COVID-19 and rheumatic musculoskeletal disease patients: infection rates, attitudes and medication adherence in an Irish population.

OBJECTIVES: To establish, amongst Irish rheumatic musculoskeletal disease (RMD) patients, rates of COVID-19 symptoms and positive tests, DMARD adherence and attitudes to virtual clinics. METHODS: An online survey assessing COVID-19 status, RMD diagnoses, adherence and information sources was disseminated via the Arthritis Ireland website and social media channels. RESULTS: There were 1381 respondents with 74.8% on immunosuppressive medication. Symptoms of COVID-19 were reported by 3.7% of respondents of which 0.46% tested positive, consistent with the general Irish population. The frequency of COVID-19 symptoms was higher for respondents with spondyloarthropathy [odds ratio (OR) 2.06, 95% CI: 1.14, 3.70] and lower in those on immunosuppressive medication (OR 0.48, 95% CI: 0.27, 0.88), and those compliant with health authority (HSE) guidance (OR 0.47, 95% CI: 0.25, 0.89). Adherence to RMD medications was reported in 84.1%, with 57.1% using health authority guidelines for information on medication use. Importantly, adherence rates were higher amongst those who cited guidelines (89.3% vs 79.9%, P <0.001), and conversely lower in those with COVID-19 symptoms (64.0% vs 85.1%, P =0.009). Finally, the use of virtual clinics was supported by 70.4% of respondents. CONCLUSION: The rate of COVID-19 positivity in RMD patients was similar to the general population. COVID-19 symptoms were lower amongst respondents on immunosuppressive medication and those adherent to medication guidelines. Respondents were supportive of HSE advice and virtual clinics.

Systemic Bioavailability of Sublingual Atropine Ophthalmic Solution: a Phase I Study in Healthy Volunteers with Implications for Use as a Contingency Medical Countermeasure.

INTRODUCTION: Atropine sulfate is an FDA-approved medical countermeasure (MCM) for the treatment of organophosphorus nerve agent and organophosphate pesticide toxicity. Sufficient MCM supplies must be available in an incident involving a mass human exposure either from an accidental chemical release or a terrorist attack. METHODS: We performed a randomized, 3-sequence, 3-period phase I crossover study to assess the bioavailability and pharmacokinetics (PK) of a single dose (0.5 mg and 1.0 mg) of 1% ophthalmic atropine sulfate solution administered sublingually to 15 healthy adult volunteers. The primary endpoint was evaluation of the bioavailability of each of the two sublingual doses against a 1.0 mg reference intravenous (IV) atropine dose. Secondary endpoints included the safety and tolerability (xerostomia scale) of atropine sulfate administered sublingually. RESULTS: Sublingual atropine was safe (no severe AEs or SAEs were reported with either dose) and well tolerated, with a single subject reaching maximum xerostomia on a single dosing day. The geometric mean AUC∞ was 286.40, 493.81, and 816.47 min*ng/mL for the 0.5 mg and 1.0 mg sublingual doses, and the 1.0 mg IV dose, respectively. Compared to IV administration, the 1.0 mg sublingual dose produced 0.60 (90% CI: 0.55-0.66) of the overall concentration of atropine over time (AUC∞). CONCLUSION: Sublingual atropine sulfate 1% ophthalmic solution may be an alternative formulation and route of administration combination which expands the capacity and dosing options of atropine as a nerve agent MCM.

Safety and Immunogenicity of a Novel Intranasal Influenza Vaccine (NasoVAX): A Phase 2 Randomized, Controlled Trial.

