Cultural contributions to adults' self-rated mental health problems and strengths: 7 culture clusters, 28 societies, 16 906 adults.

BACKGROUND: It is unknown how much variation in adult mental health problems is associated with differences between societal/cultural groups, over and above differences between individuals. METHODS: To test these relative contributions, a consortium of indigenous researchers collected Adult Self-Report (ASR) ratings from 16 906 18- to 59-year-olds in 28 societies that represented seven culture clusters identified in the Global Leadership and Organizational Behavioral Effectiveness study (e.g. Confucian, Anglo). The ASR is scored on 17 problem scales, plus a personal strengths scale. Hierarchical linear modeling estimated variance accounted for by individual differences (including measurement error), society, and culture cluster. Multi-level analyses of covariance tested age and gender effects. RESULTS: Across the 17 problem scales, the variance accounted for by individual differences ranged from 80.3% for DSM-oriented anxiety problems to 95.2% for DSM-oriented avoidant personality (mean = 90.7%); by society: 3.2% for DSM-oriented somatic problems to 8.0% for DSM-oriented anxiety problems (mean = 6.3%); and by culture cluster: 0.0% for DSM-oriented avoidant personality to 11.6% for DSM-oriented anxiety problems (mean = 3.0%). For strengths, individual differences accounted for 80.8% of variance, societal differences 10.5%, and cultural differences 8.7%. Age and gender had very small effects. CONCLUSIONS: Overall, adults' self-ratings of mental health problems and strengths were associated much more with individual differences than societal/cultural differences, although this varied across scales. These findings support cross-cultural use of standardized measures to assess mental health problems, but urge caution in assessment of personal strengths.

Inflammatory Biomarkers in the Diagnosis and Prognosis of Rheumatoid Arthritis-Associated Interstitial Lung Disease.

This study aimed to identify inflammatory factors and soluble cytokines that act as biomarkers in the diagnosis and prognosis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). We performed a nested prospective observational case-control study of patients with RA-ILD matched by sex, age, and time since the diagnosis of RA. All participants underwent pulmonary function testing and high-resolution computed tomography. ILD was defined according to the criteria of the American Thoracic Society/European Respiratory Society; the progression of lung disease was defined as the worsening of FVC > 10% or DLCO > 15%. Inflammation-related variables included the inflammatory activity measured using the DAS28-ESR and a multiplex cytokine assay. Two Cox regression models were run to identify factors associated with ILD and the progression of ILD. The study population comprised 70 patients: 35 patients with RA-ILD (cases) and 35 RA patients without ILD (controls). A greater percentage of cases had higher DAS28-ESR (p = 0.032) and HAQ values (p = 0.003). The variables associated with RA-ILD in the Cox regression analysis were disease activity (DAS28) (HR [95% CI], 2.47 [1.17-5.22]; p = 0.017) and high levels of ACPA (HR [95% CI], 2.90 [1.24-6.78]; p = 0.014), IL-18 in pg/mL (HR [95% CI], 1.06 [1.00-1.12]; p = 0.044), MCP-1/CCL2 in pg/mL (HR [95% CI], 1.03 [1.00-1.06]; p = 0.049), and SDF-1 in pg/mL (HR [95% CI], 1.00 [1.00-1.00]; p = 0.010). The only variable associated with the progression of ILD was IL-18 in pg/mL (HR [95% CI], 1.25 [1.07-1.46]; p = 0.004). Our data support that the inflammatory activity was higher in patients with RA-ILD than RA patients without ILD. Some cytokines were associated with both diagnosis and poorer prognosis in patients with RA-ILD.

Polymerizable Skin Hydrogel for Full Thickness Wound Healing.

The skin is the largest organ in the human body, comprising the main barrier against the environment. When the skin loses its integrity, it is critical to replace it to prevent water loss and the proliferation of opportunistic infections. For more than 40 years, tissue-engineered skin grafts have been based on the in vitro culture of keratinocytes over different scaffolds, requiring between 3 to 4 weeks of tissue culture before being used clinically. In this study, we describe the development of a polymerizable skin hydrogel consisting of keratinocytes and fibroblast entrapped within a fibrin scaffold. We histologically characterized the construct and evaluated its use on an in vivo wound healing model of skin damage. Our results indicate that the proposed methodology can be used to effectively regenerate skin wounds, avoiding the secondary in vitro culture steps and thus, shortening the time needed until transplantation in comparison with other bilayer skin models. This is achievable due to the instant polymerization of the keratinocytes and fibroblast combination that allows a direct application on the wound. We suggest that the polymerizable skin hydrogel is an inexpensive, easy and rapid treatment that could be transferred into clinical practice in order to improve the treatment of skin wounds.

miRNA-Mediated Epigenetic Regulation of Treatment Response in RA Patients-A Systematic Review.

