Non-invasive ventilation for cancer patients with life-support techniques limitation

Goals of work The study was conducted to determine the usefulness and efficacy of non-invasive ventilation (NIV) in cancer patients with life-support techniques limitation admitted for an acute respiratory distress, in terms of intensive care unit (ICU) and hospital discharges.Patients and methods A total of 18 consecutive cancer patients (17 with solid tumours and one with haematological malignancy) with life-support techniques limitation in acute respiratory failure and who benefited from NIV were included. NIV was provided with a standard face mask by the BiPAP Vision ventilator (Respironics Inc.). Variables related to the demographic parameters, SAPS II score, cancer characteristics, intensive care data and hospital discharge were recorded.Main results Complications leading to NIV were hypoxemic respiratory failure in 11 patients and hypercapnic respiratory failure in seven. Total median duration of NIV was 29 h. NIV was applied during a median of 2.5 days with a median of 16 h per day. Total median ICU stay was 7 days (range 1–21). Fourteen and ten patients were discharged from ICU and from hospital, respectively.Conclusion NIV appears to be an effective ventilation support for cancer patients with life-support techniques limitation.     

Repeat charcoal hemoperfusion treatments in life threatening carbamazepine overdose

A 16-month-old female experienced a massive carbamazepine ingestion resulting in a peak serum carbamazepine concentration of 55 μg/ml. Clinical manifestations included generalized seizures, coma, shock, and gastrointestinal hypomotility. Gut decontamination was attempted using multiple-dose activated charcoal and cathartics. Because of the severity of illness, charcoal hemoperfusion was initiated. The patient underwent three sessions of charcoal hemoperfusion, each utilizing a fresh cartridge, with one session immediately following the other. Serum carbamazepine and carbamazepine-10,11-epoxide concentrations decreased from 54 μg/ml to 23 μg/ml, and 30 μg/ml to 17 μg/ml, respectively, during charcoal hemoperfusion. There were no complications. The patient recovered completely and was discharged on the 4th hospital day. Charcoal hemoperfusion should be considered for life-threatening carbamazepine intoxication, especially when drug-induced gastrointestinal hypomotility prevents elimination via the gut. Received: 12 October 1998 / Revised: 11 December 1998 / Accepted: 17 December 1998     

A modeling approach to the analysis of nerve regenerative experiments

Many experiments aiming at the investigation of nerve repair involve elaborate testing over a certain time period. Data arising from such experiments are often analyzed by time-point. Such a cross-sectional approach is often very inefficient. In this paper, we consider a case study in which repeated measurements of two response variables assumed to be Poisson distributed are obtained. We show how a repeated measures modeling approach, based on generalized linear models, can handle both responses in one model and improve the inference in the nerve repair experiments. The benefits of the model as well as problems that can occur are illustrated and discussed.     

Pharmacological correlation between the formalin test and the neuropathic pain behavior in different species with chronic constriction injury

Research on mechanisms of drug action, and preclinical screening of molecules with a potential activity on neuropathic pain requires extensive animal work. The chronic constriction injury model is one of the best-characterized models of neuropathic pain behavior in rats, but requires extensive time consuming operations and animal handling. The formalin test is easier to perform, and a well validated model. The latter may serve as an effective prescreening test of molecules and may facilitate drug targeting. In the present study the activity of different pharmacological reference compounds was tested in rats and gerbils on the cold plate for animals that had undergone chronic constriction injury and in the second phase of the formalin test. In rats, a comparable outcome in both test conditions was observed for morphine, fentanyl, MK-801 and flunarizine. Clonidine had more activity in the second phase of the formalin test, whereas baclofen, tramadol, amitryptiline, ketamine and topiramate showed more activity in the cold plate. In gerbils, both test conditions yielded comparable results for fentanyl and ketoprofen. Tramadol and CP-96345 tended to have more activity in the second phase of the formalin test, whereas morphine, SR-48968, SR-142801 and R116301 demonstrated more activity in the cold plate test. This study demonstrates a good correlation between the second phase of the formalin test and the cold allodynia in the CCI model for, both for rats and gerbils. Drugs with a proven activity in humans, used as reference compounds, also showed good pharmacological activity in this animal study.     

Early evaluation of the risk of functional decline following hospitalization of older patients: development of a predictive tool

OBJECTIVE: To develop a predictive tool that could be used on admission to identify older hospitalized people at risk of functional decline 3 months after discharge. METHODS: This was a prospective cohort study that included 625 patients aged 70 years and older (mean age 80.0 +/- 5.6 years) hospitalized by the way of the emergency room, for at least 48 h, in two academic hospitals. Three months after discharge, 550 patients remained for analysis. On admission, people were assessed for premorbid functional status with the activities of daily living (ADL) scale and instrumental ADL scale. Demographic and medical data, including cognitive function, falls, polypharmacy, comorbidity, continence, mobility and self-rated health, were collected. ADL functioning was re-assessed at discharge and 1 and 3 months later. Functional decline was defined as the loss of at least one point on the ADL scale between the premorbid and 3-month evaluation. Univariate analyses were used to select variables associated with functional decline. A logistic regression model was then constructed to predict functional status 3 months after discharge. RESULTS: Three months after discharge, 165 (31.5%) patients had declined. The predictive tool SHERPA includes five factors: age, impairment in premorbid instrumental ADLs, falls in the year before hospitalization, cognitive impairment (Abbreviated Mini Mental State below 15/21) and poor self-rated health. Sensitivity and specificity were 67.9% and 70.8%, respectively. CONCLUSIONS: Older people are at high risk of functional decline following hospitalization. On admission, a simple instrument can easily identify these patients, even though the performance of this instrument is moderate.     

