Siblings, asthma, rhinoconjunctivitis and eczema: a worldwide perspective from the International Study of Asthma and Allergies in Childhood.

BACKGROUND: Associations of larger families with lower prevalences of hay fever, eczema and objective markers of allergic sensitization have been found fairly consistently in affluent countries, but little is known about these relationships in less affluent countries. METHODS: Questionnaire data for 210,200 children aged 6-7 years from 31 countries, and 337,226 children aged 13-14 years from 52 countries, were collected by Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC). Associations of disease symptoms and labels of asthma, rhinoconjunctivitis and eczema were analysed by numbers of total, older and younger siblings, using mixed (multi-level) logistic regression models to adjust for individual covariates and at the centre level for region, language and national affluence. RESULTS: In both age groups, inverse trends (P < 0.0001) were observed for reported 'hay fever ever' and 'eczema ever' with increasing numbers of total siblings, and more specifically older siblings. These inverse associations were significantly (P < 0.005) stronger in more affluent countries. In contrast, symptoms of severe asthma and severe eczema were positively associated (P < 0.0001) with total sibship size in both age groups. These associations with disease severity were largely independent of position within the sibship and national GNI per capita. CONCLUSIONS: These global findings on sibship size and childhood asthma, rhinoconjunctivitis and eczema suggest at least two distinct trends. Inverse associations with older siblings (observations which prompted the 'hygiene hypothesis' for allergic disease) are mainly a phenomenon of more affluent countries, whereas greater severity of symptoms in larger families is globally more widespread

Global variation in the prevalence and severity of asthma symptoms : phase three of the International Study of Asthma and Allergies in Childhood (ISAAC)

Background: Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC) measured the global prevalence and severity of asthma symptoms in children. Methods: A cross-sectional questionnaire survey of 798 685 children aged 13–14 years from 233 centres in 97 countries, and 388 811 children aged 6–7 years from 144 centres in 61 countries, was conducted between 2000 and 2003 in .90% of the centres. Results: The prevalence of wheeze in the past 12 months (current wheeze) ranged from 0.8% in Tibet (China) to 32.6% in Wellington (New Zealand) in the 13–14 year olds, and from 2.4% in Jodhpur (India) to 37.6% in Costa Rica in the 6–7 year olds. The prevalence of symptoms of severe asthma, defined as >4 attacks of wheeze or >1 night per week sleep disturbance from wheeze or wheeze affecting speech in the past 12 months, ranged from 0.1% in Pune (India) to 16% in Costa Rica in the 13–14 year olds and from 0% to 20.3% in the same two centres, respectively, in the 6–7 year olds. Ecological economic analyses revealed a significant trend towards a higher prevalence of current wheeze in centres in higher income countries in both age groups, but this trend was reversed for the prevalence of severe symptoms among current wheezers, especially in the older age group. Conclusion: Wide variations exist in the symptom prevalence of childhood asthma worldwide. Although asthma symptoms tend to be more prevalent in more affluent countries, they appear to be more severe in less affluent countries.peer-reviewe

Value of individual surgeon performance metrics as quality assurance measures in oesophagogastric cancer surgery

Background Surgeon‐level operative mortality is widely seen as a measure of quality after gastric and oesophageal resection. This study aimed to evaluate this alongside a compound‐level outcome analysis. Methods Consecutive patients who underwent treatment including surgery delivered by a multidisciplinary team, which included seven specialist surgeons, were studied. The primary outcome was death within 30 days of surgery; secondary outcomes were anastomotic leak, Clavien–Dindo morbidity score, lymph node harvest, circumferential resection margin (CRM) status, disease‐free (DFS), and overall (OS) survival. Results The median number of annual resections per surgeon was 10 (range 5–25), compared with 14 (5–25) for joint consultant teams (P = 0·855). The median annual surgeon‐level mortality rate was 0 (0–9) per cent versus an overall network annual operative mortality rate of 1·8 (0–3·7) per cent. Joint consultant team procedures were associated with fewer operative deaths (0·5 per cent versus 3·4 per cent at surgeon level; P = 0·027). The median surgeon anastomotic leak rate was 12·4 (range 9–20) per cent (P = 0·625 versus the whole surgical range), overall morbidity 46·5 (31–60) per cent (P = 0·066), lymph node harvest 16 (9–29) (P < 0·001), CRM positivity 32·0 (16–46) per cent (P = 0·003), 5‐year DFS rate 44·8 (29–60) per cent and OS rate 46·5 (35–53) per cent. No designated metrics were independently associated with DFS or OS in multivariable analysis. Conclusion Annual surgeon‐level metrics demonstrated wide variations (fivefold), but these performance metrics were not associated with survival

