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1.
Age Ageing ; 53(7)2024 Jul 02.
Article in English | MEDLINE | ID: mdl-39023234

ABSTRACT

BACKGROUND: Hospital falls continue to be a persistent global issue with serious harmful consequences for patients and health services. Many clinical practice guidelines now exist for hospital falls, and there is a need to appraise recommendations. METHOD: A systematic review and critical appraisal of the global literature was conducted, compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Web of Science, Embase, CINAHL, MEDLINE, Epistemonikos, Infobase of Clinical Practice Guidelines, Cochrane CENTRAL and PEDro databases were searched from 1 January 1993 to 1 February 2024. The quality of guidelines was assessed by two independent reviewers using Appraisal of Guidelines for Research and Evaluation Global Rating Scale and Appraisal of Guidelines of Research and Evaluation Recommendation Excellence (AGREE-REX). Certainty of findings was rated using Grading of Recommendations Assessment, Development and Evaluation Confidence in Evidence from Reviews of Qualitative Research. Data were analysed using thematic synthesis. RESULTS: 2404 records were screened, 77 assessed for eligibility, and 20 hospital falls guidelines were included. Ten had high AGREE-REX quality scores. Key analytic themes were as follows: (i) there was mixed support for falls risk screening at hospital admission, but scored screening tools were no longer recommended; (ii) comprehensive falls assessment was recommended for older or frail patients; (iii) single and multifactorial falls interventions were consistently recommended; (iv) a large gap existed in patient engagement in guideline development and implementation; (v) barriers to implementation included ambiguities in how staff and patient falls education should be conducted, how delirium and dementia are managed to prevent falls, and documentation of hospital falls. CONCLUSION: Evidence-based hospital falls guidelines are now available, yet systematic implementation across the hospital sector is more limited. There is a need to ensure an integrated and consistent approach to evidence-based falls prevention for a diverse range of hospital patients.


Subject(s)
Accidental Falls , Practice Guidelines as Topic , Accidental Falls/prevention & control , Humans , Practice Guidelines as Topic/standards , Risk Assessment , Aged , Risk Factors , Hospitalization
2.
Prev Vet Med ; 230: 106261, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38964208

ABSTRACT

Salmonellosis is one of the most common foodborne diseases worldwide, with the ability to infect humans and animals. Antimicrobial resistance (AMR) and, particularly, multidrug resistance (MDR) among Salmonella enterica poses a risk to human health. Antimicrobial use (AMU) regulations in livestock have been implemented to reduce AMR and MDR in foodborne pathogens. In this study, we used an integrated machine learning approach to investigate Salmonella AMR and MDR patterns before and after the implementation of AMU restrictions in agriculture in the United States. For this purpose, Salmonella isolates from cattle in the National Antimicrobial Resistance Monitoring System (NARMS) dataset were analysed using three descriptive models consisting of hierarchical clustering, network analysis, and association rule mining. The analysis showed the impact of the United States' 2012 extra-label cephalosporin regulations on AMR trends and revealed a distinctive MDR pattern in the Dublin serotype. The results also indicated that each descriptive model provides insights on a specific aspect of resistance patterns and, therefore, combining these approaches make it possible to gain a deeper understanding of AMR.

