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1.
Article in English | MEDLINE | ID: mdl-38866115

ABSTRACT

CONTEXT: Early palliative care referral is recommended broadly in oncology. Yet, few patients with high-grade gliomas (HGG) - highly aggressive brain tumors - receive specialty palliative care consultation. OBJECTIVES: To delineate unique needs of HGG patients relative to other oncology patients according to perceptions of a diverse sample of US palliative medicine physicians and neuro-oncologists in each of the eight domains of palliative care; and to describe contrasts between physician specialties on indications for and timing of specialty palliative care referrals in HGG. METHODS: Between September 2021 and May 2023, we conducted semi-structured, 40-minute interviews with ten palliative medicine physicians and ten neuro-oncologists. Participants were recruited via purposive sampling for diversity in geographic setting, years in practice, and practice structure. Interviews were audio-recorded, professionally transcribed, and coded by two investigators. Data were analyzed thematically using a qualitative, phenomenological approach. RESULTS: The palliative care needs of HGG relative to other cancers across palliative care domains are distinguished by poor prognosis, physical and cognitive deficits, and neuropsychiatric symptoms. Themes on indications for palliative care referral differed between neuro-oncologists and palliative physicians. Neuro-oncologists favored selective referral for clinical indications such as high non-neurologic symptom burden requiring time-intensive management. Palliative physicians favored early referral of most HGG patients, to allow for maximal benefit across HGG trajectory. CONCLUSION: Patients with HGG have unique palliative care needs that affect palliative care delivery across care domains. Bidirectional education, enhanced collaboration, and consensus guidelines may help overcome barriers to specialty palliative care referral.

2.
Talanta ; 277: 126361, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38878509

ABSTRACT

This paper presents an innovative application of chitosan material to be used as pH-responsive valves for the precise control of lateral flow in microfluidic paper-based analytical devices (µPADs). The fabrication of µPADs involved wax printing, while pH-responsive valves were created using a solution of chitosan in acetic acid. The valve-forming solution was applied, and ready when dry; by exposure to acidic solutions, the valve opens. Remarkably, the valves exhibited excellent compatibility with alkaline, neutral, and acidic solutions with a pH higher than 4. The valve opening process had no impact on the flow rate and colorimetric analysis. The potential of chitosan valves used for flow control was demonstrated for µPADs employed for nitrate determination. Valves were used to increase the conversion time of nitrate to nitrite, which was further analyzed using the Griess reaction. The µPAD showed a linear response in the concentration range of 10-100 µmol L-1, with a detection limit of 5.4 µmol L-1. As a proof of concept, the assay was successfully applied to detect nitrate levels in water samples from artificial lakes of recreational parks. For analyses that require controlled kinetics and involve multiple sequential steps, the use of chitosan pH-responsive valves in µPADs is extremely valuable. This breakthrough holds great potential for the development of simple and high-impact microfluidic platforms that can cater to a wide range of analytical chemistry applications.

3.
PLoS One ; 19(5): e0303651, 2024.
Article in English | MEDLINE | ID: mdl-38748671

ABSTRACT

BACKGROUND: Acupuncture and chiropractic care are evidence-based pain management alternatives to opioids. The Veterans Health Administration (VA) provides this care in some VA facilities, but also refers patients to community providers. We aimed to determine if patient-reported outcomes differ for acupuncture and chiropractic care from VA versus community providers. MATERIALS AND METHODS: We conducted an observational study using survey outcome data and electronic medical record utilization data for acupuncture and chiropractic care provided in 18 VA facilities or in community facilities reimbursed by VA. Study participants were users of VA primary care, mental health, pain clinic, complementary and integrative therapies, coaching or education services in 2018-2019. Patients received 1) 4+ acupuncture visits (N = 201) or 4+ chiropractic care visits (N = 178) from a VA or community provider from 60 days prior to baseline to six-months survey and 2) no acupuncture or chiropractic visits from 1 year to 60 days prior to baseline. Outcomes measured included patient-reported pain (PEG) and physical health (PROMIS) at baseline and six-month surveys. Multivariate analyses examined outcomes at six months, adjusting for baseline outcomes and demographics. RESULTS: In unadjusted analyses, pain and physical health improved for patients receiving community-based acupuncture, while VA-based acupuncture patients experienced no change. Unadjusted analyses also showed improvements in physical health, but not pain, for patients receiving VA-based chiropractic care, with no changes for community-based chiropractic care patients. Using multivariate models, VA-based acupuncture was no different from community-based acupuncture for pain (-0.258, p = 0.172) or physical health (0.539, p = 0.399). Similarly, there were no differences between VA- and community-based chiropractic care in pain (-0.273, p = 0.154) or physical health (0.793, p = 0.191). CONCLUSIONS: Acupuncture and chiropractic care were associated with modest improvements at six months, with no meaningful differences between VA and community providers. The choice to receive care from VA or community providers could be based on factors other than quality, like cost or convenience.


