Sylvie Bastuji-Garin

Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis.

Background Toxic epidermal necrolysis and Stevens–Johnson syndrome are rare, life-threatening, drug-induced cutaneous reactions. We conducted a case–control study to quantify the risks associated with the use of specific drugs. Methods Data were obtained through surveillance networks in France, Germany, Italy, and Portugal. Drug use before the onset of disease was compared in 245 people who were hospitalized because of toxic epidermal necrolysis or Stevens–Johnson syndrome and 1147 patients hospitalized for other reasons (controls). Crude relative risks were calculated and adjusted for confounding by multivariate methods when numbers were large enough. Results Among drugs usually used for short periods, the risks were increased for trimethoprim–sulfamethoxazole and other sulfonamide antibiotics (crude relative risk, 172; 95 percent confidence interval, 75 to 396), chlormezanone (crude relative risk, 62; 21 to 188), aminopenicillins (multivariate relative risk, 6.7; 2.5 to 18), quinolones (multivariate rel...

Risk factors for erysipelas of the leg (cellulitis): case-control study

Abstract Objective: To assess risk factors for erysipelas of the leg (cellulitis). Design: Case-control study. Setting: 7 hospital centres in France. Subjects: 167 patients admitted to hospital for erysipelas of the leg and 294 controls. Results: In multivariate analysis, a disruption of the cutaneous barrier (leg ulcer, wound, fissurated toe-web intertrigo, pressure ulcer, or leg dermatosis) (odds ratio 23.8, 95% confidence interval 10.7 to 52.5), lymphoedema (71.2, 5.6 to 908), venous insufficiency (2.9, 1.0 to 8.7), leg oedema (2.5, 1.2 to 5.1) and being overweight (2.0, 1.1 to 3.7) were independently associated with erysipelas of the leg. No association was observed with diabetes, alcohol, or smoking. Population attributable risk for toe-web intertrigo was 61%. Conclusion: This first case-control study highlights the major role of local risk factors (mainly lymphoedema and site of entry) in erysipelas of the leg. From a public health perspective, detecting and treating toe-web intertrigo should be evaluated in the secondary prevention of erysipelas of the leg.

Respiratory weakness is associated with limb weakness and delayed weaning in critical illness.

Objective:Although critical illness neuromyopathy might interfere with weaning from mechanical ventilation, its respiratory component has not been investigated. We designed a study to assess the level of respiratory muscle weakness emerging during the intensive care unit stay in mechanically ventilated patients and to examine the correlation between respiratory and limb muscle strength and the specific contribution of respiratory weakness to delayed weaning. Design:Prospective observational study. Setting:Two medical, one surgical, and one medicosurgical intensive care units in two university hospitals and one university- affiliated hospital. Patients:A total of 116 consecutive patients were enrolled after ≥7 days of mechanical ventilation. Interventions:None. Measurements and Main Results:Maximal inspiratory and expiratory pressures and vital capacity were measured via the tracheal tube on the first day of return to normal consciousness. Muscle strength was measured using the Medical Research Council score. After standardized weaning, successful extubation was defined as the day from which mechanical ventilatory support was no longer required within the next 15 days. The median value (interquartile range) of maximal inspiratory pressure was 30 (20–40) cm H2O, maximal expiratory pressure was 30 (20–50) cm H2O, and vital capacity was 11.1 (6.3–19.8) mL/kg. Maximal inspiratory pressure, maximal expiratory pressure, and vital capacity were significantly correlated with the Medical Research Council score. The median time (interquartile range) from awakening to successful extubation was 6 (1–17) days. Low maximal inspiratory pressure (hazard ratio, 1.86; 95% confidence interval, 1.07–3.23), maximal expiratory pressure (hazard ratio, 2.18; 95% confidence interval, 1.44–3.84), and Medical Research Council score (hazard ratio, 1.96; 95% confidence interval, 1.27–3.02) were independent predictors of delayed extubation. Septic shock before awakening was significantly associated with respiratory weakness (odds ratio, 3.17; 95% confidence interval, 1.17–8.58). Conclusions:Respiratory and limb muscle strength are both altered after 1 wk of mechanical ventilation. Respiratory muscle weakness is associated with delayed extubation and prolonged ventilation. In our study, septic shock is a contributor to respiratory weakness.

