Objective
To establish the effectiveness of a brief intervention to prevent falls in older patients presenting to the ED post‐discharge.
Methods
The present study is a prospective single‐centre, ...quasi‐randomised controlled clinical trial of a brief targeted educational intervention to prevent falls. The intervention group received brief scripted education and were advised of their percentage probability of falling in the next 6 months. The key message was to reinforce the importance of falls prevention strategies and the seriousness of falls.
Results
A total of 412 over 65 years old were recruited; 63 (32.1%) patients in the intervention group and 67 (36.8%) in the control group reported falls in the 6 month follow up period (OR 0.81, 95% confidence interval CI 0.53–1.25, P = 0.34). No significant differences were noted for mortalities (P = 0.54), ED representations (P = 0.15) and medication changes (P = 0.17). Patients receiving intervention had less hospital admissions (P = 0.002) after adjustment for confounding variables. Intervention patients who presented with a fall had significant (P = 0.007) improvement in function at 6 months, whereas those not presenting with a fall experienced functional decline.
Conclusion
A brief intervention was associated with maintenance of function in fallers and reduced hospital admissions, without preventing falls post‐discharge.
To compare the Falls Risk for Older Persons-Community Setting Screening Tool (FROP Com Screen) with the Two-Item Screening Tool in older adults presenting to the ED.
A prospective cohort study, ...comparing the efficacy of the two falls risk assessment tools by applying them simultaneously in a sample of hospital ED presentations.
Two hundred and one patients over 65 years old were recruited. Thirty-six per cent reported falls in the 6-month follow-up period. The area under the receiver operating characteristic curve was 0.57 (95% CI 0.48 to 0.66) for the FROP Com Screen and 0.54 (95% CI 0.45 to 0.63) for the Two-Item Screening Tool. FROP Com Screen had a sensitivity of 39% (95% CI 0.27 to 0.51) and a specificity of 70% (95% CI 0.61 to 0.78), while the Two-Item Screening Tool had a sensitivity of 48% (95% CI 0.36 to 0.60) and a specificity of 57% (95% CI 0.47 to 0.66).
Both tools have limited predictive ability in the ED setting.
Objectives
The study aims to describe the characteristics of patients presenting to an ED with a fall and evaluate multidisciplinary Care Coordination Team (CCT) referrals on patient outcomes.
...Methods
A single‐centred retrospective analysis of electronic data at an adult tertiary hospital was performed using data from 2004 to 2009 of presentations for patients aged 65 years or over with a fall. The primary outcome measure was representation to hospital within 30 days, comparing patients referred to CCT and those not referred. Secondary outcomes were differences in demographic characteristics, mode of arrival, triage score and readmission.
Results
The proportion of ED patients presenting with a fall and their mean age is stable over time. From 2006 to 2009, 5162 fallers were referred to CCT in a decreasing trend, but with increased urgency. Statistically significant predictors for being referred to CCT were increasing age, being female, arriving by ambulance, being transferred from a nursing home and higher socioeconomic category. Arrival by ambulance and a history of previous falls were associated with representation and readmission. A decreasing trend from 2006 to 2009 was seen in rate ratios and odds ratios via regression modelling for both representation and readmission in patients referred to CCT.
Conclusion
Maturing of the CCT is associated with a decrease in representation and readmission rate. Over time, the CCT attended higher urgency patients associated with stable admission rates. These associations were not significant and the clinical effectiveness of ED CCTs requires further examination.
Aim: To determine whether a multifactorial intervention can decrease the frequency of secondary falls in older patients presenting to an emergency department with a fall. Methods: A randomized ...control design comparing multifactorial follow-up intervention to standard care. Risk assessments included Falls Risk for Older Persons-Community Setting Screening Tool (FROP Com Screen) and the Two Item Screening Tool, which were compared for sensitivity. Results: Eight patients (14%) in the control group and 11 patients (20.8%) in the intervention group experienced falls (p = 0.373). The proportion of those identified as high risk that fell was similar between the FROP Com Screen (17%) and the Two Item Screening Tool (17%). Patients on average waited 35 days in the control group and 40 days in the intervention group for an outpatient appointment. Conclusions: There was no significant benefit of the intervention. Our findings support interdisciplinary collaboration, multifactorial intervention, and risk management for falls prevention.