3.
JMIR Public Health Surveill ; 10: e54551, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38952000

ABSTRACT

Background: Syndromic surveillance represents a potentially inexpensive supplement to test-based COVID-19 surveillance. By strengthening surveillance of COVID-19-like illness (CLI), targeted and rapid interventions can be facilitated that prevent COVID-19 outbreaks without primary reliance on testing. Objective: This study aims to assess the temporal relationship between confirmed SARS-CoV-2 infections and self-reported and health care provider-reported CLI in university and county settings, respectively. Methods: We collected aggregated COVID-19 testing and symptom reporting surveillance data from Cornell University (2020-2021) and Tompkins County Health Department (2020-2022). We used negative binomial and linear regression models to correlate confirmed COVID-19 case counts and positive test rates with CLI rate time series, lagged COVID-19 cases or rates, and day of the week as independent variables. Optimal lag periods were identified using Granger causality and likelihood ratio tests. Results: In modeling undergraduate student cases, the CLI rate (P=.003) and rate of exposure to CLI (P<.001) were significantly correlated with the COVID-19 test positivity rate with no lag in the linear models. At the county level, the health care provider-reported CLI rate was significantly correlated with SARS-CoV-2 test positivity with a 3-day lag in both the linear (P<.001) and negative binomial model (P=.005). Conclusions: The real-time correlation between syndromic surveillance and COVID-19 cases on a university campus suggests symptom reporting is a viable alternative or supplement to COVID-19 surveillance testing. At the county level, syndromic surveillance is also a leading indicator of COVID-19 cases, enabling quick action to reduce transmission. Further research should investigate COVID-19 risk using syndromic surveillance in other settings, such as low-resource settings like low- and middle-income countries.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , COVID-19/diagnosis , COVID-19/prevention & control , Retrospective Studies , Universities/statistics & numerical data , Sentinel Surveillance
4.
J Med Toxicol ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992233

ABSTRACT

BACKGROUND: Acetaminophen toxicity remains one of the most common causes of liver failure and is treated with a course of n-acetylcysteine (NAC). This exceptionally effective medication is traditionally administered using a complicated three-bag protocol that is prone to administration errors. OBJECTIVE: We aimed to assess whether switching to a novel two-bag protocol (150 mg/kg over 1 h followed by 150 mg/kg over 20 h) reduced administration errors while not increasing liver injury or anaphylactoid reactions. METHODS: This was a retrospective chart review of hospital encounters for patients with acetaminophen toxicity, comparing outcomes before and after the change from a three-bag protocol to a two-bag protocol at two affiliated institutions. The primary outcome was incidence of medication errors with secondary outcomes including acute liver injury (ALI) and incidence of non-anaphylactoid allergic reactions (NAAR). The study was approved by the health system's Institutional Review Board. RESULTS: 483 encounters were included for analysis (239 in the three-bag and 244 in the two-bag groups). NAAR were identified in 11 patients with no difference seen between groups. Similarly, no differences were seen in ALI. Medication administration errors were observed significantly less often in the two-bag group (OR 0.24) after adjusting for confounders. CONCLUSION: Transitioning to a novel two-bag NAC regimen decreased administration errors. This adds to the literature that two-bag NAC regimens are not only safe but also may have significant benefits over the traditional NAC protocol.

5.
Transl Anim Sci ; 8: txae088, 2024.
Article in English | MEDLINE | ID: mdl-38863593

ABSTRACT

Supplemental methionine (Met) is widely used within the swine industry; however, data are limited regarding the effect of Met sources on carcass cutability and meat quality. The objective was to determine the effects of L-Met (LM, 99%), DL-Met (DLM, 99%), or calcium salt of DL-Met hydroxyl analog (MHA, 84%) in finishing pig diets on carcass characteristics and meat quality. At 9 weeks of age, pigs (N = 240) were allocated to 60 single-sex pens for a four-phase finishing trial that lasted 104 d. Pigs were fed a common grower diet until day 56 where pens were randomly allotted to one of the three experimental diets. For the remaining 7 wk of the finisher phase, pigs (BW = 79.9 ±â€…0.80 kg) were fed diets containing LM, DLM, or MHA, with the supplemental Met source providing 25% of standardized ileal digestible (SID) Met + cysteine (Cys) requirement based on 65% bioefficacy for MHA in comparison with LM or DLM. One pig per pen was slaughtered at the study conclusion (on day 104), and the left sides of carcasses were fabricated into subprimal cuts to determine carcass-cutting yields. Loin quality including proximate composition and shear force were measured. Hot carcass weight was not different (P = 0.34) between treatments (LM 104.5 kg; DLM 103.0 kg; MHA 101.5 kg), moreover, loin eye area was not different (P = 0.98) between treatments (LM 52.65 cm²; DLM 52.49 cm²; MHA 52.81 cm²). Boneless carcass-cutting yield was not different (P = 0.56) between treatments (LM 54.97 kg; DLM 54.82 kg; MHA 54.52 kg). Loin pH was not different (P = 0.24) between treatments (LM 5.45; DLM 5.48; MHA 5.45). However, drip loss tended to be reduced (P = 0.11) by the DLM treatment (5.58%) compared with LM (7.03%) and MHA (6.68%) treatments. Shear force was not different (P = 0.85) between treatments (LM 3.03 kg; DLM 3.06 kg; MHA 3.10 kg). However, cook loss tended to be reduced (P = 0.06) by the DLM treatment (16.20%) compared with LM (18.18%) and MHA (18.50%) treatments. These data suggest that only minimal differences in carcass cutability and meat quality can be attributed to Met source in finishing pig diets when using 65% bioefficacy for MHA relative to L-Met or DL-Met.

