Hidden costs: The ethics of cost-effectiveness analyses for health interventions in resource-limited settings

Cost-effectiveness analysis (CEA) is an increasingly appealing tool for evaluating and comparing health-related interventions in resource-limited settings. The goal is to inform decision-makers regarding the health benefits and associated costs of alternative interventions, helping guide allocation of limited resources by prioritizing interventions that offer the most health for the least money. Although only one component of a more complex decision-making process, CEAs influence the distribution of healthcare resources, directly influencing morbidity and mortality for the world’s most vulnerable populations. However, CEA-associated measures are frequently setting-specific valuations, and CEA outcomes may violate ethical principles of equity and distributive justice. We examine the assumptions and analytical tools used in CEAs that may conflict with societal values. We then evaluate contextual features unique to resource-limited settings, including the source of health-state utilities and disability weights; implications of CEA thresholds in light of economic uncertainty; and the role of external donors. Finally, we explore opportunities to help align interpretation of CEA outcomes with values and budgetary constraints in resource-limited settings. The ethical implications of CEAs in resource-limited settings are vast. It is imperative that CEA outcome summary measures and implementation thresholds adequately reflect societal values and ethical priorities in resource-limited settings

The HAT TRICK programme for improving physical activity, healthy eating and connectedness among overweight, inactive men: Study protocol of a pragmatic feasibility trial

Introduction  Physical activity, healthy eating and maintaining a healthy weight are associated with reduced risk of cardiovascular disease, type 2 diabetes and cancer and with improved mental health. Despite these benefits, many men do not meet recommended physical activity guidelines and have poor eating behaviours. Many health promotion programmes hold little appeal to men and consequently fail to influence men's health practices. HAT TRICK was designed as a 12-week face-to-face, gender-sensitised intervention for overweight and inactive men focusing on physical activity, healthy eating and social connectedness and was delivered in collaboration with a major junior Canadian ice hockey team (age range 16-20 years). The programme was implemented and evaluated to assess its feasibility. This article describes the intervention design and study protocol of HAT TRICK.  Methods and analysis  HAT TRICK participants (n=60) were men age 35 years, residing in the Okanagan Region of British Columbia, who accumulate 150 min of moderate to vigorous physical activity a week, with a body mass index of >25 kg/m 2 and a pant waist size of >38'. Each 90 min weekly session included targeted health education and theory-guided behavioural change techniques, as well as a progressive (ie, an increase in duration and intensity) group physical activity component. Outcome measures were collected at baseline, 12 weeks and 9 months and included the following: objectively measured anthropometrics, blood pressure, heart rate, physical activity and sedentary behaviour, as well as self-reported physical activity, sedentary behaviour, diet, smoking, alcohol consumption, sleep habits, risk of depression, health-related quality of life and social connectedness. Programme feasibility data (eg, recruitment, satisfaction, adherence, content delivery) were assessed at 12 weeks via interviews and self-report.  Ethics and dissemination  Ethical approval was obtained from the University of British Columbia Okanagan Behavioural Research Ethics Board (reference no H1600736). Study findings will be disseminated through academic meetings, peer-reviewed publication, web-based podcasts, social media, plain language summaries and co-delivered community presentations.  Trial registration number  ISRCTN43361357,Pre results

Bioluminescent human breast cancer cell lines that permit rapid and sensitive in vivo detection of mammary tumors and multiple metastases in immune deficient mice

INTRODUCTION: Our goal was to generate xenograft mouse models of human breast cancer based on luciferase-expressing MDA-MB-231 tumor cells that would provide rapid mammary tumor growth; produce metastasis to clinically relevant tissues such as lymph nodes, lung, and bone; and permit sensitive in vivo detection of both primary and secondary tumor sites by bioluminescent imaging. METHOD: Two clonal cell sublines of human MDA-MB-231 cells that stably expressed firefly luciferase were isolated following transfection of the parental cells with luciferase cDNA. Each subline was passaged once or twice in vivo to enhance primary tumor growth and to increase metastasis. The resulting luciferase-expressing D3H1 and D3H2LN cells were analyzed for long-term bioluminescent stability, primary tumor growth, and distal metastasis to lymph nodes, lungs, bone and soft tissues by bioluminescent imaging. Cells were injected into the mammary fat pad of nude and nude-beige mice or were delivered systemically via intracardiac injection. Metastasis was also evaluated by ex vivo imaging and histologic analysis postmortem. RESULTS: The D3H1 and D3H2LN cell lines exhibited long-term stable luciferase expression for up to 4–6 months of accumulative tumor growth time in vivo. Bioluminescent imaging quantified primary mammary fat pad tumor development and detected early spontaneous lymph node metastasis in vivo. Increased frequency of spontaneous lymph node metastasis was observed with D3H2LN tumors as compared with D3H1 tumors. With postmortem ex vivo imaging, we detected additional lung micrometastasis in mice with D3H2LN mammary tumors. Subsequent histologic evaluation of tissue sections from lymph nodes and lung lobes confirmed spontaneous tumor metastasis at these sites. Following intracardiac injection of the MDA-MB-231-luc tumor cells, early metastasis to skeletal tissues, lymph nodes, brain and various visceral organs was detected. Weekly in vivo imaging data permitted longitudinal analysis of metastasis at multiple sites simultaneously. Ex vivo imaging data from sampled tissues verified both skeletal and multiple soft tissue tumor metastasis. CONCLUSION: This study characterized two new bioluminescent MDA-MB-231-luc human breast carcinoma cell lines with enhanced tumor growth and widespread metastasis in mice. Their application to current xenograft models of breast cancer offers rapid and highly sensitive detection options for preclinical assessment of anticancer therapies in vivo

