Abnormal Morphology and Synaptogenic Signaling in Astrocytes Following Prenatal Opioid Exposure.

In recent decades, there has been a dramatic rise in the rates of children being born after in utero exposure to drugs of abuse, particularly opioids. Opioids have been shown to have detrimental effects on neurons and glia in the central nervous system (CNS), but the impact of prenatal opioid exposure (POE) on still-developing synaptic circuitry is largely unknown. Astrocytes exert a powerful influence on synaptic development, secreting factors to either promote or inhibit synapse formation and neuronal maturation in the developing CNS. Here, we investigated the effects of the partial µ-opioid receptor agonist buprenorphine on astrocyte synaptogenic signaling and morphological development in cortical cell culture. Acute buprenorphine treatment had no effect on the excitatory synapse number in astrocyte-free neuron cultures. In conditions where neurons shared culture media with astrocytes, buprenorphine attenuated the synaptogenic capabilities of astrocyte-secreted factors. Neurons cultured from drug-naïve mice showed no change in synapses when treated with factors secreted by astrocytes from POE mice. However, this same treatment was synaptogenic when applied to neurons from POE mice, indicating a complex neuroadaptive response in the event of impaired astrocyte signaling. In addition to promoting morphological and connectivity changes in neurons, POE exerted a strong influence on astrocyte development, disrupting their structural maturation and promoting the accumulation of lipid droplets (LDs), suggestive of a maladaptive stress response in the developing CNS.

Neonatal arterial thrombosis: an arcane COVID sequelae.

We describe a case of a term neonate with a swollen right arm and weakened pulses, diagnosed with arterial thromboembolism in the right axillary and brachial arteries. Treatment involved heparin, followed by enoxaparin, resulting in significant improvement. Maternal SARS-CoV-2 infection during pregnancy was considered as a potential factor, supported by the newborn's reactive COVID antibodies. The authors hypothesise a potential correlation between neonatal thrombosis and maternal SARS-CoV-2 infection during pregnancy. It is important to note that this association remains speculative and warrants further investigation for validation. The case underscores the importance of recognising and managing neonatal arterial thrombosis, especially in the context of maternal illness. We discuss the case in detail and review current knowledge on this condition.

Health equity in heart failure.

The treatment of heart failure (HF) with reduced ejection fraction (HFrEF) has substantially developed over the past decades. More than ever before, the application of appropriate evidence-based medical therapy for HFrEF is associated with remarkable improvements in survival, noteworthy increases in quality of life, and a marked reduction in symptomatic HF sufficient to warrant hospitalization. These enhanced clinical outcomes are driven by the "four pillars" of HF therapy: 1) evidence-based beta blockers, 2) Renin-angiotensin-aldosterone system inhibitors (angiotensin-converting enzyme inhibitors /angiotensin II receptor blockers or angiotensin receptor-neprilysin inhibitors, 3) mineralocorticoid receptor antagonists, and most recently, 4) sodium-glucose cotransporter-2 inhibitors. Despite robust evidence from well-conducted randomized clinical trials, guideline-directed medical therapies with established cardiovascular benefits remain significantly underutilized in clinical practice, particularly among under-represented minority populations. This phenomenon has led to class 1 level recommendations from the 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America Guidelines to address HF disparities among vulnerable populations as follows. In this article, we highlight the difference between health equality and health equity and discuss the need to address equity in the treatment of heart failure, ensuring that the impressive progress made in the treatment of HFrEF is equally beneficial to all individuals. We discuss strategies to reduce and ultimately eliminate disparities in the determinants of health that particularly affect marginalized groups, including the socioeconomic determinants and racism as a threat to public health. Finally, we discuss and propose a combination of the four pillars of ethics with the four pillars of GDMT to optimize and personalize treatment of all patients with HFrEF, to achieve true equity in the treatment of HF.

Polypill Eligibility for Patients with Heart Failure with Reduced Ejection Fraction in the ASIAN-HF Registry: A Cross-Sectional Analysis.

Background: The rates of guideline-directed medical therapy (GDMT) prescription for heart failure with reduced ejection fraction (HFrEF) in Asia remain sub-optimal. The primary objective of this study was to examine HFrEF polypill eligibility in the context of measured baseline prescription rates of individual components of GDMT among participants with HFrEF in Asia. Methods: A retrospective analysis of 4,868 patients with HFrEF from the multi-national ASIAN-HF registry was performed, and 3,716 patients were included in the final, complete case analysis. Eligibility for a HFrEF polypill, upon which patients were grouped and characterized, was based on the following: left ventricular systolic dysfunction (LVEF < 40% on baseline echocardiography), systolic blood pressure ≥ 100 mm Hg, heart rate ≥ 50 beats/minute, eGFR ≥ 30 mL/min/1.73 m, and serum potassium ≤ 5.0 mEq/L. Regression analyses were performed to evaluate associations of the baseline sociodemographic factors with HFrEF polypill eligibility. Results: Among 3,716 patients with HFrEF in the ASIAN-HF registry, 70.3% were eligible for a HFrEF polypill. HFrEF polypill eligibility was significantly higher than baseline rates of triple therapy prescription of GDMT across sex, all studied geographical regions, and income levels. Patients were more likely to be eligible for a HFrEF polypill if they were younger and male, with higher BMI and systolic blood pressure, and less likely to be eligible if they were from Japan and Thailand. Conclusion: The majority of patients with HFrEF in ASIAN-HF were eligible for a HFrEF polypill and were not receiving conventional triple therapy. HFrEF polypills may be a feasible and scalable implementation strategy to help close the treatment gap among patients with HFrEF in Asia.

"This Won't Hurt a Bit": Is There a Role for Music in Bedside Procedures?

Music has played a long and storied role in clinical healing. However, the integration of music into clinical practice has been slow to gain traction, despite a recent meta-analysis demonstrating association of music interventions with clinically meaningful improvements in health-related quality of life. There is growing evidence that music has an active role in reducing patient pain and anxiety as well as affecting physiologic parameters, such as heart rate and blood pressure, in an ICU setting. Past studies have shown that incorporation of music into procedures in the operating room, radiology suites, and catheterization labs has reduced concurrent pharmacologic sedation requirements. In the age of patient-centered personalized medicine, we propose a call to action to implement an easily accessible, attainable checklist item offering a personal choice of music for patients during standardized bedside procedural training, to reduce anxiety, pain, and pharmacologic sedation and potentially improve clinical outcomes.

Stakeholder perspectives on the demand and supply factors driving substandard and falsified blood pressure lowering medications in Nigeria: a qualitative study.

OBJECTIVES: Although substandard and falsified (SF) blood pressure (BP) lowering medications are a global problem, qualitative research exploring factors driving this in Nigeria has not been reported. This study provides information on factors driving demand for and supply of low-quality BP lowering medications in Nigeria and potential strategies to address these factors. METHODS: This was a cross-sectional qualitative study. Between August 2020 and September 2020, we conducted 11 in-depth interviews and 7 focus group discussions with administrators of health facilities, major manufacturers and distributors of BP lowering medications, pharmacists, drug regulators, patients and primary care physicians purposively sampled from the Federal Capital Territory, Nigeria. Data were analysed using directed content analysis, with the aid of Dedoose. RESULTS: We found that demand for SF BP lowering medications in Nigeria was driven by high out-of-pocket expenditure and stockouts of quality-assured BP lowering medications. Supply of low-quality BP lowering medications was driven by limited in-country manufacturing capacity, non-adherence to good manufacturing and distribution practices, under-resourced drug regulatory systems, ineffective healthcare facility operations, poor distribution practices, limited number of trained pharmacists and the COVID-19 pandemic which led to stockouts. Central medicine store procurement procedures, active pharmaceutical ingredient quality check and availability of trained pharmacists were existing strategies perceived to lower the risk of supply and demand of SF BP lowering medications. CONCLUSION: Our findings suggest that demand for and supply of SF BP lowering medications in Nigeria are driven by multi-level, interrelated factors. Multi-pronged strategies need to target stakeholders and systems involved in drug production, distribution, prescription, consumption, regulation and pricing.

Relation of Menopause With Cardiovascular Risk Factors in South Asian American Women (from the MASALA Study).

