Hôtel-Dieu de France

BACKGROUND: Serious complications related to regional anesthesia have previously been described primarily in case reports and retrospective surveys. The authors prospectively evaluated a multicenter series of regional anesthetics, using preplanned criteria to measure the incidence and characteristics of associated serious complications. METHODS: Requests were sent to 4,927 French anesthesiologists in advance of a subsequent 5-month study period. Participating anesthesiologists were asked for detailed reports of serious complications occurring during or after regional anesthetics performed by them during the study interval. Details regarding each complication then were obtained via a second questionnaire. RESULTS: The number of responding anesthesiolgists was 736. The number of regional anesthetics performed was 103,730, corresponding to 40,640 spinal anesthetics, 30,413 epidural anesthetics, 21,278 peripheral nerve blocks, and 11,229 intravenous regional anesthetics. Reports of 98 severe complications were received, with follow-up information being obtained for 97. In 89 cases, complications were attributed fully or partially to regional anesthesia. Thirty-two cardiac arrests, seven of which were fatal, occurred during the study. Of these, 26 occurred during spinal anesthesia, with 6 being fatal, 3 occurred during epidural anesthesia, and 3 more occurred during peripheral blocks. The higher incidence of cardiac arrest during spinal anesthesia (6.4 +/- 1.2 per 10,000 patients) compared with all other regional anesthesia (1.0 +/- 0.4 per 10,000 patients) was statistically significant (P < 0.05). Of 34 neurologic complications (radiculopathy, cauda equina syndrome, paraplegia), 21 were associated either with paresthesia during puncture (n = 19) or with pain during injection (n = 2), suggesting nerve trauma or intraneural injection. Twelve patients who had neurologic complications after spinal anesthetics had no paresthesia during needle placement and no pain on injection. Of these 12 patients (7 with radiculopathy and 5 with cauda equina syndrome), 9 received intrathecal hyperbaric lidocaine, 5%. The incidence of neurologic injury was significantly greater after spinal anesthesia (6 +/- 1 per 10,000 cases; P < 0.05) than after each of the other types of regional procedures (1.6 +/- 0.5 per 10,000 cases for the weighted average). Seizures attributed to elevated serum levels of local anesthetics occurred in 23 patients, but none suffered a cardiac arrest. CONCLUSIONS: (1) The incidence of cardiac arrest and neurologic injury related to regional anesthesia were very low, but both were more than three SDs greater after spinal anesthesia than after other regional procedures. (2) Two thirds of the patients with neurologic deficits had either a paresthesia during needle placement or pain on injection. (3) Seventy-five percent of the neurologic deficits after nontraumatic spinal anesthesia occurred in patients who had received hyperbaric lidocaine, 5%.

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease that affects approximately one-quarter of the global adult population, causing a substantial burden of ill health with wide-ranging social and economic implications. It is a multisystem disease and is considered the hepatic component of metabolic syndrome. Unlike other highly prevalent conditions, NAFLD has received little attention from the global public health community. Health system and public health responses to NAFLD have been weak and fragmented, and, despite its pervasiveness, NAFLD is largely unknown outside hepatology and gastroenterology. There is only a nascent global public health movement addressing NAFLD, and the disease is absent from nearly all national and international strategies and policies for non-communicable diseases, including obesity. In this global Delphi study, a multidisciplinary group of experts developed consensus statements and recommendations, which a larger group of collaborators reviewed over three rounds until consensus was achieved. The resulting consensus statements and recommendations address a broad range of topics - from epidemiology, awareness, care and treatment to public health policies and leadership - that have general relevance for policy-makers, health-care practitioners, civil society groups, research institutions and affected populations. These recommendations should provide a strong foundation for a comprehensive public health response to NAFLD.

