Video-Assisted vs Robotic-Assisted Lung Lobectomies for Operating Room Resource Utilization and Patient Outcomes.

Importance: With increased use of robots, there is an inadequate understanding of minimally invasive modalities' time costs. This study evaluates the operative durations of robotic-assisted vs video-assisted lung lobectomies. Objective: To compare resource utilization, specifically operative time, between video-assisted and robotic-assisted thoracoscopic lung lobectomies. Design, Setting, and Participants: This retrospective cohort study evaluated patients aged 18 to 90 years who underwent minimally invasive (robotic-assisted or video-assisted) lung lobectomy from January 1, 2020, to December 31, 2022, with 90 days' follow-up after surgery. The study included multicenter electronic health record data from 21 hospitals within an integrated health care system in Northern California. Thoracic surgery was regionalized to 4 centers with 14 board-certified general thoracic surgeons. Exposures: Robotic-assisted or video-assisted lung lobectomy. Main Outcomes and Measures: The primary outcome was operative duration (cut to close) in minutes. Secondary outcomes were length of stay, 30-day readmission, and 90-day mortality. Comparisons between video-assisted and robotic-assisted lobectomies were generated using the Wilcoxon rank sum test for continuous variables and the χ2 test for categorical variables. The average treatment effects were estimated with augmented inverse probability treatment weighting (AIPTW). Patient and surgeon covariates were adjusted for and included patient demographics, comorbidities, and case complexity (age, sex, race and ethnicity, neighborhood deprivation index, body mass index, Charlson Comorbidity Index score, nonelective hospitalizations, emergency department visits, a validated laboratory derangement score, a validated institutional comorbidity score, a surgeon-designated complexity indicator, and a procedural code count), and a primary surgeon-specific indicator. Results: The study included 1088 patients (median age, 70.1 years [IQR, 63.3-75.8 years]; 704 [64.7%] female), of whom 446 (41.0%) underwent robotic-assisted and 642 (59.0%) underwent video-assisted lobectomy. The median unadjusted operative duration was 172.0 minutes (IQR, 128.0-226.0 minutes). After AIPTW, there was less than a 10% difference in all covariates between groups, and operative duration was a median 20.6 minutes (95% CI, 12.9-28.2 minutes; P < .001) longer for robotic-assisted compared with video-assisted lobectomies. There was no difference in adjusted secondary patient outcomes, specifically for length of stay (0.3 days; 95% CI, -0.3 to 0.8 days; P = .11) or risk of 30-day readmission (adjusted odds ratio, 1.29; 95% CI, 0.84-1.98; P = .13). The unadjusted 90-day mortality rate (1.3% [n = 14]) was too low for the AIPTW modeling process. Conclusions and Relevance: In this cohort study, there was no difference in patient outcomes between modalities, but operative duration was longer in robotic-assisted compared with video-assisted lung lobectomy. Given that this elevated operative duration is additive when applied systematically, increased consideration of appropriate patient selection for robotic-assisted lung lobectomy is needed to improve resource utilization.

Evaluation of an outreach programme for patients with COVID-19 in an integrated healthcare delivery system: a retrospective cohort study.