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

Among new biological markers that could become useful prognostic factors for lung carcinoma, Ki-67 is a nuclear protein involved in cell proliferation regulation. Some studies have suggested an association between Ki-67 and poor survival in lung cancer patients. In order to clarify this point, we have performed a systematic review of the literature, using the methodology already described by our Group, the European Lung Cancer Working Party. In total, 37 studies, including 3983 patients, were found to be eligible. In total, 49% of the patients were considered as having a tumour positive for the expression of Ki-67 according to the authors cutoff. In all, 29 of the studies dealt with non-small-cell lung carcinoma (NSCLC), one with small-cell carcinoma (SCLC), two with carcinoid tumours and five with any histology. In terms of survival results, Ki-67 was a bad prognosis factor for survival in 15 studies while it was not in 22. As there was no statistical difference in quality scores between the significant and nonsignificant studies evaluable for the meta-analysis, we were allowed to aggregate the survival results. The combined hazard ratio for NSCLC, calculated using a random-effects model was 1.56 (95% CI: 1.30-1.87), showing a worse survival when Ki-67 expression is increased. In conclusion, our meta-analysis shows that the expression of Ki-67 is a factor of poor prognosis for survival in NSCLC.     

Effects of pre-treatment with amantadine on morphine induced antinociception during second phase formalin responses in rats

The clinically available NMDA-receptor antagonist drug, amantadine, has been shown to result in morphine sparing effects in humans after surgery. However, no data are available to describe the exact form of interaction. The present study aims to profile the possible effects of amantadine (0, 12.5, 25 or 50 mgkg(-1) i.p.) pre-treatment on morphine (0, 0.63, 1.25, 2.5 or 5 mgkg(-1) s.c.) induced antinociception in rats. The (automated) formalin test (5% formalin, 50 microl) was used to assess if amantadine enhances the antinociceptive activity of morphine. Possible motor impairment was assessed with a rotarod test. Morphine was measured in serum of amantadine or vehicle treated rats to search for possible pharmacokinetic interactions between amantadine and morphine. Isobolographic analysis provided evidence for a synergistic interaction between amantadine and morphine in the second phase of the formalin test. No evidence was found to indicate that amantadine induced motor impairment at the doses potentiating morphine during the second phase of the formalin test. There was no evidence for a pharmacokinetic interaction between amantadine and morphine. Since, the second phase of the formalin test is dependent on activation of the NMDA receptor system it is concluded that an antagonistic activity of amantadine at the NMDA receptor most likely contributes to the synergistic interaction observed between amantadine and morphine in rats.     

Mekong malaria. II. Update of malaria, multi-drug resistance and economic development in the Mekong region of Southeast Asia

In an expansion of the first Mekong Malaria monograph published in 1999, this second monograph updates the malaria database in the countries comprising the Mekong region of Southeast Asia. The update adds another 3 years' information to cover cumulative data from the 6 Mekong countries (Cambodia, China/Yunnan, Lao PDR, Myanmar, Thailand, Viet Nam) for the six-year period 1999-2001. The objective is to generate a more comprehensive regional perspective in what is a global epicenter of drug resistant falciparum malaria, in order to improve malaria control on a regional basis in the context of social and economic change. The further application of geographical information systems (GIS) to the analysis has underscored the overall asymmetry of disease patterns in the region, with increased emphasis on population mobility in disease spread. Of great importance is the continuing expansion of resistance of P. falciparum to antimalarial drugs in common use and the increasing employment of differing drug combinations as a result. The variation in drug policy among the 6 countries still represents a major obstacle to the institution of region-wide restrictions on drug misuse. An important step forward has been the establishment of 36 sentinel sites throughout the 6 countries, with the objective of standardizing the drug monitoring process; while not all sentinel sites are fully operational yet, the initial implementation has already given encouraging results in relation to disease monitoring. Some decreases in malaria mortality have been recorded. The disease patterns delineated by GIS are particularly instructive when focused on inter-country distribution, which is where more local collaborative effort can be made to rationalize resource utilization and policy development. Placing disease data in the context of socio-economic trends within and between countries serves to further identify the needs and the potential for placing emphasis on resource rationalization on a regional basis. Despite the difficulties, the 6-year time frame represented in this monograph gives confidence that the now well established collaboration is becoming a major factor in improving malaria control on a regional basis and hopefully redressing to a substantial degree the key problem of spread of drug resistance regionally and eventually globally.