULTS: We observed very poor reproducibility on both sides of the back in all three studied subgroups. The reproducibility rates and Cohen's kappa values did not improve when we did not consider the side of the back. There were no differences in the prevalence of atopy between the subjects with reproducible and nonreproducible APT results. All three groups studied showed no difference in the prevalence rates of atopy. There was no relationship between APT and skin prick test positivity for the same allergen. Questionnaire-derived data about previous food-related reactions did not help in the evaluation of the doubtful nonreproducible APT results with food allergens. CONCLUSIONS: Our results show that the reproducibility of food APTs is poor and unsatisfactory over time, and there is an urgent need for the development of optimal, stable, and good-quality APT testing substances.

Relationship between atopic asthma and the population prevalence rates for asthma or atopy in children: atopic and nonatopic asthma in epidemiology.

Innumerable articles have tried to solve the "continuing enigma of atopic and nonatopic asthma" but notwithstanding the strenuous efforts to substantiate the few well-known clinico-epidemiologic differences between these two forms of asthma most studies have hitherto generated inconclusive statements. In a recent study based on the review of epidemiologic studies conducted worldwide in unselected populations of children, we documented that the prevalence of atopic asthma (AA) was high in the populations with a high prevalence of atopy. We systematically reviewed 36 articles that studied 48 populations of unselected children and reported prevalence rates for asthma and atopy in the total sample and in the subpopulations. No significant difference was found in the prevalence of asthma cases in the quartiles of childhood populations subdivided for the prevalence of atopy. In addition, atopy did not increase significantly in the subgroups of populations subdivided by asthma quartiles. In both subgroups, however, AA increased with increasing atopy or with increasing asthma (p < 0.001). Using a positive skin-prick test reaction to define cases of asthma as cases of AA is misleading because the prevalence of subjects so defined is heavily influenced by the environmentally generated changes in the prevalence of atopy or asthma. Asthma in a child should be labeled as a case of AA only if skin-prick tests yield a positive reaction and the clinical history documents asthma symptoms triggered by allergen exposure.

Variations in exhaled nitric oxide in children with asthma during a 1-week stay in a mountain village sanatorium.

Knowing about spontaneous variations in the fractional concentration of exhaled nitric oxide (FE(NO)) could improve monitoring of airway inflammation in asthmatic children. We aimed to assess FE(NO) variations (expiratory flow 50 mL/sec) in subjects maintained in similar environmental conditions. We tested spirometry and FE(NO) in symptom-free asthmatic children (9 corticosteroid-naive, 8 corticosteroid-treated) during a 1-week stay in a countryside sanatorium and in their healthy relatives (n = 12) staying in the immediate neighborhood on summer holiday (total 29 children, M/F:14/15, 5.8-16.8 yrs). Testing sessions were repeated every 12 hours (8:00 am, 8:00 pm) for 2 days and again on day 7. Measurements were defined as reproducible when they agreed with an intraclass correlation coefficient (ICC) above 0.60; deviation from mean differences was assessed by the coefficient of repeatability (CR = 2 SD). Lung function remained constant throughout the week in all groups. Baseline FE(NO) levels in corticosteroid-naive asthmatic children tended to decrease at the end of the week (from 13.9 ppb, 95% CI 12.2-19.1 to 9.2 ppb, 95% CI 5.8-15.9, p = 0.057). No differences were found between nocturnal and diurnal FE(NO). Within-session reproducibility for two FE(NO) measurements was high (ICC 0.99 in all groups and CR, 0.9 to 1.3 ppb). Between-session FE(NO) reproducibility at 12 hours and 24 hours was still high for each group but decreased markedly after 6 days in corticosteroid-naive asthmatic children (ICC 0.79 and CR 9.6 ppb at 24 hours vs. ICC 0.13 and CR 20.8 ppb after 6 days), whereas it decreased slightly in corticosteroid-treated asthmatics (from ICC 0.89 and CR 3.1 ppb to ICC 0.88 and CR 3.0 ppb) and healthy children (from ICC 0.79 and CR 4.8 ppb to ICC 0.65 and CR 5.7 ppb). In conclusion, in healthy subjects and in asthmatic children receiving therapy with inhaled corticosteroids (but not in corticosteroid-naive subjects), FE(NO) measurements are reproducible across a week.

Epidemiology of atopy patch tests with food and inhalant allergens in an unselected population of children.

Atopy patch test (APT) has been used as a diagnostic tool in patients with suspected food or inhalant allergy. This study assessed the prevalence of positive APT with food or inhalant allergens in an unselected population of schoolchildren. We also evaluated the link between positive APT reactions and skin-prick tests (SPT) for food and inhalant allergens, circulating eosinophils and histamine skin reactivity. We studied an unselected population of 380 children aged 9 or 13 yr living in Rome, Italy. APTs were carried out with food (native or standardized) and inhalant allergens. All the children also underwent skin-prick testing with five common inhalant and four food allergens. We also measured eosinophil cell counts and histamine skin reactivity. The prevalence of positive APT reactions for foods in unselected children ranged between 4% and 11% for hen's egg, tomato, and wheat flour and was similar for both age groups studied. The prevalence of positive APT for milk was significantly lower in children aged 13 than in children aged 9 (p = 0.013). No concordance emerged between positive APT and SPT for foods. Conversely, APT and SPT for inhalant allergens yielded statistically significant concordance (p < 0.001). APT produces positive reactions for food or inhalant allergens in a significant number of subjects in the general population of schoolchildren. Age influences the prevalence of positive APTs with cow's milk to some extent. Inhalant allergens probably induce a positive APT reaction through an immunoglobulin E-linked process, while food allergens probably do not.

Rapid maxillary expansion in children with obstructive sleep apnea syndrome: 12-month follow-up.

OBJECTIVES: To assess the outcome of rapid maxillary expansion in the treatment of obstructive sleep apnea syndrome (OSAS) in children, we studied 16 patients (mean age 6.6+/-2.0; 9 males) with dental malocclusion, a body mass index < or =85 percentile, and OSAS confirmed by polysomnography. METHODS: At baseline and after the trial, all patients underwent physical examination, standard polysomnography and orthodontic assessment. The Brouillette questionnaire investigating symptoms of OSA was administered to parents before and during the trial to assess the clinical severity of their sleep-disordered breathing. Two treated patients were lost to follow-up and excluded from the final study. RESULTS: In the 14 treated subjects who completed the study and follow-up, polysomnography showed a significant decrease in the apnea-hypopnea index (p=0.005), hypopnea obstructive index (p=0.002) and arousal index (p=0.001). Questionnaire responses before and after treatment showed a significant decrease in the severity of symptoms. CONCLUSION: A rapid maxillary expander is an effective appliance for treating children with OSAS.

Today's epidemics in children: possible relations to environmental pollution and suggested preventive measures.

BACKGROUND: Facts and hypotheses on the relationship between some children's diseases or disorders and external stressors during the developmental stage of a child, both prenatally and postnatally are described in literature. In this paper the following changes in patterns and causes of the main childhood illnesses are summarized and recommendations for actions are made. Prematurity. Intra-uterine growth restriction. Testicular dysgenesis syndrome. Type I and Type II diabetes. Asthma, atopy and hay fever. Autism. Attention deficit hyperactivity disorder (ADHD). Learning disabilities. Cancer. Obesity. Hearing problems. RESULTS: Literature provides a growing amount of information on changing patterns in childhood diseases. CONCLUSIONS: The following recommendations for action are formulated: Immediate research on endocrine disrupters in relation to prematurity. Diabetes: avoid Maillard Compounds in liquid baby food and in food in general: promote breastfeeding. Asthma: avoid exposure to smoking, the use of chemical household products, dioxin and dioxin-like chemicals, and avoid air pollution with high levels of particulate matter, especially around conception, during pregnancy and in the first years of life. Autism: more research on incidence and causes. ADHD and learning disabilities: more research on prevalence and causes. Preventions: 1) preconception counselling to avoid potentially harmful substances; 2) controlling and further lowering levels of polychlorinated biphenyls, lead and methyl mercury. Cancer: promote breastfeeding, carry out research into effects of foetal exposure to internal fission-product radionuclides. Obesity: stop smoking in pregnancy, avoid parental obesity, longer night sleep. Hearing problems: lower noise levels in discothèques, promote the day-evening-night level to avoid noise (longer night sleep).