The menopausal transition is a time of accelerating risk of cardiovascular disease (CVD), and promoting cardiovascular health during midlife is an important period of time to prevent CVD in women. The association of menopause with cardiovascular risk factors or subclinical atherosclerosis has not previously been evaluated in South Asian American women, a population with a disproportionately higher CVD burden compared with other race/ethnic groups. The objective of this study was to evaluate the association of menopause with CVD risk factors and subclinical cardiometabolic disease markers. We studied women aged 40 to 84 years from the Mediators of Atherosclerosis in South Asians Living in America study. The association of self-reported menopausal status with multiple demographic and clinical variables was assessed with linear and logistic regression adjusted for age and cardiovascular health behaviors. In a secondary ("age-restricted") analysis, postmenopausal participants outside the age range of premenopausal participants were excluded. In the age-restricted sample, menopause was associated with a higher adjusted odds of hypertension (odds ratio = 1.19, 95% confidence interval [CI] 1.02 to 1.41), and higher systolic blood pressure (ß = 6.34, 95% CI 0.82 to 11.87), and significantly higher subcutaneous fat area (ß = 42.8, 95% CI 5.8 to 91.4). No significant associations between menopause and ectopic fat deposition, coronary artery calcium, or carotid intima-media thickness were observed. In South Asian American women in the Mediators of Atherosclerosis in South Asians Living in America study, menopause was associated with cardiovascular risk factors and higher subcutaneous fat deposition. Menopausal status is an important factor to examine and address CVD risk factors.

Hands-on engineering courses in the COVID-19 pandemic: adapting medical device design for remote learning.

The COVID-19 pandemic has challenged the status quo of engineering education, especially in highly interactive, hands-on design classes. Here, we present an example of how we effectively adjusted an intensive hands-on, group project-based engineering course, Medical Device Design & Innovation, to a remote learning curriculum. We first describe the modifications we made. Drawing from student pre and post feedback surveys and our observations, we conclude that our adaptations were overall successful. Our experience may guide educators who are transitioning their engineering design courses to remote learning.

Management of stuttering using cognitive behavior therapy and mindfulness meditation.

Stuttering is a speech fluency disorder with varied etiological explanations. It is important to identify symptoms early so that adequate and timely intervention can be delivered with focus on management and recovery. Stuttering, besides affecting speech fluency, might have a number of negative psychosocial consequences for the sufferer that may lead to immense anxiety, besides other symptoms. Therefore, it is thus imperative to include multiple dimensions in the holistic treatment of stuttering. Cognitive behavior therapy and mindfulness equip the client with the skills to manage the problems that occur as a result of stuttering. Since the rate of relapse in this condition is high, the chosen therapeutic paradigm must involve booster sessions over a long term. Periodic, detailed assessment would update the therapist about the barriers in treatment and would help in devising appropriate methods to get rid of these hindrances.

Toxicity screening of two prevalent metal organic frameworks for therapeutic use in human lung epithelial cells.

INTRODUCTION: The flexibility and tunability of metal organic frameworks (MOFs), crystalline porous materials composed of a network of metal ions coordinated by organic ligands, confer their variety of applications as drug delivery systems or as sensing and imaging agents. However, such properties also add to the difficulty in ensuring their safe implementation when interaction with biological systems is considered. METHODS: In the current study, we used real-time sensorial strategies and cellular-based approaches to allow for fast and effective screening of two MOFs of prevalent use, namely, MIL-160 representative of a hydrophilic and ZIF-8 representative of a hydrophobic framework. The two MOFs were synthesized "in house" and exposed to human bronchial epithelial (BEAS-2B) cells, a pertinent toxicological screening model. RESULTS: Analysis allowed evaluation and differentiation of particle-induced cellular effects as well identification of different degrees and routes of toxicity, all in a high-throughput manner. Our results show the importance of performing screening toxicity assessments before introducing MOFs to biomedical applications. DISCUSSION: Our proposed screening assays could be extended to a wider variety of cell lines to allow for identification of any deleterious effects of MOFs, with the range of toxic mechanisms to be differentiated based on cell viability, morphology and cell-substrate interactions, respectively. CONCLUSION: Our analysis highlights the importance of considering the physicochemical properties of MOFs when recommending a MOF-based therapeutic option or MOFs implementation in biomedical applications.