Subject(s)
Acupuncture Therapy , Manipulation, Chiropractic , Pain Management , Patient Reported Outcome Measures , United States Department of Veterans Affairs , Humans , Male , Female , Middle Aged , United States , Manipulation, Chiropractic/statistics & numerical data , Aged , Pain Management/methods , Veterans , Adult
4.
Acta Trop ; 256: 107265, 2024 May 19.
Article in English | MEDLINE | ID: mdl-38772434

ABSTRACT

In this present study, carried out between November 2020 and July 2023 at Londrina's University Hospital, patients with active lesions of cutaneous leishmaniasis (CL) were analyzed regarding pain perception and anatomopathological aspects of the ulcers. Pain was assessed using a numerical rating scale (NRS) to compare five patients diagnosed with CL with four control patients diagnosed with vascular skin ulcers. Histopathological evaluations were used to investigate the nociceptor neuron-Leishmania interface. Patients with CL ulcers reported less pain compared to patients with vascular ulcers (2.60 ± 2.30 and 7.25 ± 0.95, respectively, p = 0.0072). Histopathology evidenced Leishmania spp. amastigote forms nearby sensory nerve fibers in profound dermis. Schwann cells marker (S100 protein) was detected, and caspase-3 activation was not evidenced in the in the nerve fibers of CL patients' samples, suggesting absence of apoptotic activity in nerve endings. Additionally, samples taken from the active edge of the lesion were negative for bacilli acid-alcohol resistant (BAAR), which excludes concomitant leprosy, in which painless lesions are also observed. Thus, the present data unveil for the first time anatomopathological and microbiological details of painless ulcers in CL patients, which has important clinical implications for a better understanding on the intriguing painless clinical characteristic of CL.

5.
Neurosci Lett ; 834: 137845, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38821202

ABSTRACT

Sepsis-associated encephalopathy, which manifests in severe cognitive and depressive symptoms, is directly linked to neuroinflammation. Our study investigates the efficacy of 25H-NBOMe, a phenethylamine, in alleviating these symptoms, potentially offering an innovative treatment for post-sepsis depression. Wistar rats, weighing between 250-300 g, were subjected to cecal ligation and puncture (CLP) surgery to induce sepsis. Depressive-like behaviors were assessed using the forced swim test (FST) on either day 7 or 14 post-surgery, to establish the presence of depressive symptoms. The impact of 25H-NBOMe treatment was then evaluated, focusing on the head-twitch response (HTR), performance in the FST, and GFAP expression in the prefrontal cortex. Treatment with 25H-NBOMe resulted in significant behavioral changes, demonstrated by decreased immobility and increased swimming times in the FST, along with a rise in the HTR. These outcomes indicate a reduction in depressive-like symptoms post-sepsis and the psychoactive effects of the compound. Furthermore, a notable decrease in GFAP expression in the study highlights the compound's impact on mitigating sepsis-induced astrogliosis. This study demonstrates the effectiveness of 25H-NBOMe, a psychedelic in the phenethylamine class, in treating post-sepsis depression and reducing astrogliosis. However, the psychedelic nature of 25H-NBOMe calls for further investigation into similar compounds with less psychoactive impact, crucial for advancing treatment options for neuropsychiatric symptoms following sepsis.


