Severe Scabies: A French Multi-centre Study Involving 95 Patients with Crusted and Profuse Disease and Review of the Literature.

The aim of this multi-centre French retrospective study was to identify severe, i.e. crusted and profuse, scabies patients. Records were retrieved from 22 Dermatology or Infectious Diseases departments in the Ile-de-France from January 2009 to January 2015 to characterize epidemiology, demography, diagnosis, contributing factors, treatment features, and outcomes in severe scabies. A total of 95 inpatients (57 crusted and 38 profuse) were included. A higher number of cases was observed among elderly patients (>75 years), mostly living in institutions. Thirteen patients (13.6%) reported a history of previously treated scabies. Sixty-three patients (66.3%) had been seen by a previous practitioner for the current episode (up to 8 previous visits). Initial misdiagnosis (e.g. eczema, prurigo, drug-related eruptions, psoriasis) was documented in 41 patients (43.1%). Fifty-eight patients (61%) had already received 1 or more previous treatments for their current episode. Forty percent received corticosteroids or acitretin for an initial diagnosis of eczema or psoriasis. Median time from the onset of symptoms to the diagnosis of severe scabies was 3 months (range 0.3-22). Itch was present in all patients at diagnosis. Most patients (n=84, 88.4%) had comorbidities. Diagnostic and therapeutic approaches varied. Complications occurred in 11.5% of cases. To date, there is no consensus for diagnosis and treatment, and future standardization of is required for optimal management.

Impact of two waves of Sars-Cov2 outbreak on the number, clinical presentation, care trajectories and survival of patients newly referred for a colorectal cancer: A French multicentric cohort study from a large group of university hospitals.

The SARS-Cov2 may have impaired care trajectories, patient overall survival (OS), tumor stage at initial presentation for new colorectal cancer (CRC) cases. This study aimed at assessing those indicators before and after the beginning of the pandemic in France. In this retrospective cohort study, we collected prospectively the clinical data of the 11.4 million of patients referred to the Greater Paris University Hospitals (AP-HP). We identified new CRC cases between 1 January 2018 and 31 December 2020, and compared indicators for 2018-2019 to 2020. pTNM tumor stage was extracted from postoperative pathology reports for localized colon cancer, and metastatic status was extracted from CT-scan baseline text reports. Between 2018 and 2020, 3602 and 1083 new colon and rectal cancers were referred to the AP-HP, respectively. The 1-year OS rates reached 94%, 93% and 76% for new CRC patients undergoing a resection of the primary tumor, in 2018-2019, in 2020 without any Sars-Cov2 infection and in 2020 with a Sars-Cov2 infection, respectively (HR 3.78, 95% CI 2.1-7.1). For patients undergoing other kind of anticancer treatment, the percentages are 64%, 66% and 27% (HR 2.1, 95% CI 1.4-3.3). Tumor stage at initial presentation, emergency level of primary tumor resection, delays between the first multidisciplinary meeting and the first anticancer treatment did not differ over time. The SARS-Cov2 pandemic has been associated with less newly diagnosed CRC patients and worse 1-year OS rates attributable to the infection itself rather than to its impact on hospital care delivery or tumor stage at initial presentation.

Diagnostic yield of routine daily blood culture in patients on veno-arterial extracorporeal membrane oxygenation.

BACKGROUND: Bloodstream infections (BSIs) are frequent on veno-arterial extracorporeal membrane oxygenation (V-A ECMO). Performing routine blood cultures (BCs) may identify early paucisymptomatic BSIs. We investigated the contribution of systematic daily BCs to detect BSIs on V-A ECMO. METHODS: This was a retrospective study including all adult patients requiring V-A ECMO and surviving more than 24 h. Our protocol included routine daily BCs, from V-A ECMO insertion up to 5 days after withdrawal; other BCs were performed on-demand. RESULTS: On the 150 V-A ECMO included, 2146 BCs were performed (1162 routine and 984 on-demand BCs); 190 (9%) were positive, including 68 contaminants. Fifty-one (4%) routine BCs revealed BSIs; meanwhile, 71 (7%) on-demand BCs revealed BSIs (p = 0.005). Performing routine BCs was negatively associated with BSIs diagnosis (OR 0.55, 95% CI [0.38; 0.81], p = 0.002). However, 16 (31%) BSIs diagnosed by routine BCs would have been missed by on-demand BCs. Independent variables for BSIs diagnosis after routine BCs were: V-A ECMO for cardiac graft failure (OR 2.43, 95% CI [1.20; 4.92], p = 0.013) and sampling with on-going antimicrobial therapy (OR 2.15, 95% CI [1.08; 4.27], p = 0.029) or renal replacement therapy (OR 2.05, 95% CI [1.10; 3.81], p = 0.008). Without these three conditions, only two BSIs diagnosed with routine BCs would have been missed by on-demand BCs sampling. CONCLUSIONS: Although routine daily BCs are less effective than on-demand BCs and expose to contamination and inappropriate antimicrobial therapy, a policy restricted to on-demand BCs would omit a significant proportion of BSIs. This argues for a tailored approach to routine daily BCs on V-A ECMO, based on risk factors for positivity.