Annual influenza vaccination greatly reduces morbidity and mortality, but effectiveness remains sub-optimal. Weaknesses of current vaccines include low effectiveness against mismatched strains, lack of mucosal and other effective tissue-resident immune responses, weak cellular immune responses, and insufficiently durable immune responses. The safety and immunogenicity of NasoVAX, a monovalent intranasal influenza vaccine based on a replication-deficient adenovirus type 5 platform, were evaluated in a placebo-controlled single ascending-dose study. Sixty healthy adults (18-49 years) received a single intranasal dose of 1×109 viral particles (vp), 1 × 1010 vp, or 1 × 1011 vp of NasoVAX or placebo. NasoVAX was well-tolerated and elicited robust influenza-specific systemic and mucosal immune responses. The highest NasoVAX dose and the approved Fluzone® influenza vaccine elicited comparable hemagglutination inhibition (HAI) geometric mean titers (152.8 vs. 293.4) and microneutralization (MN) geometric mean titers (142.5 vs. 162.8), with NasoVAX HAI titers maintained more than 1-year on average following a single dose. Hemagglutinin-specific T cells responses were also documented in peripheral mononuclear cell (PBMC) preparations. Consistent with the intranasal route of administration, NasoVAX elicited antigen-specific mucosal IgA responses in the nasopharyngeal cavity with an increase of approximately 2-fold over baseline GMT at the mid- and high-doses. In summary, NasoVAX appeared safe and elicited a broad immune response, including humoral, cellular, and mucosal immunity, with no impact of baseline anti-adenovirus antibody at the most immunogenic dose.

A quality improvement intervention failed to significantly increase pneumococcal and influenza vaccination rates in immunosuppressed inflammatory arthritis patients.

OBJECTIVES: Pneumococcal and influenza vaccination rates have been suboptimal in studies of immunosuppressed patients. We aimed to assess barriers to and increase rates of 23-valent pneumococcal polysaccharide vaccine (PPSV23) and influenza vaccination in this group. The primary endpoint was a statistically significant increase in adequate PPSV23 and influenza vaccination. METHODS: In 2017, rheumatology outpatients completed an anonymous questionnaire recording vaccination knowledge, status, and barriers. Simultaneously, a low-cost multifaceted quality improvement (QI) intervention was performed. All outpatients on oral steroids, immunosuppressant conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biologics disease-modifying antirheumatic drugs (bDMARDs) were included in the study. In 2018, post-intervention, the clinic was re-assessed. Demographics, diagnosis, medications, smart phone access, and willingness to use this for vaccination reminders were assessed for independent vaccination predictors using binary logistic regression analysis. RESULTS: Four hundred twenty-five patients were included (72.6% rheumatoid arthritis, 74% women, 45.6% ≥ 60 years old). From 2017 to 2018, PPSV23 vaccination rates changed from 41.0 to 47.2% (P = 0.29) and influenza from 61.8 to 62.1% (P = 0.95). The most common reason for non-vaccination was lack of awareness. Following the intervention, this changed for influenza (36.7 to 34.2%) and PPSV23 (82.1 to 76.4%). General practitioners performed most vaccinations, only 3.6% were delivered in the hospital. Significant predictors of PPSV23 vaccination were older age {≥ 80 years had an OR 41.66 (95% CI 3.69-469.8, P = 0.003), compared with ≤ 39 years}, bDMARD use (OR 2.80, 95% CI 1.24-6.32, P = 0.013), and adequate influenza vaccination (OR 9.01, 95% CI 4.40-18.42, P < 0.001). Up-to-date PPSV23 vaccination (OR 8.93, 95% CI 4.39-18.17, P < 0.001) predicted influenza vaccination. CONCLUSIONS: PPSV23 and influenza vaccination rates were suboptimal. The intervention did not cause a statistically significant change in vaccination rates. Point-of-care vaccination may be more effective.Key Points• Low vaccination rates amongst immunosuppressed inflammatory arthritis outpatients• Less than 5% of vaccinations occurred in hospital• There was no statistically significant difference in the rates of adequate PPSV23 (41.0 to 47.2%) or influenza (61.8 to 62.1%) vaccination following our intervention.

Prevalence and acquisition of the genes for zoocin A and zoocin A resistance in Streptococcus equi subsp. zooepidemicus.

