Adherence to a treat-to-target strategy in early rheumatoid arthritis:results of the DREAM remission induction cohort

INTRODUCTION: Clinical trials have demonstrated that treatment-to-target (T2T) is effective in achieving remission in early rheumatoid arthritis (RA). However, the concept of T2T has not been fully implemented yet and the question is whether a T2T strategy is feasible in daily clinical practice. The objective of the study was to evaluate the adherence to a T2T strategy aiming at remission (Disease Activity Score in 28 joints (DAS28) < 2.6) in early RA in daily practice. The recommendations regarding T2T included regular assessment of the DAS28 and advice regarding DAS28-driven treatment adjustments. METHODS: A medical chart review was performed among a random sample of 100 RA patients of the DREAM remission induction cohort. At all scheduled visits, it was determined whether the clinical decisions were compliant to the T2T recommendations. RESULTS: The 100 patients contributed to a total of 1,115 visits. The DAS28 was available in 97.9% (1,092/1,115) of the visits, of which the DAS28 was assessed at a frequency of at least every three months in 88.3% (964/1,092). Adherence to the treatment advice was observed in 69.3% (757/1,092) of the visits. In case of non-adherence when remission was present (19.5%, 108/553), most frequently medication was tapered off or discontinued when it should have been continued (7.2%, 40/553) or treatment was continued when it should have been tapered off or discontinued (6.2%, 34/553). In case of non-adherence when remission was absent (42.1%, 227/539), most frequently medication was not intensified when an intensification step should have been taken (34.9%, 188/539). The main reason for non-adherence was discordance between disease activity status according to the rheumatologist and DAS28. CONCLUSIONS: The recommendations regarding T2T were successfully implemented and high adherence was observed. This demonstrates that a T2T strategy is feasible in RA in daily clinical practice

The role of cystatin C as a biomarker for prognosis in pulmonary arterial hypertension due to congenital heart disease

AbstractBackgroundAdults with pulmonary arterial hypertension due to congenital heart disease (PAH-CHD) have a poor prognosis. Identifying patients with a high risk for clinical events and death is important because their prognosis can be improved by intensifying their treatment. Cystatin C, a novel cardiac biomarker, correlates with right ventricular dimensions in patients with idiopathic PAH, giving it potential to determine prognosis in PAH-CHD patients. We investigated the predictive value of cystatin C for long-term mortality and clinical events.MethodsFifty-nine PAH-CHD patients (mean age 42 SD 13 years, 42% male) were included in this prospective observational study, with cystatin C measurements between 2005 and 2015 on the outpatient clinic. Patients were evaluated with a standardized evaluation protocol including laboratory, functional and echocardiographic variables. Clinical events comprised worsening functional classification, worsening heart failure, symptomatic hyperviscosity, haemoptysis and arrhythmia. We used Cox regression to determine predictors for mortality and clinical events.ResultsMean follow-up was 4.4years, during which 12 (20%) patients died. Cystatin C (HR 1.3, p<0.001), creatinine (HR 1.2, p<0.001), NT-pro-BNP (HR 2.0, p=0.012), hs-troponin T (HR 1.9, p=0.005), 6-MWD (HR 0.8, p=0.044) and TAPSE (HR 0.8, p<0.001) predicted mortality. Similar results were found for the prediction of clinical events. When adjusted for NT-pro-BNP or glomerular filtration rate in multivariate analysis, cystatin C remained predictive for mortality.ConclusionsCystatin C, a novel cardiac biomarker, predicts long-term mortality and clinical events in patients with PAH-CHD. Consequently, cystatin C may attribute to clinical decision making regarding treatment intensity

Recommendations on scuba diving in Birt-Hogg-Dubé syndrome

Introduction: Although very uncommon, severe injury and death can occur during scuba diving. One of the main causes of scuba diving fatalities is pulmonary barotrauma due to significant changes in ambient pressure. Pathology of the lung parenchyma, such as cystic lesions, might increase the risk of pulmonary barotrauma. Areas covered: Birt–Hogg–Dubé syndrome (BHD), caused by pathogenic variants in the FLCN gene, is characterized by skin fibrofolliculomas, an increased risk of renal cell carcinoma, multiple lung cysts and spontaneous pneumothorax. Given the pulmonary involvement, in some countries patients with BHD are generally recommended to avoid scuba diving, although evidence-based guidelines are lacking. We aim to provide recommendations on scuba diving for patients with BHD, based on a survey of literature on pulmonary cysts and pulmonary barotrauma in scuba diving. Expert opinion: In our opinion, although the absolute risks are likely to be low, caution is warranted. Given the relative paucity of literature and the potential fatal outcome, patients with BHD with a strong desire for scuba diving should be informed of the potential risks in a personal assessment. If available a diving physician should be consulted, and a low radiation dose chest computed tomography (CT)-scan to assess pulmonary lesions could be considered.</p