6.
Physiotherapy ; 124: 116-125, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38878590

ABSTRACT

OBJECTIVES: To determine the prevalence of metabolic syndrome in clients presenting for primary care physiotherapy within private practice settings, and the factors that may be associated with metabolic syndrome. The secondary aim was to determine client's attitudes towards lifestyle change. DESIGN: A cross-sectional study in which self-report and biometric data were collected. The study was conducted in physiotherapy private practices across metropolitan and regional areas, Australia. PARTICIPANTS: 230 clients (mean age 54 (SD18) years, 64% women) presenting for physiotherapy participated. MAIN OUTCOME MEASURES: Participant socio-demographic and lifestyle characteristics were collected. Metabolic syndrome presence was determined by the existence of three or more risk factors on physical examination and capillary blood sample: abdominal obesity, hypertension, elevated random blood glucose, elevated triglycerides and/or reduced HDL cholesterol. RESULTS: Thirty-seven percent of participants had metabolic syndrome, but none knew they had it. Metabolic syndrome was associated with older age and poorer socio-economic status and may have been associated with lower levels of physical activity but not diet. Of those identified as having hypertension and elevated triglycerides, many were undiagnosed (56% and 29% respectively). CONCLUSION: Metabolic syndrome is prevalent and undiagnosed in clients attending private practice physiotherapy. Clients felt lifestyle change was important and they were willing to make changes. This study highlights the need for greater screening of metabolic risk factors in primary care and presents an opportunity for physiotherapists in private practice to identify risk and intervene to improve the overall health of their clients and contribute to chronic disease prevention. CONTRIBUTION OF THE PAPER.

7.
Physiotherapy ; 124: 75-84, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38875840

ABSTRACT

OBJECTIVES: To determine the knowledge, attitudes, and current practice of primary care physiotherapists in recognising and managing clients with metabolic syndrome. DESIGN: Mixed-methods research design comprising an online survey and focus groups. PARTICIPANTS: Australian and English physiotherapists (n = 183) working in a primary care setting responded to the survey. Twelve physiotherapists participated in focus groups. RESULTS: Metabolic syndrome was not on physiotherapists radar. They did not screen for metabolic syndrome nor provide management for it in primary care. Although most physiotherapists had some awareness of metabolic syndrome, they were not knowledgeable. Physiotherapists reported a need to focus on their clients' presenting condition, and there was uncertainty on whether metabolic syndrome management was within their scope of practice. Despite this, physiotherapists felt they had an important role to play in exercise and physical activity prescription for chronic disease management and were keen to further their knowledge and skills related to metabolic syndrome. Survey responses and focus group data were convergent. CONCLUSION: Physiotherapists working in primary care settings are well-placed to identify metabolic risk factors in their clients and provide physical activity interventions to enhance management but currently lack knowledge to embed this in clinical practice. Training and resources are required to enable physiotherapists to identify and manage metabolic syndrome within their practice. CONTRIBUTION OF PAPER.

