Modeling the potential effects of rooftop solar on household energy burden in the United States.

Policymakers at the federal and state level have begun to incorporate energy burden into equity goals and program evaluations, aiming to reduce energy burden below a high level of 6% for lower income households in the United States. Pairing an empirical household-level dataset spanning United States geographies together with modeled hourly energy demand curves, we show that rooftop solar reduces energy burden across a majority of adopters during our study period from a median of 3.3% to 2.6%. For low- and moderate-income adopters (at or below 80% and 120% of area median income, respectively), solar reduces median 2021 energy burden from 7.7% to 6.2%, and 4.1% to 3.3%, respectively. Importantly, solar reduces the rate of high or severe energy burden from 67% of all low-income households before adoption to 52% of households following adoption, and correspondingly from 21% to 13% for moderate-income households. Here, we show rooftop solar can support policy goals to reduce energy burden along with strategies such as weatherization and bill assistance.

Development of a Complex Care Transition Team to Improve the Transition of Patients With Complex Care Needs to the Community.

PURPOSE: Health care systems have historically struggled to provide adequate care for patients with complex care needs that often result in overuse of hospital and emergency department resources. Patients with complex care needs generally have increased expenses, longer length of hospital stays, an increased need for care management resources during hospitalization, and high readmission rates. Mayo Clinic in Arizona aimed to ensure successful transitions for hospitalized patients with complex care needs to the community by developing a complex care transition team (CCTT) program. With typical care management models, patients are assigned to registered nurse case managers and social workers according to the inpatient nursing unit rather than patient care complexity. Patients with complex care needs may not receive the amount of time needed to ensure an efficient and effective transition to the community setting. Furthermore, after transitioning to the community, patients with complex care needs often do not have access to care management resources if further care coordination needs arise. PRIMARY PRACTICE SETTING: Acute care hospital in the US Southwest. METHODOLOGY AND SAMPLE: The CCTT was composed of a registered nurse case manager, social worker, and care management assistant, with physician advisor support. The CCTT followed patients with complex care needs during their hospitalization and transition to the community for 90 days after discharge. The number of inpatient admissions and hospital readmission rates were compared between 6 months before and after enrollment in the CCTT program. Cost savings for decreased hospital length of stay, emergency department visits, and hospital readmissions were also determined. RESULTS: The CCTT selected patients according to a complex care algorithm , which identified patients who required high use of the health care system. The CCTT then followed this cohort of patients for an average of 90 days after discharge. A total of 123 patients were enrolled in the CCTT program from July 1, 2019, to April 30, 2021, and 80 patients successfully graduated from the program. Readmission rates decreased from 51.2% at 6 months before the intervention to 22.0% at 6 months after the intervention. This reduced readmission rate resulted in a cost savings of more than $1 million. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: The outcomes resulting from implementation of the multidisciplinary CCTT highlight the need for a patient-specific approach to transitioning care to the outpatient setting. The patient social determinants of health that often contributed to overuse of health care resources included poor access to outpatient specialists, difficulty navigating the health care system due to illness or poor health literacy, and limited social support. The success of the CCTT program prompted the implementation of other specialty-specific pilot programs at Mayo Clinic in Arizona. The investment of time and resources, including dedicated personnel to follow patients with high hospital service usage, allows health care systems to reduce emergency department visits and hospital admissions and to provide patients with the best opportunity for success as they transition from the inpatient to outpatient setting.

Sex difference in the effect of environmental enrichment on food restriction-induced persistence of cocaine conditioned place preference and mechanistic underpinnings.

