Incidence of hypersensitivity reactions in patients on H1-receptor antagonists receiving oxaliplatin-based chemotherapy.

OBJECTIVE: This study determined the incidence of hypersensitivity reactions in patients receiving oxaliplatin-based chemotherapy while on H1-receptor antagonists (H1RAs). Prophylaxis for patients receiving oxaliplatin is not currently recommended. H1RAs are used for the treatment of reactions; however, prophylactic H1RAs have not been well-studied. METHODS: This retrospective chart review included patients with solid tumor malignancies who received H1RAs while on oxaliplatin-based chemotherapy between August 1, 2016 and October 31, 2019. RESULTS: Of fifty-one patients, there were four hypersensitivity reactions (8%), most of which were mild, occurred within 60 minutes of the start of the infusion, and did not result in an interruption in treatment. One severe reaction occurred, which required discontinuation of therapy. Forty-two patients (82%) were able to receive at least 9 cycles of oxaliplatin without a reported reaction. CONCLUSION: In this observational study, the incidence rate of hypersensitivity reactions in patients receiving oxaliplatin while on H1RAs was lower than reported in previous literature. Most reactions were mild, and patients were able to continue oxaliplatin-based therapy. With future, randomized controlled trials, H1RAs may prove to be effective in preventing or delaying the onset of hypersensitivity reactions related to oxaliplatin.

Improved asthma outcomes among at-risk children in a pharmacist-led, interdisciplinary school-based health clinic: A pilot study of the CAReS program.

BACKGROUND: Disparities in access to care and outcomes have been identified among children with asthma living in underserved communities. The Caring for Asthma in our Region's Schoolchildren program was established to reduce disparities by providing school-based, comprehensive asthma care by a pharmacist-led, interdisciplinary team to high-risk pediatric populations in the Greater Pittsburgh area. OBJECTIVE: To investigate program impact on follow-up appointment attendance, delivery of guideline-based care, asthma control, asthma morbidity (emergency department [ED] visits, oral corticosteroid [OCS] requirement), and asthma-related knowledge and quality of life. METHODS: The study enrolled 50 children with asthma from 6 elementary schools (September 2014-December 2017). Children completed 5 visits over a 3-month period. McNemar's test assessed improvement in guideline-based controller therapy use and reduced morbidity (ED visits or OCS requirement). Generalized estimating equation analyses determined the significance of monthly improvements in asthma control, asthma knowledge, and quality of life. RESULTS: A 100% show rate was achieved in nearly all participants (92.0%). Most of the patients were African-American (56%). In children with persistent disease, only 21.4% were prescribed controller therapy at baseline, which improved to 78.5% upon enrollment (P < 0.05). Asthma control statistically significantly improved (P < 0.05), and a reduction in percentage of patients who required an ED visit or an OCS burst pre-to postintervention was also statistically significant (31.3% vs. 14.6%, P < 0.05). The goal of 100% treatment plan knowledge was achieved in 67% of caregivers within 1 month and increased from 6% to 60% in children over 3 months (P < 0.05). Asthma-related quality of life also improved statistically significantly pre-to postintervention (P < 0.05). CONCLUSIONS: Disparities in asthma outcomes owing to inadequate access to health care can be addressed. Improved asthma control, asthma medication knowledge, quality of life, and reduced morbidity in high-risk pediatric patients are achievable as demonstrated by our study. Our findings support the feasibility and value of a pharmacist-led, interdisciplinary school-based health care delivery model in providing comprehensive asthma care to at-risk pediatric populations.

Knowledge and perceptions of Alzheimer's disease in three ethnic groups of younger adults in the United Kingdom.

BACKGROUND: Alzheimer's disease (AD) is a global public health problem with an ageing population. Knowledge is essential to promote early awareness, diagnosis and treatment of AD symptoms. AD knowledge is influenced by many cultural factors including cultural beliefs, attitudes and language barriers. This study aims: (1) to define AD knowledge level and perceptions amongst adults between 18 and 49 years of age in the UK; (2) to compare knowledge and perceptions of AD among three main ethnic groups (Asian, Blacks, and Whites); and (3) to assess potential associations of age, gender, education level, affinity with older people (65 or over), family history and caregiving history with AD knowledge. METHODS: Data was collected from 186 participants as a convenience sample of younger adults of three different ethnicities (16.1% Asian, 16.7% Black, 67.2% White), living in the UK, recruited via an online research platform. The majority of the participants were in the 18-34 years age group (87.6%). Demographic characteristics of participants and AD knowledge correlation were assessed by the 30-item Alzheimer's Disease Knowledge Scale (ADKS), comprising 7 content domains. ANOVA/ANCOVA were used to assess differences in AD knowledge by ethnicity, gender, education level, age and affinity with dementia and Alzheimer's patients. RESULTS: For AD general knowledge across all respondents only 45.0% answers were correct. No significant differences were found for the total ADKS score between ethnicities in this younger age group, who did not differ in education level. However, there were significant knowledge differences for the ADKS symptom domain score even after controlling for other demographics variables such as gender, education level (p = 0.005). White respondents were more likely to know about AD symptoms than their Black counterparts (p = 0.026). CONCLUSION: The study's findings suggest that the AD knowledge level is not adequate for all ethnic groups. Meanwhile, significant differences were observed in symptoms, between ethnic groups, and therefore, differ in their needs regards health communication. The study contributes to an understanding of ethnicity differences in AD knowledge amongst adults from 18 to 49 years of age in the UK and may also provide input into an intervention plan for different ethnicities' information needs.

