Warfarin is characterized by marked variations in individual dose requirements and a narrow therapeutic window. Pharmacogenetics (PG) could improve dosing efficiency and safety, but clinical trials ...evidence is meager.
A Randomized and Clinical Effectiveness Trial Comparing Two Pharmacogenetic Algorithms and Standard Care for Individualizing Warfarin Dosing (CoumaGen-II) comprised 2 comparisons: (1) a blinded, randomized comparison of a modified 1-step (PG-1) with a 3-step algorithm (PG-2) (N=504), and (2) a clinical effectiveness comparison of PG guidance with use of either algorithm with standard dosing in a parallel control group (N=1866). A rapid method provided same-day CYP2C9 and VKORC1 genotyping. Primary outcomes were percentage of out-of-range international normalized ratios at 1 and 3 months and percentage of time in therapeutic range. Primary analysis was modified intention to treat. In the randomized comparison, PG-2 was noninferior but not superior to PG-1 for percentage of out-of-range international normalized ratios at 1 month and 3 months and for percentage of time in therapeutic range at 3 months. However, the combined PG cohort was superior to the parallel controls (percentage of out-of-range international normalized ratios 31% versus 42% at 1 month; 30% versus 42% at 3 months; percentage of time in therapeutic range 69% versus 58%, 71% versus 59%, respectively, all P<0.001). Differences persisted after adjustment for age, sex, and clinical indication. There were fewer percentage international normalized ratios ≥4 and ≤1.5 and serious adverse events at 3 months (4.5% versus 9.4% of patients, P<0.001) with PG guidance.
These findings suggest that PG dosing should be considered for broader clinical application, a proposal that is being tested further in 3 major randomized trials. The simpler 1-step PG algorithm provided equivalent results and may be preferable for clinical application.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00927862.
Characteristics of the neighborhood built environment influence health and health behavior. Google Street View (GSV) images may facilitate measures of the neighborhood environment that are ...meaningful, practical, and adaptable to any geographic boundary. We used GSV images and computer vision to characterize neighborhood environments (green streets, visible utility wires, and dilapidated buildings) and examined cross-sectional associations with chronic health outcomes among patients from the University of California, San Francisco Health system with outpatient visits from 2015 to 2017. Logistic regression models were adjusted for patient age, sex, marital status, race/ethnicity, insurance status, English as preferred language, assignment of a primary care provider, and neighborhood socioeconomic status of the census tract in which the patient resided. Among 214,163 patients residing in California, those living in communities in the highest tertile of green streets had 16-29% lower prevalence of coronary artery disease, hypertension, and diabetes compared to those living in communities in the lowest tertile. Conversely, a higher presence of visible utility wires overhead was associated with 10-26% more coronary artery disease and hypertension, and a higher presence of dilapidated buildings was associated with 12-20% greater prevalence of coronary artery disease, hypertension, and diabetes. GSV images and computer vision models can be used to understand contextual factors influencing patient health outcomes and inform structural and place-based interventions to promote population health.
Collecting neighborhood data can both be time- and resource-intensive, especially across broad geographies. In this study, we leveraged 1.4 million publicly available Google Street View (GSV) images ...from Utah to construct indicators of the neighborhood built environment and evaluate their associations with 2017-2019 health outcomes of approximately one-third of the population living in Utah. The use of electronic medical records allows for the assessment of associations between neighborhood characteristics and individual-level health outcomes while controlling for predisposing factors, which distinguishes this study from previous GSV studies that were ecological in nature. Among 938,085 adult patients, we found that individuals living in communities in the highest tertiles of green streets and non-single-family homes have 10-27% lower diabetes, uncontrolled diabetes, hypertension, and obesity, but higher substance use disorders-controlling for age, White race, Hispanic ethnicity, religion, marital status, health insurance, and area deprivation index. Conversely, the presence of visible utility wires overhead was associated with 5-10% more diabetes, uncontrolled diabetes, hypertension, obesity, and substance use disorders. Our study found that non-single-family and green streets were related to a lower prevalence of chronic conditions, while visible utility wires and single-lane roads were connected with a higher burden of chronic conditions. These contextual characteristics can better help healthcare organizations understand the drivers of their patients' health by further considering patients' residential environments, which present both risks and resources.
Nearly 25% of patients with peripartum cardiomyopathy (PPCM) will require cardiac transplantation. Whether post-transplant outcomes differ among patients with PPCM compared with other recipients ...remains unsettled.
The United Network for Organ Sharing database was queried for cardiac transplants, comparing characteristics and outcomes for PPCM, other women, and all others.
