How Blackouts during Heat Waves Amplify Mortality and Morbidity Risk.

The recent concurrence of electrical grid failure events in time with extreme temperatures is compounding the population health risks of extreme weather episodes. Here, we combine simulated heat exposure data during historical heat wave events in three large U.S. cities to assess the degree to which heat-related mortality and morbidity change in response to a concurrent electrical grid failure event. We develop a novel approach to estimating individually experienced temperature to approximate how personal-level heat exposure changes on an hourly basis, accounting for both outdoor and building-interior exposures. We find the concurrence of a multiday blackout event with heat wave conditions to more than double the estimated rate of heat-related mortality across all three cities, and to require medical attention for between 3% (Atlanta) and more than 50% (Phoenix) of the total urban population in present and future time periods. Our results highlight the need for enhanced electrical grid resilience and support a more spatially expansive use of tree canopy and high albedo roofing materials to lessen heat exposures during compound climate and infrastructure failure events.

Safety of subcutaneous immunotherapy in patients with severe asthma.

BACKGROUND: Severe asthma (SA) has been identified as a risk factor for severe systemic reactions (SR) to allergen subcutaneous immunotherapy (SCIT). However, the incidence and characterization of SRs in SA in comparison to less severe or no asthma is not known. OBJECTIVE: The objective of this study was to characterize the incidence of SRs in patients with SA receiving SCIT in comparison to patients with no asthma or less SA. METHODS: A retrospective cohort study was performed on patients receiving SCIT from a multicenter national network of private allergy practices between January 2015 and December 2019. Demographics, asthma severity (International Classification of Diseases-10 codes), concomitant medications, aeroallergen skin testing, measures of asthma control with the asthma control test and forced expiratory volume in 1 second values, SCIT prescription, and an SR standardized form were assessed. RESULTS: A total of 65,855 patients, with 1072 patients having SA receiving SCIT, were included with a total of 4415 SRs (19.9 SR per 10,000 injection visits). Severe asthma had 23.9 SRs per 10,000 injection visits (incidence rate, 0.239; 95% confidence interval [0.189-0.298]). There were 155 grade III or IV SRs; 5 (3.2%) occurred in the SA group. There was no difference in rates of grade III or IV SRs between SA and no asthma and in rates of total SRs between SA and less SA. CONCLUSION: In a large cohort of patients with SA undergoing multiallergen SCIT drawn from a diverse outpatient allergy population, the diagnosis of SA was not associated with increased moderate-severe SRs compared with patients without asthma and any severity of asthma.

Compound Climate and Infrastructure Events: How Electrical Grid Failure Alters Heat Wave Risk.

The potential for critical infrastructure failures during extreme weather events is rising. Major electrical grid failure or "blackout" events in the United States, those with a duration of at least 1 h and impacting 50,000 or more utility customers, increased by more than 60% over the most recent 5 year reporting period. When such blackout events coincide in time with heat wave conditions, population exposures to extreme heat both outside and within buildings can reach dangerously high levels as mechanical air conditioning systems become inoperable. Here, we combine the Weather Research and Forecasting regional climate model with an advanced building energy model to simulate building-interior temperatures in response to concurrent heat wave and blackout conditions for more than 2.8 million residents across Atlanta, Georgia; Detroit, Michigan; and Phoenix, Arizona. Study results find simulated compound heat wave and grid failure events of recent intensity and duration to expose between 68 and 100% of the urban population to an elevated risk of heat exhaustion and/or heat stroke.

Real-world mapping of allergy immunotherapy in the United States: The argument for improving adherence.

