Inhaled corticosteriod use and the risk of pneumonia and COPD exacerbations in the UPLIFT study

Rationale Unlike many other COPD studies, the 4-year UPLIFT trial permitted inhaled corticosteroid (ICS) use during run-in and treatment phases. This provided the opportunity to prospectively observe the continuing effects of ICS on respiratory events in closely observed COPD population. Objectives We aimed to determine rate and number of episodes of pneumonia and exacerbations of COPD in patients entering the study on no ICS, fluticasone proprionate (FP), and other ICS. Methods The UPLIFT dataset was examined retrospectively, and patients were divided into three groups based on their medications at entry: no ICS, FP and other ICS. Poisson regression was used to compare the frequency of respiratory adverse events. Measurements and main results At entry, the groups were well matched apart from a higher FEV1% predicted (38 vs. 41%; ICS vs. no ICS, respectively) and prevalence of current smoking (26 vs. 36%; ICS vs. no ICS, respectively). Incidence rates of pneumonia were significantly higher in patients taking ICS compared to no ICS (0.068 vs. 0.056 respectively; p = 0.012). When the FP group was compared to the other ICS, the event rate was even higher (0.077 vs. 0.058, respectively; p < 0.001). COPD exacerbations were more frequent in patients taking ICS, with significantly greater rate in the FP group compared to that seen with other ICS (0.93 vs. 0.84 respectively; p = 0.013). Conclusions ICS use was associated an increase in respiratory adverse event rates, but whether this was due to more severe illness at entry is unknown. In subgroup analysis, the excess of morbidity in the ICS group appeared to be mainly associated with those receiving FP at randomisation

The value of democracy in the world’s poorest region: evidence from Kenya’s road building

Just how significant is ethnic favouritism in Africa? It’s a common aspect of Africa’s perception and many of the continents ills have been blamed on it. Yet, it has been quite difficult to find concrete evidence of this behaviour. So how much does it actually exist and what are the effects? We look at the case of Kenya and find strong empirical evidence of ethnic favouritism but, during periods of democracy, our measures of favouritism disappear entirely. Africa’s recent improved economic performance may be due, then, to democracy placing greater constraints on the executive which in turn limits ethnic favouritism

Impact of ocular disease on circadian rhythms and brain connectivity

Investigation into the impact of ocular disease on sleep and mood has shown that in humans eyes have an important role, and that absence of eyes or interference with light reaching the retina can have deleterious effects. Light is the main zeitgeber ‘time-giver’ used by most species for the regulation of circadian rhythms and is detected by rods, cones and photosensitive retinal ganglion cells (pRGCs) in mammals. The aims of this research project were to investigate this from three different perspectives. Three prospective studies were undertaken. The first, studied the impact of ocular disease on the sleep/wake cycle in diabetic retinopathy (DR) and in bilateral anophthalmia. There was no significant difference found between the severity of DR and global sleep scores, however the acquired anophthalmic groups have significantly raised global sleep scores compared to controls and the congenital anophthalmic group. Both anophthalmic groups had varying sleep/wake cycles on their actograms depending on the lifestyle (independent of the urinary melatonin). All the anophthalmic participants showed a non 24 hour sleep-wake rhythm disorder after melatonin profiling. The second study investigates the evidence for the presence of extraocular circadian photoreceptors (EOCP) in participants with anophthalmia and sighted controls. Changes in brain activity using a functional MRI scan was assessed, when a bright white light is shining in different locations. This study did not reveal any evidence of EOCP.Finally, structural brain MRI differences in anophthalmic groups were investigated. While similar changes in structural reorganisation occur in all anophthalmic groups in the occipital cortex, the acquired anophthalmic groups show an inverse relation with the time since becoming anophthalmic and the volume of optic radiation and optic nerve volume. The acquired anophthalmic group did not show increase in hippocampal volume (memory areas) or in the precuneus (spatial navigation) contrast to the congenital anophthalmic groups

The release of nicotine from chewing gum formulations

The first clinically proven nicotine replacement product to obtain regulatory approval was Nicorette® gum. It provides a convenient way of delivering nicotine directly to the buccal cavity, thus, circumventing 'first-pass' elimination following gastrointestinal absorption. Since launch, Nicorette® gum has been investigated in numerous studies (clinical) which are often difficult to compare due to large variations in study design and degree of sophistication. In order to standardise testing, in 2000 the European Pharmacopoeia introduced an apparatus to investigate the in vitro release of drug substances from medical chewing gum. With use of the chewing machine, the main aims of this project were to determine factors that could affect release from Nicorette® gum, to develop an in vitro in vivo correlation and to investigate formulation variables on release of nicotine from gums. A standard in vitro test method was developed. The gum was placed in the chewing chamber with 40 mL of artificial saliva at 37'C and chewed at 60 chews per minute. The chew rate, the type of dissolution medium used, pH, volume, temperature and the ionic strength of the dissolution medium were altered to investigate the effects on release in vitro. It was found that increasing the temperature of the dissolution media and the rate at which the gums were chewed resulted in a greater release of nicotine, whilst increasing the ionic strength of the dissolution medium to 80 mM resulted in a lower release. The addition of 0.1 % sodium Jauryl sulphate to the artificial saliva was found to double the release of nicotine compared to the use of artificial saliva and water alone. Although altering the dissolution volume and the starting pH did not affect the release. The increase in pH may be insufficient to provide optimal conditions for nicotine absorption (since the rate at which nicotine is transported through the buccal membrane was found to be higher at pH values greater than 8.6 where nicotine is predominately unionised). Using a time mapping function, it was also possible to establish a level A in vitro in vivo correlation. 4 mg Nicorette® gum was chewed at various chew rates in vitro and correlated to an in vivo chew-out study. All chew rates used in vitro could be successfully used for IVIVC purposes, however statistically, chew rates of 10 and 20 chews per minute performed better than all other chew rates. Finally a series of nicotine gums was made to investigate the effect of formulation variables on release of nicotine from the gum. Using a directly compressible gum base, in comparison to Nicorette® the gums crumbled when chewed in vitro, resulting in a faster release of nicotine. To investigate the effect of altering the gum base, the concentration of sodium salts, sugar syrup, the form of the active drug, the addition sequence and the incorporation of surfactant into the gum, the traditional manufacturing method was used to make a series of gum formulations. Results showed that the time of addition of the active drug, the incorporation of surfactants and using different gum base all increased the release of nicotine from the gum. In contrast, reducing the concentration of sodium carbonate resulted in a lower release. Using a stronger nicotine ion-exchange resin delayed the release of nicotine from the gum, whilst altering the concentration of sugar syrup had little effect on the release but altered the texture of the gum

