Acetylcholine Engages Distinct Amygdala Microcircuits to Gate Internal Theta Rhythm.

Acetylcholine (ACh) is released from basal forebrain cholinergic neurons in response to salient stimuli and engages brain states supporting attention and memory. These high ACh states are associated with theta oscillations, which synchronize neuronal ensembles. Theta oscillations in the basolateral amygdala (BLA) in both humans and rodents have been shown to underlie emotional memory, yet their mechanism remains unclear. Here, using brain slice electrophysiology in male and female mice, we show large ACh stimuli evoke prolonged theta oscillations in BLA local field potentials that depend upon M3 muscarinic receptor activation of cholecystokinin (CCK) interneurons (INs) without the need for external glutamate signaling. Somatostatin (SOM) INs inhibit CCK INs and are themselves inhibited by ACh, providing a functional SOM→CCK IN circuit connection gating BLA theta. Parvalbumin (PV) INs, which can drive BLA oscillations in baseline states, are not involved in the generation of ACh-induced theta, highlighting that ACh induces a cellular switch in the control of BLA oscillatory activity and establishes an internally BLA-driven theta oscillation through CCK INs. Theta activity is more readily evoked in BLA over the cortex or hippocampus, suggesting preferential activation of the BLA during high ACh states. These data reveal a SOM→CCK IN circuit in the BLA that gates internal theta oscillations and suggest a mechanism by which salient stimuli acting through ACh switch the BLA into a network state enabling emotional memory.

Differential Regulation of Prelimbic and Thalamic Transmission to the Basolateral Amygdala by Acetylcholine Receptors.

The amygdalar anterior basolateral nucleus (BLa) plays a vital role in emotional behaviors. This region receives dense cholinergic projections from basal forebrain which are critical in regulating neuronal activity in BLa. Cholinergic signaling in BLa has also been shown to modulate afferent glutamatergic inputs to this region. However, these studies, which have used cholinergic agonists or prolonged optogenetic stimulation of cholinergic fibers, may not reflect the effect of physiological acetylcholine release in the BLa. To better understand these effects of acetylcholine, we have used electrophysiology and optogenetics in male and female mouse brain slices to examine cholinergic regulation of afferent BLa input from cortex and midline thalamic nuclei. Phasic ACh release evoked by single pulse stimulation of cholinergic terminals had a biphasic effect on transmission at cortical input, producing rapid nicotinic receptor-mediated facilitation followed by slower mAChR-mediated depression. In contrast, at this same input, sustained ACh elevation through application of the cholinesterase inhibitor physostigmine suppressed glutamatergic transmission through mAChRs only. This suppression was not observed at midline thalamic nuclei inputs to BLa. In agreement with this pathway specificity, the mAChR agonist, muscarine more potently suppressed transmission at inputs from prelimbic cortex than thalamus. Muscarinic inhibition at prelimbic cortex input required presynaptic M4 mAChRs, while at thalamic input it depended on M3 mAChR-mediated stimulation of retrograde endocannabinoid signaling. Muscarinic inhibition at both pathways was frequency-dependent, allowing only high-frequency activity to pass. These findings demonstrate complex cholinergic regulation of afferent input to BLa that is pathway-specific and frequency-dependent.SIGNIFICANCE STATEMENT Cholinergic modulation of the basolateral amygdala regulates formation of emotional memories, but the underlying mechanisms are not well understood. Here, we show, using mouse brain slices, that ACh differentially regulates afferent transmission to the BLa from cortex and midline thalamic nuclei. Fast, phasic ACh release from a single optical stimulation biphasically regulates glutamatergic transmission at cortical inputs through nicotinic and muscarinic receptors, suggesting that cholinergic neuromodulation can serve precise, computational roles in the BLa. In contrast, sustained ACh elevation regulates cortical input through muscarinic receptors only. This muscarinic regulation is pathway-specific with cortical input inhibited more strongly than midline thalamic nuclei input. Specific targeting of these cholinergic receptors may thus provide a therapeutic strategy to bias amygdalar processing and regulate emotional memory.

Pharmacist-Community-Based Organization Collaboration to Address Health-Related Social Needs.

