Calmette Hospital

BACKGROUND: Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy. METHODS: We tested the hypothesis that the timing of ART initiation would significantly affect mortality among adults not previously exposed to antiretroviral drugs who had newly diagnosed tuberculosis and CD4+ T-cell counts of 200 per cubic millimeter or lower. After beginning the standard, 6-month treatment for tuberculosis, patients were randomly assigned to either earlier treatment (2 weeks after beginning tuberculosis treatment) or later treatment (8 weeks after) with stavudine, lamivudine, and efavirenz. The primary end point was survival. RESULTS: A total of 661 patients were enrolled and were followed for a median of 25 months. The median CD4+ T-cell count was 25 per cubic millimeter, and the median viral load was 5.64 log(10) copies per milliliter. The risk of death was significantly reduced in the group that received ART earlier, with 59 deaths among 332 patients (18%), as compared with 90 deaths among 329 patients (27%) in the later-ART group (hazard ratio, 0.62; 95% confidence interval [CI]; 0.44 to 0.86; P=0.006). The risk of tuberculosis-associated immune reconstitution inflammatory syndrome was significantly increased in the earlier-ART group (hazard ratio, 2.51; 95% CI, 1.78 to 3.59; P<0.001). Irrespective of the study group, the median gain in the CD4+ T-cell count was 114 per cubic millimeter, and the viral load was undetectable at week 50 in 96.5% of the patients. CONCLUSIONS: Initiating ART 2 weeks after the start of tuberculosis treatment significantly improved survival among HIV-infected adults with CD4+ T-cell counts of 200 per cubic millimeter or lower. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis and the National Institutes of Health; CAMELIA ClinicalTrials.gov number, NCT01300481.).

Sepsis is a major contributor to the global burden of disease. The majority of sepsis cases and deaths are estimated to occur in low and middle-income countries. Barriers to reducing the global burden of sepsis include difficulty quantifying attributable morbidity and mortality, low awareness, poverty and health inequity, and under-resourced and low-resilience public health and acute health care delivery systems. Important differences in the populations at risk, infecting pathogens, and clinical capacity to manage sepsis in high and low-resource settings necessitate context-specific approaches to this significant problem. We review these challenges and propose strategies to overcome them. These strategies include strengthening health systems, accurately identifying and quantifying sepsis cases, conducting inclusive research, establishing data-driven and context-specific management guidelines, promoting creative clinical interventions, and advocacy.

The polymorphic cytochrome P450 CYP2D6 is involved in the metabolism of various drugs of wide therapeutic use and is a presumed susceptibility factor for certain environmentally-induced diseases. Our aim was to define the mutations and alleles of the CYP2D6 gene and to evaluate their frequencies in the European population. Using polymerase chain reaction-single strand conformation polymorphism analysis, 672 unrelated subjects were screened for mutations in the 9 exons of the gene and their exon-intron boundaries. A total of 48 point mutations were identified, of which 29 were novel. Mutations 1749 G-->C, 2938 C-->T and 4268 G-->C represented 52.6%, 34.3% and 52.9% of the mutations in the total population, respectively. Of the eight detrimental mutations detected, the 1934 G-->A, the 1795 Tdel and the 2637 Adel accounted for 65.8%, 6.2% and 4.8% respectively, within the poor metabolizer subgroup. Fifty-three different alleles were characterized from the mutation pattern and by allele-specific sequencing. They are derived from three major alleles, namely the wild-type CYP2D6*1A, the functional CYP2D6*2 and the null CYP2D6*4A. Five allelic variants (CYP2D6*1A, *2, *2B, *4A and *5) account for about 87% of all alleles, while the remaining alleles occur with a frequency of 0.1%-2.7%. These data provide a solid basis for future epidemiological, clinical as well as interethnic studies of the CYP2D6 polymorphism and highlight that the described single strand conformation polymorphism method can be successfully used in designing such studies.

