Neuronal alterations in AKT isotype expression in schizophrenia.

Schizophrenia is characterized by substantial alterations in brain function, and previous studies suggest insulin signaling pathways, particularly involving AKT, are implicated in the pathophysiology of the disorder. This study demonstrates elevated mRNA expression of AKT1-3 in neurons from schizophrenia subjects, contrary to unchanged or diminished total AKT protein expression reported in previous postmortem studies, suggesting a potential decoupling of transcript and protein levels. Sex-specific differential AKT activity was observed, indicating divergent roles in males and females with schizophrenia. Alongside AKT, upregulation of PDPK1, a critical component of the insulin signaling pathway, and several protein phosphatases known to regulate AKT were detected. Moreover, enhanced expression of the transcription factor FOXO1, a regulator of glucose metabolism, hints at possible compensatory mechanisms related to insulin signaling dysregulation. Findings were largely independent of antipsychotic medication use, suggesting inherent alterations in schizophrenia. These results highlight the significance of AKT and related signaling pathways in schizophrenia, proposing that these changes might represent a compensatory response to a primary defect of conical insulin signaling pathways. This research underscores the need for a detailed understanding of these signaling pathways for the development of effective therapeutic strategies.

Association between Covid-19 sources of information, beliefs, and vaccination rates: an EU-wide survey.

BACKGROUND: Misinformation hampers vaccine uptake. The European Union (EU) employed a coordinated effort to curb misinformation during the Covid-19 pandemic. In this context, we investigated relationships between sources of information, vaccine safety/effectiveness, satisfaction with government vaccination strategy, and vaccination intent. METHODS: We used cross-sectional survey data (May 2021) from Flash Eurobarometer 494, a population-adjusted dataset comprised of a representative sample of those ≥15 years from 27 EU nations. We employed a latent class analysis to create clusters of information sources as the independent variable and beliefs in vaccine safety/efficacy, satisfaction with government vaccination strategy, and vaccine intent as four outcome variables. We first estimated the association between source clusters and each of the first three outcomes separately. Then, using these three as intermediate variables, we employed structural equation modeling to estimate the relationship between sources and vaccine intent. We adjusted for individual and country-level variables. RESULTS: Among 23 012 respondents, four clusters of information sources emerged: (1) national authorities/health professionals (n = 9602; 42%), (2) mostly health professionals (6184; 27%), (3) mixed (n = 1705; 17%) and (4) social media/family/friends (n = 5524; 24%). Using cluster (3) as the referent, we found decreasing odds of beliefs in vaccine safety/effectiveness, satisfaction and vaccine intent across clusters (1), (2) and (4), respectively. Demographics played a role. CONCLUSION: In the context of the Covid pandemic, these results provide the first EU-wide estimates of the association between sources of information about vaccine safety/effectiveness, satisfaction and vaccine intent. The coordinated approach promulgated by the EU to minimize misinformation provides a model for managing future pandemics.

Exploring Providers' Perception to Naloxone Education for Opioid Overdose After Receiving Academic Detailing at the U.S. Department of Veterans Affairs.

Introduction: The U.S. Department of Veterans Affairs (VA), in partnership with the Opioid Overdose Education and Naloxone Distribution (OEND) Program, implemented the National Academic Detailing Service to deliver naloxone education to providers with patients at-risk for opioid-related overdose. Methods: We administered a 26-item online survey to VA providers to explore their perceptions about prescribing naloxone for opioid overdose emergencies and their experience with academic detailing between August 2017 and April 2018. Responses were analyzed using descriptive statistics to (1) explore their current perceptions of naloxone prescribing and their experience with academic detailing, (2) identify differences across provider types [primary care providers (PCP), specialists, and others], and (3) assess perceived naloxone prescribing behavior change after an academic detailing visit. Results: Providers (N = 137) indicated that they were practicing at a level that was consistent with VA goals to promote take-home naloxone to reverse opioid-related overdose events. Average domain scores were similar across PCP, specialist, and other provider types. Specialists reported a higher average attitude domain score (+.56, P = .011) and perceived barriers domain score (+.82, P = .009) than PCPs. Most providers agreed that they prescribed naloxone more frequently due to academic detailing (53%) and indicated that they synthesized information from the academic detailer to change their naloxone prescribing practice (60%). Discussion: VA providers' perceptions of take-home naloxone were aligned with current evidence-based practice. Moreover, providers reported increasing their naloxone prescribing and synthesizing OEND-related information after an academic detailing interaction. Understanding providers' perceptions can be used to improve and enhance the academic detailing program's effectiveness.

