Cost-Effectiveness of Strategies to Improve HIV Testing and Receipt of Results: Economic Analysis of a Randomized Controlled Trial

The CDC recommends routine voluntary HIV testing of all patients 13-64 years of age. Despite this recommendation, HIV testing rates are low even among those at identifiable risk, and many patients do not return to receive their results. To examine the costs and benefits of strategies to improve HIV testing and receipt of results. Cost-effectiveness analysis based on a Markov model. Acceptance of testing, return rates, and related costs were derived from a randomized trial of 251 patients; long-term costs and health outcomes were derived from the literature. Primary-care patients with unknown HIV status. Comparison of three intervention models for HIV counseling and testing: Model A = traditional HIV counseling and testing; Model B = nurse-initiated routine screening with traditional HIV testing and counseling; Model C = nurse-initiated routine screening with rapid HIV testing and streamlined counseling. Life-years, quality-adjusted life-years (QALYs), costs and incremental cost-effectiveness. Without consideration of the benefit from reduced HIV transmission, Model A resulted in per-patient lifetime discounted costs of $48,650 and benefits of 16.271 QALYs. Model B increased lifetime costs by$53 and benefits by 0.0013 QALYs (corresponding to 0.48 quality-adjusted life days). Model C cost $66 more than Model A with an increase of 0.0018 QALYs (0.66 quality-adjusted life days) and an incremental cost-effectiveness of$36,390/QALY. When we included the benefit from reduced HIV transmission, Model C cost $10,660/QALY relative to Model A. The cost-effectiveness of Model C was robust in sensitivity analyses. In a primary-care population, nurse-initiated routine screening with rapid HIV testing and streamlined counseling increased rates of testing and receipt of test results and was cost-effective compared with traditional HIV testing strategies

Leukotriene biosynthesis inhibition ameliorates acute lung injury following hemorrhagic shock in rats

<p>Abstract</p> <p>Background</p> <p>Hemorrhagic shock followed by resuscitation is conceived as an insult frequently induces a systemic inflammatory response syndrome and oxidative stress that results in multiple-organ dysfunction syndrome including acute lung injury. MK-886 is a leukotriene biosynthesis inhibitor exerts an anti inflammatory and antioxidant activity.</p> <p>Objectives</p> <p>The objective of present study was to assess the possible protective effect of MK-886 against hemorrhagic shock-induced acute lung injury via interfering with inflammatory and oxidative pathways.</p> <p>Materials and methods</p> <p>Eighteen adult Albino rats were assigned to three groups each containing six rats: group I, sham group, rats underwent all surgical instrumentation but neither hemorrhagic shock nor resuscitation was done; group II, Rats underwent hemorrhagic shock (HS) for 1 hr then resuscitated with Ringer's lactate (1 hr) (induced untreated group, HS); group III, HS + MK-886 (0.6 mg/kg i.p. injection 30 min before the induction of HS, and the same dose was repeated just before reperfusion period). At the end of experiment (2 hr after completion of resuscitation), blood samples were collected for measurement of serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The trachea was then isolated and bronchoalveolar lavage fluid (BALF) was carried out for measurement of leukotriene B₄(LTB₄), leukotriene C₄(LTC₄) and total protein. The lungs were harvested, excised and the left lung was homogenized for measurement of malondialdehyde (MDA) and reduced glutathione (GSH) and the right lung was fixed in 10% formalin for histological examination.</p> <p>Results</p> <p>MK-886 treatment significantly reduced the total lung injury score compared with the HS group (<it>P </it>< 0.05). MK-886 also significantly decreased serum TNF-α & IL-6; lung MDA; BALF LTB₄, LTC₄& total protein compared with the HS group (<it>P </it>< 0.05). MK-886 treatment significantly prevented the decrease in the lung GSH levels compared with the HS group (<it>P </it>< 0.05).</p> <p>Conclusions</p> <p>The results of the present study reveal that MK-886 may ameliorate lung injury in shocked rats via interfering with inflammatory and oxidative pathways implicating the role of leukotrienes in the pathogenesis of hemorrhagic shock-induced lung inflammation.</p

Phagocytosis is the main CR3-mediated function affected by the lupus-associated variant of CD11b in human myeloid cells.

The CD11b/CD18 integrin (complement receptor 3, CR3) is a surface receptor on monocytes, neutrophils, macrophages and dendritic cells that plays a crucial role in several immunological processes including leukocyte extravasation and phagocytosis. The minor allele of a non-synonymous CR3 polymorphism (rs1143679, conversation of arginine to histidine at position 77: R77H) represents one of the strongest genetic risk factor in human systemic lupus erythematosus, with heterozygosity (77R/H) being the most common disease associated genotype. Homozygosity for the 77H allele has been reported to reduce adhesion and phagocytosis in human monocytes and monocyte-derived macrophages, respectively, without affecting surface expression of CD11b. Herein we comprehensively assessed the influence of R77H on different CR3-mediated activities in monocytes, neutrophils, macrophages and dendritic cells. R77H did not alter surface expression of CD11b including its active form in any of these cell types. Using two different iC3b-coated targets we found that the uptake by heterozygous 77R/H macrophages, monocytes and neutrophils was significantly reduced compared to 77R/R cells. Allele-specific transduced immortalized macrophage cell lines demonstrated that the minor allele, 77H, was responsible for the impaired phagocytosis. R77H did not affect neutrophil adhesion, neutrophil transmigration in vivo or Toll-like receptor 7/8-mediated cytokine release by monocytes or dendritic cells with or without CR3 pre-engagement by iC3b-coated targets. Our findings demonstrate that the reduction in CR3-mediated phagocytosis associated with the 77H CD11b variant is not macrophage-restricted but demonstrable in other CR3-expressing professional phagocytic cells. The association between 77H and susceptibility to systemic lupus erythematosus most likely relates to impaired waste disposal, a key component of lupus pathogenesis

Water Availability Is the Main Climate Driver of Neotropical Tree Growth

• Climate models for the coming century predict rainfall reduction in the Amazonian region, including change in water availability for tropical rainforests. Here, we test the extent to which climate variables related to water regime, temperature and irradiance shape the growth trajectories of neotropical trees. • We developed a diameter growth model explicitly designed to work with asynchronous climate and growth data. Growth trajectories of 205 individual trees from 54 neotropical species censused every 2 months over a 4-year period were used to rank 9 climate variables and find the best predictive model. • About 9% of the individual variation in tree growth was imputable to the seasonal variation of climate. Relative extractable water was the main predictor and alone explained more than 60% of the climate effect on tree growth, i.e. 5.4% of the individual variation in tree growth. Furthermore, the global annual tree growth was more dependent on the diameter increment at the onset of the rain season than on the duration of dry season. • The best predictive model included 3 climate variables: relative extractable water, minimum temperature and irradiance. The root mean squared error of prediction (0.035 mm.d–1) was slightly above the mean value of the growth (0.026 mm.d–1). • Amongst climate variables, we highlight the predominant role of water availability in determining seasonal variation in tree growth of neotropical forest trees and the need to include these relationships in forest simulators to test, in silico, the impact of different climate scenarios on the future dynamics of the rainforest

Sequencing three crocodilian genomes to illuminate the evolution of archosaurs and amniotes

The International Crocodilian Genomes Working Group (ICGWG) will sequence and assemble the American alligator (Alligator mississippiensis), saltwater crocodile (Crocodylus porosus) and Indian gharial (Gavialis gangeticus) genomes. The status of these projects and our planned analyses are described

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030