OBJECTIVES: In the first year of the COVID-19 pandemic, health systems implemented programmes to manage outpatients with COVID-19. The goal was to expedite patients' referral to acute care and prevent overcrowding of medical centres. We sought to evaluate the impact of such a programme, the COVID-19 Home Care Team (CHCT) programme. DESIGN: Retrospective cohort. SETTING: Kaiser Permanente Northern California. PARTICIPANTS: Adult members before COVID-19 vaccine availability (1 February 2020-31 January 2021) with positive SARS-CoV-2 tests. INTERVENTION: Virtual programme to track and treat patients with 'CHCT programme'. OUTCOMES: The outcomes were (1) COVID-19-related emergency department visit, (2) COVID-19-related hospitalisation and (3) inpatient mortality or 30-day hospice referral. MEASURES: We estimated the average effect comparing patients who were and were not treated by CHCT. We estimated propensity scores using an ensemble super learner (random forest, XGBoost, generalised additive model and multivariate adaptive regression splines) and augmented inverse probability weighting. RESULTS: There were 98 585 patients with COVID-19. The majority were followed by CHCT (n=80 067, 81.2%). Patients followed by CHCT were older (mean age 43.9 vs 41.6 years, p<0.001) and more comorbid with COmorbidity Point Score, V.2, score ≥65 (1.7% vs 1.1%, p<0.001). Unadjusted analyses showed more COVID-19-related emergency department visits (9.5% vs 8.5%, p<0.001) and hospitalisations (3.9% vs 3.2%, p<0.001) in patients followed by CHCT but lower inpatient death or 30-day hospice referral (0.3% vs 0.5%, p<0.001). After weighting, there were higher rates of COVID-19-related emergency department visits (estimated intervention effect -0.8%, 95% CI -1.4% to -0.3%) and hospitalisation (-0.5%, 95% CI -0.9% to -0.1%) but lower inpatient mortality or 30-day hospice referral (-0.5%, 95% CI -0.7% to -0.3%) in patients followed by CHCT. CONCLUSIONS: Despite CHCT following older patients with higher comorbidity burden, there appeared to be a protective effect. Patients followed by CHCT were more likely to present to acute care and less likely to die inpatient.

Broadly neutralizing antibodies targeting HIV: Progress and challenges.

Anti-HIV broadly neutralizing antibodies (bNAbs) offer a novel approach to treating, preventing, or curing HIV. Pre-clinical models and clinical trials involving the passive transfer of bNAbs have demonstrated that they can control viremia and potentially serve as alternatives or complement antiretroviral therapy (ART). However, antibody decay, persistent latent reservoirs, and resistance impede bNAb treatment. This review discusses recent advancements and obstacles in applying bNAbs and proposes strategies to enhance their therapeutic potential. These strategies include multi-epitope targeting, antibody half-life extension, combining with current and newer antiretrovirals, and sustained antibody secretion.

Antiretrovirals to CCR5 CRISPR/Cas9 gene editing - A paradigm shift chasing an HIV cure.

The evolution of drug-resistant viral strains and anatomical and cellular reservoirs of HIV pose significant clinical challenges to antiretroviral therapy. CCR5 is a coreceptor critical for HIV host cell fusion, and a homozygous 32-bp gene deletion (∆32) leads to its loss of function. Interestingly, an allogeneic HSCT from an HIV-negative ∆32 donor to an HIV-1-infected recipient demonstrated a curative approach by rendering the recipient's blood cells resistant to viral entry. Ex vivo gene editing tools, such as CRISPR/Cas9, hold tremendous promise in generating allogeneic HSC grafts that can potentially replace allogeneic ∆32 HSCTs. Here, we review antiretroviral therapeutic challenges, clinical successes, and failures of allogeneic and allogeneic ∆32 HSCTs, and newer exciting developments within CCR5 editing using CRISPR/Cas9 in the search to cure HIV.

Principles for Continuing Professional Development (CPD) Programs: A Statement by the ACPE CPD Advisory Committee.

Continuing Professional Development (CPD) has received increased attention within the pharmacy profession in the United States and is recognized as a potential pathway for ongoing professional development and practice transformation. Despite potential benefits of CPD, adoption in the United States has remained limited. A CPD program accreditation pathway, including principles, guidance, and a credit system for CPD programs, has recently been approved by the Accreditation Council for Pharmacy Education Board of Directors. This commentary reviews existing literature regarding pharmacy CPD, introduces CPD program principles and guidance for CPD program providers, and describes the model for awarding CPD units.

A passive dorsiflexing ankle prosthesis to increase minimum foot clearance during swing.