BACKGROUND: Patients with homozygous familial hypercholesterolemia have markedly elevated cholesterol levels, which respond poorly to drug therapy, and a very high risk of premature cardiovascular disease. Inhibition of the microsomal triglyceride transfer protein may be effective in reducing cholesterol levels in these patients. METHODS: We conducted a dose-escalation study to examine the safety, tolerability, and effects on lipid levels of BMS-201038, an inhibitor of the microsomal triglyceride transfer protein, in six patients with homozygous familial hypercholesterolemia. All lipid-lowering therapies were suspended 4 weeks before treatment. The patients received BMS-201038 at four different doses (0.03, 0.1, 0.3, and 1.0 mg per kilogram of body weight per day), each for 4 weeks, and returned for a final visit after a 4-week drug washout period. Analysis of lipid levels, safety laboratory analyses, and magnetic resonance imaging of the liver for fat content were performed throughout the study. RESULTS: All patients tolerated titration to the highest dose, 1.0 mg per kilogram per day. Treatment at this dose decreased low-density lipoprotein (LDL) cholesterol levels by 50.9% and apolipoprotein B levels by 55.6% from baseline (P<0.001 for both comparisons). Kinetic studies showed a marked reduction in the production of apolipoprotein B. The most serious adverse events were elevation of liver aminotransferase levels and accumulation of hepatic fat, which at the highest dose ranged from less than 10% to more than 40%. CONCLUSIONS: Inhibition of the microsomal triglyceride transfer protein by BMS-201038 resulted in the reduction of LDL cholesterol levels in patients with homozygous familial hypercholesterolemia, owing to reduced production of apolipoprotein B. However, the therapy was associated with elevated liver aminotransferase levels and hepatic fat accumulation.

BACKGROUND AND AIMS: Internet addiction (IA) could be a major concern in university medical students aiming to develop into health professionals. The implications of this addiction as well as its association with sleep, mood disorders and self-esteem can hinder their studies, impact their long-term career goals and have wide and detrimental consequences for society as a whole. The objectives of this study were to: 1) Assess potential IA in university medical students, as well as factors associated with it; 2) Assess the relationships between potential IA, insomnia, depression, anxiety, stress and self-esteem. METHODS: Our study was a cross-sectional questionnaire-based survey conducted among 600 students of three faculties: medicine, dentistry and pharmacy at Saint-Joseph University. Four validated and reliable questionnaires were used: the Young Internet Addiction Test, the Insomnia Severity Index, the Depression Anxiety Stress Scales (DASS 21), and the Rosenberg Self Esteem Scale (RSES). RESULTS: The average YIAT score was 30 ± 18.474; Potential IA prevalence rate was 16.8% (95% confidence interval: 13.81-19.79%) and it was significantly different between males and females (p-value = 0.003), with a higher prevalence in males (23.6% versus 13.9%). Significant correlations were found between potential IA and insomnia, stress, anxiety, depression and self-esteem (p-value < 0.001); ISI and DASS sub-scores were higher and self-esteem lower in students with potential IA. CONCLUSIONS: Identifying students with potential IA is important because this addiction often coexists with other psychological problems. Therefore, interventions should include not only IA management but also associated psychosocial stressors such as insomnia, anxiety, depression, stress, and self-esteem.