8.
Nat Commun ; 15(1): 5053, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38871684

ABSTRACT

Childhood radioactive iodine exposure from the Chornobyl accident increased papillary thyroid carcinoma (PTC) risk. While cervical lymph node metastases (cLNM) are well-recognized in pediatric PTC, the PTC metastatic process and potential radiation association are poorly understood. Here, we analyze cLNM occurrence among 428 PTC with genomic landscape analyses and known drivers (131I-exposed = 349, unexposed = 79; mean age = 27.9 years). We show that cLNM are more frequent in PTC with fusion (55%) versus mutation (30%) drivers, although the proportion varies by specific driver gene (RET-fusion = 71%, BRAF-mutation = 38%, RAS-mutation = 5%). cLNM frequency is not associated with other characteristics, including radiation dose. cLNM molecular profiling (N = 47) demonstrates 100% driver concordance with matched primary PTCs and highly concordant mutational spectra. Transcriptome analysis reveals 17 differentially expressed genes, particularly in the HOXC cluster and BRINP3; the strongest differentially expressed microRNA also is near HOXC10. Our findings underscore the critical role of driver alterations and provide promising candidates for elucidating the biological underpinnings of PTC cLNM.


Subject(s)
Chernobyl Nuclear Accident , Iodine Radioisotopes , Lymphatic Metastasis , Mutation , Thyroid Cancer, Papillary , Thyroid Neoplasms , Humans , Thyroid Cancer, Papillary/genetics , Thyroid Cancer, Papillary/pathology , Lymphatic Metastasis/genetics , Male , Adult , Female , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Adolescent , Proto-Oncogene Proteins B-raf/genetics , Young Adult , Lymph Nodes/pathology , Proto-Oncogene Proteins c-ret/genetics , Child , Genomics , Middle Aged , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Gene Expression Profiling , MicroRNAs/genetics , MicroRNAs/metabolism , Neoplasms, Radiation-Induced/genetics , Neoplasms, Radiation-Induced/pathology , Neck/pathology , Gene Expression Regulation, Neoplastic
9.
Clin Neurophysiol ; 164: 30-39, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38843758

ABSTRACT

OBJECTIVE: High frequency oscillations (HFOs) are a biomarker of the seizure onset zone (SOZ) and can be visually or automatically detected. In theory, one can optimize an automated algorithm's parameters to maximize SOZ localization accuracy; however, there is no consensus on whether or how this should be done. Therefore, we optimized an automated detector using visually identified HFOs and evaluated the impact on SOZ localization accuracy. METHODS: We detected HFOs in intracranial EEG from 20 patients with refractory epilepsy from two centers using (1) unoptimized automated detection, (2) visual identification, and (3) automated detection optimized to match visually detected HFOs. RESULTS: SOZ localization accuracy based on HFO rate was not significantly different between the three methods. Across patients, visually optimized detector settings varied, and no single set of settings produced universally accurate SOZ localization. Exploratory analysis suggests that, for many patients, detection settings exist that would improve SOZ localization. CONCLUSIONS: SOZ localization accuracy was similar for all three methods, was not improved by visually optimizing detector settings, and may benefit from patient-specific parameter optimization. SIGNIFICANCE: Visual HFO marking is laborious, and optimizing automated detection using visual markings does not improve localization accuracy. New patient-specific detector optimization methods are needed.


Subject(s)
Drug Resistant Epilepsy , Humans , Female , Male , Adult , Drug Resistant Epilepsy/physiopathology , Drug Resistant Epilepsy/diagnosis , Electroencephalography/methods , Middle Aged , Electrocorticography/methods , Electrocorticography/standards , Seizures/physiopathology , Seizures/diagnosis , Brain Waves/physiology , Algorithms , Young Adult , Adolescent , Epilepsy/physiopathology , Epilepsy/diagnosis
10.
PLoS One ; 19(6): e0297917, 2024.
Article in English | MEDLINE | ID: mdl-38857268

ABSTRACT

What is the role of working memory over the course of non-native speech category learning? Prior work has predominantly focused on how working memory might influence learning assessed at a single timepoint. Here, we substantially extend this prior work by examining the role of working memory on speech learning performance over time (i.e., over several months) and leverage a multifaceted approach that provides key insights into how working memory influences learning accuracy, maintenance of knowledge over time, generalization ability, and decision processes. We found that the role of working memory in non-native speech learning depends on the timepoint of learning and whether individuals learned the categories at all. Among learners, across all stages of learning, working memory was associated with higher accuracy as well as faster and slightly more cautious decision making. Further, while learners and non-learners did not have substantially different working memory performance, learners had faster evidence accumulation and more cautious decision thresholds throughout all sessions. Working memory may enhance learning by facilitating rapid category acquisition in initial stages and enabling faster and slightly more careful decision-making strategies that may reduce the overall effort needed to learn. Our results have important implications for developing interventions to improve learning in naturalistic language contexts.


