Therapist-Level Moderators of Patient-Therapist Match Effectiveness in Community Psychotherapy.

Based on patient-reported outcomes data analyzed at the provider level, there is evidence that psychotherapists can possess effectiveness strengths and weaknesses when treating patients with different presenting concerns. These within-therapist differences hold promise for personalizing care by prospectively matching patients to therapists' historical effectiveness strengths. In a double-masked randomized controlled trial (RCT; NCT02990000), such matching outperformed pragmatically determined usual case assignment-which leaves personalized, measurement-based matching to chance-in naturalistic outpatient psychotherapy (Constantino et al., JAMA Psychiatry 78:960-969, 2021). Demonstrating that personalization can be even more precise, some research has demonstrated that the strength of this positive match effect was moderated by certain patient characteristics. Notably, though, it could also be that matching is especially important for some therapists to achieve more effective outcomes. Examining this novel question, the present study drew on the Constantino et al. (JAMA Psychiatry 78:960-969, 2021) trial data to explore three therapist-level moderators of matching: (a) effectiveness "spread" (i.e., greater performance variability across patients' presenting problem domains), (b) overestimation of their measurement-based and problem-specific effectiveness, and (c) the frequency with which they use patient-reported routine outcomes monitoring in their practice. Patients were 206 adults, randomized to the match or control condition, treated by 40 therapists who were crossed over conditions. The therapist variables were assessed at the trial's baseline and patients' symptomatic/functional impairment and global distress were assessed regularly up to 16 weeks of treatment. Hierarchical linear models revealed that only therapist effectiveness spread significantly moderated the match effect for the global distress outcome; for therapists with more spread, the match effect was more pronounced, whereas the match effect was minimal for therapists with less effectiveness spread. Notably, two therapist-level covariates unexpectedly emerged as significant moderators for the symptomatic/functional impairment outcome; for clinicians who consistently treated patients with higher versus lower average severity levels and who relatedly treated a higher proportion of patients with primary presenting problems of substance misuse or violence, the beneficial match effect was even stronger. Thus, measurement-based matching may be especially potent for therapists with more variable effectiveness across problem domains, and who consistently treat patients with more severe presenting concerns or with particular primary problems, which provides further precision in conceptualizing personalized care.

Predicting Successful Placements for Youth in Child Welfare with Machine Learning.

Out-of-home placement decisions have extremely high stakes for the present and future well-being of children in care because some placement types, and multiple placements, are associated with poor outcomes. We propose that a clinical decision support system (CDSS) using existing data about children and their previous placement success could inform future placement decision-making for their peers. The objective of this study was to test the feasibility of developing machine learning models to predict the best level of care placement (i.e., the placement with the highest likelihood of doing well in treatment) based on each youth's behavioral health needs and characteristics. We developed machine learning models to predict the probability of each youth's treatment success in psychiatric residential care (i.e., Psychiatric Residential Treatment Facility [PRTF]) versus any other placement (AUROCs > 0.70) using data collected in standard care at a behavioral health organization. Placement recommendations based on these machine learning models distinguished between youth who did well in residential care versus non-residential care (e.g., 80% of those who received care in the recommended setting with the highest predicted likelihood of success had above average risk-adjusted outcomes). Then we developed and validated machine learning models to predict the probability of each youth's treatment success across specific placement types in a state-wide system, achieving an average AUROC score of greater than 0.75. Machine learning models based on risk-adjusted behavioral health and functional data show promise in predicting positive placement outcomes and informing future placement decisions for youth in care. Related ethical considerations are discussed.

A Qualitative Analysis of Stakeholder Attitudes Regarding Personalized Provider Selection and Patient-Therapist Matching.

