Opioid prescribing in the Netherlands during the COVID-19 pandemic: a national register-based study.

OBJECTIVES: The COVID-19 pandemic and related lockdown measures disrupted global healthcare provision, including opioid prescribing. In North America, opioid sales declined while opioid-related deaths increased. In Europe, the effect of the pandemic on prescribing is not yet known. Given the ongoing increase in opioid-related harm and mortality, it is crucial to analyse the impact of the COVID-19 crisis and lockdown measures on opioid prescribing. Therefore, the objective of this study was to characterise opioid prescribing in the Netherlands during the COVID-19 pandemic. DESIGN: A nationwide register-based study characterising opioid prescribing using aggregated insurance reimbursement data. SETTING: Dutch healthcare during the first 2 years of the COVID lockdown. PARTICIPANTS: The whole Dutch population. PRIMARY AND SECONDARY OUTCOME MEASURES: Comparing the number of opioid prescriptions during the pandemic with a prepandemic period using a risk ratio (RR), with separate analysis on the prescription type (first-time or repeat prescription), patients' sex, age and socioeconomic status. We also explored lockdown effects. RESULTS: During the first lockdown, the total number of new opioid prescriptions and prescriptions to young patients (briefly) decreased (RR 0.88, 95% CI 0.88 to 0.89 and RR 0.73, 95% CI 0.70 to 0.75, respectively), but the overall number of opioid prescriptions remained stable throughout the pandemic compared with prepandemic. Women, older patients and patients living in lower socioeconomic areas received more opioids per capita, but the pandemic did not amplify these differences. CONCLUSIONS: The pandemic appears to have had a limited impact on opioid prescribing in the Netherlands. Yet, chronic use of opioids remains an important public health issue.

Marine Fish Movement: home range sizes for commercially relevant species.

Estimates of home range sizes for marine fishes are essential for designing and assessing the effects of spatial wildlife conservation policies and management interventions. However, in situ studies of marine species movement are challenging and often expensive, resulting in a paucity of data on the home range size of the vast majority of marine fishes. Here, we develop a set of new datasets, which we have collectively named Marine Fish Movement, that synthesises published empirically evaluated home ranges reported for adult marine fishes that interact with fisheries and leverage these data to estimate home range sizes for unstudied species. The empirical data contain estimated home range sizes (km2) for 193 species across 63 family groups from 179 studies published between 1971 and 2022. We use a random forest regression model to estimate home range sizes (km2) for 664 fished marine species currently lacking home range estimates. Marine Fish Movement can inform spatial interventions including the design and management of marine protected areas and dynamic fisheries management to meet sustainability goals.

Trauma's distinctive and combined effects on subsequent substance use, mental health, and neurocognitive functioning with the NCANDA sample.

PURPOSE: Traumatic brain injury (TBI) and potentially traumatic events (PTEs) contribute to increased substance use, mental health issues, and cognitive impairments. However, there's not enough research on how TBI and PTEs combined impact mental heath, substance use, and neurocognition. METHODS: This study leverages a subset of The National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) multi-site dataset with 551 adolescents to assess the combined and distinctive impacts of TBI, PTEs, and TBI+PTEs (prior to age 18) on substance use, mental health, and neurocognitive outcomes at age 18. RESULTS: TBI, PTEs, and TBI+PTEs predicted greater lifetime substance use and past-year alcohol and cannabis use. PTEs predicted greater internalizing symptoms, while TBI+PTEs predicted greater externalizing symptoms. Varying effects on neurocognitive outcomes included PTEs influencing attention accuracy and TBI+PTEs predicting faster speed in emotion tasks. PTEs predicted greater accuracy in abstraction-related tasks. Associations with working memory were not detected. CONCLUSION: This exploratory study contributes to the growing literature on the complex interplay between TBI, PTEs, and adolescent mental health, substance use, and neurocognition. The developmental implications of trauma via TBIs and/or PTEs during adolescence are considerable and worthy of further investigation.

Quantitative assessment of morphological changes in lipid droplets and lipid-mito interactions with aging in brown adipose.