Data sharing: not as simple as it seems

In recent years there has been a major change on the part of funders, particularly in North America, so that data sharing is now considered to be the norm rather than the exception. We believe that data sharing is a good idea. However, we also believe that it is inappropriate to prescribe exactly when or how researchers should preserve and share data, since these issues are highly specific to each study, the nature of the data collected, who is requesting it, and what they intend to do with it. The level of ethical concern will vary according to the nature of the information, and the way in which it is collected - analyses of anonymised hospital admission records may carry a quite different ethical burden than analyses of potentially identifiable health information collected directly from the study participants. It is striking that most discussions about data sharing focus almost exclusively on issues of ownership (by the researchers or the funders) and efficiency (on the part of the funders). There is usually little discussion of the ethical issues involved in data sharing, and its implications for the study participants. Obtaining prior informed consent from the participants does not solve this problem, unless the informed consent process makes it completely clear what is being proposed, in which case most study participants would not agree. Thus, the undoubted benefits of data sharing does not remove the obligations and responsibilities that the original investigators hold for the people they invited to participate in the study

Species-selective killing of bacteria by antimicrobial peptide-PNAs

This is an open-access article distributed under the terms of the Creative Commons Attribution License, CC BY 4.0 which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Broad-spectrum antimicrobials kill indiscriminately, a property that can lead to negative clinical consequences and an increase in the incidence of resistance. Species-specific antimicrobials that could selectively kill pathogenic bacteria without targeting other species in the microbiome could limit these problems. The pathogen genome presents an excellent target for the development of such antimicrobials. In this study we report the design and evaluation of species-selective peptide nucleic acid (PNA) antibacterials. Selective growth inhibition of B. subtilis, E. coli, K. pnuemoniae and S. enterica serovar Typhimurium in axenic or mixed culture could be achieved with PNAs that exploit species differences in the translation initiation region of essential genes. An S. Typhimurium-specific PNA targeting ftsZ resulted in elongated cells that were not observed in E. coli, providing phenotypic evidence of the selectivity of PNA-based antimicrobials. Analysis of the genomes of E. coli and S. Typhimurium gave a conservative estimate of >150 PNA targets that could potentially discriminate between these two closely related species. This work provides a basis for the development of a new class of antimicrobial with a tuneable spectrum of activity.Peer reviewedFinal Published versio

Combined impact of healthy lifestyle factors on risk of asthma, rhinoconjunctivitis and eczema in school children: ISAAC phase III

Background Asthma is not the key focus of prevention strategies. A Healthy Lifestyle Index (HLI) was developed to examine the combined effect of modifiable lifestyle factors on asthma, rhinoconjunctivitis and eczema using data from the International Study of Asthma and Allergies in Childhood (ISAAC) phase III. Methods Information on symptoms of asthma, rhinoconjunctivitis, eczema and several lifestyle factors was obtained from children aged 6-7 years through written questionnaires. The HLI combined five lifestyle factors: no parental smoking, child's adherence to Mediterranean diet, child's healthy body mass index, high physical activity and non-sedentary behaviour. The association between the HLI and risk of asthma, rhinoconjunctivitis and eczema was evaluated using multilevel mixed-effects logistic regression models. Findings Data of 70 795 children from 37 centres in 19 countries were analysed. Each additional healthy lifestyle factor was associated with a reduced risk of current wheeze (OR 0.87, 95% CI 0.84 to 0.89), asthma ever (OR 0.89, 95% CI 0.87 to 0.92), current symptoms of rhinoconjunctivitis (OR 0.95, 95% CI 0.92 to 0.97) and current symptoms of eczema (OR 0.92, 95% CI 0.92 to 0.98). Theoretically, if associations were causal, a combination of four or five healthy lifestyle factors would result into a reduction up to 16% of asthma cases (ranging from 2.7% to 26.3 % according to region of the world). Conclusions These findings should be interpreted with caution given the limitations to infer causality from cross-sectional observational data. Efficacy of interventions to improve multiple modifiable lifestyle factors to reduce the burden asthma and allergy in childhood should be assessed