PURPOSE: To analyze the influence of multi-detector row spiral computed tomography (CT) on identification of peripheral pulmonary arteries. MATERIALS AND METHODS: Peripheral pulmonary arteries were analyzed on optimally opacified contrast material-enhanced spiral CT angiograms in 30 patients devoid of pleuroparenchymal disease who underwent scanning with multi-detector row CT (collimation, 4 x 1 mm; pitch, 1.7-2.0; scanning time, 0.5 second). Two series of scans were systematically generated from each data set, 1.25-mm-thick (group 1) and 3-mm-thick (group 2) sections, leading to the analysis of 600 segmental (20 arteries per patient), 1,200 subsegmental (40 arteries per patient), 2,400 fifth-order (80 arteries per patient), and 4,800 sixth-order (160 arteries per patient) pulmonary arteries in each group. RESULTS: Multi-detector row CT with reconstructed scans of 1.25-mm-thick sections (group 1) allowed (a) analysis of a significantly higher percentage of subsegmental arteries (94% in group 1 vs 82% in group 2; P <.001) and (b) a significantly higher percentage of fifth- and sixth-order arteries, respectively, identified in 74% and 35% of cases in group 1 and 47% and 16% in group 2 (P <.001). The causes for inadequate depiction of subsegmental branches in group 1 were partial volume effect (43%), anatomic variants (39%), and cardiac (17%) and respiratory (1%) motion artifacts. CONCLUSION: Multi-detector row CT with reconstructed scans of 1.25-mm-thick sections enables accurate analysis of peripheral pulmonary arteries down to the fifth order on spiral CT angiograms.

BACKGROUND: Diagnosis of pulmonary embolism (PE) is difficult in patients with chronic obstructive pulmonary disease (COPD) and exacerbation. OBJECTIVE: To evaluate PE in patients with COPD and exacerbation of unknown origin and explore factors associated with PE. DESIGN: Prospective cohort study. SETTING: University-affiliated hospital in France. PATIENTS: 211 consecutive patients, all current or former smokers with COPD, who were admitted to the hospital for severe exacerbation of unknown origin and did not require invasive mechanical ventilation. MEASUREMENTS: Spiral computed tomography angiography (CTA) and ultrasonography within 48 hours of admission and assessment of the Geneva score. Patients were classified as PE positive (positive results on CTA or negative results on CTA and positive results on ultrasonography) or PE negative (negative results on CTA and negative results on ultrasonography or negative results on CTA and no recurrence of PE at follow-up 3 months later). RESULTS: 49 of 197 patients (25% [95% CI, 19% to 32%]) met the diagnostic criteria for PE. Clinical factors associated with PE were previous thromboembolic disease (risk ratio, 2.43 [CI, 1.49 to 3.94]), malignant disease (risk ratio, 1.82 [CI, 1.13 to 2.92]), and decrease in PaCO2 of at least 5 mm Hg (risk ratio, 2.10 [CI, 1.23 to 3.58]). A total of 9.2% (CI, 4.7% to 15.9%) of patients with a low-probability Geneva score received a diagnosis of PE. An exploratory analysis suggested that substituting malignant disease for recent surgery in the Geneva score might improve its performance in excluding PE in this sample who were more likely to have malignant disease than to have had recent surgery. However, this improvement seems insufficient to exclude PE with enough certainty to withhold therapy for low-risk patients on the basis of the modified score. LIMITATIONS: This study was done in only 1 center. Patients with COPD requiring invasive mechanical ventilation in the intensive care unit were not included. The upper bound of the 95% CI for the low probability of PE according to the Geneva score is too high to rule out PE. The classification of COPD exacerbation of unknown origin was based on the clinician's assessment, not on a standard evaluation for all patients. CONCLUSION: This study showed a 25% prevalence of PE in patients with COPD hospitalized for severe exacerbation of unknown origin. Three clinical factors are associated with the increased risk for PE. The Geneva score and the modified Geneva score should be prospectively evaluated in patients with COPD.

