Understanding Diversity of Policies, Functionalities, and Operationalization of Immunization Information Systems and Their Impact: A Targeted Review of the Literature.

The COVID-19 pandemic has focused attention on the use of immunization information systems (IIS) to record and consolidate immunization records from a variety of sources to generate comprehensive patient immunization histories. Operationalization of IIS in the United States is decentralized, and as such, there are over 60 different IIS with wide variations in enabling policies and functionalities. As such, the policies that inform the development and operation of those sub-national IIS exist at the state and sometimes city levels. A targeted literature review was conducted to identify IIS policies and functionalities and assess their impact. The authors identified articles published from 2012 to 2022 that discussed or evaluated IIS policies and functionalities and screened titles, abstracts, and full text for inclusion. When selected for inclusion, authors extracted IIS policy/functionality characteristics and qualitative or quantitative outcomes of their implementation, where applicable. The search terms yielded 86 articles, of which 39 were included in the analysis. The articles were heterogeneous with respect to study design, interventions, outcomes, and effect measures. Out of the 17 IIS policies and functional components identified in the targeted literature review, the most commonly evaluated were provider-based patient reminder/recall, IIS-based centralized reminder/recall, and clinical decision support. Patient reminder/recall had the most published research and was associated with increased vaccination rates and vaccine knowledge. Despite the lack of quantitative evidence, there is a consensus that immunization data interoperability is critical to supporting IIS data quality, access, and exchange. Significant evidence gaps remain about the effectiveness of IIS functionalities and policies. Future research should evaluate the impact of policies and functionalities to guide improved utilization of IIS, increase national interoperability and standardization, and ultimately improve vaccination coverage and population health.

Using Quality Measures to Drive Improvements in Immunization Rates: Findings from a Real-World Evaluation from 3 US Health Care Organizations.

Adult immunization rates are low and continue to fail to meet national targets. The coronavirus disease 2019 pandemic halted routine health care services for many, including vaccinations. This study explored whether the National Committee for Quality Assurance's Adult Immunization Status (AIS) measure, which had previously only been evaluated for reporting by health plans, could be leveraged by health care organizations (HCOs) as a tactic to improve immunization rates. Methods included a quantitative analysis of deidentified patient electronic health record data from 3 HCOs, supplemented by qualitative interviews to further understand opportunities and barriers. The analysis indicated that the data necessary for calculation of the AIS measure are available within HCOs and that measure performance could be enhanced with supplemental data from external sources, such as state immunization registries. Although HCOs rates were consistent with national estimates, this research further validated that adult immunization rates in the United States are low and highlighted the profound disparities that exist. For instance, the likelihood of completing all age-appropriate vaccinations was lower if patients were Black or African American, enrolled in Medicaid, or without health insurance. As a result of this study, the authors concluded that the AIS measure is feasible for use in medical groups and could potentially help drive quality improvements in immunization rates; however, there are considerations for implementation particularly if providers are being held accountable for measure performance.

Assessing opportunities to advance quality measures in adult obesity.

OBJECTIVES: To evaluate the methodological soundness and performance of 3 obesity quality measures aimed at promoting improvements in obesity care. STUDY DESIGN: Retrospective, clinical, and administrative data-based observational research study to evaluate scientific soundness, feasibility, and performance of obesity quality measures. METHODS: Four test sites (clinicians/clinician groups) submitted clinical and administrative health data including patient demographics, diagnoses, and encounter information for patient panels encompassing individuals aged 18 to 79 years with at least 1 ambulatory visit between July 1, 2017, and June 30, 2018 (measurement period). Clinician/clinician group data were supplemented by an Optum data set contributing patient information from 21 health care organizations with approximately 6 million qualifying patients to assess the impact of using a larger data set for measure testing. Patients were excluded if they met any of the following criteria: were pregnant during the measurement period or in the 6 months prior to the measurement period, had died during the measurement year, or had evidence of palliative or hospice care during the measurement period. RESULTS: This study resulted in the identification of a clinician/clinician group-level measure, Documentation of Obesity Diagnosis, as being feasible and reliable; however, the measure requires additional evaluation and potential adjustments to determine validity. Other measures included in our evaluation had feasibility and methodological challenges due to data capture and coding limitations. CONCLUSIONS: Findings of our current study suggest that there are emerging opportunities to capture data and advance obesity measurement incrementally. A process measure focused on obesity diagnosis has the most potential for immediate implementation by clinicians, and additional measures focused on change in body mass index over time and use of evidence-based obesity treatment remain challenging to implement due to data capture and benefit coverage.

The impact of cocaine and heroin drug history on motivation and cue sensitivity in a rat model of polydrug abuse.

RATIONALE: Comorbid use of heroin and cocaine is highly prevalent among drug users and can greatly increase addiction risk. Nonetheless, little is known regarding how a multi-drug history impacts motivation and cue responsivity to individual drugs. OBJECTIVE: We used behavioral-economic procedures to examine motivation to maintain drug consumption and tests of drug-seeking to drug-associated cues to assess sensitivity to heroin and cocaine-associated cues in rats that had a self-administration history of heroin, cocaine, or both drugs. RESULTS: Unexpectedly, we found that groups with a polydrug history of heroin and cocaine did not have higher levels of motivation or cue-induced reinstatement of drug-seeking for either cocaine or heroin compared to single drug groups. Nonetheless, we did find drug-specific differences in both economic price and cue sensitivity. Specifically, demand elasticity was lower for cocaine compared to heroin in animals with a single drug history, but not with polydrug groups. In addition, cocaine demand was predictive of the degree of cue-induced reinstatement of drug-seeking for cocaine following extinction, whereas heroin demand was predictive of the degree of reactivity to a heroin-associated cue. Furthermore, although cue reactivity following the initial self-administration phase did not differ across cues and drug history, reactivity to both heroin and cocaine cues was greater during subsequent heroin use compared to cocaine use, and this enhanced reactivity to heroin cues persisted during forced abstinence. CONCLUSIONS: These results indicate that there is a greater motivation to maintain cocaine consumption, but higher sensitivity to drug-associated cues with a history of heroin use, suggesting that cocaine and heroin may drive continued drug use through different behavioral processes.

