Identifying prehospital trauma patients from ambulance patient care records; comparing two methods using linked data in New South Wales, Australia.

BACKGROUND: Linked datasets for trauma system monitoring should ideally follow patients from the prehospital scene to hospital admission and post-discharge. Having a well-defined cohort when using administrative datasets is essential because they must capture the representative population. Unlike hospital electronic health records (EHR), ambulance patient-care records lack access to sources beyond immediate clinical notes. Relying on a limited set of variables to define a study population might result in missed patient inclusion. We aimed to compare two methods of identifying prehospital trauma patients: one using only those documented under a trauma protocol and another incorporating additional data elements from ambulance patient care records. METHODS: We analyzed data from six routinely collected administrative datasets from 2015 to 2018, including ambulance patient-care records, aeromedical data, emergency department visits, hospitalizations, rehabilitation outcomes, and death records. Three prehospital trauma cohorts were created: an Extended-T-protocol cohort (patients transported under a trauma protocol and/or patients with prespecified criteria from structured data fields), T-protocol cohort (only patients documented as transported under a trauma protocol) and non-T-protocol (extended-T-protocol population not in the T-protocol cohort). Patient-encounter characteristics, mortality, clinical and post-hospital discharge outcomes were compared. A conservative p-value of 0.01 was considered significant RESULTS: Of 1 038 263 patient-encounters included in the extended-T-population 814 729 (78.5 %) were transported, with 438 893 (53.9 %) documented as a T-protocol patient. Half (49.6 %) of the non-T-protocol sub-cohort had an International Classification of Disease 10th edition injury or external cause code, indicating 79644 missed patients when a T-protocol-only definition was used. The non-T-protocol sub-cohort also identified additional patients with intubation, prehospital blood transfusion and positive eFAST. A higher proportion of non-T protocol patients than T-protocol patients were admitted to the ICU (4.6% vs 3.6 %), ventilated (1.8% vs 1.3 %), received in-hospital transfusion (7.9 vs 6.8 %) or died (1.8% vs 1.3 %). Urgent trauma surgery was similar between groups (1.3% vs 1.4 %). CONCLUSION: The extended-T-population definition identified 50 % more admitted patients with an ICD-10-AM code consistent with an injury, including patients with severe trauma. Developing an EHR phenotype incorporating multiple data fields of ambulance-transported trauma patients for use with linked data may avoid missing these patients.

The Effects of GreenShell Mussel Powder (Brand-Named PERNAULTRA) on Physical Performance and Subjective Pain, Symptoms, and Function Measures in Knee Osteoarthritis: A 6-Mo Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Osteoarthritis (OA) can cause disability and reduce quality of life (QoL). Objectives: This study aimed to determine whether GreenShell mussel (GSM) powder (PERNAULTRA) consumption was more effective than placebo at improving physical performance and subjective measures of symptoms and function in adults with early signs of knee OA. Methods: The Researching Osteoarthritis and GSM study was a 6-mo randomized, double-blind, placebo-controlled trial in adults aged 55-80 y, screened for signs of OA (n = 120, 65.9 ± 6.43 y, 63% female). Participants consumed either 3 g of powdered whole GSM or placebo (pea protein) daily. Baseline and end data collection included 30-s chair stand, stair test, 40-m fast-paced walk test, Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire categorized into 5 subscales [pain (P), symptoms except pain (S), function in activities of daily living (ADL), function in sports/recreation (SP), and QoL], a measure of Intermittent and Constant Osteoarthritis Pain, and visual analog scale of pain and symptoms. Results: Visual analog scale symptoms showed a significantly greater reduction in percentage change for GSM than that for placebo [-28.1 (-59.2, 43.2) compared with 0.00 (-28.6, 100); P = 0.03]. Further, a trend for improvement in percentage change for GSM compared with placebo was seen in 40m fast-paced walk [2.51 (-3.55, 8.12) compared with 0.20 (-6.58, 4.92); P = 0.09], KOOS-SP [11.4 (-4.48, 27.0) compared with 0.00 (-11.1, 17.7); P = 0.09], and Intermittent and Constant Osteoarthritis Pain intermittent pain scale [-27.7 (-77.3, 0.00) compared with -14.6 (-50.0, 36.4); P = 0.08]. In those with body mass index (BMI; in kg/m2) <25, GSM consumption significantly improved KOOS-S compared with placebo [6.35 (3.49, 12.7) compared with 0.00 (-4.65, 4.49); P = 0.03] and showed a trend for improvement in KOOS-ADL [3.29 (1.01, 8.79) compared with 1.01 (-5.75, 4.30); P = 0.07]. Those with BMI of ≥25, consuming GSM showed a trend for improvement in KOOS-SP [13.6 (-4.76, 33.3) compared with 0.00 (-12.5, 20.0); P = 0.07]. Conclusions: This research suggests consumption of GSM has potential to alleviate symptoms and improve functionality in OA.This trial was registered at Clinical Trial Registry as ACTRN12620001112954p (https://www.anzctr.org.au/ACTRN12620001112954p.aspx).

