Anionic Ring-Opening Polymerization of N-(tolylsulfonyl)azetidines To Produce Linear Poly(trimethylenimine) and Closed-System Block Copolymers.

The anionic ring-opening copolymerization of N-( p-tolylsulfonyl)azetidine ( pTsAzet) and N-( o-tolylsulfonyl)azetidine ( oTsAzet) produces poly( pTsAzet- co- oTsAzet) as a statistical copolymer. The pTsAzet/ oTsAzet copolymerization is living and allows for the synthesis of poly(sulfonylazetidine) of target molecular weights with narrow dispersities. 1H NMR spectroscopy was used to monitor the kinetics of the polymerization and estimate the monomer reactivity ratios. It was found that the reactivity ratios for oTsAzet and pTsAzet at 180 °C are 1.66 and 0.60, respectively. The tosyl groups of p( pTsAzet- co- oTsAzet) were reductively removed to produce linear poly(trimethylenimine) (LPTMI). This represents the first route to LPTMI of controlled molecular weight and low dispersity. Finally, the slow kinetics of the sulfonylazetidine polymerization facilitated the synthesis of a block copolymer without requiring the sequential addition of monomer. Specifically, pTsAzet, oTsAzet, and ( N- p-toluenesulfonyl-2-methylaziridine) ( pTsMAz) were combined in solution. pTsMAz selectively polymerizes to form the first block at moderate temperature. After consumption of pTsMAz, the temperature was increased to copolymerize pTsAzet and oTsAzet and produce the block copolymer p( pTsMAz)- b-p( pTsAzet- co- oTsAzet).

Early detection of eating disorders in general practice.

BACKGROUND: General practitioners (GPs) are often the first health professional consulted in regard to eating disorders and their varied presentations. Given the prognostic significance of early detection of, and intervention for, such conditions, it is important that GPs feel confident to do so. OBJECTIVE: The aim of this article was to heighten awareness of the role of early identification and diagnosis of eating disorders, especially anorexia nervosa and bulimia nervosa, in the primary care setting. The focus will be on their presentations and diagnosis, including changes to the Diagnostic and statistical manual of mental disorders, 5th edition (DSM-5), with a brief overview of management recommendations and admission criteria. DISCUSSION: Eating disorders are complex, potentially life-threatening illnesses with significant medical and psychosocial consequences. Early detection and intervention can significantly contribute to better outcomes, and GPs are ideally placed to effect this.

CYP17 genotype modifies the impact of anthropometric variation on salivary estradiol in healthy women.

Several studies demonstrate that human ovarian function is responsive to the energetic environment, which has led to the development of theoretical models that explain this phenomenon. Although many genes are involved in ovarian hormone production, the possibility that genetic polymorphism may affect ovarian response to energetic conditions has not been considered. Cytochrome P450c17α is an enzyme that produces androgen precursors used to make estrogens during ovarian steroidogenesis, and is encoded by the CYP17 gene. A functionally significant variant within the promoter region of CYP17 has been linked to variation in steroid production, and some evidence suggests that this polymorphism could alter transcription of CYP17 in an insulin-dependent manner. We tested the hypothesis that the CYP17 variant affected the relationship between anthropometric measurements and salivary estradiol in healthy women in the United States (n = 28). PCR-RLFP analysis was used to genotype women for the genetic variant, and estradiol was assayed from saliva by EIA. Moderated regression analysis of these preliminary data revealed a significant interaction between waist-to-hip ratio and CYP17 genotype (P = 0.004). Our study provides evidence that gene-environment interactions should be considered in future adaptive models for human ovarian function. Moreover, our results stand to illuminate possible associations between this genetic variant and reproductive disease.

Primary mode of communication for people with total laryngectomy in the UK: a cross-sectional survey.

OBJECTIVE: This study aimed to report on the UK rate of surgical voice restoration usage and investigate the factors that influence its uptake. METHOD: A national multicentre audit of people with total laryngectomy was completed over a six-month period (March to September 2020) in response to the coronavirus disease 2019 pandemic. This study is a secondary analysis of the data collected, focusing on the primary communication methods used by people with total laryngectomy. RESULTS: Data on surgical voice restoration were available for 1196 people with total laryngectomy; a total of 852 people with total laryngectomy (71 per cent) used surgical voice restoration. Another type of communication method was used by 344 people. The factors associated with surgical voice restoration in the multiple regression analysis were sex (p = 0.003), employment (employed vs not employed, p < 0.001) and time post-laryngectomy (p < 0.001). CONCLUSION: This study provides an important benchmark for the current status of surgical voice restoration usage across the UK. It found that 71 per cent of people with total laryngectomy used surgical voice restoration as their primary communication method.

