Non-Concordance between Patient and Clinician Estimates of Prognosis in Advanced Heart Failure.

IMPORTANCE: Despite efforts to enhance serious illness communication, patients with advanced heart failure (HF) lack prognostic understanding. OBJECTIVES: To determine rate of concordance between HF patients' estimation of their prognosis and their physician's estimate of the patient's prognosis, and to compare patient characteristics associated with concordance. DESIGN: Cross-sectional analysis of a cluster randomized controlled trial with 24-month follow-up and analysis completed on 09/01/2020. Patients were enrolled in inpatient and outpatient settings between September 2011 to February 2016 and data collection continued until the last quarter of 2017. SETTING: Six teaching hospitals in the U.S. PARTICIPANTS: Patients with advanced HF and implantable cardioverter defibrillators (ICDs) at high risk of death. Of 537 patients in the parent study, 407 had complete data for this analysis. INTERVENTION: A multi-component communication intervention on conversations between HF clinicians and their patients regarding ICD deactivation and advance care planning. MAIN OUTCOME(S) AND MEASURE(S): Patient self-report of prognosis and physician response to the "surprise question" of 12-month prognosis. Patient-physician prognostic concordance (PPPC) measured in percentage agreement and kappa. Bivariate analyses of characteristics of patients with and without PPPC. RESULTS: Among 407 patients (mean age 62.1 years, 29.5% female, 42.4% non-white), 300 (73.7%) dyads had non-PPPC; of which 252 (84.0%) reported a prognosis >1 year when their physician estimated <1 year. Only 107 (26.3%) had PPPC with prognosis of ≤ 1 year (n=20 patients) or > 1 year (n=87 patients); (Κ = -0.20, p = 1.0). Of those with physician estimated prognosis of < 1 year, non-PPPC was more likely among patients with lower symptom burden- number and severity (both p ≤.001), without completed advance directive (p=.001). Among those with physician prognosis estimate > 1 year, no patient characteristic was associated with PPPC or non-PPPC. CONCLUSIONS AND RELEVANCE: Non-PPPC between HF patients and their physicians is high. HF patients are more optimistic than clinicians in estimating life expectancy. These data demonstrate there are opportunities to improve the quality of prognosis disclosure between patients with advanced HF and their physicians. Interventions to improve PPPC might include serious illness communication training.

Cost-effective screening for acute hepatitis C virus infection in HIV-infected men who have sex with men.

BACKGROUND: We used a Monte Carlo computer simulation to estimate the effectiveness and cost-effectiveness of screening for acute hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected men who have sex with men. METHODS: One-time screening for prevalent HCV infection was performed at the time of enrollment in care, followed by either symptom-based screening, screening with liver function tests (LFTs), HCV antibody (Ab) screening, or HCV RNA screening in various combinations and intervals. We considered both treatment with pegylated interferon and ribavirin (PEG/RBV) alone and with an HCV protease inhibitor. Outcome measures were life expectancy, quality-adjusted life expectancy, direct medical costs, and cost-effectiveness, assuming a societal willingness to pay $100000 per quality-adjusted life-year (QALY) gained. RESULTS: All strategies increased life expectancy (from 0.49 to 0.94 life-months), quality-adjusted life expectancy (from 0.47 to 1.00 quality-adjusted life-months), and costs (from $1900 to $7600), compared with symptom-based screening. The incremental cost-effectiveness ratio of screening with 6-month LFTs and a 12-month HCV Ab test, compared with symptom-based screening, was $43 700/QALY (for PEG/RBV alone) and $57 800/QALY (for PEG/RBV plus HCV protease inhibitor). The incremental cost-effectiveness ratio of screening with 3-month LFTs, compared with 6-month LFTs plus a 12-month HCV Ab test, was $129 700/QALY (for PEG/RBV alone) and $229 900/QALY (for PEG/RBV plus HCV protease inhibitor). With HCV protease inhibitor-based therapy, screening with 6-month LFTs and a 12-month HCV Ab test was the optimal strategy when the HCV infection incidence was ≤1.25 cases/100 person-years. The 3-month LFT strategy was optimal when the incidence was >1.25 cases/100 person-years. CONCLUSIONS: Screening for acute HCV infection in HIV-infected MSM prolongs life expectancy and is cost-effective. Depending on incidence, regular screening with LFTs, with or without an HCV Ab test, is the optimal strategy.

Candida virulence properties and adverse clinical outcomes in neonatal candidiasis.

OBJECTIVE: To determine whether premature infants with invasive Candida infection caused by strains with increased virulence properties have worse clinical outcomes than those infected with less virulent strains. STUDY DESIGN: Clinical isolates were studied from 2 populations of premature infants, those colonized with Candida spp (commensal; n = 27) and those with invasive candidiasis (n = 81). Individual isolates of C albicans and C parapsilosis were tested for virulence in 3 assays: phenotypic switching, adhesion, and cytotoxicity. Invasive isolates were considered to have enhanced virulence if detected at a level >1 SD above the mean for the commensal isolates in at least one assay. Outcomes of patients with invasive isolates with enhanced virulence were compared with those with invasive isolates lacking enhanced virulence characteristics. RESULTS: Enhanced virulence was detected in 61% of invasive isolates of C albicans and 42% of invasive isolates of C parapsilosis. All C albicans cerebrospinal fluid isolates (n = 6) and 90% of urine isolates (n = 10) had enhanced virulence, compared with 48% of blood isolates (n = 40). Infants with more virulent isolates were younger at the time of positive culture and had higher serum creatinine levels. CONCLUSION: Individual isolates of Candida species vary in their virulence properties. Strains with higher virulence are associated with certain clinical outcomes.

Patient- and population-level health consequences of discontinuing antiretroviral therapy in settings with inadequate HIV treatment availability.

BACKGROUND: In resource-limited settings, HIV budgets are flattening or decreasing. A policy of discontinuing antiretroviral therapy (ART) after HIV treatment failure was modeled to highlight trade-offs among competing policy goals of optimizing individual and population health outcomes. METHODS: In settings with two available ART regimens, we assessed two strategies: (1) continue ART after second-line failure (Status Quo) and (2) discontinue ART after second-line failure (Alternative). A computer model simulated outcomes for a single cohort of newly detected, HIV-infected individuals. Projections were fed into a population-level model allowing multiple cohorts to compete for ART with constraints on treatment capacity. In the Alternative strategy, discontinuation of second-line ART occurred upon detection of antiretroviral failure, specified by WHO guidelines. Those discontinuing failed ART experienced an increased risk of AIDS-related mortality compared to those continuing ART. RESULTS: At the population level, the Alternative strategy increased the mean number initiating ART annually by 1,100 individuals (+18.7%) to 6,980 compared to the Status Quo. More individuals initiating ART under the Alternative strategy increased total life-years by 15,000 (+2.8%) to 555,000, compared to the Status Quo. Although more individuals received treatment under the Alternative strategy, life expectancy for those treated decreased by 0.7 years (-8.0%) to 8.1 years compared to the Status Quo. In a cohort of treated patients only, 600 more individuals (+27.1%) died by 5 years under the Alternative strategy compared to the Status Quo. Results were sensitive to the timing of detection of ART failure, number of ART regimens, and treatment capacity. Although we believe the results robust in the short-term, this analysis reflects settings where HIV case detection occurs late in the disease course and treatment capacity and the incidence of newly detected patients are stable. CONCLUSIONS: In settings with inadequate HIV treatment availability, trade-offs emerge between maximizing outcomes for individual patients already on treatment and ensuring access to treatment for all people who may benefit. While individuals may derive some benefit from ART even after virologic failure, the aggregate public health benefit is maximized by providing effective therapy to the greatest number of people. These trade-offs should be explicit and transparent in antiretroviral policy decisions.

Priorities for screening and treatment of latent tuberculosis infection in the United States.

RATIONALE: To improve the effectiveness of tuberculosis (TB) control programs in the United States by identifying cost-effective priorities for screening for latent tuberculosis infection (LTBI). OBJECTIVES: To estimate the cost-effectiveness of LTBI screening using the tuberculin skin test (TST)and interferon-g release assays (IGRAs). METHODS: A Markov model of screening for LTBI with TST and IGRA in risk-groups considered in current LTBI screening guidelines. MEASUREMENTS AND MAIN RESULTS: In all risk-groups, TST and IGRA screening resulted in increased mean life expectancy, ranging from 0.03­0.24 life-months per person screened. IGRA screening resulted in greater life expectancy gains than TST. Screening always cost more than not screening, but IGRA was cost-saving compared with TST in some groups. Four patterns of cost-effectiveness emerged, related to four risk categories. (1) Individuals at highest risk of TB reactivation (close contacts and those infected with HIV): the incremental cost-effectiveness ratio (ICER) of IGRA compared with TST was less than $100,000 per quality-adjusted life year (QALY) gained. (2) The foreign-born: IGRA was cost-saving compared with TST and cost-effective compared with no screening (ICER ,$100,000 per QALY gained). (3) Vulnerable populations (e.g., homeless, drug user, or former prisoner): the ICER of TST screening was approximately $100,000­$150,000 per QALY gained, but IGRA was not cost-effective. (4) Medical comorbidities (e.g., diabetes): the ICER of screening with TST or IGRA was greater than $100,000 per QALY. CONCLUSIONS: LTBI screening guidelines could make progress toward TB elimination by prioritizing screening for close contacts, those infected with HIV, and the foreign-born regardless of time living in the United States. For these groups, IGRA screening was more cost-effective than TST screening.

Rapid De-Escalation and Triaging Patients in Community-Based Palliative Care.

CONTEXT: The coronavirus disease 2019 (COVID-19) pandemic created a rapid and unprecedented shift in our medical system. Medical providers, teams, and organizations have needed to shift their visits away from face-to-face visits and toward telehealth (both by phone and through video). Palliative care teams who practice in the community setting are faced with a difficult task: How do we actively triage the most urgent visits while keeping our vulnerable patients safe from the pandemic? MEASURES: The following are recommendations created by the Palo Alto Medical Foundation Palliative Care and Support Services team to help triage and coordinate for timely, safe, and effective palliative care in the community and outpatient setting during the ongoing COVID-19 pandemic. Patients are initially triaged based on location followed by acuity. Interdisciplinary care is implemented using strict infection control guidelines in the setting of limited personal protective equipment resources. We implement thorough screening for COVID-19 symptoms at multiple levels before a patient is seen by a designated provider. CONCLUSIONS/LESSONS LEARNED: We recommend active triaging, communication, and frequent screening for COVID-19 symptoms for palliative care patients been evaluated in the community setting. An understanding of infection risk, mutual consent between designated providers, patients, and their families are crucial to maintaining safety while delivering community-based palliative care during the COVID-19 pandemic.

Diagnosis and primary care management of focal segmental glomerulosclerosis in children.

Focal segmental glomerulosclerosis (FSGS) is a pattern of kidney damage that can occur in individuals at any age, including children. Pediatric patients with FSGS require medication monitoring, growth, and psychological health. This article discusses the NP's role in the clinical presentation, diagnostic workup, and treatment of FSGS in pediatric patients.

Clinical impact and cost-effectiveness of making third-line antiretroviral therapy available in sub-Saharan Africa: a model-based analysis in Côte d'Ivoire.

OBJECTIVE: In sub-Saharan Africa, HIV-infected adults who fail second-line antiretroviral therapy (ART) often do not have access to third-line ART. We examined the clinical impact and cost-effectiveness of making third-line ART available in Côte d'Ivoire. METHODS: We used a simulation model to compare 4 strategies after second-line ART failure: continue second-line ART (C-ART2), continue second-line ART with an adherence reinforcement intervention (AR-ART2), immediate switch to third-line ART (IS-ART3), and continue second-line ART with adherence reinforcement, switching patients with persistent failure to third-line ART (AR-ART3). Third-line ART consisted of a boosted-darunavir plus raltegravir-based regimen. Primary outcomes were 10-year survival and lifetime incremental cost-effectiveness ratios (ICERs), in $/year of life saved (YLS). ICERs below $3585 (3 times the country per capita gross domestic product) were considered cost-effective. RESULTS: Ten-year survival was 6.0% with C-ART2, 17.0% with AR-ART2, 35.4% with IS-ART3, and 37.2% with AR-ART3. AR-ART2 was cost-effective ($1100/YLS). AR-ART3 had an ICER of $3600/YLS and became cost-effective if the cost of third-line ART decreased by <1%. IS-ART3 was less effective and more costly than AR-ART3. Results were robust to wide variations in the efficacy of third-line ART and of the adherence reinforcement, as well as in the cost of second-line ART. CONCLUSIONS: Access to third-line ART combined with an intense adherence reinforcement phase, used as a tool to distinguish between patients who can still benefit from their current second-line regimen and those who truly need third-line ART would provide substantial survival benefits. With minor decreases in drug costs, this strategy would be cost-effective.

Projecting the clinical benefits and risks of using efavirenz-containing antiretroviral therapy regimens in women of childbearing age.

OBJECTIVES: To project the outcomes of using either efavirenz or nevirapine as part of initial antiretroviral therapy (ART) in women of childbearing age in Côte d'Ivoire. METHODS: We used an HIV computer simulation model to project both the mother's survival and the birth defects at 10 years for a cohort of women who started ART with either efavirenz or nevirapine. The primary outcome was the ratio at 10 years of the difference in the number of women alive to the difference in the cumulative number of birth defects in women who started ART with efavirenz compared with nevirapine. In the base case analysis, the birth defect rate was 2.9% on efavirenz and 2.7% on nevirapine. In sensitivity analyses, we varied all inputs across confidence intervals reported in the literature. RESULTS: In the base case analysis, for a cohort of 100 000 women, the additional number of women alive initiating ART with efavirenz at 10 years was 15 times the additional number of birth defects (women alive: nevirapine 67 969, efavirenz 68 880, difference =  911; birth defects: nevirapine 1128, efavirenz 1187, difference = 59). In sensitivity analysis, the teratogenicity rate with efavirenz had to be 6.3%, or 2.3 times higher than the rate with nevirapine, for the excess number of birth defects to outweigh the additional number of women alive at 10 years. CONCLUSION: In Côte d'Ivoire, initiating ART with efavirenz instead of nevirapine is likely to substantially increase the number of women alive at 10 years with a smaller potential number of birth defects.

Effect of margins on ipsilateral breast tumor recurrence after breast conservation therapy for lymph node-negative breast carcinoma.

BACKGROUND: Breast conservative surgery (CS) with radiotherapy (RT) is the most commonly used treatment for early-stage breast carcinoma. However, there is controversy regarding the importance of the pathologic margin status on the risk of ipsilateral breast tumor recurrence (IBTR). The current study evaluated the effect of the pathologic margin status on IBTR rates in a cohort of women with lymph node-negative breast carcinoma treated with CS and RT. METHODS: Between August 1980 and December 1994, 452 women with pathologically lymph node-negative breast carcinoma were treated with CS and RT at Westmead Hospital (Westmead, Australia). Central pathology review was performed for all women. The final margins were negative for 352 women (77.9%), positive (invasive and/or in situ) for 42 women (9.3%), and indeterminate for 58 women (12.8%). Information regarding an extensive intraductal component (EIC), lymphovascular invasion, pathologic tumor size, histologic grade, and nuclear grade was available for most women. After macroscopic total excision of the tumor, all women received whole-breast irradiation (usually 45-50.4 grays [Gy]) and the majority of women also received a local tumor bed boost (range, 8-30 Gy). RESULTS: After a median follow-up of 80 months, 34 women (7.5%) developed an IBTR. The crude 5-year rates of IBTR for women with negative margins, positive margins, and indeterminate margins were 3.1%, 11.9%, and 6.9%, respectively. For women with negative margins, the 5-year and 10-year actuarial rates of freedom from IBTR were 96% and 92%, respectively, compared with 88% and 75%, respectively, for women with positive margins (P = 0.003). Univariate analysis demonstrated that the only factors associated with a significantly higher risk of IBTR were age at diagnosis (P < 0.050) and margin status (P = 0.005). Multivariate analysis showed that both age and margin status were independent predictors of IBTR. None of 24 patients with an EIC and negative margins were found to have developed an IBTR. CONCLUSIONS: The results of the current study were comparable to other published reports and supported the association of higher IBTR rates with positive or indeterminate margins compared with negative, pathologic margins. Furthermore, young age (age < 35 years at diagnosis) was associated with the highest risk of IBTR regardless of margin status.