Costs and Cost-Effectiveness of Training Traditional Birth Attendants to Reduce Neonatal Mortality in the Lufwanyama Neonatal Survival Study (LUNESP)

The Lufwanyama Neonatal Survival Project (“LUNESP”) was a cluster randomized, controlled trial that showed that training traditional birth attendants (TBAs) to perform interventions targeting birth asphyxia, hypothermia, and neonatal sepsis reduced all-cause neonatal mortality by 45%. This companion analysis was undertaken to analyze intervention costs and cost-effectiveness, and factors that might improve cost-effectiveness.We calculated LUNESP's financial and economic costs and the economic cost of implementation for a forecasted ten-year program (2011–2020). In each case, we calculated the incremental cost per death avoided and disability-adjusted life years (DALYs) averted in real 2011 US dollars. The forecasted 10-year program analysis included a base case as well as ‘conservative’ and ‘optimistic’ scenarios. Uncertainty was characterized using one-way sensitivity analyses and a multivariate probabilistic sensitivity analysis. The estimated financial and economic costs of LUNESP were $118,574 and$127,756, respectively, or $49,469 and$53,550 per year. Fixed costs accounted for nearly 90% of total costs. For the 10-year program, discounted total and annual program costs were $256,455 and$26,834 respectively; for the base case, optimistic, and conservative scenarios, the estimated cost per death avoided was $1,866,$591, and $3,024, and cost per DALY averted was$74, $24, and$120, respectively. Outcomes were robust to variations in local costs, but sensitive to variations in intervention effect size, number of births attended by TBAs, and the extent of foreign consultants' participation.Based on established guidelines, the strategy of using trained TBAs to reduce neonatal mortality was ‘highly cost effective’. We strongly recommend consideration of this approach for other remote rural populations with limited access to health care

Revising the WHO verbal autopsy instrument to facilitate routine cause-of-death monitoring.

OBJECTIVE: Verbal autopsy (VA) is a systematic approach for determining causes of death (CoD) in populations without routine medical certification. It has mainly been used in research contexts and involved relatively lengthy interviews. Our objective here is to describe the process used to shorten, simplify, and standardise the VA process to make it feasible for application on a larger scale such as in routine civil registration and vital statistics (CRVS) systems. METHODS: A literature review of existing VA instruments was undertaken. The World Health Organization (WHO) then facilitated an international consultation process to review experiences with existing VA instruments, including those from WHO, the Demographic Evaluation of Populations and their Health in Developing Countries (INDEPTH) Network, InterVA, and the Population Health Metrics Research Consortium (PHMRC). In an expert meeting, consideration was given to formulating a workable VA CoD list [with mapping to the International Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) CoD] and to the viability and utility of existing VA interview questions, with a view to undertaking systematic simplification. FINDINGS: A revised VA CoD list was compiled enabling mapping of all ICD-10 CoD onto 62 VA cause categories, chosen on the grounds of public health significance as well as potential for ascertainment from VA. A set of 221 indicators for inclusion in the revised VA instrument was developed on the basis of accumulated experience, with appropriate skip patterns for various population sub-groups. The duration of a VA interview was reduced by about 40% with this new approach. CONCLUSIONS: The revised VA instrument resulting from this consultation process is presented here as a means of making it available for widespread use and evaluation. It is envisaged that this will be used in conjunction with automated models for assigning CoD from VA data, rather than involving physicians

Weekly full-dose gemcitabine and single-dose cisplatin with concurrent radiotherapy in patients with locally advanced pancreatic cancer

The aim of this study was to evaluate the efficacy and the toxicity of a full dose of gemcitabine and a single dose of cisplatin with concurrent radiotherapy in patients with locally advanced pancreatic cancer. Forty-one patients with locally advanced pancreatic cancer were enrolled. Patients received gemcitabine (1000 mg m−2 on days 1, 8, 15, 29, and 36) and cisplatin (70 mg m−2 on days 1 and 29) with concurrent radiotherapy (45 Gy in 25 fractions). Treatment was completed in 38 out of 41 patients (92.7%). The overall response rate was 24.4% (two complete and eight partial). Six patients (14.6%) underwent definite pancreatic resection and four had negative surgical margins. The intention of the treatment analysis showed that the median survival time and median time to tumour progression were 16.7 and 8.9 months. The 1- and 2-year survival rates were 63.3 and 27.9%, respectively. Overall survival was significantly longer in the low baseline CA19-9 group and therapeutic responders. Toxicities were tolerable and successfully managed by conservative treatments. The therapeutic scheme of a weekly full dose of gemcitabine and a single dose of cisplatin combined with external radiation is effective and might prolong the survival of patients with locally advanced pancreatic cancer

Comparison of minimally invasive surgical approaches for hysterectomy at a community hospital: robotic-assisted laparoscopic hysterectomy, laparoscopic-assisted vaginal hysterectomy and laparoscopic supracervical hysterectomy

The study reported here compares outcomes of three approaches to minimally invasive hysterectomy for benign indications, namely, robotic-assisted laparoscopic (RALH), laparoscopic-assisted vaginal (LAVH) and laparoscopic supracervical (LSH) hysterectomy. The total patient cohort comprised the first 237 patients undergoing robotic surgeries at our hospital between August 2007 and June 2009; the last 100 patients undergoing LAVH by the same surgeons between July 2006 and February 2008 and 165 patients undergoing LAVHs performed by nine surgeons between January 2008 and June 2009; 87 patients undergoing LSH by the same nine surgeons between January 2008 and June 2009. Among the RALH patients were cases of greater complexity: (1) higher prevalence of prior abdominopelvic surgery than that found among LAVH patients; (2) an increased number of procedures for endometriosis and pelvic reconstruction. Uterine weights also were greater in RALH patients [207.4 vs. 149.6 (LAVH; P < 0.001) and 141.1 g (LSH; P = 0.005)]. Despite case complexity, operative time was significantly lower in RALH than in LAVH (89.9 vs. 124.8 min, P < 0.001) and similar to that in LSH (89.6 min). Estimated blood loss was greater in LAVH (167.9 ml) than in RALH (59.0 ml, P < 0.001) or LSH (65.7 ml, P < 0.001). Length of hospital stay was shorter for RALH than for LAVH or LSH. Conversion and complication rates were low and similar across procedures. Multivariable regression indicated that LAVH, obesity, uterine weight ≥250 g and older age predicted significantly longer operative time. The learning curve for RALH demonstrated improved operative time over the case series. Our findings show the benefits of RALH over LAVH. Outcomes in RALH can be as good as or better than those in LSH, suggesting the latter should be the choice primarily for women desiring cervix-sparing surgery

Ischaemic strokes in patients with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia: associations with iron deficiency and platelets.

<div><p>Background</p><p>Pulmonary first pass filtration of particles marginally exceeding ∼7 µm (the size of a red blood cell) is used routinely in diagnostics, and allows cellular aggregates forming or entering the circulation in the preceding cardiac cycle to lodge safely in pulmonary capillaries/arterioles. Pulmonary arteriovenous malformations compromise capillary bed filtration, and are commonly associated with ischaemic stroke. Cohorts with CT-scan evident malformations associated with the highest contrast echocardiographic shunt grades are known to be at higher stroke risk. Our goal was to identify within this broad grouping, which patients were at higher risk of stroke.</p><p>Methodology</p><p>497 consecutive patients with CT-proven pulmonary arteriovenous malformations due to hereditary haemorrhagic telangiectasia were studied. Relationships with radiologically-confirmed clinical ischaemic stroke were examined using logistic regression, receiver operating characteristic analyses, and platelet studies.</p><p>Principal Findings</p><p>Sixty-one individuals (12.3%) had acute, non-iatrogenic ischaemic clinical strokes at a median age of 52 (IQR 41–63) years. In crude and age-adjusted logistic regression, stroke risk was associated not with venous thromboemboli or conventional neurovascular risk factors, but with low serum iron (adjusted odds ratio 0.96 [95% confidence intervals 0.92, 1.00]), and more weakly with low oxygen saturations reflecting a larger right-to-left shunt (adjusted OR 0.96 [0.92, 1.01]). For the same pulmonary arteriovenous malformations, the stroke risk would approximately double with serum iron 6 µmol/L compared to mid-normal range (7–27 µmol/L). Platelet studies confirmed overlooked data that iron deficiency is associated with exuberant platelet aggregation to serotonin (5HT), correcting following iron treatment. By MANOVA, adjusting for participant and 5HT, iron or ferritin explained 14% of the variance in log-transformed aggregation-rate (p = 0.039/p = 0.021).</p><p>Significance</p><p>These data suggest that patients with compromised pulmonary capillary filtration due to pulmonary arteriovenous malformations are at increased risk of ischaemic stroke if they are iron deficient, and that mechanisms are likely to include enhanced aggregation of circulating platelets.</p></div

Isolation of a Ru(IV) side-on peroxo intermediate in the water oxidation reaction