BACKGROUND: Community-based organizations (CBOs) help address community issues, including health-related social needs (HRSNs). Community pharmacies are positioned to collaborate with CBOs to help their patients identify and address HRSNs to optimal medication use. OBJECTIVES: To develop and evaluate two models of community pharmacy-CBO collaboration to address HRSNs facing patients taking medications. METHODS: Two different pharmacy-CBO models were studied. The CBO-initiated model had two CBOs assess and refer clients to a community pharmacy to address HRSN-related medication concerns. In the pharmacy-initiated model, pharmacists screened patients for HRSNs, addressed those related to medication costs and referred patients to a CBO for other HRSNs. Documented HRSNs were extracted and analyzed. Participating pharmacy and CBO staff were interviewed. The interview recordings were transcribed and coded, using rapid qualitative analyses. RESULTS: The CBO-initiated model screened 23 clients with 17 receiving a comprehensive medication review. In the pharmacy-initiated model, 39 patients were screened for HRSNs with 6 patients having medication costs issues addressed at the pharmacy and 23 patients being referred to the CBO. The most common HRSNs were high stress levels (43%), lack of confidence filling out forms (36%), feeling overwhelmed (34%), and inability to get food (27%). Patient-related themes from interviews were patient willingness to participate in the service, obstacles patients faced in obtaining medication therapy and establishing patient trust. Pharmacy-related and CBO-related themes included fitting new activities into workflow, importance of time management and good communication and establishing relationships between pharmacy and CBO personnel. CONCLUSION: Both pharmacy-CBO models effectively identified clients in need of medication management services or patients with HRSNs affecting medication optimization. Limited trust between the patient and the party to which they were referred was an obstacle to successful referral. Developing pharmacy and CBO personal relationships is a vital key in planning and coordinating these pharmacy-CBO collaboration models.

Resource allocation in public sector programmes: does the value of a life differ between governmental departments?

BACKGROUND: The value of a life is regularly monetised by government departments for informing resource allocation. Guidance documents indicate how economic evaluation should be conducted, often specifying precise values for different impacts. However, we find different values of life and health are used in analyses by departments within the same government despite commonality in desired outcomes. This creates potential inconsistencies in considering trade-offs within a broader public sector spending budget. We provide evidence to better inform the political process and to raise important issues in assessing the value of public expenditure across different sectors. METHODS: Our document analysis identifies thresholds, explicitly or implicitly, as observed in government-related publications in the following public sectors: health, social care, transport, and environment. We include both demand-side and supply-side thresholds, understood as societies' and governments' willingness to pay for health gains. We look at key countries that introduced formal economic evaluation processes early on and have impacted other countries' policy development: Australia, Canada, Japan, New Zealand, the Netherlands, and the United Kingdom. We also present a framework to consider how governments allocate resources across different public services. RESULTS: Our analysis supports that identifying and describing the Value of a Life from disparate public sector activities in a manner that facilitates comparison is theoretically meaningful. The optimal allocation of resources across sectors depends on the relative position of benefits across different attributes, weighted by the social value that society puts on them. The value of a Quality-Adjusted Life Year is generally used as a demand-side threshold by Departments of transport and environment. It exceeds those used in health, often by a large enough proportion to be a multiple thereof. Decisions made across departments are generally based on an unspecified rationing rule. CONCLUSIONS: Comparing government expenditure across different public sector departments, in terms of the value of each department outcome, is not only possible but also desirable. It is essential for an optimal resource allocation to identify the relevant social attributes and to quantify the value of these attributes for each department.

Impact of patient-centered prescription medication labels on adherence in community pharmacy.

