Early growth characteristics and the risk of reduced lung function and asthma: A meta-analysis of 25,000 children

BACKGROUND Children born preterm or with a small size for gestational age are at increased risk for childhood asthma. OBJECTIVE We sought to assess the hypothesis that these associations are explained by reduced airway patency. METHODS We used individual participant data of 24,938 children from 24 birth cohorts to examine and meta-analyze the associations of gestational age, size for gestational age, and infant weight gain with childhood lung function and asthma (age range, 3.9-19.1 years). Second, we explored whether these lung function outcomes mediated the associations of early growth characteristics with childhood asthma. RESULTS Children born with a younger gestational age had a lower FEV1, FEV1/forced vital capacity (FVC) ratio, and forced expiratory volume after exhaling 75% of vital capacity (FEF75), whereas those born with a smaller size for gestational age at birth had a lower FEV1 but higher FEV1/FVC ratio (P < .05). Greater infant weight gain was associated with higher FEV1 but lower FEV1/FVC ratio and FEF75 in childhood (P < .05). All associations were present across the full range and independent of other early-life growth characteristics. Preterm birth, low birth weight, and greater infant weight gain were associated with an increased risk of childhood asthma (pooled odds ratio, 1.34 [95% CI, 1.15-1.57], 1.32 [95% CI, 1.07-1.62], and 1.27 [95% CI, 1.21-1.34], respectively). Mediation analyses suggested that FEV1, FEV1/FVC ratio, and FEF75 might explain 7% (95% CI, 2% to 10%) to 45% (95% CI, 15% to 81%) of the associations between early growth characteristics and asthma. CONCLUSIONS Younger gestational age, smaller size for gestational age, and greater infant weight gain were across the full ranges associated with childhood lung function. These associations explain the risk of childhood asthma to a substantial extent.

RETICULAR PSEUDODRUSEN ON INFRARED IMAGING ARE TOPOGRAPHICALLY DISTINCT FROM SUBRETINAL DRUSENOID DEPOSITS ON EN FACE OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To evaluate the quantitative and topographic relationship between reticular pseudodrusen (RPD) on infrared reflectance (IR) and subretinal drusenoid deposits (SDD) on en face volumetric spectral domain optical coherence tomography. METHODS: Reticular pseudodrusen were marked on IR images by a masked observer. Subretinal drusenoid deposits were visualized on en face sections of spectral domain optical coherence tomography below the external limiting membrane and identified by a semiautomated technique. Control RPD lesions were generated in a random distribution for each IR image. Binary maps of control and experimental RPD and SDD were merged and analyzed in terms of topographic localization and quantitative drusen load comparison. RESULTS: A total of 54 eyes of 41 patients diagnosed with RPD were included in this study. The average number of RPD lesions on IR images was 320 ± 44.62 compared with 127 ± 26.02 SDD lesions on en face (P < 0.001). The majority of RPD lesions did not overlap with SDD lesions and were located >30 μm away (92%). The percentage of total SDD lesions overlapping RPD was 2.91 ± 0.87% compared with 1.73 ± 0.68% overlapping control RPD lesions (P < 0.05). The percentage of total SDD lesions between 1 and 3 pixels of the nearest RPD lesion was 5.08 ± 1.40% compared with 3.33 ± 1.07% between 1 and 3 pixels of the nearest control RPD lesion (P < 0.05). CONCLUSION: This study identified significantly more RPD lesions on IR compared with SDD lesions on en face spectral domain optical coherence tomography and found that a large majority of SDD (>90% of lesions) were >30 μm away from the nearest RPD. Together, our findings indicate that RPD and SDD are two entities that are only occasionally topographically associated, suggesting that at some stage in their development, they may be pathologically related.

Unfair Advantage: An Intriguing Example of Legal Transformation in the Swiss Private Law

This paper demonstrates a mixed approach to the theme of the instrumentality of law by both analysing the goal of a legal transformation and the techniques adapted to achieve it. The correct recognition of a certain practical necessity has lead the Swiss Federal Tribunal to an intriguing judgement “Fussballclub Lohn-Fall” of 1997. The legal remedies provided for cases of unfair advantage have been then creatively modified praeter legem. The adaptation was strongly influenced by foreign legal patterns. The Swiss Code of Obligations of 1911 provides a norm in art. 21 on unfair advantage (unconscionable contract), prescribing that if one party takes unjustified advantage over the weaknesses of another in order to receive an excessive benefit, such a contract is avoidable. Its wording has been shaped over a hundred years ago and still remains intact. However, over the course of the 20th century the necessity for a more efficient protection has arisen. The legal doctrine and jurisprudence were constantly pointing out the incompleteness of the remedies provided by art. 21 of the Code of Obligations. In the “Fussballclub Lohn-Fall” (BGE 123 III 292) the Swiss Federal Tribunal finally introduced the possibility to modify the contract. Its decision has been described as “a sign of the zeitgeist, spirit of the time”. It was the Swiss legal doctrine that has imposed the new measure under the influence of the German “quantitative Teilnichtigkeit” (quantitative partial nullity). The historical heritage of the Roman laesio enormis has also played its role.

Nocardia infection in solid organ transplant recipients: a multicenter European case-control study.

BACKGROUND  Nocardiosis is a rare, life-threatening opportunistic infection, affecting 0.04% to 3.5% of patients after solid organ transplantation (SOT). The aim of this study was to identify risk factors for Nocardia infection after SOT and to describe the presentation of nocardiosis in these patients. METHODS  We performed a retrospective case-control study of adult patients diagnosed with nocardiosis after SOT between 2000 and 2014 in 36 European (France, Belgium, Switzerland, Netherlands, Spain) centers. Two control subjects per case were matched by institution, transplant date and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors for nocardiosis. RESULTS  One hundred and seventeen cases of nocardiosis and 234 control patients were included. Nocardiosis occurred at a median of 17.5 [range 2-244] months after transplantation. In multivariable analysis, high calcineurin inhibitor trough levels in the month before diagnosis (OR=6.11 [2.58-14.51]), use of tacrolimus (OR=2.65 [1.17-6.00]) and corticosteroid dose (OR=1.12 [1.03-1.22]) at the time of diagnosis, patient age (OR=1.04 [1.02-1.07]) and length of stay in intensive care unit after SOT (OR=1.04 [1.00-1.09]) were independently associated with development of nocardiosis; low-dose cotrimoxazole prophylaxis was not found to prevent nocardiosis. Nocardia farcinica was more frequently associated with brain, skin and subcutaneous tissue infections than were other Nocardia species. Among the 30 cases with central nervous system nocardiosis, 13 (43.3%) had no neurological symptoms. CONCLUSIONS  We identified five risk factors for nocardiosis after SOT. Low-dose cotrimoxazole was not found to prevent Nocardia infection. These findings may help improve management of transplant recipients.