Cost-effectiveness of rotavirus vaccination in the Netherlands; the results of a consensus model

Contains fulltext : 96770.pdf (publisher's version ) (Open Access)BACKGROUND: Each year rotavirus gastroenteritis results in thousands of paediatric hospitalisations and primary care visits in the Netherlands. While two vaccines against rotavirus are registered, routine immunisation of infants has not yet been implemented. Existing cost-effectiveness studies showed inconsistent results for these vaccines because of lack of consensus on the impact. We aimed to investigate which factors had a major impact on cost-effectiveness and were primarily responsible for the large differences in previously estimated cost-effectiveness ratios. METHODS: Based on updated data on health outcomes and cost estimates, we re-assessed the cost-effectiveness of routine paediatric rotavirus vaccination within the National Immunization Program for the Netherlands. Two consensus meetings were organised with national and international experts in the field to achieve consensus and resolve potential controversies. RESULTS: It was estimated that rotavirus vaccination in the Netherlands could avert 34,214 cases of rotavirus gastroenteritis in children aged less than 5 years. Notably, 2,779 hospitalisations were averted of which 315 were extensions of existing hospital stays due to nosocomial rotavirus infection. With a threshold varying from 20K euro - 50K euro per QALY and according to the base-case scenario, the full vaccination costs per child leading to cost-effectiveness was euro 57.76 -euro 77.71. Results were sensitive to the inclusion of potential vaccine induced herd protection, QALY losses and number of deaths associated with rotavirus gastroenteritis. CONCLUSIONS: Our economic analysis indicates that inclusion of rotavirus vaccination in the Dutch National Immunization Program might be cost-effective depending on the cost of the vaccine and the impact of rotavirus gastroenteritis on children's quality of life

Cue-Reactors: Individual Differences in Cue-Induced Craving after Food or Smoking Abstinence

Background: Pavlovian conditioning plays a critical role in both drug addiction and binge eating. Recent animal research suggests that certain individuals are highly sensitive to conditioned cues, whether they signal food or drugs. Are certain humans also more reactive to both food and drug cues? Methods: We examined cue-induced craving for both cigarettes and food, in the same individuals (n = 15 adult smokers). Subjects viewed smoking-related or food-related images after abstaining from either smoking or eating. Results: Certain individuals reported strong cue-induced craving after both smoking and food cues. That is, subjects who reported strong cue-induced craving for cigarettes also rated stronger cue-induced food craving. Conclusions: In humans, like in nonhumans, there may be a ‘‘cue-reactive’ ’ phenotype, consisting of individuals who are highly sensitive to conditioned stimuli. This finding extends recent reports from nonhuman studies. Further understanding this subgroup of smokers may allow clinicians to individually tailor therapies for smoking cessation

Prevalence and impact of alcohol and other drug use disorders on sedation and mechanical ventilation: a retrospective study

BACKGROUND: Experience suggests that patients with alcohol and other drug use disorders (AOD) are commonly cared for in our intensive care units (ICU's) and require more sedation. We sought to determine the impact of AOD on sedation requirement and mechanical ventilation (MV) duration. METHODS: Retrospective review of randomly selected records of adult patients undergoing MV in the medical ICU. Diagnoses of AOD were identified using strict criteria in Diagnostic and Statistical Manual of Mental Disorders, and through review of medical records and toxicology results. RESULTS: Of the 70 MV patients reviewed, 27 had AOD (39%). Implicated substances were alcohol in 22 patients, cocaine in 5, heroin in 2, opioids in 2, marijuana in 2. There was no difference between AOD and non-AOD patients in age, race, or reason for MV, but patients with AOD were more likely to be male (21 versus 15, p < 0.0001) and had a lower mean Acute Physiology and Chronic Health Evaluation II (22 versus 26, p = 0.048). While AOD patients received more lorazepam equivalents (0.5 versus 0.2 mg/kg.day, p = 0.004), morphine equivalents (0.5 versus 0.1 mg/kg.day, p = 0.03) and longer duration of infusions (16 versus 10 hours/day. medication, p = 0.002), they had similar sedation levels (Richmond Agitation-Sedation Scale (RASS) -2 versus -2, p = 0.83), incidence of agitation (RASS ≥ 3: 3.0% versus 2.4% of observations, p = 0.33), and duration of MV (3.6 versus 3.9 days, p = 0.89) as those without AOD. CONCLUSION: The prevalence of AOD among medical ICU patients undergoing MV is high. Patients with AOD receive higher doses of sedation than their non-AOD counterparts to achieve similar RASS scores but do not undergo longer duration of MV

R^4 counterterm and E7(7) symmetry in maximal supergravity

The coefficient of a potential R^4 counterterm in N=8 supergravity has been shown previously to vanish in an explicit three-loop calculation. The R^4 term respects N=8 supersymmetry; hence this result poses the question of whether another symmetry could be responsible for the cancellation of the three-loop divergence. In this article we investigate possible restrictions from the coset symmetry E7(7)/SU(8), exploring the limits as a single scalar becomes soft, as well as a double-soft scalar limit relation derived recently by Arkani-Hamed et al. We implement these relations for the matrix elements of the R^4 term that occurs in the low-energy expansion of closed-string tree-level amplitudes. We find that the matrix elements of R^4 that we investigated all obey the double-soft scalar limit relation, including certain non-maximally-helicity-violating six-point amplitudes. However, the single-soft limit does not vanish for this latter set of amplitudes, which suggests that the E7(7) symmetry is broken by the R^4 term.Comment: 33 pages, typos corrected, published versio

Hypersensitivity reactions, hepatotoxicity, and other discontinuations in persons receiving integrase strand transfer inhibitors: results from the EuroSIDA study

Background: Hypersensitivity reaction (HSR) and hepatotoxicity are rare, but potentially serious side-effects of antiretroviral use. / Objective: To investigate discontinuations due to HSR, hepatotoxicity or other reasons among users of dolutegravir (DTG) vs. raltegravir (RAL) or elvitegravir (EVG) in the EuroSIDA cohort. / Methods: We compared individuals ≥18 years and starting combination antiretroviral therapy (ART, ≥3 drugs) with DTG vs. RAL or EVG, with or without abacavir (ABC), between January 16, 2014 and January 23, 2019. Discontinuations due to serious adverse events (SAEs) were independently reviewed. / Results: Altogether 4366 individuals started 5116 ART regimens including DTG, RAL, or EVG, contributing 9180 person-years of follow-up (PYFU), with median follow-up 1.6 (interquartile range 0.7-2.8) years per treatment episode. Of these, 3074 (60.1%) used DTG (1738 with ABC, 1336 without) and 2042 (39.9%) RAL or EVG (286 with ABC, 1756 without). 1261 (24.6%) INSTI episodes were discontinued, 649 of the DTG-containing regimens (discontinuation rate 115, 95% CI 106-124/1000 PYFU) and 612 RAL or EVG-containing regimens (173, CI 160-188/1000 PYFU). After independent review, there were five HSR discontinuations, two for DTG (one with and one without ABC, discontinuation rate 0.35, CI 0.04-1.28/1000 PYFU), and three for RAL or EVG without ABC (0.85, CI 0.18-2.48/1000 PYFU). There was one hepatotoxicity discontinuation on DTG with ABC (discontinuation rate 0.18, CI 0.00-0.99/1000 PYFU). / Conclusion: During 5 years of observations in the EuroSIDA cohort independently reviewed discontinuations due to HSR or hepatotoxicity were very rare, indicating a low rate of SAEs