'The current mental health status of children and young people with JIA, and their wider family': a charity partner collaboration survey.

BACKGROUND: This paper presents insight into the scale of mental health concerns for families who have a child or young person with a diagnosis of Juvenile Idiopathic Arthritis (JIA) living in any of the four nations of the United Kingdom (UK). The study's objective is to share the current experiences of those that responded to a charity survey and consider future work to improve mental health support. METHODS: This work was initiated and led by five UK charity partner organisations working with families affected by JIA. Parents/carers of a child or young person with JIA, and young people with JIA, submitted self-completion online questionnaires. The questionnaire asked 19 core questions, with a focus on the mental health impact of having and living with a JIA diagnosis. Questionnaires were delivered via charity partner UK-wide mailing lists and social media. RESULTS: Questionnaire were completed by 291 participants over a 3-week period in February 2022. The majority of respondents were parents (229, 79%), 103 children had been diagnosed for over six years (35%), and 131 (45%) received shared care between paediatric rheumatology centres. In total, 168 (59%) children and young people with JIA had received, were currently receiving or were waiting for mental health support. Parents reported that their child's diagnosis impacted their own mental health (218, 82%). Children and young people reported never being offered mental health support during appointments for JIA (157, 54%), and 71 (50%) of these had never received support. CONCLUSION: Children and young people with JIA have significant mental health sequelae from their diagnosis. Our findings found that nearly 60% of our respondents have had or are requiring mental health support, with significant numbers of parents/carers reporting difficulties in accessing care for their child's mental health or their own mental health, due to their child's diagnosis. This unique collaborative charity-led study, illustrates the importance of timely and accessible mental health support. Further work is needed to understand why best practice guidance for mental health support is not being met consistently and to identify how to embed it into standard rheumatology care.

Convergent evolution of pain-inducing defensive venom components in spitting cobras.

Convergent evolution provides insights into the selective drivers underlying evolutionary change. Snake venoms, with a direct genetic basis and clearly defined functional phenotype, provide a model system for exploring the repeated evolution of adaptations. While snakes use venom primarily for predation, and venom composition often reflects diet specificity, three lineages of cobras have independently evolved the ability to spit venom at adversaries. Using gene, protein, and functional analyses, we show that the three spitting lineages possess venoms characterized by an up-regulation of phospholipase A2 (PLA2) toxins, which potentiate the action of preexisting venom cytotoxins to activate mammalian sensory neurons and cause enhanced pain. These repeated independent changes provide a fascinating example of convergent evolution across multiple phenotypic levels driven by selection for defense.

Putative ß-Barrel Outer Membrane Proteins of the Bovine Digital Dermatitis-Associated Treponemes: Identification, Functional Characterization, and Immunogenicity.

Bovine digital dermatitis (BDD), an infectious disease of the bovine foot with a predominant treponemal etiology, is a leading cause of lameness in dairy and beef herds worldwide. BDD is poorly responsive to antimicrobial therapy and exhibits a relapsing clinical course; an effective vaccine is therefore urgently sought. Using a reverse vaccinology approach, the present study surveyed the genomes of the three BDD-associated Treponema phylogroups for putative ß-barrel outer membrane proteins and considered their potential as vaccine candidates. Selection criteria included the presence of a signal peptidase I cleavage site, a predicted ß-barrel fold, and cross-phylogroup homology. Four candidate genes were overexpressed in Escherichia coli BL21(DE3), refolded, and purified. Consistent with their classification as ß-barrel OMPs, circular-dichroism spectroscopy revealed the adoption of a predominantly ß-sheet secondary structure. These recombinant proteins, when screened for their ability to adhere to immobilized extracellular matrix (ECM) components, exhibited a diverse range of ligand specificities. All four proteins specifically and dose dependently adhered to bovine fibrinogen. One recombinant protein was identified as a candidate diagnostic antigen (disease specificity, 75%). Finally, when adjuvanted with aluminum hydroxide and administered to BDD-naive calves using a prime-boost vaccination protocol, these proteins were immunogenic, eliciting specific IgG antibodies. In summary, we present the description of four putative treponemal ß-barrel OMPs that exhibit the characteristics of multispecific adhesins. The observed interactions with fibrinogen may be critical to host colonization and it is hypothesized that vaccination-induced antibody blockade of these interactions will impede treponemal virulence and thus be of therapeutic value.

A pilot interventional study to evaluate the impact of cholecalciferol treatment on HbA1c in type 1 diabetes (T1D).

