Evaluating prophylactic heparin in ambulatory patients with solid tumours: a systematic review and individual participant data meta-analysis.

BACKGROUND: Study-level meta-analyses provide high-certainty evidence that heparin reduces the risk of symptomatic venous thromboembolism for patients with cancer; however, whether the benefits and harms associated with heparin differ by cancer type is unclear. This individual participant data meta-analysis of randomised controlled trials examines the effect of heparin on survival, venous thromboembolism, and bleeding in patients with cancer in general and by type. METHODS: In this systematic review and meta-analysis we searched MEDLINE, Embase, and The Cochrane Library for randomised controlled trials comparing parenteral anticoagulants with placebo or standard care in ambulatory patients with solid tumours and no indication for anticoagulation published from the inception of each database to January 14, 2017, and updated it on May 14, 2020, without language restrictions. We calculated the effect of parenteral anticoagulant administration on all-cause mortality, venous thromboembolism occurrence, and bleeding related outcomes through multivariable hierarchical models with patient-level variables as fixed effects and a categorical trial variable as a random effect, adjusting for age, cancer type, and metastatic status. Interaction terms were tested to investigate effects in predefined subgroups. This study is registered with PROSPERO, CRD42013003526. FINDINGS: We obtained individual participant data from 14 of 20 eligible randomised controlled trials (8278 [79%] of 10 431 participants; 4139 included in the low-molecular-weight heparin group and 4139 in the control group). Meta-analysis showed an adjusted relative risk (RR) of mortality at 1 year of 0·99 (95% CI 0·93-1·06) and a hazard ratio of 1·01 (95% CI 0·96-1·07). The number of patients with venous thromboembolic events was 158 (4·0%) of 3958 with available data in the low-molecular-weight heparin group compared with 279 (7·1%) of 3957 in the control group. Major bleeding events occurred in 71 (1·7%) of 4139 patients in the control population and 88 (2·1%) in the low-molecular-weight heparin group, and minor bleeding events in 478 (12·1%) of 3945 patients with available data in the control group and 652 (16·6%) of 3937 patients in the low-molecular-weight heparin group. The adjusted RR was 0·58 (95% CI 0·47-0·71) for venous thromboembolism, 1·27 (0·92-1·74) for major bleeding, and 1·34 (1·19-1·51) for minor bleeding. Prespecified subgroup analysis of venous thromboembolism occurrence by cancer type identified the most certain benefit from heparin treatment in patients with lung cancer (RR 0·59 [95% CI 0·42-0·81]), which dominated the overall reduction in venous thromboembolism. Certainty of the evidence for the outcomes ranged from moderate to high. INTERPRETATION: Low-molecular-weight heparin reduces risk of venous thromboembolism without increasing risk of major bleeding compared with placebo or standard care in patients with solid tumours, but it does not improve survival. FUNDING: Canadian Institutes of Health Research.

The Khorana score for prediction of venous thromboembolism in cancer patients: An individual patient data meta-analysis.

BACKGROUND: Oncology guidelines suggest using the Khorana score to select ambulatory cancer patients receiving chemotherapy for primary venous thromboembolism (VTE) prevention, but its performance in different cancers remains uncertain. OBJECTIVE: To examine the performance of the Khorana score in assessing 6-month VTE risk, and the efficacy and safety of low-molecular-weight heparin (LMWH) among high-risk Khorana score patients. METHODS: This individual patient data meta-analysis evaluated (ultra)-LMWH in patients with solid cancer using data from seven randomized controlled trials. RESULTS: A total of 3293 patients from the control groups with an available Khorana score had lung (n = 1913; 58%), colorectal (n = 452; 14%), pancreatic (n = 264; 8%), gastric (n = 201; 6%), ovarian (n = 184; 56%), breast (n = 164; 5%), brain (n = 84; 3%), or bladder cancer (n = 31; 1%). The 6-month VTE incidence was 9.8% among high-risk Khorana score patients and 6.4% among low-to-intermediate-risk patients (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.2). The dichotomous Khorana score performed differently in lung cancer patients (OR 1.1; 95% CI, 0.72-1.7) than in the group with other cancer types (OR 3.2; 95% CI, 1.8-5.6; Pinteraction  = .002). Among high-risk patients, LMWH decreased the risk of VTE by 64% compared with controls (OR 0.36; 95% CI, 0.22-0.58), without increasing the risk of major bleeding (OR 1.1; 95% CI, 0.59-2.1). CONCLUSION: The Khorana score was unable to stratify patients with lung cancer based on their VTE risk. Among those with other cancer types, a high-risk score was associated with a three-fold increased risk of VTE compared with a low-to-intermediate risk score. Thromboprophylaxis was effective and safe in patients with a high-risk Khorana score.