Background: There is a dearth of real-world evidence studies focused on allergy immunotherapy (AIT) use among patients with allergic rhinitis (AR). Objective: This study examined claims data of AR patients residing in the United States to assess patient characteristics and health outcomes. Methods: AR patients were identified in the IBM MarketScan database between January 1, 2014, and March 31, 2017. Patients receiving AIT were identified with relevant billing codes (earliest AIT claim for vaccine as the index date); patients without AIT were identified with claims that contained a diagnosis code for AR (earliest AR claim as the index date). All the patients were required to have continuous enrollment 12 months prior to and following their index date. AIT patients reaching 25+ injection claims were analyzed as a separate maintenance cohort. Patients were assessed for demographic characteristics, comorbid conditions, and health care utilization. Results: A total of 2,334,530 AR patients were included; 103,207 had at least one AIT claim, with 45,279 (43.9%) of these patients reaching maintenance. Patients who reached AIT maintenance presented higher rates of baseline comorbidities than both the full AIT cohort and the patients with no AIT claims, including asthma (34.6% versus 30.1% versus 7.5%) and upper respiratory tract infections (63.1% versus 60.3% versus 34.2%). From baseline to follow-up, maintenance AIT patients demonstrated reductions in all AR-related comorbidities assessed, along with reductions in all-cause and AR-related service utilization. Conclusion: Patients initiating AIT presented the greatest need for therapeutic intervention, as evidenced by higher allergy-related comorbidities; those who reached maintenance demonstrated improved outcomes following the initiation of therapy. Continued efforts to increase patient awareness and adherence to AIT are needed.

How race, ethnicity, and income moderate the relationship between urban vegetation and physical activity in the United States.

To facilitate physical activity interventions, researchers identify which factors associate with physical activity, such as vegetation levels of the surrounding environment. While most studies examining vegetation and physical activity find a positive correlation, the literature does not investigate how vegetation may have a varied effect on physical activity based on demographic composition. This study examined how race, ethnicity, and income moderate the relationship between both non-tree vegetation and tree canopy on the percentage of individuals participating in leisure-time physical activity per census tract. Physical activity data from 2013 to 2014 for 7842 census tracts across 25 US cities originated from the CDC's 500 Cities project. Aerial images from the USDA's National Agriculture Imagery Program were used to classify vegetation levels per tract. Demographic variables originated from the American Community Survey 2011-2015 5-year estimates. Tracts were stratified into four types (Black + low income, Hispanic + low income, White + high income, and remaining) and assessed through multilevel modeling as to whether tract type moderated the relationship between vegetation and physical activity. Results showed that non-tree vegetation negatively associated with physical activity across all census tract types, while tree canopy exhibited a mixed association with physical activity, based on tract type. These findings can spur further research into how vegetation impacts physical activity of different demographic groups, and potentially inform greenspace and tree planting installments in those areas at greatest risk for physical inactivity-related diseases.

Long-term omalizumab outcomes in chronic idiopathic urticaria: a real-world study.

Background: Although clinical trials documented omalizumab's efficacy in U.S. patients with chronic idiopathic urticaria (CIU), the real-world evidence on its long-term effectiveness is lacking. Objective: To assess omalizumab use and the long-term response in a large sample of U.S. real-world patients. Methods: Patients with CIU and ≥ 12 years old who were initiated on omalizumab (index date) and with ≥ 6 months of postindex data were identified in an electronic medical record system (2007-2018). Omalizumab use was described. Provider assessments of disease control and course, and patient-reported symptoms were compared at 6-month intervals postindex versus baseline in the patients with values available at both time points. Results: A total of 1096 patients (mean age, 44.1 years; 74.7% women) were followed up for a mean of 19 months postindex. Patients, predominantly initiated on a 300-mg dose, received a mean of 15 omalizumab administrations and were treated continuously for a mean of 14.2 months. At 6 months postindex versus baseline, the patients (n = 708) were more likely to be well controlled (odds ratio [OR] 31.68 [95% confidence interval {CI}, 17.20-58.36]) with an improved disease course (OR 15.73 [95% CI, 11.33-21.85]). Moreover, the patients (n = 373) were less likely to report itching (OR 0.39 [95% CI, 0.21-0.76]), rash (OR 0.59 [95% CI, 0.45-0.78]), and swelling (OR 0.46 [95% CI, 0.36-0.59]). Benefits associated with omalizumab treatment were sustained through month 24 and beyond. Conclusion: This real-world study showed that the patients who received a mean of 15 omalizumab administrations over a mean of 14.2 months experienced, starting at 6 and through 24 months after omalizumab initiation and beyond, improved CIU control, course, and symptoms.

Characterizing patients with asthma who received Global Initiative for Asthma steps 4-5 therapy and managed in a specialty care setting.