Children's health and mercury exposure.

The reason why mercury is dangerous is that once released into the environment it cannot be removed and is rapidly transformed by microorganisms into organic compounds that tend to bioaccumulate and biomagnify in animals. The principal organic compound is methylmercury (MeHg). The primary route of exposure to MeHg for humans is consumption of fish. The safe dose (reference dose, RfD) of MeHg that can be consumed without neurotoxicological consequences is 0.1 microg per kg b.w./day. According to available data, the whole population of certain European countries or people who consume large quantities of fish are exposed to doses of MeHg that exceed the RfD. Given this level of mercury exposure, in order to avoid or reduce the expected neurotoxic consequences on foetuses we propose the following strategy: 1) At present the most reasonable solution for pregnant women (and small children) is to reduce substantially or completely avoid fish intake. 2) In the medium term the European Community should evaluate the technical and economic feasibility of breeding uncontaminated fish in order to reduce the drawbacks of banning fish consumption. 3) In the long term there is no alternative to substantially reducing mercury emissions worldwide.

Lead neurotoxicity in children: is prenatal exposure more important than postnatal exposure?

Numerous studies indicate that low-level lead poisoning causes mild mental retardation and low IQ scores in children. The general mean lead intake in the adult European population corresponds to a reassuring 14% (0.5-56%) of the tolerable daily intake: at this low level of exposure only few children (less than 10%) have blood lead levels (PbB) higher than 10 microg/dl, previously considered the PbB of concern. In more recent years data now suggest that even when 'the lifetime average blood lead concentration' is below 10 microg/dl an inverse association exists with intelligence quotient (IQ) scores. Two-thirds (45-75%) of lead in blood, however, comes from long-term tissue stores and this is especially true for newborn infants and pregnant women. Several data suggest that for lead the main toxic event is prenatal exposure: therefore we should focus our attention on maternal lead stores and whenever possible avoid their mobilization during pregnancy. In this regard we should design appropriate studies to confirm whether dietary supplementations can reduce bone resorption and lead mobilization during pregnancy. The hypothesis that the amount of maternal bone lead stores is the relevant parameter for predicting the level of neurotoxicity of this metal gives some optimism for the future: if we study children whose mothers never underwent high environmental pollution (born after the withdrawal of lead from gasoline) and hence have relatively low bone lead stores we could find that, at the population level, lead has little influence on children IQ scores.

Cadmium and children: exposure and health effects.

Cadmium exposure and accumulation in the body start at young age. Exposure routes in children are mainly via food, environmental tobacco smoke and house dust. Excretion from the body is limited. Cadmium accumulation in the kidney is responsible for effects such as nephrotoxicity and osteoporosis which are observed at adult age. Cadmium exposure through inhalation is also associated with lung cancer in adulthood. Although transfer to the neonate through the placenta and through breast milk is limited, teratogenic and developmental effects were observed in experimental animals. The database on human studies involving children is limited, yet effects on motoric and perceptual behaviour in children have been associated with elevated in utero cadmium exposure. In school age children urinary cadmium levels were associated with immune suppressive effects. More studies are needed to confirm these results. Experimental data in vitro and in animals refer to effects of cadmium on the hypothalamus-pituitary axis at different levels. This may lead to disorders of the endocrine and/or immune system. Cadmium exposure at early age should be limited as much as possible to prevent direct effects on children and to prevent accumulation of cadmium which may have serious health effects only becoming manifest at older age.

Environmental tobacco smoke exposure and children's health.