Psychosocial and environmental factors, including loss of natural reward, contribute to the risk of drug abuse. Reward loss has been modeled in animals by removal from social or sexual contact, transfer from enriched to impoverished housing, or restriction of food. We previously showed that food restriction increases the unconditioned rewarding effects of abused drugs and the conditioned incentive effects of drug-paired environments. Mechanistic studies provided evidence of decreased basal dopamine (DA) transmission, adaptive upregulation of signaling downstream of D1 DA receptor stimulation, synaptic upscaling and incorporation of calcium-permeable AMPA receptors (CP-AMPARs) in medium spiny neurons (MSNs) of nucleus accumbens (NAc). These findings align with the still evolving 'reward deficiency' hypothesis of drug abuse. The present study tested whether a compound natural reward that is known to increase DA utilization, environmental enrichment, would prevent the persistent expression of cocaine conditioned place preference (CPP) otherwise observed in food restricted rats, along with the mechanistic underpinnings. Because nearly all prior investigations of both food restriction and environmental enrichment effects on cocaine CPP were conducted in male rodents, both sexes were included in the present study. Results indicate that environmental enrichment curtailed the persistence of CPP expression, decreased signaling downstream of the D1R, and decreased the amplitude and frequency of spontaneous excitatory postsynaptic currents (EPSCs) in NAc MSNs of food restricted male, but not female, rats. The failure of environmental enrichment to significantly decrease food restriction-induced synaptic insertion of CP-AMPARs, and how this may accord with previous pharmacological findings that blockade of CP-AMPARs reverses behavioral effects of food restriction is discussed. In addition, it is speculated that estrous cycle-dependent fluctuations in DA release, receptor density and MSN excitability may obscure the effect of increased DA signaling during environmental enrichment, thereby interfering with development of the cellular and behavioral effects that enrichment produced in males.

Patient Attitudes Toward Deprescribing Among Community-Dwelling Older Mainers.

Background The excess use of medications has become an increasingly prevalent issue in health care. Deprescribing can be an important tool in combating polypharmacy. Objective To assess the attitudes of community-dwelling older persons in Maine toward their medications and the concept of deprescription. An additional aim of this research was to assess the association between the revised Patient Attitudes Toward Deprescribing Questionnaire (rPATDQ) domains by polypharmacy status. Methods Researchers conducted a cross-sectional study utilizing the rPATDQ. Authors recruited older Mainers via a longitudinal cohort study through the University of New England Center for Excellence in Aging in Health. Respondents were stratified by polypharmacy status (fewer than five medications, five or more medications). Results Total daily medications ranged from 1 to 30 (average of 8.6). Overall, 83.6% of respondents agreed/strongly agreed to the statement "If my doctor said it was possible, I would be willing to stop one or more of my regular medicines." 70.6% agreed/ strongly agreed to the statement "Overall, I am satisfied with my current medicines." Those with and without polypharmacy experienced low overall medication burden and a high belief in the appropriateness of their medications. There were no statistically significant differences between polypharmacy groups. Conclusion The results of this survey indicate that the factors affecting attitudes toward deprescribing are complex. While many indicated willingness to deprescribe at least one medication, there was a high degree of satisfaction with current medication regimens. This study highlights the need for further qualitative research to identify potential barriers to deprescribing.

Open access repository-scale propagated nearest neighbor suspect spectral library for untargeted metabolomics.

Despite the increasing availability of tandem mass spectrometry (MS/MS) community spectral libraries for untargeted metabolomics over the past decade, the majority of acquired MS/MS spectra remain uninterpreted. To further aid in interpreting unannotated spectra, we created a nearest neighbor suspect spectral library, consisting of 87,916 annotated MS/MS spectra derived from hundreds of millions of MS/MS spectra originating from published untargeted metabolomics experiments. Entries in this library, or "suspects," were derived from unannotated spectra that could be linked in a molecular network to an annotated spectrum. Annotations were propagated to unknowns based on structural relationships to reference molecules using MS/MS-based spectrum alignment. We demonstrate the broad relevance of the nearest neighbor suspect spectral library through representative examples of propagation-based annotation of acylcarnitines, bacterial and plant natural products, and drug metabolism. Our results also highlight how the library can help to better understand an Alzheimer's brain phenotype. The nearest neighbor suspect spectral library is openly available for download or for data analysis through the GNPS platform to help investigators hypothesize candidate structures for unknown MS/MS spectra in untargeted metabolomics data.

Leptin receptor neurons in the dorsomedial hypothalamus input to the circadian feeding network.