Use of heparins in patients with cancer: individual participant data meta-analysis of randomised trials study protocol.

INTRODUCTION: Parenteral anticoagulants may improve outcomes in patients with cancer by reducing risk of venous thromboembolic disease and through a direct antitumour effect. Study-level systematic reviews indicate a reduction in venous thromboembolism and provide moderate confidence that a small survival benefit exists. It remains unclear if any patient subgroups experience potential benefits. METHODS AND ANALYSIS: First, we will perform a comprehensive systematic search of MEDLINE, EMBASE and The Cochrane Library, hand search scientific conference abstracts and check clinical trials registries for randomised control trials of participants with solid cancers who are administered parenteral anticoagulants. We anticipate identifying at least 15 trials, exceeding 9000 participants. Second, we will perform an individual participant data meta-analysis to explore the magnitude of survival benefit and address whether subgroups of patients are more likely to benefit from parenteral anticoagulants. All analyses will follow the intention-to-treat principle. For our primary outcome, mortality, we will use multivariable hierarchical models with patient-level variables as fixed effects and a categorical trial variable as a random effect. We will adjust analysis for important prognostic characteristics. To investigate whether intervention effects vary by predefined subgroups of patients, we will test interaction terms in the statistical model. Furthermore, we will develop a risk-prediction model for venous thromboembolism, with a focus on control patients of randomised trials. ETHICS AND DISSEMINATION: Aside from maintaining participant anonymity, there are no major ethical concerns. This will be the first individual participant data meta-analysis addressing heparin use among patients with cancer and will directly influence recommendations in clinical practice guidelines. Major cancer guideline development organisations will use eventual results to inform their guideline recommendations. Several knowledge users will disseminate results through presentations at clinical rounds as well as national and international conferences. We will prepare an evidence brief and facilitate dialogue to engage policymakers and stakeholders in acting on findings. TRIAL REGISTRATION NUMBER: PROSPERO CRD42013003526.

A randomised trial comparing preoperative to perioperative chemotherapy in early-stage non-small-cell lung cancer (IFCT 0002 trial).

HYPOTHESIS: There will be a detectable increase in overall survival (OS) using preoperative (PRE) as opposed to perioperative (PERI) chemotherapy in resectable StageI-II non-small-cell lung cancer (NSCLC). METHODS: This multicenter, open-label, randomised trial with a 2×2 factorial design first compared two chemotherapy strategies (PRE versus PERI), then two chemotherapy regimens (gemcitabine-cisplatin [GP] versus paclitaxel-carboplatin [TC]). The PRE group received two preoperative cycles followed by two additional preoperative cycles, while the PERI group underwent two preoperative cycles followed by two postoperative cycles, the 3rd and 4th cycles being given only to responders in both cases. RESULTS: A total of 528 patients were randomised, 267 of which were assigned to the PRE group and 261 to the PERI group. Three-year OS did not differ between the two groups (67.4% and 67.7%, respectively; hazard ratio (HR)=1.01 [0.79-1.30], p=0.92), nor did 3-year disease-free survival, response rates, toxicity, or postoperative mortality. Pathological complete response was observed in 22 (8.2%) and 16 patients (6.1%), respectively. Although quality of life did not differ significantly, chemotherapy compliance was significantly higher in the PRE group. The proportion of responders who received Cycles 3 and 4 was significantly higher in the PRE group (90.4% versus 75.2%, p=0.001). In responders, the dose intensity of Cycles 3 and 4 was higher in the PRE group than in the PERI group (mean relative dose intensity of 90.4% versus 82.6%, respectively; p=0.0007). There was no difference between GP and TC in 3-year OS (HR=0.97 [95% confidence interval (CI): 0.76-1.25], p=0.80) or response rates. However, the regimens' toxicity profiles differed. CONCLUSIONS: This study failed to demonstrate any difference in survival between patients receiving preoperative and perioperative chemotherapy in early-stage NSCLC. The increase from two to four preoperative chemotherapy cycles did not increase the pathological response rate.

