Platinum neurotoxicity pharmacogenetics

Cisplatin, carboplatin, and oxaliplatin anticancer drugs are commonly used to treat lung, colorectal, ovarian, breast, head/neck, and genitourinary cancers. However, the efficacy of platinum-based drugs is often compromised because of the substantial risk for severe toxicities, including neurotoxicity. Neurotoxicity can result in both acute and chronic debilitation. Moreover, colorectal cancer patients treated with oxaliplatin more often discontinue therapy due to peripheral neuropathy than for tumor progression, potentially compromising patient benefit. Numerous methods to prevent neurotoxicity have so far proven unsuccessful. In order to circumvent this life-altering side effect, while taking advantage of the antitumor activities of the platinum agents, efforts to identify mechanism-based biomarkers are underway. In this review, we detail findings from the current literature for genetic markers associated with neurotoxicity induced by single agent and combination platinum chemotherapy. These data have the potential for broad clinical implications if mechanistic associations lead to the development of toxicity modulators to minimize the noxious sequelae of platinum chemotherapy

Structure, bonding and morphology of hydrothermally synthesised xonotlite

The authors have systematically investigated the role of synthesis conditions upon the structure and morphology of xonotlite. Starting with a mechanochemically prepared, semicrystalline phase with Ca/Si=1, the authors have prepared a series of xonotlite samples hydrothermally, at temperatures between 200 and 250 degrees C. Analysis in each case was by X-ray photoelectron spectroscopy, environmental scanning electron microscopy and X-ray diffraction. The authors’ use of a much lower water/solid ratio has indirectly confirmed the ‘through solution’ mechanism of xonotlite formation, where silicate dissolution is a key precursor of xonotlite formation. Concerning the role of temperature, too low a temperature (~200 degrees C) fails to yield xonotlite or leads to increased number of structural defects in the silicate chains of xonotlite and too high a temperature (>250 degrees C) leads to degradation of the xonotlite structure, through leaching of interchain calcium. Synthesis duration meanwhile leads to increased silicate polymerisation due to diminishing of the defects in the silicate chains and more perfect crystal morphologies

Home visits by family physicians during the end-of-life: Does patient income or residence play a role?

BACKGROUND: With a growing trend for those with advanced cancer to die at home, there is a corresponding increase in need for primary medical care in that setting. Yet those with lower incomes and in rural regions are often challenged to have their health care needs met. This study examined the association between patient income and residence and the receipt of Family Physician (FP) home visits during the end-of-life among patients with cancer. METHODS: Data Sources/Study Setting. Secondary analysis of linked population-based data. Information pertaining to all patients who died due to lung, colorectal, breast or prostate cancer between 1992 and 1997 (N = 7,212) in the Canadian province of Nova Scotia (NS) was extracted from three administrative health databases and from Statistics Canada census records. Study Design. An ecological measure of income ('neighbourhood' median household income) was developed using census information. Multivariate logistic regression was then used to assess the association of income with the receipt of at least one home visit from a FP among all subjects and by region of residency during the end-of-life. Covariates in the initial multivariate model included patient demographics and alternative health services information such as total days spent as a hospital inpatient. Data Extraction Methods. Encrypted patient health card numbers were used to link all administrative health databases whereas the postal code was the link to Statistics Canada census information. RESULTS: Over 45% of all subjects received at least one home visit (n = 3265). Compared to those from low income areas, the log odds of receiving at least one home visit was significantly greater among subjects who reside in middle to high income neighbourhoods (for the highest income quintile, adjusted odds ratio [OR] = 1.37, 95% confidence interval [CI] = 1.15, 1.64; for upper-middle income, adjusted OR = 1.19, 95%CI = 1.02, 1.39; for middle income, adjusted OR = 1.33, 95%CI = 1.15, 1.54). This association was found to be primarily associated with residency outside of the largest metropolitan region of the province. CONCLUSION: The likelihood of receiving a FP home visit during the end-of-life is associated with neighbourhood income particularly among patients living outside of a major metropolitan region

Comparison of the influence of cyclosporine and tacrolimus on the pharmacokinetics of prednisolone in adult male kidney transplant recipients

Cyclosporine has been observed to precipitate cushingoid features in kidney transplant recipients already on prednisolone. Some pharmacokinetic studies have demonstrated increased prednisolone exposure in patients on cyclosporine therapy compared with azathioprine, whereas other studies have found no difference. The objective of this study was to determine whether cyclosporine impacts on prednisolone exposure as compared with tacrolimus

Electrochemical characterization and surface analysis of bulk amorphous alloys in aqueous solutions at different pH