Salient cues, such as the rising sun or availability of food, entrain biological clocks for behavioral adaptation. The mechanisms underlying entrainment to food availability remain elusive. Using single-nucleus RNA sequencing during scheduled feeding, we identified a dorsomedial hypothalamus leptin receptor-expressing (DMHLepR) neuron population that up-regulates circadian entrainment genes and exhibits calcium activity before an anticipated meal. Exogenous leptin, silencing, or chemogenetic stimulation of DMHLepR neurons disrupts the development of molecular and behavioral food entrainment. Repetitive DMHLepR neuron activation leads to the partitioning of a secondary bout of circadian locomotor activity that is in phase with the stimulation and dependent on an intact suprachiasmatic nucleus (SCN). Last, we found a DMHLepR neuron subpopulation that projects to the SCN with the capacity to influence the phase of the circadian clock. This direct DMHLepR-SCN connection is well situated to integrate the metabolic and circadian systems, facilitating mealtime anticipation.

Involvement of the Receptor for Advanced Glycation End Products (RAGE) in high fat-high sugar diet-induced anhedonia in rats.

Clinical and basic science investigation indicates a link between insulin resistance and anhedonia. Previous results of this laboratory point to impaired nucleus accumbens (NAc) insulin signaling as an underpinning of diet-induced anhedonia, based on use of a glucose lick microstructure assay. The present study evaluated whether advanced glycation end products (AGEs) and their receptor (RAGE), known to mediate obesogenic diet-induced inflammation and pathological metabolic conditions, are involved in this behavioral change. Six weeks maintenance of male and female rats on a high fat-high sugar liquid diet (chocolate Ensure) increased body weight gain, and markedly increased circulating insulin and leptin, but induced anhedonia (decreased first minute lick rate and lick burst size) in males only. In these subjects, anhedonia correlated with plasma concentrations of insulin. Although the diet did not alter plasma or NAc AGEs, or the expression of RAGE in the NAc, marginally significant correlations were seen between anhedonia and plasma content of several AGEs and NAc RAGE. Importantly, a small molecule RAGE antagonist, RAGE229, administered twice daily by oral gavage, prevented diet-induced anhedonia. This beneficial effect was associated with improved adipose function, reflected in the adiponectin/leptin ratio, and increased pCREB/total CREB in the NAc, and a shift in the pCREB correlation with pThr34-DARPP-32 from near-zero to strongly positive, such that both phospho-proteins correlated with the rescued hedonic response. This set of findings suggests that the receptor/signaling pathway and cell type underlying the RAGE229-mediated increase in pCREB may mediate anhedonia and its prevention. The possible role of adipose tissue as a locus of diet-induced RAGE signaling, and source of circulating factors that target NAc to modify hedonic reactivity are discussed.

Urine Excretion, Organ Distribution, and Placental Transfer of 6PPD and 6PPD-Quinone in Mice and Potential Developmental Toxicity through Nuclear Receptor Pathways.

The rubber antioxidant 6PPD has gained significant attention due to its highly toxic transformation product, 6PPD-quinone (6PPDQ). Despite their detection in urines of pregnant women, the placental transfer and developmental toxicity of 6PPD and 6PPDQ are unknown. Here, we treated C57Bl/6 mice with 4 mg/kg 6PPD or 6PPDQ to investigate their urine excretion and placental transfer. Female and male mice exhibited sex difference in excretion profiles of 6PPD and 6PPDQ. Urine concentrations of 6PPDQ were one order of magnitude lower than those of 6PPD, suggesting lower excretion and higher bioaccumulation of 6PPDQ. In pregnant mice treated with 6PPD or 6PPDQ from embryonic day 11.5 to 15.5, 6PPDQ showed ∼1.5-8 times higher concentrations than 6PPD in placenta, embryo body, and embryo brain, suggesting higher placental transfer of 6PPDQ. Using in vitro dual-luciferase reporter assays, we revealed that 6PPDQ activated the human retinoic acid receptor α (RARα) and retinoid X receptor α (RXRα) at concentrations as low as 0.3 µM, which was ∼10-fold higher than the concentrations detected in human urines. 6PPD activated the RXRα at concentrations as low as 1.2 µM. These results demonstrate the exposure risks of 6PPD and 6PPDQ during pregnancy and emphasize the need for further toxicological and epidemiological investigations.

