Barriers to spirometry in Australian general practice: A systematic review.

BACKGROUND AND OBJECTIVES: The reasons for the underutilisation of spirometry are unclear. We undertook a systematic review assessing barriers to correct spirometry in Australian general practice. METHOD: PRISMA guidelines were followed. Six databases (MEDLINE, EMBASE, CINAHL, Scopus, PubMed, Google Scholar) were searched using terms 'primary health care', 'family physicians', 'family practice', 'general practice', 'primary care', 'Australia' and 'spirometry'. RESULTS: The 11 included studies reported multiple barriers to the use of spirometry in Australian general practice. Barriers for clinicians included spirometry having limited clinical utility in general practice (six studies), a reported low confidence with spirometry (six studies) and demonstrated poor spirometry interpretation skills (two studies). Practice-related barriers were time (six studies), cost (four studies), lack of trained staff (four studies), poor availability (four studies) and poor technique/calibration (two studies). Patient reluctance to attend for spirometry (four studies) was also reported as a barrier. DISCUSSION: To reduce barriers to correct spirometry, its perceived low clinical utility and patient reluctance require remediation. Issues of cost, confidence and competence might be addressed by reimbursement settings and ongoing training.

Chronic and acute LRRK2 silencing has no long-term behavioral effects, whereas wild-type and mutant LRRK2 overexpression induce motor and cognitive deficits and altered regulation of dopamine release.

INTRODUCTION: Germline silencing of the PD-related protein LRRK2 does not alter glutamate or dopamine release in adult mice, but some exploratory abnormalities have been reported with ageing. Contrastingly, high levels of human LRRK2 cause locomotor alterations and cognitive deficits accompanied by reduced striatal dopamine levels, with the latter also observed in G2019S mutant mice. Comparative cognitive and motor behavioral testing of LRRK2 KO, overexpressor and mutant overexpressor mice has not previously been reported. METHODS: Parallel, comparative behavioral characterization was performed assessing motor and cognitive abilities. Striatal antisense oligonucleotide injections were conducted to investigate the effects of acute LRRK2 silencing on behavior and dopamine fiber density. Striatal synaptosomes prepared from hG2019S mice assessed vesicular release of dopamine and its sensitivity to D2 autoreceptor stimulation. RESULTS: Genetic ablation of LRRK2 has no long-term consequences on motor or cognitive function. Consistently, no effects on behavior or dopaminergic fiber density were observed following acute striatal silencing. Conversely, 12-month OE mice show persistent locomotor deficits and worsening of cognitive abilities; whereas, hG2019S mice display early hyperactivity and effective learning and memory that progress to decreased motor and cognitive deficits at older ages. The G2019S mutation does not affect vesicular dopamine release, but decreases its sensitivity to D2-mediated inhibition. CONCLUSION: LRRK2 silencing is well tolerated in mouse, arguing PD does not result from LRRK2 loss of function. High levels of WT and G2019S LRRK2 produce similar but temporally distinct phenotypes, potentially modeling different stages of disease progression. The data implicate gain of LRRK2 function in the pathogenesis of PD.