This study explored mental health care patients and therapists' perspectives on using therapists' measurement-based and problem-specific effectiveness data to inform case assignments - a type of treatment personalization that has been shown to outperform non-measurement-based case assignment as usual (Constantino et al., 2021). We conducted semi-structured qualitative interviews with 8 patients (75% women; M age = 33.75 years) and 8 therapists (75% women; M age = 47.50 years). The interview protocols were unique to stakeholder group. Recorded responses were transcribed and qualitatively analyzed by four judges using a blend of consensual qualitative research and grounded theory methods. Derived patient domains included preferred characteristics of a provider, and experiences and suggestions regarding provider selection. Within the domains, most patients expressed an interest in accessing more specific provider information online. Additionally, most patients indicated that both provider outcome track records and personal preference information (e.g., therapist characteristics) should be considered in the therapist selection process. All patients endorsed being comfortable with having the ability to select a provider based on a list of empirically well-matched recommendations. Derived therapist domains included using routine outcomes monitoring for patient-provider matching, referral source and direct patient use of preferred provider lists, and improvements to the provider selection process. Within the domains, all therapists remarked that outcome data would be useful for matching patients to providers; however, most also indicated that outcome data should not be the only factor used in provider selection. All therapists expressed a willingness to be included in preferred provider lists that incorporate track record data. Overall, both patients and therapists held generally positive views toward using therapist effectiveness data to help personalize mental health care. Yet, both stakeholder groups acknowledged that other personalization factors should be considered alongside these data. Based on these results, our team is in the process of implementing patient-therapist match strategies in larger and more diverse mental health care contexts.

Revisiting our approach to behavioral health referrals.

This system of matching referrals to behavioral health practitioners' historical effectiveness seeks to strengthen patient outcomes.

Therapist perceptions of their own measurement-based, problem-specific effectiveness.

OBJECTIVE: Patient-reported outcomes data reveal differences both in therapists' global effectiveness across their average patient (between-therapist effect) and in treating different problems within their caseload (within-therapist effects). Yet, it is unclear how accurately therapists perceive their own measurement-based, problem-specific effectiveness and whether such self-perceptions predict global between-therapist performance differences. We explored these questions in naturalistic psychotherapy. METHOD: For 50 therapists, we drew on data from a mean of 27 past patients (total N = 1,363) who completed a multidimensional outcome measure-Treatment Outcome Package (TOP)-at pre- and posttreatment. For each of 12 outcome domains (e.g., depression, anxiety), TOP data classified therapists as historically "effective," "neutral," or "ineffective." Unaware of their data-driven classifications, therapists rated their perceived effectiveness for each domain. We conducted chi-square analyses to determine whether therapists predicted their own measurement-based effectiveness classifications to a level greater than chance. We then used multilevel modeling to test whether therapists' problem-specific perceptions predicted global between-therapist performance differences. RESULTS: For all but one outcome domain, therapists were no better than chance at predicting their measurement-based effectiveness classification. Additionally, controlling for patient baseline impairment, therapists who consistently overestimated their problem-specific effectiveness had patients who reported worse global outcomes than patients whose therapist more accurately estimated their effectiveness. Conversely, therapists who underestimated their problem-specific effectiveness had patients who reported better outcomes than patients whose therapist over- or accurately estimated their effectiveness. CONCLUSIONS: Therapist humility may differentiate the most from least globally effective therapists, and this virtue should be cultivated in clinical trainings. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The social and socio-political embeddedness of COVID-19 vaccination decision-making: A five-country qualitative interview study from Europe.

The uptake ofCOVID-19 vaccines has varied considerably across European countries. This study investigates people's decision-making process regarding vaccination by analyzing qualitative interviews (n = 214) with residents from five European countries: Austria, Germany, Italy, Portugal, and Switzerland. We identify three factors that shape vaccination decision-making: individual experiences and pre-existing attitudes towards vaccination, social environment, and socio-political context. Based on this analysis, we present a typology of decision-making regarding COVID-19 vaccines, where some types present stable stances towards vaccines and others change over time. Trust in government and relevant stakeholders, broader social factors, and people's direct social environment were particularly relevant to these dynamics. We conclude that vaccination campaigns should be considered long-term projects (also outside of pandemics) in need of regular adjustment, communication and fine-tuning to ensure public trust. This is particularly pertinent for booster vaccinations, such as COVID-19 or influenza.

Patient-therapist expectancy convergence and outcome in naturalistic psychotherapy.

Research on close relationships demonstrates that dyadic convergence, or two people becoming more similar in their experiences and/or beliefs over time, is commonplace and adaptive. As psychotherapy involves a close relationship, patient-therapist convergence processes may influence treatment-specific outcomes. Although prior research supports that patients and therapists tend to converge on their alliance perspectives over time, which associates with subsequent patient improvement, no research has similarly examined belief convergence during therapy. Accordingly, this study focused on patient-therapist convergence in their outcome expectations (OE), a belief variable associated with patient improvement when measured from individual participant perspectives. We predicted both that significant OE convergence would occur and relate to better posttreatment outcome. Data derived from a trial of naturalistic psychotherapy. Patients and therapists repeatedly rated their respective OE through treatment, and patients rated their symptom/functional outcomes at posttreatment. For dyads with the requisite OE data (N = 154), we tested our questions using multilevel structural equation modeling. Counter to our hypotheses, there was no discernable OE convergence pattern over treatment (γ100 = 0.01, SE = 0.03, p = .690) and OE convergence was unrelated to outcome at the between-dyad level (γ020 = 2.37, SE = 10.28, p = .818). However, on its own, higher early patient OE was significantly associated with better outcome at the between-dyad level (γ050 = -0.04, SE = 0.01, p = .007). Results suggest that OE may be more of a facilitative patient versus relational process factor. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Therapist-level moderation of within- and between-therapist process-outcome associations.

OBJECTIVE: Although higher quality patient-therapist alliance and more positive patient outcome expectation (OE) consistently predict symptomatic/functional improvement in psychotherapy, most research has failed to capture the nuance in these process-outcome relations by parsing them into within-therapist (i.e., differences between patients treated by the same therapist) and between-therapist (i.e., differences between therapists' average process/outcome ratings across all patients in their caseloads) components. Moreover, the few studies that have done so have produced mixed results, suggesting the possibility of systematic variability in these associations (i.e., moderators). One potential source of such variability could be providers themselves; that is, different therapists could use these processes to differing therapeutic benefit. This study tested the alliance- and OE-outcome associations at both the within- and between-therapist levels and explored therapist-level moderators of them. METHOD: Data derived from 212 adult outpatients treated naturalistically by 42 psychotherapists as part of a randomized trial that compared different case-assignment methods. Patients completed measures of alliance, OE, and outcome repeatedly throughout treatment. Therapist characteristics were assessed at baseline. RESULTS: Multilevel structural equation models revealed that, at the between-therapist level, only higher alliance quality, but not more optimistic OE, was associated with greater caseload-level improvement. At the within-therapist level, only more optimistic OE, but not higher alliance quality, was associated with patient improvement. Finally, therapists' self-perceived alliance-fostering effectiveness and cognitive-behavioral orientation moderated the within- and between-therapist alliance-outcome associations, respectively. CONCLUSION: Results indicate that different therapists use common treatment processes to differing therapeutic benefit, which can inform more personalized clinical practices and trainings. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

For whom does a match matter most? Patient-level moderators of evidence-based patient-therapist matching.

OBJECTIVE: A double-blind, randomized controlled trial tested the effectiveness of a personalized Match System in which patients are assigned to therapists with a "track record" of effectively treating a given patient's primary concern(s) (e.g., anxiety). Matched patients demonstrated significantly better outcomes than those assigned through usual pragmatic means. The present study examined patient-level moderators of this match effect. We hypothesized that the match benefits would be especially pronounced for patients who presented with (a) greater overall problem severity, and (b) greater problem complexity (i.e., number of elevated problem domains). We also explored if patient racial/ethnic minority status moderated the condition effect. METHOD: Patients were 218 adults randomized to the Match or as-usual assignment condition, and then treated naturalistically by 48 therapists. The primary outcome was the Treatment Outcome Package (TOP), a multidimensional assessment tool that also primed the Match algorithm (based on historical, therapist-level effectiveness data), and assessed trial patients' symptoms/functioning and demographic information at baseline. Moderator effects were tested as patient-level interactions in three-level hierarchical linear models. RESULTS: The beneficial match effect was significantly more pronounced for patients with higher initial severity (-0.03, 95% CI -0.05, -0.01) and problem complexity (-0.01, 95% CI -0.02, -0.004), yet the high correlation between severity and complexity called into question the uniqueness of the complexity moderator effect. Moreover, the match effect was more pronounced for racial/ethnic minority patients (i.e., nonwhite; -0.05, 95% CI -0.09, -0.01). CONCLUSIONS: Measurement-based matching is especially effective for patients with certain characteristics, which further informs mental health treatment personalization. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Beyond livestock carrying capacity in the Sahelian and Sudanian zones of West Africa.

We applied the process-based model, LandscapeDNDC, to estimate feed availability in the Sahelian and Sudanian agro-ecological zones of West Africa as a basis for calculating the regional Livestock Carrying Capacity (LCC). Comparison of the energy supply (S) from feed resources, including natural pasture, browse, and crop residues, with energy demand (D) of the livestock population for the period 1981-2020 allowed us to assess regional surpluses (S > D) or deficits (S < D) in feed availability. We show that in the last 40 years a large-scale shift from surplus to deficit has occurred. While during 1981-1990 only 27% of the area exceeded the LCC, it was 72% for the period 2011-2020. This was caused by a reduction in the total feed supply of ~ 8% and an increase in feed demand of ~ 37% per-decade, driven by climate change and increased livestock population, respectively. Overall, the S/D decreased from ~ 2.6 (surplus) in 1981 to ~ 0.5 (deficit) in 2019, with a north-south gradient of increasing S/D. As climate change continues and feed availability may likely further shrink, pastoralists either need to source external feed or significantly reduce livestock numbers to avoid overgrazing, land degradation, and any further conflicts for resources.

Dynamic simulation of management events for assessing impacts of climate change on pre-alpine grassland productivity.

The productivity of permanent temperate cut grasslands is mainly driven by weather, soil characteristics, botanical composition and management. To adapt management to climate change, adjusting the cutting dates to reflect earlier onset of growth and expansion of the vegetation period is particularly important. Simulations of cut grassland productivity under climate change scenarios demands management settings to be dynamically derived from actual plant development rather than using static values derived from current management operations. This is even more important in the alpine region, where the predicted temperature increase is twice as high as compared to the global or Northern Hemispheric average. For this purpose, we developed a dynamic management module that provides timing of cutting and manuring events when running the biogeochemical model LandscapeDNDC. We derived the dynamic management rules from long-term harvest measurements and monitoring data collected at pre-alpine grassland sites located in S-Germany and belonging to the TERENO monitoring network. We applied the management module for simulations of two grassland sites covering the period 2011-2100 and driven by scenarios that reflect the two representative concentration pathways (RCP) 4.5 and 8.5 and evaluated yield developments of different management regimes. The management module was able to represent timing of current management operations in high agreement with several years of field observations (r² > 0.88). Even more, the shift of the first cutting dates scaled to a +1 °C temperature increase simulated with the climate change scenarios (-9.1 to -17.1 days) compared well to the shift recorded by the German Weather Service (DWD) in the study area from 1991-2016 (-9.4 to -14.0 days). In total, the shift in cutting dates and expansion of the growing season resulted in 1-2 additional cuts per year until 2100. Thereby, climate change increased yields of up to 6 % and 15 % in the RCP 4.5 and 8.5 scenarios with highest increases mainly found for dynamically adapted grassland management going along with increasing fertilization rates. In contrast, no or only minor yield increases were associated with simulations restricted to fertilization rates of 170 kg N ha-1 yr-1 as required by national legislations. Our study also shows that yields significantly decreased in drought years, when soil moisture is limiting plant growth but due to comparable high precipitation and water holding capacity of soils, this was observed mainly in the RCP 8.5 scenario in the last decades of the century.

Effect of Matching Therapists to Patients vs Assignment as Usual on Adult Psychotherapy Outcomes: A Randomized Clinical Trial.

Importance: Psychotherapists possess strengths and weaknesses in treating different mental health problems, yet performance information is rarely harnessed in mental health care (MHC). To our knowledge, no prior studies have tested the causal efficacy of prospectively matching patients to therapists with empirically derived strengths in treating patients' specific concerns. Objective: To test the effect of measurement-based matching vs case assignment as usual (CAU) on psychotherapy outcomes. Design, Setting, and Participants: In this randomized clinical trial, adult outpatients were recruited between November 2017 and April 2019. Assessments occurred at baseline and repeatedly during treatment at 6 community MHC clinics in Cleveland, Ohio. To be eligible, patients had to make their own MHC decisions. Of 1329 individuals screened, 288 were randomized. Excluding those who withdrew or provided no assessments beyond baseline, 218 patients treated by 48 therapists were included in the primary modified intent-to-treat analyses. Interventions: Therapist performance was assessed pretrial across 15 or more historical cases based on patients' pre-post reporting across 12 problem domains of the routinely administered Treatment Outcome Package (TOP). Therapists were classified in each domain as effective (on average, patients' symptoms reliably improved), neutral (on average, patients' symptoms neither reliably improved nor deteriorated), or ineffective (on average, patients' symptoms reliably deteriorated). Trial patients were randomly assigned to good-fitting therapists (matched group) or were assigned to therapists pragmatically (CAU group). There were multiple match levels, ranging from therapists being effective on the 3 most elevated domains reported by patients and not ineffective on any others (highest) to not effective on the most elevated domains reported by patients but also not ineffective on any domain (lowest). Therapists treated patients in the matched and CAU groups, and treatment was unmanipulated. Main Outcomes and Measures: General symptomatic and functional impairment across all TOP domains (average z scores relative to the general population mean; higher scores indicate greater impairment), global distress (Symptom Checklist-10; higher scores indicate greater distress), and domain-specific impairment on each individual's most elevated TOP-assessed problem. Results: Of 218 patients, 147 (67.4%) were female, and 193 (88.5%) were White. The mean (SD) age was 33.9 (11.2) years. Multilevel modeling indicated a match effect on reductions in weekly general symptomatic and functional impairment (γ110 = -0.03; 95% CI, -0.05 to -0.01; d = 0.75), global distress (γ110 = -0.16; 95% CI, -0.30 to -0.02; d = 0.50), and domain-specific impairment (γ110 = -0.01; 95% CI -0.01 to -0.006; d = 0.60), with no adverse events. Conclusions and Relevance: Matching patients with therapists based on therapists' performance strengths can improve MHC outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02990000.

No need for secondary Pneumocystis jirovecii pneumonia prophylaxis in adult people living with HIV from Europe on ART with suppressed viraemia and a CD4 cell count greater than 100 cells/µL.