The electrons that nature uses to reduce CO2 during photosynthesis come from water oxidation at the oxygen-evolving complex of photosystem II. Molecular catalysts have served as models to understand its mechanism, in particular the O-O bond-forming reaction, which is still not fully understood. Here we report a Ru(IV) side-on peroxo complex that serves as a 'missing link' for the species that form after the rate-determining O-O bond-forming step. The Ru(IV) side-on peroxo complex (eta(2)-1(IV)-OO) is generated from the isolated Ru(IV) oxo complex (1(IV)=O) in the presence of an excess of oxidant. The oxidation (IV) and spin state (singlet) of eta(2)-1(IV)-OO were determined by a combination of experimental and theoretical studies. O-18- and H-2-labelling studies evidence the direct evolution of O-2 through the nucleophilic attack of a H2O molecule on the highly electrophilic metal-oxo species via the formation of eta(2)-1(IV)-OO. These studies demonstrate water nucleophilic attack as a viable mechanism for O-O bond formation, as previously proposed based on indirect evidence

Nanostring-based multigene assay to predict recurrence for gastric cancer patients after surgery

10.1371/journal.pone.0090133PLoS ONE93-POLN

The Antibacterial Activity of Honey Derived from Australian Flora

Chronic wound infections and antibiotic resistance are driving interest in antimicrobial treatments that have generally been considered complementary, including antimicrobially active honey. Australia has unique native flora and produces honey with a wide range of different physicochemical properties. In this study we surveyed 477 honey samples, derived from native and exotic plants from various regions of Australia, for their antibacterial activity using an established screening protocol. A level of activity considered potentially therapeutically useful was found in 274 (57%) of the honey samples, with exceptional activity seen in samples derived from marri (Corymbia calophylla), jarrah (Eucalyptus marginata) and jellybush (Leptospermum polygalifolium). In most cases the antibacterial activity was attributable to hydrogen peroxide produced by the bee-derived enzyme glucose oxidase. Non-hydrogen peroxide activity was detected in 80 (16.8%) samples, and was most consistently seen in honey produced from Leptospermum spp. Testing over time found the hydrogen peroxide-dependent activity in honey decreased, in some cases by 100%, and this activity was more stable at 4°C than at 25°C. In contrast, the non-hydrogen peroxide activity of Leptospermum honey samples increased, and this was greatest in samples stored at 25°C. The stability of non-peroxide activity from other honeys was more variable, suggesting this activity may have a different cause. We conclude that many Australian honeys have clinical potential, and that further studies into the composition and stability of their active constituents are warranted

Synergistic Anti-Tumor Effects of Combination of Photodynamic Therapy and Arsenic Compound in Cervical Cancer Cells: In Vivo and In Vitro Studies

The effects of As4O6 as adjuvant on photodynamic therapy (PDT) were studied. As4O6 is considered to have anticancer activity via several biological actions, such as free radical production and inhibition of VEGF expression. PDT or As4O6 significantly inhibited TC-1 cell proliferation in a dose-dependent manner (P<0.05) by MTT assay. The anti-proliferative effect of the combination treatment was significantly higher than in TC-1 cells treated with either photodynamic therapy or As4O6 alone (62.4 and 52.5% decrease compared to vehicle-only treated TC-1 cells, respectively, P<0.05). In addition, cell proliferation in combination of photodynamic therapy and As4O6 treatment significantly decreased by 77.4% (P<0.05). Cell survival pathway (Naip1, Tert and Aip1) and p53-dependent pathway (Bax, p21Cip1, Fas, Gadd45, IGFBP-3 and Mdm-2) were markedly increased by combination treatment of photodynamic therapy and As4O6. In addition, the immune response in the NEAT pathway (Ly-12, CD178 and IL-2) was also modulated after combination treatment, suggesting improved antitumor effects by controlling unwanted growth-stimulatory pathways. The combination effect apparently reflected concordance with in vitro data, in restricting tumor growth in vivo and in relation to some common signaling pathways to those observed in vitro. These findings suggest the benefit of combinatory treatment with photodynamic therapy and As4O6 for inhibition of cervical cancer cell growth

Two Major Medicinal Honeys Have Different Mechanisms of Bactericidal Activity

Honey is increasingly valued for its antibacterial activity, but knowledge regarding the mechanism of action is still incomplete. We assessed the bactericidal activity and mechanism of action of Revamil® source (RS) honey and manuka honey, the sources of two major medical-grade honeys. RS honey killed Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa within 2 hours, whereas manuka honey had such rapid activity only against B. subtilis. After 24 hours of incubation, both honeys killed all tested bacteria, including methicillin-resistant Staphylococcus aureus, but manuka honey retained activity up to higher dilutions than RS honey. Bee defensin-1 and H2O2 were the major factors involved in rapid bactericidal activity of RS honey. These factors were absent in manuka honey, but this honey contained 44-fold higher concentrations of methylglyoxal than RS honey. Methylglyoxal was a major bactericidal factor in manuka honey, but after neutralization of this compound manuka honey retained bactericidal activity due to several unknown factors. RS and manuka honey have highly distinct compositions of bactericidal factors, resulting in large differences in bactericidal activity