Utility and safety of plasma exchange in paediatric neuroimmune disorders.

AIM: Our aim was to ascertain the indications, side effects, and outcomes in children receiving therapeutic plasma exchange (TPE) for neurological disorders. METHOD: Medical records were retrospectively reviewed for 58 consecutive children (age ≤16y) undergoing 67 courses of TPE across four tertiary centres. Patient characteristics, treatment schedules, complications, and outcomes were analysed. RESULTS: Median age at initiation of TPE was 9 years (range 1-15y). Indications included peripheral nervous system (PNS; n=18) and central nervous system (CNS; n=40) disorders. Courses comprised a median six exchanges (range 2-179) over 8 days (range 3-466). Forty-two out of 58 (73%) children were severely disabled (bedridden) at initiation and 24 out of 58 (41%) were admitted to intensive care units. Treating clinicians' impression of response was positive in 16 out of 18 of those with PNS disorders versus 22 out of 40 with CNS disorders (p=0.016). Improvements in disability (modified Rankin Scale) occurred in 13 out of 58 (22%) children by completion of TPE (p=0.003). Complications occurred in 40 out of 67 (60%) courses, of which 16 out of 67 (24%) were line related. Potentially life-threatening complications occurred in 2 out of 67 (3%) courses. INTERPRETATION: This cohort study provides safety and efficacy information for clinicians and families and a basis for future prospective studies. WHAT THIS PAPER ADDS: Disability scores for severe neuroimmune disorders remained stable or improved during therapeutic plasma exchange treatment. Complications occurred frequently but were typically mild and correctable.

UTILIDAD Y SEGURIDAD DEL INTERCAMBIO DE PLASMA EN TRASTORNOS NEUROINMUNES PEDIÁTRICOS: OBJETIVO: Nuestro objetivo fue determinar las indicaciones, los efectos secundarios y los resultados en niños que recibieron intercambio terapéutico de plasma (TPE) para trastornos neurológicos. MÉTODO: Se revisaron retrospectivamente los registros médicos de 58 niños consecutivos (≤16 años) que se sometieron a 67 cursos de TPE en cuatro centros terciarios. Se analizaron las características de los pacientes, los esquemas de tratamiento, las complicaciones y los resultados. RESULTADOS: La edad mediana al inicio de la TPE fue de 9 años (rango 1-15 años). Las indicaciones incluían trastornos del sistema nervioso periférico (SNP; n = 18) y del sistema nervioso central (SNC; n = 40). Los cursos comprendieron una mediana de 6 intercambios (rango 2-179) durante 8 días (rango 3-466). Cuarenta y dos de 58 (73%) niños presentaban un grado de discapacidad severa (postrados en cama) al inicio y 24 de 58 (41%) fueron ingresados en unidades de cuidados intensivos. El tratamiento de la impresión de respuesta de los médicos fue positivo en 16 de 18 de las personas con trastornos de SNP versus 22 de 40 en trastornos del SNC (p = 0,016). Las mejoras en la discapacidad (escala de Rankin modificada) se produjeron en 13 de los 58 (22%) niños al completar el TPE (p = 0,003). Las complicaciones ocurrieron en 40 de 67 cursos (60%), de los cuales 16 de 67 (24%) estaban relacionados con la línea. Complicaciones potencialmente peligrosas para la vida ocurrieron en 2 de 67 (3%) cursos. INTERPRETACIÓN: Este estudio de cohorte proporciona información de seguridad y eficacia para profesionales y familiares y una base para futuros estudios prospectivos.

UTILIDADE E SEGURANÇA DA TRANSFERÊNCIA DE PLASMA EM TRANSTORNOS NEUROIMUNES PEDIÁTRICOS: OBJETIVO: Nosso objetivo foi verificar as indicações, efeitos colaterais, e resultados em crianças recebendo transferência terapêutica de plasma (TTP) para transtornos neurológicos. MÉTODO: Registros médicos foram retrospectivamente revisados para 58 crianças (idade ≤16a) passando por 67 cursos de TTP em quatro centros terciários. Características dos pacientes, rotina de tratamento, complicações e resultados foram analisados. RESULTADOS: A idade mediana ao início da TTP foi 9 anos (variação 1-15 anos). Indicações incluíram transtornos do sistema nervoso periférico (SNP; n = 18) e sistema nervoso central (SNC; n = 40) disorders. Os cursos compreenderam uma mediana de seis transferências (variação 2-179) em 8 dias (variação 3-466). Quarenta e duas em 58 (73%) crianças estavam severamente incapacidadas (acamadas) no início e 24 em 58 (41%) foram admitidas em unidades de cuidado intensivo. A impressão de resposta dos clínicos que as tratavam foi positiva em 16 de 18 daquelas com transtornos do SNP versus 22 de 40 daquelas com desordens do SNC (p = 0,016). Melhoras na incapacidade (Escala de Rankin modificada) ocorreram em 13 de 58 (22%) crianças ao final da TTP (p = 0,003). Complicações ocorreram em 40 de 67 (60%) cursos, dos quais 16 em 67 (24%) eram relacionados à linha. Complicações com potencial risco de vida ocorreram em 2 de 67 (3%) cursos. INTERPRETAÇÃO: Este estudo de coorte fornece informação sobre a segurança e eficácia para clínicos e famílias, e uma base para futuros estudos prospectivos.