Spiral computed tomographic (CT) angiography of the pulmonary circulation has emerged recently as a potential useful diagnostic method for the evaluation of the pulmonary circulation. As a minimally invasive examination, this technique is becoming widely available and has progressively replaced conventional and digital pulmonary angiography as the standard diagnostic imaging modality of the pulmonary circulation. The purpose of this review is to capture the current state of the art of the technical aspects of spiral CT angiography, with special emphasis on the post-processing techniques currently available. As CT is responsible for a considerable part of the medical radiation dose applied to the population, the current trends for dose saving will also be emphasized. With regard to the clinical applications of spiral CT angiography, its introduction into the diagnostic work-up of pulmonary embolism has considerably modified the diagnostic algorithms. Our 8-year review of the literature presented herein is expected to provide the readers with a basis for formulating an informed opinion on this topic. In addition, a large number of congenital and acquired disorders of the pulmonary circulation are also relevant to this technique, and these indications are discussed in the context of the corresponding therapeutic options. Owing to the multiple possibilities inherent to this technique, spiral CT has the potential for cost savings without reduction in image quality or diagnostic accuracy.

We have collated the results of cystic fibrosis (CF) mutation analysis conducted in 19 laboratories in France. We have analyzed 7, 420 CF alleles, demonstrating a total of 310 different mutations including 24 not reported previously, accounting for 93.56% of CF genes. The most common were F508del (67.18%; range 61-80), G542X (2.86%; range 1-6.7%), N1303K (2.10%; range 0.75-4.6%), and 1717-1G>A (1.31%; range 0-2.8%). Only 11 mutations had relative frequencies >0. 4%, 140 mutations were found on a small number of CF alleles (from 29 to two), and 154 were unique. These data show a clear geographical and/or ethnic variation in the distribution of the most common CF mutations. This spectrum of CF mutations, the largest ever reported in one country, has generated 481 different genotypes. We also investigated a cohort of 800 French men with congenital bilateral absence of the vas deferens (CBAVD) and identified a total of 137 different CFTR mutations. Screening for the most common CF defects in addition to assessment for IVS8-5T allowed us to detect two mutations in 47.63% and one in 24.63% of CBAVD patients. In a subset of 327 CBAVD men who were more extensively investigated through the scanning of coding/flanking sequences, 516 of 654 (78. 90%) alleles were identified, with 15.90% and 70.95% of patients carrying one or two mutations, respectively, and only 13.15% without any detectable CFTR abnormality. The distribution of genotypes, classified according to the expected effect of their mutations on CFTR protein, clearly differed between both populations. CF patients had two severe mutations (87.77%) or one severe and one mild/variable mutation (11.33%), whereas CBAVD men had either a severe and a mild/variable (87.89%) or two mild/variable (11.57%) mutations.

This review is the synthesis of a working group on mild asthma. Mild asthma includes intermittent and persistent mild asthma according to the Global Initiative for Asthma (GINA) classification, and affects between 50% and 75% of asthmatic patients. Mild asthma is more frequent, more symptomatic, and less well controlled in children than in adults. Cohort studies from childhood to adulthood show that asthma severity usually remains stable over time. Nevertheless, mild asthma can lead to severe exacerbations, with a frequency ranging from 0.12 to 0.77 per patient-year. Severe exacerbations in mild asthma represent 30-40% of asthma exacerbations requiring emergency consultation. In mild asthma, inflammation and structural remodelling are constant, of varying intensity, but nonspecific. Therapy with inhaled corticosteroids (ICS) decreases bronchial inflammation, but has only a slight effect on structural remodelling, and, when stopped, inflammation immediately recurs. Permanent low-dose ICS therapy is the reference treatment for persistent mild asthma. Effectiveness is to be reassessed at 3 months, and if it is insufficient the patient is no longer considered mildly asthmatic, and treatment has to be stepped up. As mild asthma is the most frequent form of the disease, diagnosis and management require physicians' particular attention.