Cost-Effectiveness of Pre-exposure HIV Prophylaxis During Pregnancy and Breastfeeding in Sub-Saharan Africa

Antiretroviral pre-exposure prophylaxis (PrEP) for the prevention of HIV acquisition is cost-effective when delivered to those at substantial risk. Despite a high incidence of HIV infection among pregnant and breastfeeding women in sub-Saharan Africa (SSA), a theoretical increased risk of preterm birth on PrEP could outweigh the HIV prevention benefit

T violation and the unidirectionality of time

An increasing number of experiments at the Belle, BNL, CERN, DA{\Phi}NE and SLAC accelerators are confirming the violation of time reversal invariance (T). The violation signifies a fundamental asymmetry between the past and future and calls for a major shift in the way we think about time. Here we show that processes which violate T symmetry induce destructive interference between different paths that the universe can take through time. The interference eliminates all paths except for two that represent continuously forwards and continuously backwards time evolution. Evidence from the accelerator experiments indicates which path the universe is effectively following. This work may provide fresh insight into the long-standing problem of modeling the dynamics of T violation processes. It suggests that T violation has previously unknown, large-scale physical effects and that these effects underlie the origin of the unidirectionality of time. It may have implications for the Wheeler-DeWitt equation of canonical quantum gravity. Finally it provides a view of the quantum nature of time itself.Comment: 24 pages, 5 figures. Final version accepted for publishing in Foundations of Physics. The final publication is available at http://www.springerlink.com/content/y3h4174jw2w78322

Infant Human Immunodeficiency Virus-free Survival in the Era of Universal Antiretroviral Therapy for Pregnant and Breastfeeding Women: A Community-based Cohort Study From Rural Zambia.

BACKGROUND: Lifelong antiretroviral therapy (ART) is now recommended for all human immunodeficiency virus (HIV)-infected pregnant and breastfeeding women; however, few have described overall infant outcomes in this new era for the prevention of mother-to-child HIV transmission (PMTCT). METHODS: As part of an assessment of PMTCT program impact, we enrolled a prospective cohort study in 4 predominantly rural districts in Zambia. HIV-infected mothers and their newborns (≤30 days old) were recruited and followed at 6 weeks, 6 months and 12 months postpartum; infant specimens were tested via HIV DNA polymerase chain reaction. In Kaplan-Meier analyses, we estimated overall infant HIV-free survival and then stratified by district, community and maternal ART use. We investigated the relationship between community-level 12-month, self-reported maternal ART use and infant HIV-free survival via linear regression. RESULTS: From June 2014 to November 2015, we enrolled 827 mother-infant pairs in 33 communities. At 12 months, small proportions of infants had died (2.8%), were HIV-infected (3.0%) or were lost to follow-up (4.3%). Overall, infant HIV-free survival was 99.0% [95% confidence interval (CI): 98.0%-99.5%] at 6 weeks, 97.5% (95% CI: 96.1%-98.4%) at 6 months and 96.3% (95% CI: 94.8%-97.4%) at 12 months. Women reporting ART use at enrollment had higher infant HIV-free survival than those who did not (97.4% vs. 89.0%, P = 0.01). Differences were noted at the district and site levels (P = 0.01). In community-level analysis, no relationship was observed between 12-month infant HIV-free survival and self-reported maternal ART use (P = 0.65). CONCLUSION: Although encouraging, these findings highlight the need for rigorous monitoring and evaluation of PMTCT services at the population level

Vaginal progesterone to reduce preterm birth among HIV-infected pregnant women in Zambia: a feasibility study protocol