Optimization of small-cell lung cancer chemotherapy with heparin: a comprehensive retrospective study of 239 patients treated in a single specialized center.

PURPOSE: In first-line management for small-cell lung cancer (SCLC), the combination of a platinum salt and etoposide is recommended, with thoracic radiotherapy and prophylactic cranial irradiation in selected patients. Anticoagulants, including heparin, are rarely used. We analyzed the results of these different treatments in a comprehensive population of patients with SCLC. PATIENTS AND METHODS: We retrospectively analyzed clinical and therapeutic characteristics of SCLC patients managed in our center during the period 1990-2002. RESULTS: First-, second- and third-line chemotherapy was received by 98.3, 47.3 and 11.7%, respectively; 55% received curative heparin. The 2-year survival rates were 31 and 7% among patients with localized and metastatic disease, 33 and 15% among patients treated with the PCDE (cisplatin-cyclophosphamide-doxorubicin-etoposide) regimen with and without heparin, and 27 and 12% among patients treated with the PE (cisplatin or carboplatin-etoposide) regimen with and without heparin, respectively. The 2-year survival rate among the 27 patients who received an optimal combination of PCDE, heparin, thoracic radiotherapy and prophylactic cranial irradiation was 44.2%. In multivariate analysis, localized disease, younger age, use of heparin and inclusion in a clinical trial were independently associated with a better outcome. CONCLUSION: Despite the bias inherent in a retrospective, single-center study, these results support chemotherapy optimization for SCLC patients and confirm the value of heparin in this setting.

Randomized phase II trial of gefitinib or gemcitabine or docetaxel chemotherapy in patients with advanced non-small-cell lung cancer and a performance status of 2 or 3 (IFCT-0301 study).

BACKGROUND: To compare 3 treatment strategies in chemotherapy naive patients with advanced NSCLC and a PS 2-3. PATIENTS AND METHODS: Patients were assigned to gefitinib 250mg daily (n=43) or to gemcitabine (1250mg/m(2) d 1, 8 q 21d) (n=42) or docetaxel (75mg/m(2) d 1 q 21d) (n=42). Treatments were taken until progression or toxicity. The primary endpoint was progression-free survival. Secondary end points were response and overall survival. RESULTS: Disease control rates were 20.9%, 33.4% and 38.1%, respectively. Median PFS was 1.9 months in the gefitinib arm, 2.0 months in the gemcitabine arm and 2.0 months in the docetaxel arm (HR gemcitabine versus gefitinib: 0.74, 95%CI: [0.48; 1.16], HR docetaxel versus gefitinib: 0.67, 95%CI: [0.43; 1.05]). Median survival times were 2.2, 2.4 and 3.5 months, respectively (HR gemcitabine versus gefitinib: 0.76, 95%CI: [0.48; 1.20], HR docetaxel versus gefitinib: 0.69, 95%CI: [0.44; 1.09]). There were more grade 3-4 adverse events in the docetaxel arm when compared with either the gefitinib arm or the gemcitabine arm. CONCLUSION: In unselected NSCLC patients with PS 2-3, gefitinib, gemcitabine and docetaxel achieved similar results. Docetaxel was associated with higher rates of adverse events.

Oral second- and third-line lomustine-etoposide-cyclophosphamide chemotherapy for small cell lung cancer.

PURPOSE: There is no standard therapy for progressive or recurrent small cell lung cancer (SCLC). Lomustine, etoposide and cyclophosphamide oral chemotherapy were evaluated in a feasibility study of efficacy survival and toxicity. PATIENTS AND METHODS: 71 patients were included in this study, 36 in second-line and 35 in third-line chemotherapy. They received lomustine (CCNU) 80 or 120mg on D1 only, etoposide 100mg from D1 until D6 up to D14 and cyclophosphamide 100mg from D1 until D6 up to D14 every 4 weeks. The dosages of CCNU and duration of administration of the other two drugs were adapted to an original therapeutic risk level table on D1 and throughout treatment. Evaluation based on clinical status, response and weekly blood counts was performed before each cycle until progression. RESULTS: 70 patients were evaluable. They received between 1 and 20 cycles of treatment (mean=3.7 for second-line and 3.0 for third-line treatment). Complete responses were observed for 3 patients in each line, and partial responses were noted in 13 patients in second-line and 8 patients in third-line, resulting in a total response rate of 27/70=38%. Median-survival time estimated from the start of second- or third-line treatment was the same in the two subgroups: 4.4 months, but the patients in two subgroups presented different clinical characteristics. Haematological toxicity was severe with three toxic deaths as frequently observed in this setting, but hospitalisations were uncommon during this fully oral treatment that provided a very good quality of life for these out-patients. Consumption of health care resources for this low-cost and ambulatory treatment was limited. CONCLUSION: The similar efficacy with acceptable safety, the ease of administration in out-patients and the economical advantages justify comparison of this oral chemotherapy with conventional intravenous chemotherapy. A randomised phase II trial is on-going in France for second-line SCLC patients on this theme.

Lobectomy with pulmonary artery resection: morbidity, mortality, and long-term survival.

OBJECTIVE: We report our experience with 93 consecutive pulmonary artery reconstructions during pulmonary lobectomy with regard to morbidity, mortality, and long-term survival. METHODS: Clinical records of all patients who underwent lobectomy with partial or circumferential pulmonary artery resection in a single institution during an 8-year period were reviewed retrospectively. RESULTS: Lobectomy with partial (n = 90) or circumferential (n = 3) pulmonary artery resection was carried out in 93 patients. Indications for surgical intervention were non-small cell lung cancer in 87 patients and other malignancy in the remaining 6 patients. Bronchial sleeve resection was associated in 23 patients. Neoadjuvant chemotherapy had been administered in 34 cases because of cN2 disease. Operative mortality was 5.4%. Postoperative complications occurred in 27 (29.0%) patients. All the patients underwent contrast-enhanced computed tomographic scanning 6 to 8 weeks postoperatively, which always showed patency of the pulmonary arteries. In the whole population median and 5-year survivals were 40 months and 39.4%, respectively. Disease-free survival was 41.4% at 5 years. Among patients with non-small cell lung cancer, at univariate analysis, tumor size of less than 3 cm; presence of vascular peritumoral emboli, intratumoral emboli, or both; and dyspnea influenced 5-year survival. Multivariate analysis showed that the size of the primary tumor and the presence of vascular emboli were independent factors of worse outcome. CONCLUSIONS: Lobectomy with arterial sleeve resection has acceptable mortality and no specific complications. Late results in terms of survival are satisfactory.

Residual subjective daytime sleepiness under CPAP treatment in initially somnolent apnea patients: a pilot study using data mining methods.

BACKGROUND AND PURPOSE: Despite correct treatment with positive airway pressure (PAP), obstructive sleep apnea (OSA) patients sometimes remain subjectively somnolent. The reliability of the Epworth Sleepiness Scale (ESS) has been established for healthy subjects and patients under stable conditions; the ESS may eventually vary among treated OSA patients, biasing the results of a cross-sectional analysis of persisting sleepiness. The objective of this study was to depict the evolution of subjective vigilance under treatment using an index of ESS variability (DeltaESS). METHODS: In 80 OSA patients (apnea-hypopnea index [AHI]=54+/-26/h), initially somnolent (ESS=15+/-3) and treated with auto-titrating PAP (APAP) (oxyhaemoglobin desaturation index 3% [ODIapap]=3.4+/-2.2/h; daily APAP use=5.3+/-1.5 h) during 434+/-73 days, ESS scores were regularly collected four times every 109+/-36 days. DESS was calculated and data mining methods (Segmentation and Decision Tree) were used to determine homogeneous groups according to the evolution of ESS scores. RESULTS: When assessed cross-sectionally, 14-25% of the subjects were recognized as somnolent, depending on the moment when ESS was administered. Using data mining methods, three groups were clearly identifiable: two without residual somnolence - group 1, n=38 (47%), with high DeltaESS=-2.9+/-0.8, baseline ESS=16.3+/-3.3, AHI=58.5+/-26.1/h, mean ESSapap=5.1+/-2.4 and group 2, n=31 (39%), with low DeltaESS=-1.1+/-0.5, baseline ESS=13.2+/-1.4, AHI=53+/-27.3/h, mean ESSapap=8.8+/-1.9; and one with persisting sleepiness; group 3, n=11 (14%), with low DeltaESS=-0.3+/-0.8, baseline ESS=16.3+/-3, AHI=38.7+/-10.8/h, mean ESSapap=14.1+/-1.9. Compliance to PAP was high and comparable in the three groups. Age and body mass index (BMI) did not differ. CONCLUSION: Data mining methods helped to identify 14% of subjects with persisting sleepiness. Validation needs to be done on a larger population in order to determine predictive rules.

