“You’ve got to breathe,you know” – asthma patients and carers’ perceptions around purchase and use of asthma preventer medicines

Objective : To explore influences on patients’ purchase and use of asthma preventer medicines and the perceived acceptability of financial incentives via reduced patient co‐payments. Methods : Semi‐structured telephone or face‐to‐face interviews were conducted with adults and carers of children with asthma. Interviews were recorded, transcribed verbatim and coded. Data were analysed using thematic analysis via grounded theory. Results : Twenty‐four adults and 20 carers for children aged 3–17 years with asthma were interviewed. For medicines choice, most participants did not consider themselves the primary decision‐maker; cost of medicines was an issue for some, but effectiveness was described as more important. For adherence, cost, side‐effects, perceived benefit and patient behaviours were important. Conclusions : Patient barriers to adherence with asthma preventer medicines including cost are ongoing. Healthcare professionals need to encourage empathic discussion with patients about cost issues. Implications for public health : Asthma patients and carers could benefit from greater involvement and respect within shared decision‐making. Healthcare professionals should be aware that cost may be a barrier for patient adherence, and provided with information about the relative costs of guideline‐recommended asthma medicines. Patients and healthcare professionals need education around the efficacy of ICS‐alone treatment and the rationale behind co‐payments, for initiatives around quality use of medicines to succeed.     

Conatumumab (AMG 655) coated nanoparticles for targeted pro-apoptotic drug delivery

Colloidal nanoparticle drug delivery systems have attracted much interest for their ability to enable effective formulation and delivery of therapeutic agents. The selective delivery of these nanoparticles to the disease site can be enhanced by coating the surface of the nanoparticles with targeting moieties, such as antibodies. In this current work, we demonstrate that antibodies on the surface of the particles can also elicit key biological effects. Specifically, we demonstrate the induction of apoptosis in colorectal HCT116 cancer cells using PLGA nanoparticles coated with Conatumumab (AMG 655) death receptor 5-specific antibodies (DR5-NP). We show that DR5-NP preferentially target DR5-expressing cells and present a sufficient density of antibody paratopes to induce apoptosis via DR5, unlike free AMG 655 or non-targeted control nanoparticles. We also demonstrate that DR5-targeted nanoparticles encapsulating the cytotoxic drug camptothecin are effectively targeted to the tumour cells, thereby producing enhanced cytotoxic effects through simultaneous drug delivery and apoptosis induction. These results demonstrate that antibodies on nanoparticulate surfaces can be exploited for dual modes of action to enhance the therapeutic utility of the modality.     

Staggered overdose pattern and delay to hospital presentation are associated with adverse outcomes following paracetamol-induced hepatotoxicity

AIMS

Paracetamol (acetaminophen) poisoning remains the major cause of severe acute hepatotoxicity in the UK. In this large single centre cohort study we examined the clinical impact of staggered overdoses and delayed presentation following paracetamol overdose.

RESULTS

Between 1992 and 2008, 663 patients were admitted with paracetamol-induced severe liver injury, of whom 161 (24.3%) had taken a staggered overdose. Staggered overdose patients were significantly older and more likely to abuse alcohol than single time point overdose patients. Relief of pain (58.2%) was the commonest rationale for repeated supratherapeutic ingestion. Despite lower total ingested paracetamol doses and lower admission serum alanine aminotransferase concentrations, staggered overdose patients were more likely to be encephalopathic on admission, require renal replacement therapy or mechanical ventilation and had higher mortality rates compared with single time point overdoses (37.3% vs. 27.8%, P = 0.025), although this overdose pattern did not independently predict death. The King''s College poor prognostic criteria had reduced sensitivity (77.6, 95% CI 70.8, 81.5) for this pattern of overdose. Of the 396/450 (88.0%) single time point overdoses in whom accurate timings could be obtained, 178 (44.9%) presented to medical services >24 h following overdose. Delayed presentation beyond 24 h post overdose was independently associated with death/liver transplantation (OR 2.25, 95% CI 1.23, 4.12, P = 0.009).

CONCLUSIONS

Both delayed presentation and staggered overdose pattern are associated with adverse outcomes following paracetamol overdose. These patients are at increased risk of developing multi-organ failure and should be considered for early transfer to specialist liver centres.     

Predicting university undergraduates' binge-drinking behavior: a comparative test of the one- and two-component theories of planned behavior

This study provides a comparative test of the one- and two-component theories of planned behavior (TPB) in the context of university undergraduates' binge-drinking. Participants (N = 120) self-completed questionnaire measures of all TPB constructs at time 1 and subsequent binge-drinking at time 2 (two-weeks later). The data were analyzed using a combination of path analyses and bootstrapping procedures. Both models accounted for a substantial proportion of the variation in behavior. However, the two-component TPB provided a significantly better fit to the data, with the total direct and indirect effects accounting for 90% of the variance. Intention was the only direct predictor of behavior. Instrumental attitude, affective attitude and self-efficacy had indirect effects. Although health interventions could usefully target these cognitive antecedents, simulation analyses, modeling the effects of cognition change on behavior, showed that only large-sized (0.8 SD) changes to affective attitude, or moderate-sized changes to all of these cognitions in combination were sufficient to reduce binge-drinking.     