BACKGROUND: Severe asthma is recognized in the European Respiratory Society/American Thoracic Society guidelines as a major unmet need in the management of asthma. OBJECTIVE: The study objective was to describe the clinical burden of Global Initiative for Asthma (GINA) steps 4-5 asthma for patients treated by specialists in the U.S. community setting. METHODS: Patients, ages ≥12 years, with asthma who received GINA step 4 or 5 treatment and were treated at a large U.S. allergy practice network between January 1, 2010, and April 30, 2016, were retrospectively identified by using electronic health records. Clinical outcomes included lung function (forced expiratory volume in one second of expiration [FEV1] and FEV1% predicted), symptom control (Asthma Control Test [ACT]), the fractional exhaled nitric oxide (FeNO) value (FeNO ≥25 ppb indicates airway inflammation), and asthma medication use. The change in outcomes from baseline to 12 and 24 months after the index date was calculated. RESULTS: Of 120,116 patients with asthma, 12,922 (10.8%) had severe asthma, 68% (n = 8751) while on step 4 therapy. The mean baseline prebronchodilation FEV1% predicted was 79.7%, and the mean baseline ACT score was 17.0. With uncontrolled asthma defined as an ACT score of ≤19 and/or an FEV1 value of <80% predicted and/or oral corticosteroid use of ≥2 bursts, 52.5% and 57.7% of patients on step 4 and step 5 therapy, respectively, had uncontrolled asthma at baseline. Of a subset of patients, 40.9% had an eosinophil count of ≥300 cells/mm3 and 44% had an FeNO concentration of ≥25 ppb. Small increases in the FEV1 value were observed from baseline to 12 months (n = 4022) and 24 months (n = 2326) postindex (0.07 and 0.04 L, respectively). CONCLUSION: A considerable proportion of patients had uncontrolled asthma while on current GINA steps 4-5 treatment, which indicated that additional therapies may be required to reduce the clinical burden of severe asthma.

Asthma control, lung function, symptoms, and corticosteroid sparing after omalizumab initiation in patients with allergic asthma.

BACKGROUND: Omalizumab is approved in patients with moderate-to-severe allergic asthma with symptoms uncontrolled, despite the mainstay therapy. OBJECTIVE: Electronic medical records (EMR) were used to increase the knowledge of omalizumab effectiveness in a real-world setting. METHODS: Patients with uncontrolled moderate-to-severe allergic asthma, ages ≥12 years old, initiated on omalizumab (index date), with ≥12 months of pre- and postindex data, were identified in an EMR data base. An Asthma Control Test score (≥20 is considered well controlled), forced expiratory volume in 1 second as a percentage of the predicted value (<80% considered below normal), symptoms, and oral corticosteroid (OCS) and inhaled corticosteroid (ICS) use were compared in the 12-month post- versus the preindex period with univariate generalized estimating equations adjusted for repeated measurements. RESULTS: A total of 208 patients (mean ± standard deviation[SD] age, 41 ± 19 years; 64.9% women; 71.2% white; and with a mean ± SD serum total immunoglobulin E level of 455.4 ± 644.7 IU/mL) were identified. In the post- versus preindex period, the patients were significantly more likely to have well-controlled asthma (odds ratio [OR] 1.72 [95% confidence interval {CI}, 1.11-2.64]) and less likely to have a lung function value below normal (nonsignificant) after omalizumab initiation. The patients experienced significantly less coughing (OR 0.66 [95% CI, 0.49-0.91]), shortness of breath (OR 0.60 [95% CI, 0.44-0.83]), and wheezing (OR 0.59 [95% CI, 0.43-0.81]), with no improvement in chest tightness. A significantly lower likelihood of new OCS prescriptions (OR 0.58 [95% CI, 0.41-0.82]) was observed. A lower likelihood of new high- and medium-dose ICS prescriptions was nonsignificant. CONCLUSION: Omalizumab was associated with beneficial effects on asthma control and symptoms, and the likelihood of requiring new OCS prescriptions. An observed trend of improved lung function and lower likelihood of requiring high- and medium-dose ICS did not reach statistical significance.

Quantification of white matter injury following neonatal stroke with serial DTI.

