Self-administered gerocognitive examination (SAGE) aids early detection of cognitive impairment at primary care provider visits.

Introduction: Current estimates indicate that up to 50-75% of dementia cases are undiagnosed at an early stage when treatments are most effective. Conducting robust accurate cognitive assessments can be time-consuming for providers and difficult to incorporate into a time-limited Primary Care Provider (PCP) visit. We wanted to compare PCP visits with and without using the self-administered SAGE to determine differences in identification rates of new cognitive disorders. Methods: Three hundred patients aged 65-89 without diagnosed cognitive disorders completing a non-acute office visit were enrolled (ClinicalTrials.gov identifier: NCT04063371). Two PCP offices conducted routine visits for 100 consecutive eligible patients each. One office used the SAGE in an additional 100 subjects and asked available informants about cognitive changes over the previous year. Chart reviews were conducted 60 days later. One-way analysis of variance and Fisher exact tests were used to compare the groups and outcomes. Results: When SAGE was utilized, the PCP documented the detection of new cognitive conditions/concerns six times (9% versus 1.5%) as often (p = 0.003). The detection rate was nearly 4-fold for those with cognitively impaired SAGE scores (p = 0.034). Patients having impaired SAGE score and informant concerns were 15-fold as likely to have new cognitive conditions/concerns documented (p = 0.0007). Among providers using SAGE, 86% would recommend SAGE to colleagues. Discussion: SAGE was easily incorporated into PCP visits and significantly increased identification of new cognitive conditions/concerns leading to new diagnoses, treatment, or management changes. The detection rate increased 15-fold for those with impaired SAGE scores combined with informant reports.

Initiation of medication for opioid use disorder across a health system: A retrospective analysis of patient characteristics and inpatient outcomes.

Objectives: Medication for opioid use disorder (MOUD) has gained significant momentum as an evidence-based intervention for treating opioid use disorder (OUD). The purpose of this study was to characterize MOUD initiations for buprenorphine and extended release (ER) naltrexone across all care sites at a major health system in the Midwest and determine whether MOUD initiation was associated with inpatient outcomes. Methods: The study population comprised patients with OUD in the health system between 2018 and 2021. First, we described characteristics of all MOUD initiations for the study population within the health system. Second, we compared inpatient length of stay (LOS) and unplanned readmission rates between patients prescribed MOUD and patients not prescribed MOUD, including a pre-post comparison of patients prescribed MOUD before versus after initiation. Results: The 3,831 patients receiving MOUD were mostly white, non-Hispanic and generally received buprenorphine over ER naltrexone. 65.5% of most recent initiations occurred in an inpatient setting. Compared to those not prescribed MOUD, inpatient encounters where patients received MOUD on or before the admission date were significantly less likely to be unplanned readmissions (13% vs. 20%, p < 0.001) and their LOS was 0.14 days shorter (p = 0.278). Among patients prescribed MOUD, there was a significant reduction in the readmission rate after initiation compared to before (13% vs. 22%, p < 0.001). Conclusions: This study is the first to examine MOUD initiations for thousands of patients across multiple care sites in a health system, finding that receiving MOUD is associated with clinically meaningful reductions in readmission rates.

An Ambulatory Care Clinic and Community Pharmacy Collaboration to Address Prescription Abandonment.

PURPOSE: The purpose of this research is to evaluate a collaborative workflow aimed at decreasing prescription abandonment. SETTING: A federally qualified health center and a 340B contracted grocery store-based community pharmacy. PRACTICE WORKFLOW: An ambulatory care clinic with an established partnership with a community pharmacy chain identified a need to decrease prescription abandonment rates. A process was developed whereby an ambulatory care pharmacy technician received a report from the pharmacy of prescriptions filled for at least 7 days since the initial fill date and at risk for abandonment at the community pharmacy. The pharmacy technician identified health-system barriers, attempted to remedy any identified barriers, and conducted patient reminder phone calls. Health-system barriers were classified by the following categories: incorrect contact information at the community pharmacy, incorrect 340B copayment, incorrect insurance information at the community pharmacy, and need for prior authorization. EVALUATION: A prospective cohort study was conducted from February 2016 to April 2016 in order to evaluate the effectiveness of this workflow. RESULTS: 551 prescriptions and 350 patients were included in this cohort. Of the 551 prescriptions, 362 had at least one identified barrier that may have led to prescription abandonment. There were 111 health-system identified barriers, and 96 of these barriers were acted upon. Additionally, there were 459 patient identified barriers, and 179 of these barriers were acted upon. When a pharmacy technician was able to identify and act upon at least one barrier, 106 prescriptions (46.9%) were picked-up from the pharmacy. CONCLUSION: From the information gathered in this quality improvement project, operational changes have been implemented at the ambulatory care clinic and community pharmacy as a means to further decrease modifiable health-system barriers that may lead to prescription abandonment.

Impact of a Pharmacist-Provided Spirometry Service on Access to Results in a Primary Care Setting.

