Pre-exposure prophylaxis for preventing acquisition of HIV: A cross-sectional study of patients, prescribers, uptake, and spending in the United States, 2015-2016

BACKGROUND: In 2015, there were approximately 40,000 new HIV diagnoses in the United States. Pre-exposure prophylaxis (PrEP) is an effective strategy that reduces the risk of HIV acquisition; however, uptake among those who can benefit from it has lagged. In this study, we 1) compared the characteristics of patients who were prescribed PrEP with individuals newly diagnosed with HIV infection, 2) identified the specialties of practitioners prescribing PrEP, 3) identified metropolitan statistical areas (MSAs) within the US where there is relatively low uptake of PrEP, and 4) reported median amounts paid by patients and third-party payors for PrEP. METHODS AND FINDINGS: We analyzed prescription drug claims for individuals prescribed PrEP in the Integrated Dataverse (IDV) from Symphony Health for the period of September 2015 to August 2016 to describe PrEP patients, prescribers, relative uptake, and payment methods in the US. Data were available for 75,839 individuals prescribed PrEP, and findings were extrapolated to approximately 101,000 individuals, which is less than 10% of the 1.1 million adults for whom PrEP was indicated. Compared to individuals with newly diagnosed HIV infection, PrEP patients were more likely to be non-Hispanic white (45% versus 26.2%), older (25% versus 19% at ages 35-44), male (94% versus 81%), and not reside in the South (30% versus 52% reside in the South).Using a ratio of the number of PrEP patients within an MSA to the number of newly diagnosed individuals with HIV infection, we found MSAs with relatively low uptake of PrEP were concentrated in the South. Of the approximately 24,000 providers who prescribed PrEP, two-thirds reported primary care as their specialty. Compared to the types of payment methods that people living with diagnosed HIV (PLWH) used to pay for their antiretroviral treatment in 2015 to 2016 reported in the Centers for Disease Control and Prevention (CDC) HIV Surveillance Special Report, PrEP patients were more likely to have used commercial health insurance (80% versus 35%) and less likely to have used public healthcare coverage or a publicly sponsored assistance program to pay for PrEP (12% versus 45% for Medicaid). Third-party payors covered 95% of the costs of PrEP. Overall, we estimated the median annual per patient out-of-pocket spending on PrEP was approximately US$72. Limitations of this study include missing information on prescription claims of patients not included in the database, and for those included, some patients were missing information on patient diagnosis, race/ethnicity, educational attainment, and income (34%-36%). CONCLUSIONS: Our findings indicate that in 2015-2016, many individuals in the US who could benefit from being on PrEP were not receiving this HIV prevention medication, and those prescribed PrEP had a significantly different distribution of characteristics from the broader population that is at risk for acquiring HIV. PrEP patients were more likely to pay for PrEP using commercial or private insurance, whereas PLWH were more likely to pay for their antiretroviral treatment using publicly sponsored programs. Addressing the affordability of PrEP and otherwise promoting its use among those with indications for PrEP represents an important opportunity to help end the HIV epidemic

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

General Surgery – Is It Critical to Rural Hospital Performance?

Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Community and Preventive Medicine, 2011.During the past 25 years, the overall number of general surgeons per capita in the United States declined by about one quarter. The Chairman of the Board of Regents of the American College of Surgeons recently warned of the impending disappearance of the general surgeon and asked, “Can rural and small hospitals survive with the current general surgeon workforce?” To help answer the above question, this dissertation uses 10 years (1996-2005) of data from seven sources on virtually all US rural hospitals to evaluate the association between sustained drops in Medicare inpatient general surgical revenue and rural hospital financial viability, infrastructure, and quality of care. Financial viability is measured in terms of profitability (total margin) and liquidity (current ratio and days cash on hand). Infrastructure includes nurse staffing (Registered Nurse [RN] full time equivalents [FTEs] per 100 adjusted patient days, Licensed Practical Nurse [LPN] FTEs per 100 adjusted patient days, and RN-LPN skill mix) and technology (a non-medical technology/services index and a Saidin medical technology/services index). Quality of care is evaluated by the likelihood of poor performance on central line infection, accidental laceration or puncture, and iatrogenic pneumothorax. These are patient safety indicators (PSIs) developed by the Agency for Healthcare Research and Quality. Given the outcomes are continuous for the first two specific aims of this dissertation (i.e. financial performance and infrastructure), hospital fixed effects ordinary least squares regression models are used to control for time invariant hospital-specific effects. Yearly indicator variables are also included in the models to control for year-specific effects. Generalized estimating equations (GEE) logit-link regression models with an exchangeable correlation structure that include cluster means are used for the final aim (i.e. quality of care) to estimate the effect on the PSIs (risk-adjusted rates), which are transformed into binary outcome measures. Our main study findings are as follows. Sustained drops in general surgical revenue were associated with:  Sizable declines in profitability, but not with liquidity. No hospitals experiencing drops closed and they rarely converted into another type of health care facility.  Clinically insignificant declines in RN staffing levels, but not with LPN staffing levels or RN-LPN skill mix.  Minimal declines in the provision of non-medical technology, but not with the sophistication of medical technology.  A reduction in the rate of accidental laceration or puncture. However, no association was observed with the rate of iatrogenic pneumothorax and there is little evidence of an association with central line infection. In summary, this dissertation indicates that while rural hospitals with sustained drops in surgical revenue experienced substantial declines in their profitability on average, few significant repercussions were observed for the medical care they provided in terms of nurse staffing levels, technology provision, and surgical quality of care. However, only three measures of surgical quality could be analyzed, because of the small populations at risk for other adverse events among the hospitals that experienced sustained drops in surgical revenue. It seems likely that rural hospitals can continue to survive after experiencing consequential shocks to their surgical activity levels, but future research using measures of quality that are better suited to rural hospitals should evaluate the broader impact that reductions in surgical activity have on the quality of non-surgical care they provide, as well as on regional health outcomes

Assessing the health status and mortality of older people over 65 with HIV.

BackgroundNearly half of people with HIV in the United States are 50 years or older, and this proportion is growing. Between 2012 and 2016, the largest percent increase in the prevalence rate of HIV was among people aged 65 and older, the eligibility age for Medicare coverage for individuals without a disability or other qualifying condition. Previous work suggests that older people with HIV may have higher rates of chronic conditions and develop them more rapidly than older people who do not have HIV. This study compared the health status of older people with HIV with the older US population not living with HIV by comparing: (1) mortality; (2) prevalence of certain conditions, and (3) incidence of these conditions with increasing age.Methods and findingsWe used a sample of Medicare beneficiaries aged 65 and older from the Medicare Master Beneficiary Summary File for the years 2011 to 2016, including 100% of individuals with HIV (N = 43,708), as well as a random 1% sample of individuals without diagnosed HIV (N = 1,029,518). We conducted a survival analysis using a Cox proportional hazards model to assess mortality and to determine the need to adjust for differential mortality in our analyses of the incidence of certain chronic conditions. These results showed that Medicare beneficiaries living with HIV have a significantly higher hazard of mortality compared to older people without diagnosed HIV (3.6 times the hazard). We examined the prevalence of these conditions using logistic regression analysis and found that people with HIV have a statistically significant higher odds of depression, chronic kidney disease, chronic obstructive pulmonary disease (COPD), osteoporosis, hypertension, ischemic heart disease, diabetes, chronic hepatitis, end-stage liver disease, lung cancer, and colorectal cancer. To look at the rate at which older people are diagnosed with conditions as they age, we used a Fine-Gray competing risk model and showed that for individuals without diagnosis of a given condition at age 65, the future incidence of that condition over the remaining study period was higher for people with HIV even after adjusting for differential hazard of mortality and for other demographic characteristics. Many of these results also varied by personal characteristics including Medicaid dual enrollment, sex, and race and ethnicity, as well as by condition.ConclusionsIncreasing access to care and improving health outcomes for people with HIV is a critical goal of the National HIV/AIDS Strategy 2020. It is important for clinicians and policymakers to be aware that despite significant advances in the treatment and care of people with HIV, older people with HIV have a higher odds of having multiple chronic conditions at any point in time, a higher incidence of new diagnoses of these conditions over time, and a higher hazard of mortality than Medicare beneficiaries without HIV