Subject(s)
Individuality , Learning , Memory, Short-Term , Speech , Humans , Memory, Short-Term/physiology , Female , Male , Learning/physiology , Speech/physiology , Young Adult , Adult , Decision Making/physiology , Language
11.
Vaccine ; 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38853035

ABSTRACT

PURPOSE: The current study sought to determine if the release of COVID-19 vaccines influenced Alabama mothers' attitudes and behaviors regarding HPV vaccination of their adolescent children. METHODS: A social media survey was conducted August - September 2022 among mothers of adolescents ages 9-18, who self-identified as Alabama residents and their child(ren)'s primary medical decision maker. The survey assessed demographics, vaccine knowledge and opinions, vaccination history, influences on vaccination decisions, and how COVID-19 vaccine release affected vaccine opinions. Univariable and multivariable analyses were conducted. RESULTS: Of 241 responses, most participants were white (82.0 %, n = 196), non-Hispanic (96.6 %, n = 230), and privately insured (64.5 %, n = 151), with annual household incomes ≥$61,000 (45.4 %, n = 103). The majority (60.8 %) reported that their child either had or planned to receive the HPV vaccine. The release of COVID-19 vaccines did not change the majority of parental opinions towards HPV, with 78.5 % (n = 161) reporting no change. Among those who experienced a change, 25 % (n = 5) reported an increased likelihood of having their child vaccinated for HPV and 75 % (n = 15) reported a decrease in likelihood. Moderate and high HPV knowledge scores were associated in multivariable analysis with increased likelihood of having their child vaccinated for HPV ("moderate" knowledge AOR: 12.4, 95 % CI: 1.98-78.1; "high" knowledge AOR: 12.8, 95 % CI: 2.00-82.1). Positive HPV opinion scores in the univariable analysis similarly showed increased odds (AOR = 1.5). CONCLUSIONS: These findings indicate that, in this population, COVID-19 vaccine release did not significantly impact subsequent HPV vaccination decision making. Parental perceptions regarding vaccination are critical to informing future interventions.

13.
Disabil Rehabil ; : 1-10, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38720522

ABSTRACT

PURPOSE: The aim of this review was to assess the effectiveness of multidisciplinary, activity-based interventions on adults with chronic musculoskeletal or widespread pain who identify as ethnoculturally diverse (ECD) compared to adults belonging to the predominant culture of the host country. METHODS: Online databases Medline, CINAHL, AMED, Psych Info and PubMed were searched from the earliest date available until April 2023. The quality of the included studies were assessed against the Risk of Bias in Non Randomized Studies of Interventions (ROBINS-I). Postintervention data were analyzed using meta-analyses and the certainty of evidence determined using the Grading of Recommendation, Assessment, Development and Evaluation approach (GRADE). RESULTS: Nine cohort studies with 3467 participants living in America and north-western European countries were included. ECD adults had higher pain intensity (SMD 1.36, 95%CI 0.29 to 2.35, p = 0.03), higher levels of depression (SMD 0.96, 95%CI 0.40 to 1.52, p < 0.01) and a nonsignificant difference in pain-related disability (SMD -1.45, 95%CI -3.28 to 0.39, p = 0.12) following multidisciplinary pain intervention compared to adults of the predominant culture. CONCLUSION: Adults from ECD backgrounds in Western nations have poorer outcomes after multidisciplinary, activity-based chronic pain interventions compared to adults from predominant cultural groups in these countries suggesting program adaptations may be required.


Adults from ethnoculturally diverse backgrounds in Western nations have poorer outcomes after chronic pain interventions suggesting different approaches to management are needed.Programs can be adapted to reflect culture-specific beliefs, metaphors, language and concepts in their content to better address pain and improve outcomes among ethnoculturally diverse communities.