Zoocin A is a streptococcolytic enzyme produced by Streptococcus equi subsp. zooepidemicus strain 4881. The zoocin A gene (zooA) and the gene specifying resistance to zoocin A (zif) are adjacent on the chromosome and are divergently transcribed. Twenty-four S. equi subsp. zooepidemicus strains were analyzed to determine the genetic difference among three previously characterized as zoocin A producers (strains 4881, 9g, and 9h) and the 21 nonproducers. LT-PCR and Southern hybridization studies revealed that none of the nonproducer strains possessed zooA or zif. RAPD and PFGE showed that the 24 strains were a genetically diverse population with eight RAPD profiles. S. equi subsp. zooepidemicus strains 9g and 9h appeared to be genetically identical to each other but quite different from strain 4881. Sequences derived from 4881 and 9g showed that zooA and zif were integrated into the chromosome adjacent to the gene flaR. A comparison of these sequences with the genome sequences of S. equi subsp. zooepidemicus strains H70 and MGCS10565 and S. equi subsp. equi strain 4047 suggests that flaR flanks a region of genome plasticity in this species.

Readability and Quality of Online Information on Osteoarthritis: An Objective Analysis With Historic Comparison.

BACKGROUND: Osteoarthritis (OA) is the most common cause of disability in people older than 65 years. Readability of online OA information has never been assessed. A 2003 study found the quality of online OA information to be poor. OBJECTIVE: The aim of this study was to review the readability and quality of current online information regarding OA. METHODS: The term osteoarthritis was searched across the three most popular English language search engines. The first 25 pages from each search engine were analyzed. Duplicate pages, websites featuring paid advertisements, inaccessible pages (behind a pay wall, not available for geographical reasons), and nontext pages were excluded. Readability was measured using Flesch Reading Ease Score, Flesch-Kincaid Grade Level, and Gunning-Fog Index. Website quality was scored using the Journal of the American Medical Association (JAMA) benchmark criteria and the DISCERN criteria. Presence or absence of the Health On the Net Foundation Code of Conduct (HONcode) certification, age of content, content producer, and author characteristics were noted. RESULTS: A total of 37 unique websites were found suitable for analysis. Readability varied by assessment tool from 8th to 12th grade level. This compares with the recommended 7th to 8th grade level. Of the 37, 1 (2.7%) website met all 4 JAMA criteria. Mean DISCERN quality of information for OA websites was "fair," compared with the "poor" grading of a 2003 study. HONcode-endorsed websites (43%, 16/37) were of a statistically significant higher quality. CONCLUSIONS: Readability of online health information for OA was either equal to or more difficult than the recommended level.

Seroepidemiology of hepatitis A, hepatitis B and varicella virus in people living with HIV in Ireland.

Epidemiological studies investigating seroprevalence of vaccine preventable infections at both individual and population level are important in guiding screening and vaccination practices. Data on seroprevalence of common vaccine preventable infections in HIV-infected individuals is lacking. We carried out a retrospective cohort study to investigate serological immunity and factors associated with immunity to hepatitis A virus (HAV), hepatitis B virus (HBV) and varicalla virus (VZV) in a cohort of HIV-infected individuals attending a large ambulatory HIV specialist centre in Ireland. Basic demographic data including risk of acquisition of HIV and region of origin was recorded. Between-group prevalence was compared using the Chi2 test and Wilkoxin signed rank test. Univariate variables with p<0.2 were entered into a multivariate logistic regression model. Of 1287 HIV-infected individuals included in this study (median [SD] age 39 [10] years, 68% male, 46% Irish), 75% were hepatitis A IgG positive, 94% were VZV IgG positive, 3% were HBV surface antigen (sAg) positive while 29% were HBV core antibody (cAb) positive. This study identifies a significant proportion of HIV infected who were susceptible to common vaccine preventable infections. These results highlight the importance of proactive screening and immunization of HIV-infected individuals to ensure optimal protect ionagainst vaccine preventable diseases in this at risk patient group.

Factors associated with non-retention in HIV care in an era of widespread antiretroviral therapy.

