Search

Abstract Background Penicillin allergy is the most frequently reported drug allergy, yet most patients can tolerate the drug if challenged. Despite this discrepancy, large scale penicillin allergy de-labeling interventions have not been widely implemented in many health care systems. The application of a multi-method implementation science approach can provide key tools to study this evidence to practice gap and provide insight to successfully operationalize penicillin allergy evaluation in real-world clinical settings. Methods We followed a four-step process that leverages qualitative analysis to design evidence-based, actionable strategies to develop an intervention. First, we specified the clinician-perceived barriers to penicillin allergy de-labeling (intervention targets). We then mapped intervention targets onto Theoretical Domains Framework (domains and constructs) and found the root causes of behavior. Next, we linked root causes of behavior with intervention functions (BCW). In the final step, we synthesized participants’ suggestions for process improvement with implementation strategies aligning with the intervention functions. Results Evidence-based strategies such as focused education and training in penicillin allergy evaluation can address knowledge and confidence barriers reported by frontline clinicians. Other key strategies involve developing a system of champions, improving communications systems, and restructuring the healthcare team. Implementation mapping can provide a powerful multi-method framework to study, design, and customize intervention strategies. Conclusion: Empowering clinicians beyond allergy specialists to conduct penicillin allergy assessments requires designing new workflows and systems and providing additional knowledge to those clinicians.

Abstract Background Penicillin allergy is the most commonly reported drug allergy in the US. Despite evidence demonstrating that up to 90% of labels are incorrect, scalable interventions are not well established. As part of a larger mixed methods investigation, we conducted a qualitative study to describe the barriers to implementing a risk-based penicillin de-labeling protocol within a single site Veteran’s hospital. Methods We conducted individual and group interviews with multidisciplinary inpatient and outpatient healthcare teams. The interview guides were developed using the Theoretical Domains Framework (TDF) to explore workflows and contextual factors influencing identification and evaluation of patients with penicillin allergy. Three researchers iteratively developed the codebook based on TDF domains and coded the data using thematic analysis. Results We interviewed 20 clinicians. Participants included three hospitalists, five inpatient pharmacists, one infectious disease physician, two anti-microbial stewardship pharmacists, four primary care providers, two outpatient pharmacists, two resident physicians, and a nurse case manager for the allergy service. The factors that contributed to barriers to penicillin allergy evaluation and de-labeling were classified under six TDF domains; knowledge, skills, beliefs about capabilities, beliefs about consequences, professional role and identity, and environmental context and resources. Participants from all groups acknowledged the importance of penicillin de-labeling. However, they lacked confidence in their skills to perform the necessary evaluations, such as test dose challenges. The fear of inducing an allergic reaction and adding further complexity to patient care exacerbated their reluctance to de-label patients. The lack of ownership of de-labeling initiative was another significant obstacle in establishing consistent clinical workflows. Additionally, heavy workloads, competing priorities, and ease of access to alternative antibiotics prevented the prioritization of tasks related to de-labeling. Space limitations and nursing staff shortages added to challenges in outpatient settings. Conclusion Our findings demonstrated that barriers to penicillin allergy de-labeling fall under multiple behavioral domains. Better role clarification, opportunities to develop necessary skills, and dedicated resources are needed to overcome these barriers. Future interventions will need to employ a systemic approach that addresses each of the behavioral domains influencing penicillin allergy de-labeling with stakeholder engagement of the inpatient and outpatient health care teams.

Prediction of the stock market is a challenging and time-consuming process. In recent times, various research analysts and organizations have used different tools and techniques to analyze and predict stock price movements. During the early days, investors mainly depend on technical indicators and fundamental parameters for short-term and long-term predictions, whereas nowadays many researchers started adopting artificial intelligence-based methodologies to predict stock price movements. In this article, an exhaustive literature study has been carried out to understand multiple techniques employed for prediction in the field of the financial market. As part of this study, more than hundreds of research articles focused on global indices and stock prices were collected and analyzed from multiple sources. Further, this study helps the researchers and investors to make a collective decision and choose the appropriate model for better profit and investment based on local and global market conditions.

In the livestock industry, wireless sensor networks (WSNs) play a significant role in monitoring many fauna health statuses and behaviors. Energy preservation in WSNs is considered one of the critical, complicated tasks since the sensors are coupled to constrained resources. Therefore, the clustering approach has proved its efficacy in preserving energy in WSNs. In recent studies, various clustering approaches have been introduced that use optimization techniques to improve the network lifespan by decreasing energy depletion. Yet, they take longer to converge and choose the optimal cluster heads in the network. In addition, the energy is exhausted quickly in the network. This paper introduces a novel optimization technique, i.e., an artificial rabbits optimization algorithm-based energy efficient cluster formation (EECHS-ARO) approach in a WSN, to extend the network lifetime by minimizing the energy consumption rate. The EECHS-ARO technique balances the search process in terms of enriched exploration and exploitation while selecting the optimal cluster heads. The experimentation was carried out on a MATLAB 2021a platform with varying sensor nodes. The obtained results of EECHS-ARO are contrasted with other existing approaches via teaching–learning based optimization algorithm (TLBO), ant lion optimizer (ALO) and quasi oppositional butterfly optimization algorithm (QOBOA). The proposed EECHS-ARO enriches the network lifespan by ~15% and improves the packet delivery ratio by ~5%.

