Use and cost of disease-modifying therapies by Sonya Slifka Study participants: has anything really changed since 2000 and 2009?

Background:Disease-modifying therapies benefit individuals with relapsing forms of multiple sclerosis, but their utility remains unclear for those without relapses. Objective:To determine disease-modifying therapy use and costs in 2009, compare use in 2009 and 2000, and examine compliance with evidence-based guidelines. Methods:We determined the extent and characteristics of disease-modifying therapy use by participants in the Sonya Slifka Longitudinal Multiple Sclerosis Study (Slifka) in 2000 (n=2156) and 2009 (n=2361) and estimated out-of-pocket and total (payer) costs for 2009. Two multivariable logistic regressions predicted disease-modifying therapy use. Results:Disease-modifying therapy use increased from 55.3% in 2000 to 61.5% in 2009. In 2009, disease-modifying therapy use was reported by 76.5% of participants with relapsing-remitting multiple sclerosis, 73.2% with progressive-relapsing multiple sclerosis, 62.5% with secondary progressive multiple sclerosis, and 41.8% with primary progressive multiple sclerosis. Use was significantly associated with relapsing-remitting multiple sclerosis, shorter duration of illness, one to two relapses per year, non-ambulatory symptoms, using a cane, younger age, higher family income, and having health insurance. Average annual costs in 2009 were US$939-3101 for patients and US$16,302-18,928 for payers. Conclusion:Use rates were highest for individuals with relapsing-remitting multiple sclerosis, but substantial for those with progressive courses although clinical trials have not demonstrated significant benefits for them

Relation between Sexual and Gender Minority Status and Suicide Attempts Among Veterans Seeking Treatment for Military Sexual Trauma

There is limited study of suicidal behaviors among veterans identifying as sexual and gender minorities (SGMs), despite previous research indicating rates of suicide attempts are high within civilian SGM populations. Further, some research incorporating military service members suggests those identifying as SGMs are disproportionately exposed to military sexual trauma (MST), an additional risk factor for negative psychiatric sequelae. To address health care research disparities among minority veterans (i.e., women, those endorsing MST, SGMs), we examined presentations of veterans (N = 277) who attended initial consultation appointments for MST-related treatment and completed a semistructured clinical interview including demographic characteristics, history of suicide attempts (HSA), and a diagnostic evaluation. Twenty-eight (10.1%) veterans identified as SGMs. SGM/non-SGM groups were contrasted on suicidal and psychiatric morbidity outcomes. Overall, endorsement of HSA was high (30.7%). Despite similar clinical profiles, 53.6% of veterans who identified as SGM endorsed HSA in contrast with 28.1% of peers identifying as heterosexual and nontransgender, a significant effect of small-to-moderate size. Findings suggest assessment and clinical management of suicidality is of critical importance for clinicians providing services to veterans pursuing recovery from MST, generally, and may be especially so when delivering care to SGM. Further, results underscore the need for culturally competent delivery of trauma-focused interventions

The acquisitive–conservative axis of leaf trait variation emerges even in homogeneous environments

