The importance of children and young person involvement in scoping the need for a paediatric glucocorticoid-associated patient reported outcome measure.

BACKGROUND: For many children and young people (CYP) with paediatric rheumatic conditions, glucocorticoid medications and their associated side-effects have a substantial impact on disease experience. Whilst there are physician-rated measures of glucocorticoid toxicity, no parallel patient reported measure has been developed to date for CYP with rheumatic disease. This manuscript describes a series of public patient involvement (PPI) events to inform the development of a future paediatric glucocorticoid-associated patient reported outcome measure (PROM). METHODS: One large group PPI event was advertised to CYP with experience of glucocorticoid medication use and their parents through clinicians, charities and existing PPI groups. This featured education on the team's research into glucocorticoid medication and interactive polls/structured discussion to help participants share their experiences. Further engagement was sought for PPI group work to co-develop future glucocorticoid studies, including development of a glucocorticoid associated PROM. Quantitative and qualitative feedback was collected from online questionnaires. The initiative was held virtually due to the Covid-19 pandemic. RESULTS: Nine families (n = 15) including 6 CYP joined the large group PPI event. Online pre-attendance and post-attendance questionnaires showed improvement in mean self-reported confidence [1 = not at all confident, 5 = very confident] in the following: what steroid medications are (pre = 3.9, post = 4.8), steroid side effects (pre = 3.8, post = 4.6), patient-reported outcome measures (pre = 2.0, post = 4.5), available research on steroids (pre = 2.2, post = 3.5). Five families (n = 7) were involved in a monthly PPI group who worked alongside the research team to identify priorities in glucocorticoid research, produce age-appropriate study materials, identify barriers to study participation (e.g. accessibility & convenience) and recommend appropriate modalities for dissemination. The participants found discussing shared experiences and learning about research to be the most enjoyable aspects of the initiative. CONCLUSIONS: This PPI initiative provided a valuable forum for families, including young children, to share their perspectives. Here, the authors explore the effective use of PPI in a virtual setting and provide a unique case study for the involvement of CYP in PROM development. The monthly PPI group also identified a need for the development of a new PROM related to glucocorticoid medication use and provided unique insights into how such a study could be structured.

Ethanol effects of NMDA-stimulated levels of extracellular neurotransmitters by in vivo microdialysis.

To determine whether the inhibition of NMDA receptor function by ethanol observed in vitro may be reflected in vivo, we measured the effects of ethanol administration on levels of extracellular dopamine (DA) using a microdialysis method. Rats were implanted with a guide cannula under anesthesia one week prior to placement of a microdialysis probe into the striatum. At a perfusion rate of 2 microliters/min recovery of DA from a standard solution was typically 20-25%. Basal levels of dialysate DA were approximately 0.5 pg/microliter. NMDA infusion into the striatum of an awake rat caused a concentration-dependent stimulation of extracellular DA levels. A one hour infusion of NMDA caused increases in dialysate DA from 2.3-50 fold over basal at concentrations from 0.3-10 mM. MK-801 (25 microM), AP-5 (10 microM), and DNQX (10 microM) significantly inhibited the stimulation of extracellular DA levels by 1 mM NMDA for 10 minutes. This suggests complex regulation of extracellular DA levels in the striatum by NMDA. Ethanol (0.5-3 g/kg, i.p.) did not alter the extracellular DA levels in the striatum. Furthermore, ethanol administration had no significant effects on DA levels in striatal dialysates when stimulated by infusion of 1 mM NMDA for 10 minutes. Our results suggest that ethanol's actions on extracellular DA levels in vivo in the striatum may not be predicted from a single effect of ethanol on one transmitter receptor system but depend on the integration of multiple signals in this brain region.

Cholinergic modulation of N-methyl-D-aspartate-evoked [3H]norepinephrine release from rat cortical slices.

