Who still dies young in a rich city? Revisiting the case of Oxford

There are substantial inequalities in mortality and life expectancy in England, strongly linked to levels of deprivation. Mortality rates among those who are homeless are particularly high. Using the city of Oxford (UK) as a case study, we investigate ward-level premature standardised mortality ratios for several three-year and five-year periods between 2002 and 2016, and explore the extent to which the mortality of people who become homeless contributed to any rise or fall in geographical inequalities during this period. Age–sex standardised mortality ratios (SMRs) for people aged under 65 years old, with and without deaths among the homeless population, were calculated using Office for National Statistics Death Registration data for England and Wales 2002−2016. Individuals who were homeless or vulnerably housed were identified using records supplied by a local Oxford homeless charity. We found that in an increasingly wealthy, and healthy, city there were persistent ward-level inequalities in mortality, which the city-wide decrease in premature mortality over the period masked. Premature deaths among homeless people in Oxford became an increasingly important contributor to the overall geographical inequalities in health in this city. In the ward with the highest SMR, deaths among the homeless population accounted for 73% of all premature deaths of residents over the whole period; in 2014–2016 this proportion rose to 88%. Homelessness among men (the vast majority of the known homeless population) in this gentrifying English city rose to become the key explanation of geographical mortality patterns in deaths before age 65 across the entire city, particularly after 2011. Oxford reflects a broader pattern now found in many places across England of increasing homeless deaths, widening geographical inequalities in life expectancy, and sharp increases in all-age SMRs. The answer to the question, “Who dies young in a rich, and in fact an even richer, place?” is – increasingly – the homeless

Minimising treatment-associated risks in systemic cancer therapy

Aim of the review To review the consequences of drug-related problems (DRP) in systemic cancer therapy and identify specific contributions of the pharmacist to minimise treatment-associated risks. Method Searches in PubMed, Embase and the Cochrane Library were conducted. Bibliographies of retrieved articles were examined for additional references. Only papers in English between 1980 and 2007 were included. Results In systemic cancer therapy there is an enormous potential for DRP due to the high toxicity and the complexity of most therapeutic regimens. The most frequently reported DRP can be classified into adverse effects, drug–drug interactions, medication errors, and non-adherence. Pharmacists have enhanced efforts to assure quality and safety in systemic cancer therapy together with other health care providers. In consequence, oncology pharmacy has evolved as a novel specialist discipline. The endeavour to merge and co-ordinate individual activities and services of the pharmacist has led to pharmaceutical care concepts which aim at offering novel solutions to the various DRP. Conclusion Pharmaceutical care for cancer patients should be developed within research projects and integrated into disease management programs in order to ensure broad implementation

Living Bacterial Sacrificial Porogens to Engineer Decellularized Porous Scaffolds

Decellularization and cellularization of organs have emerged as disruptive methods in tissue engineering and regenerative medicine. Porous hydrogel scaffolds have widespread applications in tissue engineering, regenerative medicine and drug discovery as viable tissue mimics. However, the existing hydrogel fabrication techniques suffer from limited control over pore interconnectivity, density and size, which leads to inefficient nutrient and oxygen transport to cells embedded in the scaffolds. Here, we demonstrated an innovative approach to develop a new platform for tissue engineered constructs using live bacteria as sacrificial porogens. E.coli were patterned and cultured in an interconnected three-dimensional (3D) hydrogel network. The growing bacteria created interconnected micropores and microchannels. Then, the scafold was decellularized, and bacteria were eliminated from the scaffold through lysing and washing steps. This 3D porous network method combined with bioprinting has the potential to be broadly applicable and compatible with tissue specific applications allowing seeding of stem cells and other cell types

Optimisation and scale-up of a highly-loaded 5-ASA multi-particulate dosage form using a factorial approach

Pellets with high loading of 5-aminosalicylic acid (5-ASA, mesalamine) are desired to reduce the number of tablets required to deliver the daily dosing regimen. Recently, we reported an extrusion-spheronisation route for the development of a 90 wt% 5-ASA/microcrystalline cellulose formulation based on milled 5-ASA which gave good yields of pellets at the lab scale. In the present work, such formulation was optimised further by preliminary studies using a lab-scale ram extruder, and then scaled up to the pilot plant scale on a Nica screen extruder using a mixed fractional factorial approach. The final formulation featured 95 wt% 5-ASA and 5 wt% Avicel RC591 (all dry basis) and yielded spherical pellets suitable for use as the drug core of a multi-particulate DDS

Feasibility study of high-loaded dosage form of 5-ASA by extrusion spheronisation

Purpose. 5-aminosalicylic acid (5-ASA) has demonstrated its potential to treat IBD (Inflammatory Bowel Disease). However, formulations available on the market are generally associated with a number of limitations, including poor patient acceptability due to the high daily dose required (2.4-4.6 g/day). A high-strength solid formulation containing more than 1 g 5-ASA would be attractive for once/twice daily administration, improving compliance. High density pellets for the formulation of multiple unit dosage forms are therefore sought. A systematic study of extrusion-spheronisation was performed to determine the formulation window for this material. Methods. Microcrystalline cellulose (MCC) was used as the primary extrusion aid. Colloidal grades of MCC containing carboxymethylcellulose were also investigated. The minimal water content required to give a plastic mass was established using centrifugation testing, supported by extrusion. This also indicated the upper limit of water addition. Ram extrusion of solid-liquid paste formulations through multi-holed square-ended dies was used to assess the extrudability of different formulations. Extrudates were spheronised using a benchtop spheronisation device (Caleva) and the quality of extrudates monitored via visual and automated shape analyses. Promising formulations were tested at a small (50 g) scale on an axial screen extruder based on a domestic mincer, and final testing performed on a pilot scale screen extruder (Nica). Results. A systematic study of 5-ASA/MCC formulations was performed. Chronic liquid phase migration was observed with several batches of commercial 5-ASA. This was demonstrated to be dependent on both the drug load and the extrusion aid type, and was identified as arising from the particle shape. This was confirmed by extruding calcium sulphate/MCC pastes, where the sulphate polymorph was selected to match the 5-ASA shape. A micronisation step was adjusted accordingly and the modified 5-ASA used in the final formulations. The impacts of pH on MCC behaviour, and inhibition of rubbery transition, were also investigated. Conclusion. The feasibility of an extrusion-spheronisation route to manufacture pellets with high 5-ASA loading (90 wt%) was demonstrated. The drug particle morphologhy was identified as the critical process parameter. A colloidal MCC grade, Avicel RC 591, was identified as a promising material for extrusion alongside 5-ASA