This study aimed to evaluate the role of microRNAs (miRNA) as biomarkers of treatment response in rheumatoid arthritis (RA) patients through a systematic review of the literature. The MEDLINE and Embase databases were searched for studies including RA-diagnosed patients treated with disease-modifying antirheumatic drugs (DMARDs) that identify miRNAs as response predictors. Review inclusion criteria were met by 10 studies. The main outcome of the study was the response to treatment, defined according to EULAR criteria. A total of 839 RA patients and 67 healthy donors were included in the selected studies. RA patients presented seropositivity for the rheumatoid factor of 74.7% and anti-citrullinated C-peptide antibodies of 63.6%. After revision, 15 miRNAs were described as treatment response biomarkers for methotrexate, anti-tumour necrosis factor (TNF), and rituximab. Among treatments, methotrexate presented the highest number of predictor miRNAs: miR-16, miR-22, miR-132, miR-146a and miR-155. The most polyvalent miRNAs were miR-146a, predicting response to methotrexate and anti-TNF, and miR-125b, which predicts response to infliximab and rituximab. Our data support the role of miRNAs as biomarkers of treatment response in RA and point to DMARDs modifying the miRNAs expression. Nevertheless, further studies are needed since a meta-analysis that allows definitive conclusions is not possible due to the lack of studies in this field.

Frequency of Polyautoimmunity in Patients With Rheumatoid Arthritis and Systemic Lupus Erythematosus.

OBJECTIVE: To describe the frequency of polyautoimmunity and multiple autoimmune syndrome in patients with rheumatoid arthritis (RA) and patients with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: This was a cross-sectional observational study of patients with RA, SLE, and controls without autoimmune rheumatic disease. Cases were those with RA according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria and SLE according to the 2019 American College of Rheumatology/European League Against Rheumatism criteria, consecutively recruited in a rheumatology clinic. Controls were subjects with no rheumatic autoimmune disease (AIDs) recruited in the same area. Patients filled out a questionnaire on polyautoimmunity. Variables of interest were polyautoimmunity (RA or SLE with other AIDs), whereas secondary variables were rheumatic, skin, endocrine, digestive, and neurological AIDs. Multiple autoimmune syndrome is defined as the presence of 3 or more AIDs and a family history of AIDs. Statistical analyses performed were descriptive, bivariate, and multivariate (dependent variable: polyautoimmunity). RESULTS: The study population comprised 109 patients with RA, 105 patients with SLE, and 88 controls. Polyautoimmunity was recorded in 15 patients with RA (13.8%), 43 with SLE (41%), and 2 controls (2.2%). The most frequent AID in RA was Sjögren syndrome (53.3%), followed by Hashimoto thyroiditis and psoriasis; the most frequent AIDs in SLE were Sjögren syndrome (55.8%) and antiphospholipid syndrome (30.2%), followed by Hashimoto thyroiditis. Obesity was associated with polyautoimmunity in RA (odds ratio [OR], 3.362; p = 0.034). In SLE, joint damage (OR, 2.282; p = 0.038) and anti-RNP antibodies (OR, 5.095; p = 0.028) were risk factors for polyautoimmunity, and hydroxychloroquine was a protective factor (OR, 0.190; p = 0.004). CONCLUSIONS: Polyautoimmunity is frequent in RA and even more frequent in SLE. It was associated with obesity in RA and with joint damage and anti-RNP in SLE. Hydroxychloroquine was a protector.

Nursing bedside handover in an intensive care unit with a mixed structure: Nursing professionals' perception.

