Forum: Tuberculosis prevention in HIV-infected pregnant women in South Africa

The high burden of HIV and tuberculosis (TB) among pregnant women in South Africa contributes to a high maternal mortality rate. Isoniazid preventive therapy (IPT) is recommended for the prevention of active TB in HIV-infected individuals, including pregnant women. However, there are few data regarding IPT use in the latter, with concern regarding the concurrent use of IPT with nevirapine in pregnancy, as both treatments are hepatotoxic. The benefit and safety of IPT in HIV-infected pregnant women has not been established. We recommend a simplification of HIV and TB interventions by providing triple antiretroviral therapy to all HIV-infected pregnant women

Change in cardio-protective medication and health-related quality of life after diagnosis of screen-detected diabetes: Results from the ADDITION-Cambridge cohort.

AIMS: Establishing a balance between the benefits and harms of treatment is important among individuals with screen-detected diabetes, for whom the burden of treatment might be higher than the burden of the disease. We described the association between cardio-protective medication and health-related quality of life (HRQoL) among individuals with screen-detected diabetes. METHODS: 867 participants with screen-detected diabetes underwent clinical measurements at diagnosis, one and five years. General HRQoL (EQ5D) was measured at baseline, one- and five-years, and diabetes-specific HRQoL (ADDQoL-AWI) and health status (SF-36) at one and five years. Multivariable linear regression was used to quantify the association between change in HRQoL and change in cardio-protective medication. RESULTS: The median (IQR) number of prescribed cardio-protective agents was 2 (1 to 3) at diagnosis, 3 (2 to 4) at one year and 4 (3 to 5) at five years. Change in cardio-protective medication was not associated with change in HRQoL from diagnosis to one year. From one year to five years, change in cardio-protective agents was not associated with change in the SF-36 mental health score. One additional agent was associated with an increase in the SF-36 physical health score (2.1; 95%CI 0.4, 3.8) and an increase in the EQ-5D (0.05; 95%CI 0.02, 0.08). Conversely, one additional agent was associated with a decrease in the ADDQoL-AWI (-0.32; 95%CI -0.51, -0.13), compared to no change. CONCLUSIONS: We found little evidence that increases in the number of cardio-protective medications impacted negatively on HRQoL among individuals with screen-detected diabetes over five years.ADDITION-Cambridge was supported by the Wellcome Trust (grant reference No G061895) the Medical Research Council (grant reference no: G0001164), National Health Service R&D support funding (including the Primary Care Research and Diabetes Research Networks), and the National Institute for Health Research. We received an unrestricted grant from University of Aarhus, Denmark, to support the ADDITION-Cambridge trial. Bio-Rad provided equipment to undertake capillary glucose screening by HbA1c in general practice. The Primary Care Research Unit is supported by NIHR Research funds. SJG receives support from the Department of Health NIHR Programme Grant funding scheme (RP-PG-0606-1259). This article presents independent research funded by the NIHR under the Programme Grants for Applied Research programme (RP-PG-0606-1259]. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.diabres.2015.04.01

Direct healthcare costs of Rome IV or Rome III-defined irritable bowel syndrome in the United Kingdom

Background Previous studies have demonstrated a substantial economic impact of irritable bowel syndrome (IBS). Aims To provide contemporaneous estimates of direct healthcare costs of IBS in the United Kingdom. Methods We collected demographic, gastrointestinal and psychological symptoms, quality of life and healthcare usage data from adults with Rome IV or Rome III IBS in the United Kingdom. We calculated the mean annual direct healthcare costs of IBS per person and used contemporaneous IBS prevalence data, together with census data, to estimate annual direct costs of IBS. We also examined predictors of higher costs. Results The mean annual direct cost of IBS per person among 752 individuals with Rome IV IBS was £556.65 (SD £1023.92) and £474.16 (SD £897.86) for 995 individuals with Rome III IBS. We estimate the annual direct healthcare cost of IBS in the United Kingdom is £1.27 billion if the Rome IV criteria are used to define IBS, and £2.07 billion using Rome III. Among individuals with Rome IV IBS, mean annual costs were higher in those with opiate use (£907.90 vs £470.58, p 5 years £501.60, p = 0.002), lower quality of life (p < 0.001 for trend), and higher depression, somatisation and gastrointestinal symptom-specific anxiety scores (P < 0.001 for trend for all). Conclusion We estimate annual direct healthcare costs of IBS of between £1.3 and £2 billion in the United Kingdom