Patient-centred outcomes of imaging tests: recommendations for patients, clinicians and researchers.

BACKGROUND: Imaging tests are one of the most frequently used diagnostic modalities in healthcare, but the benefits of their direct impacts on clinical decision-making have been countered by concerns that they can be overused. Assessing the relative value of imaging tests has largely focused on measures of test accuracy, which overlooks more comprehensive benefits and risks of imaging tests, particularly their impact on patient-centred outcomes (PCOs). We present the findings of the Patient Reported Outcomes of Diagnostics (PROD) research study in response to a methodological gap in the area of diagnostic test comparative effectiveness research. METHODS: Over a 3-year period, the PROD Study engaged with multiple stakeholders to identify existing conceptual models related to PCOs for imaging testing, conducted primary research and evidence synthesis, and developed consensus recommendations to describe and categorise PCOs related to imaging testing. RESULTS: The PROD framework categorises PCOs from imaging studies within four main domains: information or knowledge yielded, physical impact, emotional outcomes and test burden. PCOs interact with each other and influence effects across domains, and can be modified by factors related to the patient, clinical situation, healthcare team and the testing environment. CONCLUSIONS: Using PCOs to inform healthcare decision-making will require ways of collating and presenting information on PCOs in ways that can inform patient-provider decision-making, and developing methods to determine the relative importance of outcomes (including test accuracy) to one another.

Adenosine Receptor mRNA Expression in Frontal Cortical Neurons in Schizophrenia.

Schizophrenia is a devastating neuropsychiatric disorder associated with the dysregulation of glutamate and dopamine neurotransmitter systems. The adenosine system is an important neuroregulatory system in the brain that modulates glutamate and dopamine signaling via the ubiquitously expressed adenosine receptors; however, adenosine A1 and A2A receptor (A1R and A2AR) mRNA expression is poorly understood in specific cell subtypes in the frontal cortical brain regions implicated in this disorder. In this study, we assayed A1R and A2AR mRNA expression via qPCR in enriched populations of pyramidal neurons, which were isolated from postmortem anterior cingulate cortex (ACC) tissue from schizophrenia (n = 20) and control (n = 20) subjects using laser microdissection (LMD). A1R expression was significantly increased in female schizophrenia subjects compared to female control subjects (t(13) = -4.008, p = 0.001). A1R expression was also significantly decreased in female control subjects compared to male control subjects, suggesting sex differences in basal A1R expression (t(17) = 2.137, p = 0.047). A significant, positive association was found between dementia severity (clinical dementia rating (CDR) scores) and A2AR mRNA expression (Spearman's r = 0.424, p = 0.009). A2AR mRNA expression was significantly increased in unmedicated schizophrenia subjects, suggesting that A2AR expression may be normalized by chronic antipsychotic treatment (F(1,14) = 9.259, p = 0.009). Together, these results provide novel insights into the neuronal expression of adenosine receptors in the ACC in schizophrenia and suggest that receptor expression changes may be sex-dependent and associated with cognitive decline in these subjects.

Schizophrenia: a disorder of broken brain bioenergetics.

A substantial and diverse body of literature suggests that the pathophysiology of schizophrenia is related to deficits of bioenergetic function. While antipsychotics are an effective therapy for the management of positive psychotic symptoms, they are not efficacious for the complete schizophrenia symptom profile, such as the negative and cognitive symptoms. In this review, we discuss the relationship between dysfunction of various metabolic pathways across different brain regions in relation to schizophrenia. We contend that several bioenergetic subprocesses are affected across the brain and such deficits are a core feature of the illness. We provide an overview of central perturbations of insulin signaling, glycolysis, pentose-phosphate pathway, tricarboxylic acid cycle, and oxidative phosphorylation in schizophrenia. Importantly, we discuss pharmacologic and nonpharmacologic interventions that target these pathways and how such interventions may be exploited to improve the symptoms of schizophrenia.