Importance: Idiopathic inflammatory myopathies are heterogeneous in their pathophysiologic features and prognosis. The emergence of myositis-specific autoantibodies suggests that subgroups of patients exist. Objective: To develop a new classification scheme for idiopathic inflammatory myopathies based on phenotypic, biological, and immunologic criteria. Design, Setting, and Participants: An observational, retrospective cohort study was performed using a database of the French myositis network. Patients identified from referral centers for neuromuscular diseases were included from January 1, 2003, to February 1, 2016. Of 445 initial patients, 185 patients were excluded and 260 adult patients with myositis who had complete data and defined historical classifications for polymyositis, dermatomyositis, and inclusion body myositis were enrolled. All patients were tested for anti-histidyl-ARN-t- synthetase (Jo1), anti-threonine-ARN-t-synthetase (PL7), anti-alanine-ARN-t-synthetase (PL12), anti-complex nucleosome remodeling histone deacetylase (Mi2), anti-Ku, anti-polymyositis/systemic scleroderma (PMScl), anti-topoisomerase 1 (Scl70), and anti-signal recognition particle (SRP) antibodies. A total of 708 variables were collected per patient (eg, cancer, lung involvement, and myositis-specific antibodies). Main Outcomes and Measures: Unsupervised multiple correspondence analysis and hierarchical clustering analysis to aggregate patients in subgroups. Results: Among 260 participants (163 [62.7%] women; mean age, 59.7 years; median age [range], 61.5 years [48-71 years]), 4 clusters of patients emerged. Cluster 1 (n = 77) included patients who were male, white, and older than 60 years and had finger flexor and quadriceps weakness and findings of vacuolated fibers and mitochondrial abnormalities. Cluster 1 regrouped patients who had inclusion body myositis (72 of 77 patients [93.5%]; 95% CI, 85.5%-97.8%; P < .001). Cluster 2 (n = 91) regrouped patients who were women and had high creatine phosphokinase levels, necrosis without inflammation, and anti-SRP or anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies corresponding to immune-mediated necrotizing myopathy (53 of 91 [58.2%]; 95% CI, 47.4%-68.5%; P < .001). Cluster 3 (n = 52) regrouped patients who had dermatomyositis rash and anti-Mi2, anti-melanoma differentiation-associated protein 5 (MDA5), or anti-transcription intermediary factor-1γ (TIF1γ) antibodies, mainly corresponding with patients who had dermatomyositis (43 of 52 [82.7%]; 95% CI, 69.7%-91.8%; P < .001). Cluster 4 (n = 40) was defined by the presence of anti-Jo1 or anti-PL7 antibodies corresponding to antisynthetase syndrome (36 of 40 [90.0%]; 95% CI, 76.3%-97.2%; P < .001). The classification of an independent cohort (n = 50) confirmed the 4 clusters (Cohen κ light, 0.8; 95% CI, 0.6-0.9). Conclusions and Relevance: These findings suggest a classification of idiopathic inflammatory myopathies with 4 subgroups: dermatomyositis, inclusion body myositis, immune-mediated necrotizing myopathy, and antisynthetase syndrome. This classification system suggests that a targeted clinical-serologic approach for identifying idiopathic inflammatory myopathies may be warranted.

OBJECTIVES: This paper examines the effect of household crowding on inter-pregnancy spacing and its association with socioeconomic indicators, among parous mothers delivered in an urban environment. DESIGN: Cross sectional survey. METHODS: Sociodemographic data were obtained on 2466 parous women delivering at eight hospitals in Greater Beirut over a one year period. Statistical methodology comprised Pearson chi(2) test and logistic regression analysis. MAIN RESULTS: A significant inverse relation was observed between household crowding and socioeconomic status, defined as education and occupation of women and their spouses. Inter-pregnancy spacing increased with higher levels of crowding. Further analysis suggested that this positive association was confounded by maternal demographic characteristics. CONCLUSIONS: These data have shown that household crowding, a correlate of low parental socioeconomic status, is associated with longer birth intervals. This association, however, seems to be largely explained by maternal age and parity.