Clinical relevance and impact of Corynebacterium isolation in lower respiratory tract of critically ill patients requiring mechanical ventilation.

PURPOSE: Corynebacterium spp. (C. spp.) is commonly considered as a contaminant in respiratory specimens. No study has ever focused on its clinical relevance in the lower respiratory tract of patients admitted to the intensive care unit (ICU) and requiring mechanical ventilation. The aims were to describe the characteristics of ICU patients with a C. spp. positive deep respiratory specimen, to investigate the impact of C. spp. on the occurrence of pneumonia, and to evaluate the outcomes of these pneumonia. METHODS: We retrospectively included all adult patients admitted to ICU in a 1000-bed University Hospital (2007-2017) who had a C. spp. positive lower respiratory tract specimen at a significant quantitative level. We used clinical, radiological, and microbiological criteria to classify the likelihood of such pneumonia. RESULTS: Among the 31 patients included, acute respiratory failure and postoperative care after major surgery were the main reasons of admission. SAPS II was 47 [34-60]. C. spp. pneumonia was considered as probable, possible and unlikely in 10, 14, and 7 patients, respectively. Fifty-two and 94% of C. spp. strains were sensitive to amoxicillin, and vancomycin/linezolid, respectively. Seventeen patients had a complete course of antibiotic against C. spp. The overall ICU mortality was 58%. CONCLUSION: Corynebacterium spp seems to be responsible for authentic pneumonia in mechanically ventilated patients. It should be considered as clinically relevant when predominantly present in respiratory specimen from patients suspected with pneumonia in ICU, and empirically treated.

Safety of laparoscopic hepatectomy in patients with hepatocellular carcinoma and portal hypertension: interim analysis of an open prospective study.

BACKGROUND: The laparoscopic approach might increase the number of cirrhotic patients with hepatocellular carcinoma (HCC) indicated for liver resection, otherwise contraindicated due to portal hypertension. The goal of this study was to confirm the safety of laparoscopic liver resection (LLR) in patients with portal hypertension. METHODS: This prospective, single-center, open study (ClinicalTrials.gov ID: NCT02145013) included all consecutive cirrhotic patients who underwent LLR for HCC from 2014 to 2017. Short-term outcomes were compared between patients with and without clinically significant portal hypertension (CSPH, defined by hepatic venous pressure gradient ≥ 10 mmHg). RESULTS: The study population included 45 patients, comprising 27 patients (60%) in the no CSPH group and 18 patients (40%) in the CSPH group. All planned procedures could be performed. The two groups did not differ in the extent of resection, transfusion, duration of clamping, and need for conversion. Overall, the 90-day mortality and severe morbidity rates were nil. Moderate morbidity was significantly higher in the CSPH group (39 vs. 4%, p = 0.01); however, the two groups did not differ in the rate of unresolved liver decompensation. Intensive care unit and hospital stays were significantly longer in the CSPH group. At 2 years, overall survival was 77% in the no CSPH group and 100% in the CSPH group (p = 0.17), and recurrence-free survival was 55% in the no CSPH group and 79% in the CSPH group (p = 0.10). CONCLUSION: LLR is safe in BCLC 0-A patients with CSPH, with no mortality and good short-term outcomes. Re-evaluation of the BCLC guidelines is needed.

Economic burden of preemptive treatment of CMV infection after allogeneic stem cell transplantation: a retrospective study of 208 consecutive patients.