The biological ankle dorsiflexes several degrees during swing to provide adequate clearance between the foot and ground, but conventional energy storage and return (ESR) prosthetic feet remain in their neutral position, increasing the risk of toe scuffs and tripping. We present a new prosthetic ankle intended to reduce fall risk by dorsiflexing the ankle joint during swing, thereby increasing the minimum clearance between the foot and ground. Unlike previous approaches to providing swing dorsiflexion such as powered ankles or hydraulic systems with dissipative yielding in stance, our ankle device features a spring-loaded linkage that adopts a neutral angle during stance, allowing ESR, but adopts a dorsiflexed angle during swing. The ankle unit was designed, fabricated, and assessed in level ground walking trials on a unilateral transtibial prosthesis user to experimentally validate its stance and swing phase behaviors. The assessment consisted of three conditions: the ankle in an operational configuration, the ankle in a locked configuration (unable to dorsiflex), and the subject's daily use ESR prosthesis. When the ankle was operational, minimum foot clearance (MFC) increased by 13 mm relative to the locked configuration and 15 mm relative to his daily use prosthesis. Stance phase energy return was not significantly impacted in the operational configuration. The increase in MFC provided by the passive dorsiflexing ankle prosthesis may be sufficient to decrease the rate of falls experienced by prosthesis users in the real world.

Evaluating board certification within international advance pharmacy practice frameworks.

Utilizing board certification to advance practice and promote specializationthrough  formal assessment of pharmacists' knowledge and skills is one way the profession  demonstrates its commitment to improving knowledge and competence as well as  assuring optimal outcomes for patients. Credentialing and privileging in health  care provides an opportunity for selfregulation, peer recognition, and evaluation of  a professional's education, training, experience, and competence. Board of  Pharmacy Specialties currently recognizes more than 51,500 active pharmacist  board certifications in 14 specialties. While oriented primarily to pharmacy practice  in the United States, at least one board-certified pharmacist is located in  more than 50 countries, including Spain. The purpose of this paper is to highlight the intersections of board certification and international advanced  pharmacy practice frameworks.

El uso de las certificaciones para impulsar el perfeccionamiento y la especialización profesional mediante la evaluación formal de los  onocimientos y habilidades de los profesionales de farmacia es una de las maneras en que la profesión farmacéutica demuestra su compromiso con la  mejora del nivel de competencia profesional de los farmacéuticos y la obtención de los mejores resultados clínicos de los pacientes. La certificación y la acreditación en el ámbito sanitario brindan oportunidades de autorregulación, de reconocimiento entre colegas y de evaluación de la educación, formación, experiencia y competencias de los profesionales. El Board of Pharmacy Specialties actualmente reconoce a más de 51.500  armacéuticos con certificaciones activas en 14 especialidades farmacéuticas. Aunque las certificaciones están orientadas principalmente a  profesionales que ejercen en los Estados Unidos, hay al menos un farmacéutico  certificado en más de 50 países, incluido España. El objetivo de  ste artículo es poner de manifiesto el papel de las certificaciones otorgadas por  el Board of Pharmacy Specialties con los mecanismos de especialización  profesional existentes a nivel internacional. sound, defensible process. The  verriding concern of BPS is to ensure that the public receives the level of  harmacy services that will improve a patient's quality of life.  A total of 14  specialties are currently recognized by BPS13,14, including: • Board Certified  Nuclear Pharmacist (BCNP), since 1978. • Board Certified Nutrition Support  Pharmacist (BCNSP), since 1988. • Board Certified Pharmacotherapy Specialist  (BCPS), since 1988. • Board Certified Psychiatric Pharmacist (BCPP), since  1994. • Board Certified Oncology Pharmacist (BCOP), since 1996. • Board  Certified Ambulatory Care Pharmacist (BCACP), since 2009. • Board Certified  Critical Care Pharmacist (BCCCP), since 2013. • Board Certified Pediatric  pharmacy Specialist (BCPPS), since 2013. • Board Certified Geriatric  Pharmacist (BCGP), since 2017. • Board Certified Cardiology Pharmacist  (BCCP), since 2017. • Board Certified Infectious Diseases Pharmacist (BCIDP),  since 2017. • Board Certified Sterile Compounding Pharmacist (BCSCP), since  2018. • Board Certified Transplant Pharmacist (BCTXP), since 2018. • Board  Certified Emergency Medicine Pharmacist (BCEMP), since 2020.

Adults hospitalized with breakthrough COVID-19 have lower mortality than matched unvaccinated adults.

