Outcomes and Attributes Patients Value When Choosing Glucose-Lowering Medications: A Mixed-Methods Study.

This mixed-methods study sought to identify pharmacotherapy preferences among 40 noninsulin-treated adults with type 2 diabetes receiving care at two U.S. health care systems. Participants ranked by relative importance various health outcomes and medication attributes and then contextualized their rankings. Most participants ranked blindness (63%), death (60%), heart attack (48%), and heart failure (48%) as the most important health outcomes and glucose-lowering efficacy (68%) as the most important medication attribute, followed by oral administration (45%) and lack of gastrointestinal side effects (38%).

COVID-19 health information system assessments in eight European countries: identified gaps, best practices and recommendations.

BACKGROUND: Global threats, such as the coronavirus disease 2019 (COVID-19) pandemic, have highlighted the critical importance of robust and well-functioning health information systems (HIS) in effectively addressing public health emergencies. To enhance the understanding and the functioning of such systems, it is crucial to perform HIS assessments. This article explores key gaps and identifies best practices in the COVID-19 HIS of eight European countries. Furthermore, it provides recommendations to strengthen European systems for better pandemic preparedness. METHODS: Assessments were carried out in eight European countries using an adapted version of the WHO support tool to strengthen HIS and the Joint Action on Health Information assessment tool. The assessments took place between January 2022 and April 2023. RESULTS: Four main themes emerged regarding the gaps and best practices identified in the various HIS: organizational, technical, legal and resources. The results of these assessments show different approaches implemented by countries to improve their HIS and respond to the demands of the pandemic. CONCLUSIONS: It is imperative for countries to draw valuable insights from the COVID-19 pandemic and strengthen their HIS. This involves the adaptation or development of pandemic preparedness plans, strengthening legislative framework for data sharing and privacy protection, promotion of data standards and international definitions and implementation of a unique person identifier. Additionally, countries will have to act in this post-pandemic era and integrate the newly developed systems and innovations into existing structures, maintain and develop trust by citizens through transparent communication and engage in infodemic management and address resource gaps in the workforce.

Has the COVID-19 pandemic changed existing patterns of non-COVID-19 health care utilization? A retrospective analysis of six regions in Europe.

BACKGROUND: Resilience of national health systems in Europe remains a major concern in times of multiple crises and as more evidence is emerging relating to the indirect effects of the COVID-19 pandemic on health care utilization (HCU), resulting from de-prioritization of regular, non-pandemic healthcare services. Most extant studies focus on regional, disease specific or early pandemic HCU creating difficulties in comparing across multiple countries. We provide a comparatively broad definition of HCU across multiple countries, with potential to expand across regions and timeframes. METHODS: Using a cross-country federated research infrastructure (FRI), we examined HCU for acute cardiovascular events, elective surgeries and serious trauma. Aggregated data were used in forecast modelling to identify changes from predicted European age-standardized counts via fitted regressions (2017-19), compared against post-pandemic data. RESULTS: We found that elective surgeries were most affected, universally falling below predicted levels in 2020. For cardiovascular HCU, we found lower-than-expected cases in every region for heart attacks and displayed large sex differences. Serious trauma was the least impacted by the COVID-19 pandemic. CONCLUSION: The strength of this study comes from the use of the European Population Health Information Research Infrastructure's (PHIRI) FRI, allowing for rapid analysis of regional differences to assess indirect impacts of events such as pandemics. There are marked differences in the capacity of services to return to normal in terms of elective surgery; additionally, we found considerable differences between men and women which requires further research on potential sex or gender patterns of HCU during crises.

Non-Small Cell Lung Cancer Imaging Using a Phospholipase A2 Activatable Fluorophore.