BACKGROUND: Diffusion tensor imaging (DTI) can be used to predict outcome following perinatal arterial ischemic stroke (PAIS), although little is known about white matter changes over time. METHODS: Infants with PAIS were serially scanned in the neonatal period (n = 15), at 3 mo (n = 16), and at 24 mo (n = 8). Fractional anisotropy (FA) values in five regions of interest (anterior and posterior limb of the internal capsule, corpus callosum, optic radiation, and posterior thalamic radiation) were obtained and compared with FA values of healthy controls and neurodevelopmental outcome. RESULTS: In the neonatal period, no differences in FA values were found. At 3 mo, the six infants who ultimately developed motor deficits showed lower FA values in all affected regions. Four infants developed a visual field defect and showed lower FA values in the affected optic radiation at 3 mo (0.22 vs. 0.29; P = 0.03). Finally, a correlation between FA values of the corpus callosum at 3 mo and the Griffiths developmental quotients was found (r = 0.66; P = 0.03). At 24 mo, a similar pattern was observed. CONCLUSION: Neonatal FA measurements may underestimate the extent of injury following PAIS. FA measurements at 3 mo could be considered a more reliable predictor of neurodevelopmental outcome and correlate with DTI findings at 24 mo.

Climate change adaptation through urban heat management in Atlanta, Georgia.

This study explores the potential effectiveness of metropolitan land cover change as a climate change adaptation strategy for managing rising temperatures in a large and rapidly warming metropolitan region of the United States. Through the integration of a mesoscale meteorological model with estimated land cover data for the Atlanta, Georgia region in 2010, this study quantifies the influence of extensive land cover change at the periphery of a large metropolitan region on temperature within the city center. The first study to directly model a metropolitan scale heat transfer mechanism, we find both enhanced tree canopy and impervious cover in the suburban zones of the Atlanta region to produce statistically significant cooling and warming effects in the urban core. Based on these findings, we conclude that urban heat island management both within and beyond the central developed core of large cities may provide an effective climate change adaptation strategy for large metropolitan regions.

The importance of land cover change across urban-rural typologies for climate modeling.

Land cover changes affect local surface energy balances by changing the amount of solar energy reflected, the magnitude and duration over which absorbed energy is released as heat, and the amount of energy that is diverted to non-heating fluxes through evaporation. However, such local influences often are only crudely included in climate modeling exercises, if at all. A better understanding of local land conversion dynamics can serve to inform inputs for climate models and increase the role for land use planning in climate management policy. Here we present a new approach for projecting and incorporating metropolitan land cover change into mesoscale climate and other environmental assessment models. Our results demonstrate the relative contributions of different land development patterns to land cover change and conversion and suggest that regional growth management strategies serving to increase settlement densities over time can have a significant influence on the rate of deforestation per unit of population growth. Employing the approach presented herein, the impacts of land conversion on climate change and on parallel environmental systems and services, such as ground water recharge, habitat provision, and food production, may all be investigated more closely and managed through land use planning.

How tufted capuchin monkeys (Cebus apella spp) and common chimpanzees (Pan troglodytes) align objects to surfaces: insights into spatial reasoning and implications for tool use.

This report addresses phylogenetic variation in a spatial skill that underlies tool use: aligning objects to a feature of a surface. Fragaszy and Cummins-Sebree's [Behavioral and Cognitive Neuroscience Reviews 4:282-306, 2005] model of relational spatial reasoning and Skill Development and Perception-Action theories guided the design of the study. We examined how capuchins and chimpanzees place stick objects of varying shapes into matching grooves on a flat surface. Although most individuals aligned the long axis of the object with the matching groove more often than expected by chance, all typically did so with poor precision. Some individuals managed to align a second feature, and only one (a capuchin monkey) achieved above-chance success at aligning three features with matching grooves. Our findings suggest that capuchins and chimpanzees do not reliably align objects along even one axis, and that neither species can reliably or easily master object placement tasks that require managing two or more spatial relations concurrently. Moreover, they did not systematically vary their behavior in a manner that would aid discovery of the affordances of the stick-surface combination beyond sliding the stick along the surface (which may have provided haptic information about the location of the groove). These limitations have profound consequences for the forms of tool use we can expect these individuals to master.

A Premature Infant With Neonatal Actinomyces odontolyticus Sepsis.

We describe the presentation, diagnosis and management of a premature newborn with Actinomyces odontolyticus bacteremia; this is the first case report of neonatal sepsis secondary to this bacteria. Maternal dental infection was the likely source of the pathogen. The outcome was favorable, with good response to antimicrobial therapy with ampicillin/amoxicillin.

Applications of surgical navigational systems for craniofacial bone-anchored implant placement.

