Outdoor pollen is a trigger of child and adolescent asthma emergency department presentations: A systematic review and meta‐analysis

Background

In the context of increased asthma exacerbations associated with climatic changes such as thunderstorm asthma, interest in establishing the link between pollen exposure and asthma hospital admissions has intensified. Here, we systematically reviewed and performed a meta‐analysis of studies on pollen and emergency department (ED) attendance.

Methods

A search for studies with appropriate search strategy in MEDLINE, EMBASE, Web of Science and CINAHL was conducted. Each study was assessed for quality and risk of bias. The available evidence was summarized both qualitatively and meta‐analysed using random‐effects models when moderate heterogeneity was observed.

Results

Fourteen studies were included. The pollen taxa investigated differed between studies, allowing meta‐analysis only of the effect of grass pollen. A statistically significant increase in the percentage change in the mean number of asthma ED presentations (MPC) (pooled results from 3 studies) was observed for an increase in 10 grass pollen grains per cubic metre of exposure 1.88% (95% CI = 0.94%, 2.82%). Time series studies showed positive correlations between pollen concentrations and ED presentations. Age‐stratified studies found strongest associations in children aged 5‐17 years old.

Conclusion

Exposure to ambient grass pollen is an important trigger for childhood asthma exacerbations requiring ED attendance. As pollen exposure is increasingly a problem especially in relation to thunderstorm asthma, studies with uniform measures of pollen and similar analytical methods are necessary to fully understand its impact on human health.     

Alu‐Alu mediated intragenic duplications in IFT81 and MATN3 are associated with skeletal dysplasias

Skeletal dysplasias are a diverse group of rare Mendelian disorders with clinical and genetic heterogeneity. Here, we used targeted copy number variant (CNV) screening and identified intragenic exonic duplications, formed through Alu‐Alu fusion events, in two individuals with skeletal dysplasia and negative exome sequencing results. First, we detected a homozygous tandem duplication of exon 9 and 10 in IFT81 in a boy with Jeune syndrome, or short‐rib thoracic dysplasia (SRTD) (MIM# 208500). Western blot analysis did not detect any wild‐type IFT81 protein in fibroblasts from the patient with the IFT81 duplication, but only a shorter isoform of IFT81 that was also present in the normal control samples. Complementary zebrafish studies suggested that loss of full‐length IFT81 protein but expression of a shorter form of IFT81 protein affects the phenotype while being compatible with life. Second, a de novo tandem duplication of exons 2 to 5 in MATN3 was identified in a girl with multiple epiphyseal dysplasia (MED) type 5 (MIM# 607078). Our data highlights the importance of detection and careful characterization of intragenic duplication CNVs, presenting them as a novel and very rare genetic mechanism in IFT81‐related Jeune syndrome and MATN3‐related MED.     

颈动脉内中膜厚度与初诊2型糖尿病视网膜病变的关系

目的:研究发现,糖尿病视网膜病变和动脉粥样硬化终点事件相关。试验拟验证颈动脉内中膜厚度与初诊汉族2型糖尿病患者糖尿病视网膜病变相关危险因素的关系。方法:①试验对象:选择2006-06/2007-06本院住院的初诊2型糖尿病患者187例,男114例,女73例;平均年龄(51±14)岁;平均体质量指数(24.7±4.7)kg/m2。均符合1997年美国糖尿病协会的2型糖尿病诊断标准,排除既往已存在心血管疾病者。患者对治疗及试验均知情同意。根据眼底照相检查结果,将所有受检者分为糖尿病视网膜病变组及非糖尿病视网膜病变组进行统计分析。②试验方法及评估:所有患者询问一般情况,测量颈动脉内中膜厚度以及相关生化指标,对糖尿病视网膜病变相关因素进行单因素及多因素Logistic回归分析。结果:纳入2型糖尿病患者187例,均进入结果分析。单因素Logistic回归分析显示,高血压、糖尿病家族史、颈动脉内中膜厚度、尿白蛋白、低密度脂蛋白胆固醇与糖尿病视网膜病变发生呈显著正相关,多因素Logistic回归分析未见显效因素。结论:单因素回归分析中颈动脉内中膜厚度及其他4项指标与糖尿病视网膜病变相关,而多因素回归分析这些因素未进入主效基因模型。     

Practical guidelines for process validation and process control of white cell-reduced blood components: report of the Biomedical Excellence for Safer Transfusion (BEST) Working Party of the International Society of Blood Transfusion (ISBT)

Background: The increased use of white (WBC)-reduced blood components has prompted many institutions to develop quality assurance programs directed to such component preparation processes. For consistent preparation of WBC-reduced blood components that meet clinical needs as well as national standards, a program of process validation and control should be instituted. This involves controlling key factors that affect WBC reduction as well as periodic monitoring of the residual cellular content of components. Practical guidelines for the implementation of such a program are provided. Study Design and Methods: A program involving three phases of monitoring was developed by individuals belonging to an international working party of the International Society of Blood Transfusion. Results: The first phase, process validation, evaluates a minimum of 20 consecutive units (a minimum of 60 units when nonparametric measurements are used) to document the successful local implementation of a new or substantially modified process. Ongoing process control employing Levey-Jennings type control charts is used to demonstrate that the process remains stable over time. Process capability assessment and conformance with standards are evaluated once residual WBCs are counted in a sufficient number of units. This enables a facility to claim with a specified degree of confidence that a stated proportion of WBC-reduced units will meet national standards. Two approaches to determine the number of units that should be selected for counting are presented. The first approach considers units as either acceptable or not acceptable and assumes that the distribution of failed (or nonconforming) units approximates the Poisson distribution. The second approach takes into consideration the observed WBC content of the tested units, with the assumption that the residual WBC content in WBC-reduced components follows a lognormal distribution. A method to assess the lognormal distribution of residual WBCs is presented. Specific tables based on each of these approaches are provided to guide the reader in the design of a program that will verify conformance with any national standard at specific confidence levels. The approach can be generalized to other process control applications. Conclusion: Guidelines are presented for process validation, process control, and assessment of conformance in the production of WBC-reduced blood components. Policy makers retain the responsibility to establish, on the basis of the expected use of WBC- reduced components, requirements for the frequency of testing and for the proportion of prepared units that are expected with a stated degree of confidence to meet the standards. Facilities preparing WBC-reduced components can monitor key factors that influence the preparation of WBC-reduced blood, can periodically assess their conformance with the standards, and can intervene to correct adverse changes in the process. This approach can be used to ensure the consistent quality of WBC- reduced blood components.     