Complete response following preoperative chemotherapy for resectable non-small cell lung cancer: accuracy of clinical assessment using the French trial database.

BACKGROUND: Pathologic complete response (CR) to preoperative chemotherapy has been shown to be a strong prognostic factor in resected non-small cell lung cancer (NSCLC). This preoperative setting offers the opportunity to evaluate the clinical prediction of CR by investigators and an evaluation committee (EC) using the "gold standard" pathologic examination as the reference. The only published large randomized trial of preoperative chemotherapy (to our knowledge), the French neoadjuvant study, constitutes an interesting database to evaluate CT scan-based CR assessment. STUDY OBJECTIVES AND DESIGN: The French trial compared mitomycin-ifosfamide-cisplatin followed by surgery with surgery alone in stage I (except T1N0) to IIIa resectable NSCLC. Response was prospectively assessed in all patients receiving preoperative chemotherapy by the investigator in charge of the patient and by an EC, and was compared with pathologic postoperative data. RESULTS: In the preoperative chemotherapy study, 167 patients were operated on. Nineteen patients were found to have a pathologic CR. Only seven patients were classified as having a CR by investigators and five patients by the EC. Evaluation of CR was correct in six of these seven cases and in three of these five cases, respectively. Sensitivity of the CR diagnosis was 31.6% for investigators and 15.8% for the EC. Specificities of the CR diagnosis were 99.4% and 98.8%, respectively. Positive predictive values were 85.7% and 60%, respectively. Negative predictive values were 91.9% and 90.1%, respectively. Accuracies were 91.6% and 89.2%, respectively. CONCLUSION: Investigator assessment of CR was highly predictive of pathologic CR. However, this study showed that clinical CT scan-based assessment, whether performed by investigators or the EC, underestimated the frequency of CR after preoperative chemotherapy in resectable NSCLC.

Impact of computed tomography and 18F-deoxyglucose coincidence detection emission tomography image fusion for optimization of conformal radiotherapy in non-small-cell lung cancer.

PURPOSE: To report a retrospective study concerning the impact of fused 18F-fluoro-deoxy-D-glucose (FDG)-hybrid positron emission tomography (PET) and CT images on three-dimensional conformal radiotherapy planning for patients with non-small-cell lung cancer. METHODS AND MATERIALS: A total of 101 patients consecutively treated for Stage I-III non-small-cell lung cancer were studied. Each patient underwent CT and FDG-hybrid PET for simulation treatment in the same treatment position. Images were coregistered using five fiducial markers. Target volume delineation was initially performed on the CT images, and the corresponding FDG-PET data were subsequently used as an overlay to the CT data to define the target volume. RESULTS: 18F-fluoro-deoxy-D-glucose-PET identified previously undetected distant metastatic disease in 8 patients, making them ineligible for curative conformal radiotherapy (1 patient presented with some positive uptake corresponding to concomitant pulmonary tuberculosis). Another patient was ineligible for curative treatment because the fused PET-CT images demonstrated excessively extensive intrathoracic disease. The gross tumor volume (GTV) was decreased by CT-PET image fusion in 21 patients (23%) and was increased in 24 patients (26%). The GTV reduction was > or = 25% in 7 patients because CT-PET image fusion reduced the pulmonary GTV in 6 patients (3 patients with atelectasis) and the mediastinal nodal GTV in 1 patient. The GTV increase was > or = 25% in 14 patients owing to an increase in the pulmonary GTV in 11 patients (4 patients with atelectasis) and detection of occult mediastinal lymph node involvement in 3 patients. Of 81 patients receiving a total dose of > or = 60 Gy at the International Commission on Radiation Units and Measurements point, after CT-PET image fusion, the percentage of total lung volume receiving >20 Gy increased in 15 cases and decreased in 22. The percentage of total heart volume receiving >36 Gy increased in 8 patients and decreased in 14. The spinal cord volume receiving at least 45 Gy (2 patients) decreased. Multivariate analysis showed that tumor with atelectasis was the single independent factor that resulted in a significant effect on the modification of the size of the GTV by FDG-PET: tumor with atelectasis (with vs. without atelectasis, p = 0.0001). CONCLUSION: The results of our study have confirmed that integrated hybrid PET/CT in the treatment position and coregistered images have an impact on treatment planning and management of non-small-cell lung cancer. However, FDG images using dedicated PET scanners and respiration-gated acquisition protocols could improve the PET-CT image coregistration. Furthermore, the impact on treatment outcome remains to be demonstrated.