Evaluation of Oral Amoxicillin/Clavulanate for Urinary Tract Infections Caused by Ceftriaxone Non-Susceptible Enterobacterales.

Urinary tract infections (UTIs) are one of the most common infections and are frequently caused by Gram-negative organisms. The rise of resistant isolates has prompted evaluation of alternative therapies, including amoxicillin-clavulanate which has potent activity against Ambler class A enzymes. This study sought to evaluate clinical outcomes of patients with ceftriaxone non-susceptible UTIs receiving amoxicillin-clavulanate or standard of care (SOC). This was a single-center, retrospective, cohort study of adult patients with urinary tract infections caused by a ceftriaxone non-susceptible pathogen who received amoxicillin-clavulanate or SOC. The primary outcome was clinical failure at 90 days. Secondary outcomes included time to failure, isolation of a resistant organism, and hospital length of stay. Fifty-nine patients met study inclusion: 26 received amoxicillin/clavulanate and 33 received SOC. Amoxicillin-clavulanate recipients did not have higher failure rates compared to SOC recipients. For patients requiring hospital admission, hospital length of stay was numerically shorter with amoxicillin-clavulanate. The frequency of amoxicillin-clavulanate and carbapenem-resistant organisms did not differ significantly between groups. Amoxicillin-clavulanate may be a useful alternative therapy for the treatment of ceftriaxone non-susceptible Enterobacterales UTIs.

Reporting and Description of Research Methodology in Studies Estimating Effects of Firearm Policies.

BACKGROUND: Evidence about which firearm policies work, to what extent, and for whom is hotly debated, perhaps partly because variation in research methodology has produced mixed and inconclusive effect estimates. We conducted a scoping review of firearm policy research in the health sciences in the United States, focusing on methodological considerations for causal inference. METHODS: We identified original, empirical articles indexed in PubMed from 1/1/2000-9/1/2021 that examined any of 18 pre-specified firearm policies. We extracted key study components, including policy type(s) examined, policy operationalization, outcomes, study setting and population, study approach and design, causal language, and whether and how authors acknowledged potential sources of bias. RESULTS: We screened 7733 articles and included 124. A plurality of studies used a legislative score as their primary exposure (n=39; 32%) and did not examine change in policies over time (n=47; 38%). Most examined firearm homicide (n=51; 41%) or firearm suicide (n=40; 32%) as outcomes. One-third adjusted for other firearm policies (n=41; 33%). Three studies (2%) explicitly mentioned that their goal was to estimate causal effects, but over half used language implying causality (n=72; 58%). Most acknowledged causal identification assumptions of temporality (n=91; 73%) and exchangeability (n=111; 90%); other assumptions were less often acknowledged. One-third of studies included bias analyses (n=42; 34%). CONCLUSIONS: We identified a range of methodologic approaches in firearm policy research in the health sciences. Acknowledging limitations of data availability and quality, we identify opportunities to improve causal inferences about and reporting on the effects of firearm policies on population health.

Toward a clearer understanding of what works to reduce gun violence: the role of falsification strategies.

Strong epidemiologic evidence from ecologic and individual-level studies in the United States supports the claim that access to firearms substantially increases the risk of dying by suicide, homicide, and firearm accidents. Less certain is how well particular interventions work to prevent these deaths and other firearm-related harms. Given the limits of existing data to study firearm violence, and the infeasibility of conducting randomized trials of firearm access, it is important to do the best we can with the data we already have. We argue that falsification strategies are a critical - yet underutilized - component of any such analytic approach. The falsification strategies we focus on are versions of "negative controls" analyses in which we expect an analysis should yield a null causal effect, and thus where not obtaining a null effect estimate raises questions about the assumptions underlying causal interpretation of a study's findings. We illustrate the saliency of this issue today with examples drawn from studies published within the last five years in leading peer-reviewed journals. Collecting rich, high-quality data always takes time, urgent as the need may be. On the other hand, doing better with the data we already have can start right now.