Face ethnicity and measurement reliability affect face recognition performance in developmental prosopagnosia: evidence from the Cambridge Face Memory Test-Australian

The Cambridge Face Memory Test (CFMT, Duchaine & Nakayama, 2006) provides a validated format for testing novel face learning and has been a crucial instrument in the diagnosis of developmental prosopagnosia. Yet, some individuals who report everyday face recognition symptoms consistent with prosopagnosia, and are impaired on famous face tasks, perform normally on the CFMT. Possible reasons include measurement error, CFMT assessment of memory only at short delays, and a face set whose ethnicity is matched to only some Caucasian groups. We develop the "CFMT-Australian" (CFMT-Aus), which complements the CFMT-original by using ethnicity better matched to a different European subpopulation. Results confirm reliability (.88) and validity (convergent, divergent using cars, inversion effects). We show that face ethnicity within a race has subtle but clear effects on face processing even in normal participants (includes cross-over interaction for face ethnicity by perceiver country of origin in distinctiveness ratings). We show that CFMT-Aus clarifies diagnosis of prosopagnosia in 6 previously ambiguous cases. In 3 cases, this appears due to the better ethnic match to prosopagnosics. We also show that face memory at short (<3-min), 20-min, and 24-hr delays taps overlapping processes in normal participants. There is some suggestion that a form of prosopagnosia may exist that is long delay only and/or reflects failure to benefit from face repetition.     

Category specific deficits in Alzheimer's disease: fact or artefact?

Impairments in semantic memory commonly occur in Alzheimer's Disease (AD) but do these occur along category-specific lines? We administered a confrontation naming task comprising living and nonliving items to 68 individuals with AD and 59 age-matched control participants, in a study designed to address some of the methodological issues affecting investigation of category effects. In Experiment 1, stimuli were matched for familiarity and word frequency and also visual complexity, and the AD group showed a differential deficit in nonliving things. In Experiment 2, however, living and nonliving stimuli were matched for age-of-acquisition, name agreement, word frequency, and naming accuracy of elderly controls and there was no categorical impairment in the AD group. The AD group was subdivided first into mild and moderate AD, and then into normal or impaired overall naming groups and performance was reanalysed, but there was still no significant category deficit in any group. Converging evidence was provided by hierarchical regressions across items, as age-of-acquisition, name agreement and word frequency were significant predictors of naming performance in mild and moderate AD groups, but category was not. In Experiment 3, stimulus items were matched for familiarity and naming accuracy of elderly controls when their performance was off-ceiling, and again no differential effect of category was found. When we reduced slightly how closely matched stimuli were for familiarity we then found a differential impairment in living things in the AD group. When reviewing the changing pattern of results from use of different stimulus sets, we concluded that the main determinant of whether or not a categorical impairment of either sort is found in AD is which stimulus properties are controlled during stimulus selection. We conclude that AD does not generally lead to a selective category loss in semantic knowledge.     

Rising follicle-stimulating hormone levels with age accelerate female reproductive failure

Rising serum FSH levels is one of the earliest signs of human female reproductive aging. Whether or not elevated FSH remains a passive reflection of a diminishing ovarian follicle pool or actively contributes to declining female fertility with age has not been established. We therefore investigated female reproduction in mice expressing progressively rising serum levels of transgenic human FSH (Tg-FSH, 2.5-10 IU/liter) independently of follicle depletion. We show that serum LH and estradiol levels and uterine size remained normal in Tg-FSH females, whereas ovarian weight and corpora lutea number were significantly increased up to 1.3- and 5-fold, respectively. Furthermore, the monotrophic FSH rise produced a striking biphasic effect on female fertility. Tg-FSH females less than 22 wk old delivered increased litter sizes, then beyond 23 wk, litter sizes decreased rapidly culminating in premature infertility despite continued ovary follicle development, and increased ovulation and uterine embryo implantation sites as well as normal serum levels of anti-Mullerian hormone, a marker of ovarian follicle reserve. We found that rising circulating Tg-FSH produced premature infertility by increasing embryo-fetal resorption and parturition failure with age. Thus, our Tg-FSH mice present a novel paradigm to investigate selective contributions of elevated FSH to age-related female infertility, which revealed that rising FSH levels, despite no exhaustion of ovarian reserve, actively accelerates female reproductive aging primarily by postimplantation reduction of embryo-fetal survival.     

Presence of nonhemolytic pneumolysin in serotypes of Streptococcus pneumoniae associated with disease outbreaks

Pneumolysin is an important virulence factor of the human pathogen Streptococcus pneumoniae. Sequence analysis of the ply gene from 121 clinical isolates of S. pneumoniae uncovered a number of alleles. Twenty-two strains were chosen for further analysis, and 14 protein alleles were discovered. Five of these had been reported previously, and the remaining 9 were novel. Cell lysates were used to determine the specific hemolytic activities of the pneumolysin proteins. Six strains showed no hemolytic activity, and the remaining 16 were hemolytic, to varying degrees. We report that the nonhemolytic allele reported previously in serotype 1, sequence type (ST) 306 isolates is also present in a number of pneumococcal isolates of serotype 8 that belong to the ST53 lineage. Serotype 1 and 8 pneumococci are known to be associated with outbreaks of invasive disease. The nonhemolytic pneumolysin allele is therefore associated with the dominant clones of outbreak-associated serotypes of S. pneumoniae.