Updated Public Health Impact and Cost Effectiveness of Recombinant Zoster Vaccine in Canadian Adults Aged 50 Years and Older.

OBJECTIVES: The aim of this study was to update previously estimated public health impact and cost effectiveness of recombinant zoster vaccine (RZV) for the prevention of herpes zoster (HZ) in Canadians aged ≥50 years using longer-term RZV efficacy and waning data and real-world coverage and completion. METHODS: A multicohort Markov model was used to conduct a cost-utility analysis comparing RZV with no HZ vaccination among Canadians aged ≥50 years. Real-world data were used for first-dose coverage (17.5%) and second-dose completion (65%). Vaccine efficacy and waning data were applied from up to 8-year follow-up from the ZOE-50 and ZOE-70 clinical trials. Incremental costs and benefits were calculated using a lifetime horizon from the healthcare payer (base case) and societal perspectives. A discount rate of 1.5% was applied to costs and quality-adjusted life-years (QALYs). RESULTS: The model estimated that RZV would prevent 303,835 HZ cases, 83,256 post-herpetic neuralgia (PHN) cases, 39,653 other complications, and 99 HZ-related deaths compared with no HZ vaccination. Incremental cost-effectiveness ratios (ICERs) were estimated to be $27,486 and $22,097 per QALY (2022 Canadian dollars [CAN$]) from the healthcare payer and societal perspectives, respectively. The base-case ICER was most sensitive to a lower percentage of initial HZ cases with PHN. Almost all probabilistic sensitivity analysis simulations (98.1%) resulted in ICERs

Questions From Family Members During the Dying Process And Moral Distress Experienced by ICU Nurses.

BACKGROUND: For a hospitalized patient, transitioning to comfort measures only (CMO) involves discontinuation of life-prolonging interventions with a goal of allowing natural death. Nurses play a pivotal role during the provision of CMO, caring for both the dying patient and their family. OBJECTIVE: To examine the experiences of ICU nurses caring for patients receiving CMO. METHODS: Between October 2020 and June 2021, nurses in the neuro- and medical-cardiac intensive care units at Harborview Medical Center in Seattle, WA, completed surveys about their experiences providing CMO. Surveys addressed involvement in discussions about CMO and questions asked by family members of dying patients. We also assessed nurses' moral distress related to CMO and used ordinal logistic regression to examine predictors of moral distress. RESULTS: Surveys were completed by 82 nurses (response rate 44%), with 79 (96%) reporting experience providing CMO in the previous year. Most preferred to be present for discussions between physicians or advanced practice providers and family members about transitioning to CMO (89% most of the time or always); however, only 31% were present most of the time or always. Questions from family about time to death, changes in breathing, and medications to relieve symptoms were common. Most nurses reported moral distress at least some of the time when providing CMO (62%). Feeling well-prepared to answer specific questions from family was associated with less moral distress. CONCLUSION: There is discordance between nurses' preferences for inclusion in discussions about the transition to CMO and their actual presence. Moral distress is common for nurses when providing CMO and feeling prepared to answer questions from family members may attenuate distress.

Assessing the Impact of COVID-19 on HIV Outcomes in the United States: A Modeling Study.

BACKGROUND: The COVID-19 pandemic impacted sexual behaviors and the HIV continuum of care in the United States, reducing HIV testing and diagnosis, and use of preexposure prophylaxis and antiretroviral therapy. We aimed to understand the future implications of these effects through a modeling study. METHODS: We first ran our compartmental model of HIV transmission in the United States accounting for pandemic-related short-term changes in transmission behavior and HIV prevention and care provision in 2020 to 2021 only. We then ran a comparison scenario that did not apply pandemic effects but assumed a continuation of past HIV prevention and care trends. We compared results from the 2 scenarios through 2024. RESULTS: HIV incidence was 4·4% lower in 2020 to 2021 for the pandemic scenario compared with the no-pandemic scenario because of reduced levels of transmission behavior, despite reductions in HIV prevention and care caused by the pandemic. However, reduced care led to less viral load suppression among people with HIV in 2020, and in turn, our model resulted in a slightly greater incidence of 2·0% from 2022 to 2024 in the COVID-19 scenario, as compared with the non-COVID scenario. DISCUSSION: Disruptions in HIV prevention and care services during COVID-19 may lead to somewhat higher postpandemic HIV incidence than assuming prepandemic trends in HIV care and prevention continued. These results underscore the importance of continuing to increase HIV prevention and care efforts in the coming years.