RATIONALE: Underinflation of the tracheal cuff frequently occurs in critically ill patients and represents a risk factor for microaspiration of contaminated oropharyngeal secretions and gastric contents that plays a major role in the pathogenesis of ventilator-associated pneumonia (VAP). OBJECTIVES: To determine the impact of continuous control of tracheal cuff pressure (P(cuff)) on microaspiration of gastric contents. METHODS: Prospective randomized controlled trial performed in a single medical intensive care unit. A total of 122 patients expected to receive mechanical ventilation for at least 48 hours through a tracheal tube were randomized to receive continuous control of P(cuff) using a pneumatic device (intervention group, n = 61) or routine care of P(cuff) (control group, n = 61). MEASUREMENTS AND MAIN RESULTS: The primary outcome was microaspiration of gastric contents as defined by the presence of pepsin at a significant level in tracheal secretions collected during the 48 hours after randomization. Secondary outcomes included incidence of VAP, tracheobronchial bacterial concentration, and tracheal ischemic lesions. The pneumatic device was efficient in controlling P(cuff). Pepsin was measured in 1,205 tracheal aspirates. Percentage of patients with abundant microaspiration (18 vs. 46%; P = 0.002; OR [95% confidence interval], 0.25 [0.11-0.59]), bacterial concentration in tracheal aspirates (mean ± SD 1.6 ± 2.4 vs. 3.1 ± 3.7 log(10) cfu/ml, P = 0.014), and VAP rate (9.8 vs. 26.2%; P = 0.032; 0.30 [0.11-0.84]) were significantly lower in the intervention group compared with the control group. However, no significant difference was found in tracheal ischemia score between the two groups. CONCLUSIONS: Continuous control of P(cuff) is associated with significantly decreased microaspiration of gastric contents in critically ill patients.

The present study prospectively evaluated the diagnostic yield and safety of electromagnetic navigation-guided bronchoscopy biopsy, for small peripheral lung lesions in patients where standard techniques were nondiagnostic. The study was conducted in a tertiary medical centre on 40 consecutive patients considered unsuitable for straightforward surgery or computed tomography (CT)-guided transthoracic needle aspiration biopsy, due to comorbidities. The lung lesion diameter was mean+/-sem 23.5+/-1.5 mm and the depth from the visceral-costal pleura was 14.9+/-2 mm. Navigation was facilitated by an electromagnetic tracking system which could detect a position sensor incorporated into a flexible catheter advanced through a bronchoscope. Information obtained during bronchoscopy was superimposed on previously acquired CT data. Divergence between CT data and data obtained during bronchoscopy was calculated by the system's software as a measure of navigational accuracy. All but one of the target lesions was reached and the overall diagnostic yield was 62.5% (25-40). Diagnostic yield was significantly affected by CT-to-body divergence; yield was 77.2% when estimated divergence was <or=4 mm. Three pneumothoraces occurred and chest drainage was required in one case. Electromagnetic navigation-guided bronchoscopy has the potential to improve the diagnostic yield of transbronchial biopsies without additional fluoroscopic guidance, and may be useful in the early diagnosis of lung cancer, particularly in nonoperable patients.

Hemoptysis is symptomatic of a potentially life-threatening condition and warrants urgent and comprehensive evaluation of the lung parenchyma, airways, and thoracic vasculature. Multi-detector row computed tomographic (CT) angiography is a very useful noninvasive imaging modality for initial assessment of hemoptysis. The combined use of thin-section axial scans and more complex reformatted images allows clear depiction of the origins and trajectories of abnormally dilated systemic arteries that may be the source of hemorrhage and that may require embolization. Conditions such as bronchiectasis, chronic bronchitis, lung malignancy, tuberculosis, and chronic fungal infection are some of the most common underlying causes of hemoptysis and are easily detected with CT. "Cryptogenic" hemoptysis is common among smokers and warrants subsequent follow-up imaging to exclude possible underlying malignancy. The bronchial arteries are the source of bleeding in most cases of hemoptysis. Contributions from the non-bronchial systemic arterial system represent an important cause of recurrent hemoptysis following apparently successful bronchial artery embolization. Vascular anomalies such as pulmonary arteriovenous malformations and bronchial artery aneurysms are other important causes of hemoptysis. Multi-detector row CT angiography permits noninvasive, rapid, and accurate assessment of the cause and consequences of hemorrhage into the airways and helps guide subsequent management.