A technology-enabled multi-disciplinary team-based care model for the management of Long COVID and other fatiguing illnesses within a federally qualified health center: protocol for a two-arm, single-blind, pragmatic, quality improvement professional cluster randomized controlled trial.

BACKGROUND: The clinical burden of Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other post-infectious fatiguing illnesses (PIFI) is increasing. There is a critical need to advance understanding of the effectiveness and sustainability of innovative approaches to clinical care of patients having these conditions. METHODS: We aim to assess the effectiveness of a Long COVID and Fatiguing Illness Recovery Program (LC&FIRP) in a two-arm, single-blind, pragmatic, quality improvement, professional cluster, randomized controlled trial in which 20 consenting clinicians across primary care clinics in a Federally Qualified Health Center system in San Diego, CA, will be randomized at a ratio of 1:1 to either participate in (1) weekly multi-disciplinary team-based case consultation and peer-to-peer sharing of emerging best practices (i.e., teleECHO (Extension for Community Healthcare Outcomes)) with monthly interactive webinars and quarterly short courses or (2) monthly interactive webinars and quarterly short courses alone (a control group); 856 patients will be assigned to participating clinicians (42 patients per clinician). Patient outcomes will be evaluated according to the study arm of their respective clinicians. Quantitative and qualitative outcomes will be measured at 3- and 6-months post-baseline for clinicians and every 3-months post assignment to a participating clinician for patients. The primary patient outcome is change in physical function measured using the Patient-Reported Outcomes Measurement Information System (PROMIS)-29. Analyses of differences in outcomes at both the patient and clinician levels will include a linear mixed model to compare change in outcomes from baseline to each post-baseline assessment between the randomized study arms. A concurrent prospective cohort study will compare the LC&FIRP patient population to the population enrolled in a university health system. Longitudinal data analysis approaches will allow us to examine differences in outcomes between cohorts. DISCUSSION: We hypothesize that weekly teleECHO sessions with monthly interactive webinars and quarterly short courses will significantly improve clinician- and patient-level outcomes compared to the control group. This study will provide much needed evidence on the effectiveness of a technology-enabled multi-disciplinary team-based care model for the management of Long COVID, ME/CFS, and other PIFI within a federally qualified health center. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05167227 . Registered on December 22, 2021.

Student Perspectives on the Pharmacist's Role in Deprescribing Opioids: A Qualitative Study.

INTRODUCTION: Opioid over-prescribing has led to changes in prescribing habits and a reduction in the amount of opioid prescriptions per patient. Deprescribing has proved to be an effective way of decreasing the number of opioids patients are receiving, and pharmacists are in the optimal position to provide these services for their patients. However, student pharmacists require additional education and training to be able to understand their role in deprescribing opioids upon entering the profession. METHODS: Student pharmacists at three United States of America schools of pharmacy were invited to participate in virtual focus groups about deprescribing opioids in Fall 2021. A trained qualitative researcher conducted the focus groups, which were audio-recorded and later transcribed verbatim for thematic analysis. Two independent qualitative researchers coded the transcripts using both inductive and deductive approaches. The researchers then met to identify, discuss, and describe themes from the data. RESULTS: Thematic analysis revealed two themes: (1) perceived obstacles and enablers to initiate deprescribing for opioid medications and (2) additional pharmacy curricula experiences are necessary to better equip student pharmacists to address deprescribing. These themes emphasize the challenges student pharmacists face as well as opportunities to enhance their knowledge to be practice-ready. CONCLUSION: Varying educational approaches to teaching deprescribing in the pharmacy curriculum, including objective structured clinical exams, interprofessional education, and motivational interviewing, should be further assessed.

Temporal changes in glucose metabolism reflect polarization in resident and monocyte-derived macrophages after myocardial infarction.

