AIMTo investigate the impact of physical frailty on risk of hospitalisation in cirrhotic patients on the liver transplant waitlist.METHODSCirrhotics listed for liver transplantation at a single centre underwent frailty assessments using the Fried Frailty Index, consisting of grip strength, gait speed, exhaustion, weight loss, and physical activity. Clinical and biochemical data including MELD score as collected at the time of assessment. The primary outcome was number of hospitalised days per year; secondary outcomes included incidence of infection. Univariable and multivariable analysis was performed using negative binomial regression to associate baseline parameters including frailty with clinical outcomes and estimated incidence rate ratios (IRR).RESULTSOf 587 cirrhotics, 64% were male, median age (interquartile range) was 60 (53-64) years and MELD score was 15 (12-18). Median Fried Frailty Index was 2 (1-3); 31.6% were classified as frail (fried frailty ≥ 3). During 12 mo of follow-up, 43% required at least 1 hospitalisation; 38% of which involved major infection. 107/184 (58%) frail and 142/399 (36%) non-frail patients were hospitalised at least once (P < 0.001). In univariable analysis, Fried Frailty Index was associated with total hospitalisation days per year (IRR = 1.51, 95%CI: 1.28-1.77; P ≤ 0.001), which remained significant on multivariable analysis after adjustment for MELD, albumin, and gender (IRR for frailty of 1.21, 95%CI: 1.02-1.44; P = 0.03). Incidence of infection was not influenced by frailty.CONCLUSIONIn cirrhotics on the liver transplant waitlist, physical frailty is a significant predictor of hospitalisation and total hospitalised days per year, independent of liver disease severity.

BackgroundHyperkyphosis, an excessive anterior curvature in the thoracic spine, is associated with reduced health status in older adults. Hyperkyphosis is highly prevalent, more common in older women than men. There is no standard intervention to reduce age-related hyperkyphosis. Sex differences in response to a kyphosis-specific exercise intervention are not known.MethodsWe conducted a randomized controlled trial of a targeted kyphosis-specific exercise and postural training program on the primary outcome Cobb angle of kyphosis, and investigated whether the magnitude of change differed between men and women. One hundred twelve participants aged ≥60 years with kyphosis ≥40° were enrolled and randomized to exercise or waitlist control, and 101 participants had analyzable baseline and follow-up radiographs for Cobb angle measurements. A group intervention including 10 participants per group was delivered by a physical therapist, 1-h, twice a week for 3-months. Controls were placed on a waitlist for 3 months before receiving a delayed intervention. Primary outcome was change from baseline to 3-months in Cobb angle measured from standing lateral spine radiographs. Secondary outcomes included change over 3-months in kyphometer-measured kyphosis, physical function and quality of life. Groups were combined for analysis after both received the intervention, and sex differences in response to the intervention were tested with ANOVA.ResultsParticipants (60 women, 41 men) were 70.0 (SD = 5.7) years old with mean Cobb angle 55.9 (SD = 12.2) degrees at baseline. The active group had higher baseline modified Physical Performance Test scores than control, p = 0.03. Men had greater baseline kyphometer-measured kyphosis, p = 0.09, and higher bone mineral density (BMD), spine strength, more vertebral fractures and diffuse idiopathic skeletal hyperostosis (DISH) than women, p ≤ 0.01. There was no statistically significant difference between groups in change in Cobb at 3-months, p = 0.09, however change in kyphometer-measured kyphosis differed by 4.8 (95% CI:-6.8,-2.7) degrees, p < 0.001, favoring the active group. There were no differences between men and women in change in either kyphosis measurement after intervention, p > 0.1.ConclusionsA 3-month targeted spine strengthening exercise and posture training program reduced kyphometer-measured, but not radiographic-measured kyphosis. Despite sex differences in baseline kyphosis, BMD, spine strength, fractures and DISH, sex did not affect treatment response.Trial registration ClinicalTrials.gov Identifier: NCT01766674.