BACKGROUND: Higher 25(OH)D3 levels are associated with lower HbA1c, but there are limited UK interventional trials assessing the effect of cholecalciferol on HbA1c. AIMS: (1) To assess the baseline 25(OH)D3 status in a Manchester cohort of children with type 1 diabetes (T1D). (2) To determine the effect of cholecalciferol administration on HbA1c. METHODS: Children with T1D attending routine clinic appointments over three months in late winter/early spring had blood samples taken with consent. Participants with a 25(OH)D3 level <50 nmol/L were treated with a one-off cholecalciferol dose of 100,000 (2-10 years) or 160,000 (>10 years) units. HbA1c levels before and after treatment were recorded. RESULTS: Vitamin D levels were obtained from 51 children. 35 were Caucasian, 11 South Asian and 5 from other ethnic groups. 42 were vitamin D deficient, but 2 were excluded from the analysis. All South Asian children were vitamin D deficient, with mean 25(OH)D3 of 28 nmol/L. In Caucasians, there was a negative relationship between baseline 25(OH)D3 level and HbA1c (r = -0.484, P < 0.01). In treated participants, there was no significant difference in mean HbA1c at 3 months (t = 1.010, P = 0.328) or at 1 year (t = -1.173, P = 0.248) before and after treatment. One-way ANCOVA, controlling for age, gender, ethnicity, BMI and diabetes duration showed no difference in Δ HbA1c level. CONCLUSION: We report important findings at baseline, but in children treated with a stat dose of cholecalciferol, there was no effect on HbA1c. Further studies with larger sample sizes and using maintenance therapy are required.

Percutaneous central venous catheters versus peripheral cannulae for delivery of parenteral nutrition in neonates.

BACKGROUND: Parenteral nutrition for neonates may be delivered via a short peripheral cannula or a central venous catheter. The latter may either be inserted via the umbilicus or percutaneously. Because of the complications associated with umbilical venous catheter use, many neonatal units prefer to use percutaneously inserted catheters following the initial stabilisation period. The method of parenteral nutrition delivery may affect nutrient input and consequently growth and development. Although potentially more difficult to place, percutaneous central venous catheters may be more stable than peripheral cannulae, and need less frequent replacement. These delivery methods may also be associated with different risks of adverse events, including acquired systemic infection and extravasation injury. OBJECTIVES: To determine the effect of infusion via a percutaneous central venous catheter versus a peripheral cannula on nutrient input, growth and development, and complications including systemic infection, or extravasation injuries in newborn infants who require parenteral nutrition. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2007), MEDLINE (1966 - February 2007), EMBASE (1980 - February 2007), conference proceedings, and previous reviews. SELECTION CRITERIA: Randomised controlled trials that compared the effect of delivering parenteral nutrition via a percutaneous central venous catheter versus a peripheral cannulae in neonates. DATA COLLECTION AND ANALYSIS: Data were extracted the data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by each author, and synthesis of data using relative risk, risk difference and mean difference. MAIN RESULTS: Four trials eligible for inclusion were found. These trials recruited a total of 368 infants and reported a number of different outcomes. One study showed that the use of a percutaneous central venous catheter was associated with a decreased risk of cumulative nutritional deficit during the trial period: Mean difference in the percentage of the prescribed nutritional intake actually received: -7.1% (95% confidence interval -11.02, -3.2). In another trial, infants in the percutaneous central venous catheter group needed significantly fewer catheters/cannulae per infant during the trial period: Mean difference in the number of catheters/cannulae per infant: -3.2 (95% confidence interval -5.13, -1.27). Meta-analysis of data from all four trials did not find any evidence of an effect on the incidence of systemic infection: Typical relative risk: 0.94 (95% confidence interval 0.70, 1.25); typical risk difference: -0.02 (95% confidence interval -0.12, 0.08). AUTHORS' CONCLUSIONS: Data from one small study suggest that the use of a percutaneous central venous catheter to deliver parenteral nutrition in newborn infants improves nutrient input. The significance of this in relation to long-term growth and developmental outcomes is unclear. Another study suggested that the use of a percutaneous central venous catheter rather than a peripheral cannula decreases the number of catheters/cannulae needed to deliver the nutrition. No evidence was found to suggest that percutaneous central venous catheter use increased the risk of adverse events, particularly systemic infection.

Thrombocytopenia among extremely low birth weight neonates: data from a multihospital healthcare system.