BACKGROUND: Prescription medication labels are often constructed in a manner which hinders safe and appropriate use of medicines. The United States Pharmacopeia released voluntary standards to revise medication labels in an effort to support patients' understanding and improve medication use. OBJECTIVE: To examine the impact of label changes on medication adherence before and after pharmacy implementation of the United States Pharmacopeia patient-centered prescription medication label standards. METHODS: This study used a retrospective pre-post cohort design. Prescription fill claims data were obtained from a community health plan serving Medicaid patients for 1 independent community pharmacy organization across 8 retail pharmacy sites. We calculated medication possession ratios (MPR) and proportion of days covered (PDC) for medications used for contraception, asthma, hypertension, and depression from 15 months before to 13 months after implementation of the label changes. RESULTS: Findings showed significant increases in mean MPR for asthma controller (increased by 0.111 [t = 0.290, P<0.0001]), antihypertensives (increased by 0.062 [t = 0.146, P < 0.0002]), and contraceptives medications (increased 0.133 [t = 0.209, P < 0.0001]) from preintervention to postintervention periods. Results also revealed increases in mean PDC for asthma controllers (increased by 0.193 [t = 0.267, P < 0.0001]), antihypertensives (increased by 0.067 [t = 0.175, P = 0.049]), and contraceptives (increased by 0.111 [t = 0.208, P < 0.0119]) from preintervention to postintervention periods. CONCLUSION: We report an association between a change to more patient-centered prescription medication labels and increased medication adherence based on MPR and PDC among Medicaid recipients.

Leadership aspiration: An intersectional analysis of racial and gender equity in pharmacy.

BACKGROUND: The glass ceiling is a metaphor used to describe an invisible barrier that prevents an underrepresented group from rising beyond a certain level. Among pharmacists, underrepresented groups face various barriers and limitations to their successes. OBJECTIVES: The purpose of this study was to apply the intersectionality framework to data collected from the 2019 National Pharmacist Workforce Study (NPWS) to understand the association of gender and race with leadership aspiration among pharmacists, including differences in perceived barriers and attractors for pursuing leadership. METHODS: The 2019 NPWS was conducted using an electronic Qualtrics survey. Three e-mails containing the survey link were sent to a systematic random sample of 94,803 pharmacists through the National Association of Boards of Pharmacy Foundation e-profile system. The 2019 NPWS had an overall response rate of 6% (5705/94,803). A total of 8466 pharmacists clicked on the survey link, resulting in a usable response rate of 67.3% (5705/8466). Data were analyzed in SPSS software using descriptive and Pearson's r and chi-square test statistics. RESULTS: Black, Indigenous, and People of Color (BIPOC) pharmacists reported holding 10.7% of all leadership positions. Leadership positions included manager, assistant manager, executive, dean, director, chief pharmacy officer, owner or partner, and other leadership position types. White men and women reported the lowest interest in leadership (38.8% and 37.7%), whereas Black men (65.1%), Latinas (59.2%), Black women (58.5%), and Latinos (57.1%) had the highest interest in leadership. "The ability to make an impact" was the most frequently selected attractor for wanting to pursue leadership, selected by 92.5% and 79.6% of Black men and women, respectively, 77.8% of Other women, and 76.9% of Latinos. At graduation from pharmacy school, the student debt loan average of all graduation years ranged from $63,886 (± $73,701) for Other men to $112,384 (± $105,417) for Black women. Higher student loan debt was positively correlated with wanting to pursue a leadership position (r = 0.22, P < 0.001). Black women graduating 2011-2019 had the highest student loan debt at graduation ($194,456 ± $88,898). CONCLUSION: Interest in leadership positions by BIPOC pharmacists compared with reported leadership roles were inversely correlated. Understanding the discrepancy in interest in leadership and reported leadership positions held, particularly with relation to race and gender, is essential to understanding equity in pharmacy leadership. Further research is warranted to understand the factors that impede the ascension of women and underrepresented pharmacists into leadership positions.

A European, prospective, observational study of enzalutamide in patients with metastatic castration-resistant prostate cancer: PREMISE.