The physical characteristics of brown adipose tissue (BAT) are defined by the presence of multilocular lipid droplets (LDs) within the brown adipocytes and a high abundance of iron-containing mitochondria, which give it its characteristic color. Normal mitochondrial function is, in part, regulated by organelle-to-organelle contacts. For example, the contact sites that mediate mitochondria-LD interactions are thought to have various physiological roles, such as the synthesis and metabolism of lipids. Aging is associated with mitochondrial dysfunction, and previous studies show that there are changes in mitochondrial structure and the proteins that modulate organelle contact sites. However, how mitochondria-LD interactions change with aging has yet to be fully clarified. Therefore, we sought to define age-related changes in LD morphology and mitochondria-lipid interactions in BAT. We examined the three-dimensional morphology of mitochondria and LDs in young (3-month) and aged (2-year) murine BAT using serial block face-scanning electron microscopy and the Amira program for segmentation, analysis, and quantification. Our analyses showed reductions in LD volume, area, and perimeter in aged samples in comparison to young samples. Additionally, we observed changes in LD appearance and type in aged samples compared to young samples. Notably, we found differences in mitochondrial interactions with LDs, which could implicate that these contacts may be important for energetics in aging. Upon further investigation, we also found changes in mitochondrial and cristae structure for the mitochondria interacting with LDs. Overall, these data define the nature of LD morphology and organelle-organelle contacts during aging and provide insight into LD contact site changes that interconnect biogerontology with mitochondrial function, metabolism, and bioactivity in aged BAT.

Towards IVDR-compliance by implementing quality control steps in a quantitative extracellular vesicle-miRNA liquid biopsy assay for response monitoring in patients with classic Hodgkin lymphoma.

Previously, we showed that quantification of lymphoma-associated miRNAs miR-155-5p, -127-3p and let-7a-5p levels in plasma extracellular vesicles (EVs) report treatment response in patients with classic Hodgkin lymphoma (cHL). Prior to clinical implementation, quality control (QC) steps and validation are required to meet international regulatory standards. Most published EV-based diagnostic assays have yet to meet these requirements. In order to advance the assay towards regulatory compliance (e.g., IVDR 2017/746), we incorporated three QC steps in our experimental EV-miRNA quantitative real-time reverse-transcription PCR (q-RT-PCR) assay in an ISO-13485 certified quality-management system (QMS). Liposomes encapsulated with a synthetic (nematode-derived) miRNA spike-in controlled for EV isolation by automated size-exclusion chromatography (SEC). Additional miRNA spike-ins controlled for RNA isolation and cDNA conversion efficiency. After deciding on quality criteria, in total 107 out of 120 samples from 46 patients passed QC. Generalized linear mixed-effect modelling with bootstrapping determined the diagnostic performance of the quality-controlled data at an area under the curve (AUC) of 0.84 (confidence interval [CI]: 0.76-0.92) compared to an AUC of 0.87 (CI: 0.80-0.94) of the experimental assay. After the inclusion of QC steps, the accuracy of the assay was determined to be 78.5% in predicting active disease status in cHL patients during treatment. We demonstrate that a quality-controlled plasma EV-miRNA assay is technically robust, taking EV-miRNA as liquid biopsy assay an important step closer to clinical evaluation.

Cyanotoxin accumulation and growth patterns of biocrust communities under variable environmental conditions.

Biocrusts dominate the soil surface in deserts and are composed of diverse microbial communities that provide important ecosystem services. Cyanobacteria in biocrusts produce many secondary metabolites, including the neurotoxins BMAA, AEG, DAB, anatoxin-a(S) (guanitoxin), and the microcystin hepatotoxins, all known or suspected to cause disease or illness in humans and other animals. We examined cyanobacterial growth and prevalence of these toxins in biocrusts at millimeter-scales, under a desert-relevant illumination gradient. In contrast to previous work, we showed that hydration had an overall positive effect on growth and toxin accumulation, that nitrogen was not correlated with growth or toxin production, and that phosphorus enrichment negatively affected AEG and BMAA concentrations. Excess illumination positively correlated with AEG, and negatively correlated with all other toxins and growth. Basic pH negatively affected only the accumulation of BMAA. Anatoxin-a(S) (guanitoxin) was not correlated with any tested variables, while microcystins were not detected in any of the samples. Concerning toxin pools, AEG and BMAA were good predictors of the presence of one another. In a newly conceptualized scheme, we integrate aspects of biocrust growth and toxin pool accumulations with arid-relevant desertification drivers.