The acquisitive-conservative axis of plant ecological strategies results in a pattern of leaf trait covariation that captures the balance between leaf construction costs and plant growth potential. Studies evaluating trait covariation within species are scarcer, and have mostly dealt with variation in response to environmental gradients. Little work has been published on intraspecific patterns of leaf trait covariation in the absence of strong environmental variation.Methods: We analysed covariation of four leaf functional traits (SLA: specific leaf area, LDMC: leaf dry matter content, Ft: force to tear, and Nm: leaf nitrogen content) in six Poaceae and four Fabaceae species common in the dry Chaco forest of Central Argentina, growing in the field and in a common garden. We compared intraspecific covariation patterns (slopes, correlation and effect size) of leaf functional traits with global interspecific covariation patterns. Additionally, we checked for possible climatic and edaphic factors that could affect the intraspecific covariation pattern.Key Results: We found negative correlations for the LDMC-SLA, Ft-SLA, LDMC-Nm , and Ft-Nm trait pairs. This intraspecific covariation pattern found both in the field and in the common garden and not be explained by climatic or edaphic variation in the field follows the expected acquisitive-conservative axis. At the same time, we found quantitative differences in slopes among different species, and between these intraspecific patterns and the interspecific ones. Many of these differences seem to be idiosyncratic, but some appear consistent among species (e.g.all the intraspecific LDMC-SLA and LDMC-Nm slopes tend to be shallower than the global).Conclusions: Our study indicates that the acquisitive-conservative leaf functional trait covariation pattern occurs at the intraspecific level even in the absence of relevant environmental variation in the field. This suggests a high degree of variation-covariation in leaf functional traits not driven by environmental variables.Fil: Gorne, Lucas Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; ArgentinaFil: Díaz, Sandra Myrna. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; ArgentinaFil: Minden, Vanessa. University of Oldenburg; Alemania. Vrije Universiteit Brussel; BélgicaFil: Onoda, Yusuke. Kyoto University. School of Agriculture; JapónFil: Kramer, Koen. Wageningen University; Países BajosFil: Muir, Christopher. University Of Hawaii; Estados UnidosFil: Michaletz, Sean T. University of British Columbia; CanadáFil: Lavorel, Sandra. Centre National de la Recherche Scientifique; FranciaFil: Sharpe, Joanne. Sharplex Services, Edgecomb; Estados UnidosFil: Jansen, Steven. Universitat Ulm; AlemaniaFil: Slot, Martijn. Smithsonian Tropical Research Institute; PanamáFil: Chacon, Maximiliano Eduardo. Universidad de Costa Rica; Costa RicaFil: Boenisch, Gerhard. Max Planck Institute For Biogeochemistry; Alemani

COVID-19: treatment strategies of German-speaking pediatric rheumatologists Results of an online survey

Zusammenfassung Hintergrund Zuverlässige Daten zu Verlauf und Therapie von COVID-19 („corona virus disease 2019“) bei Kindern mit rheumatischen Erkrankungen unter Immunsuppression fehlen. Ziel der Arbeit Abbildung individueller Strategien der Mitglieder der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR) im Umgang mit COVID-19. Methodik Mittels Online-Umfrage wurden im Mai 2020 das Meinungsbild der GKJR-Mitglieder zum Umgang mit DMARDs („disease-modifying anti-rheumatic drugs“) bei COVID-19-Erkrankung sowie die Bereitschaft zum Einsatz spezieller Therapieansätze bei Patienten mit unterschiedlicher Schwere von COVID-19 erhoben. Ergebnisse Es nahmen 71 Kollegen (27,3 % aller befragten ärztlichen Mitglieder) an der Umfrage teil; davon hatten 28,2 % bereits Patienten mit COVID-19 betreut. Über 95 % der Teilnehmer lehnten eine präventive Anpassung der antirheumatischen Therapie im Rahmen der SARS-CoV-2-Pandemie ab. Bei ambulanten Patienten unter Immunsuppression mit nachgewiesener COVID-19-Erkrankung würden mehr als 50 % der Teilnehmer folgende Therapien aussetzen: intravenöse hoch dosierte Steroide, Cyclophosphamid, Anti-CD20-Antikörper, sowie eine BAFF-, CTLA-4-, TNF-α-Blockade. Hingegen würden nichtsteroidale Antiphlogistika, Hydroxychloroquin (HCQ), orale Steroide, Mycophenolat, IL-1-Blockade sowie Immunglobuline (Ig) von >70 % der Kollegen weiter fortgeführt. Bei stationären Patienten mit COVID-19 würden insgesamt 74,6 % der Kollegen eine COVID-19-gerichtete Therapie erwägen. Bei stabilem Verlauf unter O 2 -Therapie (Stufe I) würden am häufigsten HCQ (18,3 %), Azithromycin (16,9 %) und Ig (9,9 %) in Betracht gezogen. Bei drohendem (Stufe II) bzw. manifestem Zytokinsturm (Stufe III) würden am häufigsten Anakinra (40,8 % bei Stufe II bzw. 46,5 % bei Stufe III), Tocilizumab (26,8 % bzw. 40,8 %), Steroide (25,4 % bzw. 33,8 %) und Remdesivir (29,6 % bzw. 38,0 %) eingesetzt. Von vielen Kollegen wurde betont, dass die Therapiestrategie individuell und der klinischen Situation entsprechend angepasst werden soll. Diskussion Die Ergebnisse der Online-Umfrage sind vor dem Hintergrund einer aktuell in Deutschland niedrigen Prävalenz von COVID-19 zu sehen und spiegeln somit theoretische Überlegungen der Befragten wider. Da Kinder derzeit nicht im Fokus von prospektiven COVID-19-Studien stehen, scheint der kontinuierliche und kritische kollegiale Fachaustausch bei Therapieentscheidungen umso wichtiger zu sein

Blockade of T-cell activation by dithiocarbamates involves novel mechanisms of inhibition of nuclear factor of activated T cells.

