A priori clinical diagnosis of CKD is defined as pre-WES clinical diagnosis per referral by primary nephrologist. CAKUT, congenital anomalies of the kidney and urinary tract; CKD, chronic kidney disease; ESKD, end-stage kidney disease; GN, glomerulonephritis; SRNS, steroid-resistant nephrotic syndrome; TIKD, tubulointerstitial kidney disease; WES, whole exome sequencing. a Age at first presentation to medical services with evidence of CKD. b Age at start of renal replacement therapy, i.e., dialysis or kidney transplantation. DM Connaughton et al.: Monogenic causation of chronic kidney disease in Ireland c l i n i c a l i n v e s t i g a t i o n Kidney International (2019) 95, 914-928 DM Connaughton et al.: Monogenic causation of chronic kidney disease in Ireland c l i n i c a l i n v e s t i g a t i o n
Neutrophil-lymphocyte ratio (NLR) is a marker of systemic inflammatory response and its elevation has recently been shown to be a poor prognostic factor in many malignancies including colon, prostate and bladder cancer. The primary aim of this study was to assess the prognostic impact of NLR in a clinically annotated cohort of patients with glioblastoma multiforme (GBM). We hypothesised that elevated NLR would be associated with worse prognosis. Between 2004 and 2009, 137 patients had surgery for GBM and were assessed for consideration of adjuvant therapy at our institution. Of these, 84 patients with an evaluable pre-corticosteroid full blood count result were identified and included in the final analysis. Median overall survival was 9.3 months (range 0.7-82.1). On univariate analysis, age >65 years, gender, ECOG performance status ≥2, frontal tumour, extent of surgical resection, completion of adjuvant chemoradiation protocol and NLR > 4 were significantly correlated with overall survival. Patients with NLR > 4, had a worse median overall survival at 7.5 months versus 11.2 months in patients with NLR ≤ 4 (hazard ratio 1.6, 95 % CI 1.00-2.52, p = 0.048). On multivariate analysis NLR > 4 remained an independent prognostic indicator for poor outcome. These data are an important reminder of the potential relevance of host immunity in GBM. In our cohort, NLR > 4 conferred a worse prognosis independent of other well established prognostic factors. If validated in other cohorts NLR may prove to be a useful addition in predicting prognosis in GBM patients. The demonstration that host immunity plays a role in GBM biology suggests that investigation of emerging therapies which modulate host immune response are warranted in this disease.
Background The value of quantitative computed tomography (QCT) to identify chronic obstructive pulmonary disease (COPD) phenotypes is increasingly appreciated. We hypothesized that QCT-defined emphysema and airway abnormalities relate to St. George's Respiratory Questionnaire (SGRQ) and BODE. Methods 1,200 COPDGene subjects meeting GOLD criteria for COPD with QCT analysis were included. Total lung emphysema was measured using density mask technique with a -950 HU threshold. An automated program measured mean wall thickness (WT), wall area percent (WA%) and pi10 in six segmental bronchi. Separate multivariate analyses examined the relative influence of airway measures and emphysema on SGRQ and BODE. Results In separate models predicting SGRQ score, a one unit standard deviation (SD) increase in each airway measure predicted higher SGRQ scores (for WT, 1.90 points higher, p=0.002; for WA%, 1.52 points higher, p=0.02; for pi10, 2.83 points higher p<0.001). The comparable increase in SGRQ for a one unit SD increase in percent emphysema in these models was relatively weaker, significant only in the pi10 model (for percent emphysema, 1.45 points higher, p=0.01). In separate models predicting BODE, a one unit SD increase in each airway measure predicted higher BODE scores (for WT, 1.07 fold increase, p<0.001; for WA%, 1.20 fold increase, p<0.001; for pi10, 1.16 fold increase, p<0.001). In these models, emphysema more strongly influenced BODE (range 1.24-1.26 fold increase, p<0.001). Conclusion Emphysema and airway disease both relate to clinically important parameters. The relative influence of airway disease is greater for SGRQ; the relative influence of emphysema is greater for BODE.