Does "Dr. Google" improve discussion and decisions in small animal practice? Dog and cat owners use of internet resources to find medical information about their pets in three European countries.

Modern dog and cat owners increasingly use internet resources to obtain information on pet health issues. While access to online information can improve owners' knowledge of patient care and inform conversations with their veterinarian during consultations, there is also a risk that owners will misinterpret online information or gain a false impression of current standards in veterinary medicine. This in turn can cause problems or tensions, for example if the owner delays consulting their veterinarian about necessary treatment, or questions the veterinarian's medical advice. Based on an online questionnaire aimed at dog and cat owners in Austria, Denmark and the United Kingdom (N = 2117) we investigated the use of internet resources to find veterinary medical information, the type of internet resources that were used, and whether owner beliefs explain how often they used the internet to find medical information about their pet. Approximately one in three owners reported that they never used internet resources prior to (31.7%) or after (37.0%) a consultation with their veterinarian. However, when owners do make use of the internet, our results show that they were more likely to use it before than after the consultation. The most common internet resources used by owners were practice websites (35.0%), veterinary association websites (24.0%), or 'other' websites providing veterinary information (55.2%). Owners who believe that the use of internet resources enables them to have a more informed discussion with their veterinarians more often use internet resources prior to a consultation, whereas owners who believed that internet resources help them to make the right decision for their animal more often use internet resources after a consultation. The results suggest that veterinarians should actively ask pet owners if they use internet resources, and what resources they use, in order to facilitate open discussion about information obtained from the internet. Given that more than a third of pet owners use practice websites, the findings also suggest that veterinarians should actively curate their own websites where they can post information that they consider accurate and trustworthy.

Comparative evaluation of selected concentrations of sodium hypochlorite on the outcome of endodontic therapy among Ghanaians.

BACKGROUND: Endodontic treatment is one of the main dental treatments to manage inflamed or infected root canal systems of teeth. The success of endodontic treatment principally depends on eradicating microorganisms in the root canal by chemo-mechanical debridement with irrigation solutions like sodium hypochlorite (NaOCl). NaOCl has been used in concentrations ranging from 0.5% to 5.25%. This study determined the antimicrobial effectiveness of selected concentrations (0.5%, 1.0%, 2.6%, and 5.2%) of NaOCl in endodontic treatment. METHODS: The study sites were the University of Ghana Dental School (UGDS) and Noguchi Memorial Institute for Medical Research (NMIMR). Sixty infected single-rooted single-canal teeth were used. Before (S1) and after (S2), root canal samples during the endodontic treatment with the selected concentrations of NaOCl were examined via anaerobic and aerobic cultures. The isolates were identified using Matrix Assisted Laser Desorption Ionization-Time Of Flight Mass Spectrometry (MALDI-TOF MS). RESULTS: All S1 samples were positive for cultivable bacteria. Fifty-three (53) different microbial species belonging to 20 different microbial genera were isolated. Streptococcus viridans was the most frequently isolated microbe. There were zero isolates in the root canals irrigated with 2.6% and 5.2% NaOCl. Two teeth had isolates in the groups irrigated with the lower concentrations (0.5% and 1.0%) of NaOCl. The persistent bacteria were one species each of Streptococcus mitis and Streptococcus oralis, respectively. CONCLUSION: Root canal treatments using chemo-mechanical preparation with the selected concentrations (0.5%, 1.0%, 2.6%, and 5.2%) of NaOCl were effective in significantly reducing the microbial load, and for the 5.2% and 2.6% concentrations, in eliminating all the microorganisms.

Feasibility and Acceptability of an Agenda-Setting Kit in the Care of People With Type 2 Diabetes: The QBSAFE ASK Feasibility Study.

This article reports on a study to assess the feasibility of research procedures and acceptability of QBSAFE, a set of conversation cards focused on quality of life, treatment burden, safety, and avoidance of future events in people with type 2 diabetes. The study enrolled 84 patients and 7 clinicians. Of the 58 patients who completed questionnaires, 64% agreed that the QBSAFE agenda-setting kit (ASK) helped them discuss their situation, 78% agreed that others could benefit from it, and 38% said they would use it again. Most clinicians felt confident responding to issues (in 89% of encounters) and said they would use the kit again (78%) and recommend it to colleagues (82%). The QBSAFE ASK can be feasibly implemented and holds promise in facilitating discussion and collaborative problem-solving.