Maladaptive personality traits in adolescence: Psychometric properties of the Personality Diagnostic Questionnaire-4+

AbstractThe Personality Diagnostic Questionnaire-4+ (PDQ-4+) is a self-report used for the assessment of personality disorder traits, however, its psychometric characteristics have yet to be tested in community samples of adolescents. The main goal was to analyze the psychometric properties of the PDQ-4+ scores in a large sample of non-clinical adolescents (N=1,443; M=15.9 years; SD=1.2). The PDQ-4+ scores showed adequate psychometric properties. Reliability of the subscales, incorporating a Likert-type 5-point response format, ranged from .62 to .85. The study of the internal structure at item level revealed that the PDQ-4+ subscales were essentially one-dimensional. Analysis of the internal structure at the subscale level by means of exploratory factor analysis and exploratory structural equation modeling yielded a possible three-dimensional solution. The PDQ-4+ subscales correlated moderately with emotional and behavioural variables measured by the Strengths and Difficulties Questionnaire. The results have clear implications for the understanding of maladaptive personality traits in adolescents

Is secondary chemical exposure of hospital personnel of clinical importance?

INTRODUCTION: There is increasing concern among hospital personnel about potential secondary exposure when treating chemically contaminated patients. OBJECTIVE: To assess which circumstances and chemicals require the use of Level C Personal Protective Equipment (chemical splash suit and air-purifying respirator), to prevent secondary contamination of hospital personnel treating a chemically contaminated patient. METHODS: The US National Library of Medicine PubMed database was searched for the years 1985 to 2020 utilizing combinations of relevant search terms. This yielded 557 papers which were reviewed by title and abstract. After excluding papers on biological or radiological agents, or those not related to hospital personnel, 38 papers on chemicals remained. After a full-text review, 13 papers without an in-depth discussion on the risk for secondary contamination were omitted, leaving 25 papers for review. The references of these papers were searched and this yielded another seven additional citations, bringing the total to 32 papers. INCIDENCE OF SECONDARY TOXICITY: Secondary toxicity in hospital personnel is rare: a large-scale inventory of 120,000 chemical incidents identified only nine cases, an occurrence of 0.0075%. SKIN CONTACT AS A SECONDARY EXPOSURE ROUTE: Skin exposure is rare under normal hygienic working conditions, reflected by the very small number of cases reported in the literature: two cases with corrosive effects due to unprotected contact and one case of presumed skin absorption. INHALATION AS A SECONDARY EXPOSURE ROUTE: Most case reports described secondary toxicity as a result of inhalation. The chemicals involved were irritating solid particles (capsaicin spray/CS), toxic gases formed in the stomach of patients (arsine/hydrazoic acid/phosphine) and vapours from volatile liquids (solvents). FEATURES OF SECONDARY TOXICITY: Reported symptoms after secondary inhalation were generally mild and reversible (mostly irritation of eyes and respiratory tract, nausea, headache, dizziness/light-headedness) and did not require treatment. In many cases, special circumstances increased exposure: treatment/decontamination of multiple patients, regurgitation of the chemical agent from the stomach, or inadequate room ventilation. USE OF MORE THAN STANDARD PERSONAL PROTECTIVE EQUIPMENT: Normal hygienic precautions prevent direct skin contact from exposure to common chemical agents. When solid particle contamination is extensive, a mask and eye protection should be applied. Splash proof outer clothing (splash suit) and eye protection is preferred if (partial) wet decontamination is performed on single patients. Adequate ventilation, careful removal of clothing in case of solid particles contamination and adequate disposal of gastric content reduces exposure. Hospital staff can be rotated if symptoms occur, which can be odour-mediated. The use of more elaborate personal protective equipment with an air-purifying respirator (Level C) is only necessary in exceptional cases of contamination with highly toxic volatile chemicals (e.g., sarin). It should also be considered when decontaminating a large number of patients. CONCLUSIONS: The risk of secondary contamination and subsequent toxicity in hospital personnel decontaminating or treating chemically contaminated patients is small. Normal hygienic precautions (gloves and water-resistant gown) will adequately protect hospital staff when treating the majority of chemically contaminated patients. More extensive protection is only necessary infrequently and there is no reason to delay critical care, even if more elaborate protection is not immediately available

Testing for the association of the KIAA1109/Tenr/IL2/IL21 gene region with rheumatoid arthritis in a European family-based study

