Definition and Validation of the American College of Rheumatology 2021 Juvenile Arthritis Disease Activity Score Cutoffs for Disease Activity States in Juvenile Idiopathic Arthritis

Export Date: 16 February 2023; Cited By: 10Peer reviewe

Enteral lactoferrin supplementation for very preterm infants: a randomised placebo-controlled trial

Background Infections acquired in hospital are an important cause of morbidity and mortality in very preterm infants. Several small trials have suggested that supplementing the enteral diet of very preterm infants with lactoferrin, an antimicrobial protein processed from cow's milk, prevents infections and associated complications. The aim of this large randomised controlled trial was to collect data to enhance the validity and applicability of the evidence from previous trials to inform practice. Methods In this randomised placebo-controlled trial, we recruited very preterm infants born before 32 weeks' gestation in 37 UK hospitals and younger than 72 h at randomisation. Exclusion criteria were presence of a severe congenital anomaly, anticipated enteral fasting for longer than 14 days, or no realistic prospect of survival. Eligible infants were randomly assigned (1:1) to receive either enteral bovine lactoferrin (150 mg/kg per day; maximum 300 mg/day; lactoferrin group) or sucrose (same dose; control group) once daily until 34 weeks' postmenstrual age. Web-based randomisation minimised for recruitment site, gestation (completed weeks), sex, and single versus multifetal pregnancy. Parents, caregivers, and outcome assessors were unaware of group assignment. The primary outcome was microbiologically confirmed or clinically suspected late-onset infection (occurring >72 h after birth), which was assessed in all participants for whom primary outcome data was available by calculating the relative risk ratio with 95% CI between the two groups. The trial is registered with the International Standard Randomised Controlled Trial Number 88261002. Findings We recruited 2203 participants between May 7, 2014, and Sept 28, 2017, of whom 1099 were assigned to the lactoferrin group and 1104 to the control group. Four infants had consent withdrawn or unconfirmed, leaving 1098 infants in the lactoferrin group and 1101 in the sucrose group. Primary outcome data for 2182 infants (1093 [99·5%] of 1098 in the lactoferrin group and 1089 [99·0] of 1101 in the control group) were available for inclusion in the modified intention-to-treat analyses. 316 (29%) of 1093 infants in the intervention group acquired a late-onset infection versus 334 (31%) of 1089 in the control group. The risk ratio adjusted for minimisation factors was 0·95 (95% CI 0·86–1·04; p=0·233). During the trial there were 16 serious adverse events for infants in the lactoferrin group and 10 for infants in the control group. Two events in the lactoferrin group (one case of blood in stool and one death after intestinal perforation) were assessed as being possibly related to the trial intervention. Interpretation Enteral supplementation with bovine lactoferrin does not reduce the risk of late-onset infection in very preterm infants. These data do not support its routine use to prevent late-onset infection and associated morbidity or mortality in very preterm infants. Funding UK National Institute for Health Research Health Technology Assessment programme (10/57/49)

Enteral lactoferrin supplementation for very preterm infants: a randomised placebo-controlled trial

