Effectiveness of Belimumab After Rituximab in Systemic Lupus Erythematosus: A Randomized Controlled Trial

BACKGROUND: B-cell depletion with rituximab is commonly used for patients with systemic lupus erythematosus (SLE) that is refractory to conventional therapy, but it yields variable responses. We hypothesized that high B-cell activating factor (BAFF) levels after rituximab can cause disease flares, thereby limiting its effectiveness. OBJECTIVE: To obtain preliminary evidence for efficacy of the anti-BAFF therapeutic belimumab after rituximab in SLE. DESIGN: Phase 2, randomized, double-blind (patients, assessors, researchers, care providers), placebo-controlled, parallel-group, superiority trial. (ISRCTN: 47873003). SETTING: England. PARTICIPANTS: Fifty-two patients who had SLE that was refractory to conventional treatment and whose physicians had recommended rituximab therapy were recruited between 2 February 2017 and 28 March 2019. INTERVENTION: Participants were treated with rituximab and 4 to 8 weeks later were randomly assigned (1:1) to receive intravenous belimumab or placebo for 52 weeks. MEASUREMENTS: The prespecified primary end point was serum IgG anti-double-stranded DNA (anti-dsDNA) antibody levels at 52 weeks. Secondary outcomes included incidence of disease flares and adverse events. RESULTS: At 52 weeks, IgG anti-dsDNA antibody levels were lower in patients treated with belimumab compared with placebo (geometric mean, 47 [95% CI, 25 to 88] vs. 103 [CI, 49 to 213] IU/mL; 70% greater reduction from baseline [CI, 46% to 84%]; P < 0.001). Belimumab reduced risk for severe flare (BILAG-2004 grade A) compared with placebo (hazard ratio, 0.27 [CI, 0.07 to 0.98]; log-rank P = 0.033), with 10 severe flares in the placebo group and 3 in the belimumab group. Belimumab did not increase incidence of serious adverse events. Belimumab significantly suppressed B-cell repopulation compared with placebo (geometric mean, 0.012 [CI, 0.006 to 0.014] vs. 0.037 [CI, 0.021 to 0.081] × 109/L) at 52 weeks in a subset of patients (n = 25) with available data. LIMITATIONS: Small sample size; biomarker primary end point. CONCLUSION: Belimumab after rituximab significantly reduced serum IgG anti-dsDNA antibody levels and reduced risk for severe flare in patients with SLE that was refractory to conventional therapy. The results suggest that this combination could be developed as a therapeutic strategy. PRIMARY FUNDING SOURCE: Versus Arthritis

Cell walls of the dimorphic fungal pathogens Sporothrix schenckii and Sporothrix brasiliensis exhibit bilaminate structures and sloughing of extensive and intact layers

This work was supported by the Fundação Carlos Chagas de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), grants E-26/202.974/2015 and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), grants 229755/2013-5, Brazil. LMLB is a senior research fellow of CNPq and Faperj. NG acknowledged support from the Wellcome Trust (Trust (097377, 101873, 200208) and MRC Centre for Medical Mycology (MR/N006364/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Occupational health legislation and practices related to seafarers on passenger ships focused on communicable diseases: results from a European cross-sectional study (EU SHIPSAN PROJECT)

<p>Abstract</p> <p>Background</p> <p>Seafarers play an important role in the transmission of communicable diseases. The aim of the present study is to draw information and identify possible gaps on occupational health practices related to seafarers sailing on ships within the European Union Member States (EU MS) with focus on communicable diseases.</p> <p>Methods</p> <p>A structured questionnaire was sent to competent authorities from 21 EU MS. The questionnaire included questions about occupational health policies, medical certification of seafarers, communicable diseases reporting and relevant legislation. Descriptive analysis of the data was conducted by the use of Epi Info software: EU MS were categorized in four priority groups (A, B, C, D) based on: number of passenger ships visits, volume of passengers, and number of ports in each country. Moreover, EU MS were categorized to old and new, based on the date of entry in the EU.</p> <p>Results</p> <p>All 21 countries with relevant competent authorities responded to the questionnaire. The existence of specific national legislation/regulation/guidelines related to vaccination of seafarers was reported by three out of the 21 (14%) responding authorities. Surveillance data of communicable diseases related to seafarers are collected and analyzed by 4 (19%) authorities. Five out of 21 of the responding countries (24%) reported that tuberculin test result is required for the issuance of seafarer's medical certificate while a great variety of medical examination is required for the issuance of this certificate among countries.</p> <p>Gaps on occupational health services focused on communicable diseases related to maritime occupation have been reported by 33% of the responding countries.</p> <p>Responding authorities from Group A and B had the highest percentage of reported gaps followed by groups C and D. Old MS reported a higher frequency regarding gaps on occupational health services in comparison to new MS.</p> <p>Conclusion</p> <p>Our results revealed heterogeneity regarding occupational health of maritime employees in EU MS. This work provides some evidence that further work at international and European level could be considered, in order to explore the potential for harmonized initiatives regarding occupational health of seafarers.</p

Long term geological record of a global deep subsurface microbial habitat in sand injection complexes

Peer reviewedPublisher PD

Minimally Invasive Periodontal Treatment Using the Er,Cr: YSGG Laser. A 2-year Retrospective Preliminary Clinical Study