Previous work has shown that N-methyl-D-aspartate (NMDA) receptor activation inhibits muscarinic receptor-mediated phosphoinositide hydrolysis in brain slices. To further explore the potential interactions between NMDA receptors and cholinergic receptors, the effects of cholinergic agonists and NMDA on [3H]norepinephrine (NE) release from rat cortical slices were determined. Slices were labeled with [3H]NE, washed and treated with various agonists by transferring the slices through a series of vials at 1-min intervals. Radioactivity remaining in the medium was then quantitated to determine the fractional release of [3H]NE from the slices. Carbachol (30-3000 microM) slightly stimulated [3H]NE release from a basal level of 0.10 to approximately 0.35 fractional release by itself and significantly enhanced the effect of 250 microM NMDA (3.6 fractional release for NMDA and 5.3 for carbachol + NMDA) in a concentration-dependent manner. Carbachol (1 mM) increased the maximal response but had no effect on the EC50 of NMDA. Atropine (1 microM) significantly attenuated the effect of carbachol alone and the potentiation of NMDA-evoked [3H]NE release by carbachol, whereas d-tubocurarine (10 microM) inhibited the effect of carbachol alone but had no effect on the enhancement of the NMDA response by carbachol. Mecamylamine (100 microM) inhibited the effect of carbachol alone, but also inhibited the NMDA-evoked response with an IC50 of 16 microM. The nicotinic agonist, dimethylphenylpiperazinium (DMPP) stimulated [3H]NE release (approximately 0.4 fractional release at 30 microM) and also potentiated NMDA-stimulated [3H]NE release (2.0 above NMDA alone). d-Tubocurarine, but not atropine, partially inhibited DMPP-stimulated [3H]NE release, but neither antagonist altered the enhancement of NMDA-stimulated [3H]NE release by DMPP.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal transplantation at Hartford Hospital: results of combined and flexible immunosuppression.

1. Three groups of first cadaver kidney transplant recipients at Hartford Hospital were analyzed. All received AZA and P, and most received pretransplant blood transfusions. The first group, 41 patients transplanted from 1977-1979, had a 2 year graft survival of 49%; the second group, 72 patients transplanted from 1980 to 1984 had an emphasis on DR typing and 2-year graft survival of 61%. The third group had the addition of CsA (triple immunosuppression) from 1984 to October, 1988. These 200 patients had a 2-year graft survival of 87%. The 2-year patient survival was 82%, 85%, and 94% for the 3 groups, respectively. 2. Triple immunosuppression resulted in less frequent and less severe rejection activity. There was no increase in serious infection and no significant elevation in mean serum creatinine at a 2-year follow-up, when compared to a control group receiving AZA and P. 3. DST was used selectively for one haplotype living-related donor kidney transplants, and in HLA-identical sibling kidney transplantation. Triple immunosuppression was also used in living-related donor kidney transplants, but in a very low-dose range. Only 3 of 58 grafts in living-related donor kidney transplants have been lost in the past 4 years; none due to rejection. 4. OKT3 therapy has been used primarily for steroid-resistant rejection, usually resulting in reversal, but also in a significant increase in CMV infection. When an "OKT3 available" group of cadaver kidney transplant recipients was compared to a previous control group, OKT3 therapy did not appear to improve the overall results. 5. Patients receiving retransplantation experienced a better success rate than reported at many other centers, (72% graft survival at 2 years). The use of OKT3 or ATG and DR matching contributed to the success. 6. The average ATN rate for all perfused kidneys was 36%; 50% for those preserved longer than 28 hours. Imported kidneys preserved with Euro Collins solution had a 63% ATN rate versus 36% for locally procured kidneys. There was no significant difference in graft survival in patients with or without posttransplant ATN.

[Paper on sterilization in the family planning programs of Colombia: a national debate]. / El papel de la esterlizacion en los programas de planificacion familiar de Colombia: un debate nacional

PIP: During 1984, family planning became the object of heated public debate in Colombia. In particular, considerable controversy surrounded the practice of sterilization. In Colombia in 1980, 49% of married women were practicing family planning. The main protagonist has been Profamilia, an IPPF affliate, which runs clinics and advisory services throughout Colombia. Sterilization is performed quite extensively on men of at least 28 years and women of 25 with 3 living children. Further activities of Profamilia include community distribution and social marketing programs. Many of the health facilities used are those of the Ministry of Public Health. The Minister of Health responded to criticism levelled by the Catholic church and others by instituting an investigation into alleged practices of mass sterilization. Profamilia declared publicy that sterilization was performed only under certain conditions, after waiting periods, and under no circumstances with coersion. Various groups including medical associations publicy supported Profamilia. Although recognizing the need for families to be limited in size, religious and other commentators suggested that sterilization was often presented as a solution to family ills, and that it represented foreign involvement in Colombian social policy. The opposing opinions were that church-supported natural family planning was not an effective enough strategy. The ministry has resolved to invoke more stringent screening of women desiring sterilization to include natural family planning in its programs, and to deal with international organizations only on the ministry level. The number of sterilizations has diminished. The controversy helped to expose political weaknesses of Profamilia's programs (e.g. the use of monetary incentives; lack of supervision).^ieng