BACKGROUND: Coronavirus disease 2019 (COVID-19) breakthrough infections are common. OBJECTIVE: Evaluate in-hospital mortality of patients with COVID-19 by vaccination status using retrospective cohort study. METHODS: We generated propensity scores for receipt of full vaccination in adults requiring supplemental oxygen hospitalized at Kaiser Permanente Northern California (1 April 2021 to 30 November 2021) with positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction tests. Optimal matching of fully vaccinated/unvaccinated patients was performed comparing in-hospital mortality. RESULTS: Of 7305 patients, 1463 (20.0%) were full, 138 (1.9%) were partial, and 5704 (78.1%) were unvaccinated. Fully vaccinated were older than partial or unvaccinated (71.0, 63.0, and 54.0 years, respectively, p < 0.001) with more comorbidities (Comorbidity Point Scores 33.0, 22.0, and 10.0, p < 0.001) and immunosuppressant (11.5%, 8.7%, and 3.0%, p < 0.001) or chemotherapy exposure (2.8%, 0.7%, and 0.4%, p < 0.001). Fewer fully vaccinated patients died compared to matched unvaccinated (9.0% vs. 16.3%, p < 0.0001). CONCLUSION: Fully vaccinated patients are less likely to die compared to matched unvaccinated patients.

Análisis de la certificación en el marco de especialización farmacéutica a nivel internacional / Evaluating board certification within international advance pharmacy practice frameworks

El uso de las certificaciones para impulsar el perfeccionamiento y laespecialización profesional mediante la evaluación formal de los conocimientosy habilidades de los profesionales de farmacia es una de lasmaneras en que la profesión farmacéutica demuestra su compromiso conla mejora del nivel de competencia profesional de los farmacéuticos y laobtención de los mejores resultados clínicos de los pacientes. La certificacióny la acreditación en el ámbito sanitario brindan oportunidades deautorregulación, de reconocimiento entre colegas y de evaluación de laeducación, formación, experiencia y competencias de los profesionales. ElBoard of Pharmacy Specialties actualmente reconoce a más de 51.500 farmacéuticoscon certificaciones activas en 14 especialidades farmacéuticas.Aunque las certificaciones están orientadas principalmente a profesionalesque ejercen en los Estados Unidos, hay al menos un farmacéutico certificadoen más de 50 países, incluido España. El objetivo de este artículo esponer de manifiesto el papel de las certificaciones otorgadas por el Boardof Pharmacy Specialties con los mecanismos de especialización profesionalexistentes a nivel internacional.

Utilizing board certification to advance practice and promote specializationthrough formal assessment of pharmacists’ knowledge and skills is oneway the profession demonstrates its commitment to improving knowledgeand competence as well as assuring optimal outcomes for patients. Credentialingand privileging in health care provides an opportunity for selfregulation,peer recognition, and evaluation of a professional’s education,training, experience, and competence. Board of Pharmacy Specialtiescurrently recognizes more than 51,500 active pharmacist board certificationsin 14 specialties. While oriented primarily to pharmacy practice in theUnited States, at least one board-certified pharmacist is located in morethan 50 countries, including Spain. The purpose of this paper is to highlightthe intersections of board certification and international advanced pharmacypractice frameworks.

Exploratory analysis of novel electronic health record variables for quantification of healthcare delivery strain, prediction of mortality, and prediction of imminent discharge.

OBJECTIVE: To explore the relationship between novel, time-varying predictors for healthcare delivery strain (eg, counts of patient orders per hour) and imminent discharge and in-hospital mortality. MATERIALS AND METHODS: We conducted a retrospective cohort study using data from adults hospitalized at 21 Kaiser Permanente Northern California hospitals between November 1, 2015 and October 31, 2020 and the nurses caring for them. Patient data extracted included demographics, diagnoses, severity measures, occupancy metrics, and process of care metrics (eg, counts of intravenous drip orders per hour). We linked these data to individual registered nurse records and created multiple dynamic, time-varying predictors (eg, mean acute severity of illness for all patients cared for by a nurse during a given hour). All analyses were stratified by patients' initial hospital unit (ward, stepdown unit, or intensive care unit). We used discrete-time hazard regression to assess the association between each novel time-varying predictor and the outcomes of discharge and mortality, separately. RESULTS: Our dataset consisted of 84 162 161 hourly records from 954 477 hospitalizations. Many novel time-varying predictors had strong associations with the 2 study outcomes. However, most of the predictors did not merely track patients' severity of illness; instead, many of them only had weak correlations with severity, often with complex relationships over time. DISCUSSION: Increasing availability of process of care data from automated electronic health records will permit better quantification of healthcare delivery strain. This could result in enhanced prediction of adverse outcomes and service delays. CONCLUSION: New conceptual models will be needed to use these new data elements.

Model Based Design of a Low Cost and Compliant Low Profile Prosthetic Foot.

This paper describes the design of a simple and low-cost compliant low-profile prosthetic foot based on a cantilevered beam of uniform strength. The prosthetic foot is developed such that the maximum stress experienced by the beam is distributed approximately evenly across the length of the beam. Due to this stress distribution, the prosthetic foot exhibits compliant behavior not achievable through standard design approaches (e.g., designs based on simple cantilevered beams). Additionally, due to its simplicity and use of flat structural members, the foot can be manufactured at low cost. An analytical model of the compliant behavior of the beam is developed that facilitates rapid design changes to vary foot size and stiffness. A characteristic prototype was designed and constructed to be used in both a benchtop quasi-static loading test as well as a dynamic walking test for validation. The model predicted the rotational stiffness of the prototype with 5% error. Furthermore, the prototype foot was tested alongside two commercially available prosthetic feet (a low profile foot and an energy storage and release foot) in level walking experiments with a single study participant. The prototype foot displayed the lowest stiffness of the three feet (6.0, 7.1, and 10.4 Nm/deg for the prototype foot, the commercial low profile foot, and the energy storage and release foot, respectively). This foot design approach and accompanying model may allow for compliant feet to be developed for individuals with long residual limbs.

Development and Validation of an Obstetric Comorbidity Risk Score for Clinical Use.

Background: A comorbidity summary score may support early and systematic identification of women at high risk for adverse obstetric outcomes. The objective of this study was to conduct the initial development and validation of an obstetrics comorbidity risk score for automated implementation in the electronic health record (EHR) for clinical use. Methods: The score was developed and validated using EHR data for a retrospective cohort of pregnancies with delivery between 2010 and 2018 at Kaiser Permanente Northern California, an integrated health care system. The outcome used for model development consisted of adverse obstetric events from delivery hospitalization (e.g., eclampsia, hemorrhage, death). Candidate predictors included maternal age, parity, multiple gestation, and any maternal diagnoses assigned in health care encounters in the 12 months before admission for delivery. We used penalized regression for variable selection, logistic regression to fit the model, and internal validation for model evaluation. We also evaluated prenatal model performance at 18 weeks of pregnancy. Results: The development cohort (n = 227,405 pregnancies) had an outcome rate of 3.8% and the validation cohort (n = 41,683) had an outcome rate of 2.9%. Of 276 candidate predictors, 37 were included in the final model. The final model had a validation c-statistic of 0.72 (95% confidence interval [CI] 0.70-0.73). When evaluated at 18 weeks of pregnancy, discrimination was modestly diminished (c-statistic 0.68 [95% CI 0.67-0.70]). Conclusions: The obstetric comorbidity score demonstrated good discrimination for adverse obstetric outcomes. After additional appropriate validation, the score can be automated in the EHR to support early identification of high-risk women and assist efforts to ensure risk-appropriate maternal care.

Assessment of Tooth Preparations Submitted to Dental Laboratories for Fabrication of Monolithic Zirconia Crowns.

PURPOSE: The objective of this study was to assess the quality of posterior teeth prepared for monolithic zirconia crowns. MATERIALS AND METHODS: A total of 392 STL-files of posterior preparations for monolithic zirconia crowns were evaluated in this study. Three-dimensional (3D) images were evaluated using a software (3D Viewer; 3Shape A/S, Copenhagen, Denmark) for finish line design, finish line width, occluso-cervical dimension, total occlusal convergence (TOC), intercuspal angulation, finish line quality, line angle form, and presence or absence of undercut at the axial wall and unsupported lip of enamel. The assessment was performed by two calibrated evaluators. Then, data were descriptively analyzed. Data for occluso-cervical dimension and TOC were descriptively analyzed according to their location. RESULTS: Thirty-nine percent of premolars, 77% of first molars, and 91% of second molars had an average occluso-cervical dimension of less than 3 mm (premolars) and 4 mm (molars), with most of the preparations having a TOC of more than 20 degrees. More than 50% of preparations had undercut, unsupported enamel and/or unacceptable finish line quality. CONCLUSIONS: The quality of tooth preparation including finish line quality, absence of unsupported enamel and undercut at the axial wall should be evaluated when preparing monolithic zirconia crowns.

