Tofacitinib versus Biologic Treatments in Moderate-to-Severe Rheumatoid Arthritis Patients Who Have Had an Inadequate Response to Nonbiologic DMARDs: Systematic Literature Review and Network Meta-Analysis

Objective. To compare the efficacy and tolerability of tofacitinib, an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), as monotherapy and combined with disease-modifying antirheumatic drugs (DMARDs) versus biological DMARDs (bDMARDs) and other novel DMARDs for second-line moderate-to-severe rheumatoid arthritis (RA) patients by means of a systematic literature review (SLR) and network meta-analysis (NMA). Methods. MEDLINE®, EMBASE®, and Cochrane Central Register of Controlled Trials were searched to identify randomized clinical trials (RCTs) published between 1990 and March 2015. Efficacy data based on American College of Rheumatology (ACR) response criteria, improvements in the Health Assessment Questionnaire Disability Index (HAQ-DI) at 6 months, and discontinuation rates due to adverse events were analyzed by means of Bayesian NMAs. Results. 45 RCTs were identified, the majority of which demonstrated a low risk of bias. Tofacitinib 5 mg twice daily (BID) and 10 mg BID monotherapy exhibited comparable efficacy and discontinuation rates due to adverse events versus other monotherapies. Tofacitinib 5 mg BID and 10 mg BID + DMARDs or methotrexate (MTX) were mostly comparable to other combination therapies in terms of efficacy and discontinuation due to adverse events. Conclusion. In most cases, tofacitinib had similar efficacy and discontinuation rates due to adverse events compared to biologic DMARDs

Meaningful Changes in What Matters to Individuals with Vitiligo: Content Validity and Meaningful Change Thresholds of the Vitiligo Area Scoring Index (VASI)

INTRODUCTION: This study explored patients\u27 and dermatologists\u27 priority outcomes for treatment to address, clinical outcome assessments (COA) for use in vitiligo clinical trials, and perceptions of within-patient meaningful change in facial and total body vitiligo. METHODS: Semistructured, individual, qualitative interviews were conducted with patients living with non-segmental vitiligo in the USA and with expert dermatologists in vitiligo. Concept elicitation discussions included open-ended questions to identify patient priority outcomes. Vitiligo COAs were reviewed by dermatologists. Tasks were completed by patients to explore their perceptions of meaningful changes in vitiligo outcomes; dermatologists\u27 opinions were elicited. Data were analyzed using thematic methods; meaningful change tasks were descriptively summarized. RESULTS: Individuals with vitiligo (N = 60) included adults (n = 48, 63% female) and adolescents (n = 12, 67% female). All Fitzpatrick Skin Types were represented. Eight (13%) were first- or second-generation immigrants to the USA. Expert dermatologists (N = 14) participated from the USA (n = 8), EU (n = 4), India (n = 1), and Egypt (n = 1). All individuals with vitiligo reported experiencing skin depigmentation; an observable clinical sign of vitiligo. Most confirmed that lesion surface area (n = 59/60, 98%) and level of pigmentation (n = 53/60, 88%) were important to include in disease assessments. Following an explanation, participants (n = 49/60, 82%) felt that the Facial Vitiligo Area Scoring Index (F-VASI) measurement generally made sense and understood that doctors would use it to assess facial vitiligo. Most participants felt that a 75% (n = 47/59, 80%) or 9 0% improvement in their facial vitiligo would be indicative of treatment success (n = 55/59, 93%). In the context of evaluating a systemic oral treatment for vitiligo, dermatologists perceived a 75% improvement on the F-VASI as successful (n = 9/14, 64%). Regarding the Total VASI (T-VASI) score, n = 30 participants considered 33% improvement as treatment success; an additional n = 10 endorsed 50% improvement and a further n = 5 endorsed 75% improvement. Clinicians most frequently identified 50% (n = 6/14, 43%) or 75% (n = 4/14, 29%) improvement in T-VASI as successful. CONCLUSION: Repigmentation is a priority outcome for patients. The VASI was considered an appropriate tool to assess the extent of vitiligo. A minimum 75% improvement from baseline in the F-VASI and minimum 50% improvement from baseline in the T-VASI were identified as within-patient clinically meaningful thresholds

Cytotoxicity of Glass Ionomer Cement on Human Exfoliated Deciduous Teeth Stem Cells Correlates with Released Fluoride, Strontium and Aluminum Ion Concentrations