Minimally invasive surgery (MIS) using the erbium, chromium: yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser (Waterlase MD, Biolase, Irvine, CA) to treat moderate to advanced periodontal disease is presented as an alternative to conventional therapies. To date, there are few short- or long-term studies to demonstrate the effects of this laser in treating and maintaining periodontal health. Electronic clinical records from 16 patients – total of 126 teeth, with pocket depths ranging from 4 mm to 9 mm – were treated with the same protocol using the Er,Cr:YSGG laser. The mean baseline probing depths (PD) were 5 mm and clinical attachment levels (CAL) were 5 mm in the 4 - 6 mm pretreated laser group. The mean baseline probing depths were 7.5 and 7.6 mm for PD and CAL respectfully in the 7 – 9 mm pretreatment laser group. At the 2 year mark, the average PD was 3.2 ± 1.1 mm for the 4-6 mm pocket group and the 7-9 mm pocket group had a mean PD of 3.7 ± 1.2 mm. mean CAL was 3.1 ± 1.1 mm for the 4-6 mm group and 3.6 ± 1.2 for the 7-9 mm group with an overall reduction of 1.9 mm and 4.0 mm respectively. At one and two years, both groups remained stable with PD comparable to the three-month gains. The CAL measurements at one and two years were also comparable to the three-month gains

Surveillance and control of communicable diseases related to passenger ships in Europe

This study was conducted within the European SHIPSAN (ship sanitation) project and aims at exploring the legislative framework and current practices related to surveillance of communicable diseases and response aboard passenger ships in Europe. A detailed questionnaire was disseminated and completed by 59 competent authorities in 27 European countries. The majority of competent authorities used national legislation without special provisions for passenger ships. Only 20% had specific provisions for ships regarding quarantine, while a smaller proportion of new Member States (MS) have specific legislation in comparison with old MS (p = 0.01). The Maritime Declaration of Health (MDH) was the main reporting tool used. About 30.5% of the competent authorities declared that they require submission of MDH by all arriving ships, but 28.8% only from affected areas, and 11.9% never require MDH. A total of 45 outbreaks or incidents (36 gastrointestinal, 1 incident of legionellosis, 3 respiratory, and 1 influenza-like illness outbreak, occupational tuberculosis, varicella, scabies, and meningitis) were reported to EU competent authorities during 2006. About 75% of the responders stated that there are gaps in the surveillance and control of communicable diseases. A diversity of approaches in EU countries, and gaps regarding surveillance and response and training needs of personnel were identified. (Int Marit Health 2011; 62, 2: 138&#8211;147

Mindfulness in schools: a health promotion approach to improving adolescent mental health.

Between 10 and 20% of adolescents worldwide experience a mental health problem within a given 12-month period. Mental health problems impact on an adolescent’s potential to live a fulfilling and productive life and lead to challenges such as stigma, isolation and discrimination. To address this need, in recent years, there has been growing interest into broad-based school-integrated health promotion interventions that seek to build resilience and augment protective factors in adolescents. Mindfulness-based interventions (MBIs) reflect one such approach that have been administered to adolescent populations in both resilience building and treatment contexts. This paper discusses the utility of school-based MBIs as an adolescent health promotion approach and makes recommendations for intervention design, delivery and evaluation. Emerging evidence indicates that school-integrated MBIs may be a cost-effective means of not only meeting government objectives relating to adolescent mental health, but also for improving the wellbeing of teachers and parents. Furthermore, there is growing evidence indicating that mindfulness can elicit improvements in student learning performance and general classroom behaviour. However, notwithstanding these beneficial properties, there remains a need to conduct large-scale empirical investigations that seek to evaluate the effectiveness of school-integrated MBIs at a regional or national level. A further challenge is the need to ensure that mindfulness instructors are able to impart to adolescents an experiential understanding of this ancient contemplative technique.N

Six-Month Mortality among HIV-Infected Adults Presenting for Antiretroviral Therapy with Unexplained Weight Loss, Chronic Fever or Chronic Diarrhea in Malawi.

In sub-Saharan Africa, early mortality is high following initiation of antiretroviral therapy (ART). We investigated 6-month outcomes and factors associated with mortality in HIV-infected adults being assessed for ART initiation and presenting with weight loss, chronic fever or diarrhea, and with negative TB sputum microscopy

PGA: power calculator for case-control genetic association analyses

<p>Abstract</p> <p>Background</p> <p>Statistical power calculations inform the design and interpretation of genetic association studies, but few programs are tailored to case-control studies of single nucleotide polymorphisms (SNPs) in unrelated subjects.</p> <p>Results</p> <p>We have developed the "Power for Genetic Association analyses" (PGA) package which comprises algorithms and graphical user interfaces for sample size and minimum detectable risk calculations using SNP or haplotype effects under different genetic models and study constrains. The software accounts for linkage disequilibrium and statistical multiple comparisons. The results are presented in graphs or tables and can be printed or exported in standard file formats.</p> <p>Conclusion</p> <p>PGA is user friendly software that can facilitate decision making for association studies of candidate genes, fine-mapping studies, and whole-genome scans. Stand-alone executable files and a Matlab toolbox are available for download at: <url>http://dceg.cancer.gov/bb/tools/pga</url></p