Hepatitis C virus detection and management after implementation of universal screening in pregnancy.

BACKGROUND: Accurately identifying cases of hepatitis C virus has important medical and public health consequences. In the setting of rising hepatitis C virus prevalence and highly effective treatment with direct-acting antivirals, the Society for Maternal-Fetal Medicine guidelines recently changed to recommend universal screening for hepatitis C virus during pregnancy. However, there is little data on the influence of this policy change on case identification and management. OBJECTIVE: We aimed to examine the influence of universal hepatitis C virus screening on our patient population. Our primary objective was to determine if there was a difference in the detected hepatitis C virus prevalence after the policy change. Our secondary objectives were to determine which factors were associated with a positive test for hepatitis C virus and to examine postpartum management of pregnant patients living with hepatitis C virus, including the (1) gastroenterology referral rate, (2) treatment rate, (3) infantile hepatitis C virus screening rate, and (4) factors associated with being referred for treatment. STUDY DESIGN: We conducted a single-center, retrospective cohort study of deliveries that occurred before (July 2018-June 2020) and after (July 2020-December 2021) the implementation of universal hepatitis C virus screening. Information on hepatitis C virus and HIV status, if patients were screened for hepatitis C virus, history of intravenous drug use, and basic demographic information were abstracted from the electronic medical records. A subset of patients was administered a questionnaire regarding hepatitis C virus risk factors. For all patients who tested positive for hepatitis C virus, information on if they were referred for treatment in the postpartum period and if their infant was screened for hepatitis C virus were abstracted from the electronic medical records. RESULTS: A total of 8973 deliveries occurred during this study period. A total of 71 (0.79%) patients had a detectable viral load. With implementation of universal screening, hepatitis C virus screening rates increased from 5.78% to 77.25% of deliveries (P<.01). The hepatitis C virus prevalence rates before and after universal screening was implemented were 0.78% and 0.81%, respectively (P=.88). There were significant demographic shifts in our pregnant population over this time period, including a reduction in intravenous drug use. A subset of 958 patients completed a hepatitis C virus risk factor questionnaire, in addition to undergoing universal hepatitis C virus screening. Ten patients screened positive with universal screening; only 8 of these individuals would have been identified with risk-based screening. Among the patients with a detectable viral load, 67.61% were referred for treatment and 18.75% were treated. A multivariate logistic regression model indicated that intravenous drug use was associated with significantly decreased odds of being referred for treatment (odds ratio, 0.14; 95% confidence interval, 0.04-0.59; P=.01). At the time of our evaluation, 52 infants were at least 18 months old and thus eligible for hepatitis C virus screening. Among these infants, 8 (15.38%) were screened for hepatitis C virus, and all were negative. CONCLUSION: Following the practice shift, we saw a significant increase in hepatitis C virus screening during pregnancy. However, postpartum treatment and infant screening remained low. Intravenous drug use was associated with a decreased likelihood of being referred for treatment. Pregnancy represents a unique time for hepatitis C virus case identification, although better linkage to care is needed to increase postpartum treatment.

Gene x environment interactions impact endometrial function and the menstrual cycle: PROGINS, life history, anthropometry, and physical activity.

OBJECTIVES: We assessed the impact of a high frequency, functionally significant allelic variant of the progesterone receptor gene (PROGINS) on endometrial function and menstrual cycle characteristics. Further we asked whether PROGINS moderates the impact of life history characteristics, anthropometric measures, and physical activity on endometrial function. METHODS: Fifty-two women were genotyped for the PROGINS variant, provided life history information, and had anthropometric measurements made. Women monitored their menstrual bleeding for three cycles, performed mid-cycle urinary ovulation tests, and recorded physical activity. A subset of women provided daily saliva samples and had mid-luteal endometrial thickness measurements taken during the third menstrual cycle. Salivary progesterone was assayed using ELISAs. The direct impact of PROGINS on endometrial and menstrual cycle characteristics was determined via independent t-tests with Bonferroni correction. Interactions between PROGINS and covariates were assessed by moderated regression. RESULTS: PROGINS did not directly impact any indicator of endometrial function. However, PROGINS caused an increase in menstrual cycle length with increasing mid-luteal progesterone levels; the opposite relationship was present in noncarriers (P < 0.05). Additionally, PROGINS interacted with four of six anthropometric measures (BMI, waist circumference, height, and waist-hip ratio) to impact endometrial function, however, interactions between PROGINS and life history variables, or physical activity was limited. CONCLUSIONS: The gene x environment interactions we report suggest that PROGINS alters endometrial sensitivity to maternal energetic condition. Thus, the possibility of genetically-based variation in sensitivity to energetic stress should be considered in future adaptive models of women's reproduction.