Characterization of an Acinetobacter baumannii Monofunctional Phosphomethylpyrimidine Kinase That Is Inhibited by Pyridoxal Phosphate.

Thiamin and its phosphate derivatives are ubiquitous molecules involved as essential cofactors in many cellular processes. The de novo biosynthesis of thiamin employs the parallel synthesis of 4-methyl-5-(2-hydroxyethyl)thiazole (THZ-P) and 4-amino-2-methyl-5(diphosphooxymethyl) pyrimidine (HMP) pyrophosphate (HMP-PP), which are coupled to generate thiamin phosphate. Most organisms that can biosynthesize thiamin employ a kinase (HMPK or ThiD) to generate HMP-PP. In nearly all cases, this enzyme is bifunctional and can also salvage free HMP, producing HMP-P, the monophosphate precursor of HMP-PP. Here we present high-resolution crystal structures of an HMPK from Acinetobacter baumannii (AbHMPK), both unliganded and with pyridoxal 5-phosphate (PLP) noncovalently bound. Despite the similarity between HMPK and pyridoxal kinase enzymes, our kinetics analysis indicates that AbHMPK accepts HMP exclusively as a substrate and cannot turn over pyridoxal, pyridoxamine, or pyridoxine nor does it display phosphatase activity. PLP does, however, act as a weak inhibitor of AbHMPK with an IC50 of 768 µM. Surprisingly, unlike other HMPKs, AbHMPK catalyzes only the phosphorylation of HMP and does not generate the diphosphate HMP-PP. This suggests that an additional kinase is present in A. baumannii, or an alternative mechanism is in operation to complete the biosynthesis of thiamin.

An Embedded Curriculum to Teach Critical Incident Debriefing to Internal Medicine Residents.

Background Internal medicine residents frequently experience distressing clinical events; critical event debriefing is one tool to help mitigate their effects. Objective To evaluate the effectiveness of a 1-hour workshop teaching residents a novel, efficient approach to leading a team debrief after emotionally charged clinical events. Methods An internal needs assessment identified time and confidence as debriefing barriers. In response, we created the STREAM (Structured, Timely, Reflection, tEAM-based) framework, a 15-minute structured approach to leading a debrief. Senior residents participated in a 1-hour workshop on the first day of an inpatient medicine rotation to learn the STREAM framework. To evaluate learning outcomes, participants completed the same survey immediately before and after the session, and at the end of their 4-week rotation. Senior residents at another site who did not complete the workshop also evaluated their comfort leading debriefs. Results Fifty out of 65 senior residents (77%) participated in the workshop. After the workshop, participants felt more prepared to lead debriefs, learned a structured format for debriefing, and felt they had enough time to lead debriefs. Thirty-four of 50 (68%) workshop participants and 20 of 41 (49%) comparison residents completed the end-of-rotation survey. Senior residents who participated in the workshop were more likely than nonparticipants to report feeling prepared to lead debriefs. Conclusions A brief workshop is an effective method for teaching a framework for leading a team debrief.

Rebamipide and Derivatives are Potent, Selective Inhibitors of Histidine Phosphatase Activity of the Suppressor of T Cell Receptor Signaling Proteins.