In randomized clinical trials, the androgen-receptor inhibitor enzalutamide has demonstrated efficacy and safety in metastatic castration-resistant prostate cancer (mCRPC). This study captured efficacy, safety and patient-reported outcomes (PROs) of enzalutamide in mCRPC patients in a real-world European setting. PREMISE (NCT0249574) was a European, long-term, prospective, observational study in mCRPC patients prescribed enzalutamide as part of standard clinical practice. Patients were categorized based on prior docetaxel and/or abiraterone use. The primary endpoint was time to treatment failure (TTF), defined as time from enzalutamide initiation to permanent treatment discontinuation for any reason. Secondary endpoints included prostate-specific antigen (PSA) response, time to PSA progression, time to disease progression and safety. PROs included EuroQol 5-Dimension, 5-Level questionnaire, Functional Assessment of Cancer Therapy-Prostate and Brief Pain Inventory-Short Form. Overall, 1732 men were enrolled. Median TTF with enzalutamide was 12.9 months in the chemotherapy- and abiraterone-naïve cohort (Cohort 1) and 8.4 months in the postchemotherapy and abiraterone-naïve cohort (Cohort 2). Clinical outcomes based on secondary endpoints also varied between cohorts. Cohorts 1 and 2 showed small improvements in health-related quality of life and pain status. The proportions of patients reporting treatment-emergent adverse events (TEAEs) were 51.0% and 62.2% in Cohorts 1 and 2, respectively; enzalutamide-related TEAEs were similar in both cohorts. The most frequent TEAE across cohorts was fatigue. These data from unselected mCRPC patients in European, real-world, clinical-practice settings confirmed the benefits of enzalutamide previously shown in clinical trial outcomes, with safety results consistent with enzalutamide's known safety profile.

Considering Severity in Health Technology Assessment: Can We Do Better?

There is strong evidence that individuals and the public assign relatively greater value to health gains from relatively more severe health states. This preference is increasingly reflected in health technology assessment, with some consideration of severity incorporated by health technology assessment bodies in, among others, The Netherlands, England and Wales, Norway, Sweden, and the United States. If a societal "severity premium" is to be considered fairly and consistently, we argue that a more explicit and quantitative approach is needed. We highlight drawbacks of categorical approaches, especially discontinuities between severity categories that arguably violate concepts of vertical equity, and argue that a more continuous approach to understanding severity is needed. We also note challenges to more explicit approaches, including implications of a lower threshold for less severe conditions and the relative complexity of calculating a continuous severity adjustment.

Does Changing the Age of a Child to be Considered in 3-Level Version of EQ-5D-Y Discrete Choice Experiment-Based Valuation Studies Affect Health Preferences?

OBJECTIVES: There has been some debate about the choice of perspective and the age of the child considered when completing preference elicitation tasks in the 3-level version of EQ-5D-Y (EQ-5D-Y-3L) valuation protocol. This study aimed to clarify the impact on latent scale EQ-5D-Y-3L values of varying the age of the child experiencing the health state considered by respondents completing the discrete choice experiment (DCE) tasks of the protocol. METHODS: We conducted an online DCE with a representative sample of 1000 adults in the United Kingdom and 1000 adults in the United States. Respondents selected the health state they prefer from a series of DCE paired EQ-5D-Y-3L health state comparisons using their own perspective and that of a hypothetical child from the following age groups: "5-7 years old," "8-10 years old," "11-13 years old," and "14-15 years old." Data analysis was conducted using separate multinomial logit models for each perspective and country. We also estimated combined models including data from each possible pair of perspectives and used interactions between EQ-5D-Y-3L levels and perspective to determine whether any differences were statistically significant. RESULTS: No statistically significant differences in coefficients between perspectives were found in the United States. In the United Kingdom, there were differences between the own perspective and the 5 to 7 years old perspective (looking after myself level 3) and between the 5 to 7 years old perspective and the 8 to 10 years old perspective (usual activities level 3). CONCLUSIONS: Our results suggest that there is minimal impact on latent scale values when using different ages of the hypothetical child in the current EQ-5D-Y-3L valuation protocol.

Accounting for Preference Heterogeneity in Discrete-Choice Experiments: An ISPOR Special Interest Group Report.