Subject(s)
Depression , Rats, Wistar , Sepsis , Animals , Male , Sepsis/complications , Sepsis/drug therapy , Sepsis/metabolism , Sepsis/psychology , Depression/drug therapy , Depression/etiology , Rats , Hallucinogens/pharmacology , Hallucinogens/therapeutic use , Phenethylamines/pharmacology , Phenethylamines/therapeutic use , Prefrontal Cortex/drug effects , Prefrontal Cortex/metabolism , Sepsis-Associated Encephalopathy/drug therapy , Sepsis-Associated Encephalopathy/metabolism
6.
Alzheimers Dement (Amst) ; 16(2): e12584, 2024.
Article in English | MEDLINE | ID: mdl-38623385

ABSTRACT

INTRODUCTION: Depression is a risk factor and possible prodromal symptom of Alzheimer's disease (AD), but little is known about subsequent risk of developing depression in persons with AD. METHODS: National matched cohort study was conducted of all 129,410 persons diagnosed with AD and 390,088 with all-cause dementia during 1998-2017 in Sweden, and 3,900,880 age- and sex-matched controls without dementia, who had no prior depression. Cox regression was used to compute hazard ratios (HRs) for major depression through 2018. RESULTS: Cumulative incidence of major depression was 13% in persons with AD and 3% in controls. Adjusting for sociodemographic factors and comorbidities, risk of major depression was greater than two-fold higher in women with AD (HR, 2.21; 95% confidence interval [CI], 2.11-2.32) or men with AD (2.68; 2.52-2.85), compared with controls. Similar results were found for all-cause dementia. DISCUSSION: Persons diagnosed with AD or related dementias need close follow-up for timely detection and treatment of depression. Highlights: In a large cohort, women and men with AD had >2-fold subsequent risk of depression.Risks were highest in the first year (>3-fold) but remained elevated ≥3 years later.Risk of depression was highest in persons aged ≥85 years at AD diagnosis.Persons with AD need close follow-up for detection and treatment of depression.

7.
Glob Adv Integr Med Health ; 13: 27536130241241259, 2024.
Article in English | MEDLINE | ID: mdl-38585239

ABSTRACT

Background: Assessing the use and effectiveness of complementary and integrative health (CIH) therapies via survey can be complicated given CIH therapies are used in various locations and formats, the dosing required to have an effect is unclear, the potential health and well-being outcomes are many, and describing CIH therapies can be challenging. Few surveys assessing CIH therapy use and effectiveness exist, and none sufficiently reflect these complexities. Objective: In a large-scale Veterans Health Administration (VA) quality improvement effort, we developed the "Complementary and Integrative Health Therapy Patient Experience Survey", a longitudinal, electronic patient self-administered survey to comprehensively assess CIH therapy use and outcomes. Methods: We obtained guidance from the literature, subject matter experts, and Veteran patients who used CIH therapies in designing the survey. As a validity check, we completed cognitive testing and interviews with those patients. We conducted the survey (March 2021-April 2023), inviting 15,608 Veterans with chronic musculoskeletal pain with a recent CIH appointment or referral identified in VA electronic medical records (EMR) to participate. As a second validity check, we compared VA EMR data and patient self-reports of CIH therapy utilization a month after survey initiation and again at survey conclusion. Results: The 64-item, electronic survey assesses CIH dosing (amount and timing), delivery format and location, provider location, and payor. It also assesses 7 patient-reported outcomes (pain, global mental health, global physical health, depression, quality of life, stress, and meaning/purpose in life), and 3 potential mediators (perceived health competency, healthcare engagement, and self-efficacy for managing diseases). The survey took 17 minutes on average to complete and had a baseline response rate of 45.3%. We found high degrees of concordance between self-reported and EMR data for all therapies except meditation. Conclusions: Validly assessing patient-reported CIH therapy use and outcomes is complex, but possible.

8.
bioRxiv ; 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38586037

ABSTRACT

Hearing-impaired listeners struggle to understand speech in noise, even when using cochlear implants (CIs) or hearing aids. Successful listening in noisy environments depends on the brain's ability to organize a mixture of sound sources into distinct perceptual streams (i.e., source segregation). In normal-hearing listeners, temporal coherence of sound fluctuations across frequency channels supports this process by promoting grouping of elements belonging to a single acoustic source. We hypothesized that reduced spectral resolution-a hallmark of both electric/CI (from current spread) and acoustic (from broadened tuning) hearing with sensorineural hearing loss-degrades segregation based on temporal coherence. This is because reduced frequency resolution decreases the likelihood that a single sound source dominates the activity driving any specific channel; concomitantly, it increases the correlation in activity across channels. Consistent with our hypothesis, predictions from a physiologically plausible model of temporal-coherence-based segregation suggest that CI current spread reduces comodulation masking release (CMR; a correlate of temporal-coherence processing) and speech intelligibility in noise. These predictions are consistent with our behavioral data with simulated CI listening. Our model also predicts smaller CMR with increasing levels of outer-hair-cell damage. These results suggest that reduced spectral resolution relative to normal hearing impairs temporal-coherence-based segregation and speech-in-noise outcomes.