Background Infections acquired in hospital are an important cause of morbidity and mortality in very preterm infants. Several small trials have suggested that supplementing the enteral diet of very preterm infants with lactoferrin, an antimicrobial protein processed from cow's milk, prevents infections and associated complications. The aim of this large randomised controlled trial was to collect data to enhance the validity and applicability of the evidence from previous trials to inform practice. Methods In this randomised placebo-controlled trial, we recruited very preterm infants born before 32 weeks' gestation in 37 UK hospitals and younger than 72 h at randomisation. Exclusion criteria were presence of a severe congenital anomaly, anticipated enteral fasting for longer than 14 days, or no realistic prospect of survival. Eligible infants were randomly assigned (1:1) to receive either enteral bovine lactoferrin (150 mg/kg per day; maximum 300 mg/day; lactoferrin group) or sucrose (same dose; control group) once daily until 34 weeks' postmenstrual age. Web-based randomisation minimised for recruitment site, gestation (completed weeks), sex, and single versus multifetal pregnancy. Parents, caregivers, and outcome assessors were unaware of group assignment. The primary outcome was microbiologically confirmed or clinically suspected late-onset infection (occurring >72 h after birth), which was assessed in all participants for whom primary outcome data was available by calculating the relative risk ratio with 95% CI between the two groups. The trial is registered with the International Standard Randomised Controlled Trial Number 88261002. Findings We recruited 2203 participants between May 7, 2014, and Sept 28, 2017, of whom 1099 were assigned to the lactoferrin group and 1104 to the control group. Four infants had consent withdrawn or unconfirmed, leaving 1098 infants in the lactoferrin group and 1101 in the sucrose group. Primary outcome data for 2182 infants (1093 [99·5%] of 1098 in the lactoferrin group and 1089 [99·0] of 1101 in the control group) were available for inclusion in the modified intention-to-treat analyses. 316 (29%) of 1093 infants in the intervention group acquired a late-onset infection versus 334 (31%) of 1089 in the control group. The risk ratio adjusted for minimisation factors was 0·95 (95% CI 0·86–1·04; p=0·233). During the trial there were 16 serious adverse events for infants in the lactoferrin group and 10 for infants in the control group. Two events in the lactoferrin group (one case of blood in stool and one death after intestinal perforation) were assessed as being possibly related to the trial intervention. Interpretation Enteral supplementation with bovine lactoferrin does not reduce the risk of late-onset infection in very preterm infants. These data do not support its routine use to prevent late-onset infection and associated morbidity or mortality in very preterm infants. Funding UK National Institute for Health Research Health Technology Assessment programme (10/57/49)

Biophysical and electrochemical studies of protein-nucleic acid interactions

This review is devoted to biophysical and electrochemical methods used for studying protein-nucleic acid (NA) interactions. The importance of NA structure and protein-NA recognition for essential cellular processes, such as replication or transcription, is discussed to provide background for description of a range of biophysical chemistry methods that are applied to study a wide scope of protein-DNA and protein-RNA complexes. These techniques employ different detection principles with specific advantages and limitations and are often combined as mutually complementary approaches to provide a complete description of the interactions. Electrochemical methods have proven to be of great utility in such studies because they provide sensitive measurements and can be combined with other approaches that facilitate the protein-NA interactions. Recent applications of electrochemical methods in studies of protein-NA interactions are discussed in detail

Opportunistic infections in immunosuppressed patients with juvenile idiopathic arthritis: analysis by the Pharmachild Safety Adjudication Committee

Background To derive a list of opportunistic infections (OI) through the analysis of the juvenile idiopathic arthritis (JIA) patients in the Pharmachild registry by an independent Safety Adjudication Committee (SAC). Methods The SAC (3 pediatric rheumatologists and 2 pediatric infectious disease specialists) elaborated and approved by consensus a provisional list of OI for use in JIA. Through a 5 step-procedure, all the severe and serious infections, classified as per MedDRA dictionary and retrieved in the Pharmachild registry, were evaluated by the SAC by answering six questions and adjudicated with the agreement of 3/5 specialists. A final evidence-based list of OI resulted by matching the adjudicated infections with the provisional list of OI. Results A total of 772 infectious events in 572 eligible patients, of which 335 serious/severe/very severe non-OI and 437 OI (any intensity/severity), according to the provisional list, were retrieved. Six hundred eighty-two of 772 (88.3%) were adjudicated as infections, of them 603/682 (88.4%) as common and 119/682 (17.4%) as OI by the SAC. Matching these 119 opportunistic events with the provisional list, 106 were confirmed by the SAC as OI, and among them infections by herpes viruses were the most frequent (68%), followed by tuberculosis (27.4%). The remaining events were divided in the groups of non-OI and possible/patient and/or pathogen-related OI. Conclusions We found a significant number of OI in JIA patients on immunosuppressive therapy. The proposed list of OI, created by consensus and validated in the Pharmachild cohort, could facilitate comparison among future pharmacovigilance studies

Genome-wide association study identifies risk loci for progressive chronic lymphocytic leukemia