BACKGROUND: Cytomegalovirus (CMV) infection and disease (CMV episodes) are global concerns after allogeneic hematopoietic stem cell transplantation (HSCT). They affect survival, both by direct and indirect effects. Due to safety issues of current anti-CMV antivirals, long-term CMV prophylaxis is poorly tolerated and the most common strategy to decrease the incidence of CMV disease is preemptive. New, less toxic, molecules are currently being assessed for CMV prophylaxis which should replace or considerably decrease the preemptive approach. The aim of this study was to assess the economic burden of CMV episodes after HSCT with a preemptive approach. METHODS: We analyzed data from 208 consecutive adults transplanted in our institution, between 2008 and 2013. Hospital resource utilization was retrieved via the linked hospital admissions and Diagnostic Related Groups for the period of conditioning to 12 months after transplant. RESULTS: CMV episodes occurred in 70 patients (34%) over the first 12 months following HSCT, after a mean of 75 days (median: 46 (7-334)). The mean total length of stay was significantly associated with the occurrence of a CMV episode (113.9 vs. 87.5 days, p = 0.0002) but was associated neither with the pre-transplant CMV serology of donors/recipients nor with survival. The mean cost of transplant was €104,016 (SD = €37,281) after 12 months. Bivariate and multivariate analyses indicated that the occurrence of >1 CMV episode increased the costs of allogeneic HSCT by 25-30% (p < 0.0001). CONCLUSION: Our study, which is the largest, single-institution cost study of allogeneic HSCT in Europe, shows that two or more CMV episodes significantly increased the transplant cost. New prophylactic strategies to prevent CMV infection and disease should decrease transplant costs.

Prognostic factors in necrotizing soft-tissue infections (NSTI): A cohort study.

BACKGROUND: Necrotizing soft-tissue infection (NSTI) is uncommon but life-threatening. A recent meta-analysis estimated the overall mortality at 23.5%. OBJECTIVE: We sought to identify risk factors associated with mortality in a cohort of patients with NSTI in a tertiary care center. METHODS: We identified 512 patients with NSTI between 1996 and 2012 in the national hospital database Program for Medicalization of Information Systems and examined risk factors of mortality with NSTI by univariate and multivariate analysis. RESULTS: We included 109 patients with a confirmed diagnosis of NSTI; 31 (28%) died at a median follow-up of 274 days (range 2-6135 days). On multivariate analysis, independent risk factors of mortality were age older than 75 years (hazard ratio [HR] 4.4, 95% confidence interval [CI] 1.8-10.3), multifocal NSTI (HR 5.9, 95% CI 1.9-18.5), severe peripheral vascular disease (HR 5.1, 95% CI 1.5-17.0), hospital-acquired infection (HR 3.9, 95% CI 1.4-10.7), severe sepsis (HR 7.4, 95% CI 1.7-33.1), and septic shock on hospital admission (HR 13.9, 95% CI 3.8-50.4). LIMITATIONS: This was a retrospective cohort, which disallows a precise record of the delay between diagnosis and surgery. CONCLUSION: Our findings for this robust cohort of patients with a definite diagnosis of NSTI could help clinicians stratify NSTI severity at clinical course onset.

Influence of atmospheric pressure on infrarenal abdominal aortic aneurysm rupture.

BACKGROUND: Meteorologic conditions have a significant impact on the occurrence of cardiovascular events. Previous studies have shown that abdominal aortic aneurysm rupture (AAAR) may be associated with atmospheric pressure, with conflicting results. Therefore, we aimed to further investigate the nature of the correlation between atmospheric pressure variations and AAAR. METHOD: Hospital admissions related to AAAR between 2005-2009 were assessed in 19 districts of metropolitan France and correlated with geographically and date-matched mean atmospheric pressures. In parallel and from 2005-2009, all fatal AAARs as reported by death certificates were assessed nationwide and correlated to local atmospheric pressures at the time of aortic rupture. RESULTS: Four hundred ninety-four hospital admissions related to AAAR and 6,358 deaths nationwide by AAAR were identified between 2005-2009. Both in-hospital ruptures and aneurysm-related mortality had seasonal variations, with peak/trough incidences in January and June, respectively. Atmospheric pressure peaks occurred during winter. Univariate analysis revealed a significant association (P < 0.001) of high mean atmospheric pressure values and AAAR. After multivariate analysis, mean maximum 1-month prerupture atmospheric pressure had a persistent correlation with both in-hospital relative risk (1.05 [95% confidence interval: 1.03-1.06]; P < 0.0001) and aneurysm rupture-related mortality relative risk (1.02 [95% confidence interval: 1.01-1.03]; P < 0.0001). CONCLUSION: The annual incidence of AAAR is nonhomogeneous with a peak incidence in winter, and is independently associated with mean maximum 1-month prerupture atmospheric pressure.

