Causes of Death and Risk Factors for Mortality in Patients With Severe Chronic Obstructive Pulmonary Disease

ObjectiveThe objective of this study was to assess the causes of death and risk factors for mortality in a cohort of patients with severe chronic obstructive pulmonary disease (COPD).Patients and methodsWe studied 203 patients with severe COPD (forced expiratory volume in 1 second [FEV₁] <50%), who were attended in our respiratory department day hospital (2001-2006). Clinical variables were recorded on inclusion, and clinical course and causes of death were retrospectively reviewed.ResultsThe mean (SD) age of patients was 69 (8) years and the mean FEV₁ was 30.8% (8.2%). One-hundred and nine patients died (53.7%); death was attributed to respiratory causes in 72 (80.9%), with COPD exacerbation being the most frequent specific cause within this category (48.3%). During follow-up, 18.7% required admission to the intensive care unit (ICU). Survival at 1, 3, and 5 years was 80%, 53%, and 26%, respectively. The multivariate analysis showed that mortality was associated with age, stage IV classification according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), cor pulmonale, and hospital admission during the year prior to inclusion. Need for admission to the ICU during follow-up was a factor independently associated with higher mortality.ConclusionsMortality in patients with severe COPD was high and exacerbation of the disease was one of the most frequent causes of death. Age, GOLD stage, cor pulmonale, prior admission to hospital, and need for admission to the ICU during follow-up were independent predictors of mortality.     

Oxycodone: a pharmacological and clinical review

Oxycodone is a semi-synthetic opioid with an agonist activity on mu, kappa and delta receptors. Equivalence with regard to morphine is 1:2. Its effect commences one hour after administration and lasts for 12 h in the controlled-release formulation. Plasma half-life is 3–5 h (half that of morphine) and stable plasma levels are reached within 24 h (2–7 days for morphine). Oral bioavailability ranges from 60 to 87%, and plasma protein binding is 45%. Most of the drug is metabolised in the liver, while the rest is excreted by the kidney along with its metabolites. The two main metabolites are oxymorphone — which is also a very potent analgesic — and noroxycodone, a weak analgesic. Oxycodone metabolism is more predictable than that of morphine, and therefore titration is easier. Oxycodone has the same mechanism of action as other opioids: binding to a receptor, inhibition of adenylyl-cyclase and hyperpolarisation of neurons, and decreased excitability. These mechanisms also play a part in the onset of dependence and tolerance. The clinical efficacy of oxycodone is similar to that of morphine, with a ratio of 1/1.5–2 for the treatment of cancer pain. Long-term administration may be associated with less toxicity in comparison with morphine. In the future, both opioids could be used simultaneously at low doses to reduce toxicity. It does not appear that there are any differences between immediate and slow-release oxycodone, except their half-life is 3–4 h, and 12 h, respectively. In Spain, controlled-release oxycodone (OxyContin®) is marketed as 10-, 20-, 40-or 80-mg tablets for b.i.d. administration. Tablets must be taken whole and must not be broken, chewed or crushed. There is no food interference. The initial dose is 10 mg b.i.d. for new treatments and no dose reduction is needed in the elderly or in cases of moderate hepatic or renal failure. Immediate-release oxycodone (OxyNorm®) is also available in capsules and oral solution. Side effects are those common to opioids: mainly nausea, constipation and drowsiness. Vomiting, pruritus and dizziness are less common. The intensity of these side effects tends to decrease over the course of time. Oxycodone causes somewhat less nausea, hallucinations and pruritus than morphine.     