OBJECTIVES: Discrete choice experiments (DCEs) are increasingly used to elicit preferences for health and healthcare. Although many applications assume preferences are homogenous, there is a growing portfolio of methods to understand both explained (because of observed factors) and unexplained (latent) heterogeneity. Nevertheless, the selection of analytical methods can be challenging and little guidance is available. This study aimed to determine the state of practice in accounting for preference heterogeneity in the analysis of health-related DCEs, including the views and experiences of health preference researchers and an overview of the tools that are commonly used to elicit preferences. METHODS: An online survey was developed and distributed among health preference researchers and nonhealth method experts, and a systematic review of the DCE literature in health was undertaken to explore the analytical methods used and summarize trends. RESULTS: Most respondents (n = 59 of 70, 84%) agreed that accounting for preference heterogeneity provides a richer understanding of the data. Nevertheless, there was disagreement on how to account for heterogeneity; most (n = 60, 85%) stated that more guidance was needed. Notably, the majority (n = 41, 58%) raised concern about the increasing complexity of analytical methods. Of the 342 studies included in the review, half (n = 175, 51%) used a mixed logit with continuous distributions for the parameters, and a third (n = 110, 32%) used a latent class model. CONCLUSIONS: Although there is agreement about the importance of accounting for preference heterogeneity, there are noticeable disagreements and concerns about best practices, resulting in a clear need for further analytical guidance.

Criteria for developing, assessing and selecting candidate EQ-5D bolt-ons.

PURPOSE: 'Bolt-on' dimensions are additional items added to multi-attribute utility instruments (MAUIs) such as EQ-5D that measure constructs not included in the core descriptive system. The use of bolt-ons has been proposed to improve the content validity and responsiveness of the descriptive system in certain settings and health conditions. EQ-5D bolt-ons serve a particular purpose and thus satisfy a certain set of criteria. The aim of this paper is to propose a set of criteria to guide the development, assessment and selection of candidate bolt-on descriptors. METHODS: Criteria were developed using an iterative approach. First, existing criteria were identified from the literature including those used to guide the development of MAUIs, the COSMIN checklist and reviews of existing bolt-ons. Second, processes used to develop bolt-ons based on qualitative and quantitative approaches were considered. The information from these two stages was formalised into draft development and selection criteria. These were reviewed by the project team and iteratively refined. RESULTS: Overall, 23 criteria for the development, assessment and selection of candidate bolt-ons were formulated. Development criteria focused on issues relating to i) structure, ii) language, and iii) consistency with the existing EQ-5D dimension structure. Assessment and selection criteria focused on face and content validity and classical psychometric indicators. CONCLUSION: The criteria generated can be used to guide the development of bolt-ons across different health areas. They can also be used to assess existing bolt-ons, and inform their inclusion in studies and patient groups where the EQ-5D may lack content validity.

Photopotentiation of the GABAA receptor with caged diazepam.

As the inhibitory γ-aminobutyric acid-ergic (GABAergic) transmission has a pivotal role in the central nervous system (CNS) and defective forms of its synapses are associated with serious neurological disorders, numerous versions of caged GABA and, more recently, photoswitchable ligands have been developed to investigate such transmission. While the complementary nature of these probes is evident, the mechanisms by which the GABA receptors can be photocontrolled have not been fully exploited. In fact, the ultimate need for specificity is critical for the proper synaptic exploration. No caged allosteric modulators of the GABAA receptor have been reported so far; to introduce such an investigational approach, we exploited the structural motifs of the benzodiazepinic scaffold to develop a photocaged version of diazepam (CD) that was tested on basolateral amygdala (BLa) pyramidal cells in mouse brain slices. CD is devoid of any intrinsic activity toward the GABAA receptor before irradiation. Importantly, CD is a photoreleasable GABAA receptor-positive allosteric modulator that offers a different probing mechanism compared to caged GABA and photoswitchable ligands. CD potentiates the inhibitory signaling by prolonging the decay time of postsynaptic GABAergic currents upon photoactivation. Additionally, no effect on presynaptic GABA release was recorded. We developed a photochemical technology to individually study the GABAA receptor, which specifically expands the toolbox available to study GABAergic synapses.

Influenza vaccination rates and location for receiving the influenza vaccination among older adult Medicare beneficiaries.