Objective: Post-surgical hypoparathyroidism (PoSH) usually settles within few months after thyroid surgery, but several patients require long-term s upplementation with calcium/activated vitamin D. When PoSH persists beyond 6 months , it is considered ‘chronic’ or ‘permanent’, however, late recovery has been repor ted. The aim of this study was to determine the frequency of late recovery and explore fac tors predicting late recovery of parathyroid function. Methods: Adult patients undergoing total/completion thyroidectomy between 2009 and 2018 were included in this retrospective cohort observational s tudy. The records of patients with evidence of PoSH were reviewed to identify those with persisting PoSH at 6 months. Demographic, biochemical, surgical, pathological, and clinical follow-up data were collected and analysed. Results: Out of 911 patients undergoing thyroidectomy, 270 were identifi ed with PoSH. Of these, 192 were started on supplements and 138 (71.9%) recov ered within 6 months. Of the remaining 54 patients, 35 had ongoing PoSH with median ( range) follow-up of 3.4 (0.5–11.1) years. Nineteen patients were weaned off suppleme nts and achieved remission at median (range) follow-up of 1.3 (0.6–4.8) years. A ll of those who recovered had a PTH of ≥1.6 pmol/L at 6 months. There was no difference in age, gender, diagnosis, type, and extent of surgery between those who did an d did not show late recovery. Conclusions: Recovery from PoSH is common beyond 6 months, raising the ques tion whether a 6-month threshold to define ‘long-term’ PoSH is approp riate. The chances of recovery are high (~50%) in patients with PTH level ≥1.6 pmol/L at 6 months, where attempts at weaning may be focussed.

Primary lymphomas of the central nervous system (PCNSL) are defined as diffuse large B-cell lymphomas (DLBCL) confined to the CNS. Here, the authors complete whole genome sequencing and RNA-seq to characterize 51 PCNSLs, and find common mutations in immune pathways and upregulated TERT expression and find distinct pathway differences between DLBCL and other primary CNS lymphomas.

Radiation-induced gliomas (RIGs) have been reported in patients after treatment with cranial irradiation for various primary malignancies but their origin are still unclear. Here, the authors define the genomic, epigenetic and transcriptional landscape of 32 RIGs cases.

Abstract Background Pediatric patients with relapsed or refractory disease represent a population with a desperate medical need. The aim of the INFORM (INdividualized Therapy FOr Relapsed Malignancies in Childhood) program is to translate next generation molecular diagnostics into a biomarker driven treatment strategy. The program consists of two major foundations: the INFORM registry providing a molecular screening platform and the INFORM2 series of biomarker driven phase I/II trials. The INFORM2 NivEnt trial aims to determine the recommended phase 2 dose (RP2D) of the combination treatment of nivolumab and entinostat (phase I) and to evaluate activity and safety (phase II). Methods This is an exploratory non-randomized, open-label, multinational and multicenter seamless phase I/II trial in children and adolescents with relapsed / refractory or progressive high-risk solid tumors and CNS tumors. The phase I is divided in 2 age cohorts: 12–21 years and 6–11 years and follows a 3 + 3 design with two dose levels for entinostat (2 mg/m2 and 4 mg/m2 once per week) and fixed dose nivolumab (3 mg/kg every 2 weeks). Patients entering the trial on RP2D can seamlessly enter phase II which consists of a biomarker defined four group basket trial: high mutational load (group A), high PD-L1 mRNA expression (group B), focal MYC(N) amplification (group C), low mutational load and low PD-L1 mRNA expression and no MYC(N) amplification (group D). A Bayesian adaptive design will be used to early stop cohorts that fail to show evidence of activity. The maximum number of patients is 128. Discussion This trial intends to exploit the immune enhancing effects of entinostat on nivolumab using an innovative biomarker driven approach in order to maximize the chance of detecting signs of activity. It prevents exposure to unnecessary risks by applying the Bayesian adaptive design for early stopping for futility. The adaptive biomarker driven design provides an innovative approach accelerating drug development and reducing exposure to investigational treatments in these vulnerable children at the same time. Trial registration ClinicalTrials.gov, NCT03838042 . Registered on 12 February 2019.

The evolution and genetic nature of metastatic lesions is not completely characterized. Here the authors perform a comprehensive whole-genome study of colorectal metastases in comparison to matched primary tumors and define a multistage progression model and metastasis-specific changes that, in part, are therapeutically actionable.

Introduction: Vitamin D deficiency has reached epidemic proportions in India with prevalence rates of 70-100% in the general population. Low vitamin D levels are associated with worse outcomes in ischemic strokes. The outcome of stroke after vitamin D replenishment has not been much studied. Aim: To compare the stroke outcome between patients receiving vitamin D supplementation and patients without vitamin D supplementation by Scandinavian Stroke Scale (SSS) and thus, to assess the long term outcome of ischemic stroke patients with low vitamin D level by supplementation of vitamin D. Materials and Methods: This is a non blinded randomized controlled trial conducted in ischemic stroke patients. The patients were divided into two groups (A and B) where Group A received a single dose of 6 lac IU of Cholecalciferol Intramascular (IM) injection and Group B were not given vitamin D. Finally 30 patients in each group were analyzed. SSS was applied to evaluate the stroke severity at the onset and at the follow up after three months in both groups. The difference in SSS was analyzed using SPSS software. Independent t-test was applied and p-value < 0.05 was taken as significant. Results: Mean±SD of vitamin D levels in Group A and Group B were 17.98±3.81ng/ml and 18.44±4.69 ng/ml respectively. Mean±SD of SSS at time of admission and after three months for Group A was 32.50±11.61 and 38.89±8.34; and for Group B 35.82±8.56 and 38.32±7.10. The difference in SSS from time of admission and after three months, in Group A (6.39±4.56) and Group B (2.50±2.20) were analyzed statistically and found to be highly significant (p