Transcriptional profile of pyramidal neurons in chronic schizophrenia reveals lamina-specific dysfunction of neuronal immunity.

While the pathophysiology of schizophrenia has been extensively investigated using homogenized postmortem brain samples, few studies have examined changes in brain samples with techniques that may attribute perturbations to specific cell types. To fill this gap, we performed microarray assays on mRNA isolated from anterior cingulate cortex (ACC) superficial and deep pyramidal neurons from 12 schizophrenia and 12 control subjects using laser-capture microdissection. Among all the annotated genes, we identified 134 significantly increased and 130 decreased genes in superficial pyramidal neurons, while 93 significantly increased and 101 decreased genes were found in deep pyramidal neurons, in schizophrenia compared to control subjects. In these differentially expressed genes, we detected lamina-specific changes of 55 and 31 genes in superficial and deep neurons in schizophrenia, respectively. Gene set enrichment analysis (GSEA) was applied to the entire pre-ranked differential expression gene lists to gain a complete pathway analysis throughout all annotated genes. Our analysis revealed overrepresented groups of gene sets in schizophrenia, particularly in immunity and synapse-related pathways, suggesting the disruption of these pathways plays an important role in schizophrenia. We also detected other pathways previously demonstrated in schizophrenia pathophysiology, including cytokine and chemotaxis, postsynaptic signaling, and glutamatergic synapses. In addition, we observed several novel pathways, including ubiquitin-independent protein catabolic process. Considering the effects of antipsychotic treatment on gene expression, we applied a novel bioinformatics approach to compare our differential expression gene profiles with 51 antipsychotic treatment datasets, demonstrating that our results were not influenced by antipsychotic treatment. Taken together, we found pyramidal neuron-specific changes in neuronal immunity, synaptic dysfunction, and olfactory dysregulation in schizophrenia, providing new insights for the cell-subtype specific pathophysiology of chronic schizophrenia.

Communication Training, Adverse Events, and Quality Measures: 2 Retrospective Database Analyses in Washington State Hospitals.

OBJECTIVE: Washington State's HealthPact program was launched in 2011 as part of AHRQ's Patient Safety and Medical Liability Reform initiative. HealthPact delivered interdisciplinary communication training to health-care professionals with the goal of enhancing safety. We conducted 2 exploratory, retrospective database analyses to investigate training impact on the frequency of adverse events (AEs) and select quality measures across 3 time frames: pretraining (2009-2011), transition (2012), and posttraining (2013). METHODS: Using administrative data from Washington State's Comprehensive Hospital Abstract Reporting System (CHARS) and clinical registry data from the Surgical Care and Outcomes Assessment Program (SCOAP), we compared proportions of AEs and quality measures between HealthPact (n = 4) and non-HealthPact (n = 93-CHARS; n = 48-SCOAP) participating hospitals. Risk ratios enabled comparisons between the 2 groups. Multivariable logistic regression enabled investigation of the association between training and the frequency of AEs. RESULTS: Approximately 9.4% (CHARS) and 7.7% (SCOAP) of unique patients experienced 1 AE or greater. In CHARS, the odds of a patient experiencing an AE in a HealthPact hospital were initially (pretraining) higher than in a non-HealthPact hospital (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.10-1.17), lower in transition (OR, 0.80; 95% CI, 0.76-0.83) and posttraining (OR, 0.72; 95% CI, 0.69-0.75) periods. In SCOAP, ORs were consistently lower in HealthPact hospitals: pretraining (OR, 0.87; 95% CI, 0.80-0.95), transition (OR, 0.75; 95% CI, 0.70-0.81), and posttraining (OR, 0.63; 95% CI, 0.58-0.68). The proportion of at-risk patients that experienced each individual AE was low (<1%) throughout. Adherence to quality measures was high. CONCLUSIONS: Interprofessional communication training is an area of intense activity nationwide. A broad-based training initiative may play a role in mitigating AEs.