9.
Am J Vet Res ; : 1-6, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38640949

ABSTRACT

OBJECTIVE: This study evaluates the amplitude of the anatomical-mechanical angle (AMA-angle) using 4 measuring methods of the tibial distal anatomical axes (DAA) previously described, comparing the literature results to determine if there are significant differences in patients with cranial cruciate ligament (CrCL) rupture. ANIMALS: This study was comprised of 30 tibiae (29 dogs), including 1 bilateral case. METHODS: A retrospective study was selected for this research. DAA measurements were performed on all surgically confirmed cases of canine CrCL rupture at Hospital Veterinário de Especialidades Bruselas from 2019 to 2022. Four different published methods (identified by surname of the corresponding author of the original publication) were compared. Tibial measurements were made using Veterinary Preoperative Orthopedic Planning Pro software (https://vpop-pro.com/) on mediolateral radiographic projections obtained from a digital database. RESULTS: The mean (range) in the DAA method conducted by Hulse obtained a AMA-angle of 5.4° (3.3 to 8.1°), 3.0° (0 to 5.8°) for Osmond et al, 3.2° (0.9 to 6°) for Miles, and 5.9° (2.4 to 8.8°) for Tudury. Differences among the means of the AMA-angle of the authors methods were found with a statistical difference (P < .05), except between Osmond and Miles. The mean AMA-angle with the Osmond method concurred with previous study results that determined the magnitude using the same measurement method of DAA in patients with CrCL rupture. CLINICAL RELEVANCE: The AMA-angle magnitude has been associated with higher sensitivity and specificity for predicting the development of CrCL rupture compared to other anatomical factors evaluated; therefore, future comparisons with different methods of measurement of the DAA between healthy and affected patients are recommended to determine whether any of them can increase the percentage value as a predictive factor for the occurrence of this condition.

10.
JASA Express Lett ; 4(3)2024 03 01.
Article in English | MEDLINE | ID: mdl-38526127

ABSTRACT

Listeners performed two different tasks in which they remembered short sequences comprising either complex tones (generally heard as one melody) or everyday sounds (generally heard as separate objects). In one, listeners judged whether a probe item had been present in the preceding sequence. In the other, they judged whether a second sequence of the same items was identical in order to the preceding sequence. Performance on the first task was higher for everyday sounds; performance on the second was higher for complex tones. Perceptual organization strongly shapes listeners' memory for sounds, with implications for real-world communication.


Subject(s)
Auditory Perception , Memory, Short-Term , Sound , Hearing , Communication
12.
Ann Neurol ; 95(3): 432-441, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38270253

ABSTRACT

The rapidly accelerating translation of biomedical advances is leading to revolutionary therapies that are often inaccessible to historically marginalized populations. We identified and synthesized recent guidelines and statements to propose 7 strategies to integrate equity within translational research in neurology: (1) learn history; (2) learn about upstream forces; (3) diversify and liberate; (4) change narratives and adopt best communication practices; (5) study social drivers of health and lived experiences; (6) leverage health technologies; and (7) build, sustain, and lead culturally humble teams. We propose that equity should be a major goal of translational research, equally important as safety and efficacy. ANN NEUROL 2024;95:432-441.


