Retrospective studies suggest that online hemodiafiltration (OL-HDF) may reduce the risk of mortality compared with standard hemodialysis in patients with ESRD. We conducted a multicenter, ...open-label, randomized controlled trial in which we assigned 906 chronic hemodialysis patients either to continue hemodialysis (n=450) or to switch to high-efficiency postdilution OL-HDF (n=456). The primary outcome was all-cause mortality, and secondary outcomes included cardiovascular mortality, all-cause hospitalization, treatment tolerability, and laboratory data. Compared with patients who continued on hemodialysis, those assigned to OL-HDF had a 30% lower risk of all-cause mortality (hazard ratio HR, 0.70; 95% confidence interval 95% CI, 0.53-0.92; P=0.01), a 33% lower risk of cardiovascular mortality (HR, 0.67; 95% CI, 0.44-1.02; P=0.06), and a 55% lower risk of infection-related mortality (HR, 0.45; 95% CI, 0.21-0.96; P=0.03). The estimated number needed to treat suggested that switching eight patients from hemodialysis to OL-HDF may prevent one annual death. The incidence rates of dialysis sessions complicated by hypotension and of all-cause hospitalization were lower in patients assigned to OL-HDF. In conclusion, high-efficiency postdilution OL-HDF reduces all-cause mortality compared with conventional hemodialysis.
Mortality rates remain high for haemodialysis (HD) patients and simply increasing the HD dose to remove more small solutes does not improve survival. Online haemodiafiltration (HDF) provides ...additional clearance of larger toxins compared with standard HD. Randomized controlled trials (RCTs) comparing HDF with conventional HD on all-cause and cause-specific mortality in end-stage kidney disease (ESKD) patients reported inconsistent results and were at high risk of bias. We conducted a pooled individual participant data analysis of RCTs to provide the most reliable evidence to date on the effects of HDF on mortality outcomes in ESKD patients.
Individual participant data were used from four trials that compared online HDF with HD and were designed to examine the effects of HDF on mortality endpoints. Bias by informative censoring of patients was resolved. Hazard ratios (HRs) and 95% confidence intervals (95% CI) comparing the effect of online HDF versus HD on all-cause and cause-specific mortality were calculated using the Cox proportional hazard regression models. The relationship between convection volume and the study outcomes was examined by delivered convection volume standardized to body surface area.
After a median follow-up of 2.5 years (Q1-Q3: 1.9-3.0), 769 of the 2793 participants had died (292 cardiovascular deaths). Online HDF reduced the risk of all-cause mortality by 14% (95% CI: 1%; 25%) and cardiovascular mortality by 23% (95% CI: 3%; 39%). There was no evidence for a differential effect in subgroups. The largest survival benefit was for patients receiving the highest delivered convection volume >23 L per 1.73 m(2) body surface area (BSA) per session, with a multivariable-adjusted HR of 0.78 (95% CI: 0.62; 0.98) for all-cause mortality and 0.69 (95% CI: 0.47; 1.00) for cardiovascular disease mortality.
This pooled individual participant analysis on the effects of online HDF compared with conventional HD indicates that online HDF reduces the risk of mortality in ESKD patients. This effect holds across a variety of important clinical subgroups of patients and is most pronounced for those receiving a higher convection volume normalized to BSA.
Alport syndrome is a common genetic kidney disease accounting for approximately 2% of patients receiving kidney replacement therapy (KRT). It is caused by pathogenic variants in the gene COL4A3, ...COL4A4, or COL4A5. The aim of this study was to evaluate the clinical and genetic spectrum of patients with autosomal dominant Alport syndrome (ADAS).
Retrospective cohort study.
82 families (252 patients) with ADAS were studied. Clinical, genetic, laboratory, and pathology data were collected.
A pathogenic DNA variant in COL4A3 was identified in 107 patients (35 families), whereas 133 harbored a pathogenic variant in COL4A4 (43 families). Digenic/complex inheritance was observed in 12 patients. Overall, the median kidney survival was 67 (95% CI, 58-73) years, without significant differences across sex (P=0.8), causative genes (P=0.6), or type of variant (P=0.9). Microhematuria was the most common kidney manifestation (92.1%), and extrarenal features were rare. Findings on kidney biopsies ranged from normal to focal segmental glomerulosclerosis. The slope of estimated glomerular filtration rate change was−1.46 (−1.66 to−1.26) mL/min/1.73m2 per year for the overall group, with no significant differences between ADAS genes (P=0.2).
The relatively small size of this series from a single country, potentially limiting generalizability.
Patients with ADAS have a wide spectrum of clinical presentations, ranging from asymptomatic to kidney failure, a pattern not clearly related to the causative gene or type of variant. The diversity of ADAS phenotypes contributes to its underdiagnosis in clinical practice.