U.S. prescribing trends of fentanyl, opioids, and other pain medications in outpatient and emergency department visits from 2006 to 2015.

The United States is currently facing an epidemic of opioid-related deaths, increasingly associated with fentanyl use. Our objective was to characterize rates of fentanyl, general opioid and non-opioid pain medication prescription at a national level in both outpatient and emergency department settings. We used a retrospective cross-sectional research design using data from the 2006-2015 National Ambulatory Medical Care Surveys and National Hospital Ambulatory Medical Care Surveys. Between 2006-2015, 66,987 (17.4%) of 390,538 office-based outpatient visits (nationally-representative of 961 million visits) and 134,953 (45.0%) of 305,570 ED visits (nationally-representative of 130 million visits) listed a pain medication prescription. The proportion of all outpatient visits in which any pain medication was prescribed increased from 15.0% in 2006-2007 to 20.5% in 2014-2015 (p < 0.001). The proportion of all outpatient visits in which any fentanyl product was prescribed remained stable at 0.3% and 0.4% (p = 0.32), but increased among ED visits from 0.5% to 1.1% (p = 0.006). In contrast, the proportion of all outpatient visits in which any opioid product was prescribed increased from 6.6% to 9.7% (p < 0.001), but remained relatively stable among ED visits from 26.2% to 24.4% (p = 0.07). Non-opioid pain medication prescription increased in both settings, from 9.7% to 13.7% (p < 0.001) in the outpatient setting and from 25.6% to 27.6% (p = 0.02) in the ED setting between 2006-2007 and 2014-2015, respectively. To address current opioid crisis, both clinical and public health interventions are needed, such as targeted education outreach on evidence-based opioid prescribing and non-opioid alternatives.

Mycoplasma Pneumoniae Pericarditis.

Mycoplasma pneumoniae is an atypical bacterium that is frequently implicated in respiratory infections, but uncommonly identified as a cause of pericarditis. We report 2 cases of pericarditis attributed to M. pneumoniae that were characterized by prolonged respiratory prodromes, pericardial, and pleural effusions, elevated inflammatory markers, and relapsing clinical courses. In conclusion, our experience suggests that M. pneumoniae should be considered as a potential cause in cases of pericarditis associated with upper respiratory symptoms, pneumonia, pleural effusions, arthralgia, and/or a recurrent/refractory clinical course. The availability of effective antibiotic treatment makes this an important diagnosis to make.

Partial-volume correction increases estimated dopamine D2-like receptor binding potential and reduces adult age differences.

The relatively modest spatial resolution of positron emission tomography (PET) increases the likelihood of partial volume effects such that binding potential (BPND) may be underestimated. Given structural grey matter losses across adulthood, partial volume effects may be even more problematic in older age leading to overestimation of adult age differences. Here we examined the effects of partial volume correction (PVC) in two studies from different sites using different high-affinity D2-like radioligands (18 F-Fallypride, 11C-FLB457) and different PET camera resolutions (∼5 mm, 2.5 mm). Results across both data sets revealed that PVC increased estimated BPND and reduced, though did not eliminate, age effects on BPND. As expected, the effects of PVC were smaller in higher compared to lower resolution data. Analyses using uncorrected data that controlled for grey matter volume in each region of interest approximated PVC corrected data for some but not all regions. Overall, the findings suggest that PVC increases estimated BPND in general and reduces adult age differences especially when using lower resolution cameras. The findings suggest that the past 30 years of research on dopamine receptor availability, for which very few studies use PVC, may overestimate effects of aging on dopamine receptor availability.

PET imaging reveals lower kappa opioid receptor availability in alcoholics but no effect of age.