Prevalence and factors associated with hidradenitis suppurativa: Results from two case-control studies

BACKGROUND Conflicting opinions have been reported regarding the epidemiology of hidradenitis suppurativa. OBJECTIVE We sought to evaluate the prevalence of hidradenitis suppurativa and to identify associated factors. METHODOLOGY Prevalence was evaluated using a representative sample of the French population (n=10,000). Associated risk factors were assessed using two case-control studies, one population-based with 67 self-reported patients and 200 control subjects, and the other clinic-based with 302 medically assessed patients and 906 control subjects. RESULTS The prevalence was 1% of the French population. Multivariate analyses showed a strong association with current smoking in self-reported (odds ratio=4.16, 95% confidence interval [2.99-8.69]) and in medically assessed (odds ratio=12.55 [8.58-18.38]) populations. Association with body mass index was significant in medically assessed patients (odds ratio=1.12 [1.08-1.15]) for each increase of 1 U of BMI. LIMITATIONS A causal relationship could not be established with such a cross-sectional study. CONCLUSION Hidradenitis suppurativa is a common disease, frequently associated with smoking and being overweight.

Sedation algorithm in critically ill patients without acute brain injury

Objective:To determine whether use of a sedation algorithm to promote a high level of tolerance to the intensive care environment and preserve consciousness affected time to arousal and duration of mechanical ventilation in patients without acute brain injury. Design:Two-phase, prospective, controlled study. Setting:University-affiliated medical intensive care unit. Patients:Patients without acute brain injury requiring mechanical ventilation for at least 24 hrs. Interventions:During the control phase, sedatives and analgesics were adjusted according to the physician’s decision. During the algorithm phase, sedatives and analgesics were adjusted according to an algorithm developed by a multidisciplinary team including nurses and physicians. The algorithm was based on regular assessments of consciousness and tolerance to the intensive care unit environment using the Adaptation to Intensive Care Environment instrument and was designed to achieve tolerance and maintain a high level of consciousness. Standard practices, including weaning from the ventilator, were the same during both study phases. Measurements and Main Results:A total of 102 patients were enrolled (control group, n = 54; algorithm group, n = 48). Median duration of mechanical ventilation was significantly shorter in the algorithm group (4.4 days [interquartile range, 2.1–9.8]) compared with the control group (10.3 days [3.5–17.2], p = .014), representing a 57.3% reduction. In Cox multivariate analysis, the risk of remaining on mechanical ventilation was 0.48 times (95% confidence interval, 0.29–0.78) lower for algorithm patients compared with controls. The median time to arousal was also significantly shorter in patients in the algorithm group (2 days [2–5]) compared with the control group (4 days [2–9], p = .006). Conclusions:The use of a sedation algorithm to promote tolerance to the intensive care environment and preserve consciousness in patients without acute brain injury resulted in a marked decrease in the duration of mechanical ventilation. This reduction was at least partly attributable to a shorter time to arousal after initiation of mechanical ventilation.

Comprehensive Geriatric Assessment in the Decision-Making Process in Elderly Patients With Cancer: ELCAPA Study