The suppressor of T cell receptor signaling (Sts) proteins are negative regulators of immune signaling. Genetic inactivation of these proteins leads to significant resistance to infection. From a 590,000 compound high-throughput screen, we identified the 2-(1H)-quinolinone derivative, rebamipide, as a putative inhibitor of Sts phosphatase activity. Rebamipide, and a small library of derivatives, are competitive, selective inhibitors of Sts-1 with IC50 values from low to submicromolar. SAR analysis indicates that the quinolinone, the acid, and the amide moieties are all essential for activity. A crystal structure confirmed the SAR and reveals key interactions between this class of compound and the protein. Although rebamipide has poor cell permeability, we demonstrated that a liposomal preparation can inactivate the phosphatase activity of Sts-1 in cells. These studies demonstrate that Sts-1 enzyme activity can be pharmacologically inactivated and provide foundational tools and insights for the development of immune-enhancing therapies that target the Sts proteins.

Ligand bound structure of a 6-hydroxynicotinic acid 3-monooxygenase provides mechanistic insights.

6-Hydroxynicotinic acid 3-monooxygenase (NicC) is a bacterial enzyme involved in the degradation of nicotinic acid. This enzyme is a Class A flavin-dependent monooxygenase that catalyzes a unique decarboxylative hydroxylation. The unliganded structure of this enzyme has previously been reported and studied using steady- and transient-state kinetics to support a comprehensive kinetic mechanism. Here we report the crystal structure of the H47Q NicC variant in both a ligand-bound (solved to 2.17 Å resolution) and unliganded (1.51 Å resolution) form. Interestingly, in the liganded form, H47Q NicC is bound to 2-mercaptopyridine (2-MP), a contaminant present in the commercial stock of 6-mercaptopyridine-3-carboxylic acid(6-MNA), a substrate analogue. 2-MP binds weakly to H47Q NicC and is not a substrate for the enzyme. Based on kinetic and thermodynamic characterization, we have fortuitously captured a catalytically inactive H47Q NicC•2-MP complex in our crystal structure. This complex reveals interesting mechanistic details about the reaction catalyzed by 6-hydroxynicotinic acid 3-monooxygenase.

The Annual Economic Burden of Respiratory Syncytial Virus in Adults in the United States.

BACKGROUND: Current estimates of the economic burden of respiratory syncytial virus (RSV) are needed for policymakers to evaluate adult RSV vaccination strategies. METHODS: A cost-of-illness model was developed to estimate the annual societal burden of RSV in US adults aged ≥60 years. Additional analyses were conducted to estimate the burden of hospitalized RSV in all adults aged 50-59 years and in adults aged 18-49 years with potential RSV risk factors. RESULTS: Among US adults aged ≥60 years, the model estimated 4.0 million annual RSV cases (95% UI, 2.7-5.6 million) and an annual economic burden of $6.6 billion (95% UI, $3.1-$12.9 billion; direct medical costs, $2.9 billion; indirect costs, $3.7 billion). The 4% of RSV cases that were hospitalized contributed to 94% of direct medical costs. Additional analyses estimated $422 million in annual hospitalization costs among all adults aged 50-59 years. Among adults aged 18-49 years with RSV risk factors, annual per capita burden was highest among people with congestive heart failure at $51,100 per 1000 people. DISCUSSION: The economic burden of RSV is substantial among adults aged ≥50 years, and among adults aged 18-49 years with RSV risk factors, underscoring the need for preventive interventions for these populations.

Cost-Effectiveness of Recombinant Zoster Vaccine for the Prevention of Herpes Zoster in Hematopoietic Stem Cell Transplant Recipients and Other Immunocompromised Adults in the United States.