AIM: The main objective is to determine if the infrastructure of critical care units influences the perception of professionals using this handover method. BACKGROUND: Nursing bedside handover is considered a safe information transfer method that can help reduce communication errors; however, it has some disadvantages expressed by health professionals and patients, related to confidentiality, stress and less rest. METHODS: Qualitative descriptive study. The perception of nursing professionals who work in a critical care unit with a mixed structure (open and closed boxes) in a tertiary care hospital was evaluated through a semi-structured interview with a battery of common questions (prepared after literature review) and spontaneous questions according to the objectives of the study. RESULTS: Five thematic areas related to the study objectives were observed: patient safety, message content, confidentiality/privacy, intimacy/rest/noise, and patient participation. CONCLUSIONS: Nursing bedside handover improves safe communication between professionals, because it avoids errors or distractions by double or triple checking (if we include the patient) as well as empowering the patient and including him in his recovery. Carrying it out in closed boxes increases confidentiality and improves intimacy as there are no other patients or relatives nearby who can hear the message. However, the place or shift where the handover is performed does not interfere with the effectiveness of the communication of the message. The morning shift is the busiest, which could affect the patient's rest, a fact that could be solved if it is carried out in a closed box. IMPLICATIONS FOR NURSING MANAGEMENT: Carrying out the handover in individual boxes in intensive care units would provide greater privacy to the patient and reduce the perception of external noise, contributing to the reduction of interruptions and the increase of the patient's rest. It is also a key element in patient safety through verification by double or triple check-up, the structuring of the message and the visualization of devices presented by the patient. In addition, it will allow the professional to start a process of early humanization and participation of the patient in the health process.

Do all antiphospholipid antibodies confer the same risk for major organ involvement in systemic lupus erythematosus patients?

OBJECTIVES: We aimed to investigate the association between the different antiphospholipid antibodies (aPL) and both systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) manifestations. METHODS: Patients from the RELESSER registry, a Spanish retrospective, cross-sectional, forty-five hospital registry of adult SLE patients, were included. RESULTS: Out of a total of 3,658 SLE patients, 1372 were aPL positive (555 of them fulfilled criteria for APS). All aPL types showed a negative association with cutaneous SLE manifestations. Lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) were both associated with haematological, ophthalmological and neuropsychiatric manifestations. IgG isotypes were associated with a higher risk of lupus manifestations compared with IgM. We found that the risk of neuropsychiatric and ophthalmological manifestations significantly increased with a higher number of positive aPL whereas the risk of cutaneous symptoms showed a negative correlation. All types of aPL, and more strongly LA, were associated with non-criteria antiphospholipid syndrome (APS) manifestations such as thrombocytopenia and haemolytic anaemia. Moreover, LA and aCL (particularly IgG isotype) were also associated with Libman-Sacks endocarditis and cognitive impairment. This association was stronger with more than one positive aPL. All types of aPL were also associated with classic APS manifestations, although LA, IgG isotypes, and patients with more than one aPL displayed a higher risk. CONCLUSIONS: There is a hierarchy for aPL and the risk of APS and SLE manifestations. aCL, and especially LA, confer a higher risk for major organ involvement in SLE. IgG isotypes seem to have a more important role. The load of aPL confer a higher risk for APS and certain SLE manifestations.

Incidence and case fatality rate of COVID-19 in patients with inflammatory articular diseases.

OBJECTIVE: To describe the incidence and fatality of coronavirus disease 2019 (COVID-19) and identify risk factors to fatality in patients with inflammatory articular diseases (IAD). METHODS: This is a cross-sectional observational study of IAD patients and COVID-19 with controls matched for age, sex, and RT-PCR. A control group was used to compare the cumulative incidence (CI) and case fatality rate (CFR). The main outcomes of the study were CI and CFR. Other variables included comorbidities, treatments, and characteristics of the COVID-19. Multiple logistic regression analysis was performed to investigate risk factors for fatality in patients with IAD. RESULTS: Of the 1537 patients who fulfilled the inclusion criteria, 23/1537 (1.49%) had IAD 13 (0.8%) had rheumatoid arthritis (RA), 5 psoriatic arthritis (PsA) (0.3%) and 5 axial spondyloarthritis (0.3%). There were no significant differences in CI of COVID-19 and CFR in patients with IAD compared with COVID-19 patients without IAD. In RT-PCR positive patients, the CI of COVID-19 in PsA and AS was higher. Of the 23 IAD patients, 2 RA patients (8.6%) died. The patients did no show characteristics of the COVID-19 disease different from the population. In multivariate analysis, the factor associated with fatality in patients with IAD was older age (OR [95% CI], 1.1 [1.0-1.2]). CONCLUSION: COVID-19 CI, fatality rate and other features do not seem to be increased in IAD patients. Older age was associated with fatality in patients with IAD.

Psychological factors associated with sleep disorders in patients with axial spondyloarthritis or psoriatic arthritis: A multicenter cross-sectional observational study.