OBJECTIVES: The objectives of this study were to (1) assess the trends in older adult influenza vaccination rates and (2) locations at which U.S. older adults received influenza vaccinations for the 2008-2009 to 2017-2018 influenza seasons, and (3) compare the estimates of influenza vaccination rates and locations with the estimates from other sources reported previously. METHODS: Data from the 2009 to 2017 Medicare Current Beneficiary Survey (MCBS) were used in this analysis. The weighted sample included an average of approximately 37 million community-dwelling older Medicare beneficiaries who completed questionnaires per year. The estimates for older adult influenza vaccination rates and the locations that they used to receive the influenza vaccination were weighted and reported for the 2008-2009 to 2017-2018 influenza seasons. RESULTS: The self-reported older adult influenza vaccination rates between 2008-09 and 2017-2018 ranged from 69.6% (24.6 million) to 75.0% (31.3 million). Across the study period, the percentage of older adults receiving the influenza vaccination at a physician office and clinic declined by 10.4%. The decline was more than offset by an increase in older adult influenza vaccination receipt at a community pharmacy, which substantially increased from 16.6% (4.1 million) in 2008-2009 to 34.8% (10.9 million) in 2014-2015. When compared with the estimates from other sources, the absolute value of the MCBS estimates corresponds with National Health Interview Survey estimates. The older adult influenza vaccination rate increased slightly between the 2008-2009 and 2017-2018 influenza seasons but is still below the 90% benchmark. CONCLUSION: Community pharmacies-increasingly important access points for the influenza vaccination for older adults-likely contributed to the growth in the rate of older adults vaccinated with influenza vaccines.

Snapshot of unemployed pharmacists from the 2019 National Pharmacy Workforce Survey.

BACKGROUND: Prior national surveys have quantified unemployment in the pharmacy workforce, and recent surveys have occurred in a changing environment, with increased numbers of pharmacists in the labor market. OBJECTIVES: We sought to investigate the rate of unemployment and situations of unemployed pharmacists. METHODS: Data from the 2019 National Pharmacist Workforce Survey were analyzed, focusing on an initial question about employment status and follow-up questions for unemployed respondents about whether they were seeking a job, the reason they were unemployed, and how long they had been unemployed. RESULTS: Overall, 4.4% of the respondents were unemployed, with higher rates occurring for female pharmacists, older pharmacist cohorts, and respondents of color, with the highest rate occurring (9.3%) for Black pharmacists. Most (74.4%) of the unemployed pharmacists were seeking a job in pharmacy, but 16.6% were not seeking any job. Nearly two-thirds of the unemployed pharmacist respondents had left the workforce involuntarily, with men at higher rates than women. The youngest cohort of unemployed pharmacists was the least likely to be forced to leave and more likely to leave for workplace-related or personal reasons. Black pharmacists had the overall highest rate of leaving the workforce involuntarily. On average, the unemployed pharmacists had been out of work nearly 2 years (19.2 months), and the periods out of work ranged widely. Those seeking a job in pharmacy predominantly (75.7%) had been unemployed for 1 year or less. More than half of the pharmacists involuntarily unemployed had been unemployed for 6 months or less. CONCLUSION: An increased rate of unemployment and a higher proportion of those unemployed seeking work occurred in this most recent national survey of the pharmacist workforce. Differences in the extent of unemployment and whether leaving the workforce was voluntary or involuntary occurred in pharmacists of color and in some age cohorts.

An intersectional review of discrimination and harassment experiences in pharmacy: Findings from the 2019 National Pharmacist Workforce Survey.

BACKGROUND: Most pharmacists in the United States are women, and the profession is becoming more racially diverse. The recent increase in political and social movements in the United States has heightened our awareness of the importance of better understanding the experiences of underrepresented individuals and groups. Little is known about discrimination and harassment in the profession of pharmacy in the United States. OBJECTIVES: The purpose of this study was to provide evidence that discrimination and harassment exist in the pharmacy profession and explore differences in discrimination and harassment using the intersectionality of race and sex. METHODS: The 2019 National Pharmacist Workforce Survey (NPWS) utilized an electronic survey that was distributed using a 3-contact Dillman approach by email to a randomized sample of 96,110 licensed pharmacists from all 50 U.S. states using the National Association of Boards of Pharmacy Foundation e-profile system. The 2019 NPWS included a new battery of questions to assess the prevalence of discrimination and harassment in pharmacy. RESULTS: The most common bases of discrimination experienced were based on age (31.2%), sex (29%), and race or ethnicity (16.6%). The most common type of harassment experienced was "hearing demeaning comments related to race or ethnicity" at 15.6%. The intersectionality analysis revealed different experiences among sex or race combinations. Black and Asian male pharmacists had the highest rate of "hearing demeaning comments about race or ethnicity." Nonwhite pharmacists were more likely to experience harassment from customers or patients compared with their white colleagues. Black female pharmacists had the highest rate of being "very unsatisfied" with the results of reporting discrimination and harassment to their employer. CONCLUSION: Discrimination, including harassment and sexual harassment, is illegal, immoral, and unjust. As the profession of pharmacy continues to become more diverse, there must be a conscious, systemic, and sustained effort to create and maintain workplaces that are safe, equitable, and free of discrimination.

