Mucoadhesive film for oral delivery of vaccines for protection of the respiratory tract.

The delivery of vaccines plays a pivotal role in influencing the strength and longevity of the immune response and controlling reactogenicity. Mucosal immunization, as compared to parenteral vaccination, could offer greater protection against respiratory infections while being less invasive. While oral vaccination has been presumed less effective and believed to target mainly the gastrointestinal tract, trans-buccal delivery using mucoadhesive films (MAF) may allow targeted delivery to the mucosa. Here we present an effective strategy for mucosal delivery of several vaccine platforms incorporated in MAF, including DNA plasmids, viral vectors, and lipid nanoparticles incorporating mRNA (mRNA/LNP). The mRNA/LNP vaccine formulation targeting SARS-CoV-2 as a proof of concept remained stable within MAF consisting of slowly releasing water-soluble polymers and an impermeable backing layer, facilitating enhanced penetration into the oral mucosa. This formulation elicited antibody and cellular responses comparable to the intramuscular injection, but also induced the production of mucosal IgAs, highlighting its efficacy, particularly for use as a booster vaccine and the potential advantage for protection against respiratory infections. The MAF vaccine preparation demonstrates significant advantages, such as efficient delivery, stability, and simple noninvasive administration with the potential to alleviate vaccine hesitancy.

Mortality, seasonal variation, and susceptibility to acute exacerbation of COPD in the pandemic year: a nationwide population study.

BACKGROUND: Previous studies have suggested that the coronavirus disease 2019 (COVID-19) pandemic was associated with a decreased rate of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Data on how the COVID-19 pandemic has influenced mortality, seasonality of, and susceptibility to AECOPD in the chronic obstructive pulmonary disease (COPD) population is scarce. METHODS: We conducted a national population-based retrospective study using data from the Health Insurance Institute of Slovenia from 2015 to February 2021, with 2015-2019 as the reference. We extracted patient and healthcare data for AECOPD, dividing AECOPD into severe, resulting in hospitalisation, and moderate, requiring outpatient care. The national COPD population was generated based on dispensed prescriptions of inhalation therapies, and moderate AECOPD events were analysed based on dispensed AECOPD medications. We extracted data on all-cause and non-COVID mortality. RESULTS: The numbers of severe and moderate AECOPD were reduced by 48% and 34%, respectively, in 2020. In the pandemic year, the seasonality of AECOPD was reversed, with a 1.5-fold higher number of severe AECOPD in summer compared to winter. The proportion of frequent exacerbators (⩾2 AECOPD hospitalisations per year) was reduced by 9% in 2020, with a 30% reduction in repeated severe AECOPD in frequent exacerbators and a 34% reduction in persistent frequent exacerbators (⩾2 AECOPD hospitalisations per year for 2 consecutive years) from 2019. The risk of two or more moderate AECOPD decreased by 43% in 2020. In the multivariate model, pandemic year follow-up was the only independent factor associated with a decreased risk for severe AECOPD (hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.61-0.84; p < 0.0001). In 2020, non-COVID mortality decreased (-15%) and no excessive mortality was observed in the COPD population. CONCLUSION: In the pandemic year, we found decreased susceptibility to AECOPD across severity spectrum of COPD, reversed seasonal distribution of severe AECOPD and decreased non-COVID mortality in the COPD population.

Effects of Reiki on Pain and Anxiety in Women Hospitalized for Obstetrical- and Gynecological-Related Conditions.

Purpose: To determine the effect of Reiki on pain and anxiety in women in antepartum, intrapartum, postpartum, gynecology, and gyn/oncology, settings. Method: This exploratory, comparative study used a Likert-type scale of 0 to 10 to measure pain and anxiety, and a survey asking about lingering effects of treatment. Results: Mean pain scores after Reiki significantly decreased from 3.24 to 1.52 (n = 203; z = -11.67, p < .001). Mean anxiety scores after Reiki significantly decreased from 3.56 to 1.28 (n = 195; z = -11.42, p < .001). Women were asked if the effects lingered for any length of time post-Reiki treatment, and 91 of 101 responded affirmatively that decreased pain and/or anxiety continued. Conclusion: Findings from this study confirm the positive and lingering effects of Reiki in women hospitalized for obstetrical and gynecological conditions.

Venous thromboembolism prophylaxis in hospitalized patients with pneumonia: a prospective survey.