Abstract Background Women infected with HIV have a risk of preterm birth (PTB) that is twice that among uninfected women, and treatment with antiretroviral therapy (ART) may further increase this risk. Progesterone supplementation reduces the risk of preterm delivery in women who have a shortened cervix in the midtrimester. We propose to study the feasibility of a trial of vaginal progesterone (VP) to prevent PTB among HIV-infected women receiving ART in pregnancy. Given low adherence among women self-administering vaginal study product in recent microbicide trials, we plan to investigate whether adequate adherence to VP can be achieved prior to launching a full-scale efficacy trial. Methods and design One hundred forty HIV-infected pregnant women in Lusaka, Zambia, will be randomly allocated to daily self-administration of either VP or matched placebo, starting between 20 and 24 gestational weeks. The primary outcome will be adherence, defined as the proportion of participants who achieve at least 80% use of study product, assessed objectively with a validated dye stain assay that confirms vaginal insertion of returned single-use applicators. Secondary outcomes will be study uptake, retention, and preliminary efficacy. We will concurrently perform semi-structured interviews with participants enrolled in the study and with women who decline enrollment to assess the acceptability of VP to prevent PTB and of enrollment to a randomized controlled trial. Discussion We hypothesize that VP could prevent PTB among women receiving ART in pregnancy. In preparation for a trial to test this hypothesis, we plan to assess whether participants will be adherent to study product and protocol. Trial registration ClinicalTrial.gov, NCT02970552

Progesterone and prolactin levels in pregnant women living with HIV who delivered preterm and low birthweight infants: A nested case-control study

Background Antiretroviral therapy (ART) is associated with high rates of adverse birth outcomes, including preterm birth and low birthweight. Studies suggest that progesterone and prolactin may play important intermediary roles. Methods We analyzed data from the Antenatal Component of the PROMISE trial, a multi-center study of pregnant women taking antiretroviral regimens (lopinavir/ritonavir-containing ART or zidovudine alone) to prevent mother-to-child HIV transmission. In a nested case-control study, we compared data from women who gave birth to preterm (<37 weeks gestation) and/or low birthweight (<2500 g) infants to matched individuals who did not. We measured serum progesterone and prolactin at 24–34 weeks gestation. We used conditional logistic regression to describe relationships between hormone levels, birth outcomes, and antiretroviral regimens. Results 299 women and their newborns were included (146 cases, 153 controls). When compared to women receiving zidovudine alone, those on ART had higher odds of progesterone levels under the 10th percentile (adjusted odds ratio [AOR]:2.34, 95%CI:1.41–3.89) and 25th percentile (AOR:2.07, 95%CI:1.46–2.94). However, higher levels of progesterone—rather than lower levels—were associated with our composite case outcome at the 10th percentile (AOR:1.88, 95%CI:0.77–4.59) and 25th percentile (AOR:1.96, 95%CI:1.06–3.61). Associations were not observed between prolactin, antiretroviral regimen, and birth outcomes. Conclusion We observed lower progesterone levels among women allocated to ART regimens; however, higher progesterone levels were associated with preterm birth and/or low birthweight. While features of the study design may have contributed to these findings, they nevertheless highlight the potentially complex mechanisms underpinning adverse birth outcomes and HIV

Factors related with the university degree selection in Spanish public university system. An structural equation model analysis

The final publication is available at Springer via http://dx.doi.org/10.1007/s11135-014-0008-9Students take into account different factors in their choice of university studies and college. Some are global, as the quality of the degree (ratio available places/firstchoice places in, cut-off grade, etc.), and others are subjective factors (e.g.: my friends are also taking this degree). In this work we present a partial multivariate model that takes into account the weight of the different variables shown by different works linked to this decision. We have studied three samples (n = 372 from the Universidad Pablo de Olavide; n = 2,244 from the Universitat Politécnica de Valencia, and n = 543 from the Universitat de Barcelona) from several degrees in the 2010 2011 and 2011 2012 academic years, all of them new students, coming from high school, and who had choosen these universities as first choice. The global effect shows that the structural model fits reasonably well in the three universities studied. Similarly, university and specialty models show different intensity effects, and we found that, in the case of Universitat Politécnica de Valencia (UPV) and Universitat de Barcelona (UB), they show higher intensity than in Universidad Pablo de Olavide (UPO). This makes us think that in most urban universities with a clear and regular offer of degrees (engineering in the case of UPV, and Health and Social Sciences in the case of UB), personal and social factors are more important than in the case of universities, as is the case of UPO, with an offer and dimension not yet completely defined.Guàrdia Olmos, J.; Peró Cebollero, M.; Hervás Jorge, A.; Capilla Lladró, R.; Soriano Jiménez, PP.; Porras Yañez, M. (2014). Factors related with the university degree selection in Spanish public university system. An structural equation model analysis. Quality and Quantity. 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