INTRODUCTION: Immunocompromised (IC) adults are at increased risk of developing herpes zoster (HZ) and HZ-related complications due to therapy or underlying disease. This study evaluated the cost effectiveness of recombinant zoster vaccine (RZV) versus no vaccine for the prevention of HZ in hematopoietic stem cell transplant (HSCT) recipients and other IC adults aged ≥ 18 years in the United States (US). METHODS: A static Markov model simulated cohorts of IC individuals using a 1-year cycle length and 30-year time horizon to estimate the cost effectiveness of RZV. Inputs were sourced from clinical trial results and publicly available sources/literature. Modeled populations included US adult HSCT recipients (base case), patients with human immunodeficiency virus (HIV), patients with breast cancer, patients with Hodgkin's lymphoma, and renal transplant recipients. The model reported societal costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Sensitivity and threshold analyses were conducted. RESULTS: In the base case of 19,671 US adult HSCT recipients, RZV resulted in total societal cost savings of US$0.1 million and 109 incremental QALYs versus no vaccine. RZV was a 'dominant strategy' versus no vaccine because vaccination resulted in cost savings with QALY gains. RZV was also cost saving in renal transplant recipients, and cost effective at a willingness-to-pay threshold of US$100,000 per QALY gained in patients with HIV, breast cancer, and Hodgkin's lymphoma, with ICERs of US$33,268, US$67,682, and US$95,972 per QALY gained, respectively, versus no vaccine. CONCLUSIONS: Model results show RZV is potentially cost saving for the prevention of HZ in US adult HSCT recipients and US adults with selected immunocompromising conditions, and cost effective for others, supporting the use of RZV to prevent HZ and HZ-related complications in IC adults.

Mechanism of the Multistep Catalytic Cycle of 6-Hydroxynicotinate 3-Monooxygenase Revealed by Global Kinetic Analysis.

The class A flavoenzyme 6-hydroxynicotinate 3-monooxygenase (NicC) catalyzes a rare decarboxylative hydroxylation reaction in the degradation of nicotinate by aerobic bacteria. While the structure and critical residues involved in catalysis have been reported, the mechanism of this multistep enzyme has yet to be determined. A kinetic understanding of the NicC mechanism would enable comparison to other phenolic hydroxylases and illuminate its bioengineering potential for remediation of N-heterocyclic aromatic compounds. Toward these goals, transient state kinetic analyses by stopped-flow spectrophotometry were utilized to follow rapid changes in flavoenzyme absorbance spectra during all three stages of NicC catalysis: (1) 6-HNA binding; (2) NADH binding and FAD reduction; and (3) O2 binding with C4a-adduct formation, substrate hydroxylation, and FAD regeneration. Global kinetic simulations by numeric integration were used to supplement analytical fitting of time-resolved data and establish a kinetic mechanism. Results indicate that 6-HNA binding is a two-step process that substantially increases the affinity of NicC for NADH and enables the formation of a charge-transfer-complex intermediate to enhance the rate of flavin reduction. Singular value decomposition of the time-resolved spectra during the reaction of the substrate-bound, reduced enzyme with dioxygen provides evidence for the involvement of C4a-hydroperoxy-flavin and C4a-hydroxy-flavin intermediates in NicC catalysis. Global analysis of the full kinetic mechanism suggests that steady-state catalytic turnover is partially limited by substrate hydroxylation and C4a-hydroxy-flavin dehydration to regenerate the flavoenzyme. Insights gleaned from the kinetic model and determined microscopic rate constants provide a fundamental basis for understanding NicC's substrate specificity and reactivity.

Public health impact of recombinant zoster vaccine for prevention of herpes zoster in US adults immunocompromised due to cancer.

Individuals who are immunocompromised (IC) due to therapy or underlying disease are at increased risk of herpes zoster (HZ). This study evaluates the public health impact of recombinant zoster vaccine (RZV) relative to no HZ vaccination for the prevention of HZ among adults aged ≥18 years diagnosed with selected cancers in the United States (US). A static Markov model was used to simulate three cohorts of individuals who are IC with cancer (time horizon of 30 years; one-year cycle length): hematopoietic stem cell transplant (HSCT) recipients, patients with breast cancer (BC; a solid tumor example), and patients with Hodgkin's lymphoma (HL; a hematological malignancy example). Cohort sizes reflect the estimated annual incidence of each condition in the US population (19,671 HSCT recipients, 279,100 patients with BC, and 8,480 patients with HL). Vaccination with RZV resulted in 2,297; 38,068; and 848 fewer HZ cases for HSCT recipients, patients with BC, and patients with HL, respectively (each versus no vaccine). Vaccination with RZV also resulted in 422; 3,184; and 93 fewer postherpetic neuralgia cases for HSCT, BC, and HL, respectively. Analyses estimated the quality-adjusted life years gained to be 109, 506, and 17 for HSCT, BC, and HL, respectively. To prevent one HZ case, the number needed to vaccinate was 9, 8, and 10, for HSCT, BC, and HL, respectively. These results suggest RZV vaccination may be an effective option to significantly reduce HZ disease burden among patients diagnosed with selected cancers in the US.