Background. Acute upper respiratory tract infections are a common cause of emergency department (ED) visits and often result in unnecessary antibiotic treatment.Methods. We conducted a randomized clinical trial to evaluate the impact of a rapid, multipathogen respiratory panel (RP) test vs usual care (control). Patients were eligible if they were ≥12 months old, had symptoms of upper respiratory infection or influenzalike illness, and were not on antibiotics. The primary outcome was antibiotic prescription; secondary outcomes included antiviral prescription, disposition, and length of stay (ClinicalTrials.gov# NCT02957136).Results. Of 191 patients enrolled, 93 (49%) received RP testing; 98 (51%) received usual care. Fifty-three (57%) RP and 7 (7%) control patients had a virus detected and reported during the ED visit (P = .0001). Twenty (22%) RP patients and 33 (34%) usual care patients received antibiotics during the ED visit (-12%; 95% confidence interval, -25% to 0.4%; P = .06/0.08); 9 RP patients received antibiotics despite having a virus detected. The magnitude of antibiotic reduction was greater in children (-19%) vs adults (-9%, post hoc analysis). There was no difference in antiviral use, length of stay, or disposition.Conclusions. Rapid RP testing was associated with a trend toward decreased antibiotic use, suggesting a potential benefit from more rapid viral tests in the ED. Future studies should determine if specific groups are more likely to benefit from testing and evaluate the relative cost and effectiveness of broad testing, focused testing, and a combined diagnostic and antimicrobial stewardship approach.

Patients with hepatocellular carcinoma (HCC) within the University of California, San Francisco down-staging (UCSF-DS) criteria (one lesion > 5 cm and ≤ 8 cm; two to three lesions each ≤ 5 cm; or four to five lesions each ≤ 3 cm with total tumor diameter ≤ 8 cm) who achieved successful down-staging (DS) to Milan criteria had similar outcomes after liver transplantation (LT) compared with HCC initially meeting the Milan criteria. Nevertheless, little is known about the outcome of DS in patients with initial tumor burden exceeding the UCSF-DS criteria, defined as "all-comers" (AC). We compared the intention-to-treat (ITT) outcomes of DS in 74 patients in the AC group and 133 patients in the UCSF-DS group. Successful DS to Milan was observed in 64.8% of the AC group versus 84.2% of the UCSF-DS group (P < 0.001). The sum of tumor number and largest tumor diameter was significantly associated with successful DS (hazard ratio [HR] 0.87, P < 0.05). The cumulative probability of dropout within 1 year and 3 years was 53.5% and 80.0%, respectively, for AC versus 25.0% and 36.1%, respectively, for UCSF-DS (P < 0.0001). Factors predicting dropout included sum of tumor number and largest tumor diameter greater than 8 (HR 1.79, P = 0.049) and Child class B and C (HR 2.54, P = 0.001). The AC group also had a significantly lower liver transplant (LT) rate (13.5% versus 59.0%, P < 0.001). ITT survival at 1 year and 5 years was 77.4% and 21.1%, respectively, in AC versus 85.5% and 56.0%, respectively, in UCSF-DS (P < 0.001). Three of 10 patients in the AC group who underwent LT developed HCC recurrence. Conclusion: We observed a significantly lower LT probability and inferior ITT survival with DS in the AC group versus the UCSF-DS group. Our results suggest that an upper limit in tumor burden exists beyond which successful LT after DS becomes an unrealistic goal. (Hepatology 2019;70:1185-1196). F or over two decades, the Milan criteria have been the gold standard for selecting patients with hepatocellular carcinoma (HCC) for liver transplantation (LT). (1) Use of these restrictive criteria has ensured a low rate of HCC recurrence and an acceptable post-LT survival. (1-3) Nevertheless, with the rising incidence of HCC in the United States and the high mortality associated with the diagnosis, (4,5) the demand of LT as a potentially curative treatment for HCC has also increased. Multiple studies have proposed the use of local-regional therapy (LRT) for down-staging (DS) of HCC initially exceeding the

Aims There are numerous risk or screening scores for the prediction of type-2 diabetes mellitus (DM). In contrast, few scores are available for preDM. In this paper, we compare the two screening scores from the American Diabetes Association (ADA) and Centers for Disease Control and Prevention (CDC) that can be used for DM as well as preDM. Methods Adult participants (N=9,391) without known DM from the National Health and Nutrition Examination Surveys 2009–12 were included. We fitted the factors/items in the ADA and CDC scores in logistic regression with the outcomes of undiagnosed DM, preDM, and combination, and assessed the association and discrimination accuracy. We also evaluated the suggested cutpoints that define high risk individuals. We mimicked the original models/settings but also tested various deviations/modifications often encountered in practice. Results Both scores performed well and robustly, while the ADA score performed somewhat better (e.g., AUC=0.77 for ADA and 0.73–0.74 for CDC for DM; 0.72–0.74 and 0.70–0.71 for preDM). The same predictors and scoring rules seem to be reasonably justified with different cutpoints for DM and preDM, which can make usage easier and consistent. Some factors such as race and HDL/LDL cholesterols may be useful additions to health education. Conclusions Current DM education and screening focus on the prevention and management of DM. The ADA and CDC scores could further help when we identify individuals at high risk for preDM, and teach the importance of preDM during which lifestyle intervention can be effective and urgently needed.