Microvascular Benefits of New Antidiabetic Agents: A Systematic Review and Network Meta-Analysis of Kidney Outcomes.

CONTEXT: Diabetic kidney disease affects nearly one-third of US adults with prevalent type 2 diabetes mellitus (T2DM). The use of new antidiabetic medications in the prevention and treatment of diabetic kidney disease is a growing area of research interest. OBJECTIVE: We sought to characterize the risk of developing a composite kidney outcome among patients receiving a new antidiabetic medication of the SGLT-2i, GLP-1ra, and DPP-4i drug classes. METHODS: We conducted a systematic literature search in MEDLINE to identify randomized trials observing kidney safety endpoints associated with the use of new antidiabetic medications. Two independent reviewers selected the 7 eligible studies for analysis. Included studies were published between January 2013 and March 2020, conducted with adult participantss, published full-text in English, and observed composite kidney outcomes. A network meta-analysis was conducted within a Bayesian framework using a fixed-effects model with uninformative priors. RESULTS: A qualitative assessment of transitivity was conducted to ensure similar distribution of potential modifiers across studies. Included studies were generally comparable in mean age, glycated hemoglobin A1c (HbA1c), and mean duration of T2DM at baseline. MAIN CONCLUSIONS: Compared with placebo, dapagliflozin was associated with the greatest reduction in risk of developing the composite kidney outcome (hazard ratio 0.53; 95% credible interval, 0.43-0.66) followed by empagliflozin, canagliflozin, semaglutide, and liraglutide. Linagliptin did not show a significant reduction in risk of the outcome. LIMITATIONS: This analysis was limited by the scarcity of data for kidney safety endpoints in large, randomized clinical trials. Although the heterogeneity statistic was low, there are slight differences in study design and baseline demographic characteristics across trials.

Adenosine Kinase Expression in the Frontal Cortex in Schizophrenia.

The adenosine hypothesis of schizophrenia posits that reduced availability of the neuromodulator adenosine contributes to dysregulation of dopamine and glutamate transmission and the symptoms associated with schizophrenia. It has been proposed that increased expression of the enzyme adenosine kinase (ADK) may drive hypofunction of the adenosine system. While animal models of ADK overexpression support such a role for altered ADK, the expression of ADK in schizophrenia has yet to be examined. In this study, we assayed ADK gene and protein expression in frontocortical tissue from schizophrenia subjects. In the dorsolateral prefrontal cortex (DLPFC), ADK-long and -short splice variant expression was not significantly altered in schizophrenia compared to controls. There was also no significant difference in ADK splice variant expression in the frontal cortex of rats treated chronically with haloperidol-decanoate, in a study to identify the effect of antipsychotics on ADK gene expression. ADK protein expression was not significantly altered in the DLPFC or anterior cingulate cortex (ACC). There was no significant effect of antipsychotic medication on ADK protein expression in the DLPFC or ACC. Overall, our results suggest that increased ADK expression does not contribute to hypofunction of the adenosine system in schizophrenia and that alternative mechanisms are involved in dysregulation of this system in schizophrenia.

Updating the Comparative Evidence on Second-Generation Antipsychotic Use With Schizophrenia.

Objective: The objective of this study was to conduct a systematic review of literature comparing second-generation antipsychotics (SGAs) with each other and with first-generation antipsychotics (FGAs) in treating schizophrenia. Methods: MEDLINE, the Cochrane Library, and PsycINFO databases were searched through January 2020. Following standard methods, recent high-quality systematic reviews of each drug comparison and subsequently published primary studies were included to update the meta-analyses with any new data. Two reviewers independently conducted study selection, abstraction, and quality assessment. Results: Two systematic reviews and 29 newer trials (total of 162 trials of SGAs, N=53,861; 116 trials of SGAs versus FGAs, N=119,558) were included. Most trials were of fair quality, industry-funded, and included older SGAs and a few recently approved SGAs (asenapine, lurasidone, iloperidone, cariprazine, brexpiprazole and long-acting injection [LAI] formulations of aripiprazole and paliperidone). Older SGAs had similar effects on function, quality of life, mortality, and adverse event incidence, although clozapine improved symptoms more than most other drugs and olanzapine and risperidone were superior to some other drugs. Olanzapine, risperidone, ziprasidone, and aripiprazole performed similarly on outcomes of benefit compared with haloperidol. Risperidone LAI and olanzapine resulted in fewer withdrawals due to adverse events, but risk of diabetes increased with olanzapine. Haloperidol had greater incidence of adverse events than did olanzapine and risperidone, but similar effects on other outcomes. Conclusions: Most comparative evidence favored older SGAs, with clozapine, olanzapine, and risperidone superior on more outcomes than other SGAs. Older SGAs had similar benefits as haloperidol but with fewer adverse events.

Providers' perceptions on barriers and facilitators to prescribing naloxone for patients at risk for opioid overdose after implementation of a national academic detailing program: A qualitative assessment.

BACKGROUND: Academic detailing is an educational outreach program that aligns providers' prescribing with evidence-based practice. The U.S. Department of Veterans Affairs (VA) Opioid Overdose Education and Naloxone Distribution (OEND) Program partnered with the VA Pharmacy Benefits Management National Academic Detailing Service to deliver naloxone education to providers who cared for patients at risk of opioid overdose. In this pilot study, we interviewed providers' who received academic detailing to capture their perceptions of facilitators and barriers to prescribing naloxone. OBJECTIVE: To identify providers' perceptions of facilitators and barriers to prescribing naloxone for patients at risk for opioid overdose after implementation of a national academic detailing program. METHODS: This was a hybrid inductive-deductive qualitative pilot using semi-structured interviews with VA providers to explore constructs associated with facilitators and barriers to prescribing take-home naloxone to patients at risk for opioid overdose from August 2017 to April 2018. RESULTS: Eleven participants were interviewed, six physicians, three clinical psychiatric pharmacists, and two nurse practitioners. Participants identified patient-level barriers (social stigma and lack of homeless patient support), poor data integration, and burden of data validation as barriers to prescribing naloxone. However, they also identified patient lists, repeat visits, and face-to-face/one-on-one video conferencing visits as important facilitators for naloxone prescribing. CONCLUSIONS/IMPORTANCE: Academic detailing will need to address issues of social stigma regarding naloxone, educate providers about existing support systems for homeless veterans, and develop tools for data integration to improve naloxone access for veterans at risk for an opioid overdose.

Implementation evaluation of academic detailing on naloxone prescribing trends at the United States Veterans Health Administration.

OBJECTIVE: Academic detailing in partnership with the Opioid Overdose Education and Naloxone Distribution (OEND) program was implemented to increase naloxone access for the prevention of opioid overdose mortality in veterans at the U.S. Department of Veterans Affairs (VA). However, implementation was not uniform leading to varying levels of intervention exposure potentially impacting naloxone prescribing. We examined the impact of implementation strength (proportion of providers exposed to academic detailing) at each station on naloxone prescribing from September 2014 to December 2017. STUDY DESIGN AND SETTING: Retrospective cohort design with fixed effects models at the VA. DATA COLLECTION/EXTRACTION METHODS: We used VA Corporate Data Warehouse for data on pharmacy dispensing, station-, provider- and patient-level characteristics. OEND-specific academic detailing activities came from data recorded by academic detailers using Salesforce.com. PRINCIPAL FINDINGS: VA stations wherein 100 percent of providers exposed to an OEND-related academic detailing educational outreach visit experienced an increased incident rate of naloxone prescribing that was 5.52 times the incident rate of stations where no providers were exposed; alternatively, this is equivalent to an average monthly increase of 2.60 naloxone prescriptions per 1000 population at risk for opioid overdose. CONCLUSIONS: Our findings highlight the importance of academic detailing's implementation strength on naloxone prescribing. Decision makers must carefully consider the implementation process to achieve the greatest effectiveness from the intervention.

Empowering genomic medicine by establishing critical sequencing result data flows: the eMERGE example.