Introduction: Metabolic reprogramming from glycolysis to the mitochondrial tricarboxylic acid (TCA) cycle and oxidative phosphorylation may mediate macrophage polarization from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype. We hypothesized that changes in cardiac macrophage glucose metabolism would reflect polarization status after myocardial infarction (MI), ranging from the early inflammatory phase to the later wound healing phase. Methods: MI was induced by permanent ligation of the left coronary artery in adult male C57BL/6J mice for 1 (D1), 3 (D3), or 7 (D7) days. Infarct macrophages were subjected to metabolic flux analysis or gene expression analysis. Monocyte versus resident cardiac macrophage metabolism was assessed using mice lacking the Ccr2 gene (CCR2 KO). Results: By flow cytometry and RT-PCR, D1 macrophages exhibited an M1 phenotype while D7 macrophages exhibited an M2 phenotype. Macrophage glycolysis (extracellular acidification rate) was increased at D1 and D3, returning to basal levels at D7. Glucose oxidation (oxygen consumption rate) was decreased at D3, returning to basal levels at D7. At D1, glycolytic genes were elevated (Gapdh, Ldha, Pkm2), while TCA cycle genes were elevated at D3 (Idh1 and Idh2) and D7 (Pdha1, Idh1/2, Sdha/b). Surprisingly, Slc2a1 and Hk1/2 were increased at D7, as well as pentose phosphate pathway (PPP) genes (G6pdx, G6pd2, Pgd, Rpia, Taldo1), indicating increased PPP activity. Macrophages from CCR2 KO mice showed decreased glycolysis and increased glucose oxidation at D3, and decreases in Ldha and Pkm2 expression. Administration of dichloroacetate, a pyruvate dehydrogenase kinase inhibitor, robustly decreased pyruvate dehydrogenase phosphorylation in the non-infarcted remote zone, but did not affect macrophage phenotype or metabolism in the infarct zone. Discussion: Our results indicate that changes in glucose metabolism and the PPP underlie macrophage polarization following MI, and that metabolic reprogramming is a key feature of monocyte-derived but not resident macrophages.

A leptin-responsive hypothalamic circuit inputs to the circadian feeding network.

Salient cues, such as the rising sun or the availability of food, play a crucial role in entraining biological clocks, allowing for effective behavioral adaptation and ultimately, survival. While the light-dependent entrainment of the central circadian pacemaker (suprachiasmatic nucleus, SCN) is relatively well defined, the molecular and neural mechanisms underlying entrainment associated with food availability remains elusive. Using single nucleus RNA sequencing during scheduled feeding (SF), we identified a leptin receptor (LepR) expressing neuron population in the dorsomedial hypothalamus (DMH) that upregulates circadian entrainment genes and exhibits rhythmic calcium activity prior to an anticipated meal. We found that disrupting DMHLepR neuron activity had a profound impact on both molecular and behavioral food entrainment. Specifically, silencing DMHLepR neurons, mis-timed exogenous leptin administration, or mis-timed chemogenetic stimulation of these neurons all interfered with the development of food entrainment. In a state of energy abundance, repetitive activation of DMHLepR neurons led to the partitioning of a secondary bout of circadian locomotor activity that was in phase with the stimulation and dependent on an intact SCN. Lastly, we discovered that a subpopulation of DMHLepR neurons project to the SCN with the capacity to influence the phase of the circadian clock. This leptin regulated circuit serves as a point of integration between the metabolic and circadian systems, facilitating the anticipation of meal times.

Teaching Deprescribing and Combating Polypharmacy in the Pharmacy Curriculum: Educational Recommendations from Thematic Analysis of Focus Groups.