Willingness to accept risk with medication in return for cure of symptoms among patients with Rome IV irritable bowel syndrome

Background Some drugs for irritable bowel syndrome (IBS) have serious side effects. Aims To examine the willingness of individuals with IBS to accept risks with medication in return for symptom cure. Methods We collected demographic, gastrointestinal symptoms, psychological health, quality of life and impact on work and daily activities data from 752 adults with Rome IV-defined IBS. We examined median willingness to accept death in return for cure with a hypothetical medication using a standard gamble, according to these variables. Results Participants would accept a median 2.0% (IQR 0.0%-9.0%) risk of death in return for a 98.0% (IQR 91.0%-100.0%) chance of permanent symptom cure. The median accepted risk of death was higher in men (5.0% vs 2.0%, P < 0.001), those with continuous abdominal pain (4.0% vs 1.0%, P < 0.001), more severe symptoms (P = 0.005 for trend), abnormal depression scores (P < 0.001 for trend), higher gastrointestinal symptom-specific anxiety (P < 0.001 for trend), and lower IBS-related quality of life (P < 0.001 for trend). Those willing to accept above median risk of death were more likely to be male (17.1% vs 9.1%, P < 0.001), take higher levels of risks in their daily life (P = 0.008 for trend), and report continuous abdominal pain (53.1% vs 39.4%, P < 0.001), and had higher depression (P = 0.004 for trend) and lower quality of life (P < 0.001 for trend) scores. Conclusion Patients are willing to accept significant risks in return for cure of their IBS symptoms

Willingness to pay for medications among patients with Rome IV Irritable Bowel Syndrome

Background Little is known about willingness to pay for medications among individuals with irritable bowel syndrome (IBS). Methods We collected demographic, gastrointestinal symptom, psychological health, quality of life, and healthcare usage data from 752 adults with Rome IV-defined IBS. We examined willingness to pay for a hypothetical medication in return for improvement in IBS symptoms using a contingent valuation method, according to these variables. Results The median amount of money individuals was willing to pay was £1–£50 (IQR £0–£100) per month for a medication with a 100% chance of improving IBS symptoms. Women, compared with men, (92.7% willing to pay “£0,” 89.8% “£1–£50,” 87.3% “£51–£100,” 78.9% “£101–£200,” and 78.5% “more than £200,” p = 0.008) were less likely to be willing to pay for a pill with a 100% chance of improving IBS symptoms whilst those with an annual income of £30,000 or more (12.2% willing to pay “£0,” 25.2% “£1–£50,” 33.5% “£51–£100,” 40.2% “£101–£200,” and 35.1% “more than £200,” p = 0.002) were more likely. We observed a higher willingness to pay among those with lower IBS-related quality of life (p = 0.002 for trend). Of all 752 individuals, 92.7%, 74.5%, and 58.0% would be willing to pay for a medication that would give them a 100%, 50%, or 30% chance of improving IBS symptoms, respectively. Conclusion Patients with IBS are willing to pay for medications which improve IBS symptoms. Future studies should investigate the relative importance of medication pricing, efficacy, and side effect profile among individuals with IBS

Abstract Argumentation / Persuasion / Dynamics

The act of persuasion, a key component in rhetoric argumentation, may be viewed as a dynamics modifier. We extend Dung's frameworks with acts of persuasion among agents, and consider interactions among attack, persuasion and defence that have been largely unheeded so far. We characterise basic notions of admissibilities in this framework, and show a way of enriching them through, effectively, CTL (computation tree logic) encoding, which also permits importation of the theoretical results known to the logic into our argumentation frameworks. Our aim is to complement the growing interest in coordination of static and dynamic argumentation.Comment: Arisaka R., Satoh K. (2018) Abstract Argumentation / Persuasion / Dynamics. In: Miller T., Oren N., Sakurai Y., Noda I., Savarimuthu B., Cao Son T. (eds) PRIMA 2018: Principles and Practice of Multi-Agent Systems. PRIMA 2018. Lecture Notes in Computer Science, vol 11224. Springer, Cha

