Potential Clinical and Economic Value of Long-Acting Preexposure Prophylaxis for South African Women at High-Risk for HIV Infection.

BACKGROUND: For young South African women at risk for human immunodeficiency virus (HIV) infection, preexposure prophylaxis (PrEP) is one of the few effective prevention options available. Long-acting injectable PrEP, which is in development, may be associated with greater adherence, compared with that for existing standard oral PrEP formulations, but its likely clinical benefits and additional costs are unknown. METHODS: Using a computer simulation, we compared the following 3 PrEP strategies: no PrEP, standard PrEP (effectiveness, 62%; cost per patient, $150/year), and long-acting PrEP (effectiveness, 75%; cost per patient, $220/year) in South African women at high risk for HIV infection (incidence of HIV infection, 5%/year). We examined the sensitivity of the strategies to changes in key input parameters among several outcome measures, including deaths averted and program cost over a 5-year period; lifetime HIV infection risk, survival rate, and program cost and cost-effectiveness; and budget impact. RESULTS: Compared with no PrEP, standard PrEP and long-acting PrEP cost $580 and $870 more per woman, respectively, and averted 15 and 16 deaths per 1000 women at high risk for infection, respectively, over 5 years. Measured on a lifetime basis, both standard PrEP and long-acting PrEP were cost saving, compared with no PrEP. Compared with standard PrEP, long-acting PrEP was very cost-effective ($150/life-year saved) except under the most pessimistic assumptions. Over 5 years, long-acting PrEP cost $1.6 billion when provided to 50% of eligible women. CONCLUSIONS: Currently available standard PrEP is a cost-saving intervention whose delivery should be expanded and optimized. Long-acting PrEP will likely be a very cost-effective improvement over standard PrEP but may require novel financing mechanisms that bring short-term fiscal planning efforts into closer alignment with longer-term societal objectives.

Modeling and Cost-Effectiveness in HIV Prevention.

With HIV funding plateauing and the number of people living with HIV increasing due to the rollout of life-saving antiretroviral therapy, policy makers are faced with increasingly tighter budgets to manage the ongoing HIV epidemic. Cost-effectiveness and modeling analyses can help determine which HIV interventions may be of best value. Incidence remains remarkably high in certain populations and countries, making prevention key to controlling the spread of HIV. This paper briefly reviews concepts in modeling and cost-effectiveness methodology and then examines results of recently published cost-effectiveness analyses on the following HIV prevention strategies: condoms and circumcision, behavioral- or community-based interventions, prevention of mother-to-child transmission, HIV testing, pre-exposure prophylaxis, and treatment as prevention. We find that the majority of published studies demonstrate cost-effectiveness; however, not all interventions are affordable. We urge continued research on combination strategies and methodologies that take into account willingness to pay and budgetary impact.

Large-scale empirical optimisation of statistical control charts to detect clinically relevant increases in surgical site infection rates.

OBJECTIVE: Surgical site infections (SSIs) are common costly hospital-acquired conditions. While statistical process control (SPC) use in healthcare has increased, limited rigorous empirical research compares and optimises these methods for SSI surveillance. We sought to determine which SPC chart types and design parameters maximise the detection of clinically relevant SSI rate increases while minimising false alarms. DESIGN: Systematic retrospective data analysis and empirical optimisation. METHODS: We analysed 12 years of data on 13 surgical procedures from a network of 58 community hospitals. Statistically significant SSI rate increases (signals) at individual hospitals initially were identified using 50 different SPC chart variations (Shewhart or exponentially weighted moving average, 5 baseline periods, 5 baseline types). Blinded epidemiologists evaluated the clinical significance of 2709 representative signals of potential outbreaks (out of 5536 generated), rating them as requiring 'action' or 'no action'. These ratings were used to identify which SPC approaches maximised sensitivity and specificity within a broader set of 3600 individual chart variations (additional baseline variations and chart types, including moving average (MA), and five control limit widths) and over 32 million dual-chart combinations based on different baseline periods, reference data (network-wide vs local hospital SSI rates), control limit widths and other calculation considerations. Results were validated with an additional year of data from the same hospital cohort. RESULTS: The optimal SPC approach to detect clinically important SSI rate increases used two simultaneous MA charts calculated using lagged rolling baseline windows and 1 SD limits. The first chart used 12-month MAs with 18-month baselines and best identified small sustained increases above network-wide SSI rates. The second chart used 6-month MAs with 3-month baselines and best detected large short-term increases above individual hospital SSI rates. This combination outperformed more commonly used charts, with high sensitivity (0.90; positive predictive value=0.56) and practical specificity (0.67; negative predictive value=0.94). CONCLUSIONS: An optimised combination of two MA charts had the best performance for identifying clinically relevant small but sustained above-network SSI rates and large short-term individual hospital increases.

Timeliness of access to lung cancer diagnosis and treatment: A scoping literature review.

The Institute of Medicine recently called for increased understanding of and commitment to timely care. Lung cancer can be difficult to diagnose, resulting in delays that may adversely affect survival; rapid diagnosis and treatment therefore is critical for enabling improved patient outcomes. This scoping review provides an update on timeliness of lung cancer care over the past decade. We searched PubMed for English-language articles published from 2007 to 2016 that report wait time intervals related to diagnosis and treatment of lung cancer. Two authors independently reviewed titles and abstracts for inclusion. Abstracted data included sample size, patient population, study type, dates of study, wait times, and information on disparities, survival, costs, healthcare utilization, and interventions. The final review included 65 studies from 21 different countries. A total of 96 unique variations of wait intervals were reported (e.g., time to diagnosis from first pulmonologist visit, imaging, or initial evaluation), making comparisons across studies difficult. The most common interval was diagnosis to treatment initiation, with reported medians ranging from 6 to 45 days. Fourteen articles reported information on survival, 14 on healthcare utilization, 18 on disparities, and 14 on interventions; results varied by study. Significant variation exists in how access to care time delays are reported. Many patients across different facilities and countries appear to be facing substantial waits to receive lung cancer diagnosis and care. Further research, using common wait-interval metrics, is needed to evaluate and improve timeliness of lung cancer diagnosis and treatment.

Sizanani: A Randomized Trial of Health System Navigators to Improve Linkage to HIV and TB Care in South Africa.

BACKGROUND: A fraction of HIV-diagnosed individuals promptly initiate antiretroviral therapy (ART). We evaluated the efficacy of health system navigators for improving linkage to HIV and tuberculosis (TB) care among newly diagnosed HIV-infected outpatients in Durban, South Africa. METHODS: We conducted a randomized controlled trial (Sizanani Trial, NCT01188941) among adults (≥18 years) at 4 sites. Participants underwent TB screening and randomization into a health system navigator intervention or usual care. Intervention participants had an in-person interview at enrollment and received phone calls and text messages over 4 months. We assessed 9-month outcomes via medical records and the National Population Registry. Primary outcome was completion of at least 3 months of ART or 6 months of TB treatment for coinfected participants. RESULTS: Four thousand nine hundred three participants were enrolled and randomized; 1899 (39%) were HIV-infected, with 1146 (60%) ART-eligible and 523 (28%) TB coinfected at baseline. In the intervention, 212 (39% of outcome-eligible) reached primary outcome compared to 197 (42%) in usual care (RR 0.93, 95% CI: 0.80 to 1.08). One hundred thirty-one (14%) HIV-infected intervention participants died compared to 119 (13%) in usual care; death rates did not differ between arms (RR 1.06, 95% CI: 0.84 to 1.34). In the as-treated analysis, participants reached for ≥5 navigator calls were more likely to achieve study outcome. CONCLUSIONS: ∼40% of ART-eligible participants in both study arms reached the primary outcome 9 months after HIV diagnosis. Low rates of engagement in care, high death rates, and lack of navigator efficacy highlight the urgency of identifying more effective strategies for improving HIV and TB care outcomes.