Study protocol for a 9-month randomised controlled trial assessing the effects of almonds versus carbohydrate-rich snack foods on weight loss and weight maintenance.

INTRODUCTION: Epidemiological studies indicate an inverse association between nut consumption and body mass index (BMI). However, clinical trials evaluating the effects of nut consumption compared with a nut-free diet on adiposity have reported mixed findings with some studies reporting greater weight loss and others reporting no weight change. This paper describes the rationale and detailed protocol for a randomised controlled trial assessing whether the inclusion of almonds or carbohydrate-rich snacks in an otherwise nut-free energy-restricted diet will promote weight loss during 3 months of energy restriction and limit weight regain during 6 months of weight maintenance. METHODS AND ANALYSIS: One hundred and thirty-four adults aged 25-65 years with a BMI of 27.5-34.9 kg/m2 will be recruited and randomly allocated to either the almond-enriched diet (AED) (15% energy from almonds) or a nut-free control diet (NFD) (15% energy from carbohydrate-rich snack foods). Study snack foods will be provided. Weight loss will be achieved through a 30% energy restriction over 3 months, and weight maintenance will be encouraged for 6 months by increasing overall energy intake by ~120-180 kcal/day (~500-750kJ/day) as required. Food will be self-selected, based on recommendations from the study dietitian. Body composition, resting energy expenditure, total daily energy expenditure (via doubly labelled water), physical activity, appetite regulation, cardiometabolic health, gut microbiome, liver health, inflammatory factors, eating behaviours, mood and personality, functional mobility and pain, quality of life and sleep patterns will be measured throughout the 9-month trial. The effects of intervention on the outcome measures over time will be analysed using random effects mixed models, with treatment (AED or NFD) and time (baseline, 3 months and 9 months) being the between and within factors, respectively in the analysis. ETHICS AND DISSEMINATION: Ethics approval was obtained from the University of South Australia Human Research Ethics Committee (201436). Results from this trial will be disseminated through publication in peer-reviewed journals, national and international presentations. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12618001861246).

cGAS-mediated induction of type I interferon due to inborn errors of histone pre-mRNA processing.

Inappropriate stimulation or defective negative regulation of the type I interferon response can lead to autoinflammation. In genetically uncharacterized cases of the type I interferonopathy Aicardi-Goutières syndrome, we identified biallelic mutations in LSM11 and RNU7-1, which encode components of the replication-dependent histone pre-mRNA-processing complex. Mutations were associated with the misprocessing of canonical histone transcripts and a disturbance of linker histone stoichiometry. Additionally, we observed an altered distribution of nuclear cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) and enhanced interferon signaling mediated by the cGAS-stimulator of interferon genes (STING) pathway in patient-derived fibroblasts. Finally, we established that chromatin without linker histone stimulates cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) production in vitro more efficiently. We conclude that nuclear histones, as key constituents of chromatin, are essential in suppressing the immunogenicity of self-DNA.

A cardiac rehabilitation program to improve psychosocial outcomes of women with heart disease.

BACKGROUND AND AIMS: Heart disease in women is characterised by greater disability and a higher rate of morbidity and early death after an acute coronary event compared with men. Women also have lower participation rates than men in cardiac rehabilitation. This study sought to describe development of a nurse-directed cardiac rehabilitation program tailored to the needs of women following an acute cardiac event to address their psychological and social needs. METHODS: The Heart Awareness for Women program (HAFW) commenced in 2003 with phase I involving development of program elements and seeking validation through consumers and clinical experts. The program was then trialed in an 8-week program in a convenience sample of 6 women. Phase II applied the revised program using action research principles focusing on enabling clinical staff to implement the ongoing program. A total of 54 women participated in this phase, 48 of whom completed baseline questionnaires. A mixed-method evaluation, using questionnaires, interviews, and observation, assessed the impact of the intervention on psychological and social aspects of women's recovery following an acute coronary event. RESULTS: Women welcomed the opportunity to discuss their individual stories, fears, and challenges and to derive support from contact with other women. Via health professional facilitation, women were able to develop strategies collectively to address risk factor modification and achieve optimal cardiovascular health. No statistically significant changes in depression, anxiety, stress, cardiac control, role integration, or perceived social support were found; however, descriptive and qualitative findings revealed decreases in anxiety and an increased sense of social support. CONCLUSIONS: On the basis of this study, a cardiac rehabilitation program tailored to the needs of women appears to be feasible and acceptable. The efficacy of this intervention to improve health-related outcomes needs to be tested in a randomized, controlled trial.