In an era of antiretroviral therapy (ART) for all HIV-1-infected patients, our primary aim was to describe prevalence and characteristics of patients disengaged from care at an urban ambulatory HIV clinic. We conducted a nested case-control study. All patients who disengaged from care (defined as being lost to follow-up for at least one year) from 2007 to 2014 inclusive were identified. Cases were matched to controls in a 1:4 ratio. A total of 1250 cases were included; 250/2289 (10.9%) of patients attending our HIV clinic disengaged from 2007 to 2014. One hundred and twenty-six (50.4%) were heterosexual, 81 (32.4%) were men who have sex with men and 40 (16%) were intravenous drug users. On univariate analysis only, patients with heterosexual risk were more likely to disengage from care (50.4% vs. 33.7%, p: <0.001). Those who disengaged were younger, mean age of 39 (p: <0.001). A higher proportion of patients who disengaged from care was not receiving ART and did not have a suppressed HIV-1 viral load (p: <0.001). On multivariable analysis, Irish patients were less likely to disengage from HIV care (odds ratio: 0.567, p: 0.002). Factors associated with non-retention in HIV care have been identified. A semi-structured interview of those patients who re-engaged will take place to further examine reasons for disengagement from care.

Coefficients of fat and nitrogen absorption in healthy subjects and individuals with cystic fibrosis.

BACKGROUND: We sought to compare the differences of coefficient of fat absorption (CFA) and coefficient of nitrogen absorption (CNA) in healthy individuals and those with cystic fibrosis (CF) and to study the precision of CFA and CNA. METHODS: Sixteen healthy and 23 subjects with CF and pancreatic insufficiency ate a high-fat, high-protein diet for 72 hours; stool was collected between blue food dye markers to determine CFA and CNA. Subjects with CF withheld pancreatic enzymes. Tests were repeated on 5 of the CF and 10 of the healthy subjects. RESULTS: In healthy subjects, mean CFA was 93.5% ± 2.7%; mean CNA was 88.1% ± 5%. Median test-retest in 10 healthy subjects was +0.7% CFA (range, -8.1% to + 5.9%) and +0.9% CNA (range, -14.6% to +6.8%). For subjects with CF, mean CFA was 38.5% ± 14.7% and mean CNA was 52.2% ± 11.4%. Median test-retest change in 5 subjects with CF was -6.9% CFA (range, -19.7% to +42.8%) and +14.7% CNA (range, -6.4% to +42.8%). CONCLUSIONS: CFA and CNA have inconsistent precision in CF. The limitations of CFA as a measure of steatorrhea correction in CF should be recognized in studies of pancreatic enzyme supplements.

Safety and preliminary clinical activity of a novel pancreatic enzyme preparation in pancreatic insufficient cystic fibrosis patients.

OBJECTIVES: Currently available pancreatic enzyme products are crude porcine products with few data available regarding their efficacy, safety, and manufacture. We conducted a phase 1 study of a novel pancreatic enzyme product, TheraCLEC-Total (TCT), a proprietary formulation of microbial-derived lipase, protease, and amylase, to determine its safety and preliminary efficacy in cystic fibrosis. METHODS: We conducted an open-label, dose-ranging study in 23 subjects diagnosed with pancreatic insufficiency with cystic fibrosis. The subjects received TCT containing lipase dose of 100, 500, 1000, 2500, or 5000 USP U/kg per meal with each meal or snack for 3 days. The clinical and laboratory parameters and adverse events (AEs) were monitored. RESULTS: There were no serious AEs. Most AEs were mild, although gastrointestinal complaints were common. TCT increased the coefficient of fat and nitrogen absorption in all groups except in the low-dose group. At the other dosing levels, the mean coefficient of fat and nitrogen absorption increases were 19.1% +/- 24.9% and 17.8% +/- 13.6%, respectively, whereas the mean stool weight decreased by 517 +/- 362 g. CONCLUSIONS: TCT was well tolerated in this short-term exposure study. The preliminary efficacy data demonstrate lipase and protease activity with little difference seen with lipase doses greater than 500 USP U/kg per meal. These data support a larger randomized phase 2 trial.