Prognostication in patients with chronic lymphocytic leukemia (CLL) is challenging due to heterogeneity in clinical course. We hypothesize that constitutional genetic variation affects disease progression and could aid prognostication. Pooling data from seven studies incorporating 842 cases identifies two genomic locations associated with time from diagnosis to treatment, including 10q26.13 (rs736456, hazard ratio (HR) = 1.78, 95% confidence interval (CI) = 1.47–2.15; P = 2.71 × 10−9) and 6p (rs3778076, HR = 1.99, 95% CI = 1.55–2.55; P = 5.08 × 10−8), which are particularly powerful prognostic markers in patients with early stage CLL otherwise characterized by low-risk features. Expression quantitative trait loci analysis identifies putative functional genes implicated in modulating B-cell receptor or innate immune responses, key pathways in CLL pathogenesis. In this work we identify rs736456 and rs3778076 as prognostic in CLL, demonstrating that disease progression is determined by constitutional genetic variation as well as known somatic drivers

Wpływ wypasu bydła i owiec na ekosystemy trawiaste Parku Narodowego Vel'ká Fatra

The Vel'ká Fatra National Park (declared on 1 April 2002) is extending on an area of 40,371 ha and was established to protect well-preserved ecosystems. The Vel'ká Fatra (Greater Fatra) with the highest peak Ostredok (1592 m altitude) is a typical mountain territory and ranks among the highest mountain ranges in Slovakia. Grassland areas above the forest line ("hole" in Slovak) and highland relief are typical for Vel'ká Fatra where forests cover is 85% of the area. Large areas of grassland located on gently modelled ridges resulted from deforestation many centuries ago. The alpine meadows which are rich in rare plant communities cover the area of 2000 ha. In the past, these grasslands were used by cutting and grazing. Nowadays, the meadows are not mowed at all. The reasons are low numbers of ruminants in nearby farms, high cost and poor access roads that are eroded very much. Grazing with young cattle has been banned and consequently tall grasses expanded, swards thinned as well as avalanche risk increased. Currently, it is allowed to graze young cattle again, but farmers do not exploit this option very much. About 200 heifers and 2,500 sheep graze there, but only at the lowest areas of the mountains and for short periods of time. The grassland is dominated by Deschampsia caespitosa (L.) P. Beauv. and also by very rapidly expanding Calamagrostis epigejos (L.) Roth, Brachypodium pinnatum (L.) P. Beauv. and Cirsium arvense (L.) Scop. indicating a prolonged period of abandonment.Park Narodowy Vel'ká Fatra ustanowiony 1 kwietnia 2002 r. dla ochrony dobrze zachowanych ekosystemów zajmuje powierzchnię 40 371 ha. Vel'ká Fatra (Większa Fatra) z najwyższym szczytem Ostredok (1592 m n.p.m.) jest typowym obszarem górskim i zalicza się do najwyższych grzbietów górskich Słowacji. Charakterystyczne dla parku są ekosystemy trawiaste położone powyżej linii lasów ("hole" w języku słowackim), porastających 85% obszaru i wysokogórskie ukształtowanie terenu. Rozległe obszary trawiaste, usytuowane na łagodnie uformowanych grzbietach, są wynikiem wylesiania, które miało miejsce wiele wieków temu. Alpejskie łąki, bogate w zespoły rzadkich roślin, pokrywają powierzchnię 2000 ha. W przeszłości były wykorzystywane jako użytki zielone. Obecnie łąki nie są koszone. Powodem jest niewielka liczba przeżuwaczy w okolicznych gospodarstwach, wysoki koszt i uciążliwy transport na silnie zerodowanych drogach. Zakazano wypasu młodego bydła. W konsekwencji rozwinęły się zespoły wysokich traw, ruń została przerzedzona i zwiększyło się ryzyko lawinowe. Obecnie zezwala się ponownie na wypas młodego bydła, ale rolnicy nie korzystają powszechnie z tej możliwości. Wypasa się tam jedynie 200 jałówek i 2500 owiec jedynie w najniżej położonych terenach górskich przez krótki okres. Zespoły trawiaste są zdominowane przez Deschampsia caespitosa (L.) P. Beauv. i przez bardzo ekspansywne Calamagrostis epigejos (L.) Roth, Brachypodium pinnatum (L.) P. Beauv. and Cirsium arvense (L.) Scop., co wskazuje na wydłużony okres zaniechania użytkowania