INTRODUCTION: A candidate gene approach, in a large case-control association study in the Dutch population, has shown that a 480 kb block on chromosome 4q27 encompassing KIAA1109/Tenr/IL2/IL21 genes is associated with rheumatoid arthritis. Compared with case-control association studies, family-based studies have the added advantage of controlling potential differences in population structure. Therefore, our aim was to test this association in populations of European origin by using a family-based approach. METHODS: A total of 1,302 West European white individuals from 434 trio families were genotyped for the rs4505848, rs11732095, rs6822844, rs4492018 and rs1398553 polymorphisms using the TaqMan Allelic discrimination assay (Applied Biosystems). The genetic association analyses for each SNP and haplotype were performed using the Transmission Disequilibrium Test and the genotype relative risk. RESULTS: We observed evidence for association of the heterozygous rs4505848-AG genotype with rheumatoid arthritis (P = 0.04); however, no significance was found after Bonferroni correction. In concordance with previous findings in the Dutch population, we observed a trend of undertransmission for the rs6822844-T allele and rs6822844-GT genotype to rheumatoid arthritis patients. We further investigated the five SNP haplotypes of the KIAA1109/Tenr/IL2/IL21 gene region. We observed, as described in the Dutch population, a nonsignificant undertransmission of the AATGG haplotype to rheumatoid arthritis patients. CONCLUSIONS: Using a family-based study, we have provided a trend for the association of the KIAA1109/Tenr/IL2/IL21 gene region with rheumatoid arthritis in populations of European descent. Nevertheless, we failed to replicate a significant association of this region in our rheumatoid arthritis family sample. Further investigation of this region, including detection and testing of all variants, is required to confirm rheumatoid arthritis association

A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides

Introduction. Rheumatoid arthritis (RA) patients can be classified based on presence or absence of anticitrullinated peptide antibodies (ACPA) in their serum. This heterogeneity among patients may reflect important biological differences underlying the disease process. To date, the majority of genetic studies have focused on the ACPA-positive group. Therefore, our goal was to analyse the genetic risk factors that contribute to ACPA-negative RA. Methods. We performed a large-scale genome-wide association study (GWAS) in three Caucasian European cohorts comprising 1148 ACPA-negative RA patients and 6008 controls. All patients were screened using the Illumina Human Cyto-12 chip, and controls were genotyped using different genome-wide platforms. Population-independent analyses were carried out by means of logistic regression. Meta-analysis with previously published data was performed as follow-up for selected signals (reaching a total of 1922 ACPA-negative RA patients and 7087 controls). Imputation of classical HLA alleles, aminoacid residues and single nucleotide polymorphisms was undertaken. Results. The combined analysis of the studied cohorts resulted in identification of a peak of association in the HLA-region and several suggestive non-HLA associations. Meta-analysis with previous reports confirmed the association of the HLA region with this subset and an observed association in the CLYBL locus remained suggestive. The imputation and deep interrogation of the HLA region led to identification of a two aminoacid model (HLA-B at position 9 and HLA-DRB1 at position 11) that accounted for the observed genome-wide associations in this region. Conclusions. Our study shed light on the influence of the HLA region in ACPA-negative RA and identified a suggestive risk locus for this condition

Comparative Pathogenesis of an Avian H5N2 and a Swine H1N1 Influenza Virus in Pigs

Pigs are considered intermediate hosts for the transmission of avian influenza viruses (AIVs) to humans but the basic organ pathogenesis of AIVs in pigs has been barely studied. We have used 42 four-week-old influenza naive pigs and two different inoculation routes (intranasal and intratracheal) to compare the pathogenesis of a low pathogenic (LP) H5N2 AIV with that of an H1N1 swine influenza virus. The respiratory tract and selected extra-respiratory tissues were examined for virus replication by titration, immunofluorescence and RT-PCR throughout the course of infection. Both viruses caused a productive infection of the entire respiratory tract and epithelial cells in the lungs were the major target. Compared to the swine virus, the AIV produced lower virus titers and fewer antigen positive cells at all levels of the respiratory tract. The respiratory part of the nasal mucosa in particular showed only rare AIV positive cells and this was associated with reduced nasal shedding of the avian compared to the swine virus. The titers and distribution of the AIV varied extremely between individual pigs and were strongly affected by the route of inoculation. Gross lung lesions and clinical signs were milder with the avian than with the swine virus, corresponding with lower viral loads in the lungs. The brainstem was the single extra-respiratory tissue found positive for virus and viral RNA with both viruses. Our data do not reject the theory of the pig as an intermediate host for AIVs, but they suggest that AIVs need to undergo genetic changes to establish full replication potential in pigs. From a biomedical perspective, experimental LP H5 AIV infection of pigs may be useful to examine heterologous protection provided by H5 vaccines or other immunization strategies, as well as for further studies on the molecular pathogenesis and neurotropism of AIVs in mammals