Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease: results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study.

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD). AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab. RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure. CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure.

Bilateral optic nerve compression secondary to skull hyperostosis from vitamin A deficiency.

A 15-year-old boy with a history of autism spectrum disorder presented with bilateral progressive blurry vision and nyctalopia. Initial examinations, including optical coherence tomography scans of the macula and optic nerve, were within normal limits. Subsequent examination revealed trace pallor of the right optic nerve. Computed tomography and magnetic resonance imaging of the brain demonstrated diffuse thickening of calvarial bone with bilateral optic nerve compression. Laboratory evaluation was notable for profound vitamin A deficiency. The patient underwent optic nerve decompression and vitamin A supplementation with postoperative improvement in visual acuity of both eyes.

Overcoming barriers to interprofessional education in gerontology: the Interprofessional Curriculum for the Care of Older Adults.

A fragmented workforce consisting of multiple disciplines with varying levels of training and limited ability to work as a team often provides care to older adults. Interprofessional education (IPE) is essential for preparing practitioners for the effective teamwork required for community-based, holistic, person-centered care of the older adults. Despite numerous programs and offerings to advance education and interdisciplinary patient care, there is an unmet need for geriatric IPE, especially as it relates to community-dwelling older adults and caregivers in medically underserved areas. A core group of university faculty from multiple disciplines received funding from the Health Resources and Services Administration Geriatric Workforce Enhancement Program to collaborate with community-based providers from several Area Agencies on Aging in the creation and implementation of the Interprofessional Curriculum for the Care of Older Adults (iCCOA). This geriatric curriculum is interprofessional, comprehensive, and community-based. Learners include third-year nursing students, nurse practitioner students, third-year medical students, internal medicine and family medicine residents, master's level social work students, third-year pharmacy students, pharmacy residents, third-year dental students, dental hygiene students, community-based organization professionals, practicing community organizers, and community health navigators. This article describes the efforts, successes, and challenges experienced with this endeavor, including securing funding, ensuring equal representation of the disciplines, adding new components to already crowded curricula, building curriculum on best practices, improving faculty expertise in IPE, managing logistics, and ensuring comprehensive evaluation. The results summarize the iCCOA components, as well as the interprofessional domains, knowledge, and competencies.

Magnesium nebulization utilization in management of pediatric asthma (MagNUM PA) trial: study protocol for a randomized controlled trial.

BACKGROUND: Up to 30 % of children with acute asthma are refractory to initial therapy, and 84 % of this subpopulation needs hospitalization. Finding safe, noninvasive, and effective strategies to treat this high-risk group would substantially decrease hospitalizations, healthcare costs, and the psycho-social burden of the disease. Whereas intravenous magnesium (Mg) is effective in severe refractory asthma, its use is sporadic due to safety concerns, with the main treatment goal being to prevent intensive care unit admission. In contrast, nebulized Mg is noninvasive, allows higher pulmonary drug concentrations, and has a much higher safety potential due to the lower rate of systemic delivery. Previous studies of inhaled Mg show disparate results due to the use of unknown/inefficient delivery methods and other methodological flaws. METHODS/DESIGN: The study is a randomized double-blind controlled trial in seven Canadian pediatric Emergency Departments (two-center pilot 2011 to 2014, Canada-wide November 2014 to December 2017). The trial will include 816 otherwise healthy children who are 2 to 17 years old, having had at least one previous wheezing episode, have received systemic corticosteroids, and have a Pediatric Respiratory Assessment Measure (PRAM) ≥ 5 points after three salbutamol and ipratropium treatments for a current acute asthma exacerbation. Eligible consenting children will receive three experimental treatments of nebulized salbutamol with either 600 mg of Mg sulfate or placebo 20 min apart, using an Aeroneb Go nebulizer, which has been shown to maximize pulmonary delivery while maintaining safety. The primary outcome is hospitalization within 24 h of the start of the experimental therapy for persistent respiratory distress or supplemental oxygen. Secondary outcomes include all-cause hospitalization within 24 h, PRAM, vital signs, number of bronchodilator treatments by 240 min, and the association between the difference in the primary outcome between the groups, age, gender, baseline PRAM, atopy, and "viral induced wheeze" phenotype (Fig. 1). DISCUSSION: If effective, inhaled Mg may represent an effective strategy to minimize morbidity in pediatric refractory acute asthma. Unlike previous works, this trial targets nonresponders to optimized initial therapy who are the most likely to benefit from inhaled Mg. Future dissemination of results will include knowledge translation, incorporation into a Cochrane Review, presentation at scientific meetings, and a peer-reviewed publication. TRIAL REGISTRATION: NCTO1429415 , registered 2 September 2011.

Evaluation of vitamin B12 monitoring in a veteran population on long-term, high-dose metformin therapy.

BACKGROUND: Metformin can result in vitamin B(12) deficiency, potentially leading to complications such as neuropathy. Annual monitoring of vitamin B(12) has been suggested; however, it is unknown whether current practice reflects this recommendation. OBJECTIVE: To identify vitamin B(12) monitoring patterns in patients on long-term, high-dose metformin. Secondary objective was to determine the frequency of new vitamin B(12) deficiency, anemia, and neuropathy documented after initiation of high-dose metformin. METHODS: Electronic medical records of veterans treated at the Veterans Affairs Maryland Healthcare System with high-dose metformin (≥2000 mg/day) as of November 1, 2010, were reviewed. Data regarding metformin treatment, vitamin B(12) measurements, and documentation of vitamin B(12) deficiency, cyanocobalamin supplementation, anemia, and neuropathy were collected. Subjects treated with metformin for less than 1 year or those with documented peripheral neuropathy, megaloblastic anemia, vitamin B(12) deficiency, or a condition associated with vitamin B(12) malabsorption prior to metformin initiation were excluded. RESULTS: Subjects (N = 235) had a mean metformin dose of 2050 mg/day and mean duration of treatment of 5.2 years. Sixty percent did not have vitamin B(12) measured. Of subjects receiving metformin for 10 years or more, nearly half (46%) never had vitamin B(12) measured. New documentation of vitamin B(12) deficiency or cyanocobalamin supplementation was found in 5.5% of the population, and anemia was found in 12%. Of the 14% with new neuropathy, 42% did not have vitamin B(12) measured. CONCLUSIONS: Vitamin B(12) was not routinely monitored in patients on high-dose metformin, even in those at highest risk (≥10 years of therapy), or in those with potential manifestations of vitamin B(12) deficiency (neuropathy). Cases of vitamin B(12) deficiency and resulting anemia or neuropathy may be undiagnosed and untreated because of lack of monitoring. Prospective studies examining the effect of increased vitamin B(12) monitoring on identification and treatment of vitamin B(12) deficiency in patients on metformin are warranted.