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Background. South Africa (SA) has embarked on a process to implement universal health coverage (UHC) funded by National Health Insurance (NHI). The 2019 NHI Bill proposes creation of a health technology assessment (HTA) body to inform decisions about which interventions NHI funds will cover under UHC. In practice, HTA often relies mainly on economic evaluations of cost-effectiveness and budget impact, with less attention to the systematic, specific consideration of important social, organisational and ethical impacts of the health technology in question. In this context, the South African Values and Ethics for Universal Health Coverage (SAVE-UHC) research project recognised an opportunity to help shape the health priority-setting process by providing a way to take account of multiple, ethically relevant considerations that reflect SA values. The SAVE-UHC Research Team developed and tested an SA-specific Ethics Framework for HTA assessment and analysis. Objectives. To develop and test an Ethics Framework for use in the SA context for health priority-setting. Methods. The Framework was developed iteratively by the authors and a multidisciplinary panel (18 participants) over a period of 18 months, using the principles outlined in the 2015 NHI White Paper as a starting point. The provisional Ethics Framework was then tested with multi-stakeholder simulated appraisal committees (SACs) in three provinces. The membership of each SAC roughly reflected the composition of a potential SA HTA committee. The deliberations and dedicated focus group discussions after each SAC meeting were recorded, analysed and used to refine the Framework, which was presented to the Working Group for review, comment and final approval. Results. This article describes the 12 domains of the Framework. The first four (Burden of the Health Condition, Expected Health Benefits and Harms, Cost-Effectiveness Analysis, and Budget Impact) are commonly used in HTA assessments, and a further eight cover the other ethical domains. These are Equity, Respect and Dignity, Impacts on Personal Financial Situation, Forming and Maintaining Important Personal Relationships, Ease of Suffering, Impact on Safety and Security, Solidarity and Social Cohesion, and Systems Factors and Constraints. In each domain are questions and prompts to enable use of the Framework by both analysts and assessors. Issues that arose, such as weighting of the domains and the availability of SA evidence, were discussed by the SACs. Conclusions. The Ethics Framework is intended for use in priority-setting within an HTA process. The Framework was well accepted by a diverse group of stakeholders. The final version will be a useful tool not only for HTA and other priority-setting processes in SA, but also for future efforts to create HTA methods in SA and elsewhere.

EMR is first-line therapy for colorectal laterally spreading lesions. Some colonoscopists include epinephrine in the submucosal injectate, which we observed increased postprocedure discomfort. Our aim was to determine whether inclusion of epinephrine in the submucosal injectate increases postprocedure pain after EMR.We performed a randomized, controlled, double-blind trial comparing epinephrine in submucosal injectate versus injectate alone for abdominal pain at 30 and 60 minutes after EMR.Mean polyp diameter in both arms was40 mm. There were no differences in procedure times or amounts of fluid injected. Mean pain was higher on a visual analog scale in the epinephrine group at 30 minutes (47 vs 14, P = .022) and at 60 minutes (44 vs 13, P = .035). Recovery room stay was longer in the epinephrine group (68 vs 53 minutes, P = .034).Epinephrine in the submucosal injectate for EMR increases postprocedural pain, which could cause diagnostic confusion and prolong observation time in the recovery area. (Clinical trial registration number: NCT04065451.).

Background and Aims Endocuff improves detection at colonoscopy but seems to impede terminal ileal (TI) intubation. We assessed the impact of Endocuff Vision (EV) on TI intubation using adult or pediatric colonoscopes and evaluated whether filling the cecum with gas versus water affected the impact of EV on TI intubation. Methods Using a prospectively recorded quality control database, we explored the impact of EV on TI intubation in ≤1 minute. We used adult and pediatric colonoscopes and tested the effect of filling the cecum with gas versus water. If the initial attempt failed, then the alternative (water vs gas) was tried as a rescue method. Results TI intubation in ≤1 minute occurred in 91% of colonoscopies without EV versus 65% with EV, but the use of the pediatric colonoscope with EV had a higher success rate for TI intubation in ≤1 minute compared with the adult colonoscope with EV (73% vs 57%, P = .043). TI intubation in ≤1 minute was more successful with EV when the cecum was filled with water rather than gas (74% vs 56%, P = .019), but the benefit of water filling was limited to the adult colonoscope with EV. When EV was in place, water filling was more successful as a rescue method of TI intubation (58% vs 21%, P = .011). Conclusions EV adversely affects TI intubation, particularly for adult colonoscopes. Water filling of the cecum mitigates the impact of EV on TI intubation with adult colonoscopes.