Adherence to swallowing recommendations during (chemo)radiotherapy in head and neck cancer survivors: a scoping review.

PURPOSE OF REVIEW: There is a paucity of knowledge regarding patient adherence to dysphagia recommendations. It is recognized that unique barriers and facilitators contribute to poor treatment adherence in head and neck cancer (HNC) survivors. This review aims to identify the key themes and knowledge gaps regarding adherence to swallowing recommendations in HNC survivors during (chemo)radiotherapy (C)RT. RECENT FINDINGS: Seven studies were identified. Six facilitators to adherence were extracted, namely pain relief, behavioural intervention, attendance at multidisciplinary clinic, individualised swallowing therapy, absence of prophylactic percutaneous endoscopic gastronomy (PEG) and positive social control from a spouse. Barriers to adherence included pain, depression and presence of prophylactic PEG. Adherence to swallowing recommendations positively impacted swallowing outcomes in one study. SUMMARY: Little is known about adherence to swallowing recommendations during (C)RT in HNC survivors. Capturing adherence is challenging. Several knowledge gaps were identified. Further research is needed to better understand the barriers and facilitators from the survivors' perspective. This will inform development of best practice regarding how swallowing recommendations are provided to promote adherence and improve outcomes.

Pharmacogenomics implementation across multiple clinic settings: a qualitative evaluation.

Aim: To advance clinical adoption and implementation of pharmacogenomics (PGx) testing, barriers and facilitators to these efforts must be understood. This study identified and examined barriers and facilitators to active implementation of a PGx program across multiple clinic settings in an academic healthcare system. Materials & methods: 28 contributors to the PGx implementation (e.g., clinical providers, informatics specialists) completed an interview to elicit their perceptions of the implementation. Results: Qualitative analysis identified several barriers and facilitators that spanned different stages of the implementation process. Specifically, unclear test payment mechanisms, decision support tool development, rigid workflows and provider education were noted as barriers to the PGx implementation. A multidisciplinary implementation team and leadership support emerged as key facilitators. Furthermore, participants also suggested strategies to overcome or maintain these factors. Conclusion: Assessing real-world implementation perceptions and suggested strategies from a range of implementation contributors facilitates a more comprehensive framework and best-practice guidelines for PGx implementation.

Computational pharmacogenotype extraction from clinical next-generation sequencing.

Background: Next-generation sequencing (NGS), including whole genome sequencing (WGS) and whole exome sequencing (WES), is increasingly being used for clinic care. While NGS data have the potential to be repurposed to support clinical pharmacogenomics (PGx), current computational approaches have not been widely validated using clinical data. In this study, we assessed the accuracy of the Aldy computational method to extract PGx genotypes from WGS and WES data for 14 and 13 major pharmacogenes, respectively. Methods: Germline DNA was isolated from whole blood samples collected for 264 patients seen at our institutional molecular solid tumor board. DNA was used for panel-based genotyping within our institutional Clinical Laboratory Improvement Amendments- (CLIA-) certified PGx laboratory. DNA was also sent to other CLIA-certified commercial laboratories for clinical WGS or WES. Aldy v3.3 and v4.4 were used to extract PGx genotypes from these NGS data, and results were compared to the panel-based genotyping reference standard that contained 45 star allele-defining variants within CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, CYP4F2, DPYD, G6PD, NUDT15, SLCO1B1, TPMT, and VKORC1. Results: Mean WGS read depth was >30x for all variant regions except for G6PD (average read depth was 29 reads), and mean WES read depth was >30x for all variant regions. For 94 patients with WGS, Aldy v3.3 diplotype calls were concordant with those from the genotyping reference standard in 99.5% of cases when excluding diplotypes with additional major star alleles not tested by targeted genotyping, ambiguous phasing, and CYP2D6 hybrid alleles. Aldy v3.3 identified 15 additional clinically actionable star alleles not covered by genotyping within CYP2B6, CYP2C19, DPYD, SLCO1B1, and NUDT15. Within the WGS cohort, Aldy v4.4 diplotype calls were concordant with those from genotyping in 99.7% of cases. When excluding patients with CYP2D6 copy number variation, all Aldy v4.4 diplotype calls except for one CYP3A4 diplotype call were concordant with genotyping for 161 patients in the WES cohort. Conclusion: Aldy v3.3 and v4.4 called diplotypes for major pharmacogenes from clinical WES and WGS data with >99% accuracy. These findings support the use of Aldy to repurpose clinical NGS data to inform clinical PGx.