Relationship between recommended chronic heart failure treatments and mortality over 8 years in real-world conditions: a pharmacoepidemiological study.

PURPOSE: We previously reported that chronic heart failure (CHF) treatments reduce the duration of hospitalisation, even in elderly patients. The present study aimed to determine whether CHF treatment also provides long-term benefits in terms of reduced mortality at 8 years. METHODS: A cohort of 281 patients who were admitted to a French teaching hospital with a main diagnosis of CHF were followed through the health insurance databases for 1 year and through the national mortality database for 8 years. RESULTS: Diuretics (236 patients, 84 %) and angiotensin-converting enzyme (ACE) inhibitors (193 patients, 69 %) were the most-frequently prescribed medications. The median duration of survival was 46 months. Mortality rates were significantly lower for patients administered beta-blockers (59 %) and statins (56 %) than for patients not exposed to these drugs (82 %, p < 0.001 and 78 %, p = 0.001 respectively). No significant differences in mortality were observed for spironolactone, diuretics or ACE inhibitors. After adjustment, beta-blocker treatment remained associated with a significantly lower risk of mortality (hazard ratio, HR = 0.54 [0.34-0.84]). After adjustment, the use of two or three CHF drugs was associated with longer survival (HR = 0.53 [0.36-0.77]) than the use of zero or one CHF drug. Statins were also associated with longer survival after adjustment (HR = 0.53 [0.31-0.89]). In patients 75 years of age or older (n = 73), only beta-blocker treatment was associated with a significantly lower risk of mortality (HR = 0.31 [0.16-0.63]) in multivariate analysis. CONCLUSIONS: The use of beta-blockers was associated with better survival rates. The use of statins was also associated with better survival at 8 years. Randomised controlled trials are required to confirm these observations.

In-Hospital Clinical Features, Morbidity, and Mortality of Patients with Neurofibromatosis 1 in France: A Nationwide, Population-Based Retrospective Cohort Study.

Neurofibromatosis 1 (NF1) is a multisystem disease that can affect nearly every organ system. The aim of our study was to describe the in-hospital population with NF1 in France. We conducted a nationwide retrospective cohort study using the French hospital administrative database. A total of 11,425 patients with NF1 (53.4% female, 19,080 person years) were identified from January 2013 to December 2019. A total of 23% had at least one diagnosis of a comorbidity or NF1-associated complication or disease, and it was highest in the age group of 10-15 years. A total of 2,601 (22.8%) had a diagnosis of cancer. There were 366 (3.2%) in-hospital deaths, and we observed a standardized mortality ratio of 4.14 (95% confidence interval = 3.71-4.56), with a higher standardized mortality ratio in women and in the age group of 10-15 years. The standardized incident ratio (SIR) of cancer was 10.3 (95% confidence interval = 9.6-11.1). We observed high SIR values for cancer in childhood, with a decrease toward that of the general population by age 70 years. We observed high SIRs for NF1-associated cancers: CNS SIR of 195.4 (95% confidence interval = 172.2-220.9) and small intestine SIR of 102.9 (95% confidence interval = 71.7-143.2). The study provides a better understanding of the prognosis in people living with NF1.

The 10-month mortality rate among older patients treated for digestive system cancer during the first wave of the COVID-19 pandemic: The CADIGCOVAGE multicentre cohort study.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has had a dramatic impact on cancer diagnosis and care pathways. Here, we assessed the mid-term impact of the COVID-19 pandemic on older adults with cancer before, during and after the lockdown period in 2020. MATERIALS AND METHODS: We performed a retrospective, observational, multicentre cohort study of prospectively collected electronic health records. All adults aged 65 or over and having been newly treated for a digestive system cancer in our institution between January 2018 until August 2020 were enrolled. RESULTS: Data on 7,881 patients were analyzed. Although the overall 10-month mortality rate was similar in 2020 vs. 2018-2019, the mortality rate among for patients newly treated in the 2020 post-lockdown period was (after four months of follow-up) significantly higher. A subgroup analysis revealed higher mortality rates for (i) patients diagnosed in the emergency department during the pre-lockdown period, (ii) patients with small intestine cancer newly treated during the post-lockdown period, and (iii) patients having undergone surgery with curative intent during the post-lockdown period. However, when considering individuals newly treated during the lockdown period, we observed lower mortality rates for (i) patients aged 80 and over, (ii) patients with a biliary or pancreatic cancer, and (iii) patients diagnosed in the emergency department. DISCUSSION: There was no overall increase in mortality among patients newly treated in 2020 vs. 2018-2019. Longer follow-up is needed to assess the consequences of the pandemic. A subgroup analysis revealed significant intergroup differences in mortality.