Public Opinions on Strategies for Managing Stray Cats and Predictors of Opposition to Trap-Neuter and Return in Brisbane, Australia.

A survey of Brisbane residents was undertaken to investigate community attitudes toward urban stray cats and their management. Surveys were distributed to 84 medical and dental practices across Brisbane City, and were completed by 305 patients and staff. Practices were targeted to achieve a sample of respondents from a representative distribution of socioeconomic backgrounds. After being informed about trap, neuter, and return (TNR) programs for management of urban stray cats, most respondents (79%), chose TNR as their preferred management strategy, while a lesser proportion (18%) expressed a preference to continue the current Brisbane City Council lethal control program (catching and culling ~1,000 cats annually), and 3.4% selected to leave the cats alone. Differences in beliefs and attitudes toward urban stray cats as a function of demographic variables were investigated. Statistical analyses indicated that respondents who were male, older, non-cat owners, those who believed euthanasia of stray cats was humane, and that urban stray cats spread disease to humans were significantly more likely to express a preference for lethal control, as opposed to non-lethal population management. Based on these findings, we recommend that information is disseminated to mitigate these concerns or negative beliefs, where warranted. Ultimately, findings from this study demonstrate that current Queensland legislation does not reflect public views and opinions on stray cat management and should be reviewed. Formal research evaluating the efficacy of TNR programs for urban stray cats in Australia would be in the public interest.

Caring for others, but not themselves: implications for health care interventions in women with cardiovascular disease.

Cardiovascular disease is the largest killer of women internationally and women often suffer inferior outcomes following an acute cardiac event as compared to men. A gendered approach to investigating cardiovascular disease in women incorporates the unique social, cultural, and economic circumstances that being a woman brings to the health encounter. The multiple roles enacted by many women may be important factors in this health discrepancy. In order to more fully understand the impact of the roles of women on health, a questionnaire was administered to participants of the Heart Awareness for Women group cardiac rehabilitation program which assessed women's role perceptions followed by discussions. We found that caregiving can be both positive and negative. It gives a sense of purpose, meaning, and community connection as well as burden and conflict. Emphasis must be placed on promoting strategies in women to achieve a balance between caregiving responsibilities and prioritisation of cardiovascular health.

Influence of moving to the UK on maternal health behaviours: prospective cohort study.

OBJECTIVE: To compare health behaviours during pregnancy (smoking and alcohol consumption) and after birth (initiation and duration of breast feeding) between British/Irish white mothers and mothers from ethnic minority groups; and, in mothers from ethnic minority groups, to examine whether indicators of acculturation (generational status, language spoken at home, length of residency in the United Kingdom) were associated with these health behaviours. DESIGN: Prospective nationally representative cohort study. SETTING: England. PARTICIPANTS: 6478 British/Irish white mothers and 2110 mothers from ethnic minority groups. MAIN OUTCOME MEASURES: Any smoking during pregnancy; any alcohol consumption during pregnancy; initiation of breast feeding; breast feeding for at least four months. RESULTS: Compared with British/Irish white mothers, mothers from ethnic minority groups were less likely to smoke (15% v 37%) or consume alcohol (14% v 37%) during pregnancy but more likely to initiate breast feeding (86% v 69%) and breast feed for at least four months (40% v 27%). Among mothers from ethnic minority groups, first and second generation mothers were more likely to smoke during pregnancy (odds ratio 3.85, 95% confidence interval 2.50 to 5.93, and 4.70, 2.49 to 8.90, respectively), less likely to initiate breast feeding (0.92, 0.88 to 0.97, and 0.86, 0.75 to 0.99), and less likely to breast feed for at least four months (0.72, 0.62 to 0.83, and 0.52, 0.30 to 0.89) than immigrants, after adjustment for sociodemographic characteristics. There were no consistent differences in alcohol consumption. Among immigrants, for every additional five years spent in the UK the likelihood of mothers smoking during pregnancy increased by 31% (4% to 66%) and they were 5% (0% to 10%) less likely to breast feed for at least four months. CONCLUSIONS: After immigration, maternal health behaviours worsen with length of residency in the UK. Health professionals should not underestimate women's likelihood of engaging in risky health behaviours because of their ethnicity.