Subject(s)
Neurology , Translational Research, Biomedical , Humans , Translational Science, Biomedical
13.
Neonatal Netw ; 43(1): 19-34, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38267090

ABSTRACT

Medically complex infants experiencing NICU stays can be difficult to manage, exhibiting refractory agitation, disengagement, or both-all signs of delirium, which can present in a hypoactive, hyperactive, or mixed form. Though documented in other settings, delirium is under-recognized in NICUs. Pediatric studies show that a high percentage of patients with delirium are under the age of 12 months. Delirium is associated with increased ventilation days, hospital days, and costs. It negatively affects neurodevelopment and social interaction. Studies show that pediatric nurses are unprepared to recognize delirium. Our nurse-led multidisciplinary group created a best practice recommendation (BPR) focused on detecting delirium and minimizing risk through thoughtful sedation management, promotion of sleep hygiene and mobility, and facilitation of meaningful caregiver presence. Occasionally, medications, including melatonin and risperidone, are helpful. In 2019, we introduced this BPR to reduce delirium risk in our NICU. Practice changes tied to this initiative correlate with a significant reduction in delirium scores and risk including exposure to deliriogenic medications. A multidisciplinary care bundle correlates with decreased delirium screening scores in NICU patients.


Subject(s)
Delirium , Intensive Care Units, Neonatal , Infant , Infant, Newborn , Humans , Child , Delirium/diagnosis , Delirium/etiology , Delirium/prevention & control
14.
Health Commun ; 39(3): 529-540, 2024 Mar.
Article in English | MEDLINE | ID: mdl-36734475

ABSTRACT

This paper focuses on the development and feasibility of a digitally-based educational intervention, titled Recognize & Resist (R&R), for writers of One Direction (1D) fanfiction on Wattpad.com. The goal of R&R is to reduce the prevalence of social norms that are supportive of sexual violence within 1D fanfiction. 1D fanfictions, or fictional romance stories written by fans of this British boy band, have hundreds of millions of views on Wattpad.com. Formative research has found that social norms supportive of sexual violence are prevalent in 1D fanfictions and that some authors have internalized these norms. R&R aims to motivate 1D fanfiction writers to highlight sexual consent and egalitarian gender roles in their writing. To evaluate the intervention's feasibility, 15 1D fanfiction authors completed a survey and participated in an interview or focus group. Results demonstrate R&R's feasibility, with high ratings of its acceptability and demand. Insights from the interviews and focus groups provide suggestions for revising R&R before rigorously evaluating its efficacy. Additionally, results demonstrate the utility of using popular culture as a vehicle for attitude-change regarding sensitive health issues.


Subject(s)
Gender Role , Sex Offenses , Humans , Sexual Behavior , Social Norms , Attitude
15.
Arch Gynecol Obstet ; 309(1): 1-8, 2024 01.
Article in English | MEDLINE | ID: mdl-36869940

ABSTRACT

PURPOSE: The aim of this systematic review was to shed light on the disease-trajectory of vulvodynia and identify potential risk factors which may affect such trajectory. METHODS: We searched Pubmed to identify articles providing evidence on vulvodynia trajectory (i.e., remission, relapse or persistence rates) with a minimum follow-up of 2 years. A narrative approach was used for data synthesis. RESULTS: Four articles were included (total participants: 741 women with vulvodynia; 634 controls). At a 2-year follow-up, 50.6% of women reported remission, remission with relapse was observed in 39.7% and persistence throughout time occurred in 9.6%. A decrease in pain was observed in 71.1% of patients at a 7-year follow-up. Mean pain scores and depressive symptoms resulted lower at 2-year follow-up, whereas sexual function and satisfaction were increased. Factors associated with remission of vulvodynia were greater couple cohesion, decreased reporting of pain after intercourse and lower levels of worst pain. Risk factors for symptom persistence included marriage, more severe pain ratings, depression, pain with partner touch, interstitial cystitis, pain with oral sex, fibromyalgia, older age and anxiety. Recurrence was associated with: longer duration of pain, more severe ratings of the worst pain ever and pain described as provoked. CONCLUSIONS: Symptoms of vulvodynia seem to improve over time, regardless of treatment. This finding contains a key message for patients and their physicians, considering the deleterious consequences of vulvodynia on women's lives.