The Relative Contributions of Occupational and Community Risk Factors for COVID-19 among Hospital Workers: The HOP-COVID Cohort Study.

The relative contributions of occupational and community sources of COVID-19 among health-care workers (HCWs) are still subject to debate. In a cohort study at a 2814-bed tertiary medical center (five hospitals) in the Paris area of France, we assessed the proportion of hospital-acquired cases among staff and identified risk factors. Between May 2020 and June 2021, HCWs were invited to complete a questionnaire on their COVID-19 risk factors. RT-PCR and serology test results were retrieved from the virology department. Mixed-effects logistic regression was used to account for clustering by hospital. The prevalence of COVID-19 was 15.6% (n = 213/1369 respondents) overall, 29.7% in the geriatric hospitals, and 56.8% of the infections were hospital-acquired. On multivariable analyses adjusted for COVID-19 incidence and contact in the community, a significantly higher risk was identified for staff providing patient care (especially nursing assistants), staff from radiology/functional assessment units and stretcher services, and staff working on wards with COVID-19 clusters among patients or HCWs. The likelihood of infection was greater in geriatric wards than in intensive care units. The presence of significant occupational risk factors after adjustment for community exposure is suggestive of a high in-hospital risk and emphasizes the need for stronger preventive measures-especially in geriatric settings. Clinicaltrials.gov NCT04386759.

PM2.5 and PM10 air pollution peaks are associated with emergency department visits for psychotic and mood disorders.

Particulate matters with a diameter of less than 10 µm (PM10) or less than 2.5 µm (PM2.5) are major air pollutants. Their relationship to psychiatric disorders has not yet been extensively studied. We aimed to explore the relationship between PM10 and PM2.5 air pollution peaks and the daily number of emergency visits for psychotic and mood disorders. Clinical data were collected from the Emergency Department of a Paris suburb (Créteil, France) from 2008 to 2018. Air pollution data were measured by the Paris region air quality network (Airparif) and collected from public databases. Pollution peak periods were defined as days for which the daily mean level of PM was above nationally predefined warning thresholds (20 µg/m3 for PM2.5, and 50 µg/m3 for PM10), and the 6 following days. Multivariable analyses compared the number of daily visits for psychotic and mood (unipolar and bipolar) disorders according to pollution peak, using negative binomial regression. After adjustment on meteorological variables (temperature, humidity, amount of sunshine in minutes), the daily number of emergency visits for psychotic disorders was significantly higher during PM2.5 and PM10 air pollution peak periods; while the number of visits for unipolar depressive disorders was higher only during PM10 peak periods (ß = 0.059, p-value = 0.034). There were no significant differences between peak and non-peak periods for bipolar disorders. Differences in the effects of PM air pollution on psychotic and mood disorders should be analyzed in further studies.

Effect of lockdown on digestive system cancer care amongst older patients during the first wave of COVID-19: The CADIGCOVAGE multicentre cohort study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a dramatic impact on cancer diagnosis and treatment. Most patients newly diagnosed with digestive system cancer are aged 65 and over. METHODS: We performed a retrospective, observational, multicentre cohort study based on prospectively collected electronic health records. All adults aged 65 or over and having been newly treated for a digestive system cancer between January 2018 until August 2020 were enroled. RESULTS: Data on 7882 patients were analysed. The first COVID-19 lockdown period led to a 42.4% decrease in newly treated digestive system cancers, and the post-lockdown period was associated with a 17% decrease. The decrease in newly treated digestive system cancer did not differ as a function of age, sex, comorbidities, primary tumour site, and disease stage. The proportion of patients admitted to an emergency department increased during the lockdown period. We do not observe a higher 3-month mortality rate in 2020, relative to the corresponding calendar periods in 2018 and 2019. CONCLUSION: To avoid a decrease in newly treated cancers during future lockdown periods, access to healthcare will have to be modified. Although 3-month mortality did not increase in any of the patient subgroups, the 2020 cohort must be followed up for long-term mortality.