A Semi-Powered Ankle Prosthesis and Unified Controller for Level and Sloped Walking.

This paper describes a semi-powered ankle prosthesis and corresponding unified controller that provides biomimetic behavior for level and sloped walking without requiring identification of ground slope or modulation of control parameters. The controller is based on the observation that healthy individuals maintain an invariant external quasi-stiffness (spring like behavior between the shank and ground) when walking on level and sloped terrain. Emulating an invariant external quasi-stiffness requires an ankle that can vary the set-point (i.e., equilibrium angle) of the ankle stiffness. A semi-powered ankle prosthesis that incorporates a novel constant-volume power-asymmetric actuator was developed to provide this behavior, and the unified controller was implemented on it. The device and unified controller were assessed on three subjects with transtibial amputations while walking on inclines, level ground, and declines. Experimental results suggest that the prosthesis and accompanying controller can provide a consistent external quasi-stiffness similar to healthy subjects across all tested ground slopes.

Automated Identification of Adults at Risk for In-Hospital Clinical Deterioration.

BACKGROUND: Hospitalized adults whose condition deteriorates while they are in wards (outside the intensive care unit [ICU]) have considerable morbidity and mortality. Early identification of patients at risk for clinical deterioration has relied on manually calculated scores. Outcomes after an automated detection of impending clinical deterioration have not been widely reported. METHODS: On the basis of a validated model that uses information from electronic medical records to identify hospitalized patients at high risk for clinical deterioration (which permits automated, real-time risk-score calculation), we developed an intervention program involving remote monitoring by nurses who reviewed records of patients who had been identified as being at high risk; results of this monitoring were then communicated to rapid-response teams at hospitals. We compared outcomes (including the primary outcome, mortality within 30 days after an alert) among hospitalized patients (excluding those in the ICU) whose condition reached the alert threshold at hospitals where the system was operational (intervention sites, where alerts led to a clinical response) with outcomes among patients at hospitals where the system had not yet been deployed (comparison sites, where a patient's condition would have triggered a clinical response after an alert had the system been operational). Multivariate analyses adjusted for demographic characteristics, severity of illness, and burden of coexisting conditions. RESULTS: The program was deployed in a staggered fashion at 19 hospitals between August 1, 2016, and February 28, 2019. We identified 548,838 non-ICU hospitalizations involving 326,816 patients. A total of 43,949 hospitalizations (involving 35,669 patients) involved a patient whose condition reached the alert threshold; 15,487 hospitalizations were included in the intervention cohort, and 28,462 hospitalizations in the comparison cohort. Mortality within 30 days after an alert was lower in the intervention cohort than in the comparison cohort (adjusted relative risk, 0.84, 95% confidence interval, 0.78 to 0.90; P<0.001). CONCLUSIONS: The use of an automated predictive model to identify high-risk patients for whom interventions by rapid-response teams could be implemented was associated with decreased mortality. (Funded by the Gordon and Betty Moore Foundation and others.).

Associations of CYP2C9 and CYP2C19 Pharmacogenetic Variation with Phenytoin-Induced Cutaneous Adverse Drug Reactions.