UNLABELLED: Almost half of the child population is involuntarily exposed to environmental tobacco smoke (ETS). The ETS exposure gives rise to an excessive risk of several diseases in infancy and childhood, including sudden infant death syndrome, upper and lower respiratory infections, asthma and middle ear diseases. It is also linked to cancer, and behavioural problems and neurocognitive deficits in children. CONCLUSIONS: Protecting children from ETS exposure is a complex and important issue. The best improvement in children's health is to be gained when parents stop smoking or, when that is not possible, they stop smoking in their children's environment. Paediatricians, because of their authority, and their frequent and regular contact with parents, play a leading role in protecting children from ETS exposure. An ideal approach to help parents to stop smoking seems to be initial minimal-contact advice provided by their paediatrician with feedback and supplemental printed materials, leading to greater intensity and duration of follow-up home visits.

Air pollution: a threat to the health of our children.

BACKGROUND/METHODS: Current air pollution levels pose a threat to the health of children starting from conception. The scientific evidence is presented for mortality, morbidity, and sub-clinical effects. The first section deals with exposure data, the following sections with the evidence of health effects from epidemiology and toxicology leading to recommendations. RESULTS: Improved air quality reduces the number of infants' deaths as well as disease and pain. CONCLUSIONS: Medical doctors have a responsibility to know the facts and to advise their patients. Doctors when visiting their patients' homes should be aware of the possibly grave impact of the indoor environment for the respiratory health of their patients. They should recognize and advise the parents on problems associated with environmental tobacco smoke, poor ventilation, mould growth, and maintenance of heating installations. With regard to outdoor air pollution, doctors could serve as role models and also advise their patients and parents on environmentally friendly behaviour. Such behaviour not only calls for personal commitment but also for the right infrastructure to be provided (e.g. public transport, district heating). Doctors should be proactive in the community and in their country as advocates for a healthier environment for our children.

Policy and science in children's health and environment: recommendations from the PINCHE project.

BACKGROUND: Policy recommendations result from the discussions and analysis of the present situation in environment and health. Such analysis was performed in PINCHE. This led to recommendations based on the scientific literature. In the field of children's environmental health the policy process will follow more or less fixed rules, but this process is still at an early level of development. The link between science and policy still faces many challenges. Scientific assessment of environmental risk must recognize and tackle the problems of data sets, variability of human and environmental systems, the range, spatial and temporal diffusion of potential health effects and many biases and confounding factors. RESULTS: The PINCHE network recommends a general improvement of the supporting scientific fields in environment and health. Assessments from epidemiology or toxicology should play a key role in influencing science-policy decisions in programmes that are intended to inform the public policy process. Scientific committees at a local level could play a role. The relation between health and environment needs to be better incorporated in training and education. There is a need for harmonization of data production and use. The priorities in PINCHE focus on the most important issues. A classification of low, medium or high priority for action was used to describe a range of different environmental stressors. CONCLUSIONS: PINCHE provided recommendations to reduce exposure for children. Exposure reduction is not always linked to improved health in the short term, but it will reduce the body burden of accumulating chemicals in children. A strategic choice is reduction of exposure of children to compounds by changing production techniques or by increasing the distance of child specific settings to sources. The contribution of all players in the production, distribution and use of scientific knowledge in the field of children's environmental health is necessary.

Exposure to multiple environmental agents and their effect.