Immuno-proteomic screening has identified several tumor-associated autoantibodies (AAb) that may have diagnostic capacity for invasive epithelial ovarian cancer, with AAbs to P53 proteins and cancer-testis antigens (CTAGs) as prominent examples. However, the early detection potential of these AAbs has been insufficiently explored in prospective studies. We performed ELISA measurements of AAbs to CTAG1A, CTAG2, P53 and NUDT11 proteins, for 194 patients with ovarian cancer and 705 matched controls from the European EPIC cohort, using serum samples collected up to 36 months prior to diagnosis under usual care. CA125 was measured using electrochemo-luminiscence. Diagnostic discrimination statistics were calculated by strata of lead-time between blood collection and diagnosis. With lead times ≤6 months, ovarian cancer detection sensitivity at 0.98 specificity (SE98) varied from 0.19 [95% CI 0.08–0.40] for CTAG1A, CTAG2 and NUDT1 to 0.23 [0.10–0.44] for P53 (0.33 [0.11–0.68] for high-grade serous tumors). However, at longer lead-times, the ability of these AAb markers to distinguish future ovarian cancer cases from controls declined rapidly; at lead times >1 year, SE98 estimates were close to zero (all invasive cases, range: 0.01–0.11). Compared to CA125 alone, combined logistic regression scores of AAbs and CA125 did not improve detection sensitivity at equal level of specificity. The added value of these selected AAbs as markers for ovarian cancer beyond CA125 for early detection is therefore limited. © 2018 UICC

Receptor activator of nuclear factor-kappa B (RANK)-RANK ligand (RANKL) signaling promotes mammary tumor development in experimental models. Circulating concentrations of soluble RANKL (sRANKL) may influence breast cancer risk via activation of RANK signaling; this may be modulated by osteoprotegerin (OPG), the decoy receptor for RANKL. sRANKL and breast cancer risk by hormone receptor subtype has not previously been investigated. A case-control study was nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. This study included 1, 976 incident invasive breast cancer cases [estrogen receptor positive (ER+), n=1, 598], matched 1:1 to controls. Women were pre- or postmenopausal at blood collection. Serum sRANKL was quantified using an ELISA, serum OPG using an electrochemiluminescent assay. Risk ratios (RR) and95% confidence intervals (95% CI) were calculated using conditional logistic regression. Associations between sRANKL and breast cancer risk differed by tumor hormone receptor status (Phet = 0.05). Higher concentrations of sRANKL were positively associated with risk of ER+ breast cancer [5th vs. 1st quintile RR 1.28 (95% CI, 1.01-1.63); Ptrend=0.20], but not ER-disease. For both ER+and estrogen and progesterone receptor positive (ER+PR+) breast cancer, results considering the sRANKL/OPG ratio were similar to those for sRANKL; we observed a suggestive inverse association between the ratio and ER-PR-disease [5th vs. 1st quintile RR = 0.60 (0.31-1.14); Ptrend=0.03]. This study provides the first largescale prospective data on circulating sRANKLand breast cancer. We observed limited evidence for an association between sRANKLand breast cancer risk. Cancer Prev Res; 10(9); 525-34. © 2017 American Association for Cancer Research.