Fatal Police Shootings of Victims with Mental Health Crises: A Descriptive Analysis of Data from the 2014-2015 National Violent Death Reporting System.

One in five fatal police shooting victims may have been experiencing a mental health crisis (MHC) at the time of their death [1]. We use data on fatal police shootings from the National Violent Death Reporting System (2014-2015) to (a) identify incidents where the victim is reported to have experienced an MHC at the time of their death, (b) describe the characteristics of these incidents, and (c) compare the characteristics of MHC to fatal police shootings where the victim was not experiencing an MHC at the time of their death. We systematically coded 633 fatal police shootings from 27 states. Descriptive statistics characterized fatal police shootings, including victim characteristics; their mental health status; and contextual information regarding the police encounter (e.g., reason for police call). Overall, 203 of 633 fatal police encounters (32%) involved victims who showed signs of an MHC at the time of their death. Victims were predominantly white, male, and in possession of a firearm. In 3 of 4 cases, the MHC manifested as suicidal ideation despite any relevant documented history among most victims. Among half of suicidal victims, suicidal ideation was expressed verbally and in-person to a family member/intimate partner who subsequently called the police. Dispatch was aware of the MHC in 1 of 4 of total police calls. Overall, fatal police encounters involving those experiencing an MHC accounted for 1 in 3 of our caseloads. Approximately, 3 of 4 mental health calls involved a suicidal person who mainly expressed intent to a loved one in-person.

Demystifying the Digital Divide: Disparities in Telerehabilitation Readiness Among Older Adults in the United States.

OBJECTIVE: To estimate readiness of older rehabilitation users in the United States to participate in video-based telerehabilitation and assess disparities in readiness among racial and ethnic minoritized populations, socioeconomically disadvantaged populations, and rural-dwelling older adults. DESIGN: Retrospective cohort study using nationally representative survey data from the National Health and Aging Trends Study from 2015 and 2020. Survey-weighted regression models, accounting for complex survey design, were used to generate estimates of readiness and evaluate disparities across racial and ethnic, socioeconomic, and geographic subgroups. Odds ratios (OR) and 95% confidence intervals (CIs) were estimated for each comparison. SETTING: Home or community rehabilitation environments. PARTICIPANTS: A cohort of 5274 home or community-based rehabilitation users aged 70 years or older (N=5274), representing a weighted 33,576,313 older adults in the United States. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): Video-based telerehabilitation readiness was defined consistent with prior work; unreadiness was defined as lacking ownership of internet-enabled devices, limited proficiency of use, or living with severe cognitive, visual, or hearing impairment. Telerehabilitation readiness was categorized as "Ready" or "Unready". RESULTS: Approximately 2 in 3 older rehabilitation users were categorized as ready to participate in video-based rehabilitation. Significantly lower rates of readiness were observed among those living in rural areas (OR=0.75, 95% CI: 0.60-0.94), financially strained individuals (OR=0.37, 95% CI: 0.26-0.53), and among individuals identifying as Black or Hispanic (as compared with non-Hispanic White older adults: Non-Hispanic Black [OR=0.23, 95% CI: 0.18-0.30]; Hispanic [OR=0.17, 95% CI: 0.11, 0.27]). CONCLUSIONS: Our findings highlight significant disparities in the readiness to uptake video-based telerehabilitation. Policy and practice interventions to address telerehabilitation readiness should focus not only on improving broadband access but also on technology ownership and training to ensure equitable adoption in populations with lower baseline readiness.

ALK upregulates POSTN and WNT signaling to drive neuroblastoma.