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With a global increased use of psychotropics in pediatrics, their off-label use is a concern due to uncertainty and risk. Data on psychotropics use in the Greek pediatric population do not exist to ...date. We analyzed retrospective data from the nationwide pharmacy claim database, to estimate the prevalence of psychotropics in pediatrics focusing on off-label use (March 2016-October 2019). In total 63,782 pediatric subjects had at least one identified psychotropic prescription. The prevalence of psychotropics use was 5.1-14.6/1,000 pediatric inhabitants. When excluding 42,508 subjects who received only short-time hydroxyzine, the prevalence was 3.1-6.5/1,000 pediatric inhabitants; adolescents and boys had higher exposures. An in-depth analysis of 21,274 subjects accounting for 222,307 psychotropic dispensations, showed antiepileptics as the most frequent psychotropics, consistently with the finding on epilepsy being the most frequent diagnosis; diazepam was the single drug with the highest exposure in almost all ages. 14% of subjects have received at least one medicine with no pediatric information in the labelling, corresponding to 5.5% of dispensed psychotropics. 7.6% of all dispensed psychotropics were used in a non-authorized age range with quetiapine being the most frequent psychotropic as off-label age range; antipsychotics and antidepressants were first as off-label for non-authorized indication. Data from Greece show that a relevant number of patients are prescribed psychotropics, with 1 in 7 being under off-label use. Due to the limitations inherent to pharmacy claims databases, further research using clinical data for a longer follow-up period could confirm and identify trends in psychotropics use in Greece.
Psychotropics are increasingly used in pediatrics, often as off-label medicines. The guarantees of safety and efficacy are not always granted in clinical practice compared to adult authorised ...indications. A retrospective observational study was done to estimate the prevalence of psychotropic use in pediatric subjects of Catalonia (Spain). Anonymised data on dispensation of psychotropics to pediatric patients, demography and other related data were obtained by the local healthcare management for the period 2008-2017. Estimation of off-label use was done through description of drug dispensations with no authorised use related to age range. The prevalence of psychotropics was 40.8-64.2 per 1,000 pediatric inhabitants. Hydroxyzine-only represented two-thirds of dispensations, and when removed, the prevalence dropped to 26.4-32.2 per 1,000 pediatric inhabitants. Adolescents and boys were more likely to receive a psychotropic. Psychostimulants had the highest exposure rate, mainly due to methylphenidate. Off-label use was observed in 12% of subjects, corresponding to 4.6% of all dispensed psychotropics with boys being more exposed. The proportion of off-label use vs. labelled use was higher in younger populations. Aripiprazole had the highest off-label frequency. Our data support the frequent reality of off-label use in pediatrics, despite the potential underestimation related to the selected off-label definition. There is an urgent need to systematically ascertain effectiveness and any potential adverse events in the off-label pediatric setting, and to generate valuable information for risk-benefit assessment in these populations where extrapolation from adults is not reliable.
Summary Introduction Uric acid is an antioxidant with neuroprotective effects in experimental models of stroke. We assessed whether uric acid therapy would improve functional outcomes at 90 days in ...patients with acute ischaemic stroke. Methods URICO-ICTUS was a randomised, double-blind, placebo-controlled, phase 2b/3 trial that recruited patients with acute ischaemic stroke admitted to ten Spanish stroke centres. Patients were included if they were aged 18 years or older, had received alteplase within 4·5 h of symptom onset, and had an eligible National Institutes of Health Stroke Scale (NIHSS) score (>6 and ≤25) and premorbid (assessed by anamnesis) modified Rankin Scale (mRS) score (≤2). Patients were randomly allocated (1:1) to receive uric acid 1000 mg or placebo (both infused intravenously in 90 min during the infusion of alteplase), stratified by centre and baseline stroke severity. The primary outcome was the proportion of patients with excellent outcome (ie, an mRS score of 0–1, or 2 if premorbid score was 2) at 90 days, analysed in the target population (all randomly assigned patients who had been correctly diagnosed with ischaemic stroke and had begun study medication). The study is registered with ClinicalTrials.gov , number NCT00860366. Findings Between July 1, 2011, and April 30, 2013, we randomly assigned 421 patients, of whom 411 (98%) were included in the target population (211 received uric acid and 200 received placebo). 83 (39%) patients who received uric acid and 66 (33%) patients who received placebo had an excellent outcome (adjusted risk ratio 1·23 95% CI 0·96–1·56; p=0·099). No clinically relevant or statistically significant differences were reported between groups with respect to death (28 13% patients who received uric acid vs 31 16% who received placebo), symptomatic intracerebral haemorrhage (nine 4% vs six 3%), and gouty arthritis (one <1% vs four 2%). 516 adverse events occurred in the uric acid group and 532 in the placebo group, of which 61 (12%) and 67 (13%), respectively, were serious adverse events (p=0·703). Interpretation The addition of uric acid to thrombolytic therapy did not increase the proportion of patients who achieved excellent outcome after stroke compared with placebo, but it did not lead to any safety concerns. Funding Institute of Health Carlos III of the Spanish Ministry of Health and Fundación Doctor Melchor Colet.