Subject(s)
Vulvodynia , Female , Humans , Pain , Recurrence , Sexual Behavior , Surveys and Questionnaires , Vulvodynia/epidemiology , Vulvodynia/therapy , Time Factors
16.
J Gen Intern Med ; 39(1): 84-94, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37653207

ABSTRACT

BACKGROUND: Whole Health (WH) is a patient-centered model of care being implemented by the Veterans Health Administration. Little is known about how use of WH services impacts patients' health and well-being. OBJECTIVE: We sought to assess the association of WH utilization with pain and other patient-reported outcomes (PRO) over 6 months. DESIGN: A longitudinal observational cohort evaluation, comparing changes in PRO surveys for WH users and Conventional Care (CC) users. Inverse probability of treatment weighting was used to balance the two groups on observed demographic and clinical characteristics. PARTICIPANTS: A total of 9689 veterans receiving outpatient care at 18 VA medical centers piloting WH. INTERVENTIONS: WH services included goal-setting clinical encounters, Whole Health coaching, personal health planning, and well-being services. MAIN OUTCOME MEASURES: The primary outcome was change in pain intensity and interference at 6 months using the 3-item PEG. Secondary outcomes included satisfaction, experiences of care, patient engagement in healthcare, and well-being. KEY RESULTS: By 6 months,1053 veterans had utilized WH and 3139 utilized only CC. Baseline pain PEG scores were 6.2 (2.5) for WH users and 6.4 (2.3) for CC users (difference p = 0.028), improving by - 2.4% (p = 0.006) and - 2.3% (p < 0.001), respectively. In adjusted analyses, WH use was unassociated with greater improvement in PEG scores compared to CC - 1.0% (- 2.9%, 1.2%). Positive trends were observed for 8 of 15 exploratory outcomes for WH compared to CC. WH use was associated with greater improvements at 6 months in likelihood to recommend VA 2.0% (0.9%, 3.3%); discussions of goals 11.8% (8.2%, 15.5%); perceptions of healthcare interactions 2.5% (0.4%, 4.6%); and engagement in health behaviors 2.2% (0.3%, 3.9%). CONCLUSION: This study provides early evidence supporting the delivery of WH patient-centered care services to improve veterans' experiences of and engagement in care. These are important first-line impacts towards the goals of better overall health and well-being outcomes for Veterans.


Subject(s)
Veterans , United States/epidemiology , Humans , United States Department of Veterans Affairs , Patient-Centered Care , Patient Reported Outcome Measures , Pain
17.
J Spinal Cord Med ; 47(1): 100-109, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37249362

ABSTRACT

CONTEXT/OBJECTIVE: Our objective was to describe early participation in Whole Health programs across the Veterans Health Administration (VHA) Spinal Cord Injuries and Disorders (SCI/D) System of Care. DESIGN: Retrospective analysis of VHA administrative data. SETTING: The VHA SCI/D System of Care. PARTICIPANTS: Veterans with SCI/D included in the FY2019 cumulative VHA SCI/D Registry cohort with living status during FY2017, FY2018, and FY2019. INTERVENTIONS: N/A. OUTCOME MEASURES: We assessed the number of encounters and unique Veterans with SCI/D, and the percent of Veterans with SCI/D, who utilized each Whole Health (WH) program available in VA. RESULTS: Utilization of WH Pathway and well-being Programs increased from 62 encounters to 1703 encounters between FY2017 and FY2019 (representing 0.09% to 3.13% of Veterans with SCI/D). Utilization of chiropractic care rose from 130 encounters to 418 encounters during the same time period. Similarly, utilization of complementary and integrative health programs increased from 886 encounters to 2655 encounters (representing 1.09% to 3.11% of Veterans; FY2017 to 2019). We also report utilization of specific WH programs. CONCLUSION: Participation in WH services has been increasing among Veterans with SCI/D who receive health care from the VHA SCI/D System of Care. However, utilization among Veterans with SCI/D remains low overall, and targeted efforts to increase WH program reach are needed. Additional information about the relative effectiveness of different strategies to support WH implementation is also needed, to ensure strategies likely to have the most impact are prioritized.


Subject(s)
Spinal Cord Diseases , Spinal Cord Injuries , Veterans Health Services , Veterans , Humans , Health Promotion , Retrospective Studies , Spinal Cord Injuries/epidemiology , Spinal Cord Injuries/therapy , United States/epidemiology , United States Department of Veterans Affairs
18.
Regul Toxicol Pharmacol ; 146: 105517, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37838350