Introduction Autosomal dominant tubulo-interstitial kidney disease due to UMOD mutations (ADTKD- UMOD ) is a rare condition associated with high variability in the age of end-stage kidney disease (ESKD). The minor allele of rs4293393, located in the promoter of the UMOD gene, is present in 19% of the population and downregulates uromodulin production by approximately 50% and might affect the age of ESKD. The goal of this study was to better understand the genetic and clinical characteristics of ADTKD- UMOD and to perform a Mendelian randomization study to determine if the minor allele of rs4293393 was associated with better kidney survival. Methods An international group of collaborators collected clinical and genetic data on 722 affected individuals from 249 families with 125 mutations, including 28 new mutations. The median age of ESKD was 47 years. Men were at a much higher risk of progression to ESKD (hazard ratio 1.78, P < 0.001). Results The allele frequency of the minor rs4293393 allele was only 11.6% versus the 19% expected ( P < 0.01), resulting in Hardy-Weinberg disequilibrium and precluding a Mendelian randomization experiment. An in vitro score reflecting the severity of the trafficking defect of uromodulin mutants was found to be a promising predictor of the age of ESKD. Conclusion We report the clinical characteristics associated with 125 UMOD mutations. Male gender and a new in vitro score predict age of ESKD.
BackgroundNHS Stop Smoking Services (SSSs) provide free at the point of use treatment for smokers who would like to stop. Since their inception in 1999 they have evolved to offer a variety of support options. Given the changes that have happened in the provision of services and the ongoing need for evidence on effectiveness, the Evaluating Long-term Outcomes for NHS Stop Smoking Services (ELONS) study was commissioned.ObjectivesThe main aim of the study was to explore the factors that determine longer-term abstinence from smoking following intervention by SSSs. There were also a number of additional objectives.DesignThe ELONS study was an observational study with two main stages: secondary analysis of routine data collected by SSSs and a prospective cohort study of service clients. The prospective study had additional elements on client satisfaction, well-being and longer-term nicotine replacement therapy (NRT) use.SettingThe setting for the study was SSSs in England. For the secondary analysis, routine data from 49 services were obtained. For the prospective study and its added elements, nine services were involved. The target population was clients of these services.ParticipantsThere were 202,804 cases included in secondary analysis and 3075 in the prospective study.InterventionsA combination of behavioural support and stop smoking medication delivered by SSS practitioners.Main outcome measuresAbstinence from smoking at 4 and 52 weeks after setting a quit date, validated by a carbon monoxide (CO) breath test.ResultsJust over 4 in 10 smokers (41%) recruited to the prospective study were biochemically validated as abstinent from smoking at 4 weeks (which was broadly comparable with findings from the secondary analysis of routine service data, where self-reported 4-week quit rates were 48%, falling to 34% when biochemical validation had occurred). At the 1-year follow-up, 8% of prospective study clients were CO validated as abstinent from smoking. Clients who received specialist one-to-one behavioural support were twice as likely to have remained abstinent than those who were seen by a general practitioner (GP) practice and pharmacy providers [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.2 to 4.6]. Clients who received group behavioural support (either closed or rolling groups) were three times more likely to stop smoking than those who were seen by a GP practice or pharmacy providers (OR 3.4, 95% CI 1.7 to 6.7). Satisfaction with services was high and well-being at baseline was found to be a predictor of abstinence from smoking at longer-term follow-up. Continued use of NRT at 1 year was rare, but no evidence of harm from longer-term use was identified from the data collected.ConclusionsStop Smoking Services in England are effective in helping smokers to move away from tobacco use. Using the 52-week CO-validated quit rate of 8% found in this study, we estimate that in the year 2012–13 the services supported 36,249 clients to become non-smokers for the remainder of their lives. This is a substantial figure and provides one indicator of the ongoing value of the treatment that the services provide. The study raises a number of issues for future research including (1) examining the role of electronic cigarettes (e-cigarettes) in smoking cessation for service clients [this study did not look at e-cigarette use (except briefly in the longer-term NRT study) but this is a priority for future studies]; (2) more detailed comparisons of rolling groups with other forms of behavioural support; (3) further exploration of the role of practitioner knowledge, skills and use of effective behaviour change techniques in supporting service clients to stop smoking; (4) surveillance of the impact of structural and funding changes on the future development and sustainability of SSSs; and (5) more detailed analysis of well-being over time between those who successfully stop smoking and those who relapse. Further research on longer-term use of non-combustible nicotine products that measures a wider array of biomarkers of smoking-related harm such as lung function tests or carcinogen metabolites.FundingThe National Institute for Health Research Health Technology Assessment programme. The UK Centre for Tobacco and Alcohol Studies provided funding for the longer-term NRT study.