In the last two decades in the United States (US), the previous research has focused on medication optimization, including polypharmacy. Polypharmacy is associated with several negative outcomes, which may be resolved by deprescribing medications that are no longer necessary. Although deprescribing is a critical aspect of a pharmacist's role, some studies have demonstrated that student pharmacists are less familiar with their future role in deprescribing. Thus, this study aimed to explore student pharmacists' perceptions of deprescribing in the pharmacy curriculum. This qualitative study was conducted with student pharmacists enrolled in three Doctor of Pharmacy (Pharm.D.) programs in the US. The participants, all student pharmacists at the time of the study, were identified via an email requesting their voluntary participation in a focus group study. The focus groups were conducted via an online platform over three months in 2022, and recruitment continued until thematic saturation was obtained. Using thematic analysis, the corpus of the transcribed data was imported into Dedoose®, a qualitative software that facilitated the analysis. Three themes emerged from the data: (1) the importance of deprescribing; (2) barriers to deprescribing; (3) education recommendations. The data highlight that the student pharmacists believe integrating deprescribing content into the clinical, didactic, and simulation education would help them overcome the identified obstacles. Colleges of pharmacy should consider emphasizing the importance of deprescribing in their curriculum, creating programs to assist future pharmacists in addressing the barriers to deprescribing, and adopting the suggested educational strategies to improve the deprescribing education that is offered.

COVID-19 monoclonal antibody treatment impact on symptoms and post-COVID conditions among high-risk patients at a Federally Qualified Health Center.

BACKGROUND: Monoclonal antibody (mAb) treatment for COVID-19 is associated with improved clinical outcomes. However, there is limited information regarding the impact of treatment on symptoms and the prevalence of post-COVID Conditions (PCC). Understanding of the association between time to mAb infusion and the development of PCC is also limited. METHODS: This longitudinal study was conducted among patients with COVID-19 who received mAb infusions at a Federally Qualified Health Center in San Diego, CA. A series of telephone interviews were conducted at baseline and follow-up (14 days and 28+ days). A comprehensive symptom inventory was completed and physical and mental health status were measured using PROMIS-29 and PHQ-2. Pearson's Chi-squared tests and independent two-sample t-tests were performed to test for association between time to mAb infusion and outcomes at follow-up. A Poisson regression model was used to analyze whether time to mAb infusion predicts risk of developing PCC. RESULTS: Participants (N = 411) were 53% female, ranged in age from 16 to 92 years (mean 50), and a majority (56%) were Latino/Hispanic. Cross-sectional findings revealed a high symptom burden at baseline (70% of patients had cough, 50% had fever, and 44% had headache). The prevalence of many symptoms decreased substantially by the final follow-up survey (29% of patients had cough, 3% had fever, and 28% had headache). Longitudinal findings indicated that 10 symptoms decreased in prevalence from baseline to final follow-up, 2 remained the same, and 14 increased. The severity of symptoms and most patient-reported physical and mental health measure scores decreased over time. The prevalence of PCC was 69% when PCC was defined as ≥ 1 symptom at final follow-up. Time to mAb infusion was not significantly associated with any outcome at follow-up. Time to infusion was not associated with PCC status at final follow-up in the crude or adjusted Poisson regression models. CONCLUSIONS: The prevalence of PCC was high among this patient population following COVID-19 mAb treatment. Time to mAb infusion did not predict the development of PCC. Further research in these areas is essential to answer urgent clinical questions about effective treatments of COVID-19.

Unexpected Term Neonatal Intensive Care Unit Admissions and a Potential Role for Centralized Remote Fetal Monitoring.