The eMERGE Network is establishing methods for electronic transmittal of patient genetic test results from laboratories to healthcare providers across organizational boundaries. We surveyed the capabilities and needs of different network participants, established a common transfer format, and implemented transfer mechanisms based on this format. The interfaces we created are examples of the connectivity that must be instantiated before electronic genetic and genomic clinical decision support can be effectively built at the point of care. This work serves as a case example for both standards bodies and other organizations working to build the infrastructure required to provide better electronic clinical decision support for clinicians.

Automating Electronic Clinical Data Capture for Quality Improvement and Research: The CERTAIN Validation Project of Real World Evidence.

BACKGROUND: The availability of high fidelity electronic health record (EHR) data is a hallmark of the learning health care system. Washington State's Surgical Care Outcomes and Assessment Program (SCOAP) is a network of hospitals participating in quality improvement (QI) registries wherein data are manually abstracted from EHRs. To create the Comparative Effectiveness Research and Translation Network (CERTAIN), we semi-automated SCOAP data abstraction using a centralized federated data model, created a central data repository (CDR), and assessed whether these data could be used as real world evidence for QI and research. OBJECTIVES: Describe the validation processes and complexities involved and lessons learned. METHODS: Investigators installed a commercial CDR to retrieve and store data from disparate EHRs. Manual and automated abstraction systems were conducted in parallel (10/2012-7/2013) and validated in three phases using the EHR as the gold standard: 1) ingestion, 2) standardization, and 3) concordance of automated versus manually abstracted cases. Information retrieval statistics were calculated. RESULTS: Four unaffiliated health systems provided data. Between 6 and 15 percent of data elements were abstracted: 51 to 86 percent from structured data; the remainder using natural language processing (NLP). In phase 1, data ingestion from 12 out of 20 feeds reached 95 percent accuracy. In phase 2, 55 percent of structured data elements performed with 96 to 100 percent accuracy; NLP with 89 to 91 percent accuracy. In phase 3, concordance ranged from 69 to 89 percent. Information retrieval statistics were consistently above 90 percent. CONCLUSIONS: Semi-automated data abstraction may be useful, although raw data collected as a byproduct of health care delivery is not immediately available for use as real world evidence. New approaches to gathering and analyzing extant data are required.

Cell-subtype-specific changes in adenosine pathways in schizophrenia.

Prior work in animal models implicates abnormalities of adenosine metabolism in astrocytes as a possible pathophysiological mechanism underlying the symptoms of schizophrenia. In the present study, we sought to reverse-translate these findings back to the human brain in schizophrenia, focusing on the following questions: (1) Which components of the adenosine system are dysregulated in schizophrenia, and (2) are these changes limited to astrocytes? To address these questions, we captured enriched populations of DLPFC pyramidal neurons and astrocytes from schizophrenia and control subjects using laser capture microdissection and assessed expression of adenosine system components using qPCR. Interestingly, we found changes in enriched populations of astrocytes and neurons spanning metabolic and catabolic pathways. Ectonucleoside triphosphate diphosphohydrolase-1 (ENTPD1) and ENTPD2 mRNA levels were significantly decreased (p < 0.05, n = 16 per group) in enriched populations of astrocytes; in pyramidal neurons equilibrative nucleoside transporter 1 (ENT1) and adenosine A1 receptor mRNA levels were significantly decreased, with an increase in adenosine deaminase (ADA) (p < 0.05, n = 16 per group). Rodent studies suggest that some of our findings (A1R and ENTPD2) may be due to treatment with antipsychotics. Our findings suggest changes in expression of genes involved in regulating metabolism of ATP in enriched populations of astrocytes, leading to lower availability of substrates needed to generate adenosine. In pyramidal neurons, changes in ENT1 and ADA mRNA may suggest increased catabolism of adenosine. These results offer new insights into the cell-subtype-specific pathophysiology of the adenosine system in this illness.

Nine years of comparative effectiveness research education and training: initiative supported by the PhRMA Foundation.

The term comparative effectiveness research (CER) took center stage with passage of the American Recovery and Reinvestment Act (2009). The companion US$1.1 billion in funding prompted the launch of initiatives to train the scientific workforce capable of conducting and using CER. Passage of the Patient Protection and Affordable Care Act (2010) focused these initiatives on patients, coining the term 'patient-centered outcomes research' (PCOR). Educational and training initiatives were soon launched. This report describes the initiative of the Pharmaceutical Research and Manufacturers Association of America (PhRMA) Foundation. Through provision of grant funding to six academic Centers of Excellence, to spearheading and sponsoring three national conferences, the PhRMA Foundation has made significant contributions to creation of the scientific workforce that conducts and uses CER/PCOR.

Preliminary validation of the Claudication Symptom Instrument (CSI).

This article describes the development of the Claudication Symptom Instrument (CSI) and its measurement properties for evaluating the symptom experience of patients diagnosed with intermittent claudication (IC). We conducted semi-structured qualitative interviews with IC patients for item development and cognitive interviews in which patient comprehension of items was tested. We evaluated measurement properties using data collected and analyzed in the context of an observational comparative effectiveness study of IC treatments. Items measuring five symptom important to patients were developed and cognitively tested: Pain, Numbness, Heaviness, Cramping, and Tingling. Item means (higher means worse) ranged from 1.1 (Tingling) to 2.3 (Pain) (range: 0 'none' to 4 'extreme'). Rasch analysis yielded support for an overall score (χ2=26.5, df=20, p=0.15). The total CSI score differed by clinician-rated severity of mild versus moderate ( p<0.05), but not moderate versus severe. Re-administration of the CSI 5-10 days after baseline yielded an intra-class correlation coefficient of 0.86. Changes in CSI total score and VASCUQOL total score between baseline and 6 months post-treatment were correlated at -0.52 ( p<0.05). The CSI preliminarily meets accepted measurement standards for content validity, internal consistency and test-retest reliability, construct validity, and sensitivity for detecting change. Because of its high test-retest reliability, it may also be useful in clinical care with individual patients. It takes approximately 3 minutes to complete.

Favorable and publicly funded studies are more likely to be published: a systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to identify and quantify the characteristics of studies associated with the likelihood of publication. STUDY DESIGN AND SETTING: We searched for manuscripts that tracked cohorts of clinical studies ("cohorts") that from launch to publication. We explored the association of study characteristics with the probability of publication via traditional meta-analyses and meta-regression using random effects models. RESULTS: The literature review identified 85 cohorts of studies that met our inclusion criteria. The probability of publication was significantly higher for studies whose characteristics were favorable (odds ratio [OR] = 2.04; 95% confidence interval [CI]: 1.62, 2.57) or statistically significant (OR = 2.07; 95% CI: 1.52, 2.81), had a multicenter design (OR = 1.32; 95% CI: 1.16, 1.45), and were of later regulatory phase (3/4 vs. 1/2, OR = 1.34; 95% CI: 1.14, 1.49). Industry funding was modestly associated with lower (OR = 0.81; 95% CI: 0.67, 0.99) probability of publication. An exploratory analysis of effect modification revealed that the effect of the study characteristic "favorable results" on likelihood for publication was stronger for industry-funded studies. CONCLUSION: The study characteristics of favorable and significant results were associated with greater probability of publication.

Design Recommendations for Pharmacogenomics Clinical Decision Support Systems.

The use of pharmacogenomics (PGx) in clinical practice still faces challenges to fully adopt genetic information in targeting drug therapy. To incorporate genetics into clinical practice, many support the use of Pharmacogenomics Clinical Decision Support Systems (PGx-CDS) for medication prescriptions. This support was fueled by new guidelines to incorporate genetics for optimizing drug dosage and reducing adverse events. In addition, the complexity of PGx led to exploring CDS outside the paradigm of the basic CDS tools embedded in commercial electronic health records. Therefore, designing the right CDS is key to unleashing the full potential of pharmacogenomics and making it a part of clinicians' daily workflow. In this work, we 1) identify challenges and barriers of the implementation of PGx-CDS in clinical settings, 2) develop a new design approach to CDS with functional characteristics that can improve the adoption of pharmacogenomics guidelines and thus patient safety, and 3) create design guidelines and recommendations for such PGx-CDS tools.