Abstract Background Data on long-term dietary changes and nutritional deficiencies after sleeve gastrectomy (SG) in grade 3 obese patients are scarce. Objective To prospectively compare dietary ...changes and nutritional deficiencies in grade 3 obese patients 5 years after SG and Roux-en-y gastric bypass (GBP). Participants/setting Three hundred and fifty-five patients who had SG (n=61) or GBP (n=294) (May 2001-December 2006) at a Spanish university hospital. Design Longitudinal, prospective, observational study. Primary outcomes/statistical analyses Changes in energy, macronutrient, and micronutrient intake, and weight loss were analyzed using mixed models for repeated measurements. Results At the 5-year follow-up visit, the percentage of excess weight loss ( P =0.420) and daily energy intake ( P =0.826), as well as the proportion of energy from carbohydrates ( P =0.303), protein ( P =0.600), and fat ( P =0.541) did not differ between surgical groups. Energy intake ( P =0.004), baseline weight ( P <0.001), and time period ( P <0.001), but not the proportion of different macronutrients or the type of surgery, independently predicted the percentage excess weight loss over time. After SG or GBP, the mean daily dietary intake of calcium, magnesium, phosphorus, and iron was less than the current recommendations. Despite universal supplementation, the prevalence of nutritional deficiencies was comparable after SG or GBP, with 25-hydroxyvitamin D being the most commonly observed deficiency (SG, 93.3% to 100%; GBP, 90.9% to 85.7%, P =not significant). In an adjusted multivariate regression model, energy intake and lipid intake independently predicted plasma 25(OH)-vitamin D levels. Conclusions Data show that SG and GBP are associated with similar long-term weight loss with no differences in terms of dietary intake. Furthermore, data demonstrate that both types of surgeries carry comparable nutritional consequences.
Reliable methods are needed to diagnose hypersensitivity pneumonitis. The aim of the study was to establish the diagnostic yield of specific inhalation challenge (SIC) in patients with ...hypersensitivity pneumonitis. All patients with suspected hypersensitivity pneumonitis in whom SIC was performed (n=113) were included. SIC was considered positive when patients showed a decrease of >15% in forced vital capacity (FVC) or >20% in diffusing capacity of the lung for carbon dioxide, or a decrease of 10% to 15% in FVC accompanied by a temperature increase of 0.5°C within 24 h of inhalation of the antigen. SIC was positive to the agents tested in 68 patients: 64 received a diagnosis of hypersensitivity pneumonitis and SIC results were considered false-positive in the remaining four patients. In the SIC-negative group (n=45), 24 patients received a diagnosis of hypersensitivity pneumonitis and SIC results were considered false-negative, and 21 patients were diagnosed with other respiratory diseases. The sensitivity and specificity of the test were 72.7% and 84%, respectively. Having hypersensitivity pneumonitis caused by an antigen other than birds or fungi predicted a false-negative result (p=0.001). In hypersensitivity pneumonitis, positive SIC testing virtually confirms the diagnosis, whereas negative testing does not rule it out, especially when the antigenic sources are not birds or fungi.
Stigmatization is a well-documented problem of some diseases. Perceived stigma is common in alcohol-related liver disease and hepatitis C, but little information exists on stigma in patients with ...non-alcoholic fatty liver disease (NAFLD). Aim of the study was to investigate frequency and characteristics of perceived stigma among patients with NAFLD.
One-hundred and ninety-seven patients seen at the liver clinic were included: a study group of 144 patients with NAFLD, 50 with cirrhosis (34 compensated, 16 decompensated), and a control group of 53 patients with alcohol-related cirrhosis. Demographic, clinical, and laboratory data were collected. Quality-of-life was assessed by chronic liver disease questionnaire (CLDQ). Perceived stigma was assessed using a specific questionnaire for patients with liver diseases categorized in 4 domains: stereotypes, discrimination, shame, and social isolation.
Perceived stigma was common in patients with NAFLD (99 patients, 69%) and affected all 4 domains assessed. The frequency was slightly higher, yet not significant, in patients with NAFLD cirrhosis vs those without (72% vs 67%, respectively; p = 0.576). In patients without cirrhosis perceived stigma was unrelated to stage of disease, since frequency was similar in patients with no or mild fibrosis compared to those with moderate/severe fibrosis (66% vs 68%, respectively). There were no differences in perceived stigma between patients with compensated cirrhosis and these with decompensated cirrhosis. Among patients with cirrhosis, stigmatization was more common in alcohol-related vs NAFLD-cirrhosis, yet differences were only significant in two domains. In patients with NAFLD, perceived stigma correlated with poor quality-of-life, but not with demographic or clinical variables.
Perceived stigmatization is common among patients with NAFLD independently of disease stage, is associated with impaired quality-of-life, and may be responsible for stereotypes, discrimination, shame, and social isolation, which may affect human and social rights of affected patients.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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