Bulk amorphous alloys are a new class of materials with a variety of characteristics that make them useful for applications in aqueous environments. While some bulk amorphous metals show increased corrosion resistance, there is still a lack of fundamental electrochemical studies of these materials. Two different compositions of BeCuNiTiZr bulk amorphous alloys have been studied at pH 5, 7, and 10 using cyclic voltammetry (CV), x-ray photoelectron spectroscopy (XPS), depth profiling methods, and optical microscopy. While XPS is used to determine the composition of the resulting oxide films, the CV curves and optical micrographs are compared to pinpoint differences in the corrosion resistance of the amorphous multicomponent alloys. The effect of the amorphicity, multicomponent structure and the presence of elements with widely varying interfacial reactivities on the oxidation process and on the corrosion resistance of the alloys, are discussed with the desire to provide some electrochemical background for the expected wide spread use of bulk amorphous alloys

Age as a Risk Factor for Severe Manifestations and Fatal Outcome of Falciparum Malaria in European Patients: Observations from TropNetEurop and SIMPID Surveillance Data

Previous studies have indicated that age is a risk factor for severe falciparum malaria in nonimmune patients. The objectives of this study were to reevaluate previous findings with a larger sample and to find out how strongly clinical outcomes for elderly patients differ from those for younger patients. Results of adjusted analyses indicated that the risks of death due to falciparum malaria, of experiencing cerebral or severe disease in general, and of hospitalization increased significantly with each decade of life. The case-fatality rate was almost 6 times greater among elderly patients than among younger patients, and cerebral complications occurred 3 times more often among elderly patients. Antimalarial chemoprophylaxis was significantly associated with a lower case-fatality rate and a lower frequency of cerebral complications. Women were more susceptible to cerebral complications than were men. Our study provides evidence that falciparum malaria is more serious in older patients and demonstrates that clinical surveillance networks are capable of providing quality data for investigation of rare events or disease

Living arrangements and place of death of older people with cancer in England and Wales: a record linkage study

The main objectives of the study were to (1) see whether the household circumstances of people aged 50 years and over with cancer, and trends in these, differ from those of the rest of the population and (2) whether living arrangements and presence and health status of a primary coresident are associated with place of death among older people dying of cancer and those dying from other causes. The design included prospective record linkage study of people aged 50 years and over included in a 1% sample of the population of England and Wales (the Office for National Statistics Longitudinal Study). The main outcome measures comprised family and household type, and death at home. The household circumstances of older people with cancer were very similar to those of the rest of the population of the same age and both showed a large increase in living alone, and decrease in living with relatives, between 1981 and 1991. The primary coresident of cancer sufferers who did not live alone was in most cases a spouse, with much smaller proportions living with a child, sibling or other person. In all, 30% of spouse, and 23% of other, primary coresidents had a limiting long-term illness. Compared with people who lived alone in 1991, odds of a home death among those dying of cancer between 1991 and 1995 were highest for those who lived with a spouse who had no limiting long-term illness (odds ratio (OR) 2.52, 95% confidence interval (CI) 2.15-2.97) and raised for those living with a spouse with a long-term illness (OR 2.14, CI 1.79-2.56) and those living with someone else who was free of long-term illness (OR 2.13, CI 1.69-2.68). Higher socioeconomic status, both individual and area, was positively associated with increased chance of a home death, while older age reduced the chance of dying at home. The changing living arrangements of older people have important implications for planning and provision of care and treatment for cancer sufferers

Personal continuity and access in UK general practice: a qualitative study of general practitioners' and patients' perceptions of when and how they matter

BACKGROUND: Personal continuity is a core value for family practice, but policy and performance targets emphasise other aspects of care, particularly waiting times for consultation. This study examined patient and general practitioner (GP) perceptions of the value of personal continuity and rapid access, and the relationship between them. METHODS: Qualitative analysis of semi-structured interviews with a purposive sample of 16 GPs and 32 patients in the Lothian region of Scotland, to identify whether, how, why and in which circumstances personal continuity and rapid access were valued. RESULTS: From the patients' perspective, what mattered was 'access to appropriate care' depending on the problem to be dealt with. For a few patients, rapid access was the only priority. For most, rapid access was balanced against greater involvement in the consultation when seeing 'their' trusted doctor, which was particularly valued for chronic, complex and emotional problems. GPs focused on the value of personal continuity in the consultation for improving the diagnosis and management of the same kinds of problem. GPs did not perceive enabling access to be a core part of their work. There was little evidence that GPs routinely discussed with patients when or how personal continuity and access should be balanced. CONCLUSION: 'Access to appropriate care' from the patients' perspective is not fully addressed by GPs' focus on personal continuity, nor by performance targets focused only on speed of access. GPs need to make enabling access as much a part of their core values as personal continuity, and access targets need to be based on less simplistic measures that account for the appropriateness of care as well as speed of access