Aspirin and non-steroidal anti-inflammatory drug use and the risk of upper aerodigestive tract cancer.

BACKGROUND: Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are widely used as analgesics and preventative agents for vascular events. It is unclear whether their long-term use affects cancer risk. Data on the chemopreventative role of these drugs on the risk of the upper aerodigestive tract cancer (UADT) are insufficient and mostly refer to oesophageal cancer. The aim of this study was to investigate the effect of aspirin and other NSAIDs on the risk of UADT cancers. METHODS: A nested case-control study using the Primary Care Clinical Informatics Unit (PCCIU) database. Conditional logistics regression was used for data analysis. RESULTS: There were 2392 cases of UADT cancer diagnosed between 1996 and 2010 and 7165 age-, gender- and medical practice-matched controls from 131 general medical practices. Mean age of cases was 66 years (s.d. 12) and most were male (63%). Aspirin was prescribed in a quarter of cases and controls, COX-2 inhibitors in 4% of cases and 5% of controls and other NSAIDs in 33% of cases and 36% of controls. Aspirin prescription was associated with a nonsignificant risk reduction of cancer of UADT (adjusted OR=0.9, 95% CI=0.8, 1.0), head and neck (HN; adjusted OR=0.9, 95% CI=0.7, 1.1) or the oesophagus (adjusted OR=0.8, 95% CI=0.7, 1.0). Similar results were found for COX-2 inhibitors prescription. Prescription of other NSAIDs was associated with significantly reduced risk of cancer of UADT (adjusted OR=0.8, 95% CI=0.7, 0.9), HN (adjusted OR=0.8, 95% CI=0.7, 0.9) and the oesophagus (adjusted OR=0.8, 95% CI=0.7, 0.9). An increased volume of aspirin prescriptions was associated with a significant risk reduction (test for trend P<0.001). CONCLUSIONS: The decreased risk of cancer of the UADT associated with the use of non-COX-2 inhibitors, NSAIDs and long-term aspirin therapy warrants further exploration of the benefits vs risks of the use of these agents.

Incidence and drug treatment of emotional distress after cancer diagnosis: a matched primary care case-control study.

BACKGROUND: Emotional distress is common in cancer patients. This study aimed to describe, in the year after a cancer diagnosis: the incidence of anxiety, depression and excessive alcohol use; the pattern of these diagnoses and treatment over time; and the nature and duration of the prescribed treatment. METHODS: A matched case-control study was conducted using routinely collected primary care data from 173 Scottish general practices. A presumptive diagnosis of emotional distress (anxiety, depression and/or excessive alcohol use) was based on prescription data or diagnostic code. Prescriptions for psychotropic drugs were described in terms of drug class, volume and treatment duration. RESULTS: In total, 7298 cancer cases and 14 596 matched-controls were identified. Overall, 1135 (15.6%) cases and 201 (1.4%) controls met criteria for emotional distress (odds ratio 13.7, 95% confidence interval 11.6-16.1). Psychotropic drugs were prescribed in the 6 months following initial cancer diagnosis for 1066 (14.6%) cases and 161 (1.1%) controls. The volume and duration of anxiolytic and antipsychotic prescribing was significantly different between cases and controls. CONCLUSION: This study quantified the higher incidence of new emotional distress in cancer patients in the first year post diagnosis. Clinicians should be aware of the possibility of emotional distress at any time in the year after cancer diagnosis.

Introduction of a new incentive and target-based contract for family physicians in the UK: good for older patients with diabetes but less good for women?

AIMS: To determine whether the recording of diabetes-related health indicators has increased and differences diminished between age, gender and deprivation groups, following the introduction of the new General Medical Services contract (nGMS), an incentive- and target-based contract for UK family physicians. METHODS: A serial cross-sectional study set in 310 primary care practices in Scotland serving a population of 1.5 million registered patients, focussing on diabetic patients. Data were taken immediately before the introduction of the nGMS and after it had been in place for 1 year. RESULTS: One year after the introduction of the nGMS contract, there was a 54.2% relative increase in the number of patients electronically recorded as having diabetes. In addition, measurement of the quality indicators glycated haemoglobin (HbA(1c)), blood pressure, serum creatinine and cholesterol significantly increased (P < 0.05). Women were less likely than men to have HbA(1c)[odds ratio (OR) 0.85, 95% confidence intervals (CI) 0.80-0.91], serum creatinine (OR 0.90, 95% CI 0.84-0.96) and cholesterol recorded (OR 0.83, 95% CI 0.77-0.90) or achieve HbA(1c) (

Dual role of the NF-kappaB transcription factor in the death of immature neurons.

We have previously shown that the extent of axotomy-induced death of retinal ganglion cells is reduced by cycloheximide, an inhibitor of protein synthesis, and that an earlier sublethal oxidative insult induced by buthionine sulfoximine, a glutathione synthesis inhibitor, enhances the protective effects of cycloheximide. Thus, axotomy-induced ganglion cell death seems to involve an interaction between the redox status and genetic expression. The redox-sensitive transcription factor nuclear factor-kappaB (NF-kappaB) is a logical candidate for providing this interaction. In the present study, we injected intraocularly selective inhibitors of NF-kappaB in chick embryos either unlesioned, or after a unilateral tectal lesion, which axotomizes ganglion cells. The number of dying cells in the retina contralateral to the lesion was reduced in embryos receiving NF-kappaB inhibitors as compared with vehicle-injected controls. In contrast, the same NF-kappaB inhibitors administered as pretreatment before intraocular injection of buthionine sulfoximine and cycloheximide drastically raised neuronal death and induced fulgurant degenerative changes in the retina. The most parsimonious interpretation of our results is that in axotomized retinal ganglion cells of chick embryos NF-kappaB may have either death-promoting or death-inhibiting effects. We propose a theoretical model to explain these dual effects assuming the existence of parallel death pathways differently affected by NF-kappaB. These results may have implications for future redox-based therapeutic strategies for neuroprotection.

An optimal redox status for the survival of axotomized ganglion cells in the developing retina.

The neuronal redox status influences the expression of genes involved in neuronal survival. We previously showed that antioxidants may reduce the number of dying ganglion cells following axotomy in chick embryos. In the present study, we show that various antioxidants, including the new spin trap azulenyl nitrone and 1,3-dimethyl-2-thiourea, protect axotomized ganglion cells, confirming that neuronal death involves an imbalance of the cellular redox status towards oxidation. However, high concentrations of antioxidants did not protect ganglion cells, suggesting that excessive reduction is detrimental for neurons. Simultaneous injections of two different antioxidants gave results only partly supporting this view. Combinations of azulenyl nitrone and N-acetyl cysteine in fact gave greater protection than either antioxidant alone, whereas N-acetyl cysteine lost its neuroprotective effects and diminished those of alpha-phenyl-N-tert-butyl nitrone when the two compounds were injected simultaneously. The results of the combined treatments suggest that azulenyl nitrone and alpha-phenyl-N-tert-butyl nitrone do not have the same chemical effects within the ganglion cells. Moreover, N-acetyl cysteine's own antioxidant properties enhance the spin trapping effects of azulenyl nitrone but potentiate the toxicity of alpha-phenyl-N-tert-butyl nitrone. Our main conclusion is that neuronal survival requires the maintenance of the redox status near an optimal set-point. "Reductive stress" may be as dangerous as oxidative stress.

Polymyositis with plasma cell infiltrate in essential mixed cryoglobulinaemia.

A patient with essential cryoglobulinaemia who presented with polymyositis is described. Muscle biopsy showed intense plasma cell infiltration of muscle. Plasmapheresis produced a rapid resolution of the cutaneous manifestations of the disease, but little improvement in muscle strength. Oral steroids resulted in moderate improvement in muscle strength. There have been no previously reported cases of polymyositis in association with essential cryoglobulinaemia.