Chemogenetic inhibition of direct pathway striatal neurons normalizes pathological, cue-induced reinstatement of drug-seeking in rats.

Addiction to drugs such as cocaine is marked by cycles of compulsive drug-taking and drug-seeking behavior. Although the transition to addiction is thought to recruit neural processes in dorsal striatum, little is known regarding the role of dorsal striatal projections to the substantia nigra (i.e. the direct pathway) in regulating these behaviors. Combining a Cre-recombinase-dependent chemogenetic approach with a cocaine self-administration paradigm that produces both low-risk and high-risk addiction phenotypes, we examined the effect of transiently decreasing direct pathway activity in the dorsomedial striatum on drug-taking and drug-seeking under conditions of normal and pathological drug use. Surprisingly, transient inhibition of direct pathway striatal neurons had no effect on several measures of addictive behavior during ongoing drug use, including loss of control over drug intake, high motivation to obtain drug and drug use despite negative consequences (i.e. drug use paired with foot shock). However, chemogenetic inhibition of these neurons during reinstatement reduced cue-induced drug-seeking, but only in the high-risk addiction phenotype group. Cue-induced reinstatement was relatively normal in the low-risk addiction phenotype group, as well as following reinstatement to cues associated with sucrose pellet consumption. These results demonstrate that dorsomedial direct pathway striatal neurons play a very specific role in addictive behaviors, which is to regulate the pathological drug-seeking that accompanies relapse.

Chemogenetic inhibition reveals midline thalamic nuclei and thalamo-accumbens projections mediate cocaine-seeking in rats.

Drug addiction is a chronic disease that is shaped by alterations in neuronal function within the cortical-basal ganglia-thalamic circuit. However, our understanding of how this circuit regulates drug-seeking remains incomplete, and relapse rates remain high. The midline thalamic nuclei are an integral component of the cortical-basal ganglia-thalamic circuit and are poised to mediate addiction behaviors, including relapse. It is surprising that little research has examined the contribution of midline thalamic nuclei and their efferent projections in relapse. To address this, we expressed inhibitory, Gi/o -coupled DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) in a subset of the midline thalamic nuclei or in midline thalamic nuclei neurons projecting to either the nucleus accumbens or the amygdala. We examined the effect of transiently decreasing activity of these neuronal populations on cue-induced and cocaine-primed reinstatement of cocaine-seeking. Reducing activity of midline thalamic nuclei neurons attenuated both cue-induced and cocaine-primed reinstatement, but had no effect on cue-induced reinstatement of sucrose-seeking or locomotor activity. Interestingly, attenuating activity of efferent projections from the anterior portion of midline thalamic nuclei to the nucleus accumbens blocked cocaine-primed reinstatement but enhanced cue-induced reinstatement. Decreasing activity of efferent projections from either the posterior midline thalamic nuclei to the nucleus accumbens or the midline thalamic nuclei to amygdala had no effect. These results reveal a novel contribution of subsets of midline thalamic nuclei neurons in drug-seeking behaviors and suggest that modulation of midline thalamic nuclei activity may be a promising therapeutic target for preventing relapse.

Excessive Sensory Stimulation during Development Alters Neural Plasticity and Vulnerability to Cocaine in Mice.

Early life experiences affect the formation of neuronal networks, which can have a profound impact on brain function and behavior later in life. Previous work has shown that mice exposed to excessive sensory stimulation during development are hyperactive and novelty seeking, and display impaired cognition compared with controls. In this study, we addressed the issue of whether excessive sensory stimulation during development could alter behaviors related to addiction and underlying circuitry in CD-1 mice. We found that the reinforcing properties of cocaine were significantly enhanced in mice exposed to excessive sensory stimulation. Moreover, although these mice displayed hyperactivity that became more pronounced over time, they showed impaired persistence of cocaine-induced locomotor sensitization. These behavioral effects were associated with alterations in glutamatergic transmission in the nucleus accumbens and amygdala. Together, these findings suggest that excessive sensory stimulation in early life significantly alters drug reward and the neural circuits that regulate addiction and attention deficit hyperactivity. These observations highlight the consequences of early life experiences and may have important implications for children growing up in today's complex technological environment.

The Valley-of-Death: reciprocal sign epistasis constrains adaptive trajectories in a constant, nutrient limiting environment.

The fitness landscape is a powerful metaphor for describing the relationship between genotype and phenotype for a population under selection. However, empirical data as to the topography of fitness landscapes are limited, owing to difficulties in measuring fitness for large numbers of genotypes under any condition. We previously reported a case of reciprocal sign epistasis (RSE), where two mutations individually increased yeast fitness in a glucose-limited environment, but reduced fitness when combined, suggesting the existence of two peaks on the fitness landscape. We sought to determine whether a ridge connected these peaks so that populations founded by one mutant could reach the peak created by the other, avoiding the low-fitness "Valley-of-Death" between them. Sequencing clones after 250 generations of further evolution provided no evidence for such a ridge, but did reveal many presumptive beneficial mutations, adding to a growing body of evidence that clonal interference pervades evolving microbial populations.