Neuroblastoma is the most common extracranial solid tumor of childhood. While MYCN and mutant anaplastic lymphoma kinase (ALKF1174L) cooperate in tumorigenesis, how ALK contributes to tumor formation remains unclear. Here, we used a human stem cell-based model of neuroblastoma. Mis-expression of ALKF1174L and MYCN resulted in shorter latency compared to MYCN alone. MYCN tumors resembled adrenergic, while ALK/MYCN tumors resembled mesenchymal, neuroblastoma. Transcriptomic analysis revealed enrichment in focal adhesion signaling, particularly the extracellular matrix genes POSTN and FN1 in ALK/MYCN tumors. Patients with ALK-mutant tumors similarly demonstrated elevated levels of POSTN and FN1. Knockdown of POSTN, but not FN1, delayed adhesion and suppressed proliferation of ALK/MYCN tumors. Furthermore, loss of POSTN reduced ALK-dependent activation of WNT signaling. Reciprocally, inhibition of the WNT pathway reduced expression of POSTN and growth of ALK/MYCN tumor cells. Thus, ALK drives neuroblastoma in part through a feedforward loop between POSTN and WNT signaling.

High-Precision Viral Detection Using Electrochemical Kinetic Profiling of Aptamer-Antigen Recognition in Clinical Samples and Machine Learning.

High-precision viral detection at point of need with clinical samples plays a pivotal role in the diagnosis of infectious diseases and the control of a global pandemic. However, the complexity of clinical samples that often contain very low viral concentrations makes it a huge challenge to develop simple diagnostic devices that do not require any sample processing and yet are capable of meeting performance metrics such as very high sensitivity and specificity. Herein we describe a new single-pot and single-step electrochemical method that uses real-time kinetic profiling of the interaction between a high-affinity aptamer and an antigen on a viral surface. This method generates many data points per sample, which when combined with machine learning, can deliver highly accurate test results in a short testing time. We demonstrate this concept using both SARS-CoV-2 and Influenza A viruses as model viruses with specifically engineered high-affinity aptamers. Utilizing this technique to diagnose COVID-19 with 37 real human saliva samples results in a sensitivity and specificity of both 100 % (27 true negatives and 10 true positives, with 0 false negative and 0 false positive), which showcases the superb diagnostic precision of this method.

Patient Experience of Women With Dense Breasts Undergoing Screening Contrast-Enhanced Mammography.

OBJECTIVE: We investigated patient experience with screening contrast-enhanced mammography (CEM) to determine whether a general population of women with dense breasts would accept CEM in a screening setting. METHODS: In this institutional review board-approved prospective study, patients with heterogeneous and extremely dense breasts on their mammogram were invited to undergo screening CEM and complete pre-CEM and post-CEM surveys. On the pre-CEM survey, patients were asked about their attitudes regarding supplemental screening in general. On the post-CEM survey, patients were asked about their experience undergoing screening CEM, including causes and severity of any discomfort and whether they would consider undergoing screening CEM again in the future or recommend it to a friend. RESULTS: One hundred sixty-three women were surveyed before and after screening CEM. Most patients, 97.5% (159/163), reported minimal or no unpleasantness associated with undergoing screening CEM. In addition, 91.4% (149/163) said they would probably or very likely undergo screening CEM in the future if it cost the same as a traditional screening mammogram, and 95.1% (155/163) said they would probably or very likely recommend screening CEM to a friend. Patients in this study, who were all willing to undergo CEM, more frequently reported a family history of breast cancer than a comparison cohort of women with dense breasts (58.2% vs 47.1%, P = .027). CONCLUSION: Patients from a general population of women with dense breasts reported a positive experience undergoing screening CEM, suggesting screening CEM might be well received by this patient population, particularly if the cost was comparable with traditional screening mammography.

The processing intermediate of human amylin, pro-amylin(1-48), has in vivo and in vitro bioactivity.

Amylin is released by pancreatic beta-cells in response to a meal and its major soluble mature form (37 amino acid-peptide) produces its biological effects by activating amylin receptors. Amylin is derived from larger propeptides that are processed within the synthesizing beta-cell. There are suggestions that a partially processed form, pro-amylin(1-48) is also secreted. We tested the hypothesis that pro-amylin(1-48) has biological activity and that human pro-amylin(1-48) may also form toxic pre-amyloid species. Amyloid formation, the ability to cross-seed and in vitro toxicity were similar between human pro-amylin(1-48) and amylin. Human pro-amylin(1-48) was active at amylin-responsive receptors, though its potency was reduced at rat, but not human amylin receptors. Pro-amylin(1-48) was able to promote anorexia by activating neurons of the area postrema, amylin's primary site of action, indicating that amylin can tolerate significant additions at the N-terminus without losing bioactivity. Our studies help to shed light on the possible roles of pro-amylin(1-48) which may be relevant for the development of future amylin-based drugs.