Chronic liver injury during obstructive sleep apnea.

Patients with obstructive sleep apnea (OSA) are at risk for the development of fatty liver as a result of being overweight. Several data suggest that OSA per se could be a risk factor of liver injury; ischemic hepatitis during OSA has been reported, and OSA is an independent risk factor for insulin resistance. Therefore, we investigated liver damage and potential mechanisms in 163 consecutive nondrinking patients with nocturnal polysomnographic recording for clinical suspicion of OSA. Serum levels of liver enzymes were measured in all patients. Liver biopsy was offered to patients with elevated liver enzymes. Intrahepatic hypoxia was assessed by the expression of vascular endothelial growth factor (VEGF) on liver biopsy specimens. Severe OSA (apnea-hypopnea index [AHI] > 50/hr) was seen in 27% of patients; 52% had moderate OSA (AHI 10-50/hr), and 21% had no OSA. Overall, 20% had elevated liver enzymes. Independent parameters associated with elevated liver enzymes were body mass index (BMI) (OR: 1.13; CI: 1.03-1.2) and severe OSA (OR: 5.9; CI: 1.2-29). Liver biopsy was performed in 18 of 32 patients with elevated liver enzymes and showed steatohepatitis in 12 cases, associated with fibrosis in 7 cases. Patients with severe OSA were more insulin-resistant according to homeostasis model assessment, had higher percentage of steatosis as well as scores of necrosis and fibrosis, despite similar BMI. Hepatic immunostaining used as an indirect marker of hypoxia was not different between patients with or without severe OSA. In conclusion, severe OSA is a risk factor for elevated liver enzymes and steatohepatitis independent of body weight. Promotion of insulin resistance is probably involved. Further studies are needed to determine whether hypoxia contributes directly to liver injury.

Mandibular advancement titration for obstructive sleep apnea: optimization of the procedure by combining clinical and oximetric parameters.

BACKGROUND: Oral appliances (OAs) have been used for the treatment of obstructive sleep apnea syndrome (OSAS), with different degrees of effectiveness having been shown in previous studies. But, in the absence of a consensual recommendation, the method of the determination of effective mandibular advancement varies from one study to another. STUDY OBJECTIVE: We prospectively evaluated an OA titration protocol based on a combined analysis of symptomatic benefit and oximetric recording to guide the progressive mandibular advancement. SETTING: University hospital sleep disorders center. PATIENTS: Forty patients with OSAS (mean [+/-SD] apnea-hypopnea index [AHI], 46 +/- 21 events per hour) found on baseline polysomnography, who were intolerant of nasal continuous positive airway pressure, completed all aspects of the study. METHODS: Two acrylic appliances connected by Herbst attachments were constructed. The mandible was advanced 1 mm every week until there was a resolution of the symptoms and a reduction in the oxygen desaturation index (ie, the number of desaturations yielding a > 3% fall in pulse oximetric saturation per hour of recording) [ODI] of <10 events per hour of recording or a maximum comfortable limit of advancement was obtained. The final response to OA was evaluated by full polysomnography recording. RESULTS: A complete response (ie, mean AHI, 5 +/- 3 events per hour; mean snoring reduction [SR], 91 +/- 13%; mean Epworth sleepiness scale [ESS] score, 5 +/- 3) was obtained in 63.6% of patients, and a limited response (ie, mean AHI, 21 +/- 11 events per hour; mean SR, 88 +/- 15%; mean ESS, 6 +/- 3) was obtained in 18.2% of patients. Twenty-five percent of mandibular advancements were motivated by an abnormal ODI (ie, 21 +/- 10 events per hour) despite resolution of the symptoms, while 20% were motivated by persistent symptoms with a normal ODI (ie, 6 +/- 2 events per hour). After a mean duration of 17 +/- 4 months, 34 patients declared that they had used the OA 5 +/- 2 days a week for 89 +/- 19% of their sleep time. CONCLUSIONS: A combination of the patient's subjective evaluation and oximetric score improves the effectiveness of the OA titration procedure.