CONTEXT: AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively. OBJECTIVE: The objective of the study was to assess clinical/therapeutic characteristics of AIPmut pituitary adenomas. DESIGN: This study was an international, multicenter, retrospective case collection/database analysis. SETTING: The study was conducted at 36 tertiary referral endocrine and clinical genetics departments. PATIENTS: Patients included 96 patients with germline AIPmut and pituitary adenomas and 232 matched AIPmut-negative acromegaly controls. RESULTS: The AIPmut population was predominantly young and male (63.5%); first symptoms occurred as children/adolescents in 50%. At diagnosis, most tumors were macroadenomas (93.3%); extension and invasion was common. Somatotropinomas comprised 78.1% of the cohort; there were also prolactinomas (n = 13), nonsecreting adenomas (n = 7), and a TSH-secreting adenoma. AIPmut somatotropinomas were larger (P = 0.00026), with higher GH levels (P = 0.00068), more frequent extension (P = 0.018) and prolactin cosecretion (P = 0.00023), and occurred 2 decades before controls (P < 0.000001). Gigantism was more common in the AIPmut group (P < 0.000001). AIPmut somatotropinoma patients underwent more surgical interventions (P = 0.00069) and had lower decreases in GH (P = 0.00037) and IGF-I (P = 0.028) and less tumor shrinkage with somatostatin analogs (P < 0.00001) vs. controls. AIPmut prolactinomas occurred generally in young males and frequently required surgery or radiotherapy. CONCLUSIONS: AIPmut pituitary adenomas have clinical features that may negatively impact treatment efficacy. Predisposition for aggressive disease in young patients, often in a familial setting, suggests that earlier diagnosis of AIPmut pituitary adenomas may have clinical utility.

BACKGROUND: After a transient ischemic attack (TIA) or minor stroke, the long-term risk of stroke and other vascular events is not well known. In this follow-up to a report on 1-year outcomes from a registry of TIA clinics in 21 countries that enrolled 4789 patients with a TIA or minor ischemic stroke from 2009 through 2011, we examined the 5-year risk of stroke and vascular events. METHODS: We evaluated patients who had had a TIA or minor stroke within 7 days before enrollment in the registry. Among 61 sites that participated in the 1-year outcome study, we selected 42 sites that had follow-up data on more than 50% of their enrolled patients at 5 years. The primary outcome was a composite of stroke, acute coronary syndrome, or death from cardiovascular causes (whichever occurred first), with an emphasis on events that occurred in the second through fifth years. In calculating the cumulative incidence of the primary outcome and secondary outcomes (except death from any cause), we treated death as a competing risk. RESULTS: score for the risk of stroke (range, 0 to 7, with higher scores indicating greater risk) of 4 or more were each associated with an increased risk of subsequent stroke. CONCLUSIONS: In a follow-up to a 1-year study involving patients who had a TIA or minor stroke, the rate of cardiovascular events including stroke in a selected cohort was 6.4% in the first year and 6.4% in the second through fifth years. (Funded by AstraZeneca and others.).

<h3>OBJECTIVE</h3> To assess the effects of high frequency stimulation of the subthalamic nucleus (STN) on axial symptoms occurring in advanced stages of Parkinson9s disease (PD). <h3>METHODS</h3> The efficacy of STN stimulation on total motor disability score (unified Parkinson9s disease rating scale (UPDRS) part III) were evaluated in 10 patients with severe Parkinson9s disease. The subscores were then studied separately for limb akinesia, rigidity, and tremor, which are known to respond to levodopa, and axial signs, including speech, neck rigidity, rising from a chair, posture, gait, and postural stability, which are known to respond less well to levodopa. Patients were clinically assessed in the “off” and “on” drug condition during a levodopa challenge test performed before surgical implantation of stimulation electrodes and repeated 6 months after surgery under continuous STN stimulation. A complementary score for axial symptoms from the “activities of daily living” (ADL)—that is, speech, swallowing, turning in bed, falling, walking, and freezing—was obtained from each patient9s questionnaire (UPDRS, part II). <h3>RESULTS</h3> Improvements in total motor disability score (62%), limb signs (62%), and axial signs (72%) obtained with STN stimulation were statistically comparable with those obtained with levodopa during the preoperative challenge (68%, 69%, and 59%, respectively). When levodopa and STN stimulation were combined there was a further improvement in total motor disability (80%) compared with preoperative levodopa administration. This consisted largely of an additional improvement in axial signs (84%) mainly for posture and postural stability, no further improvement in levodopa responsive signs being found. Axial symptoms from the ADL showed similar additional improvement when levodopa and STN stimulation were combined. <h3>CONCLUSION</h3> These findings suggest that bilateral STN stimulation improves most axial features of Parkinson9s disease and that a synergistic effect can be obtained when stimulation is used in conjunction with levodopa treatment.