14.
Am J Public Health ; 114(S4): S330-S333, 2024 May.
Article in English | MEDLINE | ID: mdl-38748961

ABSTRACT

Objectives. To examine the accessibility of hospital facilities with maternity care services in 1 rural county in Alabama in preparation for the initiation of prenatal care services at a federally qualified health center. Methods. We analyzed driving distance (in miles) from maternal city of residence in Conecuh County, Alabama to hospital of delivery, using 2019-2021 vital statistics data and geographic information system (GIS) software. Results. A total of 370 births to mothers who have home addresses in Conecuh County were reported, and 368 of those were in hospital facilities. The majority of deliveries were less than 30 miles (median = 23 miles) from the maternal city of residence. Some women traveled more than 70 miles for obstetrical care. Conclusions. Pregnant patients in Conecuh County experience significant geographic barriers related to perinatal care access. Using GIS for this analysis is a promising approach to better understand the unique challenges of pregnant individuals in this rural population. Public health policy efforts need to be geographically tailored to address these disparities. (Am J Public Health. 2024;114(S4):S330-S333. https://doi.org/10.2105/AJPH.2024.307692).


Subject(s)
Geographic Information Systems , Health Services Accessibility , Maternal Health Services , Humans , Female , Health Services Accessibility/statistics & numerical data , Pregnancy , Alabama , Maternal Health Services/statistics & numerical data , Adult , Rural Population/statistics & numerical data , Prenatal Care/statistics & numerical data , Delivery, Obstetric/statistics & numerical data
15.
J Infect Public Health ; 17(6): 1125-1133, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38723322

ABSTRACT

BACKGROUND: During the COVID-19 pandemic, analytics and predictive models built on regional data provided timely, accurate monitoring of epidemiological behavior, informing critical planning and decision-making for health system leaders. At Atrium Health, a large, integrated healthcare system in the southeastern United States, a team of statisticians and physicians created a comprehensive forecast and monitoring program that leveraged an array of statistical methods. METHODS: The program utilized the following methodological approaches: (i) exploratory graphics, including time plots of epidemiological metrics with smoothers; (ii) infection prevalence forecasting using a Bayesian epidemiological model with time-varying infection rate; (iii) doubling and halving times computed using changepoints in local linear trend; (iv) death monitoring using combination forecasting with an ensemble of models; (v) effective reproduction number estimation with a Bayesian approach; (vi) COVID-19 patients hospital census monitored via time series models; and (vii) quantified forecast performance. RESULTS: A consolidated forecast and monitoring report was produced weekly and proved to be an effective, vital source of information and guidance as the healthcare system navigated the inherent uncertainty of the pandemic. Forecasts provided accurate and precise information that informed critical decisions on resource planning, bed capacity and staffing management, and infection prevention strategies. CONCLUSIONS: In this paper, we have presented the framework used in our epidemiological forecast and monitoring program at Atrium Health, as well as provided recommendations for implementation by other healthcare systems and institutions to facilitate use in future pandemics.


Subject(s)
Bayes Theorem , COVID-19 , COVID-19/epidemiology , COVID-19/prevention & control , Humans , Delivery of Health Care/organization & administration , Forecasting/methods , SARS-CoV-2 , Pandemics , Epidemiological Monitoring , Models, Statistical
16.
Microbes Infect ; : 105369, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38815803

ABSTRACT

At present, there is no approved vaccine for prevention of infection by the opportunistic bacterium Klebsiella pneumoniae (Kp); success in treating these infections is increasingly challenged by the spread of antibiotic resistance. Preclinical investigation of adaptive immunity elicited by lung infection with live classical Kp may reveal host mechanisms of protection against this pathogen. Here, we utilize multiple virulent classical Kp strains to demonstrate that following lung infection, surviving wild-type mice develop protective immunity against both homologous and heterologous (heterotypic) reinfection. For Kp strains with low capacity to disseminate from the lung, this immunity is B-cell-independent. We further demonstrate that this immune protection is also effective against subsequent challenge with hypervirulent Kp if the strains share the same capsule type. Systemic inoculation fails to elicit the same protective effect as lung inoculation, revealing a lung-specific immune effector function is responsible for this protection. We therefore utilized clodronate-loaded liposomes to substantially deplete both alveolar macrophages and lung interstitial macrophages, finding that simultaneous depletion of both subsets entirely ablates protection. These findings indicate that following initial lung infection with Kp, lung macrophages mediate protection against ensuing Kp challenge.