BACKGROUND: Studies in axial spondyloarthritis (AxSp) have shown that intensity of pain, anxiety, depression and inflammatory activity are associated with poor sleep quality. AIM: To describe mood and sleep disorders and positive psychological factors in patients with AxSp and psoriatic arthritis (PsA) and to evaluate the psychological factors that are potentially involved in sleep disorders. DESIGN: Multicenter cross-sectional observational study based on a series of patients with AxSp and PsA. PARTICIPANTS: Participants were selected consecutively from patients aged ≥18 years with AxSp or PsA followed at the rheumatology department of 4 Spanish hospitals. INCLUSION CRITERIA: age ≥18 years, AxSp (ASAS criteria) or PsA (CASPAR criteria), ability to understand the study and prepared to complete the questionnaires. METHODS: Main outcomes: Oviedo Sleep Quality questionnaire result. SECONDARY OUTCOMES: psychological status evaluated using the Hospital Anxiety and Depression Scale (HADS) questionnaire, health-related quality of life evaluated using SF-36, perception of pain evaluated using the short questionnaire for assessment of pain (BDU) and fatigue evaluated using the Fatigue Scale (FACIT) questionnaire. We performed a descriptive multivariate linear regression analysis to study factors that were independently associated with sleep disorders. The STROBE guidelines were adopted. RESULTS: We included 301 patients (152 [50.5%] with AxSp and 149 [49.5%] with PsA). The multivariate linear regression analysis for the whole sample showed that insomnia was inversely associated with emotional recovery and biologic disease-modifying antirheumatic drugs and directly associated with depression in both groups. The analysis by disease (AxSp and PsA) showed that insomnia was independently associated with depression and emotional recovery. CONCLUSIONS: Insomnia may be associated with other mood disorders, quality of life and inflammatory activity in the patients studied here. RELEVANCE TO CLINICAL PRACTICE: A nurse intervention can be carried out to prevent sleep disorders knowing the consequences and triggers of the problem.

Fibrin-Plasma Rich in Growth Factors Membrane for the Treatment of a Rabbit Alkali-Burn Lesion.

The purpose of this work is to describe the use of Fibrin-Plasma Rich in Growth Factors (PRGF) membranes for the treatment of a rabbit alkali-burn lesion. For this purpose, an alkali-burn lesion was induced in 15 rabbits. A week later, clinical events were evaluated and rabbits were divided into five treatment groups: rabbits treated with medical treatment, with a fibrin-PRGF membrane cultured with autologous or heterologous rabbit Limbal Epithelial Progenitor Cells (LEPCs), with a fibrin-PRGF membrane in a Simple Limbal Epithelial Transplantation and with a fibrin-PRGF membrane without cultured LEPCs. After 40 days of follow-up, corneas were subjected to histochemical examination and immunostaining against corneal or conjunctival markers. Seven days after alkali-burn lesion, it was observed that rabbits showed opaque cornea, new blood vessels across the limbus penetrating the cornea and epithelial defects. At the end of the follow-up period, an improvement of the clinical parameters analyzed was observed in transplanted rabbits. However, only rabbits transplanted with cultured LEPCs were positive for corneal markers. Otherwise, rabbits in the other three groups showed positive staining against conjunctival markers. In conclusion, fibrin-PRGF membrane improved the chemically induced lesions. Nonetheless, only fibrin-PRGF membranes cultured with rabbit LEPCs were able to restore the corneal surface.

Clinical outcomes of hospitalised patients with COVID-19 and chronic inflammatory and autoimmune rheumatic diseases: a multicentric matched cohort study.

OBJECTIVES: The impact of inflammatory rheumatic diseases on COVID-19 severity is poorly known. Here, we compare the outcomes of a cohort of patients with rheumatic diseases with a matched control cohort to identify potential risk factors for severe illness. METHODS: In this comparative cohort study, we identified hospital PCR+COVID-19 rheumatic patients with chronic inflammatory arthritis (IA) or connective tissue diseases (CTDs). Non-rheumatic controls were randomly sampled 1:1 and matched by age, sex and PCR date. The main outcome was severe COVID-19, defined as death, invasive ventilation, intensive care unit admission or serious complications. We assessed the association between the outcome and the potential prognostic variables, adjusted by COVID-19 treatment, using logistic regression. RESULTS: The cohorts were composed of 456 rheumatic and non-rheumatic patients, in equal numbers. Mean age was 63 (IQR 53-78) years and male sex 41% in both cohorts. Rheumatic diseases were IA (60%) and CTD (40%). Most patients (74%) had been hospitalised, and the risk of severe COVID-19 was 31.6% in the rheumatic and 28.1% in the non-rheumatic cohort. Ageing, male sex and previous comorbidity (obesity, diabetes, hypertension, cardiovascular or lung disease) increased the risk in the rheumatic cohort by bivariate analysis. In logistic regression analysis, independent factors associated with severe COVID-19 were increased age (OR 4.83; 95% CI 2.78 to 8.36), male sex (1.93; CI 1.21 to 3.07) and having a CTD (OR 1.82; CI 1.00 to 3.30). CONCLUSION: In hospitalised patients with chronic inflammatory rheumatic diseases, having a CTD but not IA nor previous immunosuppressive therapies was associated with severe COVID-19.