Knowledge, socio-cognitive perceptions and the practice of hand hygiene and social distancing during the COVID-19 pandemic: a cross-sectional study of UK university students.

BACKGROUND: During the first wave of the COVID-19 pandemic, social distancing and hand hygiene have been the primary means of reducing transmission in the absence of effective treatments or vaccines, but understanding of their determinants is limited. This study aimed to investigate knowledge and socio-cognitive perceptions, and their associations with such protective behaviours, in UK university students. METHODS: A cross-sectional online survey of 293 students was undertaken on 13 May 2020. Survey questions addressed demographics, knowledge of the disease and effectiveness of the protective measures, risk perception, socio-cognitive perceptions (e.g. attitude, social support, and self-efficacy), habit, time factors and trust, as well as the hand hygiene and social distancing behaviours. Multiple linear regression was used to identify the strongest associations of potential determinants with behaviour. RESULTS: Participants reported high levels of social distancing with 88.9% answering "Mostly" or "Always" for every activity, but only 42.0% reporting the same for all hand hygiene activities. Knowledge of the effectiveness of each activity in preventing transmission was high, with 90.7% and 93.5% respectively identifying at least 7 of 8 hand hygiene or 9 of 10 social distancing activities correctly. Habit (ß = 0.39, p = 0.001) and time factors (ß = 0.28, p = 0.001) were the greatest contributors to unique variance in hand hygiene behaviour, followed by ethnicity (ß = - 0.13, p = 0.014) and risk perception (ß = 0.13, p = 0.016). For social distancing behaviour, the determinants were self-efficacy (ß = 0.25, p < 0.001), perceived advantages (ß = 0.15, p = 0.022), trust in policy (ß = 0.14, p = 0.026) and gender (ß = - 0.14, p = 0.016). Regression models explained 40% hand hygiene and 25% social distancing variance. CONCLUSIONS: This study indicated that communications about effectiveness of hand hygiene and social distancing behaviours had been effective in terms of knowledge acquisition. However, in the light of likely second waves of COVID-19, attention to maintaining social distancing behaviour and improving hand hygiene behaviour may need to address more difficult areas of changing habits, overcoming time factors and building trust, as well as interventions to increase self-efficacy and address risk perception concerns.

Depletion of LAG-3+ T Cells Translated to Pharmacology and Improvement in Psoriasis Disease Activity: A Phase I Randomized Study of mAb GSK2831781.

Activated T cells drive a range of immune-mediated inflammatory diseases. LAG-3 is transiently expressed on recently activated CD4+ and CD8+ T cells. We describe the engineering and first-in-human clinical study (NCT02195349) of GSK2831781 (an afucosylated humanized IgG1 monoclonal antibody enhanced with high affinity for Fc receptors and LAG-3 and antibody-dependent cellular cytotoxicity capabilities), which depletes LAG-3 expressing cells. GSK2831781 was tested in a phase I/Ib, double-blind, placebo-controlled clinical study, which randomized 40 healthy participants (part A) and 27 patients with psoriasis (part B) to single doses of GSK2831781 (up to 0.15 and 5 mg/kg, respectively) or placebo. Adverse events were generally balanced across groups, with no safety or tolerability concern identified. LAG-3+ cell depletion in peripheral blood was observed at doses ≥ 0.15 mg/kg and was dose-dependent. In biopsies of psoriasis plaques, a reduction in mean group LAG-3+ and CD3+ T-cell counts was observed following treatment. Downregulation of proinflammatory genes (IL-17A, IL-17F, IFNγ, and S100A12) and upregulation of the epithelial barrier integrity gene, CDHR1, was observed with the 5 mg/kg dose of GSK2831781. Psoriasis disease activity improved up to day 43 at all GSK2831781 doses (0.5, 1.5, and 5 mg/kg) compared with placebo. Depletion of LAG-3-expressing activated T cells is a novel approach, and this first clinical study shows that GSK2831781 is pharmacologically active and provides encouraging early evidence of clinical effects in psoriasis, which warrants further investigation in T-cell-mediated inflammatory diseases.

Effect of belimumab on proteinuria and anti-phospholipase A2 receptor autoantibody in primary membranous nephropathy.