OBJECTIVES: The primary objective of this study was to determine the effect of a pharmacist-provided spirometry service within a federally qualified health center on the percentage of spirometry referrals completed with results reviewed by the ordering provider. Secondary objectives evaluated differences between internal and external referrals, medication recommendations made by the pharmacist, and revenue brought in by the service. METHODS: Chart reviews were completed to determine the referral completion rates between patients who received a spirometry referral before (December 2014-September 2015) and after (January 2016-October 2016) the implementation of the pharmacy-provided spirometry service. Chart reviews were also used to determine the number and completion rate among referrals for internal and external services in the postimplementation time frame. Chart reviews also assessed medication recommendations made by the pharmacist. RESULTS: The results demonstrate an increase in referral completion rate from 38.1% to 47.0% ( P = .08) between the pre- and postimplementation time frames. In the postimplementation time frame, there was a statistically significant difference in the percentage of referrals completed between in-house referrals and external referrals (70.0% and 40.9%, respectively, P = .0004). Comparing clinics with and without the spirometry service, there was a statistically significant difference in the total number of spirometry referrals (1.13% and 0.59%, respectively, P < .0001) and the percent of referrals completed (0.55% and 0.27%, respectively, P = .0002). CONCLUSION: The results suggest that offering spirometry within the primary care setting helps to increase the rate of completed spirometry tests with results available to the primary care provider. Additionally, the results show that there is an increased completion rate in patients who receive an internal spirometry referral, which may be due to reduced barriers in obtaining this testing. Overall, these results demonstrate that providing spirometry in the primary care setting helps to increase spirometry results obtained and could be beneficial in other primary care settings.

Seasonal modulation of testosterone during breeding of the rufous-collared sparrow (Zonotrichia capensis australis) in Southern Patagonia.

The roles of testosterone (T) during reproduction are often complex and vary among and within vertebrate taxa and locations, making general hypotheses relating T to breeding behavior and success difficult to integrate. In birds, T is thought to influence degrees of territoriality and associated aggression in males to maximize breeding success. Importantly, most work supporting these ideas has been conducted in the Northern Hemisphere. However, accumulating work on tropical species has shown divergent patterns of T in association with breeding behavior. The compilation of work from northern temperate and tropical species suggests that the function of T in relation to breeding behavior varies across latitude and environmental conditions. We investigate the patterns of T in relation to breeding behavior in a subspecies of the rufous-collared sparrow Zonotrichia capensis australis breeding at high latitude in the Southern Hemisphere (55°S). We then compare the T profiles and breeding behaviors of male Z. c. australis to conspecifics breeding in the tropics and congeners in North America to test the hypothesis that environments with breeding seasons of similar lengths will drive similar patterns of T in relation to breeding behavior. We found that Z. c. australis have high levels of T during the early-breeding periods when territories are being established and low levels of T during the parental phase of breeding, similar to temperate and Arctic birds in the Northern Hemisphere but unlike tropical Zonotrichia capensis costaricensis. In contrast, we found that Z. c. australis also exhibit similar aggressive behaviors in early breeding and midbreeding, unlike many birds in the Northern Hemisphere.

Modulation of androgens in southern hemisphere temperate breeding sparrows (Zonotrichia capensis): an altitudinal comparison.

Most work investigating modulation of testosterone (T) levels in birds has focused on northern temperate and Arctic species, and to a lesser degree, tropical species. Studies exploring modulation of T in birds in temperate regions of the Southern Hemisphere are lacking. Here we explore patterns of T secretion across the breeding season in two populations of temperate Zonotrichia capensis in Chile, located only 130 km apart, but separated by 2000 m in elevation. We then compared these T profiles to those of conspecifcs in the tropics and congeners in northern zones. We measured baseline T levels during pre-breeding in lowland Z. c. chilensis, early breeding in highland Z. c. chilensis and mid-breeding in both populations. We also tested for social stimulation of T secretion during mid-breeding in both populations. Lastly, we challenged the hypothalamic-pituitary-gonadal (HPG) axis of the lowland population with gonadotropin-releasing hormone (GnRH) to determine maximum possible T production. We found that the highland population adjusted T secretion across the breeding season like northern species. Neither Z. c. chilensis population modulated T in response to social stimuli, nor the HPG axis of the lowland population was not maximally active during either pre- or mid-breeding. These results suggest that patterns of circulating T in the highland population of Z. c. chilensis in the Southern Hemisphere are similar to congeners in the temperate Northern Hemisphere, but those of the lowland population of Z. c. chilensis are not, and are more similar to conspecifics breeding in the tropics.

Seasonal and social modulation of testosterone in Costa Rican rufous-collared sparrows (Zonotrichia capensis costaricensis).