BACKGROUND: Guidelines for prevention of venous thromboembolism recognize pneumonia and changes in respiratory status as risk factors. There is little information on the preventive use of low-molecular-weight heparin (LMWH) in hospitalized patients with pneumonia. METHODS: We prospectively screened 1067 admissions to our hospital for preventive use of LMWH according to the American College of Chest Physicians (ACCP) guidelines. The analysis included 168 patients with pneumonia (age 74 +/- 16 years, 56% men). The primary and secondary outcomes were treatment with LMWH in eligible patients and LMWH use according to guidelines (daily dose, duration of treatment). RESULTS: LMWH use was indicated in 126 (75%) patients and 119 (94%) were actually treated. In 41% of patients treatment was according to the ACCP guidelines. The dose and duration of LMWH treatment were appropriate in 61% and 66% of patients, respectively. Non-use of LMWHs was not associated with clinical and demographic characteristics. Adverse effects included bleeding (N = 7) and thrombocytopenia (N = 2) but were not associated with fatality. Prolonged treatment with LMWH was associated with adverse effects (P < 0.05). CONCLUSIONS: Implementation of LMWH prophylaxis for venous thromboembolism in hospitalized patients with pneumonia reached 94%. Adherence to ACCP guidelines was complete in 41% of patients. Prolonged treatment with LMWH was associated with non-fatal adverse effects, which calls for timely withdrawal of LMWH once no longer indicated.

Aspirin-induced COX-2 overexpression in monocytes of aspirin-intolerant patients.

BACKGROUND: We hypothesize that alternate regulation of cyclooxygenase-2 (COX-2) may predispose patients to aspirin-induced exacerbations.Therefore, we want to examine the dynamics of COX-2 up-regulation in whole blood monocytes in the presence and absence of aspirin. METHODS: COX-2 expression was evaluated by flow cytometry through intracellular staining of whole blood monocytes with anti-COX-2 antibodies. Enzyme up-regulation was monitored after in vitro stimulation with lipopolysaccharide (LPS) and/or aspirin in 19 aspirin-intolerant (AI) patients (8 aspirin-sensitive asthmatics and 11 urticaria-angioedema patients) and 14 healthy controls. RESULTS: We found significantly higher COX-2 expression levels after stimulation with LPS and aspirin (mean 78.8, range 44.9-92.3; p = 0.0002) in comparison to LPS alone (mean 65.9%, range 33.6-82.6) in AI patients. A comparable, but lower up-regulation was also observed after aspirin stimulation alone (median 2.1%, range 0.5-15.9; p = 0.004) in comparison with baseline values (median 1%, range 0.1-5.4). There was no significant difference in COX-2 expression between LPS and aspirin stimulation (mean 61.8%, range 26.8-89.2; p = 0.09) and LPS stimulation (mean 55.5%, range 28.1-74.3) nor between aspirin stimulation alone (median 0.5%, range 0-8.6; p = 0.8) and baseline values (median 0.4%, range 0-5.4) in healthy control subjects. CONCLUSIONS: The main finding of this study is that COX-2 appears to be differentially regulated in aspirin-sensitive patients. What is really new is the observation that aspirin and LPS increase COX-2 expression on blood monocytes of AI asthmatics, a finding in contrast with the lack of an effect of the same stimuli on COX-2 expression on monocytes from healthy subjects.

Perceived cognitive dysfunction and observed neuropsychological performance: longitudinal relation in persons with multiple sclerosis.

The relation between self-reported cognitive dysfunction and neuropsychological performance over 24 weeks was assessed in a sample of 53 multiple sclerosis patients. Subjects were assessed at Weeks Zero and 24 as part of a clinical trial to enhance cognition. At baseline, subjects had at least mild cognitive impairment on the Rey Auditory Verbal Learning Test and an absence of depression. Neuropsychological performance was assessed with a modification of the well standardized Brief Repeatable Battery. The 5-item Perceived Deficits Questionnaire and a 2-item memory and attention/concentration questionnaire assessed self-perceived cognitive impairment. Self-assessed cognition did not correlate with neuropsychological performance at either baseline or 24 weeks. However, changes in the self-assessment measures did correlate with changes in neuropsychological performance. Patients accurately perceived some changes in their level of cognitive dysfunction, though they were insensitive to the degree of their current dysfunction. Possible explanations of this pattern of results are discussed.

Normative data for the selective reminding test: a random digit dialing sample.

Healthy control participants (46 women, M age=44.3 yr., SD=7.6; 29 men) were recruited to undergo a comprehensive neuropsychological battery and serve as a comparison group in a study of cognitive functioning in patients with Lyme isease. Participants were selected using Mitofsky-Waksberg random digit dialing. The Buschke 12-word, six-trial Selective Reminding Test was administered as part of the neuropsychological battery and normative data are presented stratified by age and sex. Performance on alternate forms of this measure were examined. Mean education, intelligence quotient, and Wide Range Achievement Test-3 Reading scores are reported.