Lung cancer, the most common cause of cancer-related death in the United States, requires advanced intraoperative detection methods to improve evaluation of surgical margins. In this study we employed DDAO-arachidonate (DDAO-A), a phospholipase A2 (PLA2) activatable fluorophore, designed for the specific optical identification of lung cancers in real-time during surgery. The in vitro fluorescence activation of DDAO-A by porcine sPLA2 was tested in various liposomal formulations, with 100 nm extruded EggPC showing the best overall characteristics. Extruded EggPC liposomes containing DDAO-A were tested for their stability under various storage conditions, demonstrating excellent stability for up to 4 weeks when stored at -20 °C or below. Cell studies using KLN 205 and LLC1 lung cancer cell lines showed DDAO-A activation was proportional to cell number. DDAO-A showed preferential activation by human recombinant cPLA2, an isoform highly specific to arachidonic acid-containing lipids, when compared to a control probe, DDAO palmitate (DDAO-P). In vivo studies with DBA/2 mice bearing KLN 205 lung tumors recapitulated these results, with preferential activation of DDAO-A relative to DDAO-P following intratumoral injection. Topical application of DDAO-A-containing liposomes to human (n = 10) and canine (n = 3) lung cancers ex vivo demonstrated the preferential activation of DDAO-A in tumor tissue relative to adjacent normal lung tissue, with fluorescent tumor-to-normal ratios (TNR) of up to 5.2:1. The combined results highlight DDAO-A as a promising candidate for clinical applications, showcasing its potential utility in intraoperative and back-table imaging and topical administration during lung cancer surgeries. By addressing the challenge of residual microscopic disease at resection margins and offering stability in liposomal formulations, DDAO-A emerges as a potentially valuable tool for advancing precision lung cancer surgery and improving curative resection rates.

Reported Xylazine Use Among Adults Aged ≥18 Years Evaluated for Substance Use Treatment - United States, July 2022-September 2023.

Xylazine has been increasingly detected in illegally manufactured fentanyl (IMF) products and overdose deaths in the United States; most xylazine-involved overdose deaths involve IMF. A convenience sample of U.S. adults aged ≥18 years was identified from those evaluated for substance use treatment during July 2022-September 2023. Data were collected using the Addiction Severity Index-Multimedia Version clinical assessment tool. Among 43,947 adults, 6,415 (14.6%) reported IMF or heroin as their primary lifetime substance-use problem; 5,344 (12.2%) reported recent (i.e., past-30-day) IMF or heroin use. Among adults reporting IMF or heroin as their primary lifetime substance-use problem, 817 (12.7%) reported ever using xylazine. Among adults reporting recent IMF or heroin use, 443 (8.3%) reported recent xylazine use. Among adults reporting IMF or heroin use recently or as their primary lifetime substance-use problem, those reporting xylazine use reported a median of two past nonfatal overdoses from any drug compared with a median of one overdose among those who did not report xylazine use; as well, higher percentages of persons who reported xylazine use reported other recent substance use and polysubstance use. Provision of nonjudgmental care and services, including naloxone, wound care, and linkage to and retention of persons in effective substance use treatment, might reduce harms including overdose among persons reporting xylazine use.

Severe colic in a newborn dairy calf caused by a large colostrum curd: a case report.

A newborn female, Holstein calf weighing approximately 38.5 kg developed severe, persistent colic caused by a large colostrum curd located within the calf's abomasum. Based upon 10% body weight, the calf had been fed 4 liters (L) of first-milking colostrum approximately 30 min after birth and an additional 2 L of first-milking colostrum 6 h after the first feeding. Both the first and second feedings used an esophageal tube feeder to deliver the colostrum. Colic developed shortly after the second colostrum feeding. The affected calf did not respond to on-farm supportive medical therapy and was humanely euthanized by a penetrating captive bolt approximately 22 h after the onset of colic. This on-farm colostrum feeding protocol is routinely observed in the current dairy industry. This case demonstrates calves that are fed large volumes of colostrum during a relatively short window of time may develop a large, firm colostrum curd within the abomasum that causes abdominal distension, colic, and occasional death. There is an urgent need for prospective analytical studies that determine the optimal immunoglobulin mass (g/L) and the ideal volume of colostrum fed to newborn calves for both the first and second colostrum feedings within the most beneficial time frame. Guidelines should be developed that minimize complications that adversely affect calf health and well-being while ensuring the successful transfer of passive immunity.

An Exploration of Contraceptive Choice Pathways in Adolescents and Young Adults.