Previous work shows that most birds breeding in northern temperate regions adjust production of testosterone in response to stage of the breeding cycle and in some cases following social interactions. In contrast, prior research suggests that tropical breeding birds are less likely to modulate testosterone in response to social interactions (the propensity to increase testosterone in response to social instability is known as the challenge hypothesis). To further test the challenge hypothesis in tropical birds, we investigated whether variation in season affects reproductive condition, aggressive behavior, and social modulation of testosterone in two populations of Costa Rican rufous-collared sparrow, Zonotrichia capensis costaricensis. We conducted our study at three distinct times of year: the dry season (March and May); the veranillo, a hiatus in the rainy season (July); and the late rainy season (November). Significantly more birds were in breeding condition in the dry season than in the rainy season or veranillo. In each time period, we collected baseline testosterone samples and conducted simulated territorial intrusions (STIs). Our study shows that testosterone is modulated with season independent of breeding condition, as testosterone levels were affected by season, breeding condition, and an interaction of the two factors. Males breeding in the dry season had higher plasma testosterone levels than non-breeding males in the dry season and both breeding and non-breeding males in the veranillo and rainy season. Males did not socially modulate testosterone in any season. Aggressive behaviors expressed during STIs did not differ among seasons with the exception that males sang fewer songs during the rainy season.

Disentangling the effects of environment and life-history stage on corticosterone modulation in Costa Rican rufous-collared sparrows, Zonotrichia capensis costaricensis.

This study explores the factors that influence modulation of baseline corticosterone levels and the hypothalamo-pituitary-adrenal cortex (HPA) axis response to stress in Costa Rican rufous-collared sparrows (Zonotrichia capensis costaricensis). Individuals in our study population vary in their timing of breeding and molt. Thus, at multiple times of the year, we were able to investigate how the HPA axis changes with life-history stage (breeding, molt) and the interaction of season and life-history stage. Season explained most of the variation in corticosterone data. During the dry season, males had higher baseline corticosterone levels and both females and males had a higher stress response, regardless of breeding or molting condition. Breeding did not significantly affect corticosterone levels in either males or females. There was no direct effect of molt on corticosterone levels in males or in females, but there was a significant interaction between season and molt for male baseline corticosterone levels and HPA axis responsiveness. Baseline corticosterone levels were not correlated with body condition, suggesting that body condition is not an explanatory factor for HPA axis change. Our data indicate that environmental conditions may affect how the HPA axis in birds is modulated during different life-history stages. They also emphasize the importance of studying species with diverse life cycles and seasonality.

Hemimethylation and non-CpG methylation levels in a promoter region of human LINE-1 (L1) repeated elements.

DNA methylation within the promoter region of human LINE1 (L1) transposable elements is important for maintaining transcriptional inactivation and for inhibiting L1 transposition. Determining methylation patterns on the complementary strands of repeated sequences is difficult using standard bisulfite methylation analysis. Evolutionary changes in each repeat and the variations between cells or alleles of the same repeat lead to a heterogeneous population of sequences. Potential sequence biases can arise during analyses that are different for the converted sense and antisense strands. These problems can be avoided with hairpin-bisulfite PCR, a double-stranded PCR method in which complementary strands of individual molecules are attached by a hairpin linker ligated to genomic DNA. Using human L1 elements to study methylation of repeated sequences, (i) we distinguish valid L1 sequences from redundant and contaminant sequences by applying the powerful new method of molecular barcodes, (ii) we resolve a controversy on the level of hemimethylation of L1 sequences in fetal fibroblasts in favor of relatively little hemimethylation, (iii) we report that human L1 sequences in different cell types also have primarily concordant CpG methylation patterns on complementary strands, and (iv) we provide evidence that non-CpG cytosines within the regions analyzed are rarely methylated.

Hairpin-bisulfite PCR: assessing epigenetic methylation patterns on complementary strands of individual DNA molecules.

Epigenetic inheritance, the transmission of gene expression states from parent to daughter cells, often involves methylation of DNA. In eukaryotes, cytosine methylation is a frequent component of epigenetic mechanisms. Failure to transmit faithfully a methylated or an unmethylated state of cytosine can lead to altered phenotypes in plants and animals. A central unresolved question in epigenetics concerns the mechanisms by which a locus maintains, or changes, its state of cytosine methylation. We developed "hairpin-bisulfite PCR" to analyze these mechanisms. This method reveals the extent of methylation symmetry between the complementary strands of individual DNA molecules. Using hairpin-bisulfite PCR, we determined the fidelity of methylation transmission in the CpG island of the FMR1 gene in human lymphocytes. For the hypermethylated CpG island of this gene, characteristic of inactive-X alleles, we estimate a maintenance methylation efficiency of approximately 0.96 per site per cell division. For de novo methylation efficiency (E(d)), remarkably different estimates were obtained for the hypermethylated CpG island (E(d) = 0.17), compared with the hypomethylated island on the active-X chromosome (E(d) < 0.01). These results clarify the mechanisms by which the alternative hypomethylated and hypermethylated states of CpG islands are stably maintained through many cell divisions. We also analyzed a region of human L1 transposable elements. These L1 data provide accurate methylation patterns for the complementary strand of each repeat sequence analyzed. Hairpin-bisulfite PCR will be a powerful tool in studying other processes for which genetic or epigenetic information differs on the two complementary strands of DNA.