Randomized Clinical Trial Design to Assess Abatacept in Resistant Nephrotic Syndrome

Introduction: Treatment-resistant nephrotic syndrome is a rare form of glomerular disease that occurs in children and adults. No Food and Drug Administration−approved treatments consistently achieve remission of proteinuria and preservation of kidney function. CD80 (B7-1) can be expressed on injured podocytes, and administration of abatacept (modified CTLA4-Ig based on a natural ligand to CD80) has been associated with sustained normalization of urinary protein excretion and maintenance of glomerular filtration rate in experimental and clinical settings. Methods: In this report, we describe the rationale for and design of a randomized, placebo-controlled, clinical trial of abatacept in patients with treatment-resistant nephrotic syndrome caused by focal segmental glomerulosclerosis or minimal change disease. The design is a hybrid of a parallel-group and crossover design (switchover) with the primary objectives assessed in the first period of the study and the secondary objectives assessed using data from both periods. All participants will receive the active agent in 1 of the periods. The duration of treatment will be 4 months per period. Results: The primary outcome will be improvement in nephrotic-range proteinuria to subnephrotic range, that is, reduction from baseline to 4 months in urine protein:creatinine ratio ≥ 50% and to a level < 3. The projected sample size is 90 patients, which has 80% power to detect a treatment difference of 28%. Conclusion: This study advances efforts to validate CD80 as a therapeutic target for treatment-resistant nephrotic syndrome, and implements a precision medicine-based approach to this serious kidney condition in which the selection of a therapeutic agent is guided by the underlying disease mechanism operating in individual patients

The research landscape of tuberous sclerosis complex–associated neuropsychiatric disorders (TAND)—a comprehensive scoping review

Background Tuberous sclerosis complex (TSC)–associated neuropsychiatric disorders (TAND) is an umbrella term for the behavioural, psychiatric, intellectual, academic, neuropsychological and psychosocial manifestations of TSC. Although TAND affects 90% of individuals with TSC during their lifetime, these manifestations are relatively under-assessed, under-treated and under-researched. We performed a comprehensive scoping review of all TAND research to date (a) to describe the existing TAND research landscape and (b) to identify knowledge gaps to guide future TAND research. Methods The study was conducted in accordance with stages outlined within the Arksey and O’Malley scoping review framework. Ten research questions relating to study characteristics, research design and research content of TAND levels and clusters were examined. Results Of the 2841 returned searches, 230 articles published between 1987 and 2020 were included (animal studies = 30, case studies = 47, cohort studies = 153), with more than half published since the term TAND was coined in 2012 (118/230; 51%). Cohort studies largely involved children and/or adolescents (63%) as opposed to older adults (16%). Studies were represented across 341 individual research sites from 45 countries, the majority from the USA (89/341; 26%) and the UK (50/341; 15%). Only 48 research sites (14%) were within low–middle income countries (LMICs). Animal studies and case studies were of relatively high/high quality, but cohort studies showed significant variability. Of the 153 cohort studies, only 16 (10%) included interventions. None of these were non-pharmacological, and only 13 employed remote methodologies (e.g. telephone interviews, online surveys). Of all TAND clusters, the autism spectrum disorder–like cluster was the most widely researched (138/230; 60%) and the scholastic cluster the least (53/200; 27%). Conclusions Despite the recent increase in TAND research, studies that represent participants across the lifespan, LMIC research sites and non-pharmacological interventions were identified as future priorities. The quality of cohort studies requires improvement, to which the use of standardised direct behavioural assessments may contribute. In human studies, the academic level in particular warrants further investigation. Remote technologies could help to address many of the TAND knowledge gaps identified

What are You All Going to Do to Keep Black Women in Art Therapy?