PURPOSE: To visualize contraceptive choice pathways among adolescent and young adults (AYA) designated female at birth (DFAB) as a means of exploring the relationships between current contraceptive use, desired contraceptive, and ultimately, chosen contraceptive method. METHODS: A retrospective cross-sectional study was conducted of AYA DFAB (N=2369), aged 14-24 years, presenting for initial visit at a contraceptive clinic with standardized efficacy-based counseling. Sankey diagrams were utilized to visualize patient flow through the contraceptive decision-making process. Outcomes of interest were current contraceptive method, desired contraceptive prior to contraceptive counseling, and then chosen contraception. Chi-Square tests were conducted to quantify the strength of the relationships identified by the Sankey diagrams. RESULTS: Sankey diagrams demonstrated a fair amount of change from current contraceptive to desired contraceptive and from current contraceptive to chosen contraceptive. A stronger relationship was evident between desired contraceptive method and chosen method; most patients did not change their desired contraceptive after receiving counseling except AYA who were undecided about their desired contraceptive who flowed variably into all available methods. Chi-Square test assessing the association between desired and chosen contraceptive method was significant at p-value <0.001, validating the patterns identified with the Sankey diagrams. DISCUSSION: We identified distinct contraceptive decision-making pathways among AYA which could inform the framework for a more tailored counseling approach. These findings are aligned with national medical organizations' recommendations for provision of non-coercive, patient-centered contraceptive counseling to promote adolescent reproductive autonomy.

Habitat occupancy of the threatened Diademed Plover (Phegornis mitchellii) is not affected by llama grazing or peatland size, but declines with peatland humidity.

Many habitat-specialist organisms occur in distinct, patchy habitat, yet do not occupy all patches, and an important question is why apparently suitable habitat remains unoccupied. We examined factors influencing patch occupancy in near-threatened, little-known Diademed Plovers (Phegornis mitchellii), arguably the bird most specialized to life in High Andean peatlands. Andean peatlands are well-suited to occupancy modelling because they are discrete patches of humid habitat within a matrix of high-altitude steppe. We hypothesized that Diademed Plovers occupy preferably larger and more humid peatlands, and avoid peatlands used for grazing by llamas and vicuñas, which may trample vegetation and nests. From December 2021 to February 2022 (breeding season), we conducted plover occupancy surveys (2-4) on 40 peatlands at Lagunas de Vilama, a landscape of arid steppe and wetlands above 4,500 m in NW Argentina. We measured peatland size, grazing pressure, topographic and remotely-sensed variables that correlate with humidity, and incorporated these as covariates in occupancy models. Occupancy models showed that more than 50% of the studied peatlands were used by Diademed Plovers and most showed signs of reproduction, highlighting the importance of the Vilama Wetlands for Diademed Plover conservation. Within peatlands, Diademed Plovers were most often associated with headwaters. The top ranked occupancy model included constant detection, random spatial effects, and a single occupancy covariate: mean NDWI (Normalized Difference Water Index, an index correlated with water content and humidity) over the previous three years. Contrary to our prediction, Diademed Plovers preferred less water-saturated peatlands (lower NDWI), possibly to avoid nest flooding. This may be especially important in wet years, like the year when we conducted our surveys. Neither peatland size nor grazing by llamas and vicuñas affected peatland use by Diademed Plovers, suggesting that llama grazing at current levels may be compatible with plover conservation. For organisms that specialize on humid habitats, such as peatlands, factors affecting occupancy may vary temporally with variation in climate, and we recommend follow-up surveys across multi-year timescales to untangle the impact of climate on animals' use of humid habitats.

Effects of a multidomain intervention against cognitive decline on dementia risk profiles - Results from the AgeWell.de trial.