Stem cells from human exfoliated deciduous teeth (SHED) can be used as a cell-based therapy in regenerative medicine and in immunomodulation. Pulp from human deciduous teeth can be stored as a source of SHED. Glass ionomer cements (GICs) are commonly used in restorative dentistry and in cavity lining. GICs have lower biocompatibility and are cytotoxic for dental pulp cells. In this study, seven commonly used GICs were tested for their cytotoxic effects on SHED, for their potential to arrest mitosis in cells and induce chromosome aberrations, and were compared with the effects of composite. Fuji II, Fuji VIII, Fuji IX, Fuji plus and Vitrebond had significantly higher cytotoxic effects on SHED than composite. Only SHEDs that have been treated with Fuji I, Fuji IX, Fuji plus and composite recovered the potential for proliferation, but no chromosome aberrations were found after treatment with GICs. The cytotoxic effects of GICs on SHEDs were in strong correlation with combined concentrations of released fluoride, aluminum and strontium ions. Fuji I exhibited the lowest activity towards SHEDs; it did not interrupt mitosis and did not induce chromosome aberrations, and was accompanied by the lowest levels of released F, Al and Sr ions

Efficacy of tofacitinib in reducing pain in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis

Objective: To describe the efficacy of tofacitinib in reducing pain in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS) in a post-hoc analysis of randomised controlled trials. Methods: Data were collected from patients in seven tofacitinib studies: six phase III (four RA, two PsA) and one phase II study (AS), and grouped into five analysis populations based on rheumatic disease diagnosis and category of prior inadequate response (IR) to treatment: conventional synthetic disease-modifying antirheumatic drugs-IR (RA and PsA), tumour necrosis factor inhibitors-IR (RA and PsA), or non-steroidal anti-inflammatory drugs-IR (AS). Only patients who received tofacitinib 5 or 10 mg twice daily or placebo were included. Pain assessments included: Patient’s Assessment of Arthritis Pain, Short-Form Health Survey 36v2 Question (Q)7 and Bodily Pain domain, Ankylosing Spondylitis Quality of Life Q9 and Q14, EuroQol Five Dimensions Pain/Discomfort dimension and Bath Ankylosing Spondylitis Disease Activity Index Q2 and Q3. Data were reported to month 6 (placebo to month 3) in the RA and PsA populations, and week 12 (tofacitinib and placebo) in the AS population. Results: Overall, 3330 patients were included in this analysis. In the RA and PsA populations, pain improvements in tofacitinib-treated patients compared with placebo were observed at the earliest time point assessed and at month 3 (maintained to month 6). In the AS population, pain improvements compared with placebo were observed at week 12. Conclusion: Tofacitinib was associated with rapid and sustained improvements across multiple pain measures in patients with inflammatory rheumatic musculoskeletal diseases

Seroprevalence of SARS-CoV-2 infection among children in Children’s Hospital Zagreb during the initial and second wave of COVID-19 pandemic in Croatia

The study aimed to investigate the prevalence and titres of anti-SARS-CoV-2 antibodies in children treated at the Children’s Hospital Zagreb in the first and the second wave of the COVID-19 pandemic. Statistical significance of difference at two time points was done to determine how restrictive epidemiological measures and exposure of children to COVID-19 infection affect this prevalence in different age groups. At the first time point (13th to 29th May 2020), 240 samples and in second time point (24th October to 23rd November 2020), 308 serum samples were tested for anti-SARS-CoV-2 antibodies by enzyme-linked immunosorbent assay (ELISA) and electrochemiluminescence immunoassay (ECLIA). Confirmation of results and titre determination was done using virus micro-neutralization test. Subjects were divided according to gender, age and epidemiological history. Seroprevalence of anti-SARS-CoV-2 antibodies differs significantly in two time points (P = 0.010). In first time point 2.9% of seropositive children were determined and in second time point 8.4%. Statistically significant difference (P = 0.007) of seroprevalence between two time points was found only in a group of children aged 11-19 years. At the first time point, all seropositive children were asymptomatic with titre < 8. At the second time point, 69.2% seropositive children were asymptomatic with titre ≥ 8. The prevalence of anti-SARS-CoV-2 antibodies was significantly lower at the first time point than at the second time point. Values of virus micro-neutralization test showed that low titre in asymptomatic children was not protective at the first time point but in second time point all seropositive children had protective titre of anti-SARS-CoV-2 antibodies

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Discrimination between normal and malignant breast tissues by synchronous luminescence spectroscopy

Studies of fluorescence from endogenous molecules in tissues are common for applications such as detection or characterization of early disease. Breast cancer is one of the most common malignant tumor among women and good screening methods are therefore of considerable interest. We have applied synchronous luminescence spectroscopy (SLS) to examine specimens of excised breast tissues. Measurements have been made in the 330 nm to 650 nm range of excitation wavelengths and constant wavelength interval varying from 30 nm to 120 nm on 21 normal and 21 malignant breast tissue samples. Significant differences between SLS patterns of normal and malignant tissues are detected and related to the discrepancy in concentrations of extracellular proteins and co-enzymes. Malignant tissue identification criteria are established on the basis of spectral peak areas of SLS spectra that correspond to constant wavelength intervals where the most pronounced differences are observed. These characteristic intervals are chosen from the difference of averaged three-dimensional SLS patterns of normal and malignant breast tissues. Using observed statistically significant spectral differences as classification criteria we tested classification success rate of presented SLS method