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•Fatty liver disease is a growing cause of cirrhosis and liver cancer globally.•Disease burden is expected to increase with the epidemics of obesity and diabetes.•Modeling shows slow ...growth in total cases and greater increase in advanced cases.•Mortality and advanced liver disease will more than double during 2016–2030.
Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are increasingly a cause of cirrhosis and hepatocellular carcinoma globally. This burden is expected to increase as epidemics of obesity, diabetes and metabolic syndrome continue to grow. The goal of this analysis was to use a Markov model to forecast NAFLD disease burden using currently available data.
A model was used to estimate NAFLD and NASH disease progression in eight countries based on data for adult prevalence of obesity and type 2 diabetes mellitus (DM). Published estimates and expert consensus were used to build and validate the model projections.
If obesity and DM level off in the future, we project a modest growth in total NAFLD cases (0–30%), between 2016–2030, with the highest growth in China as a result of urbanization and the lowest growth in Japan as a result of a shrinking population. However, at the same time, NASH prevalence will increase 15–56%, while liver mortality and advanced liver disease will more than double as a result of an aging/increasing population.
NAFLD and NASH represent a large and growing public health problem and efforts to understand this epidemic and to mitigate the disease burden are needed. If obesity and DM continue to increase at current and historical rates, both NAFLD and NASH prevalence are expected to increase. Since both are reversible, public health campaigns to increase awareness and diagnosis, and to promote diet and exercise can help manage the growth in future disease burden.
Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis can lead to advanced liver disease. Both conditions are becoming increasingly prevalent as the epidemics of obesity and diabetes continue to increase. A mathematical model was built to understand how the disease burden associated with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis will change over time. Results suggest increasing cases of advanced liver disease and liver-related mortality in the coming years.
Nonalcoholic fatty liver disease (NAFLD) represents an emerging cause of hepatocellular carcinoma (HCC), especially in non-cirrhotic individuals. The rs641738 C > T MBOAT7/TMC4 variant predisposes to ...progressive NAFLD, but the impact on hepatic carcinogenesis is unknown. In Italian NAFLD patients, the rs641738 T allele was associated with NAFLD-HCC (OR 1.65, 1.08-2.55; n = 765), particularly in those without advanced fibrosis (p < 0.001). The risk T allele was linked to 3'-UTR variation in MBOAT7 and to reduced MBOAT7 expression in patients without severe fibrosis. The number of PNPLA3, TM6SF2, and MBOAT7 risk variants was associated with NAFLD-HCC independently of clinical factors (p < 0.001), but did not significantly improve their predictive accuracy. When combining data from an independent UK NAFLD cohort, in the overall cohort of non-cirrhotic patients (n = 913, 41 with HCC) the T allele remained associated with HCC (OR 2.10, 1.33-3.31). Finally, in a combined cohort of non-cirrhotic patients with chronic hepatitis C or alcoholic liver disease (n = 1121), the T allele was independently associated with HCC risk (OR 1.93, 1.07-3.58). In conclusion, the MBOAT7 rs641738 T allele is associated with reduced MBOAT7 expression and may predispose to HCC in patients without cirrhosis, suggesting it should be evaluated in future prospective studies aimed at stratifying NAFLD-HCC risk.