Shingles cases can be prevented by recombinant zoster vaccine (RZV). People who have a weakened immune system (immunocompromised) due to disease or therapy are more likely to develop shingles. For example, shingles occurs in nearly a quarter of patients receiving immunosuppressive treatment for blood cancers. To estimate the public health impact of vaccination against shingles in people who are immunocompromised due to cancer in the United States (US), we used a model to simulate groups with selected types of cancer. The results indicate vaccination with RZV can significantly reduce shingles cases and related complications among these groups in the US.

Estimating the cost of university-based outbreaks of serogroup B meningococcal disease with different pre-matriculation vaccination policies in the United States.

Objective: We developed an Excel-based cost calculator to assess the economic burden of university-based Neisseria meningitidis serogroup B (MenB) outbreaks. Participants: Hypothetical university with 6,354 students. Methods: Total societal costs of outbreak were estimated for three MenB pre-matriculation immunization policies-vaccination required, vaccination recommended, and no vaccine policy-under three different cost assumptions (low/mid-range/high cost). Results: Mid-range cost estimates of an outbreak under "no policy" were $2.60 and $2.70 million (of which 35% were incurred by the university) if targeting all undergraduates for mass vaccination with a two-/three-dose vaccine, respectively. The "required" and "recommended" policies lowered the burden to $2.17-$2.18 million and $2.34-$2.39 million, respectively. For a larger university with 40,000 students, costs were almost $9 million for a two-dose vaccine with "no policy" in place. Conclusions: The economic burden of a university MenB outbreak is substantial, but could be mitigated by a pre-matriculation MenB vaccination requirement or recommendation.

Before-After Study of a Checklist to Improve Acute Care to ICU Handoffs.

Transferring care of a patient is a critical process. The objective of this study was to evaluate a checklist to standardize handoffs from acute care to the intensive care unit (ICU). This was a single-center, before-after study of a checklist to standardize transfers of patients from acute care to the medical-cardiac ICU. Clinicians completed surveys about handoffs before and after checklist implementation. The association between study period and survey data was analyzed using multivariable logistic regression with cross-classified multilevel models. Surveys were completed by 179 clinicians. After checklist implementation, handoffs were more likely to occur in the ICU (OR 17.23; 95% CI, 1.81-164.19) and cover patient treatment preferences (OR 2.73; 95% CI, 1.12-6.66). However, checklist uptake was suboptimal (30% of responses indicated checklist use). Implementation of a checklist during acute care to ICU transfers is challenging. Signals suggesting process improvement warrant additional study.

Synthesis and crystallographic characterization of 6-hydroxy-1,2-dihydropyridin-2-one.

The title compound, C5H5NO2, is a hy-droxy-lated pyridine ring that has been studied for its involvement in microbial degradation of nicotinic acid. Here we describe its synthesis as a formic acid salt, rather than the standard hydro-chloride salt that is commercially available, and its spectroscopic and crystallographic characterization.

Burden of opioid use for pain management among adult herpes zoster patients in the US and the potential impact of vaccination.

