Understanding preferences for HIV care and treatment in Zambia: evidence from a discrete choice experiment among patients who have been lost to follow-up

Background: In public health HIV treatment programs in Africa, long-term retention remains a challenge. A number of improvement strategies exist (e.g., bring services closer to home, reduce visit frequency, expand hours of clinic operation, improve provider attitude), but implementers lack data about which to prioritize when resource constraints preclude implementing all. We used a discrete choice experiment (DCE) to quantify preferences for a number of potential clinic improvements to enhance retention. Methods and findings: We sought a random sample of HIV patients who were lost to follow-up (defined as >90 days late for their last scheduled appointment) from treatment facilities in Lusaka Province, Zambia. Among those contacted, we asked patients to choose between 2 hypothetical clinics in which the following 5 attributes of those facilities were varied: waiting time at the clinic (1, 3, or 5 hours), distance from residence to clinic (5, 10, or 20 km), ART supply given at each refill (1, 3, or 5 months), hours of operation (morning only, morning and afternoon, or morning and Saturday), and staff attitude ("rude" or "nice"). We used mixed-effects logistic regression to estimate relative utility (i.e., preference) for each attribute level. We calculated how much additional waiting time or travel distance patients were willing to accept in order to obtain other desired features of care. Between December 9, 2015 and May 31, 2016, we offered the survey to 385 patients, and 280 participated (average age 35; 60% female). Patients exhibited a strong preference for nice as opposed to rude providers (relative utility of 2.66; 95% CI 1.9–3.42; p < 0.001). In a standard willingness to wait or willingness to travel analysis, patients were willing to wait 19 hours more or travel 45 km farther to see nice rather than rude providers. An alternative analysis, in which trade-offs were constrained to values actually posed to patients in the experiment, suggested that patients were willing to accept a facility located 10 km from home (as opposed to 5) that required 5 hours of waiting per visit (as opposed to 1 hour) and that dispensed 3 months of medications (instead of 5) in order to access nice (as opposed to rude) providers. This study was limited by the fact that attributes included in the experiment may not have captured additional important determinants of preference. Conclusions: In this study, patients were willing to expend considerable time and effort as well as accept substantial inconvenience in order to access providers with a nice attitude. In addition to service delivery redesign (e.g., differentiated service delivery models), current improvement strategies should also prioritize improving provider attitude and promoting patient centeredness—an area of limited policy attention to date

Sex differences in schizophrenia spectrum disorders: insights from the DiAPAson study using a data-driven approach

Purpose Schizophrenia Spectrum Disorders (SSD) display notable sex differences: males have an earlier onset and more severe negative symptoms, while females exhibit affective symptoms, better verbal abilities, and a more favourable prognosis. Despite extensive research, areas such as time perception and positivity remain underexplored, and machine learning has not yet been adequately utilised. This study aims to address these gaps by examining sex differences in a sample of Italian patients with SSD using a data-driven approach. Methods As part of the DiAPAson project, 619 Italian patients with SSD (198 females; 421 males) were assessed using standardised clinical tools. Data on socio-demographics, clinical characteristics, symptom severity, functioning, positivity, quality of life (QoL), and time perspective were collected. Descriptive and regression analyses were conducted. Principal Component Analysis (PCA) and the Gaussian Mixture Model (GMM) was used to define data-driven clusters. A leave-one-group-out validation was performed. Results Males were more likely to be single (p &lt; 0.001) and less educated (p = 0.006), while females smoked more tobacco (p = 0.011). Males were more frequently prescribed antipsychotics (p = 0.022) and exhibited more severe psychiatric (p = 0.004) and negative symptoms (p = 0.013). They also had a less negative perception of past events (p = 0.047) and a better view of their psychological condition (p = 0.004). Females showed better interpersonal functioning (p = 0.008). PCA and GMM revealed two main clusters with significant sex differences (p = 0.027). Conclusion This study identifies sex differences in SSD, suggesting tailored treatments such as enhancing interpersonal skills for females and maintaining positive self-assessment for males. Using machine learning, we highlight distinct SSD phenotypes, emphasising the need for sex-specific interventions to improve outcomes and QoL. Our findings stress the importance of a multifaceted, interdisciplinary approach to address sex-based disparities in SSD. Trial registration ISRCTN registry ID ISRCTN21141466

Oral abstracts of the 21st International AIDS Conference 18-22 July 2016, Durban, South Africa

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n=122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression.Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/μl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed.Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants.Expression of ‘exhaustion’ or ‘immune checkpoint’ markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches

Dictator Games: A Meta Study

Over the last 25 years, more than a hundred dictator game experiments have been published. This meta study summarizes the evidence. Exploiting the fact that most experiments had to fix parameters they did not intend to test, the meta study explores a rich set of control variables for multivariate analysis. It shows that Tobit models (assuming that dictators would even want to take money) and hurdle models (assuming that the decision to give a positive amount is separate from the choice of amount, conditional on giving) outperform mere meta-regression and OLS

Numerical Tracking of the Solid-Gas Interface in Rocket Motors

Paper AIAA 97-272

Numerical Tracking of the Solid-Gas Interface in Rocket Motors

Paper AIAA 97-272

Adverse outcomes in older hospitalized patients: the role of multidimensional assessment

7nonenoneMarengoni A; Cossi S; de Martinis M; Ghisla MK; Calabrese P; Zanolini G; leonardi R.Marengoni, Alessandra; Cossi, S; de Martinis, M; Ghisla, Mk; Calabrese, P; Zanolini, G; Leonardi, R

Understanding preferences for HIV care and treatment in Zambia: Evidence from a discrete choice experiment among patients who have been lost to follow-up: S4 Appendix. Study data

In public health HIV treatment programs in Africa, long-term retention remains a challenge. A number of improvement strategies exist (e.g., bring services closer to home, reduce visit frequency, expand hours of clinic operation, improve provider attitude), but implementers lack data about which to prioritize when resource constraints preclude implementing all. We used a discrete choice experiment (DCE) to quantify preferences for a number of potential clinic improvements to enhance retention We sought a random sample of HIV patients who were lost to follow-up (defined as >90 days late for their last scheduled appointment) from treatment facilities in Lusaka Province, Zambia. Among those contacted, we asked patients to choose between 2 hypothetical clinics in which the following 5 attributes of those facilities were varied: waiting time at the clinic (1, 3, or 5 hours), distance from residence to clinic (5, 10, or 20 km), ART supply given at each refill (1, 3, or 5 months), hours of operation (morning only, morning and afternoon, or morning and Saturday), and staff attitude (“rude” or “nice”). We used mixed-effects logistic regression to estimate relative utility (i.e., preference) for each attribute level. We calculated how much additional waiting time or travel distance patients were willing to accept in order to obtain other desired features of care. Between December 9, 2015 and May 31, 2016, we offered the survey to 385 patients, and 280 participated (average age 35; 60% female). Patients exhibited a strong preference for nice as opposed to rude providers (relative utility of 2.66; 95% CI 1.9–3.42; p < 0.001). In a standard willingness to wait or willingness to travel analysis, patients were willing to wait 19 hours more or travel 45 km farther to see nice rather than rude providers. An alternative analysis, in which trade-offs were constrained to values actually posed to patients in the experiment, suggested that patients were willing to accept a facility located 10 km from home (as opposed to 5) that required 5 hours of waiting per visit (as opposed to 1 hour) and that dispensed 3 months of medications (instead of 5) in order to access nice (as opposed to rude) providers. This study was limited by the fact that attributes included in the experiment may not have captured additional important determinants of preference. In this study, patients were willing to expend considerable time and effort as well as accept substantial inconvenience in order to access providers with a nice attitude. In addition to service delivery redesign (e.g., differentiated service delivery models), current improvement strategies should also prioritize improving provider attitude and promoting patient centeredness—an area of limited policy attention to date

Drug Side Effects and Retention on HIV Treatment: a Regression Discontinuity Study of Tenofovir Implementation in South Africa and Zambia.

Tenofovir is less toxic than other nucleoside reverse transcriptase inhibitors used in antiretroviral therapy (ART) and may improve retention of HIV-infected patients on ART. We assessed the impact of national guideline changes in South Africa (2010) and Zambia (2007) recommending tenofovir in first-line ART. We applied regression discontinuity in a prospective cohort of 52,294 HIV-infected adults initiating first-line ART within ±12-months of each guideline change. We compared outcomes in patients presenting just before/after the guideline changes using local linear regression and estimated intention-to-treat effects on initiation of tenofovir, retention in care, and other treatment outcomes at 24-months. We assessed complier causal effects among patients starting tenofovir. The new guidelines increased the percentage of patients initiating tenofovir in South Africa (risk difference (RD): 81%; 95% confidence interval (CI): 73, 89) and Zambia (RD: 42%; 95% CI: 38, 45). With the guideline change, single-drug substitutions decreased substantially in South Africa (RD: -15%; 95% CI:-18, -12). Starting tenofovir also reduced attrition in Zambia (intent-to-treat RD: -1.8%; 95% CI: -3.5, -0.1, complier relative risk = 0.74) but not in South Africa (RD: -0.9%; 95% CI: -5.9, 4.1, Complier Relative Risk = 0.94). These results highlight the importance of reducing side effects for increasing retention in care, as well as the differences in population impact of policies with heterogeneous treatment effects implemented in different contexts