Frequency of pharmacogenomic variation and medication exposures among All of Us Participants.

Pharmacogenomics promises improved outcomes through individualized prescribing. However, the lack of diversity in studies impedes clinical translation and equitable application of precision medicine. We evaluated the frequencies of PGx variants, predicted phenotypes, and medication exposures using whole genome sequencing and EHR data from nearly 100k diverse All of Us Research Program participants. We report 100% of participants carried at least one pharmacogenomics variant and nearly all (99.13%) had a predicted phenotype with prescribing recommendations. Clinical impact was high with over 20% having both an actionable phenotype and a prior exposure to an impacted medication with pharmacogenomic prescribing guidance. Importantly, we also report hundreds of alleles and predicted phenotypes that deviate from known frequencies and/or were previously unreported, including within admixed American and African ancestry groups.

Chronic Opioid Prescribing After Common Otolaryngology Procedures in Adults.

OBJECTIVE: (1) Describe short and long-term opioid prescribing patterns and variation after common otolaryngologic procedures and (2) assess risk factors for chronic opioid use in this cohort. STUDY DESIGN: Retrospective cohort. SETTING: Optum's deidentified Integrated Claims-Clinical data set. METHODS: An adult cohort of patients undergoing common otolaryngology procedures from 2010 to 2017 was identified. Associations between procedure and other covariates with any initial opioid prescription and continuous opioid prescriptions were assessed with multivariable modeling. Opioid use was defined as continuous if a new prescription was filled within 30 days of the previous prescription. A time-to-event analysis assessed continuous prescriptions from the index procedure to end of the last continuous opioid prescription. RESULTS: Among a cohort of 19,819 patients undergoing predominately laryngoscopy procedures (12,721, 64.2%), 2585 (13.0%) received an opioid prescription with variation in receiving a prescription, daily dose, and total initially prescribed dose varying by procedure, patient demographics, provider characteristics, and facility type. Opioids were prescribed most frequently after tonsillectomy (45.4%) and least frequently after laryngoscopy with interventions (3.9%), which persisted in the multivariable models. Overall rates of continuous use at 180 and 360 days were 0.48% and 0.27%, respectively. Among patients receiving an initial opioid prescription, maintaining continuous prescriptions was associated with tonsillectomy procedures, age (adjusted hazard ratio [aHR]: 0.997 per year, 95% confidence interval [CI]: 0.993-0.999), opioid prescriptions 6 months preprocedure (aHR: 0.42, 95% CI: 0.37-0.47), and nonotolaryngology initial prescribers (aHRs: <1, P < .05). CONCLUSION: There is substantial variation in initial prescribing practices and continuous opioid prescriptions after common Otolaryngology procedures, but the overall rate of maintaining a continuous prescription starting after these procedures is very low. LEVEL OF EVIDENCE: Level 3.

A Multidisciplinary Approach to Enhancing Sterilization Processes for Pleuravideoscopes in a Pulmonary Clinic.

PURPOSE/OBJECTIVES: The Centers for Disease Control and Prevention has highlighted the strong association between healthcare-associated infections and the reprocessing of flexible endoscopes. This process improvement project provided an evidence-based workflow analysis of pleuravideoscope reprocessing to validate and implement safe practices in the pulmonary clinic and sterile processing department. DESCRIPTION OF THE PROJECT/PROGRAM: A multidisciplinary team created an audit tool to complete infection control risk assessment using Lean Six Sigma methodology. OUTCOME: The risk assessment identified gaps in clinical practice, prompting corrective measures using a shared decision-making approach. The organization updated standard operating procedures, provided training and competency assessments, and purchased single-use pleuravideoscopes. These initiatives addressed the deficiencies and reinforced a culture of continuous process improvement and patient safety. CONCLUSION: Multidisciplinary teams should perform comprehensive reviews of facility processes and assess the risks related to infection control to identify optimal pleuravideoscope workflows for the healthcare institution. The involvement of a clinical nurse specialist is advantageous, as they possess the expertise necessary to facilitate collaborative efforts among team members spanning various departments. By leveraging the insights and skills of diverse professionals, healthcare organizations can optimize their reprocessing programs and enhance patient safety.

Exploring the Trajectory of Catatonia in Neurodiverse and Neurotypical Pediatric Hospitalizations: A Multicenter Longitudinal Analysis.

Objective: Catatonia is a neuropsychiatric disorder that occurs in pediatric patients with a range of associated medical, psychiatric, and neurodevelopmental disorders (NDDs). This study describes hospital care of pediatric catatonia patients and compares treatments for neurotypical patients and those with NDDs. Methods: Retrospective cohort study from 1/1/2018 to 6/1/2023 of two academic medical centers of patients aged 18 and younger with catatonia. Patients were retrospectively assessed using the clinical global impressions-improvement (CGI-I) by two independent reviewers. Results: One hundred sixty-five patients were hospitalized for catatonia, of whom 50.3% had an NDD. Median age was 15. One hundred sixty-four patients were treated with a benzodiazepine, with a median maximum 24-hour dose of 6 mg lorazepam-equivalents, which did not differ for patients with and without NDDs. Electroconvulsive therapy (ECT) was utilized in 14.5% of patients. Median length of medical hospitalization was 5 days and hospitalizations were longer in neurotypical patients than in patients with NDDs. In an ordinal regression model, the probability of observing at least "much improvement" (CGI < 3) was 88.3% (95% CI: 82.4% to 92.3%), with NDD diagnosis associated with a lower odds of clinical response. Conclusions: The probability of patients achieving a CGI-I score indicating at least "much improvement" was 88.3%. Administered benzodiazepine dose and ECT treatment were similar for all patients, but neurotypical patients had longer hospitalizations than those with NDDs and had a higher odds of a more favorable clinical response. Research under controlled conditions is needed to optimize and endure equitable catatonia treatment in youth.

Generalized Periodic Discharges Associated With Catatonia and Delirium: A Case Series.

OBJECTIVE: Generalized periodic discharges are a repeated and generalized electroencephalography (EEG) pattern that can be seen in the context of altered mental status. This article describes a series of five individuals with generalized periodic discharges who demonstrated signs and symptoms of catatonia, a treatable neuropsychiatric condition. METHODS: Inpatients with a clinical diagnosis of catatonia, determined with the Bush-Francis Catatonia Rating Scale (BFCRS), and EEG recordings with generalized periodic discharges were analyzed in a retrospective case series. RESULTS: Five patients with catatonia and generalized periodic discharges on EEG were evaluated from among 106 patients with catatonia and contemporaneous EEG measurements. Four of these patients showed an improvement in catatonia severity when treated with benzodiazepines, with an average reduction of 6.75 points on the BFCRS. CONCLUSIONS: Among patients with generalized periodic discharges, catatonia should be considered, in the appropriate clinical context. Patients with generalized periodic discharges and catatonia may benefit from treatment with empiric trials of benzodiazepines.

Evaluating the impact of hot water killing larvae on gene expression using the transformer gene in Cochliomyia macellaria (Diptera: Calliphoridae).

In forensic entomology, determining the age of a larva from a body to estimate time since death is commonly performed through the measurement of a physical trait. Gene expression has been studied as an alternative age estimation approach, but the storage conditions required for these studies are different than those used in forensic entomological casework. Studies analyzing gene expression prioritize the preservation of RNA, which requires fresh tissue and ultra-cold storage. Casework, in contrast, utilizes hot water killing specimens that may not be analyzed for a long period after collection. In the current study, the impact of hot water killing on gene expression was assessed for larval samples of the forensically important blow fly, Cochliomyia macellaria. Successful amplification of the sex-determining gene, transformer, was tested across larvae ranging in size from 3.22 to 16.85 mm in length after storage times of 1-2 weeks, 4-5 weeks, and 8-9 weeks at 4°C in RNAlater. Larvae hot water killed were processed in tandem with larvae stored live to allow for a direct assessment of the impact of boiling on gene expression. As expected, the transformer gene was successfully amplified in all larvae stored live. For the hot water-killed larvae, the success rate was only slightly lower, with 3 out of 75 larvae not generating a sex-specific band pattern. The results show gene expression can be used for hot water-killed samples, though future work across different genes, species, and extending to quantitative gene expression methods is needed.

Prognostic clinical decision support for pneumonia in the emergency department: A randomized trial.

BACKGROUND: Hospitalization rates for childhood pneumonia vary widely. Risk-based clinical decision support (CDS) interventions may reduce unwarranted variation. METHODS: We conducted a pragmatic randomized trial in two US pediatric emergency departments (EDs) comparing electronic health record (EHR)-integrated prognostic CDS versus usual care for promoting appropriate ED disposition in children (<18 years) with pneumonia. Encounters were randomized 1:1 to usual care versus custom CDS featuring a validated pneumonia severity score predicting risk for severe in-hospital outcomes. Clinicians retained full decision-making authority. The primary outcome was inappropriate ED disposition, defined as early transition to lower- or higher-level care. Safety and implementation outcomes were also evaluated. RESULTS: The study enrolled 536 encounters (269 usual care and 267 CDS). Baseline characteristics were similar across arms. Inappropriate disposition occurred in 3% of usual care encounters and 2% of CDS encounters (adjusted odds ratio: 0.99, 95% confidence interval: [0.32, 2.95]) Length of stay was also similar and adverse safety outcomes were uncommon in both arms. The tool's custom user interface and content were viewed as strengths by surveyed clinicians (>70% satisfied). Implementation barriers include intrinsic (e.g., reaching the right person at the right time) and extrinsic factors (i.e., global pandemic). CONCLUSIONS: EHR-based prognostic CDS did not improve ED disposition decisions for children with pneumonia. Although the intervention's content was favorably received, low subject accrual and workflow integration problems likely limited effectiveness. Clinical Trials Registration: NCT06033079.

Association of Ambulance Diversion Policy on EMS Transport and Ambulance Patient Offload Times: A Comparison of Three Strategies.

OBJECTIVES: Despite limited supporting data, hospitals continue to apply ambulance diversion (AD). Thus, we examined the impact of three different diversion policies on diversion hours, transport time (TT; leaving scene to arrival at the hospital), and ambulance patient offload time (APOT; arrival at the hospital to patient turnover to hospital staff) for 9-1-1 transports in a 22-hospital county Emergency Medical Services (EMS) system. METHODS: This retrospective study evaluated metrics during periods of three AD policies, each 27 days long: hospital-initiated (Period 1), complete suspension (Period 2), and County EMS-initiated (Period 3). We described the median transports and diversion hours, and compared the daily average and daily 90th percentile TT and APOT during the three study periods. RESULTS: Over the study period, there were 50,992 total transports in the county; Period 3 had fewer median transports per day than Period 1 (581 vs 623, p < 0.001), while Period 2 was similar to Period 1 (606 vs 623, p = 0.108). Median average daily diversion hours decreased from 98.1 h during Period 1 to zero hours during both Periods 2 (p < 0.001) and 3 (p < 0.001). Median daily average TT decreased from 18.3 min in Period 1 to 16.9 min in both Periods 2 (p < 0.001) and 3 (p < 0.001). Median daily 90th percentile TT showed a similar decrease from 30.2 min in Period 1 to 27.5 in Period 2 (p < 0.001), and to 28.1 in Period 3 (p = 0.001). Median average daily APOT was 26.0 min during Period 1, similar at 25.2 min during Period 2 (p = 0.826) and decreased to 20.4 min during Period 3 (p < 0.001). The median daily 90th percentile APOT was 53.9 min during Period 1, similar at 51.7 min during Period 2 (p = 0.553) and decreased to 40.3 min during Period 3 (p < 0.001). CONCLUSIONS: Compared to hospital-initiated AD, enacting no AD or County EMS-initiated AD was associated with less diversion time; TT and APOT showed statistically significant improvement without hospital-initiated AD but were of unclear clinical significance. EMS-initiated AD was difficult to interpret as that period had significantly fewer transports. EMS systems should consider these findings when developing strategies to improve TT, APOT, and system use of diversion.

Adherence to Parkinson's disease medication: A case study to illustrate reasons for non-adherence, implications for practice and engaging under-represented participants in research.

Parkinson's disease (PD) is a progressive neurodegenerative disease which primarily presents with the core symptoms of rigidity, postural instability, tremor, and bradykinesia. Non-adherence to prescribed PD treatments can have significant ramifications, such as poor symptom control and greater disease burden. Reasons for poor adherence are multifaceted, particularly when medication regimens are complex and often based on perceptual and practical barriers. Additionally, engaging fully non-adherent patients in research is challenging since they may have dropped out of service provision, yet their contribution is vital to fully understand the rationale for non-adherence. This paper aims to present a case study on the perspectives of one person with PD, a participant in a previously published qualitative study investigating the barriers and facilitators to medication adherence in PD. In this paper, the participant's diagnostic journey is described, and experiences of medical consultations are summarised to explain their reasons for not adhering to any of the standard UK PD treatments prescribed. The participant's preferences for using Vitamin B1 (thiamine) injections to manage the symptoms are reported and the rationale for doing so is discussed. We consider the case through the lens of a behavioural science approach, drawing on health psychology theory, the Theoretical Domains Framework (TDF), to inform the review and the practical challenges faced when analysing the data for this participant. Implications for pharmacy practice, in particular, are also put forward with view to ensuring that patients such as Mr. Wilkinson are provided with the opportunity to discuss treatment choices and self-management of long-term conditions such as PD. We also discuss the importance of reaching under-represented members of the population in medication adherence research, which embraces the principles of equality, diversity, and inclusion in research.

Optimizing Advanced Trauma Life Support (ATLS®) to Maximize Readiness.

INTRODUCTION: The Army utilizes Individual Critical Task Lists (ICTLs) to track and ensure competency and deployment readiness of its medical service members. ICTLs are the various skills and procedures that the Army has deemed foundational for each area of concentration (AOC)/military occupational specialty (MOS). While many ICTLs involve the patient care that military medical providers regularly provide, some procedures are not as commonly performed. This, when coupled with lower patient volume at military treatment facilities (MTF), poses a challenge for maintaining skill competency and deployment readiness. Fort Campbell's Blanchfield Army Community Hospital (BACH) has created a holistic and unique solution to meet many of these standardized requirements and support a ready medical force. By optimizing the Advanced Trauma Life Support (ATLS®) course curriculum to facilitate ICTL completion, BACH has increased its ICTL completion rates, ATLS® course exposure, and streamlined training requirements. The purpose of this article is to describe this best practice and suggest its applicability to other MTFs. MATERIALS AND METHODS: By cross-referencing the ATLS® course curriculum and appendices with ICTLs, BACH has augmented ATLS® course certification with the additional completion of 12 ICTLs. This new approach not only increases ICTL completion, but also increases ATLS® curriculum exposure to medical providers, such as Registered Nurses or Nurse Practitioners, who would not typically take ATLS®. RESULTS: Since starting this new approach in April 2021, 73 military medical personnel have completed the ATLS® course at BACH, with 24 different medical specialties represented. A total of 361 ICTLs have been completed with specific ICTL completion counts ranging from 13 to 48. Each ICTL tested was completed 100% of its annual requirement. CONCLUSION: ATLS® is a mandatory joint interoperability standard for military physicians and it is also an Army ICTL for many AOCs/MOSs. Only counting completion of this course as one ICTL is a missed opportunity for the time spent by Army medical providers and limits the exposure of ATLS® to select AOCs/MOSs. This optimized and novel approach has been successful at BACH, suggesting its applicability at other MTFs that serve as ATLS® testing sites.

Reproducible mass spectrometry data processing and compound annotation in MZmine 3.

Untargeted mass spectrometry (MS) experiments produce complex, multidimensional data that are practically impossible to investigate manually. For this reason, computational pipelines are needed to extract relevant information from raw spectral data and convert it into a more comprehensible format. Depending on the sample type and/or goal of the study, a variety of MS platforms can be used for such analysis. MZmine is an open-source software for the processing of raw spectral data generated by different MS platforms. Examples include liquid chromatography-MS, gas chromatography-MS and MS-imaging. These data might typically be associated with various applications including metabolomics and lipidomics. Moreover, the third version of the software, described herein, supports the processing of ion mobility spectrometry (IMS) data. The present protocol provides three distinct procedures to perform feature detection and annotation of untargeted MS data produced by different instrumental setups: liquid chromatography-(IMS-)MS, gas chromatography-MS and (IMS-)MS imaging. For training purposes, example datasets are provided together with configuration batch files (i.e., list of processing steps and parameters) to allow new users to easily replicate the described workflows. Depending on the number of data files and available computing resources, we anticipate this to take between 2 and 24 h for new MZmine users and nonexperts. Within each procedure, we provide a detailed description for all processing parameters together with instructions/recommendations for their optimization. The main generated outputs are represented by aligned feature tables and fragmentation spectra lists that can be used by other third-party tools for further downstream analysis.