Dithiocarbamates (DTCs) have recently been reported as powerful inhibitors of NF-kappaB activation in a number of cell types. Given the role of this transcription factor in the regulation of gene expression in the inflammatory response, NF-kappaB inhibitors have been suggested as potential therapeutic drugs for inflammatory diseases. We show here that DTCs inhibited both interleukin 2 (IL-2) synthesis and membrane expression of antigens which are induced during T-cell activation. This inhibition, which occurred with a parallel activation of c-Jun transactivating functions and expression, was reflected by transfection experiments at the IL-2 promoter level, and involved not only the inhibition of NF-kappaB-driven reporter activation but also that of nuclear factor of activated T cells (NFAT). Accordingly, electrophoretic mobility shift assays (EMSAs) indicated that pyrrolidine DTC (PDTC) prevented NF-kappaB, and NFAT DNA-binding activity in T cells stimulated with either phorbol myristate acetate plus ionophore or antibodies against the CD3-T-cell receptor complex and simultaneously activated the binding of AP-1. Furthermore, PDTC differentially targeted both NFATp and NFATc family members, inhibiting the transactivation functions of NFATp and mRNA induction of NFATc. Strikingly, Western blotting and immunocytochemical experiments indicated that PDTC promoted a transient and rapid shuttling of NFATp and NFATc, leading to their accelerated export from the nucleus of activated T cells. We propose that the activation of an NFAT kinase by PDTC could be responsible for the rapid shuttling of the NFAT, therefore transiently converting the sustained transactivation of this transcription factor that occurs during lymphocyte activation, and show that c-Jun NH2-terminal kinase (JNK) can act by directly phosphorylating NFATp. In addition, the combined inhibitory effects on NFAT and NF-KB support a potential use of DTCs as immunosuppressants

The evaluation of disability and its related factors among the elderly population in Kashan, Iran

<p>Abstract</p> <p>Background</p> <p>Recent literature indicates that developing countries in Asia are aging faster than other countries in the world and disability has become one of the greater public health concern in these countries. Pausity of published data on the elderly disability in Iran signifies the importance of this study designed to evaluate the disability and its related factors among the elderly population in Kashan, Iran during 2006–2007.</p> <p>Methods/Design</p> <p>A cross-sectional study is conducting on a multy-stage random sample of elderly people in Kashan ages 65 years and older. Volunteer participants were included by age 65 and older and excluded if they had the medical diagnosis of Alzhimer disease. The WHO DAS II was used as the generic disability measure in this survey. The original version of WHO DAS II was translated into Farsi according to the standardized guidelines for cross-cultural adaptation of health-related measures. Upon completion of data collection the descriptive statistics will compute all the variables. Chi-square, t-test analysis and ANOVA will be used to examine significant differences between the subgroups.</p> <p>Discussion</p> <p>This is the first research protocol to study disability among the Iranian elderly population. Presently, 80% of eligible subjects have been selected. The results of this study will help to develop more effective protocols to assist Iranian elderly population with disabilities.</p

Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia

Acute myeloid leukemia (AML) is a molecularly and clinically heterogeneous hematological malignancy. Although immunotherapy may be an attractive modality to exploit in patients with AML, the ability to predict the groups of patients and the types of cancer that will respond to immune targeting remains limited. This study dissected the complexity of the immune architecture of AML at high resolution and assessed its influence on therapeutic response. Using 442 primary bone marrow samples from three independent cohorts of children and adults with AML, we defined immune-infiltrated and immune-depleted disease classes and revealed critical differences in immune gene expression across age groups and molecular disease subtypes. Interferon (IFN)–γ–related mRNA profiles were predictive for both chemotherapy resistance and response of primary refractory/relapsed AML to flotetuzumab immunotherapy. Our compendium of microenvironmental gene and protein profiles provides insights into the immuno-biology of AML and could inform the delivery of personalized immunotherapies to IFN-γ–dominant AML subtypes