Bidirectional relations between parents' discipline strategies and children's inhibitory control from early to middle childhood.

Parents' use of harsh discipline and inductive discipline are theorized to change normatively across the transition from early to middle childhood (ages 5-7 years), with harsh discipline decreasing and inductive discipline increasing. Importantly, within-person support for these changes is lacking. Additionally, these changes are argued to be driven by improvements in children's cognitive and social abilities, including inhibitory control. The present study examined within-family bidirectional relations between parents' (primarily mothers') harsh discipline, inductive discipline, and children's inhibitory control across the transition to middle childhood. Participants were 118 4-, 5-, and 6-year-olds and their primary caregivers. At two time points, separated by 12 months, parents completed a questionnaire about their use of harsh and inductive discipline, and children completed a battery of inhibitory control tasks. A latent change score model was used to examine within-family bidirectional relations. More inductive discipline at Time 1 was related to a decline in harsh discipline over the year for parents of 5- and 6-year-olds, but not 4-year-olds. Harsh discipline at Time 1 was not related to change in inductive discipline. Parental discipline was not related to the change in children's inhibitory control, nor was inhibitory control related to the change in parental discipline. Relations between inductive discipline and change in harsh discipline provide within-person support for expectations of normative change in parents' discipline strategies across the transition to middle childhood. Further research examining when parents of 4-year-olds make this transition and predictors of change in parental discipline will inform research of normative trajectories of parental discipline. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Glioma-Associated Sialoglycans Drive the Immune Suppressive Phenotype and Function of Myeloid Cells.

The tumor microenvironment of glioblastoma IDH-wildtype is highly immune suppressive and is characterized by a strong component of myeloid-derived suppressor cells (MDSCs). To interfere with the immune suppressive functions of MDSCs, a comprehensive understanding on how MDSCs acquire their suppressive phenotype is essential. Previously, we and others have shown a distinct Sialic acid-binding immunoglobulin-like lectin (Siglec) receptor expression profile for MDSCs in glioblastoma. Siglec receptors can transmit inhibitory signals comparable to PD-1 and are suggested to act as glyco-immune checkpoints. Here, we investigated how glioma specific Siglec-sialic acid interactions influence myeloid immune suppressive functions. Co-culturing monocytes with glioblastoma cells induced CD163 expression on the monocytes. Upon desialylation of the glioblastoma cells, this induction of CD163 was hampered, and furthermore, the monocytes were now able to secrete higher amounts of IL-6 and TNFα compared to fully sialylated glioblastoma cells. Additionally, Siglec-specific triggering using anti-Siglec-7 or Siglec-9 antibodies displayed a decreased TNFα secretion by the monocytes, validating the role of the Siglec-Sialic axis in the co-culture experiments. Together, our results demonstrate that glioblastoma cells induce a myeloid immune-suppressive phenotype that could be partly rescued by lowering the glioblastoma-associated sialic acid levels. This manuscript supports further research of the Siglec-Sialic acid axis in the context of glioblastoma and its potential to improve clinical outcome.

[What importance does outpatient care have for mobility in rural areas? Results from a GPS study among persons aged 75 and older]. / Außerhäusliche Mobilität von Personen ab 75 Jahren im ländlichen Raum. Ergebnisse aus einer GPS-Studie.