Between 1987 and 2010, 42,406 patients (9,419 women and 32,987 men) received a heart transplant. Of these, 485 women who had PPCM as the indication were younger (p < 0.001), had higher sensitization (p < 0.001), required higher intensity of cardiovascular support pre-transplant (p = 0.026), and had higher listing status (p < 0.001). Those with PPCM had more post-transplant rejection during the index transplant hospitalization (p < 0.001) and during the first year (p = 0.003). Comparing PPCM with other women and all others, graft survival was inferior (p = 0.004 and p < 0.003, respectively) and age-adjusted survival was lower (p < 0.001 and p = 0.02, respectively).
This large report shows outcomes of graft failure and death are inferior for recipients with PPCM, which may be partly explained by younger age, higher allosensitization, higher pre-transplant acuity, and increased rejection. More research is needed to determine management strategies to improve outcomes in PPCM heart transplant recipients.
Deep learning and, specifically, convoltional neural networks (CNN) represent a class of powerful models that facilitate the understanding of many problems in computer vision. When combined with a ...reasonable amount of data, CNNs can outperform traditional models for many tasks, including image classification. In this work, we utilize these powerful tools with imagery data collected through Google Street View images to perform virtual audits of neighborhood characteristics. We further investigate different architectures for chronic disease prevalence regression through networks that are applied to sets of images rather than single images. We show quantitative results and demonstrate that our proposed architectures outperform the traditional regression approaches.
Trials comparing balanced crystalloids with normal saline have yielded mixed results regarding reductions in kidney complications and mortality for hospitalized patients receiving intravenous fluids.
...To evaluate the association of a multifaceted implementation program encouraging the preferential use of lactated Ringer solution with patient outcomes and intravenous fluid-prescribing practices in a large, multilevel health care system.
This type 2 hybrid implementation and comparative effectiveness study enrolled all patients 18 years or older who received 1 L or more of intravenous fluids while admitted to an emergency department and/or inpatient unit at 1 of 22 hospitals in Idaho and Utah between November 1, 2018, and February 29, 2020. An interrupted time series analysis was used to assess study outcomes before and after interventions to encourage use of lactated Ringer solution.
Implementation program combining order set modification, electronic order entry alerts, and sequential clinician-targeted education to encourage prescribing of lactated Ringer solution instead of normal saline.
The primary implementation outcome was the patient-level proportion of intravenous fluids that was balanced crystalloids. The primary effectiveness outcome was the incidence of major adverse kidney events (MAKE30)-a composite of new persistent kidney dysfunction, new initiation of dialysis, and death-at 30 days.
Among 148 423 patients (median IQR age, 47 30-67 years; 91 302 women 61%), the proportion of total fluids received that was lactated Ringer solution increased from 28% to 75% in the first week vs the last week of the study (immediate implementation effect odds ratio OR, 3.44; 95% CI, 2.79-4.24). The estimated MAKE30 absolute risk reduction was 2.2% (95% CI, 1.3%-3.3%) based on interrupted time series analysis showing a decrease in the week-on-week trend for MAKE30 (OR difference, 0.03; 95% CI, 0.03-0.03, P < .001). The immediate postimplementation OR for MAKE30 was 0.88 (95% CI, 0.76-1.01), with a decrease in persistent kidney dysfunction (OR, 0.80; 95% CI, 0.69-0.93) and mortality (OR, 0.78; 95% CI, 0.65-0.93) but not dialysis (OR, 1.00; 95% CI, 0.76-1.32).
In this comparative effectiveness study, an implementation program was associated with an increase in the proportion of fluids administered as lactated Ringer solution compared with normal saline and was associated with a reduction in MAKE30 events among patients treated in a large integrated health care system.
Background:
Pharyngitis is 1 of the most common conditions leading to inappropriate antibiotic prescriptions. When personal protective equipment (PPE) was at first constrained during the COVID-19 ...pandemic, Intermountain Healthcare recommended limiting rapid group A streptococcal pharyngitis (GAS) testing in urgent-care clinics to preserve PPE. Notably, the percentage of pharyngitis encounters prescribed an antibiotic and that underwent GAS testing is a key Healthcare Effectiveness Data and Information Set (HEDIS) measure. We have described our experience with urgent-care pharyngitis encounters and the impact of temporarily reducing GAS testing on antibiotic prescribing before and during the COVID19 pandemic.
Method:
We identified all urgent care encounters between July 2018 and August 2021 associated with a primary diagnosis of pharyngitis using ICD-10 CM codes and a validated methodology. Pharyngitis encounters were assessed for antibiotic prescriptions ordered through the electronic health record (EHR) and the use of point-of-care rapid GAS tests. Pharyngitis encounters were analyzed monthly. We assessed the percentage of encounters associated with an antibiotic prescription regardless of testing and the percentage of encounters associated with an antibiotic prescription when a GAS test was or was not performed. We examined 3 periods relating to COVID-19 and GAS testing recommendations: the prepandemic period (July 2018–March 2020), the pandemic onset period (April 2020–June 2020), and the pandemic period (July 2020–August 2021).