Smallest Clinically Meaningful Improvement in Amputation-Related Pain and Brief Pain Inventory Scores as Defined by Patient Reports of Global Improvement After Cryoneurolysis: a Retrospective Analysis of a Randomized, Controlled Clinical Trial.

BACKGROUND: The smallest meaningful improvement in pain scores (minimal clinically important difference [MCID]) after an analgesic intervention is essential information when both interpreting published data and designing a clinical trial. However, limited information is available for patients with chronic pain conditions, and what is published is derived from studies involving pharmacologic and psychological interventions. We here calculate these values based on data collected from 144 participants of a previously published multicenter clinical trial investigating the effects of a single treatment with percutaneous cryoneurolysis. METHODS: In the original trial, we enrolled patients with a lower-limb amputation and established phantom pain. Each received a single-injection femoral and sciatic nerve block with lidocaine and was subsequently randomized to receive either ultrasound-guided percutaneous cryoneurolysis or sham treatment at these same locations. Investigators, participants, and clinical staff were masked to treatment group assignment with the exception of the treating physician performing the cryoneurolysis, who had no subsequent participant interaction. At both baseline and 4 months (primary end point), participants rated their phantom limb pain based on a numeric rating scale (NRS) and their interference of pain on physical and emotional functioning as measured with the Brief Pain Inventory's interference subscale. They subsequently qualitatively defined the change using the 7-point ordinal Patient Global Impression of Change (PGIC). The smallest clinically meaningful improvements in phantom limb pain and Brief Pain Inventory scores were calculated using an anchor-based method based on the PGIC. RESULTS: The median (interquartile range [IQR]) phantom pain NRS (0-10) improvements at 4 months considered small, medium, and large were 1 [1-1], 3 [3-4], and 4 [3-6], respectively. The median improvements in the Brief Pain Inventory interference subscale (0-70) associated with a small, medium, and large analgesic changes were 16 [6-18], 24 [22-31], and 34 [22-46]. The proportions of patients that experienced PGIC ≥5 were 33% and 36% in the active and placebo groups, respectively. The relative risk of a patient experiencing PGIC ≥5 in the active group compared to the sham group with 95% confidence interval was 0.9 (0.6-1.4), P = .667. CONCLUSIONS: Amputees with phantom limb pain treated with percutaneous cryoneurolysis rate analgesic improvements as clinically meaningful similar to pharmacologic treatments, although their MCID for the Brief Pain Inventory was somewhat larger than previously published values. This information on patient-defined clinically meaningful improvements will facilitate interpretation of available studies and guide future trial design.

Patient characteristics and telehealth are associated with attendance rates in an outpatient rehabilitation infant bridge program.

OBJECTIVE: To describe the characteristics of patients who received outpatient therapy services through an infant bridge program using telehealth mode of service delivery and to identify if attendance rates vary by mode of service delivery. We hypothesized that telehealth visits will increase attendance rates. DESIGN: Retrospective, cross-sectional study. SETTING: UCSF Benioff Children's Hospital outpatient infant bridge program. PARTICIPANTS: Eighty infants with a history of NICU admission and scheduled for a therapy appointment between June 1, 2019 and December 31, 2020 were included in the study. Participants had an average(SD) gestational age of 34.63(4.41) weeks and length of stay was 43.55(56.03) weeks. The majority were English-speaking (96.3%), White (37.5%), and had commercial insurance (72.5%). MAIN OUTCOME MEASURE: Descriptive analyses were conducted across the entire group along with service delivery model subgroup analysis. Logistic regression was performed to assess patient characteristics associated with attendance and if service delivery model influences attendance. RESULTS: In the analysis of 596 scheduled visits, there were more completed telehealth sessions than for in-person sessions (90.0% versus 84.1%, p = .011). For in-person sessions, infants (N = 40) with lower birth gestational ages (p = .009), longer length of stay (p = .041), and Medi-Cal insurance (p = .006) were more likely to have ≥2 missed appointments. For the telehealth sessions, infants (N = 40) who had longer length of stay (p = .040) were more likely to have ≥2 missed appointments. There is a higher likelihood of ≥2 missed appointments for patients with a longer length of stay (OR = 1.02, 95% CI [1.01, 1.03]) and for in-person service delivery when compared to telehealth (OR = 6.25, 95% CI [1.37, 28.57]). CONCLUSIONS: Telehealth was associated with higher likelihood of attendance, revealing that telehealth has the potential to increase access to early therapy services for certain populations. Future studies with larger sample sizes to determine which populations benefit from telehealth is recommended.