Prevalence of hospital PCR-confirmed COVID-19 cases in patients with chronic inflammatory and autoimmune rheumatic diseases.

BACKGROUND: The susceptibility of patients with rheumatic diseases and the risks or benefits of immunosuppressive therapies for COVID-19 are unknown. METHODS: We performed a retrospective study with patients under follow-up in rheumatology departments from seven hospitals in Spain. We matched updated databases of rheumatology patients with severe acute respiratory syndrome coronavirus 2-positive PCR tests performed in the hospital to the same reference populations. Rates of PCR+ confirmed COVID-19 were compared among groups. RESULTS: Patients with chronic inflammatory diseases had 1.32-fold higher prevalence of hospital PCR+ COVID-19 than the reference population (0.76% vs 0.58%). Patients with systemic autoimmune or immune-mediated disease (AI/IMID) showed a significant increase, whereas patients with inflammatory arthritis (IA) or systemic lupus erythematosus did not. COVID-19 cases in some but not all diagnostic groups had older ages than cases in the reference population. Patients with IA on targeted-synthetic or biological disease-modifying antirheumatic drugs (DMARDs), but not those on conventional-synthetic DMARDs, had a greater prevalence despite a similar age distribution. CONCLUSION: Patients with AI/IMID show a variable risk of hospital-diagnosed COVID-19. Interplay of ageing, therapies and disease-specific factors seem to contribute. These data provide a basis to improve preventive recommendations to rheumatic patients and to analyse the specific factors involved in COVID-19 susceptibility.

Hydroxychloroquine is associated with a lower risk of polyautoimmunity: data from the RELESSER Registry.

OBJECTIVES: This article estimates the frequency of polyautoimmunity and associated factors in a large retrospective cohort of patients with SLE. METHODS: RELESSER (Spanish Society of Rheumatology Lupus Registry) is a nationwide multicentre, hospital-based registry of SLE patients. This is a cross-sectional study. The main variable was polyautoimmunity, which was defined as the co-occurrence of SLE and another autoimmune disease, such as autoimmune thyroiditis, RA, scleroderma, inflammatory myopathy and MCTD. We also recorded the presence of multiple autoimmune syndrome, secondary SS, secondary APS and a family history of autoimmune disease. Multiple logistic regression analysis was performed to investigate possible risk factors for polyautoimmunity. RESULTS: Of the 3679 patients who fulfilled the criteria for SLE, 502 (13.6%) had polyautoimmunity. The most frequent types were autoimmune thyroiditis (7.9%), other systemic autoimmune diseases (6.2%), secondary SS (14.1%) and secondary APS (13.7%). Multiple autoimmune syndrome accounted for 10.2% of all cases of polyautoimmunity. A family history was recorded in 11.8%. According to the multivariate analysis, the factors associated with polyautoimmunity were female sex [odds ratio (95% CI), 1.72 (1.07, 2.72)], RP [1.63 (1.29, 2.05)], interstitial lung disease [3.35 (1.84, 6.01)], Jaccoud arthropathy [1.92 (1.40, 2.63)], anti-Ro/SSA and/or anti-La/SSB autoantibodies [2.03 (1.55, 2.67)], anti-RNP antibodies [1.48 (1.16, 1.90)], MTX [1.67 (1.26, 2.18)] and antimalarial drugs [0.50 (0.38, 0.67)]. CONCLUSION: Patients with SLE frequently present polyautoimmunity. We observed clinical and analytical characteristics associated with polyautoimmunity. Our finding that antimalarial drugs protected against polyautoimmunity should be verified in future studies.

Abatacept in interstitial lung disease associated with rheumatoid arthritis: national multicenter study of 263 patients.