INTRODUCTION: All children are exposed to multiple physical, chemical and biological challenges that can result in adverse health effects before and after birth. In this context, the danger of multiple exposures cannot be assessed from a single-chemical approach as used in classical toxicology. AIM: To open up a 'negotiation space' for the problem of multiple exposure to environmental stressors, defined as any physical, chemical or biological entity that can induce an adverse response. In this context, two further questions obtain: to what extent can synergistic risks be assessed, and how far could potential adverse effects be prevented by enhanced regulation? METHODS: A discussion of two general approaches is taken: 1) the investigation of mixtures such as smoking or air pollution without specifying the individual agents, and 2) the investigation of individual substances with a focus on possible interactions in the context of dose to receptor. RESULTS: Although mixtures of compounds can have effects, it may not be possible to ascribe causation to a single compound. Furthermore, cumulative low-dose insult can, in some circumstances, be more toxic than a single high-dose exposure, e.g. endocrine disruptive effects of a combination of PCBs and dioxins which disrupt the thyroid hormone status; this tends to contradict elements of classical toxicology, . These cumulative insults may further combine with heavy metals and can disrupt the heme synthesis. It is possible that groups of pollutants could be used to test their cumulative capacity to multiple stress-susceptible receptor targets as is done in smoking and air pollution. This methodology could be used for further groups of potential pollutants, for example those associated with cleaning products, or cosmetics. Testing individual substances with a focus on interactions means that not only chemicals but also concurrent diseases should be taken into account. We suggest that the enhanced regulation of potential multiple stressors falls into two discrete categories. The first comprises a more precautionary approach (as demonstrated by the banning of chemicals such as some brominated flame retardants in Europe). The second comprises a more 'permissive' liberal approach involving the initial study of an individual compound, and subsequent interrogation of that compound in combination with another (as demonstrated by lowering the carcinogenicity of aflatoxin by vaccination against hepatitis B). CONCLUSIONS: It is necessary to define and study groups of multiple stressors as in US EPA's Framework for Cumulative Risk Assessment (U.S. EPA 2003). Recent increased knowledge of the greater sensitivity of the unborn baby, the infant and the child, has led to general recognition that a higher degree of precaution is now needed in regulating for multiple stressors on the young. The more liberal permissive approach proceeding from established effects of the individual exposures is becoming less acceptable now that we know that there is much we do not understand about chronic effects of stressors during the early development phases. Conflicts over which approach to take may have to be resolved through engagement and negotiation with a wide community of stakeholders. This "community of interest" may include fundamental research scientists, practicing clinical paediatricians, patient groups, and others concerned with the health and wellbeing of infants and children.

Reduced exhaled nitric oxide in children after testing of maximal expiratory pressures.

Spirometry in adult subjects can induce a fall in concentration of exhaled nitric oxide (FE(NO)). Scarce information is available on the FE(NO) decrease after spirometry or after other forced lung-function maneuvers in children. We compared changes in FE(NO) induced by repeated spirometry and testing of maximal expiratory pressures (P(Emax)). Twenty-four sex- and age-matched children aged 9-18 years (mean age +/- SD, 13.3 +/- 2.8 years; 12 healthy, 12 asthmatic) were allocated to 1-week-apart sessions of repeated maneuvers of either forced vital capacity (FVC) or P(Emax). Baseline FE(NO) measurements were followed by FVC or P(Emax) maneuvers every 15 min for 45 min, whereas FE(NO) was measured at each step for 60 min. After repeated P(Emax) but not after FVC maneuvers, FE(NO) values decreased significantly from baseline in both groups. In healthy children, geometric mean FE(NO) (95% confidence intervals) decreased from 9.1 (7.0-11.8) ppb at baseline to 8.2 (6.3-10.6) ppb at 15 min and 7.7 (5.6-10.6) ppb at 30 min (P < 0.05 and P < 0.01, respectively), and remained unchanged at 45 and 60 min. In asthmatic children, FE(NO) levels fell from 21.6 (13.3-34.9) ppb at baseline to 15.1 (9.1-25.1) ppb at 15 min and remained low at 30, 45, and 60 min: 17.8 (10.7-29.5) ppb, 17.5 (10.2-30.1) ppb, and 17.6 (10.6-29.2) ppb, P < 0.01, for all differences from baseline. Repeated P(Emax) and FVC maneuvers increased FE(NO) variability, as compared with repeated FE(NO) measurements alone. Previous forced lung-function maneuvers may affect FE(NO) measurements in children. Although P(Emax) testing has a greater influence than spirometry on FE(NO) levels in children, both procedures should be avoided before measuring FE(NO).