Reporting Quality of Marginal Rates of Substitution in Discrete Choice Experiments That Elicit Patient Preferences.

BACKGROUND: Discrete choice experiments (DCEs) are commonly used to elicit patient preferences as marginal rates of substitution (MRSs) between treatment or health service attributes. Because these studies are increasing in importance, it is vital that uncertainty around MRS estimates is reported. OBJECTIVE: To review recently published DCE studies that elicit patient preferences in relation to MRS reporting and to explore the accuracy of using other reported information to estimate the uncertainty of the MRSs. METHODS: A systematic literature review of DCEs conducted with patients between 2014 and July 2019 was performed. The number of studies reporting coefficients, MRSs, standard errors (SEs), and confidence intervals was recorded. If all information was reported, studies were included in an analysis to determine the impact of estimating the SEs of MRSs using coefficients and assuming zero covariance, to determine the impact of this assumption. RESULTS: Two hundred and thirty-two patient DCEs were identified in the review; 34.1% (n = 79) reported 1 or more MRS and, of these, only 62.0% (n = 49) provided an estimate of the uncertainty. Of these studies, 16 contained enough information for inclusion in the analysis, providing 116 datapoints. Actual SEs were smaller than estimated SEs in 75.0% of cases (n = 87), and estimated SEs were within 25% of the actual SE in 59.5% of cases (n = 69). CONCLUSION: Uncertainty of MRS estimates is unreported in a substantial proportion of recently published DCE studies. Estimating the SE of a MRS by solely using the SEs of the utility coefficients is likely to lead to biased estimates of the precision of patient trade-offs.

Retail clinics colocated with pharmacies: A Delphi study of pharmacist impacts and recommendations for optimization.

OBJECTIVES: To identify workforce issues likely to affect pharmacists working in retail clinics (RCs) colocated with community pharmacies and to generate recommendations for optimizing health, cost, and operations outcomes. DESIGN AND PARTICIPANTS: A Delphi expert panel process using researchers with pharmacist workforce research experience was used. Panelists responded to 2 surveys of 3 rounds each. In survey 1, panelists used a 4-point linear numeric scale to rate the importance of 15 impact factors on pharmacists working in the RC/pharmacy setting. In survey 2, panelists used a 3-point linear numeric scale to rate the importance of recommendations for optimal outcomes. Recommendations were structured around elements from collaboration theory, a framework for evaluating critical areas for success in merged operations. MAIN OUTCOME MEASURES: Consensus was defined as ≥ 80% rating an impact "very" or "moderately" important (survey 1) and "very" important (survey 2). Impact factors were rank-ordered by ratings and numeric scoring. Selected comments about consensus items were reported. RESULTS: The 8-person panel had 100% response rates for both surveys. 12 of the 15 impact variables achieved consensus (survey 1). The highest ranking impacts were ability to establish collaborative relationships, relationships with coworkers, including nurse practitioners, and location of the RC relative to the pharmacy. Of 15 recommendations (survey 2), 5 achieved consensus and focused heavily on information sharing and early and ongoing collaboration among all stakeholders. CONCLUSION: Clinical, economic, health care quality, and patient preference data suggest that RCs colocated with pharmacies are likely to play a permanent role in U.S. health care. RCs can affect pharmacists and pharmacies positively or negatively. Positive impacts are most likely where establishing collaborative partnerships with all stakeholders, including patients, throughout planning, implementation, and operation are emphasized. With only about 3% of pharmacy operations colocated with RCs now, attention and resources should be devoted to developing and testing models based on collaboration principles.

Challenges in Valuing Temporary Health States for Economic Evaluation: A Review of Empirical Applications of the Chained Time Trade-Off Method.