OBJECTIVE: Centralized remote fetal monitoring (CRFM) has been proposed as a method to improve the performance of intrapartum fetal heart rate (FHR) monitoring and perinatal outcomes. The purpose of this study is to determine whether CRFM was associated with a reduction in unexpected term neonatal intensive care unit (NICU) admissions. STUDY DESIGN: A pre-post design was used to examine the effectiveness of CRFM which was implemented in stages across five hospitals. The exposure group was all women who underwent intrapartum monitoring via CRFM. The unexposed group was of women who delivered at the same hospitals prior to implementation of CRFM. Pregnancies with expected NICU admissions, gestational age <37 weeks, birth weight <2,500 g, or major fetal anomalies detected prenatally were excluded. The primary outcome was unexpected term NICU admission; secondary outcomes were cesarean and operative vaginal delivery (OVD), and 5-minute Apgar's score of <7 rates. Maternal and delivery characteristics were examined with Student's t, Wilcoxon's, Chi-square, and Fisher's exact tests. Multivariable logistic regression was performed to control for potential confounders. RESULTS: There were 19,392 live births included in this analysis. In the univariable analysis, the odds of unexpected term NICU admission was lower among the CRFM exposed group compared with the unexposed group (odds ratio [OR] = 0.86, 95% confidence interval [CI]: 0.75-0.99; p = 0.038). In multivariable analysis, this did not reach statistical significance (OR = 0.92, 95% CI: 0.79-1.06; p = 0.24). Cesarean and OVD were less likely in the exposed group (OR = 0.91, 95% CI: 0.85-0.97; p = 0.008) and (OR = 0.70, 95% CI: 0.59-0.83, p < 0.001), respectively, in univariable analysis. When adjusted for potential confounders, the effect remained statistically significant for cesarean delivery (OR = 0.92, 95% CI: 0.85-0.98; p = 0.012). When adjusted for hospital, OVD rate was lower at the highest volume and highest acuity site (OR = 0.48, 95% CI: 0.36-0.65, p < 0.001). CONCLUSION: In some practice settings, utilization of a CRFM system may decrease the risk of unexpected term NICU admission, cesarean, and OVD rate. KEY POINTS: · CRFM may decrease unexpected term NICU admissions in some clinical settings.. · CRFM may decrease cesarean delivery rates in some clinical settings.. · CRFM may decrease OVD rates in some clinical settings..

Transfer of antibiotics and their metabolites in human milk: Implications for infant health and microbiota.

Antibiotics are an essential tool for perinatal care. While antibiotics can play a life-saving role for both parents and infants, they also cause collateral damage to the beneficial bacteria that make up the host gut microbiota. This is especially true for infants, whose developing gut microbiota is uniquely sensitive to antibiotic perturbation. Emerging evidence suggests that disruption of these bacterial populations during this crucial developmental window can have long-term effects on infant health and development. Although most current studies have focused on microbial disruptions caused by direct antibiotic administration to infants or prenatal exposure to antibiotics administered to the mother, little is known about whether antibiotics in human milk may pose similar risks to the infant. This review surveys current data on antibiotic transfer during lactation and highlights new methodologies to assess drug transfer in human milk. Finally, we provide recommendations for future work to ensure antibiotic use in lactating parents is safe and effective for both parents and infants.

Trimethylamine N-Oxide Reduces Neurite Density and Plaque Intensity in a Murine Model of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is the most common aging-associated neurodegenerative disease; nevertheless, the etiology and progression of the disease is still incompletely understood. We have previously shown that the microbially-derived metabolite trimethylamine N-oxide (TMAO) is elevated in the cerebrospinal fluid (CSF) of individuals with cognitive impairment due to AD and positively correlates with increases in CSF biomarkers for tangle, plaque, and neuronal pathology. OBJECTIVE: We assessed the direct impact of TMAO on AD progression. METHODS: To do so, transgenic 5XFAD mice were supplemented with TMAO for 12 weeks. Neurite density was assessed through quantitative brain microstructure imaging with neurite orientation dispersion and density imaging magnetic resonance imaging (MRI). Label-free, quantitative proteomics was performed on cortex lysates from TMAO-treated and untreated animals. Amyloid-ß plaques, astrocytes, and microglia were assessed by fluorescent immunohistochemistry and synaptic protein expression was quantified via western blot. RESULTS: Oral TMAO administration resulted in significantly reduced neurite density in several regions of the brain. Amyloid-ß plaque mean intensity was reduced, while plaque count and size remained unaltered. Proteomics analysis revealed that TMAO treatment impacted the expression of 30 proteins (1.5-fold cut-off) in 5XFAD mice, including proteins known to influence neuronal health and amyloid-ß precursor protein processing. TMAO treatment did not alter astrocyte and microglial response nor cortical synaptic protein expression. CONCLUSION: These data suggest that elevated plasma TMAO impacts AD pathology via reductions in neurite density.