Worldwide distribution of allelic variation at the progesterone receptor locus and the incidence of female reproductive cancers.

OBJECTIVES: Global patterns of the incidence of cancer are often attributed to environmental and lifestyle differences between regions. Less attention has been given to global patterns of allelic variation of genes that may contribute to the risk of developing cancer. METHODS: We genotyped samples from 21 populations for four variants of the progesterone receptor (PR) gene. One is an Alu insertion in intron 7 which defines the PROGINS haplotype. The others include a promoter region SNP 331+ G/A (rs10895068), a haplotype defining T/C substitution in intron 6 (rs561650), and an A/T substitution (rs608995) in the 3' untranslated region of the gene. All variants have been investigated elsewhere in association with female reproductive cancers in western populations. RESULTS: We found population differences in the frequency of each of these alleles across study populations (P < 0.01, log-likelihood G statistic, computed in FSTAT) and therefore examined the correlation between the frequency of each genetic variant and the incidence of three female reproductive cancers (breast, uterine, and ovarian) obtained from the Globocan 2008 database. Breast and ovarian cancer incidence were significantly correlated with the frequency of the Alu insertion (r = 0.86 and 0.53) and the +331 A variant (r = 0.57 and 0.73). CONCLUSIONS: Our data expand the information on genetic variation at the PR locus in non-western populations and support an argument for more work on the genetic epidemiology of cancer among nonwestern populations.

Advancing a "Good Life" for Farm Animals: Development of Resource Tier Frameworks for On-Farm Assessment of Positive Welfare for Beef Cattle, Broiler Chicken and Pigs.

There is increasing recognition that farm animal welfare standards should ensure positive welfare, as well as prevent negative welfare. Resources that are valued by an animal and that provide opportunities to engage in motivated behaviours can elicit positive physical and emotional states and therefore positive welfare and a "good life" for farmed animals. Evaluation of resource provision is considered the best way of assessing positive welfare at present, in the absence of validated and practical animal-based measures. Previous research has outlined a framework of three tiers of increasingly positive welfare (Welfare +, Welfare ++, Welfare +++) containing resources that incrementally increase the opportunities for a good life over and above the requirements of UK law and code of practice. Based on this blueprint, "Good Life Frameworks" were developed for beef cattle, broiler chickens and pigs, containing resources that increase good life opportunities according to the scientific literature and expert consultation. We describe the initial development of these frameworks, including a piloting exercise with the UK farm assurance industry, to further refine the frameworks according to auditor and farmer feedback, and test the frameworks as a method of on-farm assessment and assurance of a "good life" for farm animals.

Family support role in hospital rapid response teams: a scoping review.

OBJECTIVE: The objective of this review was to identify and understand the primary research investigating the family support role in hospital rapid response teams. INTRODUCTION: Individual studies have described the benefits of providing emotional and psychosocial support to family members of a person receiving emergency medical care from a rapid response team in a hospital setting. To the authors' knowledge, there are no studies that have identified and described these studies together. INCLUSION CRITERIA: All empirical qualitative and quantitative papers investigating a family support role delivered in a rapid response team in a hospital setting were included. METHODS: This review followed a published a priori protocol. The databases searched were MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO), Cochrane Library, and OpenGrey. The search strategy was not limited by publication date or by language. The title and abstract of all citations were reviewed by two authors independently to assess against the inclusion criteria. The full text of the studies meeting the inclusion criteria were retrieved and reviewed by two authors independently. Data from eligible studies were extracted by two authors separately using a predetermined data extraction form and summarized in tabular and narrative format. RESULTS: After a full-text review of 110 studies, six studies met all inclusion criteria. The studies were set in four countries. All rapid response teams were set in hospital locations. Charted data demonstrated that the family support role had been investigated predominantly by qualitative study designs from the perspective of staff delivering the support. One study reported health outcomes of family members who received family support. In all studies, the family support role was part of a resuscitation rapid response team. Family support was provided at all stages of the resuscitation procedure. The family support role was not consistently defined, with the activities of the family support person reported differently between studies. Twenty-five varying support activities were described, such as attending to the family members'comfort needs, explaining the process of resuscitation, and providing guidance to the family member. In all studies, the family support role was available to support the family witnessing the resuscitation. The family support role was delivered by professionals from varying disciplines, including social workers, nurses, health care workers, and health care chaplains. CONCLUSIONS: Family support roles are varied and are carried out by health professionals of diverse backgrounds, highlighting the importance of considering the support and training needs of the person performing the role. Future research using evaluation methods is recommended to deepen the understanding about the family support role in hospital-based rapid response teams.

