Infliximab belongs to the family of tumor necrosis factor (TNF) alpha inhibitors and since its development, it has revolutionized treatment for both rheumatological diseases and inflammatory bowel disease (IBD). In IBD specifically, it has shown to result in symptomatic, endoscopic, and histological remission which is why it is one of the most widely used treatments for moderate to severe IBD. While common side effects include infections due to immunosuppression, cytopenias and hepatotoxicity, interstitial lung disease (ILD) has been infrequently reported to result from inflixiamb use. We present the case of a patient with ulcerative colitis (UC) who achieved remission with infliximab, however, after about two years of infusions, developed evidence of non-specific interstitial pneumonitis (NSIP). Extensive work up was done to rule out infections, mixed connective tissue disorders, and hypersensitivity pneumonitis. Although lung biopsy remains the gold standard for diagnosing NSIP; clinical, laboratory, and radiographic findings were sufficient in establishing this diagnosis. Initiation of empiric high dose steroids, and cessation of infliximab infusions showed improvement in respiratory status and resolution of lung findings. This case highlights the importance of recognizing adverse effects of infliximab on the pulmonary status of an IBD patient given that infliximab mediated ILD does not adhere to a specific timeline. Considering that respiratory function may be compromised post any number of infusions, it is imperative to acknowledge patients' respiratory complaints and initiate prompt investigation and evaluation for this rare complication.

Background: Asthma is a frequent and potentially life-threatening disease that complicates many pregnancies. There are extensive data with regard to the diagnosis and treatment of asthma during pregnancy. Medical providers require an up-to-date summary of the critical aspects of asthma management during pregnancy. Objective: This review aimed to summarize the available data from clinical trials, cohort studies, expert opinions, and guideline recommendations with regard to asthma in pregnancy. Methods: A search through PubMed was conducted by using keywords previously mentioned and MeSH (Medical Subject Headings) terminology. Clinical trials, observational studies, expert opinions, guidelines, and other reviews were included. The quality of the studies was assessed, and data were extracted and summarized. Results: Asthma worsens in ∼40% of pregnant women, which can be associated with maternal and fetal complications. Physiologic changes in the respiratory, cardiovascular, and immune systems during pregnancy play a critical role in the manifestations of asthma. The diagnosis and the treatment of asthma are similar to that of patients who are not pregnant. Nonetheless, concern for fetal malformations, preterm birth, and low birth weight must be considered when managing pregnant patients with asthma. Importantly, cornerstones of the pharmacotherapy of asthma seem to be safe during pregnancy. Conclusion: Asthma in pregnancy is associated with adverse outcomes. Roadblocks to management include associated comorbidities, medication nonadherence, atopy, lack of education, and smoking habits. These need to be acknowledged and addressed for successful asthma management during pregnancy.

Epinephrine is the first line of treatment for anaphylaxis which can occur outside a medical setting in community environments like schools. Patients with diagnosed IgE-mediated food allergy at risk of anaphylaxis are prescribed self-injectable epinephrine and given an individualized anaphylaxis action plan. As students, such patients/families provide their school with completed medication forms, a copy of their anaphylaxis plan, and additional student-specific epinephrine. However, students approved to self-carry prescribed self-injectable epinephrine may forget to do so or have other reasons for lacking prescribed epinephrine such as familial inability to fill the prescription due to cost or other access barriers. Undiagnosed students lacking prescribed epinephrine may also experience anaphylaxis at school. The presence of non-student specific school stock epinephrine allows school nurses and other staff the ability to treat anaphylaxis on-site while awaiting emergency medical services. Notably, not all states legally mandate K-12 schools to stock epinephrine. In states with laws only voluntarily allowing schools to stock epinephrine, it provides the ability to opt-out. Herein, we present a comprehensive review of barriers to school stock epinephrine, related improvement strategies, and workgroup recommendations supporting the need for mandated stock epinephrine in all schools in every state. Proposed solutions include ensuring legal immunity from liability for prescribers; advocacy for legislation to stabilize cost of self-injectable epinephrine; educational initiatives to schools promoting merits and safety of epinephrine and related anaphylaxis training; and partnerships between patient advocacy groups, medical and nursing organizations, public health departments and other health professionals to promote laws and district policies addressing need for stock epinephrine and school nurses to train and supervise school staff.

Chlorhexidine is labelled as hidden allergen as the health care professionals (HCPs) are unaware of the wide range of products containing chlorhexidine. Adverse events from chlorhexidine allergy can be reduced by appropriate perioperative management especially heeding on positive history during preoperative assessment, awareness regarding this hidden allergen, and educating HCPs on possible chlorhexidine-containing products. The regulatory agencies all over the world have issued recommendations regarding safety and risk of hypersensitivity reactions with chlorhexidine-containing products. The onus lies on HCPs to disseminate this knowledge to the stakeholders. We present a brief update to combat chlorhexidine allergy in perioperative setting.

Suspected or confirmed antibiotic allergy is a frequently encountered clinical circumstance that influences antimicrobial prescribing and often leads to the avoidable use of less efficacious and/or more toxic or costly drugs than first-line antimicrobials. Optimizing antimicrobial therapy in patients with antibiotic allergy labels has become one of the priorities of antimicrobial stewardship programs (ASP) in several countries. This guidance document aims to make recommendations for the systematic approach to patients with suspected or confirmed antibiotic allergy based on current evidence. A panel of eleven members of involved Scientific Societies with expertise in the management of patients with suspected or confirmed antibiotic allergy formulated questions about the management of patients with suspected or confirmed antibiotic allergy. A systematic literature review was performed by a medical librarian. The questions were distributed among panel members who selected the most relevant references, summarized the evidence and formulated graded recommendations when possible. The answers to all questions were finally reviewed by all panel members. A systematic approach to patients with suspected or confirmed antibiotic allergy is recommended to improve antibiotic selection and, consequently clinical outcomes. A clinically oriented, 3-category risk-stratification strategy was recommended for patients with suspected antibiotic allergy. Complementary assessments should consider both clinical risk category and preferred antibiotic agent. Empirical therapy recommendations for the most relevant clinical syndromes in patients with suspected or confirmed β-lactam allergy were formulated. Recommendations on the implementation and monitoring of the impact of the guidelines were formulated. ASP and allergists should design and implement activities that facilitate the most adequate antibiotic use in these patients.

MASK-air® , a validated mHealth app (Medical Device regulation Class IIa) has enabled large observational implementation studies in over 58,000 people with allergic rhinitis and/or asthma. It can help to address unmet patient needs in rhinitis and asthma care. MASK-air® is a Good Practice of DG Santé on digitally-enabled, patient-centred care. It is also a candidate Good Practice of OECD (Organisation for Economic Co-operation and Development). MASK-air® data has enabled novel phenotype discovery and characterisation, as well as novel insights into the management of allergic rhinitis. MASK-air® data show that most rhinitis patients (i) are not adherent and do not follow guidelines, (ii) use as-needed treatment, (iii) do not take medication when they are well, (iv) increase their treatment based on symptoms and (v) do not use the recommended treatment. The data also show that control (symptoms, work productivity, educational performance) is not always improved by medications. A combined symptom-medication score (ARIA-EAACI-CSMS) has been validated for clinical practice and trials. The implications of the novel MASK-air® results should lead to change management in rhinitis and asthma.

Toxic epidermal necrolysis is a potentially life-threatening dermatological condition whose pathogenesis and exact treatment are not yet known. Drugs like anticonvulsants, allopurinol and non-steroidal anti-inflammatory drugs like etoricoxib, a selective cyclo-oxygenase-2 inhibitor prescribed for pain management are associated with a high risk of toxic epidermal necrolysis. It is also associated with immunodeficiency and dysregulated immune reactions like systemic lupus erythematosus, an autoimmune disease in which organs and cells undergo damage initially mediated by tissue binding auto-antibodies and immune complexes. Here, a 34 year old lady was presented in emergency with multiple maculopapular rashes over the neck and trunk region after treatment with etoricoxib for osteoarthritis of the left foot.

Background: Pirfenidone, an antifibrotic medication approved for the treatment of idiopathic pulmonary fibrosis (IPF), often requires dose reduction owing to adverse events. In this study, we evaluated if pirfenidone's reduced dose has any impact on clinical outcomes in patients with IPF. Methods: We used the data of a prospective post-marketing study of pirfenidone conducted at 10 hospitals in South Korea from 2014 to 2017. Dose reduction was defined when the pirfenidone dose was temporarily or permanently reduced to manage adverse events or when the treatment dose failed to reach the standard dose. Study patients were classified based on the most frequently administered dose during 48-week follow-up-1800 mg, 1,200 mg, and <1,200 mg/days. The following clinical outcomes were compared between the groups: death, hospitalization, acute exacerbation, pulmonary function decline, and changes in severity of dyspnea and cough. Results: The median follow-up duration in all 143 patients was 11 months. During the study period, 70.6% experienced at least one dose reduction. Patients treated with standard-dose pirfenidone tended to be young and had the lowest diffusing capacity. Pulmonary function changes did not differ depending on the pirfenidone dose. The three groups were not significantly different in terms of the proportion of death, hospitalization, and acute exacerbation. The symptom changes were also similar between the groups. Conclusion: Reduced doses did not negatively impact clinical outcomes compared with the standard-dose pirfenidone in patients with IPF. Dose reduction may be a useful method to manage adverse events while maintaining therapeutic efficacy.