Application of MALDI-TOF MS and machine learning for the detection of SARS-CoV-2 and non-SARS-CoV-2 respiratory infections.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) could aid the diagnosis of acute respiratory infections (ARIs) owing to its affordability and high-throughput capacity. MALDI-TOF MS has been proposed for use on commonly available respiratory samples, without specialized sample preparation, making this technology especially attractive for implementation in low-resource regions. Here, we assessed the utility of MALDI-TOF MS in differentiating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vs non-COVID acute respiratory infections (NCARIs) in a clinical lab setting in Kazakhstan. Nasopharyngeal swabs were collected from inpatients and outpatients with respiratory symptoms and from asymptomatic controls (ACs) in 2020-2022. PCR was used to differentiate SARS-CoV-2+ and NCARI cases. MALDI-TOF MS spectra were obtained for a total of 252 samples (115 SARS-CoV-2+, 98 NCARIs, and 39 ACs) without specialized sample preparation. In our first sub-analysis, we followed a published protocol for peak preprocessing and machine learning (ML), trained on publicly available spectra from South American SARS-CoV-2+ and NCARI samples. In our second sub-analysis, we trained ML models on a peak intensity matrix representative of both South American (SA) and Kazakhstan (Kaz) samples. Applying the established MALDI-TOF MS pipeline "as is" resulted in a high detection rate for SARS-CoV-2+ samples (91.0%), but low accuracy for NCARIs (48.0%) and ACs (67.0%) by the top-performing random forest model. After re-training of the ML algorithms on the SA-Kaz peak intensity matrix, the accuracy of detection by the top-performing support vector machine with radial basis function kernel model was at 88.0%, 95.0%, and 78% for the Kazakhstan SARS-CoV-2+, NCARI, and AC subjects, respectively, with a SARS-CoV-2 vs rest receiver operating characteristic area under the curve of 0.983 [0.958, 0.987]; a high differentiation accuracy was maintained for the South American SARS-CoV-2 and NCARIs. MALDI-TOF MS/ML is a feasible approach for the differentiation of ARI without specialized sample preparation. The implementation of MALDI-TOF MS/ML in a real clinical lab setting will necessitate continuous optimization to keep up with the rapidly evolving landscape of ARI.IMPORTANCEIn this proof-of-concept study, the authors used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and machine learning (ML) to identify and distinguish acute respiratory infections (ARI) caused by SARS-CoV-2 versus other pathogens in low-resource clinical settings, without the need for specialized sample preparation. The ML models were trained on a varied collection of MALDI-TOF MS spectra from studies conducted in Kazakhstan and South America. Initially, the MALDI-TOF MS/ML pipeline, trained exclusively on South American samples, exhibited diminished effectiveness in recognizing non-SARS-CoV-2 infections from Kazakhstan. Incorporation of spectral signatures from Kazakhstan substantially increased the accuracy of detection. These results underscore the potential of employing MALDI-TOF MS/ML in resource-constrained settings to augment current approaches for detecting and differentiating ARI.

Prospective evaluation of single-dose aminoglycosides for treatment of complicated cystitis in the emergency department.