BACKGROUND: Out-of-home mobility, defined as active and passive movement through external environments, is a resource for autonomy, quality of life, and self-realization in older age. Various factors influence out-of-home mobility, primarily studied in urban settings. The study aims to examine associated factors in a study population aged 75 and above in rural areas. METHODS: Baseline data from the MOBILE trial involving 212 participants aged 75 and above and collected between June 2021 and October 2022 were analyzed. Out-of-home mobility was measured temporally as time out of home (TOH) and spatially as convex hull (CHull) using GPS over seven days. Mixed models considered outpatient care parameters as well as personal, social, and environmental factors along with covariates such as age and gender. RESULTS: Participants in the MOBILE study (average age 81.5; SD: 4.1; 56.1% female) exhibited average out-of-home mobility of TOH: 319.3 min (SD: 196.3) and CHull: 41.3 (SD: 132.8). Significant associations were found for age (TOH: ß = -0.039, p < 0.001), social network (TOH: ß = 0.123, p < 0.001), living arrangement (CHull: ß = 0.689, p = 0.035), health literacy (CHull: ß = 0.077, p = 0.008), sidewalk quality (ß = 0.366, p = 0.003), green space ratio (TOH: ß = 0.005, p = 0.047), outpatient care utilization (TOH: ß = -0.637, p < 0.001, CHull: ß = 1.532; p = 0.025), and active driving (TOH: ß = -0.361, p = 0.004). DISCUSSION: Previously known multifactorial associations related to objectively measured out-of-home mobility in old age could be confirmed in rural areas. Novel and relevant for research and practice is the significant correlation between out-of-home mobility and outpatient care utilization.

The power of junior faculty mentoring committees.

Junior faculty mentoring committees have important roles in ensuring that faculty thrive and adjust to their new positions and institutions. Here, we describe the purpose, structure, and benefits of junior faculty mentoring committees, which can be a powerful tool for early-career academic investigators in science, technology, engineering, mathematics, and medical (STEMM) fields. There is a paucity of information about what mentoring committees are, how to use them effectively, what areas they should evaluate, and how they can most successfully help junior faculty progress in their careers. This work offers guidance for both junior faculty mentees and mentoring committee members on how to best structure and utilize mentoring committees to promote junior faculty success. A better understanding of the intricacies of the mentoring committee will allow junior faculty members to self-advocate and will equip committee mentors with tools to ensure that junior faculty are successful in thriving in academia.

How debunking biases in research and development decisions could lead to more equitable healthcare?

Decades of research have demonstrated that a variety of cognitive biases can affect our judgment and ability to make rational decisions in personal and professional environments. The lengthy, risky, and costly nature of pharmaceutical research and development (R&D) makes it vulnerable to biased decision-making. Moreover, cognitive biases can play a role in regulatory and clinical decision-making, the latter impacting diagnostic and treatment decisions in the therapeutic use of medicines. These inherent and/or institutionalized biases (e.g., in assumptions, data, or decision-making practices) could conceivably contribute to health inequities. In this mini-review, we provide a broad perspective on how cognitive biases can affect pharmaceutical R&D, regulatory evaluation, and therapeutic decision-making. Example approaches to mitigate the effect of common biases in the development, approval, and use of new therapeutics, such as quantitative decision criteria, multidisciplinary reviews, regulatory and treatment guidelines, and evidence-based clinical decision support systems are illustrated. Mitigating the impact of cognitive biases could increase pharma R&D efficiency, change the perspective and prioritization of unmet medical needs, increase representativeness and quality of evidence generated through clinical trials and real-world research, leading to higher quality insights and more effective medication use, and as such could eventually contribute to more equitable healthcare.

Prevalence and Detection of Obstructive Sleep Apnea Early after Stroke.

Background: Obstructive sleep apnea (OSA) negatively impacts post-stroke recovery. This study's purpose: examine the prevalence of undiagnosed OSA and describe a simple tool to identify those at-risk for OSA in the early phase of stroke recovery. Methods: This was a cross-sectional descriptive study of people ∼15 days post-stroke. Adults with stroke diagnosis admitted to inpatient rehabilitation over a 3-year period were included if they were alert/arousable, able to consent/assent to participation, and excluded if they had a pre-existing OSA diagnosis, other neurologic health conditions, recent craniectomy, global aphasia, inability to ambulate 150 feet independently pre-stroke, pregnant, or inability to understand English. OSA was deemed present if oxygen desaturation index (ODI) of >=15 resulted from overnight oximetry measures. Prevalence of OSA was determined accordingly. Four participant characteristics comprised the "BASH" tool (body mass index >=35, age>=50, sex=male, hypertension=yes). A receiver operator characteristics (ROC) curve analysis was performed with BASH as test variable and OSA presence as state variable. Results: Participants (n=123) were 50.4% male, averaged 64.12 years old (sd 14.08), and self-identified race as 75.6% White, 20.3% Black/African American, 2.4%>1 race, and 1.6% other; 22% had OSA. ROC analysis indicated BASH score >=3 predicts presence of OSA (sensitivity=0.778, specificity=0.656, area under the curve =0.746, p<0.001). Conclusions: Prevalence of undiagnosed OSA in the early stroke recovery phase is high. With detection of OSA post-stroke, it may be possible to offset untreated OSA's deleterious impact on post-stroke recovery of function. The BASH tool is an effective OSA screener for this application.