OBJECTIVES: Thrombocytopenia is common in neonatal intensive care units (NICU), with 18 to 35% of patients developing this problem before hospital discharge. It might be even more common among extremely low birth weight neonates (ELBW, < or = 1000 g birth weight). However, little is known about thrombocytopenia in the ELBW population. We sought to determine the incidence, timing, causes, platelet transfusions given, and outcomes of thrombocytopenia among ELBW neonates. STUDY DESIGN: We performed a cohort analysis of all 284 ELBW neonates born during 2003 and 2004 cared for in any of the Intermountain Healthcare level III NICUs. RESULTS: Multiple platelet counts were obtained in all 284 (range, 4 to 441 platelet counts/patient). Of the 284, 208 (73%) had one or more platelet counts < or =150 000/microl. Most were detected during the first days of life; 80% were detected during the first week and only 20% were detected thereafter. Thrombcytopenia was more common among the smallest patients; 85% incidence among those < or =800 g, 60% among those 801 to 900 g, and 53% among those 901 to 1000 g. Platelet transfusions were given to 129 of the 208 thrombocytopenic neonates. More than 90% were given prophylactically (the patient was not bleeding). The mortality rate among those that received platelet transfusions was twice that of those that received no platelet transfusions (P < 0.01). In 48% of cases, the cause of the thrombocytopenia went undiagnosed. The most common explanations were being small for gestational age or delivered to a hypertensive mother, DIC, bacterial infection, fungal infection, and necrotizing enterocolitis, respectively. CONCLUSIONS: We observed thrombocytopenia among ELBW neonates at a rate more than twice that reported among the general NICU population. Much remains to be discovered about the etiology and best treatments of thrombocytopenia among ELBW neonates.

Postnatal growth retardation: a universal problem in preterm infants.

BACKGROUND: Previous data from this unit suggest that postnatal growth retardation (PGR) is inevitable in preterm infants. However, the study was performed in a single level III neonatal intensive care unit and applicability of the findings to other level III or level I-II special care baby units was uncertain. OBJECTIVES: To examine postnatal hospital growth and to compare growth outcome in preterm infants discharged from four level III tertiary care units and 10 level I-II special care baby units in the former Northern Region of the United Kingdom. SUBJECTS/METHODS: Preterm infants (< or = 32 weeks gestation; < or = 1500 g) surviving to discharge were studied. Infants were weighed at birth and discharge. Body weight was converted into a z score using the British Foundation Growth Standards. To ascertain the degree of PGR, the z score at birth was subtracted from the z score at discharge. Data were evaluated using a combination of split plot (level III v I-II=main factor; individual centre=subfactor) and stepwise regression analyses. Results were considered significant at p < 0.05. RESULTS: A total of 659 (level III, n = 335; level I-II, n = 324) infants were admitted over a 24 month period (January 1998-December 1999). No differences were detected in birth characteristics, CRIB score (a measure of illness in the first 24 hours of life), length of hospital stay, weight gain, weight at discharge, or degree of PGR between infants discharged from level III and level I-II units. Significant variation was noted in length of hospital stay (approximately 35%; p < 0.001), weight gain (approximately 33%; p < 0.001), weight at discharge (approximately 20%; p < 0.001), and degree of PGR (approximately 200%; p < 0.001) between the level III units. Even greater variability was noted in the duration of hospital stay (approximately 40%; p < 0.001), weight gain (approximately 60%; p < 0.001), weight at discharge (approximately 40%, p < 0.001), and degree of PGR (approximately 300%, p < 0.001) between the level I-II units. CONCLUSIONS: These data stress the variable but universal nature of PGR in preterm infants discharged from level III and I-II neonatal intensive care units and raise important questions about nutritional support of these infants before and after hospital discharge.

Percutaneous central venous catheters versus peripheral cannulae for delivery of parenteral nutrition in neonates.