BACKGROUND: Antimicrobial resistance among Enterobacterales continues to be a growing problem, particularly in those with urinary infections. Previous studies have demonstrated safety and efficacy with the use of single-dose aminoglycosides in uncomplicated cystitis. However, data in complicated infections are limited. Single-dose aminoglycosides may provide a convenient alternative for those with or at risk for resistant pathogens causing complicated urinary infections, especially when oral options are unavailable due to resistance, allergy, intolerance, or interactions with other medications. This study evaluated the safety and effectiveness of single-dose aminoglycosides in treatment of complicated cystitis in the emergency department (ED). METHODS: This was a multicenter, prospective study performed between July 2022 and March 2023 of patients who met criteria for complicated cystitis and were otherwise stable for discharge at an academic ED. Primary outcomes were clinical or microbiologic failure within 14 days of treatment. Safety was assessed by review of adverse events. Descriptive statistics were used. RESULTS: Thirteen patients were included. Complicating factors were male sex (n = 4), kidney stone (n = 2), urinary catheter (n = 6), recent urologic procedure (n = 1), urinary hardware (n = 1), antibiotic allergy precluding use of alternate oral options (n = 4), immunocompromised status (n = 2), and <1-year history of multidrug-resistant organisms on urine culture (n = 8). Eleven patients (85%) had positive urine cultures in the preceding 12 months with no oral antimicrobial option. Eight patients (62%) received amikacin (median dose 15 mg/kg), four patients (31%) received gentamicin (median dose 5 mg/kg), and one patient (8%) received tobramycin (5 mg/kg) for treatment. Ten patients (77%) reported resolved urinary symptoms after treatment and 11 patients (85%) reported no new urinary symptoms since discharge. No patient required hospital admission for treatment failure, and no adverse events were noted. CONCLUSIONS: Single-dose aminoglycosides appear to be a reasonably effective and safe treatment for complicated cystitis, which avoided hospital admission in this cohort.

Human myofiber-enriched aging-induced lncRNA FRAIL1 promotes loss of skeletal muscle function.

The loss of skeletal muscle mass during aging is a significant health concern linked to adverse outcomes in older individuals. Understanding the molecular basis of age-related muscle loss is crucial for developing strategies to combat this debilitating condition. Long noncoding RNAs (lncRNAs) are a largely uncharacterized class of biomolecules that have been implicated in cellular homeostasis and dysfunction across a many tissues and cell types. To identify lncRNAs that might contribute to skeletal muscle aging, we screened for lncRNAs whose expression was altered in vastus lateralis muscle from older compared to young adults. We identified FRAIL1 as an aging-induced lncRNA with high abundance in human skeletal muscle. In healthy young and older adults, skeletal muscle FRAIL1 was increased with age in conjunction with lower muscle function. Forced expression of FRAIL1 in mouse tibialis anterior muscle elicits a dose-dependent reduction in skeletal muscle fiber size that is independent of changes in muscle fiber type. Furthermore, this reduction in muscle size is dependent on an intact region of FRAIL1 that is highly conserved across non-human primates. Unbiased transcriptional and proteomic profiling of the effects of FRAIL1 expression in mouse skeletal muscle revealed widespread changes in mRNA and protein abundance that recapitulate age-related changes in pathways and processes that are known to be altered in aging skeletal muscle. Taken together, these findings shed light on the intricate molecular mechanisms underlying skeletal muscle aging and implicate FRAIL1 in age-related skeletal muscle phenotypes.

Fatty acid production and associated gene pathways are altered by increased salinity and dimethyl sulfoxide treatments during cryopreservation of Symbiodinium pilosum (Symbiodiniaceae).

The Symbiodinium genus is ancestral among other Symbiodiniaceae lineages with species that are both symbiotic and free living. Changes in marine ecosystems threaten their existence and crucial ecological roles. Cryopreservation offers an avenue for their long-term storage for future habitat restoration after coral bleaching. In our previous study we demonstrated that high salinity treatments of Symbiodiniaceae isolates led to changes in their fatty acid (FA) profiles and higher cell viabilities after cryopreservation. In this study, we investigated the role of increased salinity on FA production and the genes involved in FA biosynthesis and degradation pathways during the cryopreservation of Symbiodinium pilosum. Overall, there was a twofold increase in mass of FAs produced by S. pilosum after being cultured in medium with increased salinity (54 parts per thousand; ppt). Dimethyl sulfoxide (Me2SO) led to a ninefold increase of FAs in standard salinity (SS) treatment, compared to a fivefold increase in increased salinity (IS) treatments. The mass of the FA classes returned to baseline during recovery. Transcriptomic analyses showed an acyl carrier protein gene was significantly upregulated after Me2SO treatment in the SS cultures. Cytochrome P450 reductase genes were significantly down regulated after Me2SO addition in SS treatment preventing FA degradation. These changes in the expression of FA biosynthesis and degradation genes contributed to more FAs in SS treated isolates. Understanding how increased salinity changes FA production and the roles of specific genes in regulating FA pathways will help improve current freezing protocols for Symbiodiniaceae and other marine microalgae.