Validity and interpretation of spirometric recordings to diagnose COPD in UK primary care.

BACKGROUND: The diagnosis of COPD is dependent upon clinical judgment and confirmation of the presence of airflow obstruction using spirometry. Spirometry is now routinely available; however, spirometry incorrectly performed or interpreted can lead to misdiagnosis. We aimed to determine whether spirometry undertaken in primary care for patients suspected to have COPD was of sufficient quality and whether their spirometry was correctly interpreted. METHODS: Two chest physicians re-read all spirometric readings for both quality of the procedure and interpretation, received as a part of COPD validation studies using data from the Clinical Practice Research Datalink (CPRD). We then used logistic regression to investigate predictors of correct interpretation. RESULTS: Spirometry traces were obtained for 306 patients, of which 221 (72.2%) were conducted in primary care. Of those conducted in primary care, 98.6% (n=218) of spirometry traces were of adequate quality. Of those traces that were of adequate quality and conducted in primary care, and in whom a general practitioner (GP) diagnosis of COPD had been made, 72.5% (n=218) were consistent with obstruction. Historical records for asthma diagnosis significantly decreased odds of correct interpretation. CONCLUSION: The quality of the spirometry procedure undertaken in primary care is high. However, this was not reflected in the quality of interpretation, suggesting an unmet training in primary care. The quality of the spirometry procedure as demonstrated by spirometric tracings provides a re-assurance for the use of spirometric values available in the electronic health care record databases for research purposes

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele