The cost-effectiveness of trivalent and quadrivalent influenza vaccination in communities in South Africa, Vietnam and Australia

BACKGROUND: To inform national healthcare authorities whether quadrivalent influenza vaccines (QIVs) provide better value for money than trivalent influenza vaccines (TIVs), we assessed the cost-effectiveness of TIV and QIV in low-and-middle income communities based in South Africa and Vietnam and contrasted these findings with those from a high-income community in Australia. METHODS: Individual based dynamic simulation models were interfaced with a health economic analysis model to estimate the cost-effectiveness of vaccinating 15% of the population with QIV or TIV in each community over the period 2003-2013. Vaccination was prioritized for HIV-infected individuals, before elderly aged 65+ years and young children. Country or region-specific data on influenza-strain circulation, clinical outcomes and costs were obtained from published sources. The societal perspective was used and outcomes were expressed in International$(I$) per quality-adjusted life-year (QALY) gained. RESULTS: When compared with TIV, we found that QIV would provide a greater reduction in influenza-related morbidity in communities in South Africa and Vietnam as compared with Australia. The incremental cost-effectiveness ratio of QIV versus TIV was estimated at I$4183/QALY in South Africa, I$1505/QALY in Vietnam and I$80,966/QALY in Australia. CONCLUSIONS: The cost-effectiveness of QIV varied between communities due to differences in influenza epidemiology, comorbidities, and unit costs. Whether TIV or QIV is the most cost-effective alternative heavily depends on influenza B burden among subpopulations targeted forvaccination in addition to country-specific willingness-to-pay thresholds and budgetary impact

Cost-Effective Strategies for Mitigating a Future Influenza Pandemic with H1N1 2009 Characteristics

Background: We performed an analysis of the cost-effectiveness of pandemic intervention strategies using a detailed, individual-based simulation model of a community in Australia together with health outcome data of infected individuals gathered during 2009–2010. The aim was to examine the cost-effectiveness of a range of interventions to determine the most cost-effective strategies suitable for a future pandemic with H1N1 2009 characteristics. Methodology/Principal Findings: Using transmissibility, age-stratified attack rates and health outcomes determined from H1N1 2009 data, we determined that the most cost-effective strategies involved treatment and household prophylaxis using antiviral drugs combined with limited duration school closure, with costs ranging from $632 to$777 per case prevented. When school closure was used as a sole intervention we found the use of limited duration school closure to be significantly more cost-effective compared to continuous school closure, a result with applicability to countries with limited access to antiviral drugs. Other social distancing strategies, such as reduced workplace attendance, were found to be costly due to productivity losses. Conclusion: The mild severity (low hospitalisation and case fatality rates) and low transmissibility of H1N1 2009 meant that health treatment costs were dominated by the higher productivity losses arising from workplace absence due to illness and childcare requirements following school closure. Further analysis for higher transmissibility but with the same, mild severit

Aortic valve replacement in a young patient with essential thrombocytosis

Essential Thrombocythcythaemia (ET) is an uncommon type of myeloproliferative disorder, characterised by both thrombotic and haemorrhagic diathesis. No clear guidelines exist for the pre- and post-operative management of patients undergoing cardiac surgery in the haematological and surgical literature. This condition has profound implications in patients undergoing cardiac surgery with the use of cardiopulmonary bypass, where heparin is used for anti-coagulation. This dilemma is further compounded in the setting of a young patient undergoing aortic valve replacement (AVR), where insertion of a mechanical prosthesis would be the procedure of choice. This would require life-long anticoagulation with warfarin which can predispose these patients to catastrophic bleeding. Using a tissue valve will subject the patient to multiple redo operations in the patient's lifetime. We report a young patient with ET requiring AVR and discuss the dilemmas surrounding the choice of prosthesis in this patient

The Impact of Case Diagnosis Coverage and Diagnosis Delays on the Effectiveness of Antiviral Strategies in Mitigating Pandemic Influenza A/H1N1 2009

BACKGROUND: Neuraminidase inhibitors were used to reduce the transmission of pandemic influenza A/H1N1 2009 at the early stages of the 2009/2010 pandemic. Policies for diagnosis of influenza for the purposes of antiviral intervention differed markedly between and within countries, leading to differences in the timing and scale of antiviral usage. METHODOLOGY/PRINCIPAL FINDINGS: The impact of the percentage of symptomatic infected individuals who were diagnosed, and of delays to diagnosis, for three antiviral intervention strategies (each with and without school closure) were determined using a simulation model of an Australian community. Epidemic characteristics were based on actual data from the A/H1N1 2009 pandemic including reproduction number, serial interval and age-specific infection rate profile. In the absence of intervention an illness attack rate (AR) of 24.5% was determined from an estimated R(0) of 1.5; this was reduced to 21%, 16.5% or 13% by treatment-only, treatment plus household prophylaxis, or treatment plus household plus extended prophylaxis antiviral interventions respectively, assuming that diagnosis occurred 24 hours after symptoms arose and that 50% of symptomatic cases were diagnosed. If diagnosis occurred without delay, ARs decreased to 17%, 12.2% or 8.8% respectively. If 90% of symptomatic cases were diagnosed (with a 24 hour delay), ARs decreased to 17.8%, 11.1% and 7.6%, respectively. CONCLUSION: The ability to rapidly diagnose symptomatic cases and to diagnose a high proportion of cases was shown to improve the effectiveness of all three antiviral strategies. For epidemics with R(0)< = 1.5 our results suggest that when the case diagnosis coverage exceeds ∼70% the size of the antiviral stockpile required to implement the extended prophylactic strategy decreases. The addition of at least four weeks of school closure was found to further reduce cumulative and peak attack rates and the size of the required antiviral stockpile

Analysis of the effectiveness of interventions used during the 2009 A/H1N1 influenza pandemic

<p>Abstract</p> <p>Background</p> <p>Following the emergence of the A/H1N1 2009 influenza pandemic, public health interventions were activated to lessen its potential impact. Computer modelling and simulation can be used to determine the potential effectiveness of the social distancing and antiviral drug therapy interventions that were used at the early stages of the pandemic, providing guidance to public health policy makers as to intervention strategies in future pandemics involving a highly pathogenic influenza strain.</p> <p>Methods</p> <p>An individual-based model of a real community with a population of approximately 30,000 was used to determine the impact of alternative interventions strategies, including those used in the initial stages of the 2009 pandemic. Different interventions, namely school closure and antiviral strategies, were simulated in isolation and in combination to form different plausible scenarios. We simulated epidemics with reproduction numbers R₀of 1.5, which aligns with estimates in the range 1.4-1.6 determined from the initial outbreak in Mexico.</p> <p>Results</p> <p>School closure of 1 week was determined to have minimal effect on reducing overall illness attack rate. Antiviral drug treatment of 50% of symptomatic cases reduced the attack rate by 6.5%, from an unmitigated rate of 32.5% to 26%. Treatment of diagnosed individuals combined with additional household prophylaxis reduced the final attack rate to 19%. Further extension of prophylaxis to close contacts (in schools and workplaces) further reduced the overall attack rate to 13% and reduced the peak daily illness rate from 120 to 22 per 10,000 individuals. We determined the size of antiviral stockpile required; the ratio of the required number of antiviral courses to population was 13% for the treatment-only strategy, 25% for treatment and household prophylaxis and 40% for treatment, household and extended prophylaxis. Additional simulations suggest that coupling school closure with the antiviral strategies further reduces epidemic impact.</p> <p>Conclusions</p> <p>These results suggest that the aggressive use of antiviral drugs together with extended school closure may substantially slow the rate of influenza epidemic development. These strategies are more rigorous than those actually used during the early stages of the relatively mild 2009 pandemic, and are appropriate for future pandemics that have high morbidity and mortality rates.</p

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

The Far Ultraviolet Spectroscopic Explorer Survey of OVI Absorption in the Disk of the Milky Way

To probe the distribution and physical characteristics of interstellar gas at temperatures T ~ 3e5 K in the disk of the Milky Way, we have used the Far Ultraviolet Spectroscopic Explorer (FUSE) to observe absorption lines of OVI toward 148 early-type stars situated at distances 1 kpc. After subtracting off a mild excess of OVI arising from the Local Bubble, combining our new results with earlier surveys of OVI, and eliminating stars that show conspicuous localized X-ray emission, we find an average OVI mid-plane density n_0 = 1.3e-8 cm^-3. The density decreases away from the plane of the Galaxy in a way that is consistent with an exponential scale height of 3.2 kpc at negative latitudes or 4.6 kpc at positive latitudes. Average volume densities of OVI along different sight lines exhibit a dispersion of about 0.26 dex, irrespective of the distances to the target stars. This indicates that OVI does not arise in randomly situated clouds of a fixed size and density, but instead is distributed in regions that have a very broad range of column densities, with the more strongly absorbing clouds having a lower space density. Line widths and centroid velocities are much larger than those expected from differential Galactic rotation, but they are nevertheless correlated with distance and N(OVI), which reinforces our picture of a diverse population of hot plasma regions that are ubiquitous over the entire Galactic disk. The velocity extremes of the OVI profiles show a loose correlation with those of very strong lines of less ionized species, supporting a picture of a turbulent, multiphase medium churned by shock-heated gas from multiple supernova explosions.Comment: Accepted for publication in ApJS. Preprint with full resolution images and all 148 spectra available at http://www.astro.princeton.edu/~dvb/o

A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis