Detection of signals of abuse and dependence applying disproportionality analysis.

INTRODUCTION: Prescription drug abuse and dependence is a widespread phenomenon in many countries. The use of disproportionality measures in drug abuse surveillance is rarely performed. PURPOSE: The aim of this study is to determine the occurrence of signals of abuse and dependence for different psychoactive drugs in real-life settings. METHODS: Disproportionality analysis was realised from a database specifically constructed for the monitoring of drug abuse and dependence. This database provides information on approximately 5000 patients and 8000 consumption modalities for more than 100 distinct psychoactive medications for 2010 and 2011. Proportional reporting ratio (PRR) was computed in two population groups: subjects under an opiate maintenance treatment (OMT) versus those not under OMT, and focused on four types of behaviours: abuse and dependence, illegal acquisition, diverted route of administration and concomitant alcohol use. RESULTS: Among the 100 psychoactive drugs for which a signal could be detected, those presenting the highest signals were the following: flunitrazepam, clonazepam, methylphenidate, ketamine, morphine sulfate, codeine and buprenorphine. CONCLUSIONS: The present study shows an innovative application of disproportionality measures for drug abuse monitoring based on two cross-national, annual studies. The disproportionality analysis provided the opportunity to reveal and compare the magnitude of signals between 100 psychoactive drugs. This approach helps to compare the magnitude of abuse and dependence behaviours for a large number of drugs, and allows prioritizing actions in a context where such events are usually underreported.

[Cost-effectiveness of drugs modifications for inpatients hospitalised in acute care geriatric units]. / Impact de la modification des prescriptions chez les sujets âgés hospitalisés en service de court séjour gériatrique en termes de coût.

PURPOSE: Polypharmacy in the elderly increases the risk of adverse drug reactions and leads to increased medical costs. There is little data currently available on drug modification and cost reduction during hospitalization in a geriatric unit. The aims of this study were to analyse drug modification during hospitalization in a geriatric care unit and to evaluate the repercussions in terms of cost reduction. METHODS: This monocentric study included 691 patients over a period of 3.5 years. The drugs and their daily costs were counted and classified (10 classes, 37 subclasses) upon admission and upon discharge. The modifications in the number of drugs in each class and subclass, as well as their costs, were analysed. Predictive factors in drug modification between admission and discharge were investigated. RESULTS: Our study showed a significant decrease in the number of drugs (mean ± standard error [SE], 5.2±0.11 to 4.5±0.07), as well as in the daily medical costs (4.4±0.18 to 3.67±0.12 €) between admission and discharge. The higher the number of drugs was upon admission, the greater the reduction was upon discharge. Cardiovascular, metabolic, analgesic and pulmonary drugs were significantly reduced, whereas gastrointestinal and anti-osteoporotic treatments increased. Diabetes, adverse drug events and the one-leg balance were predictive factors in drug modification. CONCLUSION: Hospitalization in a geriatric unit allows a re-evaluation of drug management with a significant reduction in the number and cost of treatments between admission and discharge. Given the multiple consequences of polypharmacy and its serious financial impact, research to develop optimal care of the elderly and to improve medication intervention is warranted.

Estimated magnitude of diversion and abuse of opioids relative to benzodiazepines in France.

INTRODUCTION: Prescription drug abuse is a major concern in several countries. France appears to be particularly prone to the abuse of opiate maintenance treatment (OMT) opioids and benzodiazepines (BZD), whereas the abuse of opioid analgesics (OA) is less commonly reported. To estimate the extent of psychoactive drug abuse, the French drug agency relies on different methods measuring various diversion indicators used as proxies for the detection of abuse/misuse: suspicion of abuse/dependence, illegal acquisition by patients seen in specialized care centers, prescription forgery and doctor shopping. The main objectives of the present study are to analyse the abuse and diversion of opioids (both OA and OMT), in comparison with those of BZDs, through the concurrent use of three different data sources. METHODS: Diversion and abuse of opioids were analysed using indicators of abuse and diversion derived from three data sources over the period 2006-2008. Then, opioids were compared to BZDs for the year 2008 using the same indicators. RESULTS: The analysis suggests that BZDs are more commonly dispensed than OAs and OMTs but that abuse and diversion are related mainly to OMT (particularly to buprenorphine), morphine and BZDs and less to OAs (except for morphine). CONCLUSION: This study presents an original approach, based on the use of multiple data sources, to evaluate and compare the estimated abuse and diversion of opioids and benzodiazepines. It provides health authorities with a global, comparative and summarized overall view of the importance of different patterns of diversion and abuse for different prescription drugs.

[Analysis of addictive behaviours among new prisoners in France using the OPPIDUM program]. / Evaluation des conduites addictives chez les personnes entrant en milieu pénitentiaire à partir du programme OPPIDUM du réseau des centres d'évaluation et d'information sur la pharmacodépendance (CEIP).

INTRODUCTION: The data on consumption of psychoactive substances among new prisoners are documented but not detailed with precision. Nevertheless, analyzing the consumption's characteristics of psychoactive products would led to a better caring of subjects at the entry in the prison. The consumption of psychoactive drugs the week before the imprisonments of subjects seen in prison were studied from the Observation of Illegal Drugs and Misuse of Psychotropic Medications (OPPIDUM) program's between 2003 and 2006. These were compared to those of others subjects with an history of abuse/dependence or under an opiate maintenance therapy presented in other structures of care. METHODS: OPPIDUM is an annual cross-sectional national study, repeated each year in October since several years. It is based on the Network of the Centres for Evaluation and Information on Pharmacodependence (CEIP) which recruits, via the medical system (drug users outpatient care centers, psychiatric units, drug-addict units...), subjects presenting a drug dependency or benefiting of an opiate maintenance treatment. RESULTS: During the four years between (2003 to 2006), 13,008 subjects were included. Seven percent (n=893) of them were in prison. They are younger and present worse social-economical indicators compared to the others subjects seen in other structures of care. In comparison to other subjects, the prisoners consume more products, more illicit ones and more benzodiazepines like flunitrazepam and clonazepam before their imprisonment. The medicines are consumed with higher doses and are more often obtained illegally (35% vs 14%). These subjects are less often under an opiate maintenance therapy (51% vs 74%). Between 2003 and 2006 the consumption of cocaine, increased from 18% to 28% for the patients before their confinement and from 11% to 21% for the heroine. Nevertheless, the consumption of benzodiazepines have decreased passing from 41% to 25%; and the consumption and of opiate maintenance treatment taken out of a protocol have decreased from 11% to 4%. DISCUSSION: This study underlines the specificity of the characteristics of consumption of psychotropic drugs before the imprisonment of the subjects with history of abuse/dependence or under an opiate maintenance therapy by report to consumers presented in other structures of care. It outlines the need to optimize the care by a better knowledge of the consumption of psychoactive products.

[Medical abortion at home and at hospital: a trial of efficacy and acceptability]. / Interruption volontaire de grossesse médicamenteuse à domicile et à l'hôpital : étude d'efficacité et d'acceptabilité

OBJECTIVES: To evaluate the efficacy and the acceptability of medical abortion at home and at hospital. PATIENTS AND METHODS: From 11 February 2008 to 16 July 2008, 399 patients were included in the study: 173 at home and 226 at hospital. RESULTS: Efficacy was evaluated for 305 patients because 94 were lost of follow-up (23.6%). Efficacy of medical abortion was 86.7% (124/143) at home and 95.8% (155/162) at hospital. There were one ongoing pregnancy and 25 surgical aspirations (8.6%). The family planning nurse received a phone call from five patients after mifepristone at home (2.9%) and seven patients after mifepristone at hospital (3.1%). Only one patient "at home" had an emergency consultation (0.6%) and nine patients "at hospital" (4%). Ten patients went back to their gynecologist before their appointment for follow-up (2.5%): five "at home" (2.9%) and five "at hospital" (2.2%). Thirteen patients were referred by the private provider to the hospital medical specialist. Acceptability is known for 70.2% of patients: 98% thought that medical abortion at home was acceptable and 92.9% at hospital. DISCUSSION AND CONCLUSION: The failure rate of medical abortion is higher at home and is due to aspirations for incomplete abortion. The procedure at home seems to be more acceptable than at hospital. It will be interesting to realize a prospective randomized study to compare the procedures at home and at hospital.

[Adverse drug events in hospitalized elderly patients in a geriatric medicine unit: study of prevalence and risk factors]. / Accidents iatrogènes médicamenteux chez le sujet âgé hospitalisé en court séjour gériatrique : étude de prévalence et des facteurs de risques.

INTRODUCTION: In the elderly, both the presence of a multiple pathology and multiple medication have been shown to be frequent risk factors for adverse drug events. However, a few studies only have included parameters of standardized geriatric assessment for the purpose of identifying other risk factors. Our study compared the parameters of standard geriatric assessment, in the presence or absence of adverse drug events and evaluated the prevalence of adverse drug events in elderly inpatients, the symptoms, and the drugs involved. METHODS: A total of 823 patients were studied during a two-year period. Two groups of patients were identified, according to the presence or absence of an adverse drug event. Eight fields of geriatric assessment were compared: comorbidities, number of drugs, functional status, nutritional status, mobility, mood, neurosensory disorders, and cognition. For patients who experienced an adverse drug event, we also analyzed the drugs involved and the symptoms of the adverse drug events. RESULTS: One hundred and twelve patients (13.6%) aged 82 years+/-7.5 experienced 144 adverse drug events. Significant differences between the two groups were observed in the following: symptoms of depression, problems of mobility, risk of malnutrition (respectively p=0.001, p=0.002, p=0.007), the female sex, number of drugs, number of comorbidities, and the administration of diuretics. Cardiovascular (23.2%), psychotropic (17.9%) and anti-infectious (17%) medicines were the most frequently involved. The symptoms that occurred most frequently were orthostatic hypotension (14.6%), gastrointestinal disorders (12.5%), and neuropsychological (10.4%) disorders. CONCLUSION: Elderly patients with multiple pathology and multiple medication are at high risk for adverse drug events. Other lesser known factors, such as depression, problems of mobility, and malnutrition must be researched, as they are evidence of the underlying the frailty of the elderly population.

[Estimation of the glomerular filtration rate in elderly inpatients: comparison of four methods]. / Quelle méthode d'évaluation de la fonction rénale utiliser chez le sujet âgé hospitalisé en unité de court séjour gériatrique ? Comparaison de quatre méthodes.

PURPOSE: High variability has been observed in the estimation of the glomerular filtration rate (GFR) in older patients, according to the formula used and no single formula has been recommended to date. The aim of this study was to quantify the precision and accuracy of the GFR estimated by means of three formulas and the measurement of cystatin C. METHODS: This prospective study was conducted in an acute care geriatric unit. Participants were patients, aged 70 years and over, having a possible 24-hour urine collection. The GFR was estimated using the Cockroft-Gault (CG), the Modification of Diet in Renal Disease (MDRD), and the Creatinine Clearance (Cl-Cr) formulas. The serum level of cystatin C was also measured. RESULTS: Eighty-one patients were included in the study. CG formula underestimated the GFR by a mean difference of 8.65 ml/min, compared with MDRD formula. Cl-Cr underestimated the GFR by a mean difference of 7.56 ml/min, compared with CG formula, and by a mean difference of 16.79 ml/min, compared with the MDRD formula. The degree of discrepancy between CG and Cl-Cr estimates, and between Cl-Cr and MDRD estimates decreased as the estimated GFR approached normal values. MDRD best matched the measurement of cystatin C, followed by CG and Cl-Cr (Kappa coefficient=0.43, 0.22 and 0.16, respectively). CONCLUSION: Our study confirms the high variability of GFR in older patients and particularly in those with abnormal renal function, depending on the formula used. Serum cystatine C level and MDRD formula appear to be the most concordant estimates of GFR in this population.

Impact of blood transfusions on outcome after pneumonectomy for thoracic malignancies.

The aim of the present study was to determine the risk factors and impact on outcome of blood transfusions following pneumonectomy for thoracic malignancies. A retrospective analysis of 432 consecutive patients was carried out, of whom 183 (42.4%) were transfused post-operatively. The associations between blood transfusions and 20 variables were assessed by univariate and multivariate analysis. Survival analysis included log-rank test and Cox regression model. Patient age, neoadjuvant treatment, completion pneumonectomy and extended procedures were independent predictors of transfusion. It was found that 30-day mortality increased significantly from 2.4% (no transfusion) to 10.9 and 21.9% (2 red blood cell packs, respectively). Blood transfusion was the strongest predictor of 30-day mortality (odds ratio (OR) 10; 95% confidence interval (CI): 3.7-27), respiratory failure (OR 19.2; 95% CI 7.4-49.4) and infectious complications (OR 3; 95% CI 1.5-6.2). In the 367 lung cancer patients, a significantly lower 5-yr survival was observed in univariate analysis of transfused patients (27.8+/-5.4% versus 39.4+/-4.5%). In a Cox regression analysis, blood transfusion was no longer found to be significant. A dose-related correlation is suggested between blood transfusion and early mortality through an increase of infectious and respiratory complications. In contrast, blood transfusion had no independent adverse impact on long-term survival.

[Phase III randomised trial of adjuvant chemotherapy with cisplatin plus docetaxel versus cisplatin plus gemcitabine in resected non-small cell bronchial carcinoma with quality of life as the primary objective]. / Essai randomisé de phase III de chimiothérapie adjuvante par CDDP/docetaxel versus CDDP/gemcitabine dans les cancers bronchiques non à petites cellules réséqués avec la qualité de vie comme objectif principal.

BACKGROUND: Adjuvant chemotherapy improves survival of completely resected non-small cell lung cancer (NSCLC). However the regimen of choice is not yet defined. METHODS: The primary objective of this comparative, open, randomised multicentre trial is to compare two chemotherapy regimens (cisplatin/docetaxel versus cisplatin/gemcitabine) in the management of resected NSCLC with quality of life (QoL) evaluated at the end of treatment as the primary objective. The secondary objectives are to study the impact of these two chemotherapy regimens on overall and relapse free survival, hematological and non-hematological toxicities, and costs. The primary judgement criterion will be the assessment of end of treatment QoL by the standardised questionnaire, EORTC QLQ-C30. Secondary judgement criteria will be Qol measured by EORTC QLQ-LC13 and SF36, overall and relapse free survival, tolerance and costs. The number of subjects needed is 75 in each group, 150 in total, to detect a difference of 10 points on the EORTC QLC-C30 scores with a standard error of 20 points (alpha 0.05; power 80%). EXPECTED RESULTS: This trial will provide clinicians with data on the impact of two currently unexplored adjuvant chemotherapy regimens on quality of life, tolerance and costs in NSCLC.

Standardization and quality control studies of 'real-time' quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia - a Europe Against Cancer program.

Detection of minimal residual disease (MRD) has proven to provide independent prognostic information for treatment stratification in several types of leukemias such as childhood acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and acute promyelocytic leukemia. This report focuses on the accurate quantitative measurement of fusion gene (FG) transcripts as can be applied in 35-45% of ALL and acute myeloid leukemia, and in more than 90% of CML. A total of 26 European university laboratories from 10 countries have collaborated to establish a standardized protocol for TaqMan-based real-time quantitative PCR (RQ-PCR) analysis of the main leukemia-associated FGs within the Europe Against Cancer (EAC) program. Four phases were scheduled: (1) training, (2) optimization, (3) sensitivity testing and (4) patient sample testing. During our program, three quality control rounds on a large series of coded RNA samples were performed including a balanced randomized assay, which enabled final validation of the EAC primer and probe sets. The expression level of the nine major FG transcripts in a large series of stored diagnostic leukemia samples (n=278) was evaluated. After normalization, no statistically significant difference in expression level was observed between bone marrow and peripheral blood on paired samples at diagnosis. However, RQ-PCR revealed marked differences in FG expression between transcripts in leukemic samples at diagnosis that could account for differential assay sensitivity. The development of standardized protocols for RQ-PCR analysis of FG transcripts provides a milestone for molecular determination of MRD levels. This is likely to prove invaluable to the management of patients entered into multicenter therapeutic trials.

Analysis of donor NK and T cells infused in patients undergoing MHC-matched allogeneic hematopoietic transplantation.

We retrospectively analyzed the percentages and absolute numbers of T cells, natural killer (NK) cells and NK cell subsets in cryopreserved samples of either bone marrow or blood non-T cell-depleted allogeneic MHC-matched hematopoietic grafts. Using flow cytometry, we found higher numbers of NK cells in aphereses than in bone marrow collections. We further investigated the distribution of NK cell subsets, defined by the cell surface expression of MHC class I-specific receptors, in these allogeneic grafts. The distribution of NK cell subsets from the two different origins were similar, with the exception of the CD158a/h(+) NK cell subset, whose size appeared to be smaller in bone marrow. The search for relations between the numbers of infused cells and post-transplantation events demonstrated that increasing numbers of infused T cells but not NK cells are related with decreased overall survival. Our study highlights the toxicity of infused T cells but not NK cells in allogeneic MHC-matched hematopoietic grafts. These data pave the way for further trials to investigate the effect of NK cell infusion in MHC-matched allogeneic transplantation, and in particular whether ex vivo NK cell expansion and activation may enhance the anti-tumoral effect of the procedure and decrease its morbidity.

VATS is an adequate oncological operation for stage I non-small cell lung cancer.

OBJECTIVES: This study was designed to determine the long-term prognosis of video-assisted thoracic surgery (VATS) vs. open lung resections for patients with pathological stage I non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The medical records of all patients who underwent lung resection for a pathological stage I NSCLC were reviewed for the period from 1990 to 1999, by screening of a database into which data were entered prospectively. There were 511 patients (430 males and 81 females) whose age averaged 63+/-10 years who underwent 515 lung resections. Our VATS experience began in 1993 with selected stage I patients, and since that date an average of one patient on four was managed with VATS. Lung resections consisted of 25 wedge resections or segmentectomies (seven VATS), 390 lobectomies (92 VATS), 19 bilobectomies (one VATS) and 81 pneumonectomies (ten VATS). Lymph node dissection was performed in all cases. RESULTS: There were significantly more females (P=0.01) and adenocarcinoma (P=0.02) in the VATS group (n=110) when compared to the open group (n=405). Tumour size averaged 4+/-2 cm in the open group and 3+/-2 cm in the VATS group (P=0.04). The distribution of T1/T2 tumours was 97/308 and 50/60, respectively (P=0.0001). At follow-up, cancer recurrence could be documented in 117 patients, with no difference of incidence between the two groups (22.5 vs. 24.5%; P=0.64). Estimated Kaplan-Meier 5-year survival rates, including the operative mortality as well as any cancer-related and unrelated death, were 62.8% (confidence interval (CI): 56.8-68.7%) vs. 62.9% (CI: 51.4-74.4%), respectively (P=0.60). The advent of VATS did not influence the patients' survival: 5-year survival rate was 63.9% (CI: 55.3-72.5%) for the period from 1990 to 1992, and 58.8% (CI: 51.7-65.9%) for the period from 1993 to 1999 (P=0.65). Subgroups survival analysis according to the T status did not show any statistically significant difference between the two groups. CONCLUSIONS: VATS lung resection with lymph node dissection achieved a 5-year survival similar to that achieved by the conventional approach. VATS is a valuable option for the management of selected patients with an early-stage NSCLC.

Increased soluble p55 and p75 tumour necrosis factor-alpha receptors in patients with hepatitis C-associated mixed cryoglobulinaemia.

To investigate whether tumour necrosis factor alpha (TNFalpha) plays a role in the pathogenesis of hepatitis C virus-associated mixed cryoglobulinaemia (HCV-MC), we measured soluble TNFalpha and its soluble p55 (sTNFR1) and p75 (sTNFR2) receptors in the serum of patients with HCV-MC. TNFalpha, sTNFR1 and sTNFR2 were measured in the serum of 32 patients with HCV-MC, 18 patients with hepatitis C without MC (HCV) and 18 healthy volunteers, using specific immunoassays. Correlations between clinical and biological parameters and the concentrations of TNFalpha and sTNFRs were established by studying detailed clinical records of the 32 HCV-MC patients. Although higher, TNFalpha levels were not significantly different in HCV-MC patients compared with healthy or HCV controls. sTNFR1 and sTNFR2, however, were significantly higher in HCV-MC compared with controls or with HCV patients, and higher concentrations of sTNFR1 and sTNFR2 were observed in patients with severe visceral vasculitis, compared with patients with limited purpura. sTNFR1 concentrations positively correlated with fibrinogen levels but TNFalpha, sTNFR1 and sTNFR2 did not correlate with other biological parameters such as rheumatoid factor concentrations, CH50 or C4 values. These data suggest a role for TNFalpha in the pathogenesis of the immune complex-mediated vasculitis associated with HCV-MC.

Buprenorphine prescription by general practitioners in a French region.

Since 1996 French general practitioners (GPs) may prescribe sublingual buprenorphine tablets as maintenance treatment for opiate dependence. The computerised data management of the main French health reimbursement system now allows surveillance of the use of this drug, and how it is prescribed. The purpose of this study is to determine the profile of maintained patients, prescribed doses, associated psychotropic treatments and how practitioners prescribe these treatments. This study analyses the 11186 buprenorphine prescriptions electronically transmitted for reimbursement between September and December 1999 in a specific French region. It was found that the 2078 treated patients consumed a mean of 11.5 mg of buprenorphine per day and 12% of them procured prescriptions from more than two prescribers. 43% of maintained patients had an associated benzodiazepine prescription, mainly flunitrazepam, often on the same prescription form. 61% of patients had regular follow-up, others had occasional consultations (21%) and another 18% had deviant maintenance treatment (more than two prescribers or more than 20 mg per day of daily buprenorphine dose). Benzodiazepine consumption was much higher in the 'deviant group' (71.4%). 85% of buprenorphine prescriptions were made by GPs. 21% of GPs prescribed buprenorphine and 61% of those had only one or two maintained patients. Buprenorphine prescription by French GPs is a procedure with no particular requirements, allowing many patients to easily access maintenance treatments. However, a high risk of abuse exists, which demands extensive investigation and evaluation of these practices.

Comparison of methadone and high dosage buprenorphine users in French care centres.

AIMS: In France, maintenance programmes for opiate users were adopted later than in other countries. Two maintenance treatments are available: methadone is only delivered in specialized centres while high dosage (HD) buprenorphine can be prescribed by all general practitioners and in specialized centres. The aim of this study was to compare the socio-demographic profiles, the practices and drug consumption patterns of the two groups attending specialized centres. METHODOLOGY: The Oppidum Programme (observation of illegal drugs and misuse of psychotropic medications), a multi-centric survey, surveys drug-dependent subjects attending specialized care centres throughout France annually. Data were collected by questionnaire on socio-demographic variables and drug use during the preceding week. RESULTS: During October 1998, 46 centres took part in the survey. The methadone group (n = 424) was older, with a better economic situation; 16% used cocaine regularly. The HD buprenorphine group (n = 616) consumed more heroin (12% vs. 8%) and engaged in more misuse, such as intravenous use, illicit acquisitions or irregular consumption. These practices were more frequent for patients consuming the drug "outwith protocol" or for patients obtaining the drug from a general practitioner. CONCLUSION: Our results suggest that patterns of consumption of methadone and buprenorphine are different in several respects: concomitant use of licit or illicit psychoactive substances, route of administration, and illegal acquisition. They also suggest that the behaviours of maintenance treatment users depend less on the nature of the maintenance drug (methadone or high dosage buprenorphine), than the nature of the delivery and monitoring practices.

Is a short trial of prone positioning sufficient to predict the improvement in oxygenation in patients with acute respiratory distress syndrome?

OBJECTIVE: To determine whether a 1-h trial of prone positioning is sufficient to identify responders. DESIGN: Prospective clinical cohort study in a medico-surgical ICU in a teaching hospital. PATIENTS: 49 patients with acute respiratory distress syndrome. INTERVENTIONS: A 6-h period of prone positioning. MEASUREMENTS AND RESULTS: Baseline measurements (blood gas analysis and respiratory parameters) were evaluated in supine position just prior to turning the patients prone. Measurements were then repeated 1 h after the beginning of prone positioning (PP1h) and at the end of the 6-h period of prone positioning (PP6h). The last measurements were performed 1 h after repositioning the patients supine. Prone position induced an increase in the PaO2/FIO2 ratio (p < 0.001). A response (increase in PaO2/FIO2 ratio of at least 20 % at PP1h and/or at PP6h) was observed in 37 of 49 patients (76%). Twenty-seven of these patients (73%) were responders at PP1h while 10 (27%) were responders only at PP6h- In all, two-thirds of the patients were considered persistent responders. However, whereas the PaO2/FIO2 ratio decreased significantly 1 h after repositioning the fast responders supine, the PaO2/ FIO2 ratio remained unchanged after repositioning slow responders. CONCLUSIONS: A short-term trial of prone positioning does not appear a sufficient method to identify patients who would benefit from the postural treatment.

Postoperative complications in relation with induction therapy for lung cancer.

OBJECTIVES: The purpose of this study was to evaluate the risk of lung cancer surgery following induction chemotherapy and/or radiotherapy. METHODS: This retrospective study included 69 patients treated from January 1990 to January 1998 for a primary lung cancer in whom surgery had been performed after induction treatment. Surgery had not been considered initially for the following reasons: N2 disease (IIIA, n = 25); temporary functional impairment (two stages IB and two stages IIIA (N2), n = 4); and doubtful resectability (stage IIIB (T4), n = 40). The medical regimen resulted in combined radio-chemotherapy in 43 patients who received two to four cycles of chemotherapy (average 2.9 +/- 0.8 cycles) and 43 +/- 8 Gy (range 20--60 Gy), or chemotherapy alone in 26 patients (3 +/- 0.7 cycles). RESULTS: Exploratory thoracotomy was performed in four patients (6%). The in-hospital mortality was 9% (n = 6) from respiratory origin in all cases. There were four re-operations (6%): three for bronchial fistula and one for bleeding. Thirty-five patients (51%) required blood transfusion (4.5 +/- 3.8 cell packs). The incidence of early and delayed bronchial fistula after pneumonectomy was 15%. Thirteen patients had a postoperative pneumonia (19%). CONCLUSIONS: Surgery for lung cancer after induction chemotherapy and/or radiotherapy is associated with an increased risk. If the mortality seems 'acceptable', the morbidity rate, however, is high.

Is ventilator-associated pneumonia an independent risk factor for death?

BACKGROUND: Ventilator-associated pneumonia (VAP) has been implicitly accused of increasing mortality. However, it is not certain that pneumonia is responsible for death or whether fatal outcome is caused by other risk factors for death that exist before the onset of pneumonia. The aim of this study was to evaluate the attributable mortality caused by VAP by performing a matched-paired, case-control study between patients who died and patients who were discharged from the intensive care unit after more than 48 h of mechanical ventilation. METHODS: During the study period, 135 consecutive deaths were included in the case group. Case-control matching criteria were as follows: (1) diagnosis on admission that corresponded to 1 of 11 predefined diagnostic groups; (2) age difference within 10 yr; (3) sex; (4) admission within 1 yr; (5) APACHE II score within 7 points; (6) ventilation of control patients for at least as long as the cases. Precise clinical, radiologic, and microbiologic definitions were used to identify VAP. RESULTS: Analysis was performed on 108 pairs that were matched with 91% of success. There were 39 patients (36.1%) who developed VAP in each group. Multivariate analysis showed that renal failure, bone marrow failure, and treatment with corticosteroids but not VAP were independent risk factors for death. There was no difference observed between cases and controls concerning the clinical and microbiologic diagnostic criteria for pneumonia. CONCLUSION: Ventilator-associated pneumonia does not appear to be an independent risk factor for death.