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BackgroundHigh rates of cannabis and illicit drug use are experienced by young people during the final stages of neurodevelopment (aged 15-24 years), a period characterized by high neuroplasticity. Frequent drug use during this time may interfere with neurophysiological and neuropsychological development pathways, potentially leading to ongoing unfavorable neuroadaptations. The dose-response relationship between illicit drug use, exposure, and individual neurodevelopmental variation is unknown but salient with global shifts in the legal landscape and increasingly liberal attitudes and perceptions of the harm caused by cannabis and illicit drugs. ObjectiveThis systematic review aims to synthesize longitudinal studies that investigate the effects of illicit drug use on structural, functional, and cognitive brain domains in individuals under the neural age of adulthood (25 years). This protocol outlines prospective methods that will facilitate an exhaustive review of the literature exploring pre- and post-drug use brain abnormalities arising during neurodevelopment. MethodsFive electronic databases (Medline, Embase, PsycINFO, ProQuest Central, and Web of Science) will be systematically searched between 1990 and 2019. The search terms will be a combination of MeSH (Medical Subject Headings), with keywords adapted to each database. Study reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and if relevant, study quality will be assessed using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. Eligible studies are those that sampled youth exposed to cannabis or illicit drugs and employed neurophysiological or neuropsychological assessment techniques. Studies will be excluded if participants had been clinically diagnosed with any psychiatric, neurological, or pharmacological condition. ResultsThis is an ongoing review. As of February 2020, papers are in full-text screening, with results predicted to be complete by July 2020. ConclusionsIntegrating data collected on the three brain domains will enable an assessment of the links between structural, functional, and cognitive brain health across individuals and may support the early detection and prevention of neurodevelopmental harm. Trial RegistrationPROSPERO CRD42020151442; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=151442 International Registered Report Identifier (IRRID)PRR1-10.2196/18349

OBJECTIVE: The lack of randomized controlled trials (RCTs) in pulmonary fibrosis in systemic sclerosis (SSc) has hampered an evidence-based approach to treatment. This RCT was undertaken to investigate the effects of intravenous (IV) cyclophosphamide (CYC) followed by azathioprine (AZA) treatment in pulmonary fibrosis in SSc. METHODS: Forty-five patients were randomized to receive low-dose prednisolone and 6 infusions (monthly) of CYC followed by oral AZA, or placebo. Primary outcome measures were change in percent predicted forced vital capacity (FVC) and change in single-breath diffusing capacity for carbon monoxide (DLCO). Secondary outcome measures included changes in appearance on high-resolution computed tomography and dyspnea scores. An intent-to-treat statistical analysis was performed. RESULTS: At baseline, there were no significant group differences in factors linked to outcome, including severity of pulmonary fibrosis and autoantibody status. Sixty-two percent of the patients completed the first year of treatment. Withdrawals included 9 patients (6 from the placebo group) with significant decline in lung function, 2 with treatment side effects (both from the active treatment group), and 6 with non-trial-related comorbidity. No hemorrhagic cystitis or bone marrow suppression was observed. Estimation of the relative treatment effect (active treatment versus placebo) adjusted for baseline FVC and treatment center revealed a favorable outcome for FVC of 4.19%; this between-group difference showed a trend toward statistical significance (P = 0.08). No improvements in DLCO or secondary outcome measures were identified. CONCLUSION: This trial did not demonstrate significant improvement in the primary or secondary end points in the active treatment group versus the group receiving placebo. However, for FVC there was a trend toward statistical significance between the 2 groups. This suggests that treatment of pulmonary fibrosis in SSc with low-dose prednisolone and IV CYC followed by AZA stabilizes lung function in a subset of patients with the disease. Therapy was well tolerated with no increase in serious adverse events. [ABSTRACT FROM AUTHOR]