The aim of this study was to determine the incidence, the organisms responsible for and the impact on outcome of nosocomial tracheobronchitis (NTB) in the intensive care unit (ICU). This prospective observational cohort study was conducted in a 30-bed medical/surgical ICU over a period of 6.5 yrs. All patients ventilated for >48 h were eligible. Patients with nosocomial pneumonia (NP) without prior NTB were excluded. Patients with first episodes of NTB were compared with those without NTB by univariate analysis. The study diagnosed 201 (10.6%) cases of NTB. Pseudomonas aeruginosa was the most common bacteria. NP rates were similar in patients with NTB compared with patients without NTB. Even in the absence of subsequent NP, NTB was associated with a significantly higher length of ICU stay and duration of mechanical ventilation in both surgical and medical populations. Mortality rates were similar in NTB patients without subsequent NP compared with patients without NTB. Antimicrobial treatment in NTB patients was associated with a trend to a better outcome. Nosocomial tracheobronchitis is common in mechanically ventilated intensive care unit patients. In this population, nosocomial tracheobronchitis was associated with longer durations of intensive care unit stay and mechanical ventilation. Further studies are needed to determine the impact of antibiotics on outcomes of patients with nosocomial tracheobronchitis.

BACKGROUND: The number of human deaths due to rabies is currently underestimated to be 55,000 deaths per year. Biological diagnostic methods for confirmation of rabies remain limited, because testing on postmortem cerebral samples is the reference method, and in many countries, sampling brain tissue is rarely practiced. There is a need for a reliable method based on a simple collection of nonneural specimens. METHODS: A new reverse-transcription, heminested polymerase chain reaction (RT-hnPCR) protocol was standardized at 3 participating centers in Cambodia, Madagascar, and France. Fifty-one patients from Cambodia, Madagascar, Senegal, and France were prospectively enrolled in the study; 43 (84%) were ultimately confirmed as having rabies. A total of 425 samples were collected from these patients during hospitalization. We studied the accuracy of the diagnosis by comparing the results obtained with use of biological fluid specimens (saliva and urine) and skin biopsy specimens with the results obtained with use of the standard rabies diagnostic procedure performed with a postmortem brain biopsy specimen. RESULTS: The data obtained indicate a high specificity (100%) of RT-hnPCR and a higher sensitivity (>/=98%) when the RT-hnPCR was performed with skin biopsy specimens than when the test was performed with fluid specimens, irrespective of the time of collection (i.e., 1 day after the onset of symptoms or just after death). Also, a sensitivity of 100% was obtained with the saliva sample when we analyzed at least 3 successive samples per patient. CONCLUSIONS: Skin biopsy specimens should be systematically collected in cases of encephalitis of unknown origin. These samples should be tested by RT-hnPCR immediately to confirm rabies; if the technique is not readily available locally, the samples should be tested retrospectively for epidemiological purposes.