BACKGROUND: Immunosuppressant drugs reduce proteinuria and anti-phospholipase A2 receptor autoantibodies (PLA2R-Ab) in primary membranous nephropathy (PMN) with varying success and associated toxicities. This study aimed to evaluate the effect of belimumab on proteinuria and PLA2R-Ab in participants with PMN. METHODS: In this prospective, open-label, experimental medicine study, 14 participants with PMN and persistent nephrotic-range proteinuria received up to 2 years belimumab monotherapy (10 mg/kg, every 4 weeks). Changes in proteinuria (urinary protein:creatinine ratio), PLA2R-Ab, albumin, cholesterol, B-cell subsets and pharmacokinetics were analysed during treatment and up to 6 months after treatment. RESULTS: Eleven participants completed to the primary endpoint (Week 28) and nine participants completed the study. In the intention-to-treat population population, baseline proteinuria of 724 mg/mmol [95% confidence interval (CI) 579-906] decreased to 498 mg/mmol (95% CI 383-649) and 130 mg/mmol (95% CI 54-312) at Weeks 28 and 104, respectively, with changes statistically significant from Week 36 (n = 11, P = 0.047). PLA2R-Ab decreased from 174 RU/mL (95% CI 79-384) at baseline to 46 RU/mL (95% CI 16-132) and 4 RU/mL (95% CI 2-6) at Weeks 28 and 104, respectively, becoming statistically significant by Week 12 (n = 13, P = 0.02). Nine participants achieved partial (n = 8) or complete (n = 1) remission. Participants with abnormal albumin and/or cholesterol at baseline gained normal/near normal levels by the last follow-up. Adverse events were consistent with those expected in this population. CONCLUSIONS: Belimumab treatment in participants with PMN can reduce PLA2R-Ab and subsequently proteinuria, important preludes to remission induction.

Antibacterials: are the new entries enough to deal with the emerging resistance problems?

Fifty years of making analogs based on less than ten antibacterial scaffolds has resulted in the development and marketing of over 100 antibacterial agents but, with the exception of the oxazolidinone core, no new scaffolds have emerged in the past 30 years to address emerging resistance problems. As the support for antibacterial research shifts away from large pharmaceutical companies, a wave of biotechnology companies have pursued a diverse choice of targets resulting in several novel classes of agent in late-stage development. Although critical for certain resistance niche needs, these agents are unlikely to provide the solution to the requirement for a major novel scaffold class of antibacterials.

Requesting and interpreting trauma radiographs: a role extension for accident & emergency nurses.

Government supported expansion of the nursing role within Accident & Emergency (A&E) departments in the United Kingdom (UK) has begun to break down the traditional barriers to professional practice. Today, many nurses working within A&E departments are both requesting and interpreting radiographic examinations as part of their normal working practice. However, role expansion does not occur without increased responsibility. Unsatisfactory requests for radiography and inaccurate radiographic interpretation may result in inappropriate patient treatment, misuse of resources, patient recall and litigation. Nurses undertaking these role extensions need to ensure that their levels of knowledge and skill to perform the role are appropriate and adequately supported. This article summarises the results of a national questionnaire survey of A&E nurse managers that aimed to identify current working practices, including education, training and limitations to practice, with respect to the requesting and interpretation of trauma radiographs by A&E nurses.

Interpreting trauma radiographs.

BACKGROUND: Many accident and emergency clinicians regard the radiographic image as an extension of the clinical examination, as a provisional diagnosis, based on clinical signs and symptoms, can be confirmed or refuted by inspection of X-rays. However, the value of radiography in this context is not determined by the actual presence of trauma or pathology on the radiograph, but is dependent on the ability of a clinician to identify any trauma or pathology present. Traditionally, the responsibility for interpreting radiographic images within the accident and emergency environment in the United Kingdom (UK) has been with medical clinicians. However, expansion of the nursing role has begun to change the boundaries of professional practice and now many nurses are both requesting and interpreting trauma radiographs. AIM: To ascertain the ability of accident and emergency doctors and nurses to interpret trauma radiographs, and identify whether there is a consistent standard of interpretive accuracy that could be used as a measure of competence. METHODS: A literature review was conducted using the Cochrane Library, Medline and CINAHL databases and the keywords radiographic interpretation, radiographic reporting, accident and emergency and emergency/nurse practitioner. FINDINGS: The ability of accident and nursing doctors and nurses to interpret trauma radiographs accurately varies markedly, and no identified published study has established an appropriate level of accuracy that should be achieved in order to demonstrate satisfactory competence in the interpretation of radiographic images. CONCLUSIONS: Determining a measure of interpretive accuracy that can be used to assess ability to interpret radiographic trauma images is fraught with difficulties. Consequently, nurses may attempt to prove their skills by directly comparing their abilities to those of their medical colleagues. However, as a result of marked variation in the ability of senior house officers to interpret trauma radiographs, a similar ability does not automatically imply that a satisfactory level of ability has been achieved.