BackgroundDisadvantaged smokers are less likely to be successful when trying to stop smoking than more affluent smokers. In the UK, NHS Stop Smoking Services (SSS) provide a range of pharmacotherapy and behavioural support, delivered by advisors with a range of backgrounds. Whether the types of support provided and who provides it influence differences in quit rates amongst low SES smokers compared with high SES smokers has not previously been examined.Methods202,084 records of smokers in England who attended a NHS Stop Smoking Service between July 2010 and June 2011 were acquired. Smokers were followed-up by services at four weeks post quit date. Multilevel logistic regression models of CO validated quits were employed. Disadvantage was explored through the National Statistics Socio-Economic Classification (NS-SEC) and by eligibility for free prescriptions, an indicator of low income amongst adults aged between 19 and 59 in England.ResultsAffluent smokers were more likely to quit than disadvantaged smokers (OR 1.38 (1.35 to 1.42) for clients who paid for prescriptions compared to those eligible for free prescriptions). 80% of service clients received one-to-one counselling but open group forms of behavioural therapy were more successful (main effect OR 1.26 (1.12 to 1.41)) except amongst some of the most disadvantaged clients (long-term unemployed and prisoners). Closed groups were little deployed and they were not significantly more successful than one-to-one behavioural therapy after controls. Who delivered treatment did make a difference for some clients, with all but the most affluent less likely to be successful if they had been treated by a nurse compared with other types of advisers, including smoking cessation specialists (main effect OR 0.73 (0.65 to 0.83)).ConclusionThis study provides further evidence that disadvantaged smokers find quitting more difficult even when they have attended a smoking cessation programme. The findings suggest that open groups should be promoted, although they may not be as effective as other forms of behavioural therapy for the long-term unemployed or prisoners. Further research is required to explore why most groups of smokers who attended services staffed by nurses were less likely to quit than those who received treatment from other types of advisors.
BackgroundUse of e-cigarettes (inhalable vapour producing battery powered devices that aim to simulate tobacco cigarettes), is rising in a number of countries, but as yet none of these products are regulated as medicinal devices or available as smoking cessation treatments. Smokers seeking support from health professionals to stop smoking are interested in e-cigarettes and may be buying them to aid a quit attempt. Determining what smokers are asking, and what health professionals think about these products may have implications for smoking treatment services in a number of countries.MethodsStop smoking service advisors, managers and commissioners in the United Kingdom were asked to take part in two surveys on e-cigarettes. Data was analysed from 587 practitioners who completed a survey in 2011 and 705 practitioners who completed a repeat survey in 2013. Responses to multiple choice questions and free text comments were analysed.ResultsResponding practitioners reported that interest in, and use of, e-cigarettes is growing among adults seeking help to stop smoking in the UK. In 2013 91% of respondents reported that interest in e-cigarettes had grown in the past year and whilst in 2011, 2% of respondents reported a ‘quarter to a half’ of their clients saying that they were regularly using e-cigarettes, by 2013 this had increased to 23.5% (p < .001). Responding practitioners’ views towards e-cigarettes became more positive between the first and second surveys (15% strongly agreed/agreed in 2011 that ‘e-cigarettes are a good thing’ rising to 26% in 2013). However, they continued to have concerns about the products. In particular, analysis of free text responses suggested practitioners were unsure about safety or efficacy for smoking cessation, and were worried that smokers may become dependent on the products. Practitioners were also aware of the potential of e-cigarettes to undermine smokers’ willingness to use evidence-based methods to stop, and to challenge policies aiming to denormalise tobacco smoking.ConclusionsHealth professionals are asking for reliable and accurate information on e-cigarettes to convey to smokers who want to quit. Randomized controlled trials and ongoing surveillance of e-cigarette use and its consequences for smoking cessation rates and smoking treatment services are required.
GPs are influenced by clinical signs and symptoms to use antibiotics for respiratory infections for which there is poor evidence of efficacy from the literature.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.