OBJECTIVE: To assess the efficacy of abatacept (ABA) in RA patients with interstitial lung disease (ILD) (RA-ILD). METHODS: This was an observational, multicentre study of RA-ILD patients treated with at least one dose of ABA. ILD was diagnosed by high-resolution CT (HRCT). We analysed the following variables at baseline (ABA initiation), 12 months and at the end of the follow-up: Modified Medical Research Council (MMRC) scale (1-point change), forced vital capacity (FVC) or diffusion lung capacity for carbon monoxide (DLCO) (improvement or worsening ≥10%), HRCT, DAS on 28 joints evaluated using the ESR (DAS28ESR) and CS-sparing effect. RESULTS: We studied 263 RA-ILD patients [150 women/113 men; mean (s.d.) age 64.6 (10) years]. At baseline, they had a median duration of ILD of 1 (interquartile range 0.25-3.44) years, moderate or severe degree of dyspnoea (MMRC grade 2, 3 or 4) (40.3%), FVC (% of the predicted) mean (s.d.) 85.9 (21.8)%, DLCO (% of the predicted) 65.7 (18.3) and DAS28ESR 4.5 (1.5). The ILD patterns were: usual interstitial pneumonia (UIP) (40.3%), non-specific interstitial pneumonia (NSIP) (31.9%) and others (27.8%). ABA was prescribed at standard dose, i.v. (25.5%) or s.c. (74.5%). After a median follow-up of 12 (6-36) months the following variables did not show worsening: dyspnoea (MMRC) (91.9%); FVC (87.7%); DLCO (90.6%); and chest HRCT (76.6%). A significant improvement of DAS28ESR from 4.5 (1.5) to 3.1 (1.3) at the end of follow-up (P < 0.001) and a CS-sparing effect from a median 7.5 (5-10) to 5 (2.5-7.5) mg/day at the end of follow-up (P < 0.001) was also observed. ABA was withdrawn in 62 (23.6%) patients due to adverse events (n = 30), articular inefficacy (n = 27), ILD worsening (n = 3) and other causes (n = 2). CONCLUSION: ABA may be an effective and safe treatment for patients with RA-ILD.

Response to immunotherapy in anti-IgLON5 disease: A systematic review.

The aim of this study was to evaluate the frequency of response to immunotherapy in patients with anti-IgLON5 disease through a systematic review of the literature. MEDLINE and Embase databases were searched for studies that included patients with anti-IgLON5 disease who received immunotherapy (IT). Review inclusion criteria were met by 18 studies. The main study variable was response to IT, defined as the frequency of patients with an improvement greater than mild in at least one of the main symptoms defined by the clinical phenotype. Data were also gathered on the rate of response to last follow-up, the line(s) of IT received, the administration of monotherapy or combination therapy, and clinical and analytical characteristics. Selected studies included a total of 46 patients. A response to IT was observed in 20 (43.4%) and the presence of response to last follow-up in 15 (32.6%). Response was achieved more frequently with combination therapy vs monotherapy (14/21 [66.6%] vs 7/22 [31.8%]) and second-line therapy vs first-line therapy (7/13 [53.8%] vs 15/46 [32.6%]). The response rate by drug was 34.2% (12/35) for steroids, 42.8% (9/21) for IVIg, 46% (7/15) for PLEX, 100% (5/5) for AZA and 75% (3/4) for MMF. Factors associated with a response to IT included the cognitive impairment and non-classical phenotypes, presence of HLA-DQB1*05:01 without HLA-DRB1*10:01 and cerebral spinal fluid inflammation. Patients with anti-IgLON5 disease respond to IT, and this response is associated with certain clinical and analytical characteristics of the patients. Also rate of response seems higher with second-line and combination treatment. However, the quality of available studies is inadequate to allow definitive conclusions to be drawn.

Characterization of Flagellum and Toxin Phase Variation in Clostridioides difficile Ribotype 012 Isolates.