Demographic fluctuations in bloodstream Staphylococcus aureus lineages configure the mobile gene pool and antimicrobial resistance.

Staphylococcus aureus in the bloodstream causes high morbidity and mortality, exacerbated by the spread of multidrug-resistant and methicillin-resistant S. aureus (MRSA). We aimed to characterize the circulating lineages of S. aureus from bloodstream infections and the contribution of individual lineages to resistance over time. Here, we generated 852 high-quality short-read draft genome sequences of S. aureus isolates from patient blood cultures in a single hospital from 2010 to 2022. A total of 80 previously recognized sequence types (ST) and five major clonal complexes are present in the population. Two frequently detected lineages, ST5 and ST8 exhibited fluctuating demographic structures throughout their histories. The rise and fall in their population growth coincided with the acquisition of antimicrobial resistance, mobile genetic elements, and superantigen genes, thus shaping the accessory genome structure across the entire population. These results reflect undetected selective events and changing ecology of multidrug-resistant S. aureus in the bloodstream.

Diagnostic features of paediatric catatonia: multisite retrospective cohort study.

BACKGROUND: Catatonia is a neuropsychiatric disorder characterised by psychomotor changes that can affect individuals across the lifespan. Although features of catatonia have been described in adults, the most common clinical symptoms among paediatric patients with catatonia are not well characterised. AIMS: The goal of this study was to characterise the symptoms of catatonia demonstrated by paediatric patients, and to explore demographic and diagnostic factors associated with greater catatonia severity. METHOD: We conducted a multicentre retrospective cohort study, from 1 January 2018 to 6 January 2023, of patients aged 18 and younger with a clinical diagnosis of catatonia and symptom assessment using the Bush Francis Catatonia Rating Scale (BFCRS). RESULTS: A total of 143 patients met inclusion criteria. The median age was 15 (interquartile range: 13-16) years and 66 (46.2%) patients were female. Neurodevelopmental disabilities were present in 55 (38.5%) patients. Patients demonstrated a mean of 6.0 ± 2.1 signs of catatonia on the Bush Francis Catatonia Screening Item, with a mean BFCRS score of 15.0 ± 5.9. Among the 23 items of the BFCRS, six were present in >50% of patients (staring, mutism, immobility/stupor, withdrawal, posturing/catalepsy, rigidity), and four were present in <20% of cases (waxy flexibility, mitgehen, gegenhalten, grasp reflex). In an adjusted model, patients with neurodevelopmental disorders demonstrated greater BFCRS severity than those with other diagnoses. CONCLUSIONS: Catatonia was diagnosed in a range of mental health conditions. Further research is needed to define optimal diagnostic criteria for catatonia in paediatric patients, and clarify the clinical course of the disorder.

Use of the spider limb positioner for fibular free flap reconstruction of head and neck bony defects.

BACKGROUND: Osseous and osteocutaneous fibular free flaps are the workhorse of maxillomandibular reconstruction over 30 years after the initial description. Since 2019, we have routinely used the Spider Limb Positioner, adapted from its use in shoulder orthopedic procedures, for fibular free flap harvest. Herein, we describe this novel technique in our cohort. METHODS: We describe our intraoperative setup and endorse the versatility and utility of this technique in comparison to other reported fibular free flap harvest techniques. RESULTS: The Spider Limb Positioner was used 61 times in 60 different patients to harvest osseous or osteocutaneous fibular free flaps. Median (range) tourniquet time for flap harvest was 90 (40-124) minutes. No iatrogenic nerve compression injuries or complications related to lower extremity positioning occurred. CONCLUSION: We describe a novel approach to fibular free flap harvest utilizing the Spider Limb Positioner, which affords optimal ergonomics, visibility, and patient repositioning. There were no nerve injuries or complications related to positioning in our series.