BACKGROUND: The time trade-off (TTO) technique is commonly used to elicit health state utilities. Nevertheless, when the health states being valued are temporary, the TTO approach may be unsuitable. A variant of TTO- chained TTO-has been suggested to be used when the health states are temporary, but little research has been done on how chained TTO should be conducted. OBJECTIVES: To systematically review the use of chained TTO in valuing temporary health states. METHODS: A systematic literature search was conducted using the following major databases: Ovid MEDLINE(R), Embase, EBM Reviews, and PsycINFO. Abstracts (full articles if necessary) were screened by two independent reviewers, with a third reviewer resolving any disagreements. RESULTS: The resulting number of articles for review was low (n = 9). All the reviewed studies used face-to-face interviews, most had small sample sizes (<100), and all studies valued a small number of health states (<7), with time horizons typically ranging from 4 weeks to 1 year. All studies discussed methodological issues of using chained TTO, and some compared the results with those generated using other preference elicitation methods. CONCLUSIONS: Chained TTO appears to be feasible, consistent, and responsive and allows the valuation of temporary health states that would improve the efficiency and accuracy of decision making in health and health care. Nevertheless, the evidence is limited due to the low number of relevant studies in the literature. Further research is needed to examine the performance and validity of chained TTO compared with conventional TTO in the valuation of temporary health states.

Functional neuroanatomy of amygdalohippocampal interconnections and their role in learning and memory.

The amygdalar nuclear complex and hippocampal/parahippocampal region are key components of the limbic system that play a critical role in emotional learning and memory. This Review discusses what is currently known about the neuroanatomy and neurotransmitters involved in amygdalo-hippocampal interconnections, their functional roles in learning and memory, and their involvement in mnemonic dysfunctions associated with neuropsychiatric and neurological diseases. Tract tracing studies have shown that the interconnections between discrete amygdalar nuclei and distinct layers of individual hippocampal/parahippocampal regions are robust and complex. Although it is well established that glutamatergic pyramidal cells in the amygdala and hippocampal region are the major players mediating interconnections between these regions, recent studies suggest that long-range GABAergic projection neurons are also involved. Whereas neuroanatomical studies indicate that the amygdala only has direct interconnections with the ventral hippocampal region, electrophysiological studies and behavioral studies investigating fear conditioning and extinction, as well as amygdalar modulation of hippocampal-dependent mnemonic functions, suggest that the amygdala interacts with dorsal hippocampal regions via relays in the parahippocampal cortices. Possible pathways for these indirect interconnections, based on evidence from previous tract tracing studies, are discussed in this Review. Finally, memory disorders associated with dysfunction or damage to the amygdala, hippocampal region, and/or their interconnections are discussed in relation to Alzheimer's disease, posttraumatic stress disorder (PTSD), and temporal lobe epilepsy. © 2016 Wiley Periodicals, Inc.

Influences on the frequency and type of community pharmacy services.

OBJECTIVES: To describe services provided by community pharmacies and to identify factors associated with services being provided in community pharmacies. DESIGN: Cross-sectional national mail survey. SETTING AND PARTICIPANTS: Pharmacists actively practicing in community pharmacies (independent, chain, mass merchandisers, and supermarkets). OUTCOME MEASURES: Frequency and type of pharmacy services available in a community pharmacy, including medication therapy management, immunization, adjusting medication therapy, medication reconciliation, disease state management, health screening or coaching, complex nonsterile compounding, and point-of-care testing. RESULTS: With a 48.4% response rate, the survey showed that community pharmacies offered on average 3 of the 8 services studied. Pharmacy chains and supermarket pharmacies reported providing significantly more services than did mass merchandise pharmacies. The number of pharmacy services provided was positively associated with involvement in an interprofessional care team, innovativeness, and perceived workload. The number of pharmacy services was negatively correlated with having 3.5 or more pharmacy technicians on duty. CONCLUSION: Pharmacy chains and supermarkets are providing the most pharmacy services among community pharmacy settings. The number of services provided was associated with innovativeness, technician staffing, and perceived workload. Also, involvement with an interprofessional care team supported greater service delivery. Community pharmacies vary in their provision of services beyond dispensing.