INTRODUCTION: Dementia risk scores constitute promising surrogate outcomes for lifestyle interventions targeting cognitive function. We investigated whether dementia risk, assessed using the LIfestyle for BRAin health (LIBRA) index, was reduced by the AgeWell.de intervention. METHODS: Secondary analyses of the AgeWell trial, testing a multicomponent intervention (including optimization of nutrition, medication, and physical, social, and cognitive activity) in older adults with increased dementia risk. We analyzed data from n = 461 participants with complete information on risk/protective factors comprised by LIBRA at the 24-month follow-up. Intervention effects on LIBRA and LIBRA components were assessed using generalized linear models. RESULTS: The intervention reduced LIBRA scores, indicating decreased dementia risk at follow-up (b = -0.63, 95% confidence interval [CI]: -1.14, -0.12). Intervention effects were particularly due to improvements in diet (odds ratio [OR]: 1.60, 95% CI: 1.16, 2.22) and hypertension (OR: 1.61, 95% CI: 1.19, 2.18). DISCUSSION: The AgeWell.de intervention reduced dementia risk. However, several risk factors did not improve, possibly requiring more intensive interventions. HIGHLIGHTS: The AgeWell.de intervention reduced dementia risk according to LIfestyle for BRAin health (LIBRA) scores. Beneficial effects on LIBRA are mainly due to changes in diet and blood pressure. A pragmatic lifestyle intervention is apt to reduce dementia risk in an at-risk population.

Structural and sequential regularities modulate phrase-rate neural tracking.

Electrophysiological brain activity has been shown to synchronize with the quasi-regular repetition of grammatical phrases in connected speech-so-called phrase-rate neural tracking. Current debate centers around whether this phenomenon is best explained in terms of the syntactic properties of phrases or in terms of syntax-external information, such as the sequential repetition of parts of speech. As these two factors were confounded in previous studies, much of the literature is compatible with both accounts. Here, we used electroencephalography (EEG) to determine if and when the brain is sensitive to both types of information. Twenty native speakers of Mandarin Chinese listened to isochronously presented streams of monosyllabic words, which contained either grammatical two-word phrases (e.g., catch fish, sell house) or non-grammatical word combinations (e.g., full lend, bread far). Within the grammatical conditions, we varied two structural factors: the position of the head of each phrase and the type of attachment. Within the non-grammatical conditions, we varied the consistency with which parts of speech were repeated. Tracking was quantified through evoked power and inter-trial phase coherence, both derived from the frequency-domain representation of EEG responses. As expected, neural tracking at the phrase rate was stronger in grammatical sequences than in non-grammatical sequences without syntactic structure. Moreover, it was modulated by both attachment type and head position, revealing the structure-sensitivity of phrase-rate tracking. We additionally found that the brain tracks the repetition of parts of speech in non-grammatical sequences. These data provide an integrative perspective on the current debate about neural tracking effects, revealing that the brain utilizes regularities computed over multiple levels of linguistic representation in guiding rhythmic computation.

Diclofenac sodium adsorption on activated carbon: experimental, modeling and bayesian statistics.

The present study modeled the adsorption process of the drug diclofenac sodium on activated charcoal. For this purpose, a mass balance-based model was used considering a fixed bed column. The mass transfer rate in the solid phase was represented by a driving force model proposed in this study, and a gamma exponent with a range of 0 > γ ≤ 2 was assigned to the model. Different isotherms were adopted to represent the equilibrium at the solid/liquid interface: the Langmuir, Freundlich, Sips and Redlich-Peterson isotherms. The modeling was approached from the perspective of Bayesian statistics, and the Markov chain Monte Carlo method was used for parameter estimation. Model validation was performed with experimental data obtained under different operating conditions of initial concentration ($C_{0.

Trends in Naloxone Dispensing From Retail Pharmacies in the US.

This cross-sectional study examines trends in naloxone dispensing by US retail pharmacies from 2019 to 2023, including prescriber specialty and product brand.

Maternal Body Mass Index Associates with Prenatal Characteristics and Fecal Microbial Communities.

The maternal microbiome plays a vital role in shaping pregnancy outcomes, but there remains a substantial gap in understanding its precise relationships to maternal health, particularly in relation to potential effects of body mass index (BMI) on gut microbial diversity. The aim of this observational study was to assess maternal characteristics in association with pre-pregnancy BMI and to further assess microbial diversity in association with specific maternal characteristics. Eighty-four pregnant women were recruited during their third trimester of pregnancy from various prenatal clinics across the state of Michigan. The participants completed an enrollment questionnaire including self-reported pre-pregnancy BMI; stool samples were collected to assess the fecal microbial community composition. Pre-pregnancy obesity (BMI 30+) was associated (univariably) with antibiotic use before pregnancy, ever smoked, lower education level, and being unmarried. The gut microbiota alpha diversity was significantly different for pregnant women by pre-pregnancy BMI category (normal, overweight, obese). The beta diversity was unique for the gut microbiotas of pregnant women within each BMI category, by education level, and by marital status. Multivariable models revealed that pre-pregnancy BMI, maternal education, marital status, and maternal age were associated with the microbial diversity of the gut microbiota during pregnancy. These results give new insight into the relationship between a woman's microbiome during pregnancy and their prenatal health, along with an understanding of the relationships between socioeconomic factors and microbial diversity.