Clostridioides difficile causes diarrheal diseases mediated in part by the secreted toxins TcdA and TcdB. C. difficile produces flagella that also contribute to motility and bacterial adherence to intestinal cells during infection. Flagellum expression and toxin gene expression are linked via the flagellar alternative sigma factor, SigD. Recently, we identified a flagellar switch upstream of the early flagellar biosynthesis operon that mediates phase variation of both flagellum and toxin production in C. difficile strain R20291. However, we were unable to detect flagellar switch inversion in C. difficile strain 630, a ribotype 012 strain commonly used in research labs, suggesting that the strain is phase locked. To determine whether a phase-locked flagellar switch is limited to 630 or present more broadly in ribotype 012 strains, we assessed the frequency and phenotypic outcomes of flagellar switch inversion in multiple C. difficile ribotype 012 isolates. The laboratory-adapted strain JIR8094, a derivative of strain 630, and six clinical and environmental isolates were all found to be phase-off, nonmotile, and attenuated for toxin production. We isolated low-frequency motile derivatives of JIR8094 with partial recovery of motility and toxin production and found that additional changes in JIR8094 impact these processes. The clinical and environmental isolates varied considerably in the frequency by which flagellar phase-on derivatives arose, and these derivatives showed fully restored motility and toxin production. Taken together, these results demonstrate heterogeneity in flagellar and toxin phase variation among C. difficile ribotype 012 strains and perhaps other ribotypes, which could impact disease progression and diagnosis.IMPORTANCEC. difficile produces flagella that enhance bacterial motility and secretes toxins that promote diarrheal disease symptoms. Previously, we found that production of flagella and toxins is coregulated via a flippable DNA element termed the flagellar switch, which mediates the phase-variable production of these factors. Here, we evaluate multiple isolates of C. difficile ribotype 012 strains and find them to be primarily flagellar phase off (flg-off state). Some, but not all, of these isolates showed the ability to switch between flg-on and -off states. These findings suggest heterogeneity in the ability of C. difficile ribotype 012 strains to phase-vary flagellum and toxin production, which may broadly apply to pathogenic C. difficile.

Adherence of rheumatoid arthritis patients to biologic disease-modifying antirheumatic drugs: a cross-sectional study.

The aims of this study were to evaluate adherence of rheumatoid arthritis (RA) patients to biological disease-modifying antirheumatic drugs (bDMARDs), identify potential risk factors, and analyze the discriminative ability of the Morisky-Green test (MGT) to detect bDMARD nonadherence. One hundred and seventy-eight adult RA patients treated with bDMARDs were included. Adherence was measured using the medication possession ratio (MPR) of the previous 6 months. An MPR >80% was considered good adherence. Patient demographics, clinical characteristics, and MGT scores were assessed through a standardized clinical interview at the cross-sectional date. One-hundred and twelve patients (63%) were taking subcutaneous bDMARDs, while 66 (37%) were taking intravenous drugs. One-hundred fifty-eight (88.8%) showed good adherence to bDMARDs, while 79 (61.2%) also correctly took concomitant conventional synthetic DMARDs (csDMARDs). In logistic regression models, nonadherence to bDMARDs was associated with higher disease activity [odds ratio (OR) 1.45; 95% CI, 1.03-2.03; p = 0.032] and subcutaneous route (OR 3.70; 95% CI 1.02-13.48; p = 0.040). MGT accurately identified an MPR >80% of bDMARDs in 76.9% of the patients. A sensitivity of 78%, specificity of 70%, positive predictive value of 95.3%, negative predictive value of 28.5%, positive likelihood ratio (LR) of 2.6, and negative LR of 0.3% were obtained. Adherence may be good for bDMARDs but is low for csDMARDs. Low adherence for bDMARDs is associated with poorer disease control during the past 6 months and use of subcutaneous route. These findings should alert doctors to consider possible low adherence before declaring treatment failure.

[Translated article] Compounding training programme for pharmacy technicians using a digital platform and simulation techniques.

OBJECTIVE: To describe a compounding training plan in a tertiary hospital pharmacy service. The project aimed pharmacy assistant technicians to use a digital training platform and simulation techniques. METHODS: Two training programs were designed, one for sterile and the other for non-sterile drugs. Each programme consists of several phases: a basic online training course (digital e-learning platform), a practical simulation workshop, a supervised practice in real conditions, and a final verification by the pharmacist to qualify the technician. Both programs include continuous and accredited evaluation by the hospital's Continued Education Commission. A satisfaction survey on training (e-lerning platform) was designed and conducted for pharmacy technicians (sterile and non-sterile). RESULTS: The project has been running for 3 years. Six specialist pharmacists from different areas involved in compounding are responsible for training and continuous evaluation. Twenty-one technicians have been trained, and nineteen have obtained qualifications. Two of them were found to be unfit. Currently, we employ13 pharmacy technicians who were initially trained. The participation rate in the satisfaction survey on training (e-learning platform) was 61.5% (n=8) out of a total number of current developers (n=13). Overall, 62.5% of technicians reported being satisfied or very satisfied, while the remaining 37.5% were indifferent. CONCLUSIONS: Compounding training program is currently in its third year. It has been crucial in delegating tasks to pharmacy technicians. The use of digital technology is essential in this training. We consider that, specific training in compounding, is indispensable and should be included in the academic plan for pharmacy technicians.