ABSTRACT

Currently there are three test guidelines (TG) for acute oral toxicity studies of substances or mixtures from the Organisation for Economic Co-operation and Development (OECD). TG 423 and TG 425 use lethality as an endpoint, while TG 420 replaces death with 'evident toxicity', defined as clear signs that exposure to a higher dose would result in death. However, the perceived subjectivity of 'evident toxicity' may be preventing wider use of TG 420. To address this, the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) and the European Partnership for Alternative Approaches to Animal Testing (EPAA) collaborated to provide recommendations on the recognition of 'evident toxicity'. Historical data from acute oral toxicity studies were analysed for clinical signs at the lower dose that could have predicted death at the higher dose. Several signs including ataxia, laboured respiration, and eyes partially closed, alone or in combination, are highly predictive. Others such as lethargy, decreased respiration, and loose faeces have lower but still appreciable positive predictive value (PPV). The data has been used to develop recommendations to promote use of TG 420 and thus reduce the suffering and numbers of animals used in acute oral toxicity studies.


Subject(s)
Diarrhea , Organisation for Economic Co-Operation and Development , Animals , Toxicity Tests, Acute
19.
Lab Chip ; 24(3): 467-479, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38126917

ABSTRACT

Multiple protocols have been reported to fabricate paper-based analytical devices (PADs). However, some of these techniques must be revised because of the instrumentation required. This paper describes a versatile and globally affordable method to fabricate PADs using office paper as a substrate and a laser printing technique to define hydrophobic barriers on paper surfaces. To demonstrate the feasibility of the alternatives proposed in this study, the fabrication of devices for three types of detection commonly associated with using PADs was demonstrated: colorimetric detection, electrochemical detection, and mass spectrometry associated with a paper-spray ionization (PSI-MS) technique. Besides that, an evaluation of the type of paper used and chemical modifications required on the substrate surface are also presented in this report. Overall, the developed protocol was suitable for using office paper as a substrate, and the laser printing technique as an efficient fabrication method when using this substrate is accessible at a resource-limited point-of-need. Target analytes were used as a proof of concept for these detection techniques. Colorimetric detection was carried out for acetaminophen, iron, nitrate, and nitrite with limits of detection of 0.04 µg, 4.5 mg mL-1, 2.7 µmol L-1, and 6.8 µmol L-1, respectively. A limit of detection of 0.048 fg mL-1 was obtained for the electrochemical analysis of prostate-specific antigen. Colorimetric and electrochemical devices revealed satisfactory performance when office paper with a grammage of 90 g m-2 was employed. Methyldopa analysis was also carried out using PSI-MS, which showed a good response in the same paper weight and behavior compared to chromatographic paper.

20.
Lancet Reg Health Am ; 28: 100641, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38076413

ABSTRACT

Background: Hypoglycaemia from diabetes treatment causes morbidity and lower quality of life, and prevention should be routinely addressed in clinical visits. Methods: This mixed methods study evaluated how primary care providers (PCPs) assess for and prevent hypoglycaemia by analyzing audio-recorded visits from five Veterans Affairs medical centres in the US. Two investigators independently coded visit dialogue to classify discussions of hypoglycaemia history, anticipatory guidance, and adjustments to hypoglycaemia-causing medications according to diabetes guidelines. Findings: There were 242 patients (one PCP visit per patient) and 49 PCPs. Two thirds of patients were treated with insulin and 40% with sulfonylureas. Hypoglycaemia history was discussed in 78/242 visits (32%). PCPs provided hypoglycaemia anticipatory guidance in 50 visits (21%) that focused on holding diabetes medications while fasting and carrying glucose tabs; avoiding driving and glucagon were not discussed. Hypoglycaemia-causing medications were de-intensified or adjusted more often (p < 0.001) when the patient reported a history of hypoglycaemia (15/51 visits, 29%) than when the patient reported no hypoglycaemia or it was not discussed (6/191 visits, 3%). Haemoglobin A1c (HbA1c) was not associated with diabetes medication adjustment, and only 5/12 patients (42%) who reported hypoglycaemia with HbA1c <7.0% had medications de-intensified or adjusted. Interpretation: PCPs discussed hypoglycaemia in one-third of visits for at-risk patients and provided limited hypoglycaemia anticipatory guidance. De-intensifying or adjusting hypoglycaemia-causing medications did not occur routinely after reported hypoglycaemia with HbA1c <7.0%. Routine hypoglycaemia assessment and provision of diabetes self-management education are needed to achieve guideline-concordant hypoglycaemia prevention. Funding: U.S. Department of Veterans Affairs and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

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