Extending the understanding of sensory neuropeptides

The tachykinins substance P and neurokinin A are present in human airways, in sensory nerves and immune cells. Tachykinins can be recovered from the airways after inhalation of ozone, cigarette smoke or allergen. They interact in the airways with tachykinin NK1, NK2 and NK3 receptors to cause bronchoconstriction, plasma protein extravasation, and mucus secretion and to attract and activate immune cells. In preclinical studies they have been implicated in the pathophysiology of asthma and chronic obstructive pulmonary disease, including allergen- and cigarette smoke induced airway inflammation and bronchial hyperresponsiveness and mucus secretion. Dual NK1/NK2 or triple NK1/NK2/NK3 tachykinin receptor antagonists offer therapeutic potential in airway diseases such as asthma and chronic obstructive pulmonary disease.     

Characterization of ternary solid dispersions of itraconazole, PEG 6000, and HPMC 2910 E5

In order to reduce the crystallinity of PEG 6000, blends were prepared by spray drying and extrusion with the following polymers; PVP K25, PVPVA 64, and HPMC 2910 E5. The maximal reduction of crystallinity in PEG 6000 was obtained by co-spray drying with HPMC 2910 E5. In the next step the model drug Itraconazole was added to the blend and the resulting ternary solid dispersions were characterized. The results of this study show that the addition of PEG 6000 to the Itraconazole/HPMC 2910 E5 system leads to phase separation that in most cases gives rise to recrystallization of either PEG 6000 or Itraconazole. For all ternary dispersions containing 20% of Itraconazole the drug was highly amorphous and the dissolution was improved compared to the binary 20/80 w/w Itraconazole/HPMC 2910 E5 solid dispersion. For all ternary dispersions containing 40% of Itraconazole, the drug was partially crystalline and the dissolution was lower than the dissolution of the binary 40/60 w/w Itraconazole/HPMC 2910 E5 dispersion. These results show that provided Itraconazole is highly amorphous the addition of PEG 6000 to HPMC 2910 E5 leads to an increase in drug release.     

Strategic response by providers to specialty hospitals, ambulatory surgery centers, and retail clinics

Radical innovation and disruptive technologies are frequently heralded as a solution to delivering higher quality, lower cost health care. According to the literature on disruption, local hospitals and physicians (incumbent providers) may be unable to competitively respond to such "creative destruction" and alter their business models for a host of reasons, thus threatening their future survival. However, strategic management theory and research suggest that, under certain conditions, incumbent providers may be able to weather the discontinuities posed by the disrupters. This article analyzes 3 disruptive innovations in service delivery: single-specialty hospitals, ambulatory surgical centers, and retail clinics. We first discuss the features of these innovations to assess how disruptive they are. We then draw on the literature on strategic adaptation to suggest how incumbents develop competitive responses to these disruptive innovations that assure their continued survival. These arguments are then evaluated in a field study of several urban markets based on interviews with both incumbents and entrants. The interviews indicate that entrants have failed to disrupt incumbent providers primarily as a result of strategies pursued by the incumbents. The findings cast doubt on the prospects for these disruptive innovations to transform health care.     

Basic patterns in national health expenditure

Analysed in this paper are national health accounts estimates for 191 WHO Member States for 1997, using simple comparisons and linear regressions to describe spending on health and how it is financed. The data cover all sources - out-of-pocket spending, social insurance contributions, financing from government general revenues and voluntary and employment-related private insurance - classified according to their completeness and reliability. Total health spending rises from around 2-3% of gross domestic product (GDP) at low incomes (< 1000 US dollars per capita) to typically 8-9% at high incomes (> 7000 US dollars). Surprisingly, there is as much relative variation in the share for poor countries as for rich ones, and even more relative variation in amounts in US dollars. Poor countries and poor people that most need protection from financial catastrophe are the least protected by any form of prepayment or risk-sharing. At low incomes, out-of-pocket spending is high on average and varies from 20-80% of the total; at high incomes that share drops sharply and the variation narrows. Absolute out-of-pocket expenditure nonetheless increases with income. Public financing increases faster, and as a share of GDP, and converges at high incomes. Health takes an increasing share of total public expenditure as income rises, from 5-6% to around 10%. This is arguably the opposite of the relation between total health needs and need for public spending, for any given combination of services. Within public spending, there is no convergence in the type of finance - general revenue versus social insurance. Private insurance is usually insignificant except in some rich countries.     

High job strain and ambulatory blood pressure in middle-aged men and women from the Belgian job stress study

OBJECTIVE: The aim of this study was to assess whether job strain is associated with 24-hour ambulatory blood pressure measurements within a subsample of the Belgian Job Stress Project (BELSTRESS) population. METHODS: A group of 89 middle-aged male and female workers perceiving high job strain and an equally large group of workers perceiving no high job strain wore an ambulatory blood pressure monitor for 24 hours on a regular working day. RESULTS: Mean ambulatory blood pressure at work, at home, and while asleep was significantly higher in workers with job strain as compared with others. The associations between job strain and ambulatory blood pressure were independent from the covariates. CONCLUSIONS: Within this study, high job strain was an important independent risk factor for higher ambulatory blood pressure at work, at home, and during sleep in a group of men and women.     

Serotonin and drug reward: focus on 5-HT2C receptors

Pharmacological manipulation of the 5-hydroxytryptamine (5-HT; serotonin) system has long been associated with a regulation of feeding behaviour, however, the initial part of this article reviews evidence that central 5-HT systems similarly modulate reward-related behaviours, particularly drug reward. The second part of this article considers what we believe to be strong emerging pharmacological and genetic evidence that many of these effects are mediated through 5-HT_2C receptor signalling mechanisms. Finally, we consider the potential for selective 5-HT_2C agonists as therapies for substance abuse disorders and the medical implications for different 5-HT_2C receptor isoforms generated by RNA editing.