A "Good Life" for Dairy Cattle: Developing and Piloting a Framework for Assessing Positive Welfare Opportunities Based on Scientific Evidence and Farmer Expertise.

On-farm welfare assessment tends to focus on minimising negative welfare, but providing positive welfare is important in order to give animals a good life. This study developed a positive welfare framework for dairy cows based on the existing scientific literature which has focused on developing positive welfare indicators, and trialled a participatory approach with farmers; refining the framework based on their recommendations, followed by a vet pilot phase on farm. The results revealed that farmers and scientists agree on what constitutes "a good life" for dairy cattle. Farmers value positive welfare because they value their cows' quality of life, and want to be proud of their work, improve their own wellbeing as well as receive business benefits. For each good life resource, the proportion of farmers going above and beyond legislation ranged from 27 to 84%. Furthermore, barriers to achieving positive welfare opportunities, including monetary and time costs, were not apparently insurmountable if implementation costs were remunerated (by the government). However, the intrinsic value in providing such opportunities also incentivises farmers. Overall, most farmers appeared to support positive welfare assessment, with the largest proportion (50%) supporting its use within existing farm assurance schemes, or to justify national and global marketing claims. Collaborating with farmers to co-create policy is crucial to showcase and quantify the UK's high welfare standards, and to maximise engagement, relevance and uptake of animal welfare policy, to ensure continuous improvement and leadership in the quality of lives for farm animals.

Longitudinal advocacy training for medical students: a virtual workshop series.

Advocacy curricula in Canadian medical schools vary significantly. Expert-led, interactive workshops can effectively teach students how to address social determinants of health and advocate for patients. The Longitudinal Advocacy Training Series (LATS) is a free-of-charge, virtual program providing advocacy training created for Canadian medical students by students. The program was straightforward to implement and had high participation rates with 1140 participants representing 9.7% of enrolled Canadian medical students. As well, the program had high satisfaction reported by 87.6% of participants. The LATS toolkit enables health professional programs to develop similar programs for empowering effective health advocates.

Au Canada, les programmes de formation en matière de promotion et de défense des droits varient considérablement d'une faculté de médecine à l'autre. Les ateliers interactifs dirigés par des experts constituent un outil efficace pour enseigner aux étudiants la façon aborder les déterminants sociaux de la santé afin de défendre les droits des patients. La Longitudinal Advocacy Training Series (LATS) est un programme virtuel gratuit de formation à la défense des droits, créé par des étudiants pour les étudiants. Le programme, facile à mettre en œuvre, a connu un taux de participation élevé, à savoir 1140 participants représentant 9,7 % des étudiants en médecine au Canada. En outre, 87,6 % des participants se sont dits très satisfaits du programme. La trousse à outils LATS permet aux programmes de formation des professions de la santé de mettre sur pied des modules similaires pour donner aux étudiants les moyens de devenir des défenseurs de la santé efficaces.

Clinical Opportunities for Germline Pharmacogenetics and Management of Drug-Drug Interactions in Patients With Advanced Solid Cancers.