Opioid receptors are implicated in alcoholism, other addictions, withdrawal, and depression, and are considered potential pharmacological targets for treatment. Our goal in the present study was to compare the availability of kappa opioid receptors (KOR) between an alcohol-dependent cohort (AD) and a healthy control cohort (HC). Sixty-four participants-36 AD and 28 HC-underwent PET scans with [11C]LY2795050, a selective kappa antagonist tracer. Partial-volume correction was applied to all PET data to correct for atrophy. Volume of distribution (VT) of the tracer was estimated regionally as a measure of KOR availability. VT values of AD versus HC were compared for 15 defined ROIs. Multivariate analysis showed a main effect of group on VT across these 15 ROIs. Post hoc tests showed that AD had significantly lower VT and thus a lower KOR availability than HC in amygdala and pallidum (corrected for multiple comparisons). Exploratory analysis of change in VT with age was conducted; VT was not found to vary significantly with age in any region. Our findings of lower VT in AD versus HC in multiple regions are in contrast to findings in the mu and delta opioid receptor systems of higher VT in AD versus HC. Although age-related decline in receptors has previously been observed in the mu opioid receptor system, we found that KOR availability does not change with age.

Patterns and predictors of off-label prescription of psychiatric drugs.

Off-label prescribing of psychiatric drugs is common, despite lacking strong scientific evidence of efficacy and potentially increasing risk for adverse events. The goal of this study was to characterize prevalence of off-label prescriptions of psychiatric drugs and examine patient and clinician predictors of off-label use. This manuscript presents a retrospective, cross-sectional study using data from the 2012 and 2013 National Ambulatory Medical Care Surveys (NAMCS). The study examined all adult outpatient visits to psychiatric practices for chronic care management with a single listed visit diagnosis in which at least one psychiatric drug was prescribed. The main outcome measure was off-label prescribing of at least one psychiatric drug, defined as prescription for a condition for which it has not been approved for use by the FDA. Among our sample representative of 1.85 billion outpatient visits, 18.5 million (1.3%) visits were to psychiatrists for chronic care management in which at least one psychiatric drug was prescribed. Overall, the rate of off-label use was 12.9% (95% CI: 12.2-15.7). The most common off-label uses were for manic-depressive psychosis treated with citalopram and primary insomnia treated with trazodone. Several patient and clinician characteristics were positively associated with off-label prescribing, including seeing a psychiatrist (OR: 1.06, 95% CI, 1.01-1.12; p = 0.03) instead of another type of clinician, the office visit taking place in the Western region of the country (OR: 1.09, 95% CI, 1.01-1.17; p = 0.02), and the patient having 3 or more chronic conditions (OR: 1.12, 95% CI, 1.02-1.14; p = 0.003). In contrast, having Medicare coverage (OR: 0.93, 95% CI, 0.84-0.97; p = 0.04) and receiving payment assistance from a medical charity (OR: 0.91, 95% CI, 0.88-0.96; p = 0.03) instead of private insurance were negatively associated with off-label prescribing. These results suggest that certain classes of psychiatric medications are being commonly prescribed to treat conditions for which they have not been determined by the FDA to be clinically efficacious and/or safe.

HIV Testing and awareness of HIV status among people who inject drugs in greater Kuala Lumpur, Malaysia.

HIV testing services are the gateway into HIV treatment and are critical for monitoring the epidemic. HIV testing is recommended at least annually in high-risk populations, including people who inject drugs (PWID). In Malaysia, the HIV epidemic is concentrated among PWID, but their adherence to testing recommendations and the proportion of HIV-positive PWID who are aware of their status remain unknown. We recruited 460 PWID in Greater Kuala Lumpur using respondent-driven sampling and conducted HIV testing. We examined past testing behaviors, estimating testing frequency, correlates of testing in the past 12 months, and the proportion of those living with HIV who were aware of their status. Results showed that most PWID living with HIV (90.4%, 95% CI: 83.6%-95.9%) were aware of their status. Among those never previously diagnosed with HIV, few had accessed HIV testing in the past 12 months (14.3%, 95% CI: 11.1%-18.0%). Prison (57.0%) and compulsory drug detention centers (36.1%) were the primary locations where PWID reported ever being HIV tested, and the main correlate of recent testing in regression was recent criminal justice involvement. Although awareness of HIV status may be high among PWID living with HIV in Kuala Lumpur, testing occurs primarily in prisons and compulsory drug detention centers, where it is involuntary and linkage to care is limited. A shift in HIV testing policy is needed to align health and human rights objectives, replacing mandatory testing with voluntary testing in settings where individuals can be rapidly linked to HIV care.