Intakes of specific fatty acids have been postulated to impact breast cancer risk but epidemiological data based on dietary questionnaires remain conflicting. We assessed the association between plasma phospholipid fatty acids and breast cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Sixty fatty acids were measured by gas chromatography in pre-diagnostic plasma phospholipids from 2982 incident breast cancer cases matched to 2982 controls. Conditional logistic regression models were used to estimate relative risk of breast cancer by fatty acid level. The false discovery rate (q values) was computed to control for multiple comparisons. Subgroup analyses were carried out by estrogen receptor (ER) and progesterone receptor expression in the tumours. A high level of palmitoleic acid [odds ratio (OR) for the highest quartile compared with the lowest OR (Q4-Q1) 1.37; 95% confidence interval (CI), 1.14-1.64; P for trend = 0.0001, q value = 0.004] as well as a high desaturation index (DI16) (16:1n-7/16:0) [OR (Q4-Q1), 1.28; 95% C, 1.07-1.54; P for trend = 0.002, q value = 0.037], as biomarkers of de novo lipogenesis, were significantly associated with increased risk of breast cancer. Levels of industrial trans-fatty acids were positively associated with ER-negative tumours [OR for the highest tertile compared with the lowest (T3-T1)=2.01; 95% CI, 1.03-3.90; P for trend = 0.047], whereas no association was found for ER-positive tumours (P-heterogeneity =0.01). No significant association was found between n-3 polyunsaturated fatty acids and breast cancer risk, overall or by hormonal receptor. These findings suggest that increased de novo lipogenesis, acting through increased synthesis of palmitoleic acid, could be a relevant metabolic pathway for breast tumourigenesis. Dietary trans-fatty acids derived from industrial processes may specifically increase ER-negative breast cancer risk.

Adsorption properties of acetylsalicylic acid (AA), ibuprofen and acetaminophen deposited from volatile solvents with varying protic/aprotic properties on vacuum-evaporated silver films were characterized using surface-enhanced infrared absorption (SEIRA) and surface-enhanced Raman spectroscopy (SERS). SERS preferentially enhances monolayer Raman shifts, while SEIRA can enhance the infrared absorbance of the monolayer and multilayers. To our best knowledge, this is the first reported study of these molecules using a combination of SERS/SEIRA. SERS revealed that AA and ibuprofen adsorbed ionically in monolayers, independent of the deposition solvents used in the process. SEIRA experiments showed that AA multilayers condensed molecularly using a deposition solvent with polar bonds. However, when an alkane deposition solvent with non-polar bonds such as n-heptane was used, AA adsorbed as acetylsalicylate ions in the first few multilayers, while ibuprofen always adsorbed as the free acid in the multilayer. These ionization trends depend upon the affinity of AA and ibuprofen for the underlying silver film. TPD experiments on silver powders further demonstrated that ibuprofen affinity for silver was less than AA. Furthermore, SEIRA indicated that acetaminophen adsorbed as multilayers of metastable polymorphs using protic or polar aprotic deposition solvents. Protic deposition solvents gave higher quality SERS spectra of an acetaminophen monolayer in comparison to polar aprotic deposition solvents. Such studies could find significant applications in biochemical and nanotechnology processes such as drug delivery, catalysis, and tissue engineering and will contribute to the understanding of the impact and fate of analgesics released into the environment.

We compare the impact of timing conditions on implementing sequentially consistent and linearizable counters using (uniform) counting networks in distributed systems. For counting problems in application domains which do not require linearizability but will run correctly if only sequential consistency is provided, the results of our investigation, and their potential payoffs, are threefold: First, we show that sequential consistency and linearizability cannot be distinguished by the timing conditions previously considered in the context of counting networks thus, in contexts where these constraints apply, it is possible to rely on the stronger semantics of linearizability, which simplifies proofs and enhances compositionality. Second, we identify local timing conditions that support sequential consistency but not linearizability thus, we suggest weaker, easily implementable timing conditions that are likely to be sufficient in many applications. Third, we show that any kind of synchronization that is too weak to support even sequential consistency may violate it significantly for some counting networks hence, we identify timing conditions that are to be totally ruled out for specific applications that rely critically on either sequential consistency or linearizability. © 2008 Springer-Verlag. 21 4 249 269