The article reflects the main links of pathogenesis and diagnostic criteria for autoimmune thyroiditis (AIT) and subclinical hypothyroidism as well as presents formulated features of signs and symptoms, diagnosis, and therapy of this disease in children. Here, we present a case report of an adolescent patient with AIT that was treated with L-thyroxine. The feature of this case was the development of laboratory-confirmed drug-induced hyperthyroidism against the background of hypersensitivity to the drug, what required correction of the therapy.

Neuropathic pain is the most difficult-to-treat pain syndrome in multiple sclerosis. Evidence relates neuropathic pain to demyelination, which often originates from unresolved neuroinflammation or altered immune response. Posttranscriptional regulation of gene expression might play a fundamental role in the regulation of these processes. The ELAV RNA-binding proteins HuR and HuD are involved in the promotion of inflammatory phenomena and in neuronal development and maintenance, respectively. Thus, the aim of this study was to investigate the role of HuR and HuD in demyelination-associated neuropathic pain in the mouse experimental autoimmune encephalomyelitis (EAE) model. HuR resulted overexpressed in the spinal cord of MOG35-55-EAE and PLP139-151-EAE mice and was detected in CD11b + cells. Conversely, HuD was largely downregulated in the MOG-EAE spinal cord, along with GAP43 and neurofilament H, while in PLP-EAE mice, HuD and neuronal markers remained unaltered. Intranasal antisense oligonucleotide (ASO) delivery to knockdown HuR, increased myelin basic protein expression, and Luxol Fast Blue staining in both EAE models, an indication of increased myelin content. These effects temporally coincided with attenuation of pain hypersensitivity. Anti-HuR ASO increased the expression of HuD in GAP43-expressing cells and promoted a HuD-mediated neuroprotective activity in MOG-EAE mice, while in PLP-EAE mice, HuR silencing dampened pro-inflammatory responses mediated by spinal microglia activation. In conclusion, anti-HuR ASO showed myelin protection at analgesic doses with multitarget mechanisms, and it deserves further consideration as an innovative agent to counteract demyelination in neuropathic pain states.

Enzymes involved in rescuing stalled ribosomes and recycling translation machinery are ubiquitous in bacteria and required for growth. Peptidyl tRNA drop-off is a type of abortive translation that results in the release of a truncated peptide that is still bound to tRNA (peptidyl tRNA) into the cytoplasm. Peptidyl tRNA hydrolase (Pth) recycles the released tRNA by cleaving off the unfinished peptide and is essential in most bacteria. We developed a sequencing-based strategy called copper sulfate-based tRNA sequencing (Cu-tRNAseq) to study the physiological role of Pth in Mycobacterium tuberculosis (Mtb). While most peptidyl tRNA species accumulated in a strain with impaired Pth expression, peptidyl prolyl-tRNA was particularly enriched, suggesting that Pth is required for robust peptidyl prolyl-tRNA turnover. Reducing Pth levels increased Mtb's susceptibility to tRNA synthetase inhibitors that are in development to treat tuberculosis (TB) and rendered this pathogen highly susceptible to macrolides, drugs that are ordinarily ineffective against Mtb. Collectively, our findings reveal the potency of Cu-tRNAseq for profiling peptidyl tRNAs and suggest that targeting Pth would open new therapeutic approaches for TB. IMPORTANCE Peptidyl tRNA hydrolase (Pth) is an enzyme that cuts unfinished peptides off tRNA that has been prematurely released from a stalled ribosome. Pth is essential in nearly all bacteria, including the pathogen Mycobacterium tuberculosis (Mtb), but it has not been clear why. We have used genetic and novel biochemical approaches to show that when Pth levels decline in Mtb, peptidyl tRNA accumulates to such an extent that usable tRNA pools drop. Thus, Pth is needed to maintain normal tRNA levels, most strikingly for prolyl-tRNAs. Many antibiotics act on protein synthesis and could be affected by altering the availability of tRNA. This is certainly true for tRNA synthetase inhibitors, several of which are drug candidates for tuberculosis. We find that their action is potentiated by Pth depletion. Furthermore, Pth depletion results in hypersensitivity to macrolides, drugs that are not active enough under ordinary circumstances to be useful for tuberculosis.

Biologic agents are a rapidly expanding class of medications, and several options are now available for the management of allergic and immunologic disorders. The risks of biologic therapy need to be understood in order to adequately counsel patients and appropriately monitor for potential adverse events. We sought to provide a comprehensive review of the risks and adverse effects reported for the current FDA-approved biologics used in management of allergic and immunologic disorders, including omalizumab, benralizumab, dupilumab, mepolizumab, reslizumab, tezepelumab and tralokinumab. Our review focuses on the risk of hypersensitivity reactions, pregnancy-specific considerations, risk of infection and risk of malignancy. We also highlight drug-specific adverse events and unique safety issues identified in case reports.

Toxicity in drug includes target toxicity, immune hypersensitivity and off target toxicity. Recently, advances in nanotechnology in the areas of drug delivery have help reduce toxicity and enhance drug solubility and deliver drugs to target sites more efficiently. In this study, we present a novel heteroatom functionalized quantum dot (QD-NBC and QD-NBS) as an effective drug delivery system for isoniazid. The said QD has been computationally modeled to assess its effectiveness in delivering isoniazid to desired target. Density functional theory (DFT) calculations were performed on the QD at the B3LYP/6-311+G(d, p) level to assess its stability through the natural bond orbital (NBO) calculations, and frontier molecular orbital (FMO) before and after interaction with isoniazid drug to understand any change in molecular behavior of the surface. Appropriate intermolecular interactions between the QD and the drug were computed through the Quantum theory of atoms in molecules (QTAIM) and Non-covalent interaction to assess the various binding mechanism and possible interactions resulting to the effective delivery of the drug target. To understand and accurately appraise the binding energy of adsorption, DFT calculations were performed with different functionals (B3LYP, CAM-B3LYP, PBEPBE, GD3BJ & WB97XD/6-311+G (d, p)). The results from DFT calculations point the functionalized QDs to be stable with appreciable energy gap suitable for delivery purposes. The adsorption energy of the drug target with the QD is in the range of -24.73 to 33.75 kcal/mol which indicates substantial interaction of the drug with the QD surface. This absorption energy is comparable with several reported literature and thus prompt the suitability of the surface for isoniazid delivery.

Investigators conducting translational research in real-world settings may experience changes that create challenges to the successful completion of the trial as well as post-trial adoption and implementation. Adaptive designs support translational research by systematically adapting content and methods to meet the needs of target populations, settings and contexts. This manuscript describes an adaptive implementation research model that provides strategies for changing content, delivery processes, and research methods to correct course when anticipated and unanticipated circumstances occur during a pragmatic trial. The Breathewell Program included two large pragmatic trials of the effectiveness of a digital communication technology intervention to improve symptom management and medication adherence in asthma care. The first trial targeted parents of children with asthma; the second targeted adults with asthma. Adaptations were made iteratively to adjust to dynamic conditions within the healthcare setting, informed by prospectively collected stakeholder input, and were categorized retrospectively by the authors as proactive or reactive. Study outcomes demonstrated improved treatment adherence and clinical efficiency. Kaiser Permanente Colorado, the setting for both studies, adopted the speech recognition intervention into routine care, however, both interventions required numerous adaptations, including changes to target population, intervention content, and internal workflows. Proactive and reactive adaptations assured that both trials were successfully completed. Adaptive research designs will continue to provide an important pathway to move healthcare delivery research into practice while conducting ongoing effectiveness evaluation.

The tibial neuroma transposition (TNT) is a rat model in which allodynia at the neuroma site (tibial nerve) can be independently evaluated from allodynia at the plantar surface of the hind paw innervated by the intact sural nerve. This TNT model is suitable to test therapies for neuroma pain, such as the potential superiority of certain surgical therapies that are already used in the clinic, or to evaluate new drugs and their effect on both pain modalities in the same animal. In this model, a distal lesion (neurotmesis) is made in the tibial nerve, and the proximal nerve end is transposed and fixed subcutaneously and pretibially to enable assessments of the neuroma site with a 15 g Von Frey monofilament. To assess allodynia over the sural nerve, Von Frey monofilaments can be used via the up-down method on the plantar lateral region of the hind paw. After cutting the tibial nerve, mechanical hypersensitivity develops at the neuroma site within 1 week after surgery and persists at least until 12 weeks after surgery. Allodynia at the sural innervated plantar surface develops within 3 weeks after surgery compared to the contralateral limb. At 12 weeks, a neuroma forms on the proximal end of the severed tibial nerve, indicated by dispersion and swirling of axons. For the TNT model surgery, multiple critical (micro)surgical steps need to be followed, and some surgery practice under terminal anesthesia is advised. Compared to other neuropathic pain models, such as the spared nerve injury model, allodynia over the neuroma site can be independently tested from sural nerve hypersensitivity in the TNT model. However, the neuroma site can be tested only in rats, not in mice. The tips and directions provided in this protocol can help research groups working on pain successfully implement the TNT model in their facility.