Insights into interoceptive and emotional processing: Lessons from studies on insular HD-tDCS.

Interoception, the processing of internal bodily signals, is proposed as the fundamental mechanism underlying emotional experiences. Interoceptive and emotional processing appear distorted in psychiatric disorders. However, our understanding of the neural structures involved in both processes remains limited. To explore the feasibility of enhancing interoception and emotion, we conducted two studies using high-definition transcranial direct current stimulation (HD-tDCS) applied to the right anterior insula. In study one, we compared the effects of anodal HD-tDCS and sham tDCS on interoceptive abilities (sensibility, confidence, accuracy, emotional evaluation) in 52 healthy subjects. Study two additionally included physical activation through ergometer cycling at the beginning of HD-tDCS and examined changes in interoceptive and emotional processing in 39 healthy adults. In both studies, HD-tDCS was applied in a single-blind cross-over online design with two separate sessions. Study one yielded no significant effects of HD-tDCS on interoceptive dimensions. In study two, significant improvements in interoceptive sensibility and confidence were observed over time with physical preactivation, while no differential effects were found between sham and insula stimulation. The expected enhancement of interoceptive and emotional processing following insula stimulation was not observed. We conclude that HD-tDCS targeting the insula does not consistently increase interoceptive or emotional variables. The observed increase in interoceptive sensibility may be attributed to the activation of the interoceptive network through physical activity or training effects. Future research on HD-tDCS involving interoceptive network structures could benefit from protocols targeting larger regions within the network, rather than focusing solely on insula stimulation.

Comparing Methods for Identifying Post-Market Patient Preferences at the Point of Decision-Making: Insights from Patients with Chronic Pain Considering a Spinal Cord Stimulator Device.

Purpose: To compare three methods for identifying patient preferences (MIPPs) at the point of decision-making: analysis of video-recorded patient-clinician encounters, post-encounter interviews, and post-encounter surveys. Patients and Methods: For the decision of whether to use a spinal cord stimulator device (SCS), a video coding scheme, interview guide, and patient survey were iteratively developed with 30 SCS decision-making encounters in a tertiary academic medical center pain clinic. Burke's grammar of motives was used to classify the attributed source or justification for a potential preference for each preference block. To compare the MIPPs, 13 patients' encounters with their clinician were video recorded and subsequently analyzed by 4 coders using the final video coding scheme. Six of these patients were interviewed, and 7 surveyed, immediately following their encounters. Results: For videos, an average of 66 (range 33-106) sets of utterances potentially indicating a patient preference (a preference block), surveys 33 (range 32-34), and interviews 25 (range 18-30) were identified. Thirty-eight unique themes (75 subthemes), each a preference topic, were identified from videos, surveys 19 themes (12 subthemes), and interviews 39 themes (54 subthemes). The proportion of preference blocks that were judged as expressing a preference that was clearly important to the patient or affected their decision was highest for interviews (72.8%), surveys (68.0%), and videos (27.0%). Videos mostly attributed preferences to the patient's situation (scene) (65%); interviews, the act of receiving or living with SCS (43%); surveys, the purpose of SCS (40%). Conclusion: MIPPs vary in the type of preferences identified and the clarity of expressed preferences in their data sets. The choice of which MIPP to use depends on projects' goals and resources, recognizing that the choice of MIPP may affect which preferences are found.

HIV and Substance Use Disorders.

Over 1.2 million Americans aged 13 years and older have been diagnosed with human immunodeficiency virus (HIV). While HIV incidence has been declining since 2017, the risk of HIV acquisition and transmission persists among persons who use drugs via injection drug use and unprotected sexual intercourse associated with substance use. Untreated substance use disorder (SUD) is associated with poor adherence to HIV antiretroviral therapy, poor HIV outcomes, and increased risk for HIV acquisition. Herein, we describe the intertwined syndemic of HIV and SUD, as well as treatment strategies and evidence-based public health efforts to engage and retain persons who use drugs into care.