The following case reports describe the use of computer-assisted image-guided surgery to plan and place craniofacial bone-anchored implants (CBAI) for facial prosthetic reconstructions. During virtual planning, the soft tissue and bone visualizations are segmented from spiral computed tomography data and the patient's normal anatomy is mirrored onto the skull of the defect side, thus providing the ability to visualize the future prosthetic form. CBAI are planned in the anatomical area that leads to the best cosmetic results. Bone quantity is directly assessed at the surgical sites with the integrated instrumentation while the clinician navigates within the images and virtual planning scheme in real time. The aim of this report is to show a technique that incorporates computer-assisted image-guided surgery into the preoperative planning and surgical placement of CBAI. The use of this technology to plan and place implants in the most ideal location for facial prosthetic treatment eliminated the need for a conventional or prototyped surgical guide.

Heat-Related Illness Is Associated with Lack of Air Conditioning and Pre-Existing Health Problems in Detroit, Michigan, USA: A Community-Based Participatory Co-Analysis of Survey Data.

The objective of the study was to investigate, using academic-community epidemiologic co-analysis, the odds of reported heat-related illness for people with (1) central air conditioning (AC) or window unit AC versus no AC, and (2) fair/poor vs. good/excellent reported health. From 2016 to 2017, 101 Detroit residents were surveyed once regarding extreme heat, housing and neighborhood features, and heat-related illness in the prior 5 years. Academic partners selected initial confounders and, after instruction on directed acyclic graphs, community partners proposed alternate directed acyclic graphs with additional confounders. Heat-related illness was regressed on AC type or health and co-selected confounders. The study found that heat-related illness was associated with no-AC (n = 96, odds ratio (OR) = 4.66, 95% confidence interval (CI) = 1.22, 17.72); living ≤5 years in present home (n = 57, OR = 10.39, 95% CI = 1.13, 95.88); and fair/poor vs. good/excellent health (n = 97, OR = 3.15, 95% CI = 1.33, 7.48). Co-analysis suggested multiple built-environment confounders. We conclude that Detroit residents with poorer health and no AC are at greater risk during extreme heat. Academic-community co-analysis using directed acyclic graphs enhances research on community-specific social and health vulnerabilities by identifying key confounders and future research directions for rigorous and impactful research.

Physical Activity in the Summer Heat: How Hot Weather Moderates the Relationship Between Built Environment Features and Outdoor Physical Activity of Adults.

BACKGROUND: Research has not yet examined how hot weather moderates the relationship between the built environment and outdoor physical activity levels. The authors posited that hot days will increase the magnitude of the expected directional effect of built environment features on physical activity. METHODS: This longitudinal study included 134 US adults from the Three city Heat and Electrical failure AdapTation study. Adults self-reported physical activity for multiple summer days (nstudy-days = 742) in 2016. Hot days were defined as ≥90th percentile of daily maximum heat index. Built environment features included density, safety, trees, hilliness, connectivity, access to parks, and access to shops + services. Separate growth curve models with interaction terms (ie, hot day × built environment feature) were run for daily minutes of outdoor physical activity (ie, any activity and recommended activity). RESULTS: Neither hot days nor built environment features impacted outdoor physical activity significantly, and hot days did not moderate the relationship between built environment features and physical activity (P > .05). CONCLUSIONS: With adults failing to modify behavior on hot days, cities may be placing adults at increased risk of exertional heat illness. The authors recommend incorporating the risk of exertional heat illness in health impact assessments and deploying heat management strategies.

Reducing Vancomycin Use in a Level IV NICU.

BACKGROUND AND OBJECTIVES: Vancomycin remains one of the most commonly prescribed antibiotics in NICUs despite recommendations to limit its use for known resistant infections. Baseline data revealing substantially higher vancomycin use in our NICU compared to peer institutions informed our quality improvement initiative. Our aim was to reduce the vancomycin prescribing rate in neonates hospitalized in our NICU by 50% within 1 year and sustain for 1 year. METHODS: In the 60-bed level IV NICU of an academic referral center, we used a quality improvement framework to develop key drivers and interventions including (1) physician education with benchmarking antibiotic prescribing rates; (2) pharmacy-initiated 48-hour antibiotic time-outs on rounds; (3) development of clinical pathways to standardize empirical antibiotic choices for early-onset sepsis, late-onset sepsis, and necrotizing enterocolitis; coupled with (4) daily prospective audit with feedback from the antimicrobial stewardship program. RESULTS: We used statistical process u-charts to show vancomycin use declined from 112 to 38 days of therapy per 1000 patient-days. After education, pharmacy-initiated 48-hour time-outs, and development of clinical pathways, vancomycin use declined by 29%, and by an additional 52% after implementation of prospective audit with feedback. Vancomycin-associated acute kidney injury also declined from 1.4 to 0.1 events per 1000 patient-days. CONCLUSIONS: Through a sequential implementation approach of education, standardization of care with clinical pathways, pharmacist-initiated 48-hour time-outs, and prospective audit with feedback, vancomycin days of therapy declined by 66% over a 1-year period and has been sustained for 1 year.

