Summary Using a health impact assessment framework, we estimated the population health effects arising from alternative land-use and transport policy initiatives in six cities. Land-use changes were ...modelled to reflect a compact city in which land-use density and diversity were increased and distances to public transport were reduced to produce low motorised mobility, namely a modal shift from private motor vehicles to walking, cycling, and public transport. The modelled compact city scenario resulted in health gains for all cities (for diabetes, cardiovascular disease, and respiratory disease) with overall health gains of 420–826 disability-adjusted life-years (DALYs) per 100 000 population. However, for moderate to highly motorised cities, such as Melbourne, London, and Boston, the compact city scenario predicted a small increase in road trauma for cyclists and pedestrians (health loss of between 34 and 41 DALYs per 100 000 population). The findings suggest that government policies need to actively pursue land-use elements—particularly a focus towards compact cities—that support a modal shift away from private motor vehicles towards walking, cycling, and low-emission public transport. At the same time, these policies need to ensure the provision of safe walking and cycling infrastructure. The findings highlight the opportunities for policy makers to positively influence the overall health of city populations.
Summary Background The prostate-specific antigen (PSA) test is used to screen for prostate cancer but has a high false-positive rate that translates into unnecessary prostate biopsies and ...overdiagnosis of low-risk prostate cancers. We aimed to develop and validate a model to identify high-risk prostate cancer (with a Gleason score of at least 7) with better test characteristics than that provided by PSA screening alone. Methods The Stockholm 3 (STHLM3) study is a prospective, population-based, paired, screen-positive, diagnostic study of men without prostate cancer aged 50–69 years randomly invited by date of birth from the Swedish Population Register kept by the Swedish Tax Agency. Men with prostate cancer at enrolment were excluded from the study. The predefined STHLM3 model (a combination of plasma protein biomarkers PSA, free PSA, intact PSA, hK2, MSMB, MIC1, genetic polymorphisms 232 SNPs, and clinical variables age, family, history, previous prostate biopsy, prostate exam), and PSA concentration were both tested in all participants enrolled. The primary aim was to increase the specificity compared with PSA without decreasing the sensitivity to diagnose high-risk prostate cancer. The primary outcomes were number of detected high-risk cancers (sensitivity) and the number of performed prostate biopsies (specificity). The STHLM3 training cohort was used to train the STHLM3 model, which was prospectively tested in the STHLM3 validation cohort. Logistic regression was used to test for associations between biomarkers and clinical variables and prostate cancer with a Gleason score of at least 7. This study is registered with ISCRTN.com , number ISRCTN84445406. Findings The STHLM3 model performed significantly better than PSA alone for detection of cancers with a Gleason score of at least 7 (p<0·0001), the area under the curve was 0·56 (95% CI 0·55–0·60) with PSA alone and 0·74 (95% CI 0·72–0·75) with the STHLM3 model. All variables used in the STHLM3 model were significantly associated with prostate cancers with a Gleason score of at least 7 (p<0·05) in a multiple logistic regression model. At the same level of sensitivity as the PSA test using a cutoff of ≥3 ng/mL to diagnose high risk prostate cancer, use of the STHLM3 model could reduce the number of biopsies by 32% (95% CI 24–39) and could avoid 44% (35–54) of benign biopsies. Interpretation The STHLM3 model could reduce unnecessary biopsies without compromising the ability to diagnose prostate cancer with a Gleason score of at least 7, and could be a step towards personalised risk-based prostate cancer diagnostic programmes. Funding Stockholm County Council (Stockholms Läns Landsting).