PLAIN LANGUAGE SUMMARYWhat is the context? Herpes zoster or shingles and its complications such as postherpetic neuralgia - a painful condition that affects the nerve fibers and skin - may lead to complex pain that can be addressed using opioids in some patients.The recombinant zoster vaccine (RZV) vaccine prevents shingles and, therefore, may reduce the use of opioids and the negative health outcomes and costs associated with it.What is new? In this retrospective medical claims study, including patients between 2012 and 2017, we evaluated the receipt of pain medication including opioids in herpes zoster patients, and assessed factors associated with opioid prescription.estimated health care resource utilization and costs associated with opioid use among patients with herpes zoster.assessed the impact of vaccination on opioid prescriptions.Among subjects receiving opioids, 78.5% started with a weak opioid dose. Dose escalation was uncommon.Postherpetic neuralgia, immunocompromised status, and comorbidities are the main risk factors associated with opioid prescription.Health care costs are almost double in patients with herpes zoster receiving opioids compared with patients without an opioid prescription.In a population of 1 million adults aged 50 years or older, vaccination with the recombinant zoster vaccine could prevent over 19,000 patients from receiving opioids.What is the impact? Prevention of herpes zoster through vaccination may be a highly effective strategy to reduce opioid prescriptions and costs related to pain management in a susceptible population.Increasing RZV vaccination coverage in adults aged ≥50 years may further reduce potential opioid prescriptions through a decrease in shingles incidence.

Optimizing HIV Prevention Efforts to Achieve EHE Incidence Targets.

BACKGROUND: A goal of the US Department of Health and Human Services' Ending the HIV Epidemic (EHE) in the United States initiative is to reduce the annual number of incident HIV infections in the United States by 75% within 5 years and by 90% within 10 years. We developed a resource allocation analysis to understand how these goals might be met. METHODS: We estimated the current annual societal funding [$2.8 billion (B)/yr] for 14 interventions to prevent HIV and facilitate treatment of infected persons. These interventions included HIV testing for different transmission groups, HIV care continuum interventions, pre-exposure prophylaxis, and syringe services programs. We developed scenarios optimizing or reallocating this funding to minimize new infections, and we analyzed the impact of additional EHE funding over the period 2021-2030. RESULTS: With constant current annual societal funding of $2.8 B/yr for 10 years starting in 2021, we estimated the annual incidence of 36,000 new cases in 2030. When we added annual EHE funding of $500 million (M)/yr for 2021-2022, $1.5 B/yr for 2023-2025, and $2.5 B/yr for 2026-2030, the annual incidence of infections decreased to 7600 cases (no optimization), 2900 cases (optimization beginning in 2026), and 2200 cases (optimization beginning in 2023) in 2030. CONCLUSIONS: Even without optimization, significant increases in resources could lead to an 80% decrease in the annual HIV incidence in 10 years. However, to reach both EHE targets, optimization of prevention funding early in the EHE period is necessary. Implementing these efficient allocations would require flexibility of funding across agencies, which might be difficult to achieve.

Estimating the HIV Effective Reproduction Number in the United States and Evaluating HIV Elimination Strategies.

CONTEXT: The reproduction number is a fundamental epidemiologic concept used to assess the potential spread of infectious diseases and whether they can be eliminated. OBJECTIVE: We estimated the 2017 United States HIV effective reproduction number, Re, the average number of secondary infections from an infected person in a partially infected population. We analyzed the potential effects on Re of interventions aimed at improving patient flow rates along different stages of the HIV care continuum. We also examined these effects by individual transmission groups. DESIGN: We used the HIV Optimization and Prevention Economics (HOPE) model, a compartmental model of disease progression and transmission, and the next-generation matrix method to estimate Re. We then projected the impact of changes in HIV continuum-of-care interventions on the continuum-of-care flow rates and the estimated Re in 2020. SETTING: United States. PARTICIPANTS: The HOPE model simulated the sexually active US population and persons who inject drugs, aged 13 to 64 years, which was stratified into 195 subpopulations by transmission group, sex, race/ethnicity, age, male circumcision status, and HIV risk level. MAIN OUTCOME MEASURES: The estimated value of Re in 2017 and changes in Re in 2020 from interventions affecting the continuum-of-care flow rates. RESULTS: Our estimated HIV Re in 2017 was 0.92 [0.82, 0.94] (base case [min, max across calibration sets]). Among the interventions considered, the most effective way to reduce Re substantially below 1.0 in 2020 was to maintain viral suppression among those receiving HIV treatment. The greatest impact on Re resulted from changing the flow rates for men who have sex with men (MSM). CONCLUSIONS: Our results suggest that current prevention and treatment efforts may not be sufficient to move the country toward HIV elimination. Reducing Re to substantially below 1.0 may be achieved by an ongoing focus on early diagnosis, linkage to care, and sustained viral suppression especially for MSM.