PURPOSE To identify Comprehensive Geriatric Assessment (CGA) components independently associated with changes in planned cancer treatment. PATIENTS AND METHODS We prospectively included 375 consecutive elderly patients with cancer (ELCAPA01 study) assessed by geriatricians using the CGA. Multivariate analysis was used to identify factors associated with changes in the cancer treatment (intensification, decrease, or delayed > 2 weeks). Change was defined as a difference between the initial treatment proposal and the final treatment selected in a multidisciplinary meeting. RESULTS Mean age was 79.6 years (standard deviation [SD], 5.6 years), and 197 (52.5%) were women. The most common tumor location was the digestive system (58.7%). The mean number of comorbidities was 4.2 (SD, 2.7) per patient, and the mean Cumulative Illness Rating Scale for Geriatrics score was 11.8 (SD, 5.3). After the CGA, the initial cancer treatment plan was modified for 78 (20.8%) of 375 patients (95% CI, 16.8 to 25.3), usually to decrease treatment intensity (63 [80.8%] of 78 patients). By univariate analysis, cancer treatment changes were associated with Eastern Cooperative Oncology Group performance status ≥ 2 (73.3% in the group with changes v 41.1% in the in the group without changes; P < .001), dependency for one or more activities of daily living (ADL; 59.0% v 24.2%; P < .001), malnutrition (81.8% v 51.2%; P < .001), cognitive impairment (38.5% v 24.9%; P = .023), depression (52.6% v 21.7%; P < .001), and greater number of comorbidities (mean, 4.8 [SD, 2.9] v 4.0 [SD, 2.6]; P = .02). By multivariate analysis, factors independently associated with cancer treatment changes were a lower ADL score (odds ratio [OR], 1.25 per 0.5-point decrease; CI, 1.04 to 1.49; P = .016) and malnutrition (OR, 2.99; CI, 1.36 to 6.58; P = .007). CONCLUSION Functional status assessed by the ADL score and malnutrition were independently associated with changes in cancer treatment.

Shortened Telomeres in Circulating Leukocytes of Patients with Chronic Obstructive Pulmonary Disease

RATIONALE Telomere length is considered a marker for biological aging. Chronic obstructive pulmonary disease (COPD) may be associated with premature aging. OBJECTIVES To test the hypothesis that patients with COPD experience accelerated telomere shortening and that inflammation is linked to this process. METHODS We measured telomere length, using a quantitative polymerase chain reaction-based method, and plasma levels of various cytokines in 136 patients with COPD, 113 age- and sex-matched smokers, and 42 nonsmokers with normal lung function. MEASUREMENTS AND MAIN RESULTS Median (range) telomere length ratio was significantly lower in patients with COPD (0.57 [0.23-1.18]) than in control smokers (0.79 [0.34-1.58]) or nonsmokers (0.85 [0.38-1.55]) (P < 0.001). The difference remained highly significant when using logistic regression analysis adjusted for age, sex, and tobacco exposure. Both females and males with COPD had shorter telomere length than same-sex control subjects. Telomere length was related to age in patients and control subjects but was shorter in patients than in control subjects in all age groups. No relationship was found between telomere length and tobacco exposure in patients or control subjects, with no difference between control smokers and nonsmokers. In patients with COPD, telomere length was related to PaO2 (P < 0.001) and PaCO2 (P < 0.001) but not to lung function parameters or the BODE Index. Patients with COPD also had elevated plasma levels of various cytokines, interleukin-6 correlating negatively with telomere length (P < 0.001). CONCLUSIONS Given that in vivo telomere length reflects cellular turnover and exposure to oxidative and inflammatory damage, our data support accelerated aging in COPD.

Medications as Risk Factors of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Children: A Pooled Analysis

OBJECTIVE. The aim of this study was to determine the relation of medications to the risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in children <15 years of age. METHODS. We conducted a pooled analysis by using data from 2 multicenter international case-control studies: the severe cutaneous adverse reaction (SCAR) study and the multinational severe cutaneous adverse reaction (EuroSCAR) study conducted in France, Germany, Italy, Portugal, the Netherlands, Austria, and Israel. We selected case subjects aged <15 years, hospitalized for Stevens-Johnson syndrome, Stevens-Johnson syndrome/toxic epidermal necrolysis-overlap, or toxic epidermal necrolysis, and age-, gender-, and country-matched hospital controls. Pooled crude odds ratios were estimated and adjusted for confounding by multivariate methods when numbers permitted. RESULTS. Our study included 80 cases and 216 matched controls. Antiinfective sulfonamides, phenobarbital, carbamazepine, and lamotrigine were strongly associated with the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. Significant associations were highlighted in univariate analysis for valproic acid and nonsteroidal antiinflammatory drugs as a group and for acetaminophen (paracetamol) in multivariate analysis. CONCLUSIONS. We confirmed 4 previously highly suspected drug risk factors for Stevens-Johnson syndrome/toxic epidermal necrolysis in children: antiinfective sulfonamides, phenobarbital, carbamazepine, and lamotrigine. Among more unexpected risk factors, we suspect that acetaminophen (paracetamol) use increases the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis.