In this viewpoint, the authors describe their impressions of a 2018 conference and the significance of participating in a learning environment that centered on arts therapists of color. Collectively, two art therapy educators, a music therapy educator, one new professional art therapist, and one art therapy graduate student, question the maintenance of professional norms that have at times motivated BIPOC students and practitioners to leave the creative arts therapies in search of other professional places to thrive. The article concludes with a Womanist Manifesto for Arts Therapies Education.Abstract&nbsp; In questa prospettiva, gli autori descrivono le loro impressioni su una conferenza del 2018 e l'importanza di partecipare a un ambiente di apprendimento incentrato sugli&nbsp;arteterapeuti&nbsp;di&nbsp;colore.&nbsp;Collettivamente, due educatori di arteterapia, un educatore di musicoterapia, un nuovo&nbsp;arteterapeuta&nbsp;professionista e uno studente laureato in arteterapia, mettono in dubbio il mantenimento di norme professionali che&nbsp;talvolta&nbsp;motivano&nbsp;studenti e professionisti BIPOC a lasciare le&nbsp;artiterapie creative&nbsp;in cerca&nbsp;di altre&nbsp;strade&nbsp;professionali in cui prosperare.&nbsp;L'articolo si conclude con un Manifesto&nbsp;‘Womanist’&nbsp;per le artiterapie educative.&nbsp;Abstract&nbsp; In diesem Standpunkt beschreiben die&nbsp;AutorInnen&nbsp;ihre Eindrücke von einer Konferenz im Jahr 2018 und die Bedeutung der Teilnahme an einer Lernumgebung, die sich auf&nbsp;KunsttherapeutInnen&nbsp;of&nbsp;Color konzentrierte. Gemeinsam hinterfragen zwei Kunsttherapie-AusbilderInnen, ein/e&nbsp;Musiktherapie-AusbilderIn, ein&nbsp;gerade ausgelernte/r&nbsp;KunsttherapeutIn&nbsp;und ein/e Kunsttherapie-StudentIn&nbsp;die Aufrechterhaltung&nbsp;berufsbezogener&nbsp;Normen, die BIPOC*-Studenten und -Praktiker zeitweise motiviert haben, die&nbsp;künstlerischen Therapien&nbsp;auf der Suche nach anderen&nbsp;beruflichen Wegen&nbsp;zu verlassen,&nbsp;um Erfolg zu haben. Der Artikel schließt mit&nbsp;dem&nbsp;„Womanist&nbsp;Manifesto&nbsp;for&nbsp;Arts&nbsp;Therapies&nbsp;Education“.&nbsp; *&nbsp;Black, Indigenous and People of&nbsp;Color&nbsp;(Schwarze&nbsp;und Indigene Menschen&nbsp;sowie&nbsp;Menschen of&nbsp;Color)&nbsp

National maternal mortality ratio in Egypt halved between 1992-93 and 2000.

Two surveys of maternal mortality conducted in Egypt, in 1992-93 and in 2000, collected data from a representative sample of health bureaus covering all of Egypt, except for five frontier governorates which were covered only by the later survey, using the vital registration forms. The numbers of maternal deaths were determined and interviews conducted. The medical causes of death and avoidable factors were determined. Results showed that the maternal mortality ratio (MMR) had dropped by 52% within that period (from 174 to 84/100,000 live births). The National Maternal Mortality Survey in 1992-93 (NMMS) revealed that the metropolitan areas and Upper Egypt had a higher MMR than Lower Egypt. In response to these results, the Egyptian Ministry of Health and Population (MOHP) intensified the efforts of its Safe Motherhood programmes in Upper Egypt with the result that the regional situation had reversed in 2000. Consideration of the intermediate and outcome indicators suggests that the greatest effect of maternal health interventions was on the death-related avoidable factors "substandard care by health providers" and "delays in recognizing problems or seeking medical care". The enormous improvements in these areas are certainly due in part to extensive training, revised curricula, the publication of medical protocols and services standards, the upgrading of facilities, and successful community outreach programmes and media campaigns. The impact on the utilization of antenatal care (ANC) has been less successful. Other areas that remain problematic are inadequate supplies of blood, drugs and equipment. Although the number of maternal deaths linked to haemorrhage has been drastically reduced, it remains the primary cause. The drop in maternal mortality in the 1990s in response to Safe Motherhood programmes was impressive and the ability to tailor interventions based on the data from the NMMS of 1992-93 and 2000 was clearly demonstrated. To ensure the continuing availability of information to guide and evaluate programmes for reducing maternal mortality, an Egyptian national maternal mortality surveillance system is being developed

Bioinspired, base- and metal-free, mild decarboxylative aldol activation of malonic acid half thioesters under phase-transfer reaction conditions

Utilizing ‘off the shelf’ commercially available, cheap, small synthetic molecules that mimic the efficient mediation of important bioreactions utilized by Nature is not only highly sought after but also currently highly topical. This paper details our preliminary efforts at developing a unique base- and metal-free phase-transfer-mediated malonic acid thioester (MAHT) ‘activation protocol’ that efficiently generates (±)-β-thioesters. Our bioinspired aldol process is exceptionally mild, conducted under near neutral pH reaction conditions, does not require an inert, oxygen-free atmosphere or anhydrous reaction conditions and is highly atom-economic. Exemplifying the utility of our protocol, the synthesis of an array of structurally and functionally diverse (±)-β-hydroxy thioesters equipped with highly prized functionality, i.e., chlorine, bromine, fluorine, nitrile and nitro groups, is reported, as is the diastereoselective potential of this important reaction