Financial Considerations II: Loans, Debt Management, Saving, and Investing.

The financial considerations of becoming a physician are often not fully understood or appreciated until after residency and fellowship training. Once training is complete, physicians face a combination of increased financial rewards mixed with significant, and seemingly overwhelming, financial responsibilities, often with limited financial knowledge or understanding. Appropriately managing debt obligations, living expenses, saving for retirement, children's education, and establishing financial safety nets through savings, investments, and insurance are critical. This article is a starting point to provide the new physician with an introduction into some of those financial considerations, to both encourage further learning and promote successful financial decisions.

Applying Human-Centered Design to Refinement of the Jumpstart Guide, a Clinician- and Patient-Facing Goals-of-Care Discussion Priming Tool.

CONTEXT: Human-centered design provides a framework to understand the needs of patients and clinicians who are the target of goals-of-care discussion priming tools. Few studies employ human-centered design to develop and refine their tools. OBJECTIVES: To describe how human-centered design can be applied to the development and refinement of clinician- and patient-facing inpatient goals-of-care discussion guides (Jumpstart guides). METHODS: Human-centered design was applied to the development and refinement of the inpatient Jumpstart guides in four phases: (1) discovering problems based on prior pilots, studies, and research team priorities; (2) further defining problems based on stakeholder and expert review of the current guides; (3) designing solutions based on consensus among stakeholders; and (4) validating solutions after research team review of stakeholder comments. RESULTS: Five initial problems were identified by the research team in phase 1. After expert and stakeholder review in phase 2, 30 additional problems were identified related to Jumpstart guide format, structure, and content. In phase 3, stakeholders proposed solutions to these 35 problems and reached consensus on 32 of these. There was disagreement in 3 areas, including how to frame discussions around cardiopulmonary resuscitation and 2 perceived barriers to inpatient goals-of-care discussions. In phase 4, the research team reviewed all stakeholder input and reached final consensus on solutions to all of the identified problems. CONCLUSION: Human-centered design is a useful tool for enhancing communication interventions in serious illness and can easily be integrated in future development and refinement of clinician- and patient-facing interventions to enhance goals-of-care discussions.

Optimal Allocation of Societal HIV Prevention Resources to Reduce HIV Incidence in the United States.

Objectives. To optimize combined public and private spending on HIV prevention to achieve maximum reductions in incidence.Methods. We used a national HIV model to estimate new infections from 2018 to 2027 in the United States. We estimated current spending on HIV screening, interventions that move persons with diagnosed HIV along the HIV care continuum, pre-exposure prophylaxis, and syringe services programs. We compared the current funding allocation with 2 optimal scenarios: (1) a limited-reach scenario with expanded efforts to serve eligible persons and (2) an ideal, unlimited-reach scenario in which all eligible persons could be served.Results. A continuation of the current allocation projects 331 000 new HIV cases over the next 10 years. The limited-reach scenario reduces that number by 69%, and the unlimited reach scenario by 94%. The most efficient funding allocations resulted in prompt diagnosis and sustained viral suppression through improved screening of high-risk persons and treatment adherence support for those infected.Conclusions. Optimal allocations of public and private funds for HIV prevention can achieve substantial reductions in new infections. Achieving reductions of more than 90% under current funding will require that virtually all infected receive sustained treatment.