Lymphoproliferative malignancies in patients with neurofibromatosis 1.

Neurofibromatosis 1 (NF1) is an inherited, autosomal-dominant, tumor predisposition syndrome with a birth incidence as high as 1:2000. A patient with NF1 is four to five times more likely to develop a malignancy as compared to the general population. The number of epidemiologic studies on lymphoproliferative malignancies in patients with NF1 is limited. The aim of this study was to determine the incidence rate of lymphoproliferative malignancies (lymphoma and leukemia) in NF1 patients followed in our referral center for neurofibromatoses. We used the Informatics for Integrated Biology and the Bedside (i2b2) platform to extract information from the hospital's electronic health records. We performed a keyword search on clinical notes generated between Jan/01/2014 and May/11/2020 for patients aged 18 years or older. A total of 1507 patients with confirmed NF1 patients aged 18 years and above were identified (mean age 39.2 years; 57% women). The total number of person-years in follow-up was 57,736 (men, 24,327 years; women, 33,409 years). Mean length of follow-up was 38.3 years (median, 36 years). A total of 13 patients had a medical history of either lymphoma or leukemia, yielding an overall incidence rate of 22.5 per 100,000 (0.000225, 95% confidence interval (CI) 0.000223-0.000227). This incidence is similar to that of the general population in France (standardized incidence ratio 1.07, 95% CI 0.60-1.79). Four patients had a medical history leukemia and 9 patients had a medical history of lymphoma of which 7 had non-Hodgkin lymphoma, and 2 had Hodgkin lymphoma. Our results show that adults with NF1 do not have an increased tendency to develop lymphoproliferative malignancies, in contrast to the general increased risk of malignancy. While our results are consistent with the recent population-based study in Finland, they are in contrast with the larger population-based study in England whereby NF1 individuals were found to be 3 times more likely to develop both non-Hodgkin lymphoma and lymphocytic leukemia. Large-scale epidemiological studies based on nationwide data sets are thus needed to confirm our findings.

Performance of six rapid diagnostic tests for SARS-CoV-2 antigen detection and implications for practical use.

BACKGROUND: Direct detection of SARS-CoV-2 viral proteins in nasopharyngeal swabs using lateral flow immunoassays is a simple, fast and cheap approach to diagnose the infection. AIMS AND METHODS: The performance of 6 SARS-CoV-2 antigen rapid diagnostic tests has been assessed in 634 hospitalized patients or outpatients including 297 patients found to be positive for SARS-CoV-2 RNA by means of RT-PCR and 337 patients presumed to be SARS-CoV-2 RNA-negative. RESULTS: The specificity of SARS-CoV-2 RDTs was generally high (398.5%). One assay had a lower specificity of 93.2%. The overall sensitivity of the 6 RDTs was variable, from 32.3% to 61.7%. Sensitivity correlated with the delay of sampling after the onset of symptoms and the viral load estimated by the Ct value in RT-PCR. Four out of 6 RDTs tested achieved sensitivities 380% when clinical specimens were collected during the first 3 days following symptom onset or with a Ct value ≤25. CONCLUSIONS: The present study shows that SARS-CoV-2 antigen can be easily and reliably detected by RDTs. These tests are easy and rapid to perform. However, the specificity and sensitivity of COVID-19 antigen RDTs may widely vary across different tests and must therefore be carefully evaluated before releasing these assays for realworld applications.

Neurofibromatosis I and multiple sclerosis.