Factors associated with lower disease-specific and generic health-related quality of life in Rome IV irritable bowel syndrome

Background Little is known about associations with reduced quality of life in irritable bowel syndrome (IBS) or impact of IBS on quality of life compared with other chronic conditions. Methods We collected demographic, gastrointestinal and psychological symptoms, healthcare usage, direct healthcare costs, impact on work and activities of daily living data from 752 individuals with Rome IV-defined IBS. We used the irritable bowel syndrome quality of life (IBS-QOL) and the EQ-5D-5L questionnaires to examine characteristics associated with lower quality of life. Results The mean IBS-QOL among all 752 individuals with Rome IV IBS was 48.4 (SD 22.3) and the mean EQ-5D score was 0.570 (SD 0.283), the latter being comparable to people with stroke, leg ulcers or chronic obstructive pulmonary disease. Lower levels of both disease-specific and generic quality of life were associated with severe IBS symptom scores, abnormal anxiety or depression scores, and higher somatoform symptom-reporting and gastrointestinal symptom-specific anxiety scores (p < 0.001 for all analyses). Those with lower quality of life had significantly higher healthcare usage and direct healthcare costs and more impairment in work and activities of daily living (p < 0.01 for all analyses). Avoidance of alcohol, lower educational level, abnormal anxiety, depression or somatoform symptom-reporting scores, and impairment in social leisure activities, home management or maintaining close relationships were all independently associated with lower quality of life. Conclusion IBS has a substantial impact on the quality of life of those affected, and worse than observed in some severe chronic organic conditions

Persistence of the immune response induced by BCG vaccination.

BACKGROUND: Although BCG vaccination is recommended in most countries of the world, little is known of the persistence of BCG-induced immune responses. As novel TB vaccines may be given to boost the immunity induced by neonatal BCG vaccination, evidence concerning the persistence of the BCG vaccine-induced response would help inform decisions about when such boosting would be most effective. METHODS: A randomised control study of UK adolescents was carried out to investigate persistence of BCG immune responses. Adolescents were tested for interferon-gamma (IFN-gamma) response to Mycobacterium tuberculosis purified protein derivative (M.tb PPD) in a whole blood assay before, 3 months, 12 months (n = 148) and 3 years (n = 19) after receiving teenage BCG vaccination or 14 years after receiving infant BCG vaccination (n = 16). RESULTS: A gradual reduction in magnitude of response was evident from 3 months to 1 year and from 1 year to 3 years following teenage vaccination, but responses 3 years after vaccination were still on average 6 times higher than before vaccination among vaccinees. Some individuals (11/86; 13%) failed to make a detectable antigen-specific response three months after vaccination, or lost the response after 1 (11/86; 13%) or 3 (3/19; 16%) years. IFN-gamma response to Ag85 was measured in a subgroup of adolescents and appeared to be better maintained with no decline from 3 to 12 months. A smaller group of adolescents were tested 14 years after receiving infant BCG vaccination and 13/16 (81%) made a detectable IFN-gamma response to M.tb PPD 14 years after infant vaccination as compared to 6/16 (38%) matched unvaccinated controls (p = 0.012); teenagers vaccinated in infancy were 19 times more likely to make an IFN-gamma response of > 500 pg/ml than unvaccinated teenagers. CONCLUSION: BCG vaccination in infancy and adolescence induces immunological memory to mycobacterial antigens that is still present and measurable for at least 14 years in the majority of vaccinees, although the magnitude of the peripheral blood response wanes from 3 months to 12 months and from 12 months to 3 years post vaccination. The data presented here suggest that because of such waning in the response there may be scope for boosting anti-tuberculous immunity in BCG vaccinated children anytime from 3 months post-vaccination. This supports the prime boost strategies being employed for some new TB vaccines currently under development