PURPOSE: Precision medicine approaches, including germline pharmacogenetics (PGx) and management of drug-drug interactions (DDIs), are likely to benefit patients with advanced cancer who are frequently prescribed multiple concomitant medications to treat cancer and associated conditions. Our objective was to assess the potential opportunities for PGx and DDI management within a cohort of adults with advanced cancer. METHODS: Medication data were collected from the electronic health records for 481 subjects since their first cancer diagnosis. All subjects were genotyped for variants with clinically actionable recommendations in Clinical Pharmacogenetics Implementation Consortium guidelines for 13 pharmacogenes. DDIs were defined as concomitant prescription of strong inhibitors or inducers with sensitive substrates of the same drug-metabolizing enzyme and were assessed for six major cytochrome P450 (CYP) enzymes. RESULTS: Approximately 60% of subjects were prescribed at least one medication with Clinical Pharmacogenetics Implementation Consortium recommendations, and approximately 14% of subjects had an instance for actionable PGx, defined as a prescription for a drug in a subject with an actionable genotype. The overall subject-level prevalence of DDIs and serious DDIs were 50.3% and 34.8%, respectively. Serious DDIs were most common for CYP3A, CYP2D6, and CYP2C19, occurring in 24.9%, 16.8%, and 11.7% of subjects, respectively. When assessing PGx and DDIs together, approximately 40% of subjects had at least one opportunity for a precision medicine-based intervention and approximately 98% of subjects had an actionable phenotype for at least one CYP enzyme. CONCLUSION: Our findings demonstrate numerous clinical opportunities for germline PGx and DDI management in adults with advanced cancer.

Association of QT interval-prolonging drugs with clinical trial eligibility in patients with advanced cancer.

Introduction: Drug-induced prolongation of the heart rate-corrected QT interval (QTc) is associated with increased risk for the potentially fatal arrhythmia torsades de pointes. Due to arrhythmia risk, clinical trials with cancer therapeutics often exclude patients based on thresholds for QTc prolongation. Our objective was to assess associations between prescriptions for QT-prolonging drugs and the odds of meeting cancer trial exclusionary QTc thresholds in a cohort of adults with advanced cancer. Methods: Electronic health records were retrospectively reviewed for 271 patients seen at our institutional molecular solid tumor clinic. Collected data included demographics, QTc measurements, ventricular arrhythmia-related diagnoses, and all inpatient and outpatient prescriptions. Potential associations were assessed between demographic and clinical variables, including prescriptions for QT-prolonging drugs, and QTc measurements. Results: Women had longer median QTc measurements than men (p = 0.030) and were prescribed more QT-prolonging drugs during the study (p = 0.010). In all patients, prescriptions for QT-prolonging drugs were associated with longer median and maximum QTc measurements at multiple assessed time points (i.e., for QT-prolonging drugs prescribed within 10, 30, 60, and 90 days of QTc measurements). Similarly, the number of QT-prolonging drugs prescribed was correlated with longer median and maximum QTc measurements at multiple time points. Common QTc-related exclusionary criteria were collected from a review of ClinicalTrials.gov for recent cancer clinical trials. Based on common exclusion criteria, prescriptions for QT-prolonging drugs increased the odds of trial exclusion. Conclusion: This study demonstrates that prescriptions for QT-prolonging drugs were associated with longer QTc measurements and increased odds of being excluded from cancer clinical trials.

Best-worst scaling methodology to evaluate constructs of the Consolidated Framework for Implementation Research: application to the implementation of pharmacogenetic testing for antidepressant therapy.

BACKGROUND: Despite the increased demand for pharmacogenetic (PGx) testing to guide antidepressant use, little is known about how to implement testing in clinical practice. Best-worst scaling (BWS) is a stated preferences technique for determining the relative importance of alternative scenarios and is increasingly being used as a healthcare assessment tool, with potential applications in implementation research. We conducted a BWS experiment to evaluate the relative importance of implementation factors for PGx testing to guide antidepressant use. METHODS: We surveyed 17 healthcare organizations that either had implemented or were in the process of implementing PGx testing for antidepressants. The survey included a BWS experiment to evaluate the relative importance of Consolidated Framework for Implementation Research (CFIR) constructs from the perspective of implementing sites. RESULTS: Participating sites varied on their PGx testing platform and methods for returning recommendations to providers and patients, but they were consistent in ranking several CFIR constructs as most important for implementation: patient needs/resources, leadership engagement, intervention knowledge/beliefs, evidence strength and quality, and identification of champions. CONCLUSIONS: This study demonstrates the feasibility of using choice experiments to systematically evaluate the relative importance of implementation determinants from the perspective of implementing organizations. BWS findings can inform other organizations interested in implementing PGx testing for mental health. Further, this study demonstrates the application of BWS to PGx, the findings of which may be used by other organizations to inform implementation of PGx testing for mental health disorders.

