Cost-Effectiveness Analysis of Smoking Cessation Interventions in the United Kingdom Accounting for Major Neuropsychiatric Adverse Events

ObjectivesSmoking is a leading cause of death worldwide. Cessation aids include varenicline, bupropion, nicotine replacement therapy (NRT), and e-cigarettes at various doses (low, standard and high) and used alone or in combination with each other. Previous cost-effectiveness analyses have not fully accounted for adverse effects nor compared all cessation aids. The objective was to determine the relative cost-effectiveness of cessation aids in the United Kingdom.MethodsAn established Markov cohort model was adapted to incorporate health outcomes and costs due to depression and self-harm associated with cessation aids, alongside other health events. Relative efficacy in terms of abstinence and major adverse neuropsychiatric events was informed by a systematic review and network meta-analysis. Base case results are reported for UK-licensed interventions only. Two sensitivity analyses are reported, one including unlicensed interventions and another comparing all cessation aids but removing the impact of depression and self-harm. The sensitivity of conclusions to model inputs was assessed by calculating the expected value of partial perfect information.ResultsWhen limited to UK-licensed interventions, varenicline standard-dose and NRT standard-dose were most cost-effective. Including unlicensed interventions, e-cigarette low-dose appeared most cost-effective followed by varenicline standard-dose + bupropion standard-dose combined. When the impact of depression and self-harm was excluded, varenicline standard-dose + NRT standard-dose was most cost-effective, followed by varenicline low-dose + NRT standard-dose.ConclusionAlthough found to be most cost-effective, combined therapy is currently unlicensed in the United Kingdom and the safety of e-cigarettes remains uncertain. The value-of-information analysis suggested researchers should continue to investigate the long-term effectiveness and safety outcomes of e-cigarettes in studies with active comparators.     

Nonshared Environmental Effects on Adulthood Psychopathic Personality Traits: Results from a Monozygotic Twin Difference Scores Analysis

An emerging body of empirical research has revealed that nonshared environmental factors are associated with explaining variance in measures of psychopathy and psychopathic personality traits. The current study adds to this existing knowledge base by analyzing a measure of psychopathy derived, in part, from the five factor model in a sample of monozygotic (MZ) twin pairs drawn from the National Longitudinal Study of Adolescent Health. The results of the MZ twin difference scores analysis revealed that nonshared environmental factors found within the family were unrelated to between-twin differences in psychopathic personality traits. Only one nonshared factor—levels of self-control—consistently predicted psychopathy. We conclude by discussing the implications of our findings and the limitations of our study.     

Evaluation of the Atypical Response scale of the Trauma Symptom Inventory-2 in detecting simulated posttraumatic stress disorder

This investigation evaluated the Atypical Response (ATR) scale of the Trauma Symptom Inventory – 2nd edition (TSI-2) in terms of its ability to distinguish genuine symptoms of posttraumatic stress disorder (PTSD) from simulated PTSD. Seventy-five undergraduate students were trained to simulate PTSD and were given monetary incentives to do so. Their responses on the PTSD Checklist (PCL), TSI-2 ATR, and Personality Assessment Inventory (PAI) validity scales were compared to responses of 49 undergraduate students with genuine symptoms of PTSD instructed to respond honestly on testing. Results indicate that the revised version of the ATR is superior to the original version in detecting malingered PTSD. Discriminant Function Analyses revealed correct classification of 75% of genuinely distressed individuals and 74% of PTSD simulators.     

Generation of HIV-1 Resistant and Functional Macrophages From Hematopoietic Stem Cell�Cderived Induced Pluripotent Stem Cells

Induced pluripotent stem cells (iPSCs) have radically advanced the field of regenerative medicine by making possible the production of patient-specific pluripotent stem cells from adult individuals. By developing iPSCs to treat HIV, there is the potential for generating a continuous supply of therapeutic cells for transplantation into HIV-infected patients. In this study, we have used human hematopoietic stem cells (HSCs) to generate anti-HIV gene expressing iPSCs for HIV gene therapy. HSCs were dedifferentiated into continuously growing iPSC lines with four reprogramming factors and a combination anti-HIV lentiviral vector containing a CCR5 short hairpin RNA (shRNA) and a human/rhesus chimeric TRIM5α gene. Upon directed differentiation of the anti-HIV iPSCs toward the hematopoietic lineage, a robust quantity of colony-forming CD133⁺ HSCs were obtained. These cells were further differentiated into functional end-stage macrophages which displayed a normal phenotypic profile. Upon viral challenge, the anti-HIV iPSC-derived macrophages exhibited strong protection from HIV-1 infection. Here, we demonstrate the ability of iPSCs to develop into HIV-1 resistant immune cells and highlight the potential use of iPSCs for HIV gene and cellular therapies.     

Modulation of intein activity by its neighboring extein substrates

Inteins comprise a large family of phylogenetically widespread self-splicing protein catalysts that colonize diverse host proteins. The evolutionary and functional relationship between the intein and the split-host protein, the exteins, is largely unknown. To probe an association, we developed an in vivo and in vitro intein assay based on FRET. The FRET assay reports cleavage of the intein from its N-terminal extein. Applying this assay to randomized extein libraries, we show that the nature of the extein substrate bordering the intein can profoundly influence intein activity. Residues proximal to the intein-splicing junction in both N- and C-terminal exteins can accelerate the N-terminal cleavage rate by >4-fold or attenuate cleavage by 1,000-fold, both resulting in compromised self-splicing efficiency. The existence and the magnitude of extein effects require consideration for maximizing the utility of inteins in biotechnological applications, and they predict biases in intein integration sites in nature.     

Influence of stimulation rate and loudness growth on modulation detection and intensity discrimination in cochlear implant users

In cochlear implants (CIs), increasing the stimulation rate typically increases the electric dynamic range (DR), mostly by reducing audibility thresholds. While CI users’ intensity resolution has been shown to be fairly constant across stimulation rates, high rates have been shown to weaken modulation sensitivity, especially at low listening levels. In this study, modulation detection thresholds (MDTs) were measured in five CI users for a range of stimulation rates (250–2000 pulses per second) and modulation frequencies (5–100 Hz) at 8 stimulation levels that spanned the DR (loudness-balanced across stimulation rates). Intensity difference limens (IDLs) were measured for the same stimulation rates and levels used for modulation detection. For all modulation frequencies, modulation sensitivity was generally poorer at low levels and at higher stimulation rates. CI users were sensitive to modulation frequency only at relatively high levels. Similarly, IDLs were poorer at low levels and at high stimulation rates. When compared directly in terms of relative amplitude, IDLs were generally better than MDTs at low levels. Differences in loudness growth between dynamic and steady stimuli might explain level-dependent differences between MDTs and IDLs. The slower loudness growth associated with high stimulation rates might explain the poorer MDTs and IDLs with high rates. In general, high stimulation rates provided no advantage in intensity resolution and a disadvantage in modulation sensitivity.     

An efficient synthesis of [13C6]‐3,5‐dichloroaniline

3,5‐Dichloroaniline is commonly found in many compounds with pharmacological and other biological activities. [¹³C₆]‐Aniline or its hydrochloride salt was converted in three steps to [¹³C₆]‐3,5‐dichloroaniline, which can be incorporated in compounds of interest and used as internal standards in drug metabolism and pharmacokinetics (DMPK) studies. Copyright © 2008 John Wiley & Sons, Ltd.     

Incidence of perforation with Goode T-tube

Two groups of patients from the same era were retrospectively studied in Cincinnati and Chicago. In Cincinnati two subgroups were studied. The first group received myringotomy with insertion of a 'T'-shaped ventilating tube (75 patients, 140 ears, 147 insertions). Fifty-eight ears still had the tube in place, 31 had healed after spontaneous extrusion, 17 had healed after removal of the tube, 20 had persistent perforation after the tube was gone, 2 had a cholesteatoma, and 4 patients (7 ears) were lost to follow-up. The second set received myringotomy and insertion of a small grommet (Donaldson tube, 71 patients, 140 ears, 164 insertions) tympanostomy tube. None could be documented to still have the tube in place, 156 ears healed after spontaneous extrusion, none required removal, 3 ears had a persistent perforation after the tube was gone, none had cholesteatoma, and 5 patients (5 ears) were lost to follow-up. The perforation rate for the T-tube is 13.6% and for the grommet is 1.8% (P = 0.0005). In Chicago, 93 patients who received the Goode T style tube (175 ears, 175 insertions) prior to March, 1986 were evaluated. The degree of retraction of the tympanic membrane preoperatively was recorded. No ears still had the tube in place, 145 had healed after spontaneous extrusion or removal of the tube, 30 had persistent perforation 12 months after the tube was gone, 4 had a cholesteatoma, and 8 patients (15 ears) were lost to follow-up. The rate of perforation is 18.8% which is not statistically different from the Cincinnati rate.(ABSTRACT TRUNCATED AT 250 WORDS)