Excess hepatic storage of triglycerides is considered a benign condition, but nonalcoholic steatohepatitis (NASH) may progress to fibrosis and promote atherosclerosis. Carriers of the TM6SF2 E167K ...variant have fatty liver as a result of reduced secretion of very‐low‐density lipoproteins (VLDLs). As a result, they have lower circulating lipids and reduced risk of myocardial infarction. In this study, we aimed to assess whether TM6SF2 E167K affects liver damage and cardiovascular outcomes in subjects at risk of NASH. Liver damage was evaluated in 1,201 patients who underwent liver biopsy for suspected NASH; 427 were evaluated for carotid atherosclerosis. Cardiovascular outcomes were assessed in 1,819 controls from the Swedish Obese Subjects (SOS) cohort. Presence of the inherited TM6SF2 E167K variant was determined by TaqMan assays. In the liver biopsy cohort, 188 subjects (13%) were carriers of the E167K variant. They had lower serum lipid levels than noncarriers (P < 0.05), had more‐severe steatosis, necroinflammation, ballooning, and fibrosis (P < 0.05), and were more likely to have NASH (odds ratio OR: 1.84; 95% confidence interval CI: 1.23‐2.79) and advanced fibrosis (OR, 2.08; 95% CI: 1.20‐3.55), after adjustment for age, sex, body mass index, fasting hyperglycemia, and the I148M PNPLA3 risk variant. However, E167K carriers had lower risk of developing carotid plaques (OR, 0.49; 95% CI: 0.25‐0.94). In the SOS cohort, E167K carriers had higher alanine aminotransferase ALT and lower lipid levels (P < 0.05), as well as a lower incidence of cardiovascular events (hazard ratio: 0.61; 95% CI: 0.39‐0.95). Conclusions: Carriers of the TM6SF2 E167K variant are more susceptible to progressive NASH, but are protected against cardiovascular disease. Our findings suggest that reduced ability to export VLDLs is deleterious for the liver. (Hepatology 2015;61:506‐514)
Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disorders and has a strong heritable component. The aim of this study was to identify new loci that contribute to severe NAFLD ...by examining rare variants.
We performed whole-exome sequencing in individuals with NAFLD and advanced fibrosis or hepatocellular carcinoma (n = 301) and examined the enrichment of likely pathogenic rare variants vs. the general population. This was followed by validation at the gene level.
In patients with severe NAFLD, we observed an enrichment of the p.P426L variant (rs143545741 C>T; odds ratio OR 5.26, 95% CI 2.1-12.6; p = 0.003) of autophagy-related 7 (ATG7), which we characterized as a loss-of-function, vs. the general population, and an enrichment in rare variants affecting the catalytic domain (OR 13.9; 95% CI 1.9-612; p = 0.002). In the UK Biobank cohort, loss-of-function ATG7 variants increased the risk of cirrhosis and hepatocellular carcinoma (OR 3.30; 95% CI 1.1-7.5 and OR 12.30, 95% CI 2.6-36, respectively; p <0.001 for both). The low-frequency loss-of-function p.V471A variant (rs36117895 T>C) was also associated with severe NAFLD in the clinical cohort (OR 1.7; 95% CI 1.2-2.5; p = 0.003), predisposed to hepatocellular ballooning (p = 0.007) evolving to fibrosis in the Liver biopsy cohort (n = 2,268), and was associated with liver injury in the UK Biobank (aspartate aminotransferase levels, p <0.001), with a larger effect in severely obese individuals in whom it was linked to hepatocellular carcinoma (p = 0.009). ATG7 protein localized to periportal hepatocytes, particularly in the presence of ballooning. In the Liver Transcriptomic cohort (n = 125), ATG7 expression correlated with suppression of the TNFα pathway, which was conversely upregulated in p.V471A carriers.
We identified rare and low-frequency ATG7 loss-of-function variants that promote NAFLD progression by impairing autophagy and facilitating ballooning and inflammation.
We found that rare mutations in a gene called autophagy-related 7 (ATG7) increase the risk of developing severe liver disease in individuals with dysmetabolism. These mutations cause an alteration in protein function and impairment of self-renewal of cellular content, leading to liver damage and inflammation.
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•NAFLD is the leading cause of liver disorders and has a strong heritable component.•Rare loss-of-function ATG7 gene mutations increase the risk of severe liver disease in patients with NAFLD.•ATG7 mutations cause altered protein function and impairment of autophagy, leading to hepatocellular ballooning and inflammation.•The most frequent variant is responsible for a meaningful fraction of predisposition to ballooning and hepatocellular carcinoma.
In patients with nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) is a risk factor for the development of fibrosis. However, fibrosis has been observed in livers of ...patients without NASH. We aimed to estimate the prevalence of fibrosis in patients without NASH and risk factors for fibrosis.