Cognitive performance in adults with post-COVID syndrome: Results from a German case-control study.

Numerous studies on post-COVID syndrome (PCS) describe persisting symptoms of cognitive impairment. Previous studies, however, often investigated small samples or did not assess covariates possibly linked to cognitive performance. We aimed to describe 1) global and domain-specific cognitive performance in adults with PCS, controls with previous SARS-CoV-2 infection and healthy controls, 2) associations of sociodemographics, depressive symptoms, anxiety, fatigue, somatic symptoms and stress with cognitive performance and subjective cognitive decline (SCD), using data of the LIFE-Long-COVID-Study from Leipzig, Germany. Group differences in cognitive performance and associations with sociodemographic and neuropsychiatric covariates were assessed using multivariable regression analyses. Our study included n = 561 adults (Mage: 48.8, SD: 12.7; % female: 70.6). Adults with PCS (n = 410) performed worse in tests on episodic memory (b = -1.07, 95 % CI: -1.66, -0.48) and visuospatial abilities (b = -3.92, 95 % CI: -6.01, -1.83) compared to healthy controls (n = 64). No impairments were detected for executive function, verbal fluency, and global cognitive performance. Odds of SCD were not higher in PCS. A previous SARS-CoV-2 infection without PCS (n = 87) was not linked to cognitive impairment. Higher age and higher levels of stress and fatigue were linked to worse performance in several cognitive domains. Routine administration of tests for episodic memory and visuospatial abilities might aid in the identification of individuals at risk for cognitive impairment when reporting symptoms of PCS. Low numbers of participants with severe COVID-19 infections possibly limit generalizability of our findings.

Understanding the causes of missingness in primary care: a realist review.

BACKGROUND: Although missed appointments in healthcare have been an area of concern for policy, practice and research, the primary focus has been on reducing single 'situational' missed appointments to the benefit of services. Little attention has been paid to the causes and consequences of more 'enduring' multiple missed appointments in primary care and the role this has in producing health inequalities. METHODS: We conducted a realist review of the literature on multiple missed appointments to identify the causes of 'missingness.' We searched multiple databases, carried out iterative citation-tracking on key papers on the topic of missed appointments and identified papers through searches of grey literature. We synthesised evidence from 197 papers, drawing on the theoretical frameworks of candidacy and fundamental causation. RESULTS: Missingness is caused by an overlapping set of complex factors, including patients not identifying a need for an appointment or feeling it is 'for them'; appointments as sites of poor communication, power imbalance and relational threat; patients being exposed to competing demands, priorities and urgencies; issues of travel and mobility; and an absence of choice or flexibility in when, where and with whom appointments take place. CONCLUSIONS: Interventions to address missingness at policy and practice levels should be theoretically informed, tailored to patients experiencing missingness and their identified needs and barriers; be cognisant of causal domains at multiple levels and address as many as practical; and be designed to increase safety for those seeking care.

Altered liver metabolism post-wean abolishes efficacy of vitamin D for breast cancer prevention in a mouse model.