Summary Background Up to 70% of patients with primary biliary cholangitis develop pruritus (itch) during the course of their disease. Treatment of pruritus in primary biliary cholangitis is ...challenging and novel therapies are needed. Ursodeoxycholic acid, the standard first-line treatment for primary biliary cholangitis, is largely ineffective for pruritus. We investigated the efficacy and safety of GSK2330672, a selective inhibitor of human ileal bile acid transporter (IBAT), in patients with primary biliary cholangitis with pruritus. Methods We conducted this phase 2a, double-blind, randomised, placebo-controlled, crossover trial in two UK medical centres. Following 2 weeks of open placebo run-in, patients were randomly assigned in a 1:1 ratio with a block size of 4 to receive GSK2330672 or placebo twice daily during two consecutive 14-day treatment periods in a crossover sequence. The treatment periods were followed by a 14-day single-blinded placebo follow-up period. The primary endpoints were safety of GSK2330672, assessed using clinical and laboratory parameters, and tolerability as rated by the Gastrointestinal Symptom Rating Scale. The secondary endpoints were changes in pruritus scores measured using the 0 to 10 numerical rating scale (NRS), primary biliary cholangitis-40 (PBC-40) itch domain score and 5-D itch scale, changes in serum total bile acids and 7 alpha hydroxy-4-cholesten-3-one (C4), and changes in the pharmacokinetic parameters of ursodeoxycholic acid and its conjugates. The trial was registered with ClinicalTrials.gov , number NCT01899703. Findings Between March 10, 2014, and Oct 7, 2015, we enrolled 22 patients. 11 patients were assigned to receive intervention followed by placebo (sequence 1), and 11 patients were assigned to receive placebo followed by intervention (sequence 2). One patient assigned to sequence 2 withdrew consent prior to receiving randomised therapy. One patient did not attend the placebo follow-up period, but was included in the final analysis. GSK2330672 treatment for 14 days was safe with no serious adverse events reported. Diarrhoea was the most frequent adverse event during treatment with GSK2330672 (seven with GSK2330672 vs one with placebo) and headache was the most frequent adverse event during treatment with placebo (seven with placebo vs six with GSK2330672). After GSK2330672 treatment, the percentage changes from baseline itch scores were −57% (95% CI −73 to −42, p<0·0001) in the NRS, −31% (−42 to −20, p<0·0001) in the PBC-40 itch domain and −35% (−45 to −25, p<0·0001) in the 5-D itch scale. GSK2330672 produced significantly greater reduction from baseline than the double-blind placebo in the NRS (−23%, 95% CI −45 to −1; p=0·037), PBC-40 itch domain, (−14%, −26 to −1; p=0·034), and 5-D itch scale (−20%, −34 to −7; p=0·0045). After GSK2330672 treatment, serum total bile acid concentrations declined by 50% (95% CI −37 to −61, p<0·0001) from 30 to 15 μM, with a significant 3·1-times increase (95% CI 2·4 to 4·0, p<0·0001) in serum C4 concentrations from 7·9 to 24·7ng/mL. Interpretation In patients with primary biliary cholangitis with pruritus, 14 days of ileal bile acid transporter inhibition by GSK2330672 was generally well tolerated without serious adverse events, and demonstrated efficacy in reducing pruritus severity. GSK2330672 has the potential to be a significant and novel advance for the treatment of pruritus in primary biliary cholangitis. Diarrhoea, the most common adverse event associated with GSK2330672 treatment, might limit the long-term use of this drug. Funding GlaxoSmithKline and National Institute for Health Research.
Abstract Introduction Endogenous dentin matrix metalloproteinases (MMPs) contribute to extracellular collagen matrix degradation in hybrid layers after adhesive dentin bonding procedures. Endodontic ...irrigants, including chlorhexidine and ethylenediaminetetraacetic acid (EDTA), might help protect the hybrid layer from this process. The objective of the present study was to determine the exposure time necessary for EDTA to inactivate endogenous MMP activity in human dentin. Methods Dentin beams (2 × 1 × 3 mm) were prepared from mid-coronal dentin of extracted third molars. The beams were demineralized in 10 wt% phosphoric acid, which also activated endogenous MMPs, and were divided into 4 experimental groups on the basis of exposure time to 17% EDTA (0, 1, 2, or 5 minutes). A generic colorimetric MMP assay measured MMP activity via absorbance at 412 nm. Data were evaluated by Kruskal-Wallis analysis of variance, followed by Dunn pair-wise comparisons at α = 0.05. Results All exposure times resulted in significant inhibition ( P < .001) compared with unexposed controls. Specifically, percent inhibition for 1-, 2-, and 5-minute exposure times was 55.1% ± 21.5%, 72.8% ± 11.7%, and 74.7% ± 19.7%, respectively. Conclusions Seventeen percent EDTA significantly inhibits endogenous MMP activity of human dentin within 1–2 minutes. This might minimize hybrid layer degradation after resin bonding procedures in the root canal space.