INTRODUCTION: Ventilator-associated tracheobronchitis (VAT) is associated with increased duration of mechanical ventilation. We hypothesized that, in patients with VAT, antibiotic treatment would be associated with reduced duration of mechanical ventilation. METHODS: We conducted a prospective, randomized, controlled, unblinded, multicenter study. Patients were randomly assigned (1:1) to receive or not receive intravenous antibiotics for 8 days. Patients with ventilator-associated pneumonia (VAP) prior to VAT and those with severe immunosuppression were not eligible. The trial was stopped early because a planned interim analysis found a significant difference in intensive care unit (ICU) mortality. RESULTS: Fifty-eight patients were randomly assigned. Patient characteristics were similar in the antibiotic (n = 22) and no antibiotic (n = 36) groups. Pseudomonas aeruginosa was identified in 32% of VAT episodes. Although no difference was found in mechanical ventilation duration and length of ICU stay, mechanical ventilation-free days were significantly higher (median [interquartile range], 12 [8 to 24] versus 2 [0 to 6] days, P < 0.001) in the antibiotic group than in the no antibiotic group. In addition, subsequent VAP (13% versus 47%, P = 0.011, odds ratio [OR] 0.17, 95% confidence interval [CI] 0.04 to 0.70) and ICU mortality (18% versus 47%, P = 0.047, OR 0.24, 95% CI 0.07 to 0.88) rates were significantly lower in the antibiotic group than in the no antibiotic group. Similar results were found after exclusion of patients with do-not-resuscitate orders and those randomly assigned to the no antibiotic group but who received antibiotics for infections other than VAT or subsequent VAP. CONCLUSION: In patients with VAT, antimicrobial treatment is associated with a greater number of days free of mechanical ventilation and lower rates of VAP and ICU mortality. However, antibiotic treatment has no significant impact on total duration of mechanical ventilation. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT00122057.

1. Characterization of allelic variants of the TPMT gene (TPMT) responsible for changes in TPMT activity, and elucidation of the mechanism by which these alleles act, are required because of the clinical importance of this polymorphism for patients receiving thiopurine drugs. 2. We defined the mutational and allelic spectrum of TPMT in a group of 191 Europeans. Using PCR-SSCP, we screened for mutation the entire coding sequence, the exon-intron boundaries, the promoter region and the 3'-flanking region of the gene. Six mutations were detected throughout the ten exons and seven TPMT alleles were characterized. Four of them, TPMT*2, *3A, *3C and *7, harbouring the known mutations, G238C, G460A, A719G or T681G, were nonfunctional and accounted for 0.5, 5.7, 0.8 and 0.3% of the allele totality, respectively. 3. Within the promoter region, six alleles corresponding to a variable number of tandem repeats (VNTR), were identified. VNTR*V4 and *V5a which harbour four or five repeats of a 17-18 bp unit, were the most frequent (55% and 34%, respectively). The other VNTR alleles, having from five to eight repeats, were rarer. 4. The TPMT phenotype was correctly predicted by genotyping for 87% of individuals. A clear negative correlation between the total number of repeats from both alleles and the TPMT activity level was observed, indicating that VNTRs contribute to interindividual variations of TPMT activity. Therefore, additional analysis of the promoter region of TPMT can improve the phenotype prediction rate by genotyping.