Young women have increased risk of vitamin D deficiency, which may increase breast cancer incidence. Here, we assessed the anti-cancer efficacy of vitamin D in mouse models of young-onset breast cancer. In never-pregnant mice, vitamin D supplementation increased serum 25(OH)D and hepatic 1,25(OH)2D3, reduced tumor size, and associated with anti-tumor immunity. These anti-tumor effects were not replicated in a mouse model of postpartum breast cancer, where hepatic metabolism of vitamin D was suppressed post-wean, which resulted in deficient serum 25(OH)D and reduced hepatic 1,25(OH)2D3. Treatment with active 1,25(OH)2D3 induced hypercalcemia exclusively in post-wean mice, highlighting metabolic imbalance post-wean. RNAseq revealed suppressed CYP450 expression postpartum. In sum, we provide evidence that vitamin D anti-tumor activity is mediated through immunomodulatory mechanisms and is ineffective in the post-wean window due to altered hepatic metabolism. These findings have implications for suppressed xenobiotic metabolism in postpartum women beyond vitamin D.

Impact of three different peak picking software tools on the quality of untargeted metabolomics data.

Data quality and control parameters are becoming more important in metabolomics. For peak picking, open-source or commercial solutions are used. Other publications consider different software solutions or data acquisition types for peak picking, a combination, including proposed and new quality parameters for the process of peak picking, does not exist. This study tries to examine the performance of three different software in terms of reproducibility and quality of their output while also considering new quality parameters to gain a better understanding of resulting feature lists in metabolomics data. We saw best recovery of spiked analytes in MS-DIAL. Reproducibility over multiple projects was good among all software. The total number of features found was consistent for DDA and full scan acquisition in MS-DIAL but full scan data leading to considerably more features in MZmine and Progenesis Qi. Feature linearity proved to be a good quality parameter. Features in MS-DIAL and MZmine, showed good linearity while Progenesis Qi produced large variation, especially in full scan data. Peak width proved to be a very powerful filtering criteria revealing many features in MZmine and Progenesis Qi to be of questionable peak width. Additionally, full scan data appears to produce a disproportionally higher number of short features. This parameter is not yet available in MS-DIAL. Finally, the manual classification of true positive features proved MS-DIAL to perform significantly better in DDA data (62 % true positive) than the two other software in either mode. We showed that currently popular solutions MS-DIAL and MZmine perform well in targeted analysis of spiked analytes as well as in classic untargeted analysis. The commercially available solution Progenesis Qi does not hold any advantage over the two in terms of quality parameters, of which we proposed peak width as a new parameter and showed that already proposed parameters such as feature linearity in samples of increasing concentration are advisable to use.

Engaging Youth Voice and Family Partnerships to Improve Children's Mental Health Outcomes.

Promoting active participation of families and youth in mental health systems of care is the cornerstone of creating a more inclusive, effective, and responsive care network. This article focuses on the inclusion of parent and youth voice in transforming our mental health care system to promote increased engagement at all levels of service delivery. Youth and parent peer support delivery models, digital innovation, and technology not only empower the individuals involved, but also have the potential to enhance the overall efficacy of the mental health care system.

The role of catchment population size, data normalization, and chronology of public health interventions on wastewater-based COVID-19 viral trends.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic presented the most challenging global crisis in recent times. A pandemic caused by a novel pathogen such as SARS-CoV-2 necessitated the development of innovative techniques for the monitoring and surveillance of COVID-19 infections within communities. Wastewater surveillance (WWS) is recognized as a non-invasive, cost-effective, and valuable epidemiological tool to monitor the prevalence of COVID-19 infections in communities. Seven municipal wastewater sampling sites representing distinct sewershed communities were selected for the surveillance of the SARS-CoV-2 virus in Durham Region, Ontario, Canada over 8 months from March 2021 to October 2021. Viral RNA fragments of SARS-CoV-2 and the normalization target pepper mild mottle virus (PMMoV) were concentrated from wastewater influent using the PEG/NaCl superspeed centrifugation method and quantified using RT-qPCR. Strong significant correlations (Spearman's rs = 0.749 to 0.862, P < 0.001) were observed between SARS-CoV-2 gene copies/mL of wastewater and clinical cases reported in each delineated sewershed by onset date. Although raw wastewater offered higher correlation coefficients with clinical cases by onset date compared to PMMoV normalized data, only one site had a statistically significantly higher Spearman's correlation coefficient value for raw data than normalized data. Implementation of community stay-at-home orders and vaccinations over the course of the study period in 2021 were found to strongly correspond to decreasing SARS-CoV-2 wastewater trends in the wastewater treatment plants and upstream pumping stations.