Background Brain health may be affected by modifiable lifestyle factors; consuming fish and antioxidative omega-3 fatty acids may reduce brain structural abnormality risk. Purpose To determine ...whether dietary fish consumption is related to brain structural integrity among cognitively normal elders. Methods Data were analyzed from 260 cognitively normal individuals from the Cardiovascular Health Study with information on fish consumption from the National Cancer Institute Food Frequency Questionnaire and brain magnetic resonance imaging (MRI). The relationship between fish consumption data collected in 1989–1990 and brain structural MRI obtained in 1998–1999 was assessed using voxel-based morphometry in multiple regression analyses in 2012. Covariates were age, gender, race, education, white matter lesions, MRI-identified infarcts, waist–hip ratio, and physical activity as assessed by the number of city blocks walked in 1 week. Volumetric changes were further modeled with omega-3 fatty acid estimates to better understand the mechanistic link between fish consumption, brain health, and Alzheimer disease. Results Weekly consumption of baked or broiled fish was positively associated with gray matter volumes in the hippocampus, precuneus, posterior cingulate, and orbital frontal cortex even after adjusting for covariates. These results did not change when including omega-3 fatty acid estimates in the analysis. Conclusions Dietary consumption of baked or broiled fish is related to larger gray matter volumes independent of omega-3 fatty acid content. These findings suggest that a confluence of lifestyle factors influence brain health, adding to the growing body of evidence that prevention strategies for late-life brain health need to begin decades earlier.
Conventional mammography is largely limited by superimposed anatomy. Digital breast tomosynthesis (DBT) and computed tomography (CT) alleviate this limitation but with added out-of-plane artifacts or ...limited chest wall coverage. This article presents a wide-angle breast tomosynthesis (WBT), aimed to provide a practical solution to these limitations, and offers an initial study of its utility in comparison with DBT and CT using a singular evaluation platform.
Using an anthropomorphic virtual breast phantom, a Monte Carlo code modeled a breast imaging system for three modalities of DBT, WBT, and breast CT (44°, 99°, and 198° total angle range, respectively) at four breast compression levels, all at a constant mean glandular dose level of 1.5 mGy. Reconstructed volumes were generated using iterative reconstruction methods. Lesion detectability was estimated using contrast-to-noise ratio and a channelized Hotelling observer model in terms of the area under the receiver operating characteristic (AUC).
Results showed improved detection with increased angular span and compression. The estimated AUCs for WBT were similar to that of CT. Comparative performance averaged over all thicknesses between CT and WBT was 4.3 ± 3.0%, whereas that between WBT and DBT was 5.6 ± 1.0%. At compression levels reflective of the modality (7-, 5-, and 4-cm thickness for CT, WBT, and DBT, respectively), WBT yielded an AUC comparable to CT (performance difference of 1.2%) but superior to DBT (performance difference of 5.5%).
The proposed imaging modality showed significant advantages over conventional DBT. WBT exhibited superior imaging performance over DBT at lower compression levels, highlighting further potential for reduced breast compression.
Background Lung function is a long-term predictor of mortality and morbidity. Objective We sought to identify single nucleotide polymorphisms (SNPs) associated with lung function. Methods We ...performed a genome-wide association study (GWAS) of FEV1 , forced vital capacity (FVC), and FEV1 /FVC in 1144 Hutterites aged 6 to 89 years, who are members of a founder population of European descent. We performed least absolute shrinkage and selection operation regression to select the minimum set of SNPs that best predict FEV1 /FVC in the Hutterites and used the GRAIL algorithm to mine the Gene Ontology database for evidence of functional connections between genes near the predictive SNPs. Results Our GWAS identified significant associations between FEV1 /FVC and SNPs at the THSD4-UACA-TLE3 locus on chromosome 15q23 ( P = 5.7 × 10−8 to 3.4 × 10−9 ). Nine SNPs at or near 4 additional loci had P < 10−5 with FEV1 /FVC. Only 2 SNPs were found with P < 10−5 for FEV1 or FVC. We found nominal levels of significance with SNPs at 9 of the 27 previously reported loci associated with lung function measures. Among a predictive set of 80 SNPs, 6 loci were identified that had a significant degree of functional connectivity (GRAIL P < .05), including 3 clusters of β-defensin genes, 2 chemokine genes ( CCL18 and CXCL12 ), and TNFRSF13B. Conclusion This study identifies genome-wide significant associations and replicates results of previous GWASs. Multimarker modeling implicated for the first time common variation in genes involved in antimicrobial immunity in airway mucosa that influences lung function.
Who Goes in and Out of the Hospital Patient Room? Arbogast, James, PhD; Quinn, Jeff, PhD; Clark, Tracy, MSN, RN ...
American journal of infection control,
06/2017, Letnik:
45, Številka:
6
Journal Article
PDF