Association between BMI z-score and body composition indexes with blood pressure and grip strength in school-age children: a cross-sectional study.

Childhood obesity is linked to diverse health outcomes, including elevated blood pressure (EBP). Emerging evidence showed that excess fat mass (FM) may have a deleterious impact on blood pressure even in normal-weight children. The primary objective of this study was to assess the association between body weight status by BMI z-score and body composition parameters by conventional bioelectrical impedance analysis (BIA) and bioelectrical impedance vector analysis (BIVA). Also, we aimed to explore the performance of BMI z-score, %FM, and FM index (FMI) in discriminating EBP in a sample of school-age Mexican children. Children were classified as having normal weight, overweight or obesity according to WHO criteria for BMI z-score. FMI was considered high when above 75th percentile, and fat free mass index (FFMI) was considered low when below 25th percentile of the reference population. Body composition was also classified according to the BIVA method and EBP was determined when systolic and/or diastolic blood pressure ≥ 90th percentile. BMI z-score groups were compared by Student´s t-test or the Mann-Whitney U test, or by the chi-square test or Fisher exact test. Receiving operating characteristic (ROC) analysis was performed. 61 children were included (52.5% boys, median age 9.8 (25th, 75th percentiles: 8.5, 11.0)) years. High FMI was observed in 32.3% of children with normal weight. Low FFMI was present in 93.5% of children with normal weight and 53.3% of those with overweight/obesity. According to BIVA, 58.1% and 43.3% of children with normal weight and overweight/obesity were classified as having cachexia. All the three adiposity indicators showed significant areas under the ROC curve (AURC) greater than 0.775 for EBP, with the largest one displayed for FM% (0.794). Hight FMI and low FFMI are common in children with normal weight. Identifying deficiency of FFM might be limited by using solely BMI indicators. Cachexia by BIVA was present in a high proportion of children with either normal weight or overweight/obesity. Both BMI z-score and FM (% and FMI) performed well at discriminating EBP, with a numerically greater AURC observed for FM%. Body composition in pediatric population is relevant for identifying body composition abnormalities at early age.

Severity and impact of digestive impairment perceived by patients with systemic sclerosis: a cross-sectional study.

OBJECTIVES: To describe the severity and impact of gastrointestinal involvement in patients with systemic sclerosis (SSc) and identify associated factors. PATIENTS AND METHODS: Non-controlled cross-sectional study of patients with SSc (2013 American College of Rheumatology/European League Against Rheumatism criteria). The main variables were severity of gastrointestinal involvement according to the University of California, Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 instrument (UCLA SCTC GIT 2.0) and dysphagia according to the Eating Assessment Tool-10 (EAT-10). We evaluated reflux, distension, diarrhoea, faecal soilage, constipation, emotional well-being and social functioning, as well as dysphagia. Clinical and epidemiological data were collected using the Mini Nutritional Assessment Short Form (MNA-SF) and the EuroQol-5D-3L. The degree of skin fibrosis was assessed using the modified Rodnan skin score (mRSS). Multivariate models were constructed to analyse factors associated with gastrointestinal involvement and dysphagia. RESULTS: Of the 75 patients with SSc included, 58.7% had moderate, severe or very severe reflux, 57.4% had constipation according to UCLA SCTC GIT 2.0 and 49.7% had abdominal distension. Gastrointestinal symptoms interfered significantly with social functioning (42.7%) and emotional well-being (40.0%). Dysphagia (EAT-10≥3) was recorded in 52% of patients, and according to MNA-SF poor nutrition in 30.7%, and clear malnutrition requiring a nutritional intervention in 5.3%. Multivariate adjustment revealed an association between severity of gastrointestinal symptoms according to the mRSS (ß=0.249; p=0.002) and Visual Analogue Scale 3-Level EuroQol-5D (VAS-EQ-5D-3L) (ß=-0.302; p=0.001), whereas presence of dysphagia was associated with the mRSS (OR=2.794; p=0.015), VAS-EQ-5D-3L (OR=0.950; p=0.005) and malnutrition (MNA-SF≤7; OR=3.920; p=0.041). CONCLUSIONS: Patients with SSc frequently present severe gastrointestinal symptoms. These are associated with poor quality of life, more severe skin involvement and malnutrition.