Collection and transfusion of blood and blood components in the United States, 1992

BACKGROUND: Studies were conducted to measure the state of the United States' national blood resource in 1992 and changes therein from 1989. STUDY DESIGN AND METHODS: With data supplied by the American Red Cross and the American Association of Blood Banks, as well as data from a stratified random-sample survey of 3350 non-American Association of Blood Banks hospitals, statistical methods were applied to estimate national blood activities in 1992. RESULTS: The total US blood supply in 1992 was 13,794,000 units, a decrease of 3.1 percent from 1989. Some 11,307,000 red cell units were transfused to 3,772,000 patients, an average of 3.0 units per transfused patient. Preoperative autologous blood deposits totaled 1,117,000 units, a 70-percent increase over 1989. Of this number, 566,000 units (50.7%) were transfused, 5,000 (4.4%) transferred to the allogeneic supply, and 546,000 (48.9%) discarded. Of 436,000 directed-donation units, 136,000 (31.2%) were transfused, 57,000 (13.1%) transferred to allogeneic supply, and 243,000 (55.7%) discarded. The total allogeneic blood supply, including imports, decreased by 7.4 percent from 1989, and allogeneic blood transfusions, including those to children, decreased by 8.6 percent. Over 8,300,000 platelet units were transfused; of these, some 3,600,000 were apheresis platelets. In addition, 2,255,000 units of plasma and 939,000 units of cryoprecipitate were transfused. CONCLUSION: While the US blood supply was adequate for transfusion needs in 1992, blood collections and red cell transfusions had decreased substantially since 1989.     

Dopaminergic regulation of striatal acetylcholine release: importance of D1 and N-methyl-D-aspartate receptors.

The dopaminergic regulation of striatal cholinergic activity was studied using in vivo microdialysis to measure interstitial concentrations of acetylcholine (ACh) and choline in the striata of freely moving rats. The quaternary acetylcholinesterase inhibitor neostigmine (100 nM) was included in the perfusion solution to increase the recovery of ACh. d-Amphetamine (2 mg/kg, s.c.) and nomifensine (5 mg/kg, s.c.) increased the concentration of ACh in the striatal dialysate by 40 to 60%. Interstitial choline concentrations were reduced by both drugs. Administration of the selective D1 receptor antagonist SCH 23390 (0.3 mg/kg, s.c.) decreased the concentration of ACh in the striatal dialysate by 15 to 20%; in contrast, the selective D2 antagonist raclopride (1 mg/kg, s.c.) increased striatal ACh release by 50 to 60%. Raclopride also briefly increased the extracellular concentration of choline. Raclopride blocked the increase in locomotor activity produced by d-amphetamine, but did not further enhance ACh release. In contrast, SCH 23390 completely antagonized the increases in locomotion and striatal ACh release produced by d-amphetamine. These results indicate that d-amphetamine increases ACh release in the striatum via a D1 receptor mechanism. Consistent with this hypothesis, the selective D1 receptor agonist CY 208-243 (1 mg/kg, s.c.) increased striatal ACh release by approximately 60%. In contrast, local application of CY 208-243 (10 microM) and SCH 23390 (10 microM) failed to alter ACh concentrations in the striatal dialysate. Inclusion of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (10 microM) in the striatal perfusion solution significantly attenuated the increase in striatal ACh release produced by systemic CY 208-243.(ABSTRACT TRUNCATED AT 250 WORDS)     

Analysis of serious non‐AIDS events among HIV‐infected adults at Latin American sites

Objective

Acquired immune deficiency appears to be associated with serious non‐AIDS (SNA)‐defining conditions such as cardiovascular disease, liver and renal insufficiency and non‐AIDS‐related malignancies. We analysed the incidence of, and factors associated with, several SNA events in the LATINA retrospective cohort.

Materials and methods

Cases of SNA events were recorded among cohort patients. Three controls were selected for each case from cohort members at risk. Conditional logistic models were fitted to estimate the effect of traditional risk factors as well as HIV‐associated factors on non‐AIDS‐defining conditions.

Results

Among 6007 patients in follow‐up, 130 had an SNA event (0.86 events/100 person‐years of follow‐up) and were defined as cases (40 with cardiovascular events, 54 with serious liver failure, 35 with non‐AIDS‐defining malignancies and two with renal insufficiency). Risk factors such as diabetes, hepatitis B and C virus coinfections and alcohol abuse showed an association with events, as expected. The last recorded CD4 T‐cell count prior to index date (P=0.0056, with an average difference of more than 100 cells/μL) and area under the CD4 cell curve in the year previous to index date (P=0.0081) were significantly lower in cases than in controls. CD4 cell count at index date was significantly associated with the outcome after adjusting for risk factors.

Conclusions

The incidence and type of SNA events found in this Latin American cohort are similar to those reported in other regions. We found a significant association between immune deficiency and the risk of SNA events, even in patients under antiretroviral treatment.