High prevalence of Foxp3 and IL17 in MMR-proficient colorectal carcinomas

Background and aims: Colorectal cancer (CRC) harbours different types of DNA alterations, including microsatellite instability (MSI). Cancers with high levels of MSI (MSI-H) are considered to have a good prognosis, probably related to lymphocyte infiltration within tumours. The aim of the present study was to characterise the intratumoural expression of markers associated with the antitumour immune response in mismatch repair (MMR)-proficient (MSS) colon cancers. Methods: Ninety human colon cancers (T) and autologous normal colon mucosa (NT) were quantified for the expression of 15 markers of the immune response with quantitiative reverse transcription-PCR (qRT-PCR). mRNA expression levels were correlated with MMR status. Immunohistochemistry (IHC) was performed using both interleukin 17 (IL17) and CD3 antibodies. Results: Expression of cytotoxic markers (FasL, granzyme B and perforin), inflammatory cytokines (IL1β, IL6, IL8, IL17 and transforming growth factor β (TGFβ)) and a marker of regulatory T cells (forkhead box P3 (Foxp3)) was significantly higher in tumours than in autologous normal tissues. Adjusting for MMR status, higher tumoural expression of both granzyme B and perforin was associated with the MSI-H phenotype, and the perforin T/NT ratio was higher in MSI-H tissues than in MSS tissues. Higher tumoural expression of Foxp3, IL17, IL1β, IL6 and TGFβ was associated with the MSS phenotype, and the IL17 T/NT ratio was higher in MSS tissues than in MSI-H tissues as assessed by both qRT-PCR and IHC. Conclusions: Immune gene expression profiling in CRC displayed different patterns according to MMR status. Higher Foxp3, IL6, TGFβ and IL17 expression is a particular determinant in MMR-proficient CRC. These may be potential biomarkers for a new prognostic “test set” in sporadic CRCs.

Risk factors for bullous pemphigoid in the elderly: a prospective case-control study.

A rise in the incidence of bullous pemphigoid (BP) was documented recently in Europe, and the main risk factors for BP remain unknown. We conducted a multicenter case-control study to evaluate risk factors for BP. We identified 201 incident BP cases and 345 controls individually matched for age, gender, center, and place of residence (home, nursing home, or extended-care facility). We used univariate and multivariate logistic regression analyses to compare drugs used for over 3 months, comorbidities, and physical and cognitive impairments between cases and controls. Mean age of BP patients was 84.2 (±8.7) years. Factors independently associated with BP by multivariate analysis were major cognitive impairment (odds ratio (OR), 2.19; 95% confidence interval (95% CI), 1.24-3.87), bedridden condition (OR, 2.19; 95% CI, 1.23-3.89), Parkinsons disease (OR, 2.16; 95% CI, 1.09-4.27), unipolar or bipolar disorder (OR, 5.25; 95% CI, 1.21-22.86), and chronic use of spironolactone (OR, 2.30; 95% CI, 1.20-4.46) or phenothiazines with aliphatic side chains (OR, 3.70; 95% CI, 1.21-11.34). Chronic analgesic use was associated with a lower risk of BP (OR, 0.49; 95% CI, 0.30-0.81). Thus, risk factors for BP include neurological disorders, particularly dementia and Parkinsons disease, psychiatric disorders (unipolar and bipolar disorders), bedridden condition, and chronic use of several drugs.