We analyzed data from 1738 subjects (44.9% with severe obesity) in a cross-sectional liver biopsy cohort enrolled at referral centers in Italy and Finland. Biopsy specimens were analyzed histologically by a blinded pathologist at each center, and a diagnosis of NASH was made based on steatosis (≥5% of hepatocytes), hepatocellular ballooning, and lobular inflammation. We also collected data on demographic features, metabolic comorbidities, and genetic factors, and performed logistic regression analyses. Findings were validated using data from 118 consecutive patients with NAFLD who underwent sequential liver biopsies at tertiary referral centers in Italy.
In the cross-sectional cohort, 132 of 389 patients (33.9%) with significant fibrosis had no NASH and 39 patients (10.0%) had no inflammation. The dissociation between NASH and fibrosis was significantly greater in patients with severe obesity (P < .005). Steatosis, ballooning, and lobular inflammation each were associated independently with significant fibrosis (P < .001); age, adiposity, fasting hyperglycemia, and the PNPLA3 I148M variant also were associated with fibrosis. In patients without, but not in those with NASH, significant fibrosis was associated with steatosis grade and the PNPLA3 I148M variant. In patients without NASH, age, fasting hyperglycemia, ballooning, and inflammation were associated with fibrosis. In the validation cohort, 16 of 47 patients (34.0%) with clinically significant fibrosis did not have NASH at baseline. In patients with fibrosis without baseline NASH, worsening of fibrosis (based on later biopsies) was associated with fasting hyperglycemia and more severe steatosis (P = .016).
In an analysis of biopsy specimens collected from patients with NAFLD at a single time point, one third of patients with significant fibrosis did not have NASH. We validated this finding in a separate cohort. In patients without NASH, fasting hyperglycemia, severe steatosis, mild inflammation or ballooning, and the PNPLA3 I148M variant identified those at risk of significant fibrosis.
Studies have produced conflicting results of the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus–associated cirrhosis treated with direct-acting antivirals (DAAs). Data ...from clinics are needed to accurately assess the occurrence rate of HCC in patients with cirrhosis in the real world.
We collected data from a large prospective study of 2,249 consecutive patients (mean age = 65.4 years, 56.9% male) with hepatitis C virus–associated cirrhosis (90.5% with Child-Pugh class A and 9.5% with Child-Pugh class B) treated with DAAs from March 2015 through July 2016 at 22 academic and community liver centers in Sicily, Italy. HCC occurrence was evaluated by Kaplan-Meier curves. Cox regression analysis was used to identify variables associated with HCC development.
A sustained virologic response (SVR) was achieved by 2,140 patients (total = 95.2%; 95.9% with Child Pugh class A and 88.3% with Child Pugh class B; P < .001). Seventy-eight patients (3.5%) developed HCC during a mean follow-up of 14 months (range = 6–24 months). At 1 year after exposure to DAAs, HCC developed in 2.1% of patients with Child-Pugh class A with an SVR and 6.6% of patients with no SVR and in 7.8% of patients with Child-Pugh class B with an SVR and 12.4% of patients with no SVR (P < .001 by log-rank test). Albumin level below 3.5 g/dL (hazard ratio = 1.77, 95% confidence interval = 1.12–2.82, P = .015), platelet count below 120 × 109/L (hazard ratio = 3.89, 95% confidence interval = 2.11–7.15, P < .001), and absence of an SVR (hazard ratio = 3.40, 95% confidence interval = 1.89–6.12, P < .001) were independently associated increased risk for HCC. The mean interval from exposure to DAAs to an HCC diagnosis was 9.8 months (range = 2–22 months) and did not differ significantly between patients with (n = 64, 9.2 months) and without (n = 14, 12.0 months) an SVR (P = .11). A larger proportion of patients with an SVR had a single HCC lesion (78% vs 50% without an SVR; P = .009) or an HCC lesion smaller than 3 cm (58% vs 28% without an SVR; P = .07).
In an analysis of data from a large prospective study of patients with hepatitis C virus–associated compensated or decompensated cirrhosis, we found that the SVR to DAA treatment decreased the incidence of HCC over a mean follow-up of 14 months.
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