INTRODUCTION: Since the beginning of the HIV epidemic in resource-rich countries, Pneumocystis jirovecii pneumonia (PjP) is one of the most frequent opportunistic AIDS-defining infections. The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) has shown that primary Pneumocystis jirovecii Pneumonia (PjP) prophylaxis can be safely withdrawn in patients with CD4 counts of 100 to 200 cells/µL if plasma HIV-RNA is suppressed on combination antiretroviral therapy. Whether this holds true for secondary prophylaxis is not known, and this has proved difficult to determine due to the much lower population at risk. METHODS: We estimated the incidence of secondary PjP by including patient data collected from 1998 to 2015 from the COHERE cohort collaboration according to time-updated CD4 counts, HIV-RNA and use of PjP prophylaxis in persons >16 years of age. We fitted a Poisson generalized additive model in which the smoothed effect of CD4 was modelled by a restricted cubic spline, and HIV-RNA was stratified as low (<400), medium (400 to 10,000) or high (>10,000copies/mL). RESULTS: There were 373 recurrences of PjP during 74,295 person-years (py) in 10,476 patients. The PjP incidence in the different plasma HIV-RNA strata differed significantly and was lowest in the low stratum. For patients off prophylaxis with CD4 counts between 100 and 200 cells/µL and HIV-RNA below 400 copies/mL, the incidence of recurrent PjP was 3.9 (95% CI: 2.0 to 5.8) per 1000 py, not significantly different from patients on prophylaxis in the same stratum (1.9, 95% CI: 0.1 to 3.7). CONCLUSIONS: HIV viraemia importantly affects the risk of recurrent PjP. In virologically suppressed patients on ART with CD4 counts of 100 to 200/µL, the incidence of PjP off prophylaxis is below 10/1000 py. Secondary PjP prophylaxis may be safely withheld in such patients. While European guidelines recommend discontinuing secondary PjP prophylaxis only if CD4 counts rise above 200 cells/mL, the latest US Guidelines consider secondary prophylaxis discontinuation even in patients with a CD4 count above 100 cells/µL and suppressed viral load. Our results strengthen and support this US recommendation.

A Path to Clinical Quality Integration Through a Clinically Integrated Network: The Experience of an Academic Health System and Its Community Affiliates.

INTRODUCTION: Academic medical centers (AMCs) and community physicians seeking to establish a clinically integrated network (CIN) may benefit from a road map to navigate the opportunities and challenges of such an organizational structure. Creating and participating in a CIN requires careful consideration, investment of time, financial resources, alignment of a new quality infrastructure, shared governance, and vision. POTENTIAL BENEFITS, CHALLENGES, AND REGULATORY CONSIDERATIONS: Potential AMC benefits include geographic clinical expansion, the ability to provide care for a broader population of patients, a mechanism to collaborate with regional physician graduates, and an expansion of available teaching sites for trainees. Potential benefits to community practices include propagation of high-value care, enhanced access to evidence-based protocols and priority measures, preparation for value-based reimbursement structures, and connection to an institution that produces future health care practitioners. Challenges to CIN creation include goal alignment, trust between AMC and community partners, acceptance of common quality measures and benchmarks, access to shared data, and local adoption of quality improvement activities. QUALITY AND INFORMATION TECHNOLOGY CONSIDERATIONS: At inception the mission was to create an innovative academic-community alliance delivering high-quality, high-value, personalized care. Defining the clinical quality goals, measurement, governance, and improvement strategy, as well as information technology structure and decision making, are described. FUTURE DIRECTIONS: The network continues to grow and now includes more than 350 physicians, in 16 different specialties across 50 different independent medical practices throughout Southern California. We believe this builds a firm foundation for value-based health care.

Transcriptional regulation by σ factor phosphorylation in bacteria.

A major form of transcriptional regulation in bacteria occurs through the exchange of the primary σ factor of RNA polymerase (RNAP) with an alternative extracytoplasmic function (ECF) σ factor1. ECF σ factors are generally intrinsically active and are retained in an inactive state via the sequestration into σ factor-anti-σ factor complexes until their action is warranted2-20. Here, we report a previously uncharacterized mechanism of transcriptional regulation that relies on intrinsically inactive ECF σ factors, the activation of which and interaction with the ß'-subunit of RNAP depends on σ factor phosphorylation. In Vibrio parahaemolyticus, the threonine kinase PknT phosphorylates the σ factor EcfP, which results in EcfP activation and expression of an essential polymyxin-resistant regulon. EcfP phosphorylation occurs at a highly conserved threonine residue, Thr63, positioned within a divergent region in the σ2.2 helix. Our data indicate that EcfP is intrinsically inactive and unable to bind the ß'-subunit of RNAP due to the absence of a negatively charged DAED motif in this region. Furthermore, our results indicate that phosphorylation at residue Thr63 mimics this negative charge and licenses EcfP to interact with the ß'-subunit in the formation of the RNAP holoenzyme, which in turn results in target gene expression. This regulatory mechanism is a previously unrecognized paradigm in bacterial signal transduction and transcriptional regulation, and our data suggest that it is widespread in bacteria.

Incidence of hepatocellular carcinoma in HIV/HBV-coinfected patients on tenofovir therapy: Relevance for screening strategies.

BACKGROUND & AIMS: Robust data on hepatocellular carcinoma (HCC) incidence among HIV/hepatitis B virus (HBV)-coinfected individuals on antiretroviral therapy (ART) are needed to inform HCC screening strategies. We aimed to evaluate the incidence and risk factors of HCC among HIV/HBV-coinfected individuals on tenofovir disoproxil fumarate (TDF)-containing ART in a large multi-cohort study. METHODS: We included all HIV-infected adults with a positive hepatitis B surface antigen test followed in 4 prospective European cohorts. The primary outcome was the occurrence of HCC. Demographic and clinical information was retrieved from routinely collected data, and liver cirrhosis was defined according to results from liver biopsy or non-invasive measurements. Multivariable Poisson regression was used to assess HCC risk factors. RESULTS: A total of 3,625 HIV/HBV-coinfected patients were included, of whom 72% had started TDF-containing ART. Over 32,673 patient-years (py), 60 individuals (1.7%) developed an HCC. The incidence of HCC remained stable over time among individuals on TDF, whereas it increased steadily among those not on TDF. Among individuals on TDF, the incidence of HCC was 5.9 per 1,000 py (95% CI 3.60-9.10) in cirrhotics and 1.17 per 1,000 py (0.56-2.14) among non-cirrhotics. Age at initiation of TDF (adjusted incidence rate ratio per 10-year increase: 2.2, 95% CI 1.6-3.0) and the presence of liver cirrhosis (4.5, 2.3-8.9) were predictors of HCC. Among non-cirrhotic individuals, the incidence of HCC was only above the commonly used screening threshold of 2 cases per 1,000 py in patients aged >45 years old at TDF initiation. CONCLUSIONS: Whereas the incidence of HCC was high in cirrhotic HIV/HBV-coinfected individuals, it remained below the HCC screening threshold in patients without cirrhosis who started TDF aged <46 years old. LAY SUMMARY: We investigated the incidence of hepatocellular carcinoma in HIV/hepatitis B virus-coinfected individuals from a large multi-cohort study in Europe. Over 32,673 patient-years, 60 individuals (1.7%) developed hepatocellular carcinoma. The incidence of hepatocellular carcinoma remained low in patients without cirrhosis, who started on tenofovir disoproxil fumarate when aged <46 years old.

Heart Failure Site-Based Research in the United States: Results of the Heart Failure Society of America Research Network Survey.

OBJECTIVES: This study sought to determine clinician and scientist involvement in heart failure (HF) clinical research and to describe the challenges of conducting clinical trials in the United States. BACKGROUND: Improvements in the current capability, potential, and deficiencies of the HF clinical research infrastructure in the United States are needed in order to enhance efficiency and impact. METHODS: The Heart Failure Society of America (HFSA) distributed an electronic survey regarding HF clinical trial activity for the purpose of understanding the barriers that exist to conducting high-quality HF clinical research. RESULTS: Overall, 1,794 HFSA members were queried, and 434 members (24%) completed surveys, whereas a total of 7,589 individuals with interest in HF were queried, and 615 completed surveys. Of the respondents, 410 (67%) were actively engaged in HF research and 120 (20%) were interested in research. Most respondents, 270, were physicians (44%); 311 of the total (76% of the total and 80% of physicians) practiced in academic institutions; 333 respondents (81%) had served as principal investigators and 73 (18%) as site coordinators. Respondents active in clinical research usually participated in 1 to 5 trials and enrolled 1 to 20 patients annually. Institutional review board (IRB) approval typically required 3 months, and contract completion required 3 to 6 months per site. The greatest barriers to research were insufficient site budgets, delay in contracting, inability to find participants meeting trial entry criteria, and unavailability of qualified study coordinators. CONCLUSIONS: Many U.S. clinical research sites are constrained by budgetary, staffing, and contractual issues. The HFSA Research Network seeks to unify interested sites and deconstruct barriers to permit high-value HF research.

Constraining N cycling in the ecosystem model LandscapeDNDC with the stable isotope model SIMONE.

The isotopic composition (ic) of soil nitrogen (N) and, more recently, the intramolecular distribution of 15 N in the N2 O molecule (site preference, SP) are powerful instruments to identify dominant N turnover processes, and to attribute N2 O emissions to their source processes. Despite the process information contained in the ic of N species and the associated potential for model validation, the implementation of isotopes in ecosystem models has lagged behind. To foster the validation of ecosystem models based on the ic of N species, we developed the stable isotope model for nutrient cycles (SIMONE). SIMONE uses fluxes between ecosystem N pools (soil organic N, mineral N, plants, microbes) calculated by biogeochemical models, and literature isotope effects for these processes to calculate the ic of N species. Here, we present the concept of SIMONE, apply it to simulations of the biogeochemical model LandscapeDNDC, and assess the capability of 15 N-N2 O and, to our knowledge for the first time, SP, to constrain simulated N fluxes by LandscapeDNDC. LandscapeDNDC successfully simulated N2 O emission, soil nitrate, and ammonium, as well as soil environmental conditions of an intensively managed grassland site in Switzerland. Accordingly, the dynamics of 15 N-N2 O and SP of soil N2 O fluxes as simulated by SIMONE agreed well with measurements, though 15 N-N2 O was on average underestimated and SP overestimated (root-mean-square error [RMSE] of 8.4‰ and 7.3‰, respectively). Although 15 N-N2 O could not constrain the N cycling process descriptions of LandscapeDNDC, the overestimation of SP indicated an overestimation of simulated nitrification rates by 10-59% at low water content, suggesting the revision of the corresponding model parameterization. Our findings show that N isotope modeling in combination with only recently available high- frequency measurements of the N2 O ic are promising tools to identify and address weaknesses in N cycling of ecosystem models. This will finally contribute to augmenting the development of model-based strategies for mitigating N pollution.

Postfire nitrogen balance of Mediterranean shrublands: Direct combustion losses versus gaseous and leaching losses from the postfire soil mineral nitrogen flush.

Fire is a major factor controlling global carbon (C) and nitrogen (N) cycling. While direct C and N losses caused by combustion have been comparably well established, important knowledge gaps remain on postfire N losses. Here, we quantified both direct C and N combustion losses as well as postfire gaseous losses (N2 O, NO and N2 ) and N leaching after a high-intensity experimental fire in an old shrubland in central Spain. Combustion losses of C and N were 9.4 Mg C/ha and 129 kg N/ha, respectively, representing 66% and 58% of initial aboveground vegetation and litter stocks. Moreover, fire strongly increased soil mineral N concentrations by several magnitudes to a maximum of 44 kg N/ha 2 months after the fire, with N largely originating from dead soil microbes. Postfire soil emissions increased from 5.4 to 10.1 kg N ha-1  year-1 for N2 , from 1.1 to 1.9 kg N ha-1  year-1 for NO and from 0.05 to 0.2 kg N ha-1  year-1 for N2 O. Maximal leaching losses occurred 2 months after peak soil mineral N concentrations, but remained with 0.1 kg N ha-1  year-1 of minor importance for the postfire N mass balance. 15 N stable isotope labelling revealed that 33% of the mineral N produced by fire was incorporated in stable soil N pools, while the remainder was lost. Overall, our work reveals significant postfire N losses dominated by emissions of N2 that need to be considered when assessing fire effects on ecosystem N cycling and mass balance. We propose indirect N gas emissions factors for the first postfire year, equalling to 7.7% (N2 -N), 2.7% (NO-N) and 5.0% (N2 O-N) of the direct fire combustion losses of the respective N gas species.