RATIONALE: Lung inflammation and injury is critical in cystic fibrosis. An ideal antiinflammatory agent has not been identified but inhaled corticosteroids are widely used despite lack of evidence. OBJECTIVES: To test the safety of withdrawal of inhaled corticosteroids with the hypothesis this would not be associated with an earlier onset of acute chest exacerbations. METHODS: Multicenter randomized double-blind placebo-controlled trial in 18 pediatric and adult UK centers. Eligibility criteria included age>6.0 yr, FEV1>or=40% predicted, and corticosteroid use>3 mo. During the 2-mo run-in period, all patients received fluticasone; they then took either fluticasone or placebo for 6 mo. MEASUREMENTS AND MAIN RESULTS: Fluticasone group: n=84, median age 14.6 yr, mean (SD) FEV1 76% (18); placebo group: n=87, median age 15.8 yr, mean (SD) FEV1 76% (18). There was no difference in time to first exacerbation (primary outcome) with hazard ratio (95% confidence interval) of 1.07 (0.68 to 1.70) for fluticasone versus placebo. There was no effect of age, atopy, corticosteroid dose, FEV1, or Pseudomonas aeruginosa status. There was no change in lung function or differences in antibiotic or rescue bronchodilator use. Fewer patients in the fluticasone group withdrew from the study due to lung-related adverse events (9 vs. 15%); with a relative risk (95% confidence interval) of 0.59 (0.23-1.48) fluticasone versus placebo. CONCLUSIONS: In this study population (applicable to 40% of patients with cystic fibrosis in the UK), it appears safe to consider stopping inhaled corticosteroids. Potential advantages will be to reduce the drug burden on patients, reduce adverse effects, and make financial savings. [ABSTRACT FROM AUTHOR]

A new ultrasound bone densitometer has been developed that measures ultrasonic properties of the os calcis, namely, the speed of sound (SOS), broadband ultrasound attenuation (BUA), and a proprietary factor derived from SOS and BUA, termed "stiffness." Short-term precision of ultrasound measurements was 1.4% for BUA, 0.2% for SOS, and 1.5% for stiffness in healthy women, and 1.1% for BUA, 0.1% for SOS, and 1.5% for stiffness in osteopenic women. One hundred seven women underwent measurements by ultrasound, together with dual energy X-ray absorptiometry (DXA) bone mineral density (BMD) measurements of the lumbar spine and proximal femur. Correlations between SOS, BUA, and stiffness measurements and DXA BMD measurements were all highly significant (P < 0.001) with r values varying from 0.54 to 0.67. BUA, SOS, and stiffness measurements were all significantly different between normal and osteopenic women even after adjusting for age, height, and weight (P < 0.05, P < 0.001, and P < 0.01, respectively). These results demonstrate that this ultrasound system measures ultrasonic properties of the os calcis with good precision, the measurements correlate moderately well with DXA BMD measurements and they can differentiate between normals and those with osteopenia. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To determine whether postmenopausal women with cardiological syndrome X (chest pain and abnormal exercise electrocardiogram despite normal coronary angiography) exhibit disturbances in the full range of proposed components of the putative "insulin resistance syndrome". PATIENTS AND METHODS--20 postmenopausal women with syndrome X and 20 healthy controls each underwent measurement of insulin resistance (by minimal model analysis of the intravenous glucose tolerance test), lipid, lipoprotein, and apolipoprotein concentrations, a range of haemostatic variables, serum uric acid concentration, and centrality of body fat distribution (by dual energy x ray absorptiometry). RESULTS--Women with syndrome X had higher fasting triglyceride concentrations than controls (median: 1.60 v 1.02 mmol/l, P < 0.05). Concentrations of high density lipoprotein cholesterol were lower (1.33 v 1.61 mmol/l, P < 0.05) as were those of the high density lipoprotein apolipoproteins AI and AII. Insulin and C peptide responses to the intravenous glucose tolerance test were higher (27.6 v 19.8 microU/ml/min, P < 0.01; 101 v 72 pmol/ml/min, P < 0.05, respectively), and insulin sensitivity was lower (1.89 v 3.09 min/microU/ml, P < 0.05). There were, however, no significant differences between other proposed components of the insulin resistance syndrome (blood pressure, glucose tolerance, proportion of central body fat, serum uric acid concentration, and plasminogen activator inhibitor-1 activity). Antithrombin III activity was higher in women with syndrome X (121 v 113%, P < 0.01). CONCLUSIONS--Women with syndrome X tend to be insulin resistant and have lipid and lipoprotein abnormalities, but do not exhibit all characteristics of the insulin resistance syndrome. Such variation in correlated risk factors is consistent with underlying heterogeneity in the insulin resistance syndrome and cardiological syndrome X. [ABSTRACT FROM PUBLISHER]