18.
medRxiv ; 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38746238

ABSTRACT

Background: Adaptive treatment strategies that can dynamically react to individual cancer progression can provide effective personalized care. Longitudinal multi-omics information, paired with an artificially intelligent clinical decision support system (AI-CDSS) can assist clinicians in determining optimal therapeutic options and treatment adaptations. However, AI-CDSS is not perfectly accurate, as such, clinicians' over/under reliance on AI may lead to unintended consequences, ultimately failing to develop optimal strategies. To investigate such collaborative decision-making process, we conducted a Human-AI interaction case study on response-adaptive radiotherapy (RT). Methods: We designed and conducted a two-phase study for two disease sites and two treatment modalities-adaptive RT for non-small cell lung cancer (NSCLC) and adaptive stereotactic body RT for hepatocellular carcinoma (HCC)-in which clinicians were asked to consider mid-treatment modification of the dose per fraction for a number of retrospective cancer patients without AI-support (Unassisted Phase) and with AI-assistance (AI-assisted Phase). The AI-CDSS graphically presented trade-offs in tumor control and the likelihood of toxicity to organs at risk, provided an optimal recommendation, and associated model uncertainties. In addition, we asked for clinicians' decision confidence level and trust level in individual AI recommendations and encouraged them to provide written remarks. We enrolled 13 evaluators (radiation oncology physicians and residents) from two medical institutions located in two different states, out of which, 4 evaluators volunteered in both NSCLC and HCC studies, resulting in a total of 17 completed evaluations (9 NSCLC, and 8 HCC). To limit the evaluation time to under an hour, we selected 8 treated patients for NSCLC and 9 for HCC, resulting in a total of 144 sets of evaluations (72 from NSCLC and 72 from HCC). Evaluation for each patient consisted of 8 required inputs and 2 optional remarks, resulting in up to a total of 1440 data points. Results: AI-assistance did not homogeneously influence all experts and clinical decisions. From NSCLC cohort, 41 (57%) decisions and from HCC cohort, 34 (47%) decisions were adjusted after AI assistance. Two evaluations (12%) from the NSCLC cohort had zero decision adjustments, while the remaining 15 (88%) evaluations resulted in at least two decision adjustments. Decision adjustment level positively correlated with dissimilarity in decision-making with AI [NSCLC: ρ = 0.53 ( p < 0.001); HCC: ρ = 0.60 ( p < 0.001)] indicating that evaluators adjusted their decision closer towards AI recommendation. Agreement with AI-recommendation positively correlated with AI Trust Level [NSCLC: ρ = 0.59 ( p < 0.001); HCC: ρ = 0.7 ( p < 0.001)] indicating that evaluators followed AI's recommendation if they agreed with that recommendation. The correlation between decision confidence changes and decision adjustment level showed an opposite trend [NSCLC: ρ = -0.24 ( p = 0.045), HCC: ρ = 0.28 ( p = 0.017)] reflecting the difference in behavior due to underlying differences in disease type and treatment modality. Decision confidence positively correlated with the closeness of decisions to the standard of care (NSCLC: 2 Gy/fx; HCC: 10 Gy/fx) indicating that evaluators were generally more confident in prescribing dose fractionations more similar to those used in standard clinical practice. Inter-evaluator agreement increased with AI-assistance indicating that AI-assistance can decrease inter-physician variability. The majority of decisions were adjusted to achieve higher tumor control in NSCLC and lower normal tissue complications in HCC. Analysis of evaluators' remarks indicated concerns for organs at risk and RT outcome estimates as important decision-making factors. Conclusions: Human-AI interaction depends on the complex interrelationship between expert's prior knowledge and preferences, patient's state, disease site, treatment modality, model transparency, and AI's learned behavior and biases. The collaborative decision-making process can be summarized as follows: (i) some clinicians may not believe in an AI system, completely disregarding its recommendation, (ii) some clinicians may believe in the AI system but will critically analyze its recommendations on a case-by-case basis; (iii) when a clinician finds that the AI recommendation indicates the possibility for better outcomes they will adjust their decisions accordingly; and (iv) When a clinician finds that the AI recommendation indicate a worse possible outcome they will disregard it and seek their own alternative approach.