"I Think Deprescribing as a Whole Is a Gap!": A Qualitative Study of Student Pharmacist Perceptions about Deprescribing.

INTRODUCTION: Older adults often manage multiple medications simultaneously, contributing to significant pill burden. Pill burden is a major concern for both patients and providers alike, and student pharmacists may play a role in decreasing that burden. Few studies exist evaluating student pharmacists' roles in and perceptions of deprescribing in the healthcare team. Thus, the aim of this study was to explore student pharmacist perceptions regarding deprescribing in their pharmacy curricula. METHODS: This study used a focus group discussion (FGD) methodology to facilitate discussion on deprescribing among student pharmacists. The theory of planned behavior (TPB) informed the conceptualization of this study, data collection, and thematic analysis. Student pharmacists enrolled in three different colleges of pharmacy across various geographical regions of the U.S. were recruited to participate in the study. Data collection occurred in the Fall of 2021, and recruitment proceeded until thematic saturation was achieved. The audio recordings were transcribed verbatim, and the transcripts were uploaded into Dedoose®, a qualitative software that facilitated the data analysis. The inductive codes were grouped into categories based on similarities that resulted in the themes. RESULTS: Three colleges, totaling 1366 student pharmacists across different geographic regions of the U.S., were invited to participate in this study (UTHSC, N = 682; UNE, N = 158, University of Arizona, N = 526). Twenty-six student pharmacists participated in four FGDs. Of 26 participants, fourteen self-identified as male and two declined to state their gender identity. The mean age was 24 years old, with participants ranging from 21 to 37 years old. Thematic analysis revealed two major themes: (1) student pharmacists indicated that they possessed limited information about the deprescribing process, which is best illustrated by the following quote: "I think deprescribing as a whole is a gap!"; and (2) student pharmacists recommended increasing emphasis on deprescribing in pharmacy curricula. CONCLUSIONS: Student pharmacists identified few educational experiences on deprescribing in their curriculum while demonstrating a strong desire for more emphasis on deprescribing in the pharmacy curricula. This study highlights an opportunity to improve the integration of deprescribing education into pharmacy curricula, and colleges of pharmacy should evaluate whether, where, and to what extent the incorporation of this topic into their curricula is appropriate.

Effect of Deintensifying Diabetes Medications on Negative Events in Older Veteran Nursing Home Residents.

OBJECTIVE: Guidelines advocate against tight glycemic control in older nursing home (NH) residents with advanced dementia (AD) or limited life expectancy (LLE). We evaluated the effect of deintensifying diabetes medications with regard to all-cause emergency department (ED) visits, hospitalizations, and death in NH residents with LLE/AD and tight glycemic control. RESEARCH DESIGN AND METHODS: We conducted a national retrospective cohort study of 2,082 newly admitted nonhospice veteran NH residents with LLE/AD potentially overtreated for diabetes (HbA1c ≤7.5% and one or more diabetes medications) in fiscal years 2009-2015. Diabetes treatment deintensification (dose decrease or discontinuation of a noninsulin agent or stopping insulin sustained ≥7 days) was identified within 30 days after HbA1c measurement. To adjust for confounding, we used entropy weights to balance covariates between NH residents who deintensified versus continued medications. We used the Aalen-Johansen estimator to calculate the 60-day cumulative incidence and risk ratios (RRs) for ED or hospital visits and deaths. RESULTS: Diabetes medications were deintensified for 27% of residents. In the subsequent 60 days, 28.5% of all residents were transferred to the ED or acute hospital setting for any cause and 3.9% died. After entropy weighting, deintensifying was not associated with 60-day all-cause ED visits or hospitalizations (RR 0.99 [95% CI 0.84, 1.18]) or 60-day mortality (1.52 [0.89, 2.81]). CONCLUSIONS: Among NH residents with LLE/AD who may be inappropriately overtreated with tight glycemic control, deintensification of diabetes medications was not associated with increased risk of 60-day all-cause ED visits, hospitalization, or death.