BACKGROUND: Parenteral nutrition for newborn infants may be delivered via short peripheral cannulae or central venous catheters, which are usually sited percutaneously. The method of delivery may affect nutrient input, and consequently growth and development. Although potentially more difficult to site, percutaneous central venous catheters may be more stable than peripheral cannulae, and need less frequent replacement. These methods may also be associated with different risks of adverse events, including acquired systemic infection and extravasation injury. OBJECTIVES: To review the evidence from randomised controlled trials that, in newborn infants who require parenteral nutrition, infusion via a percutaneous central venous catheter versus a peripheral cannula improves nutrient input, and growth and development, without increasing adverse consequences including systemic infection, or extravasation injuries. SEARCH STRATEGY: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2003), MEDLINE (1966 - October 2003), EMBASE (1980 - October 2003), conference proceedings, and previous reviews. SELECTION CRITERIA: Randomised controlled trials that compared the effect of delivering parenteral nutrition via percutaneous central venous catheters versus peripheral cannulae in newborn infants. DATA COLLECTION AND ANALYSIS: We extracted the data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by each author, and synthesis of data using relative risk, risk difference and mean difference. MAIN RESULTS: We found three trials eligible for inclusion. These recruited a total of 262 infants and reported a number of different outcomes. One study showed that the use of a percutaneous central venous catheter was associated with a decreased risk of cumulative nutritional deficit during the trial period: Mean difference in the percentage of the prescribed nutritional intake actually received: -7.1% (95% confidence interval -11.2, -3.2). In another trial, infants in the percutaneous central venous catheter group needed significantly fewer catheters/cannulae per infant during the trial period: Mean difference in the number of catheters/cannulae per infant: -3.2 (95% confidence interval -5.13, -1.27). Meta-analysis of data from two trials did not find any evidence of an effect on the incidence of systemic infection: Typical relative risk: 0.90 (95% confidence interval 0.62, 1.32); typical risk difference: -0.04 (95% confidence interval -0.17, 0.10). REVIEWERS' CONCLUSIONS: Data from one small study suggest that the use of percutaneous central venous catheters to deliver parenteral nutrition in newborn infants improves nutrient input. The significance of this in relation to longer-term growth and developmental outcomes is unclear. Another study suggested that the use of percutaneous central venous catheters rather than peripheral cannulae decreases the number of catheters/cannulae needed to deliver the nutrition. We have not found any evidence that percutaneous central venous catheter use increases the risk of adverse events, particularly systemic infection.

General practice. Resigned to the job.

More than half the GPs in the UK have said they will consider resigning from the NHS if the government will not agree improvements in their contracts. GPs have been threatening to resign from public healthcare in the UK for the past 90 years. In March 1948, 90 per cent of doctors voted against the proposed NHS. By September 1948, 90 per cent of GPs had signed up with the NHS. GPs' threats to resign need to be seen in the context of history.

Randomized comparative trial between percutaneous longlines and peripheral cannulae in the delivery of neonatal parenteral nutrition.

UNLABELLED: Percutaneously inserted central venous catheters (CVCs) are frequently used for parenteral nutrition (PN) in neonates. Catheter-related sepsis (CRS) is the most commonly reported complication. The aim of this study was to compare sepsis rates between neonates receiving PN by CVC and by peripheral cannula. Neonates were randomized to receive PN either by CVC or by peripheral cannula. Primary outcomes were sepsis rates and efficacy of PN delivery. Interim analysis (49 neonates) revealed no difference in sepsis rates (CVC group 46%, cannula group 40%, p = 0.57). There was a significant discrepancy in PN delivered (median deficit 3.2% in the CVC group, 10.3% in the cannula group, p=0.0014). After consideration of these findings the study was terminated. CONCLUSION: Because the trial was stopped early, small but clinically important differences in the rates of sepsis may have been missed. Neonates in the cannula group accrued significant deficits of PN owing to a lack of venous access. This may contribute to undernutrition in neonates. CVC can be advocated for PN administration, in that sepsis appears to be no higher than when using cannulae and delivery of nutrition is significantly better.

Animal-derived or synthetic surfactant for the treatment of neonatal respiratory distress syndrome: a review.

Animal-derived surfactants containing SP-B and SP-C are more effective in vitro and in animal models than their synthetic counterparts, but are not as effective as unmodified, naturally occurring surfactant. In clinical trials involving newborn babies with respiratory distress syndrome (RDS) these short-term differences are reflected as improvements in gas exchange and lung function. Treatment with animal-derived surfactants results in fewer air leaks and lower neonatal mortality. The evidence is now strong enough to recommend routine use of animal-derived surfactants in very preterm infants with RDS. The newer generation of synthetic surfactants may be important in the future as they have the advantages of currently available animal products with the addition of better resistance to inactivation.

Risk perception and cigar smoking behavior.