[Mucoregulators in acute bronchitis syndromes: focus on use by general practitioners and data from the literature]. / Les mucorégulateurs dans les syndromes bronchiques aigus: point sur les pratiques en médecine générale et les données de la littérature.

Antibiotics have long been used in the initial treatment of acute bronchitis (AB) and acute exacerbations of chronic bronchitis (AECB). However, their lack of value in AB has been clearly demonstrated and antibiotic therapy is justified in only a few cases of AECB. In parallel, although the value of mucoregulators in these diseases is still debated, their prescription remains important in general practice. In this context, our aim was to determine the prescribing behaviour of general practitioners (GPs) with regard to these drugs, as well as the beliefs of GPs concerning the place of mucoregulators in the treatment of AB in children and adult smokers, as well as in patients with non-obstructive AECB. A survey was carried out in 370 GPs, who were presented with three standardised and computerised medical cases: (i) rhinopharyngitis + AB in a child; (ii) AB in an adult smoker without a previous medical history; and (iii) a patient with non-obstructive AECB. The results showed that mucoregulators are frequently prescribed by GPs for children and adults with AB, or in AECB. This high prescribing rate is due to the belief of the GPs that these drugs are effective and well tolerated, which is confirmed by the literature. Their use avoids the frequent and unjustified prescription of antibiotics in situations where they are not recommended but where the patients request drug therapy.

Eosinophilic lung disease under chemotherapy with oxaliplatin for colorectal cancer.

A 60-year-old woman with a history of unresectable colon adenocarcinoma was treated by chemotherapy with a combination of oxaliplatin with leucovorin and fluorouracil. Progressive dyspnea and bilateral pulmonary interstitial infiltrates developed. Bronchoscopy with bronchoalveolar lavage confirmed pulmonary eosinophilia. Clinical and radiologic aspects of eosinophilic lung disease cleared after cessation of this combination of chemotherapy and did not recur after reintroduction of leucovorin/fluorouracil alone, suggesting that oxaliplatin was the causative agent. Care was taken to rule out other possible causes for eosinophilic pneumonia.

Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer.

PURPOSE: To evaluate whether preoperative chemotherapy (PCT) could improve survival in resectable stage I (except T1N0), II, and IIIA non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A randomized trial compared PCT to primary surgery (PRS). PCT consisted of two cycles of mitomycin (6 mg/m(2), day 1), ifosfamide (1.5 g/m(2), days 1 to 3) and cisplatin (30 mg/m(2), days 1 to 3), and two additional postoperative cycles for responding patients. In both arms, patients with pT3 or pN2 disease received thoracic radiotherapy. RESULTS: Three hundred fifty-five eligible patients were randomized. Overall response to PCT was 64%. There were two preoperative toxic deaths. Postoperative mortality was 6.7% in the PCT arm and 4.5% in the PRS arm (P =.38). Median survival was 37 months (95% confidence interval [CI], 26.7 to 48.3) for PCT and 26.0 months (95% CI, 19.8 to 33.6) for PRS (P =.15). Survival differences between both arms increased from 3.8% (95% CI, 1.3% to 25.1%) at 1 year to 8.6% (95% CI, 2.64% to 24.4%) at 4 years. A quantitative interaction between N status and treatment was observed, with benefit confined to N0 to N1 disease (relative risk [RR], 0.68; 95% CI, 0.49 to 0.96; P =.027). After a nonsignificant excess of deaths during treatment, the effect of PCT was significantly favorable on survival (RR, 0.74; 95% CI, 0.56 to 0.99; P =.044). Disease-free survival time was significantly longer in the PCT arm (P =.033). CONCLUSION: Although impressive differences in median, 3-year, and 4-year survival were observed, they were not statistically significant, except for stage I and II disease.