19.
Int J Pharm Compd ; 28(3): 246-248, 2024.
Article in English | MEDLINE | ID: mdl-38768504

ABSTRACT

Amiloride is a U.S. Food and Drug Administration-approved diuretic agent used to treat hypertension and congestive heart failure. Recent human and animal studies have suggested that amiloride may also have a role in treating anxiety through its acid-sensing ion channel antagonism. Intranasal administration of amiloride nasal spray via an extemporaneously compounded preparation has the potential for rapid delivery to the site of action to achieve therapeutic outcomes in individual patients with anxiety disorders. However, these patient-specific preparations do not have the pre-formulation characterization, including chemical stability, that conventional manufactured dosage forms have. The objective of this study was to assess the estimated chemical stability of compounded amiloride nasal spray over 6 months and 12 months utilizing accelerated degradation with high heat and the Arrhenius equation. A stability-indicating highperformance liquid chromatography analytical method was employed at appropriate intervals over a 12-month period to reveal that amiloride remained chemically stable over the period tested and by extrapolation. Physical stability and compatibility with the preservative benzyl alcohol were also confirmed via visual inspection, pH monitoring, and measurement of turbidity.


Subject(s)
Amiloride , Drug Compounding , Drug Stability , Nasal Sprays , Amiloride/chemistry , Amiloride/administration & dosage , Amiloride/analysis , Administration, Intranasal , Chromatography, High Pressure Liquid , Hydrogen-Ion Concentration
20.
Influenza Other Respir Viruses ; 18(5): e13303, 2024 May.
Article in English | MEDLINE | ID: mdl-38757258

ABSTRACT

BACKGROUND: Data available for RSV and influenza infections among children < 2 years in Mongolia are limited. We present data from four districts of Ulaanbaatar from April 2015 to June 2021. METHODS: This study was nested in an enhanced surveillance project evaluating pneumococcal conjugate vaccine (PCV13) impact on the incidence of hospitalized lower respiratory tract infections (LRTIs). Our study was restricted to children aged < 2 years with arterial O2 saturation < 93% and children with radiological pneumonia. Nasopharyngeal (NP) swabs collected at admission were tested for RSV and influenza using qRT-PCR. NP swabs of all patients with radiological pneumonia and of a subset of randomly selected NP swabs were tested for S. pneumoniae (S.p.) by qPCR and for serotypes by culture and DNA microarray. RESULTS: Among 5705 patients, 2113 (37.0%) and 386 (6.8%) had RSV and influenza infections, respectively. Children aged 2-6 months had a higher percentage of very severe RSV infection compared to those older than 6 months (42.2% versus 31.4%, p-value Fisher's exact = 0.001). S.p. carriage was detected in 1073/2281 (47.0%) patients. Among S.p. carriage cases, 363/1073 (33.8%) had S.p. and RSV codetection, and 82/1073 (7.6%) had S.p. and influenza codetection. S.p. codetection with RSV/influenza was not associated with more severe LRTIs, compared to only RSV/influenza cases. CONCLUSION: In Mongolia, RSV is an important pathogen causing more severe LRTI in children under 6 months of age. Codetection of RSV or influenza virus and S.p. was not associated with increased severity.


Subject(s)
Influenza, Human , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human , Humans , Mongolia/epidemiology , Respiratory Syncytial Virus Infections/epidemiology , Infant , Influenza, Human/epidemiology , Influenza, Human/virology , Female , Male , Respiratory Syncytial Virus, Human/genetics , Respiratory Syncytial Virus, Human/isolation & purification , Child, Preschool , Nasopharynx/virology , Infant, Newborn , Incidence , Hospitalization/statistics & numerical data , Streptococcus pneumoniae/isolation & purification , Streptococcus pneumoniae/genetics , Streptococcus pneumoniae/classification , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology
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