The role of cytochrome P450 (CYP)2C9 and CYP2C19 genetic variation in risk for phenytoin-induced cutaneous adverse drug events is not well understood independently of the human leukocyte antigen B (HLA-B)*15:02 risk allele. In the multi-ethnic resource for Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort, we identified 382 participants who filled a phenytoin prescription between 2005 and 2017. These participants included 21 people (5%) who self-identified as Asian, 18 (5%) as black, 29 (8%) as white Hispanic, and 308 (81%) as white non-Hispanic. We identified 264 (69%) CYP2C9*1/*1, 77 (20%) CYP2C9*1/*2, and 29 (8%) CYP2C9*1/*3. We also determined CYP2C19 genotypes, including 112 with the increased activity CYP2C19*17 allele. Using electronic clinical notes, we identified 32 participants (8%) with phenytoin-induced cutaneous adverse events recorded within 100 days of first phenytoin dispensing. Adjusting for age, sex, daily dose, and race/ethnicity, participants with CYP2C9*1/*3 or CYP2C9*2/*2 genotypes were more likely to develop cutaneous adverse events compared with CYP2C9*1/*1 participants (odds ratio 4.47; 95% confidence interval 1.64-11.69; P < 0.01). Among participants with low-intermediate and poor CYP2C9 metabolizer genotypes, eight (22%) who also had extensive and rapid CYP2C19 metabolizer genotypes experienced cutaneous adverse events, compared with none of those who also had intermediate CYP2C19 metabolizer genotypes (P = 0.17). Genetic variation reducing CYP2C9 metabolic activity may increase risk for phenytoin-induced cutaneous adverse events in the absence of the HLA-B*15:02 risk allele.

Assessing the clinical impact of CYP2C9 pharmacogenetic variation on phenytoin prescribing practice and patient response in an integrated health system.

OBJECTIVE: To assess the impact of CYP2C9 variation on phenytoin patient response and clinician prescribing practice where genotype was unknown during treatment. METHODS: A retrospective analysis of Resource on Genetic Epidemiology Research on Adult Health and Aging cohort participants who filled a phenytoin prescription between 1996 and 2017. We used laboratory test results, medication dispensing records, and medical notes to identify associations of CYP2C9 genotype with phenytoin blood concentration, neurologic side effects, and medication dispensing patterns reflecting clinician prescribing practice and patient response. RESULTS: Among 993 participants, we identified 69% extensive, 20% high-intermediate, 10% low-intermediate, and 2% poor metabolizers based on CYP2C9 genotypes. Compared with extensive metabolizer genotype, low-intermediate/poor metabolizer genotype was associated with increased dose-adjusted phenytoin blood concentration [21.3 pg/mL, 95% confidence interval (CI): 13.6-29.0 pg/mL; P < 0.01] and increased risk of neurologic side effects (hazard ratio: 2.40, 95% CI: 1.24-4.64; P < 0.01). Decreased function CYP2C9 genotypes were associated with medication dispensing patterns indicating dose decrease, use of alternative anticonvulsants, and worse adherence, although these associations varied by treatment indication for phenytoin. CONCLUSION: CYP2C9 variation was associated with clinically meaningful differences in clinician prescribing practice and patient response, with potential implications for healthcare utilization and treatment efficacy.

Assessing clinical heterogeneity in sepsis through treatment patterns and machine learning.

OBJECTIVE: To use unsupervised topic modeling to evaluate heterogeneity in sepsis treatment patterns contained within granular data of electronic health records. MATERIALS AND METHODS: A multicenter, retrospective cohort study of 29 253 hospitalized adult sepsis patients between 2010 and 2013 in Northern California. We applied an unsupervised machine learning method, Latent Dirichlet Allocation, to the orders, medications, and procedures recorded in the electronic health record within the first 24 hours of each patient's hospitalization to uncover empiric treatment topics across the cohort and to develop computable clinical signatures for each patient based on proportions of these topics. We evaluated how these topics correlated with common sepsis treatment and outcome metrics including inpatient mortality, time to first antibiotic, and fluids given within 24 hours. RESULTS: Mean age was 70 ± 17 years with hospital mortality of 9.6%. We empirically identified 42 clinically recognizable treatment topics (eg, pneumonia, cellulitis, wound care, shock). Only 43.1% of hospitalizations had a single dominant topic, and a small minority (7.3%) had a single topic comprising at least 80% of their overall clinical signature. Across the entire sepsis cohort, clinical signatures were highly variable. DISCUSSION: Heterogeneity in sepsis is a major barrier to improving targeted treatments, yet existing approaches to characterizing clinical heterogeneity are narrowly defined. A machine learning approach captured substantial patient- and population-level heterogeneity in treatment during early sepsis hospitalization. CONCLUSION: Using topic modeling based on treatment patterns may enable more precise clinical characterization in sepsis and better understanding of variability in sepsis presentation and outcomes.

The Impact of Pharmacy-specific Predictors on the Performance of 30-Day Readmission Risk Prediction Models.

RESEARCH OBJECTIVE: Pharmacists are an expensive and limited resource in the hospital and outpatient setting. A pharmacist can spend up to 25% of their day planning. Time spent planning is time not spent delivering an intervention. A readmission risk adjustment model has potential to be used as a universal outcome-based prioritization tool to help pharmacists plan their interventions more efficiently. Pharmacy-specific predictors have not been used in the constructs of current readmission risk models. We assessed the impact of adding pharmacy-specific predictors on performance of readmission risk prediction models. STUDY DESIGN: We used an observational retrospective cohort study design to assess whether pharmacy-specific predictors such as an aggregate pharmacy score and drug classes would improve the prediction of 30-day readmission. A model of age, sex, length of stay, and admission category predictors was used as the reference model. We added predictor variables in sequential models to evaluate the incremental effect of additional predictors on the performance of the reference. We used logistic regression to regress the outcomes on predictors in our derivation dataset. We derived and internally validated our models through a 50:50 split validation of our dataset. POPULATION STUDIED: Our study population (n=350,810) was of adult admissions at hospitals in a large integrated health care delivery system. PRINCIPAL FINDINGS: Individually, the aggregate pharmacy score and drug classes caused a nearly identical but moderate increase in model performance over the reference. As a single predictor, the comorbidity burden score caused the greatest increase in model performance when added to the reference. Adding the severity of illness score, comorbidity burden score and the aggregate pharmacy score to the reference caused a cumulative increase in model performance with good discrimination (c statistic, 0.712; Nagelkerke R, 0.112). The best performing model included all predictors: severity of illness score, comorbidity burden score, aggregate pharmacy score, diagnosis groupings, and drug subgroups. CONCLUSIONS: Adding the aggregate pharmacy score to the reference model significantly increased the c statistic but was out-performed by the comorbidity burden score model in predicting readmission. The need for a universal prioritization tool for pharmacists may therefore be potentially met with the comorbidity burden score model. However, the aggregate pharmacy score and drug class models still out-performed current Medicare readmission risk adjustment models. IMPLICATIONS FOR POLICY OR PRACTICE: Pharmacists have a great role in preventing readmission, and therefore can potentially use one of our models: comorbidity burden score model, aggregate pharmacy score model, drug class model or complex model (a combination of all 5 major predictors) to prioritize their interventions while exceeding Medicare performance measures on readmission. The choice of model to use should be based on the availability of these predictors in the health care system.

Agreement Between Faculty and %Comparison for Preparation Depth Assessment in a Dental Technique Skills Course.

The aim of this retrospective study was to assess agreement between faculty and virtual assessment software in depth evaluation of rounded rectangular preparations in non-anatomical teeth prepared by second-year dental students. A total of 184 non-anatomical ivorine mandibular first molars prepared by second-year students were retrospectively evaluated in 2018. Each tooth was prepared to a depth of 1.5 mm within a laser-marked outline using a 330 bur, as detailed in the technique skills course syllabus. Preparations were recorded using an intraoral scanner. Then, virtual assessment software was used to superimpose a three-dimensional (3D) image of each preparation on a 3D image of a standard preparation produced by a faculty member. The software was used to calculate percentage comparison (%Comparison) values at 200 µm tolerance. Values of %Comparison ≥72% were considered satisfactory. In addition, each preparation depth was evaluated by two calibrated faculty members using a periodontal probe and a 330 bur. The preparation depth was considered satisfactory when more than 50% of the tooth preparation had a depth of 1.5 mm. The results showed almost perfect agreement (0.81 < kappa < 0.99) between faculty assessment and %Comparison value. The findings suggest that %Comparison values may be used to assess the tooth preparation depth of rounded rectangular preparations in non-anatomical teeth when prepared in a laser-marked outline.