OBJECTIVE: To examine the cigar smoking perceptions and behaviors of US adults. METHODS: A national sample of 1,012 adults was interviewed by telephone. RESULTS: Current cigar smokers differed from nonsmokers in perceptions of personal risk for cancer and views about cigar smoking as a cancer cause. Both groups showed substantial acceptance of the glamorized image of cigarsmokers. CONCLUSION: Although recognizing smoking as a cancer cause in general, cigar smokers tended to show a self-exempting "optimistic bias" with regard to perceptions of their own risks.

Health risks associated with cigar smoking.

This article summarizes principal findings from a conference convened by the American Cancer Society in June 1998 to examine the health risks of cigar smoking. State-of-the-science reports were presented and 120 attendees (representing government and private agencies, academia, health educators, and tobacco control experts) participated in panels and summary development discussions. The following conclusions were reached by consensus: (1) rates of cigar smoking are rising among both adults and adolescents; (2) smoking cigars instead of cigarettes does not reduce the risk of nicotine addiction; (3) as the number of cigars smoked and the amount of smoke inhaled increases, the risk of death related to cigar smoking approaches that of cigarette smoking; (4) cigar smoke contains higher concentrations of toxic and carcinogenic compounds than cigarettes and is a major source of fine-particle and carbon monoxide indoor air pollution; and (5) cigar smoking is known to cause cancers of the lung and upper aerodigestive tract. JAMA. 2000;284:735-740

Pumactant and poractant alfa for treatment of respiratory distress syndrome in neonates born at 25-29 weeks' gestation: a randomised trial.

BACKGROUND: Exogenous surfactant preparations vary in their constitution and biophysical properties. Synthetic and animal-derived preparations lower the rate of death compared with controls. No significant differences in mortality or important long-term clinical outcomes have been shown between them in randomised trials. We did a randomised controlled trial to compare pumactant, a synthetic surfactant, with poractant alfa, an animal-derived surfactant, both of which are widely used in the UK. METHODS: We enrolled 212 neonates born between 25 weeks' and 29 weeks and 6 days' gestation who were intubated for presumed surfactant deficiency and were free from life-threatening malformations. We randomly assigned 105 neonates poractant alfa, and 107 pumactant. The primary outcome was duration of high-dependency care and mortality was a secondary outcome. Analysis was by intention to treat. FINDINGS: Outcome data were analysed for 199 babies. The trial was stopped on the recommendation of the data and safety monitoring committee because mortality assumed a greater importance than the primary outcome. Predischarge mortality differed significantly between groups, in favour of poractant alfa (14.1 vs 31.0%, p=0.006; odds ratio 0.37 [95% CI 0.18-0.76). This difference was sustained after adjustment for centre, gestation, birthweight, sex, plurality, and use of antenatal steroids. INTERPRETATION: Mortality was unexpectedly lower among neonates who received poractant alfa than among those who received pumactant, and was independent of all the variables we investigated. Stopping the trial early may have widened the difference between the treatment groups.

NHS reorganisation. A rose-tinted spectacle.

The 1974 reorganisation of the NHS was the most radical to date. It abolished the involvement of local authorities in health, set up community health councils, introduced area health authorities and changed the management of family doctor services. The changes increased the power of hospitals.

Analysis of the immunological responses to transferrin and lactoferrin receptor proteins from Moraxella catarrhalis.

Moraxella catarrhalis expresses surface receptor proteins that specifically bind host transferrin (Tf) and lactoferrin (Lf) in the first step of the iron acquisition pathway. Acute- and convalescent-phase antisera from a series of patients with M. catarrhalis pulmonary infections were tested against Tf and Lf receptor proteins purified from the corresponding isolates. After the purified proteins had been separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting, we observed strong reactivity against Tf-binding protein B (TbpB; also called OMP1) and Lf-binding protein B (LbpB) but little or no reactivity against Tf-binding protein A (TbpA) or Lf-binding protein A (LbpA), using the convalescent-phase antisera. Considerable antigenic heterogeneity was observed when TbpBs and LbpBs isolated from different strains were tested with the convalescent-phase antisera. Comparison to the reactivity against electroblotted total cellular proteins revealed that the immune response against LbpB and TbpB constitutes a significant portion of the total detectable immune response to M. catarrhalis proteins. Preparations of affinity-isolated TbpA and LbpA reacted with convalescent-phase antisera in a solid-phase binding assay, but blocking with soluble TbpB, soluble LbpB, or extracts from an LbpA(-) mutant demonstrated that this reactivity was attributed to contaminants in the TbpA and LbpA preparations. These studies demonstrate the immunogenicity of M. catarrhalis TbpB and LbpB in humans and support their potential as vaccine candidates.