Challenges to estimating vaccine impact using hospitalization data.

Because the real-world impact of new vaccines cannot be known before they are implemented in national programs, post-implementation studies at the population level are critical. Studies based on analysis of hospitalization rates of vaccine-preventable outcomes are typically used for this purpose. However, estimates of vaccine impact based on hospitalization data are particularly prone to confounding, as hospitalization rates are tightly linked to changes in the quality, access and use of the healthcare system, which often occur simultaneously with introduction of new vaccines. Here we illustrate how changes in healthcare delivery coincident with vaccine introduction can influence estimates of vaccine impact, using as an example reductions in infant pneumonia hospitalizations after introduction of the 10-valent pneumococcal conjugate vaccine (PCV10) in Brazil. To this end, we explore the effect of changes in several metrics of quality and access to public healthcare on trends in hospitalization rates before (2008-09) and after (2011-12) PCV10 introduction in 2010. Changes in infant pneumonia hospitalization rates following vaccine introduction were significantly associated with concomitant changes in hospital capacity and the fraction of the population using public hospitals. Importantly, reduction of pneumonia hospitalization rates after PCV10 were also associated with the expansion of outpatient services in several Brazilian states, falling more sharply where primary care coverage and the number of health units offering basic and emergency care increased more. We show that adjustments for unrelated (non-vaccine) trends commonly employed by impact studies, such as use of single control outcomes, are not always sufficient for accurate impact assessment. We discuss several ways to identify and overcome such biases, including sensitivity analyses using different denominators to calculate hospitalizations rates and methods that track changes in the outpatient setting. Employing these practices can improve the accuracy of vaccine impact estimates, particularly in evolving healthcare settings typical of low- and middle-income countries

Impact of Pneumococcal Conjugate Vaccines on Pneumonia Hospitalizations in High- and Low-Income Subpopulations in Brazil.

BackgroundPneumococcal conjugate vaccines (PCVs) are being used worldwide. A key question is whether the impact of PCVs on pneumonia is similar in low- and high-income populations. However, most low-income countries, where the burden of disease is greatest, lack reliable data that can be used to evaluate the impact. Data from middle-income countries that have both low- and high-income subpopulations can provide a proxy measure for the impact of the vaccine in low-income countries.MethodsWe evaluated the impact of PCV10 on hospitalizations for all-cause pneumonia in Brazil, a middle-income country with localities that span a broad range of human development index (HDI) levels. We used complementary time series and spatiotemporal methods (synthetic controls and hierarchical Bayesian spatial regression) to test whether the decline in pneumonia hospitalizations associated with vaccine introduction varied across the socioeconomic spectrum.ResultsWe found that the declines in all-cause pneumonia hospitalizations in children and young and middle-aged adults did not vary substantially across low and high HDI subpopulations. Moreover, the estimated declines seen in infants and young adults were associated with higher levels of uptake of the vaccine at a local level.ConclusionsThese results suggest that PCVs have an important impact on hospitalizations for all-cause pneumonia in both low- and high-income populations

Evolutionary Time for Dispersal Limits the Extent but Not the Occupancy of Species’ Potential Ranges in the Tropical Plant Genus Psychotria (Rubiaceae)

Explaining the diversity in geographic range sizes among species is a central goal of ecological and evolutionary studies. We tested species age as an explanation of range size variation within a group of understory shrubs in the Neotropics (Psychotria subgenus Psychotria, Rubiaceae). We distinguish between range occupancy (filling an occupied area) and range extent (maximum distances dispersed). We used Bayesian relaxed-clock dating of molecular sequence data to estimate the relative age of species, and we used species distribution modeling to predict species\u27 potential ranges. If the range sizes of species are limited by time for dispersal, we hypothesize that older species should have (1) larger realized range occupancies and realized range extents than younger species, (2) filled a greater proportion of their potential range occupancies, and (3) colonized a greater proportion of their potential range extents. We found (1) a significant but weak positive relationship between species age versus both realized range occupancy and realized range extent, (2) no relationship between species age and filling of potential range occupancies, but (3) that older species had colonized a significantly greater proportion of their potential range extents than younger species. Our results indicate that a time-for-dispersal effect can limit the extent of ranges of species but not necessarily their occupancies

Spectroscopy of Seven Cataclysmic Variables with Periods Above Five Hours

We present spectroscopy of seven cataclysmic variable stars with orbital periods P(orb) greater than 5 hours, all but one of which are known to be dwarf novae. Using radial velocity measurements we improve on previous orbital period determinations, or derive periods for the first time. The stars and their periods are TT Crt, 0.2683522(5) d; EZ Del, 0.2234(5) d; LL Lyr, 0.249069(4) d; UY Pup, 0.479269(7) d; RY Ser, 0.3009(4) d; CH UMa, 0.3431843(6) d; and SDSS J081321+452809, 0.2890(4) d. For each of the systems we detect the spectrum of the secondary star, estimate its spectral type, and derive a distance based on the surface brightness and Roche lobe constraints. In five systems we also measure the radial velocity curve of the secondary star, estimate orbital inclinations, and where possible estimate distances based on the MV(max) vs.P(orb) relation found by Warner. In concordance with previous studies, we find that all the secondary stars have, to varying degrees, cooler spectral types than would be expected if they were on the main sequence at the measured orbital period.Comment: 25 pages, 2 figures, accepted for Publications of the Astronomical Society of the Pacifi

Spectroscopic Orbital Periods for 29 Cataclysmic Variables from the Sloan Digital Sky Survey

We report follow-up spectroscopy of 29 cataclysmic variables from the Sloan Digital Sky Survey (SDSS), 22 of which were discovered by SDSS and seven of which are previously known systems that were recovered in SDSS. The periods for 16 of these objects were included in the tabulation by Gänsicke et al. While most of the systems have periods less than 2 hr, only one has a period in the 80–86 minutes spike found by Gänsicke et al., and 11 have periods longer than 3 hr, indicating that the present sample is skewed toward longer-period, higher-luminosity objects. Seven of the objects have spectra resembling dwarf novae, but have apparently never been observed in outburst, suggesting that many cataclysmics with relatively low variability amplitude remain to be discovered. Some of the objects are notable. SDSS J07568+0858 and SDSS J08129+1911 were previously known to have deep eclipses; in addition to spectroscopy, we use archival data from the Catalina Real Time Transient Survey to refine their periods. We give a parallax-based distance of 195 (+54, −39) pc for LV Cnc (SDSS J09197+0857), which at Porb = 81 m has the shortest orbital period in our sample. SDSS J08091+3814 shows both the spectroscopic phase offset and phase-dependent absorption found in SW Sextantis stars. The average spectra of SDSS J08055+0720 and SDSS J16191+1351 show contributions from K-type secondaries, and SDSS J080440+0239 shows a contribution from an early M star. We use these to constrain the distances. SDSS J09459+2922 has characteristics typical of a magnetic system. SDSS11324+6249 may be a novalike variable, and if so, its orbital period (99 minutes) is unusually short for that subclass

Why do they do that?: Looking beyond typical reasons for non-urgent ED use among Medicaid patients

Barriers to accessing primary care, including lack of transportation and inadequate appointment times, are common reasons for non-urgent emergency department (ED) use yet even when these barriers are addressed, the problem persists. This study explored non-urgent ED use by Medicaid enrollees through interviews with patients and providers and sought to identify themes beyond the commonly mentioned logistical and access issues. Qualitative interviews with 23 Medicaid enrollees and 31 PCP and ED providers utilizing a semi-structured interview guide focused on reasons for seeking care in the ED and issues associated with PCP appointments. We identified overlap as well as surprising differences in themes identified by providers and by patients. Providers identified cultural and educational issues including that many Medicaid patients had grown up using the ED as their main source of care and lacked awareness of other sources healthcare. Patients did not mention educational and cultural factors directly, but discussed a concern that their condition was too serious for the PCP, or that the ED provided more comprehensive services. Both patients and providers raised neglected concepts, particularly those related to understanding primary care compared to emergency care. These results highlight the importance of addressing multiple paths toward more appropriate ED use, including barriers beyond logistical and access-related concerns. Considering the patient’s perception of the situation, as well as identifying opportunities to improve patients’ understanding of where to seek care may help to create interventions with broader impact than those that address access and logistical barriers alone

Neuroprotective efficacy of P7C3 compounds in primate hippocampus.

There is a critical need for translating basic science discoveries into new therapeutics for patients suffering from difficult to treat neuropsychiatric and neurodegenerative conditions. Previously, a target-agnostic in vivo screen in mice identified P7C3 aminopropyl carbazole as capable of enhancing the net magnitude of postnatal neurogenesis by protecting young neurons from death. Subsequently, neuroprotective efficacy of P7C3 compounds in a broad spectrum of preclinical rodent models has also been observed. An important next step in translating this work to patients is to determine whether P7C3 compounds exhibit similar efficacy in primates. Adult male rhesus monkeys received daily oral P7C3-A20 or vehicle for 38 weeks. During weeks 2-11, monkeys received weekly injection of 5'-bromo-2-deoxyuridine (BrdU) to label newborn cells, the majority of which would normally die over the following 27 weeks. BrdU+ cells were quantified using unbiased stereology. Separately in mice, the proneurogenic efficacy of P7C3-A20 was compared to that of NSI-189, a proneurogenic drug currently in clinical trials for patients with major depression. Orally-administered P7C3-A20 provided sustained plasma exposure, was well-tolerated, and elevated the survival of hippocampal BrdU+ cells in nonhuman primates without adverse central or peripheral tissue effects. In mice, NSI-189 was shown to be pro-proliferative, and P7C3-A20 elevated the net magnitude of hippocampal neurogenesis to a greater degree than NSI-189 through its distinct mechanism of promoting neuronal survival. This pilot study provides evidence that P7C3-A20 safely protects neurons in nonhuman primates, suggesting that the neuroprotective efficacy of P7C3 compounds is likely to translate to humans as well