OBJECTIVES: Nutritional assessment is not included yet as a major recommendation in lung cancer guidelines. The purpose of this study was thus to assess the influence on surgical outcome of the nutritional status of patients with primary lung cancer undergoing lobectomy. METHODS: We queried Epithor, the national clinical database of the French Society of Thoracic and Cardiovascular Surgery, and identified a retrospective cohort of 19 635 patients having undergone lobectomy for a primary lung cancer in the years 2005-11. Their nutritional status was categorized according to the WHO definition: underweight (BMI < 18.5): 857 patients (4.4%), normal (18.5 ≤ BMI < 25): 9391 patients (47.8%), overweight (25 ≤ BMI < 30): 6721 patients (34.2%), obese (BMI ≥ 30): 2666 patients (13.6%). Operative mortality, pulmonary, cardiovascular, infectious and surgical complications rates were collected and analysed for these various BMI groups. RESULTS: In the normal-weight category, operative mortality, pulmonary, surgical, cardiovascular and infectious complications rates were 2.7, 14.6, 13.8, 5.5 and 4.1%, respectively. When compared with that of normal BMI patients, adjusted operative mortality was significantly lower in overweight (2.3%; odd ratio (OR): 0.72 [95% confidence interval (CI): 0.59-0.89]; P = 0.002) and obese patients (1.9%, OR: 0.54 [95% CI: 0.40-0.74]; P < 0.001), and significantly higher in underweight patients (4.1%, OR: 1.89 [95% CI: 1.30-2.75]; P = 0.001). Underweight patients experienced significantly more pulmonary (21.1%; P < 0.001), surgical (23.2%; P < 0.001) and infectious (5.1%; P = 0.05) complications (P < 0.0001). Among surgical complications, prolonged air leaks (17.6%; P < 0.001) and bronchial stump dehiscence (1.5%; P = 0.001) were significantly more frequent in underweight patients than in normal BMI patients. Obesity was not associated with increased incidence of postoperative complications, except for arrhythmia (5.6%; P < 0.05), deep venous thrombosis and pulmonary embolism (1.5%; P = 0.005). Moreover, a statistical protective effect of obesity was observed regarding surgical complications (7.1%; P < 0.001). CONCLUSIONS: Despite having an increased risk of some postoperative cardiovascular complications, obese patients should undergo surgical standard of care therapy for appropriately stage-specific lung cancer. In underweight patients, in addition to preoperative rehabilitation including a nutritional program, attention should be given to aggressive prophylactic respiratory therapy in the perioperative period, and specific intraoperative actions to prevent prolonged air leaks and bronchial stump dehiscence.

OBJECTIVES: To determine the prevalence, determinants ofpositivity, and clinical utility of serum cryptococcal polysaccharide (CPS) antigen testing among HIV-infected patients in 2004 in Cambodia, an area highly endemic for cryptococcosis. METHODS: All HIV-infected patients with a CD4+ count <200 cells/mm3 attending 1 of 2 Phnom Penh hospitals for the first time were systematically screened for serum CPS. Patients with positive test results were further investigated to identify those with cryptococcal meningitis (CM), pulmonary cryptococcosis, or isolated positive cryptococcal antigenemia (IPCA). RESULTS: The median (interquartile range [IQR]) CD4+ count of 327 enrolled patients was 24 (IQR: 8 to 65) cells/mm3. The prevalence of cryptococcal infection was 59 (18.0%) of 327 cases, of which 41 were CM and 10 were IPCA. In the absence of serum CPS detection, 17 (28.8%) of 59 cryptococcal infections would have been missed on the day of consultation. In patients with no specific symptoms of meningoencephalitis, the prevalence of positive serum CPS detection was 32 (10.8%) of 295 cases. Countryside residence (adjusted odds ratio [AOR] = 3.6), headache (AOR = 3.2), body mass index <15.4 kg/m2 (AOR = 3.4), CD4+ count <50 cells/mm3 (AOR = 4.0), and male gender (marginally, AOR = 2.1) were all independently associated with a positive test results. CONCLUSION: Serum CPS screening among AIDS patients with a CD4+ count <100 cells/mm3 is useful in areas highly endemic for cryptococcosis, allowing early diagnosis and treatment of this opportunistic infection.

BACKGROUND AND OBJECTIVE: An endotracheal cuff pressure of 20-30 cmH(2)O is recommended. Underinflation and overinflation are associated with complications such as aspiration and tracheal wall damage. The aim of this study was to identify prevalence of, and risk factors for, endotracheal cuff underinflation and overinflation. METHODS: Prospective observational cohort study. All critically ill patients intubated with a high-volume lowpressure endotracheal tube were eligible. After manual adjustment of cuff pressure at 25 cmH(2)O, continuous recording of cuff pressure and airway pressure was performed for 8 h. Underinflation and overinflation of the endotracheal cuff were defined as cuff pressure less than 20 cmH(2)O and more than 30 cmH(2)O, respectively. In all patients, the time spent with normal cuff pressure or with underinflation or overinflation of the endotracheal cuff was measured. Univariate and multivariate analyses were used to determine risk factors for cuff underinflation and overinflation. RESULTS: Eight hundred and eight hours of cuff pressure recordings were analysed in 101 patients. Eighteen per cent of study patients spent 100% of recording time with normal (20-30 cmH(2)O) cuff pressure. Fifty-four per cent of study patients developed cuff underinflation, 73% developed cuff overinflation, and 44% developed both. Thirty- three per cent of study patients developed underinflation or overinflation for more than 30 min. Absence of sedation [odds ratio (95% confidence interval)=2.51 (1-6), P=0.03] and duration of prior intubation [1.16 (1.04-1.29), P<0.01] were independently associated with cuff underinflation. No risk factor for overinflation could be determined. The percentage of time spent with underinflation significantly (P<0.01) increased during the recording period. CONCLUSION: Variations in endotracheal cuff pressure are common in ICU patients. Duration of prior intubation and absence of sedation are independently associated with increased risk for cuff underinflation.