Immunomodulatory and biologic therapies for severe refractory asthma

SummaryDespite undoubted efficacy of the combination of inhaled corticosteroids and β2-agonists for most asthmatic patients with moderate-to-severe disease, there remains ∼10% of the asthmatic population with serious unremitting symptoms, resulting in considerable impact on quality of life, disproportionate use of health care resources, and adverse effects from regular systemic steroid use. In an ideal world, optimal treatment of severe refractory asthma should achieve the best possible asthma control and quality of life with the least dose of systemic corticosteroids. The choice and formulation of therapeutic agent are dictated by the severity of disease and may include immunological modifiers and biologic therapies. Unfortunately, current asthma guidelines offer little contribution to the management of the challenging patient with severe refractory asthma and none of them have addressed therapeutic alternatives to oral corticosteroids. This article reviews the current evidence for immunomodulating and biologic approaches in severe refractory asthma

Helpful developments and technologies for school eye health programmes.

School eye health programmes provide a unique opportunity to positively influence the health of 700 million children globally. The impact of school eye health (SEH) goes far beyond good vision— it encompasses education, social development and economic productivity

The value of relationships: evidence from a supply shock to Kenyan rose exports

This paper provides evidence on the importance of reputation in the context of the Kenyan rose export sector. A model of reputation and relational contracting is developed and tested. A seller's reputation is defined by buyer's beliefs about seller's reliability. We show that (i) due to lack of enforcement, the volume of trade is constrained by the value of the relationship; (ii) the value of the relationship increases with the age of the relationship; and (iii) during an exogenous negative supply shock deliveries are an inverted-U shaped function of relationship's age. Models exclusively focusing on enforcement or insurance considerations cannot account for the evidence

Acquisitions, management and efficiency in Rwanda's coffee industry

Well-functioning markets allocate assets to owners that improve firms' management and performance. We study the effects of ownership changes on coffee mills in Rwanda - an industry in which managing relationships with farmers and seasonal workers is important and that has seen many ownership changes in recent years. We combine administrative data, a survey panel of mills and an original survey of acquirers that allows us to construct acquirer-specific and target-specific control groups. A difference-in-differences design reveals that ownership changes do not improve performance unless the mill is acquired by a foreign firm. Our preferred interpretation - supported by detailed survey evidence that considers alternative hypotheses - is that foreign firms successfully implement management changes in key operational areas. Upon acquisition, both domestic and foreign owned mills attempt to implement similar changes, but domestic firms face resistance from workers and farmers. Domestic owners have relationships with their local communities, which can create opportunities to establish new mills and acquire existing ones. However, these same relationships create pressure to maintain status-quo relational arrangements, which makes it harder to implement managerial changes

Compliance and Predictors of Spectacle Wear in Schoolchildren and Reasons for Non-Wear: A Review of the Literature.

Purpose: Uncorrected refractive errors are the leading cause of visual impairment in children, affecting children in all settings. The majority of refractive errors can be corrected with spectacles. High compliance with spectacle wear is required for children to realize the benefit, such as higher academic achievement. This review collates evidence on compliance with spectacle wear, factors which predict spectacle wear and reasons for non-compliance among schoolchildren.Methods: Literature searches were conducted on Medline, Embase, Global Health and the Cochrane Library. The date range was January 2000 to November 2017 and there were no language restrictions. The search retrieved a total of 1299 references, 522 duplicate records were removed leaving 777 references to assess. Twenty-five studies were included in the review.Results: Evidence suggests that greater severity of uncorrected refractive error and lower levels of uncorrected visual acuity are associated with higher levels of spectacle wear. Addressing socio-demographic reasons for non-compliance is complex as they are context specific. Evidence that children become less compliant with spectacle wear with increasing age is not consistent. Quantitative data indicate girls are more likely to be compliant with spectacles wear than boys, but qualitative studies highlight specific challenges faced by girls.Conclusion: There was considerable variation between studies in how spectacle compliance was defined, the time interval between dispensing the spectacles and assessment, and how compliance was assessed. There is need to standardize all aspects of the assessment of compliance. Further qualitative and quantitative studies are required in a range of settings to assess the biomedical and socio-demographic factors which affect spectacle wear compliance using standard definitions