Delayed neural network degeneration after neonatal hypoxia-ischemia.

OBJECTIVE: Clinical magnetic resonance studies show delayed and ongoing neurodegeneration after neonatal hypoxia-ischemia (HI), but the mechanisms and timing of this neurodegeneration remain unclear. We used ex vivo diffusion tensor imaging (DTI) and brain neuropathology to determine whether selective injury to white matter tracts occurs after neonatal HI in mice resulting in neural system-associated attrition in remote regions and at delayed times. METHODS: The Rice-Vannucci model (unilateral carotid ligation + 45 minutes of hypoxia FiO(2) = 0.08) was used to cause brain injury in postnatal day 7 (p7) C57BL6 mice, and ex vivo DTI and correlative neuropathology were performed at p8, p11, p15, p21, p28, and p42. RESULTS: DTI provides excellent contrast visualization of unmyelinated white matter in the immature mouse brain. Severe ipsilateral injury to the hippocampus is seen with both histopathology and diffusion-weighted magnetic resonance imaging 24 hours after injury. Injury to axons is evident 24 hours after HI in the hippocampal alveus. By p11 and continuing until p28, the ipsilateral fimbria fornix degenerates. At p15, there is injury and loss of axons entering the ipsilateral septal nucleus followed by ipsilateral septal atrophy. Volume loss in the hippocampus is rapid and severe, but is subacute and significantly slower in the ipsilateral septum. Neonatal HI also interrupts the normal developmental increase in fractional anisotropy in the ipsilateral fimbria but not in the contralateral fimbria from p8 to p42. INTERPRETATION: In neonatal brain, there is progressive systems-preferential injury after HI. DTI allows unparalleled visualization of this neural network-associated attrition so that it can be followed longitudinally in developing brain.

Patient and physician preferences for attributes of biologic medications for severe asthma.

OBJECTIVE: Despite the increased availability of biologic treatments indicated for severe asthma, patient and physician preferences for these medications remains largely unknown. The purpose of this study was to understand perceptions of biologic therapies, barriers to care with biologic medications, and preferences for biologic therapy attributes. METHODS: This mixed-methods study involved quantitative surveys and qualitative telephone interviews with patients and physicians from the United States. Participants described preferences for relevant attributes, and barriers to use of biologic medications. Participants rated, ranked, and indicated importance of preferences for different levels of key attributes including: mode of administration, administration setting, dosing frequency, number of injections, and time to onset of effect. Other attributes unique to each group were also included. RESULTS: A total of 47 patients and 25 physicians participated. Patients ranked out-of-pocket costs, mode of administration, time to onset of efficacy, and administration setting as the most important attributes. Physicians ranked mode of administration, time to onset of efficacy, dosing frequency, and insurance reimbursement/access as most important. Both groups expressed preferences for less frequent administrations (Q8W over Q4W or Q2W) (all P<0.01) and subcutaneous (SC) over intravenous injection (both P<0.0001). Key patient barriers to biologic medications include location of treatment, administration time, scheduling, cost/insurance coverage, number of injections, and mode of administration. Physicians identified patient candidacy, convincing patients, administration setting, mode of administration, cost, and administrative burden as key barriers to initiating therapy; and efficacy, speed of onset, convenience of administration, cost, and patient compliance as barriers to staying on therapy. CONCLUSIONS: Patients and physicians expressed strong preferences for less frequent dosing, SC administration, and faster onset. Cost/insurance coverage and convenience issues were key barriers to use. Increased awareness and understanding of preferences and barriers may be useful in facilitating physician-patient conversations with the goal of individualizing treatment.