UNLABELLED: Lung cancer is the most frequently fatal cancer, with poor survival once the disease is advanced. Annual low-dose computed tomography has shown a survival benefit in screening individuals at high risk for lung cancer. Based on the available evidence, the European Society of Radiology and the European Respiratory Society recommend lung cancer screening in comprehensive, quality-assured, longitudinal programmes within a clinical trial or in routine clinical practice at certified multidisciplinary medical centres. Minimum requirements include: standardised operating procedures for low-dose image acquisition, computer-assisted nodule evaluation, and positive screening results and their management; inclusion/exclusion criteria; expectation management; and smoking cessation programmes. Further refinements are recommended to increase quality, outcome and cost-effectiveness of lung cancer screening: inclusion of risk models, reduction of effective radiation dose, computer-assisted volumetric measurements and assessment of comorbidities (chronic obstructive pulmonary disease and vascular calcification). All these requirements should be adjusted to the regional infrastructure and healthcare system, in order to exactly define eligibility using a risk model, nodule management and a quality assurance plan. The establishment of a central registry, including a biobank and an image bank, and preferably on a European level, is strongly encouraged. KEY POINTS: • Lung cancer screening using low dose computed tomography reduces mortality. • Leading US medical societies recommend large scale screening for high-risk individuals. • There are no lung cancer screening recommendations or reimbursed screening programmes in Europe as of yet. • The European Society of Radiology and the European Respiratory Society recommend lung cancer screening within a clinical trial or in routine clinical practice at certified multidisciplinary medical centres. • High risk, eligible individuals should be enrolled in comprehensive, quality-controlled longitudinal programmes.

PURPOSE: To evaluate the effect of pulmonary disease on diagnostic utility of spiral computed tomographic (CT) angiography in clinical practice. MATERIALS AND METHODS: Three hundred thirty-four patients, including 215 patients with pulmonary disease (group 1) and 119 patients with no history of respiratory disorder (group 2), were referred for thin-collimation CT angiography of the pulmonary circulation as the first-line diagnostic test. Patients with negative angiograms who had not received anticoagulation therapy and who could be clinically followed up at 3 months, 6 months, and 1 year were considered in the final study groups (n = 185); 135 patients had lung disease (group 3), and 50 patients had no history of a respiratory disorder (group 4). RESULTS: Between groups 3 and 4, no significant differences were found in the referral location, age, and risk factors. Confident evaluation of pulmonary arteries down to the subsegmental level was performed in 31 (23%) patients in group 3 and in 15 (30%) in group 4 (P =.5). Three episodes of acute pulmonary embolism (PE), all fatal, were diagnosed in group 3 patients; two cases occurred 14 days and one case occurred 6 months after the negative spiral CT scan. The negative predictive value of spiral CT angiography was 98% (175 of 178) in the study group in which follow-up was performed, with no significant difference between the values in groups 3 (98% [132 of 135]) and 4 (100% [50 of 50]). CONCLUSION: Underlying respiratory disease does not affect the negative predictive value of thin-collimation CT angiography, which appears to be a reliable tool in the work-up in this subgroup of patients with acute PE.