Results:
Prior to the pandemic, the monthly percentage of pharyngitis encounters for which rapid GAS testing was performed was nearly 90% (Fig. 1). The average monthly percentage of urgent-care pharyngitis encounters prescribed an antibiotic was 38.9%, and the average percentage of monthly pharyngitis encounters prescribed an antibiotic that also underwent GAS testing was 90.4%. This HEDIS measure declined from 90.4% during the prepandemic period to 29.8% in the pandemic onset period when GAS testing was limited. Following resumption of routine testing practices the monthly percentage of urgent-care pharyngitis encounters for which rapid GAS testing was performed returned to levels ≥80% by July 2020 (Fig. 1). The average percentage of monthly pharyngitis encounters prescribed an antibiotic that also underwent GAS testing rose to 87.3% during this period.
Conclusions:
Limited PPE in our urgent care centers during the initial months of the COVID-19 pandemic was associated with a mandated substantial decline in rapid GAS testing. As testing volume decreased, we noted a simultaneous relative increase of >30% in antibiotic prescribing for pharyngitis. These findings suggest that rapid streptococcal testing promotes appropriate antibiotic prescribing.
Funding:
None
Disclosures:
None
Left ventricular assist device (LVAD) implantation before heart transplantation has been associated with formation of antibodies directed against human leukocyte antigens (HLA), often referred to as ...sensitization. This study investigated whether prior sensitization or LVAD type affected the degree of post-implantation sensitization. The records of consecutive HeartMate (HM) I and HM II LVAD patients were reviewed. Panel reactive antibody (PRA) was assessed before LVAD implantation and biweekly thereafter. Sensitization was defined as PRA > 10%, and high-degree sensitization was defined as PRA > 90%. An HM LVAD was implanted in 64 patients, and 11 received a HM II LVAD as a bridge to transplant. Ten HM I patients (16%) were sensitized before LVAD implantation (HM I-S), and 54 (84%) were not (HM I-Non-S). Nine HM I-S patients (90%) became highly sensitized (PRA > 90%) compared with 9 HM I-Non-S patients (16.7%; p < 0.001). The PRA remained elevated (> 90%) in 8 of the 9 (88.9%) highly sensitized HM I-S patients vs 5 of the 9 (55.6%) HM I-Non-S highly sensitized patients. The PRA levels in the rest of the HM I-S highly sensitized patients declined from 93% +/- 4% to 55% +/- 15% (p = 0.01). Among the 11 HM II patients, 1 (9%) was sensitized before LVAD implantation (PRA, 40%) and the PRA moderately increased to 80%. No other HM II patient became sensitized after implantation. Thus, 1 of 11 (9%) HM II patients became sensitized compared with 29 of 64 (45%) HM I patients (p = 0.04). Pre-sensitized patients are at higher risk for becoming and remaining highly HLA-allosensitized after LVAD implantation. The HeartMate II LVAD appears to cause less sensitization than HeartMate I.
Chronic kidney disease continues to be a major limiting factor for long-term survival of heart transplant recipients. Little is known about the early use of renin–angiotensin system (RAS) blocking ...agents and their impact on renal function and hemodynamics in heart transplant recipients. In this cohort study all eligible recipients of orthotopic heart transplants at the UTAH cardiac transplantation program from 2001 through 2007 were divided into 2 groups—patients who were started on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers within the first 4 weeks of transplantation and continued on these for ≥4 weeks during the first 3 months (RAS blockade group, n = 75) and those who were not (non-RAS blockade group, n = 52). All patients were followed for 1 year after transplantation. There were no significant differences at baseline between the 2 groups. Estimated glomerular filtration rate at 12 months was significantly higher in the RAS blockade group compared to the non-RAS blockade group (mean ± SD, 56.3 ± 22.4 vs 47.3 ± 18.1 ml/min/1.73 m2 , p = 0.036). At 12 months pulmonary artery systolic pressure was significantly lower in the RAS blockade group compared to the non-RAS blockade group (30.2 ± 7.4 vs 32.9 ± 9.3 mm Hg, p = 0.023). Left ventricular ejection fraction and pulmonary capillary wedge pressure were similar between the 2 groups. In conclusion, early RAS blockade after heart transplantation is safe, well tolerated, and associated with better renal function and hemodynamic profile at 1 year after transplantation.
PDF