Multisite evaluation of institutional processes and implementation determinants for pharmacogenetic testing to guide antidepressant therapy.

There is growing interest in utilizing pharmacogenetic (PGx) testing to guide antidepressant use, but there is lack of clarity on how to implement testing into clinical practice. We administered two surveys at 17 sites that had implemented or were in the process of implementing PGx testing for antidepressants. Survey 1 collected data on the process and logistics of testing. Survey 2 asked sites to rank the importance of Consolidated Framework for Implementation Research (CFIR) constructs using best-worst scaling choice experiments. Of the 17 sites, 13 had implemented testing and four were in the planning stage. Thirteen offered testing in the outpatient setting, and nine in both outpatient/inpatient settings. PGx tests were mainly ordered by psychiatry (92%) and primary care (69%) providers. CYP2C19 and CYP2D6 were the most commonly tested genes. The justification for antidepressants selected for PGx guidance was based on Clinical Pharmacogenetics Implementation Consortium guidelines (94%) and US Food and Drug Administration (FDA; 75.6%) guidance. Both institutional (53%) and commercial laboratories (53%) were used for testing. Sites varied on the methods for returning results to providers and patients. Sites were consistent in ranking CFIR constructs and identified patient needs/resources, leadership engagement, intervention knowledge/beliefs, evidence strength and quality, and the identification of champions as most important for implementation. Sites deployed similar implementation strategies and measured similar outcomes. The process of implementing PGx testing to guide antidepressant therapy varied across sites, but key drivers for successful implementation were similar and may help guide other institutions interested in providing PGx-guided pharmacotherapy for antidepressant management.

Distribution of Pupil Offset and Angle Kappa in a Refractive Surgery Preoperative Population of 750 Myopic, Emmetropic, and Hyperopic Eyes.

PURPOSE: To report the distribution of pupil offset and angle kappa in 750 myopic, emmetropic, and hyperopic eyes presenting for refractive surgery. METHODS: A retrospective study included 750 consecutive eyes screened for corneal refractive surgery between January 2006 and February 2013. The eyes were divided into three equal groups based on manifest refraction spherical equivalent (SEQ): emmetropic group between -0.25 and +0.50 diopters (D) and cylinder up to 1.00 D, myopic group greater than -0.50 D, and hyperopic group greater than +0.50 D. Angle kappa was measured with the Orbscan II software (Bausch & Lomb, Inc) and pupil offset defined as the distance at the corneal plane between the corneal vertex and the pupil center. Correlations with SEQ, cylinder, scotopic pupil diameter, average keratometry, and age were performed. RESULTS: All results are reported for myopic, emmetropic, and hyperopic groups, respectively. Mean SEQ was -4.84 ± 2.89 D (range: -0.88 to -14.00 D), +0.21 ± 0.23 D (range: -0.25 to +0.50 D), and +2.44 ± 1.58 D (range: +0.63 to +7.75 D). Mean pupil offset magnitude was 0.27 ± 0.14 mm (range: 0.00 to 0.68 mm), 0.34 ± 0.14 mm (range: 0.02 to 0.78 mm), and 0.39 ± 0.13 mm (range: 0.07 to 0.75 mm). Mean pupil offset X-component was -0.18 ± 0.18, -0.28 ± 0.16, and -0.34 ± 0.15 mm (temporally displaced from the corneal vertex). Mean pupil offset Y-component was 0.06 ± 0.15, 0.03 ± 0.16, and 0.01 ± 0.16 mm (superiorly displaced from the corneal vertex). Multivariate linear regression for pupil offset magnitude found statistically significant variables were SEQ, cylinder, scotopic pupil diameter, and average keratometry. For pupil offset X-component, significant variables were SEQ, cylinder, and scotopic pupil diameter. For pupil offset Y-component, significant variables were SEQ and scotopic pupil diameter. Mean angle kappa was 5.28 ± 1.49°, 6.14 ± 1.44°, and 5.77 ± 1.29°. CONCLUSIONS: Contrary to common belief, a pupil offset is present in the vast majority of eyes regardless of refractive error, with the mean temporal offset of at least 0.18 mm. Confirming previous studies, the largest pupil offset was found in the hyperopic group. However, there was also a wide range of pupil offset in myopic and emmetropic eyes. Correlations with SEQ and keratometry support the theory that pupil offset is also correlated with axial length. [J Refract Surg. 2021;37(1):49-58.].