Neurofibromatosis 1 (NF1) is one of the most common autosomal dominant genetic disorders with a birth incidence as high as 1:2000. It is caused by mutations in the NF1 gene on chromosome 17 which encodes neurofibromin, a regulator of neuronal differentiation. While NF1 individuals are predisposed to develop benign and malignant nervous system tumors, various non-tumoral neurological conditions including multiple sclerosis (MS) have also been reported to occur more frequently in NF1. The number of epidemiologic studies on MS in NF1 individuals is very limited. The aim of this study was to determine the estimated population proportion of MS in NF1 patients followed in our Referral Centre for Neurofibromatosis using the Informatics for Integrated Biology and the Bedside (i2b2) platform to extract information from the hospital's electronic health records. We found a total 1507 patients with confirmed NF1, aged 18 years (y) and above (mean age 39.2y, range 18-88y; 57% women). Five NF1 individuals were found to have MS, yielding an estimated population proportion of 3.3 per 1000 (0.0033, 95% Confidence Interval 0.0014-0.0077). The median age at diagnosis was 45 y (range 28-49 y). Three patients had relapsing-remitting MS and two patients had secondary progressive MS. Patients with NF1 were found to be twice more likely to develop MS than the general population in France (odds ratio 2.2), however this result was not statistically significant (95% Confidence Interval 0.91-5.29). Our results show that patients with NF1 might have a slight increased tendency to develop MS; however, due to the small sample size of our study, the results may not be sufficiently powered to detect this rare association. Large-scale epidemiological studies based on nationwide datasets are needed to confirm our findings. These findings further emphasize the need for a focused follow-up of patients with NF1, as early detection and management of MS can prevent further neurological disability.

Impact of a computer-generated alert system prompting review of antibiotic use in hospitals.

OBJECTIVES: The aim of this study was to measure the impact on antibiotic use of a computer-generated alert prompting post-prescription review and direct counselling in hospital wards. METHODS: A computer-generated alert on new prescriptions of 15 antibiotics was reviewed weekly by an infectious disease physician for 41 weeks. During the first 6 months of the study, criteria selected for potential intervention were: (i) a planned duration of treatment of > or =10 days; (ii) discordance between the spectrum of the prescribed antibiotic and available microbiological results; or (iii) prescriptions of broad-spectrum beta-lactams, fluoroquinolones, glycopeptides or linezolid. During the following 5 months, the alert was restricted to any prescription of the 15 antibiotics in the 9 wards where overall antibiotic use had not decreased in the past year. RESULTS: We analysed 2385 prescriptions, 932 (39%) of which generated an alert for potential intervention. Among the latter, 482 (51.7%) prescriptions prompted direct counselling, mainly for shortening the planned duration of therapy (18.9%), withdrawing antibiotics (16.2%) or streamlining therapy (15.5%). The attending physicians' compliance with the recommendations was 80%. The overall median (interquartile range) days of therapy prescribed by the attending physicians was reduced from an initial duration of 8 (7-14) to 7 (6-11) days (P < 0.0001), resulting in 26.5% less antibiotic days prescribed. The time required for the intervention was 6 h per week. CONCLUSIONS: This computer-prompted post-prescription review led physicians to modify one half of the antibiotic courses initially prescribed and was well accepted by the majority, although they had not requested counselling.

Risk stratification of early admission to the intensive care unit of patients with no major criteria of severe community-acquired pneumonia: development of an international prediction rule.

INTRODUCTION: To identify risk factors for early (< three days) intensive care unit (ICU) admission of patients hospitalised with community-acquired pneumonia (CAP) and not requiring immediate ICU admission, and to stratify the risk of ICU admission on days 1 to 3. METHODS: Using the original data from four North American and European prospective multicentre cohort studies of patients with CAP, we derived and validated a prediction rule for ICU admission on days 1 to 3 of emergency department (ED) presentation, for patients presenting with no obvious reason for immediate ICU admission (not requiring immediate respiratory or circulatory support). RESULTS: A total of 6560 patients were included (4593 and 1967 in the derivation and validation cohort, respectively), 303 (4.6%) of whom were admitted to an ICU on days 1 to 3. The Risk of Early Admission to ICU index (REA-ICU index) comprised 11 criteria independently associated with ICU admission: male gender, age younger than 80 years, comorbid conditions, respiratory rate of 30 breaths/minute or higher, heart rate of 125 beats/minute or higher, multilobar infiltrate or pleural effusion, white blood cell count less than 3 or 20 G/L or above, hypoxaemia (oxygen saturation < 90% or arterial partial pressure of oxygen (PaO2) < 60 mmHg), blood urea nitrogen of 11 mmol/L or higher, pH less than 7.35 and sodium less than 130 mEq/L. The REA-ICU index stratified patients into four risk classes with a risk of ICU admission on days 1 to 3 ranging from 0.7 to 31%. The area under the curve was 0.81 (95% confidence interval (CI) = 0.78 to 0.83) in the overall population. CONCLUSIONS: The REA-ICU index accurately stratifies the risk of ICU admission on days 1 to 3 for patients presenting to the ED with CAP and no obvious indication for immediate ICU admission and therefore may assist orientation decisions.