Origin of renal cell carcinomas

Cancer is a heritable disorder of somatic cells: environment and heredity are both important in the carcinogenic process. The primal force is the “two hits” of Knudson’s hypothesis, which has proved true for many tumours, including renal cell carcinoma. Knudson et al. [1, 2] recognised that familial forms of cancer might hold the key to the identification of important regulatory elements known as tumour-suppressor genes. Their observations (i.e., that retinoblastoma tend to be multifocal in familial cases and unifocal in sporadic presentation) led them to propose a two-hit theory of carcinogenesis. Furthermore, Knudson postulated that patients with the familial form of the cancer would be born with one mutant allele and that all cells in that organ or tissue would be at risk, accounting for early onset and the multifocal nature of the disease. In contrast, sporadic tumours would develop only if a mutation occurred in both alleles within the same cell, and, as each event would be expected to occur with low frequency, most tumours would develop late in life and in a unifocal manner [3, 4]. The kidney is affected in a variety of inherited cancer syndromes. For most of them, both the oncogene/tumour-suppressor gene involved and the respective germline mutations have been identified. Each of the inherited syndromes predisposes to distinct types of renal carcinoma. Families with hereditary predisposition to cancer continue to provide a unique opportunity for the identification and characterisation of genes involved in carcinogenesis. A surprising number of genetic syndromes predispose to the development of renal cell carcinoma, and genes associated with five of these syndromes have been already identified: VHL, MET, FH, BHD and HRPT2. Few cancers have as many different types of genetic predisposition as renal cancer, although to date only a small proportion of renal cell cancers can be explained by genetic predisposition. Supported by an unrestricted educational grant from Pfizer.     

Observation,interview and discussion group: the silence of 3 research practices

Before entering into the opposition between quantitative perspective and qualitative perspective of social research, the need is discussed of considering the social research process as a social process and the empirical observation situations per se as social situations. Therefore, in social research, the object of observation and the ways of observation are made in the same stuff. As in any social situation, social norms come into play in the observation situation. Thus, the article develops the presentation of three qualitative social research practices from their design as producing different social situations which, in turn, take on the nature of immediate contexts which favor respective articulations between the practical norms of specific social groups and the dominant social norms in society at large. The practices presented are: participant observation, in-depth interview and discussion group. A different articulation among social norms which finds silence to be privileged way of observation. Hence, the conclusion is reached that the management and analysis of silence is fundamental both for distinguishing the qualitative from the quantitative perspective, the former opening up more to silence than the latter, and to distinguish one practice from another, especially for observing the effects proper of the observation during the observation processes.     

Internal initiation of translation by viral and cellular IRESs--a new avenue for specific inhibition of protein synthesis?

Many virus species, as well as a limited number of cellular mRNAs, initiate protein synthesis by an unusual mechanism, based on well-defined RNA structures called internal ribosome entry sites (IRES). IRES-mediated internal initiation allows recognition of the start codon by the ribosome in a cap-independent way, avoiding major regulatory steps. The IRES elements and their trans-acting factors are potential targets for developing new agents against hepatitis C, and may provide new possibilities for antitumor therapy.     

First-night effect in the chronic fatigue syndrome

Since the magnitude of the first-night effect has been shown to be a function of medical conditions and of settings in which polysomnographies are performed, it is essential to evaluate the habituation phenomenon in each case in order to determine the optimal recording methodology. A first-night effect was evidenced in certain cases of chronic fatigue syndrome, but not in others. To clarify this issue, a large group of patients with chronic fatigue syndrome who had no primary sleep disorders were selected and recorded for two consecutive nights in a hospital sleep unit. Several parameters, frequently associated with the first-night effect, were found to be influenced by the recording methodology: Total Sleep Time, Sleep Efficiency, Sleep Efficiency minus Sleep Onset, Sleep Onset Latency, Wake Time, Slow Wave Sleep, Rapid Eye Movement Sleep, Rapid Eye Movement Sleep Latency and Number of Sleep Cycles. Bland and Altman plots determined that the difference scores between the nights included a systematic bias linked to the order of recordings (first-night effect). Factorial analysis grouped the difference scores into three factors. No significant difference was observed between patients with generalized anxiety comorbidity and those with no psychiatric comorbidity, or between those with and without psychiatric comorbidity. Chronic fatigue syndrome must thus be added on the list of conditions where a clinically significant habituation effect takes place.