Hepatic portal venous gas (HPVG), an ominous radiologic sign, is associated in some cases with a severe underlying abdominal disease requiring urgent operative intervention. HPVG has been reported with increasing frequency in medical literature and usually accompanies severe or lethal conditions. The diagnosis of HPVG is usually made by plain abdominal radiography, sonography, color Doppler flow imaging or computed tomography (CT) scan. Currently, the increased use of CT scan and ultrasound in the inpatient setting allows early and highly sensitive detection of such severe illnesses and also the recognition of an increasing number of benign and non-life threatening causes of HPVG. HPVG is not by itself a surgical indication and the treatment depends mainly on the underlying disease. The prognosis is related to the pathology itself and is not influenced by the presence of HPVG. Based on a review of the literature, we discuss in this paper the pathophysiology, risk factors, radiographic findings, management, and prognosis of pathologies associated with HPVG.

Two decades following their description, the significance of Modic vertebral endplate and marrow changes remains a matter of debate. These changes are closely related to the normal degenerative process affecting the lumbar spine, and their prevalence increases with age. However, the exact pathogenesis underlying these changes and their relation to segmental instability of the lumbar spine and to low back pain remain unclear. In this paper, we review the literature relevant to this topic and discuss the currently available evidence regarding the pathologic and clinical significance of Modic changes.

Generalised lipodystrophy of the Berardinelli-Seip type (BSCL) is a rare autosomal recessive human disorder with severe adverse metabolic consequences. A gene on chromosome 9 (BSCL1) has recently been identified, predominantly in African-American families. More recently, mutations in a previously undescribed gene of unknown function (BSCL2) on chromosome 11, termed seipin, have been found to be responsible for this disorder in a number of European and Middle Eastern families. We have studied the genotype/phenotype relationships in 70 affected subjects from 44 apparently unrelated pedigrees of diverse ethnic origin. In all subjects, hepatic dysfunction, hyperlipidaemia, diabetes mellitus, and hypertrophic cardiomyopathy were significant contributors to morbidity with no clear differences in their prevalence between subjects with BSCL1 or BSCL2 and those with evidence against cosegregation with either chromosome 9 or 11 (designated BSCLX). BSCL2 appears to be a more severe disorder than BSCL1 with a higher incidence of premature death and a lower prevalence of partial and/or delayed onset of lipodystrophy. Notably, subjects with BSCL2 had a significantly higher prevalence of intellectual impairment than those with BSCL1 or BSCLX (p<0.0001, OR 17.0, CI 3.6 to 79.0). The higher prevalence of intellectual impairment and the increased risk of premature death in BSCL2 compared to BSCL1 emphasise the importance of molecular diagnosis of this syndrome and have clear implications for genetic counselling.

PURPOSE: In 1992, Georges Charpak invented a new type of X-ray detector, which in turn led to the development of the EOS(®) 2D/3D imaging system. This system takes simultaneous anteroposterior and lateral 2D images of the whole body and can be utilized to perform 3D reconstruction based on statistical models. The purpose of this review is to present the state of the art for this EOS(®) imaging technique, to report recent developments and advances in the technique, and to stress its benefits while also noting its limitations. METHODS: The review was based on a thorough literature search on the subject as well as personal experience gained from many years of using the EOS(®) system. RESULTS: While EOS(®) imaging could be proposed for many applications, it is most useful in relation to scoliosis and sagittal balance, due to its ability to take simultaneous orthogonal images while the patient is standing, to perform 3D reconstruction, and to determine various relationships among adjacent segments (cervical spine, pelvis, and lower limbs). The technique has also been validated for the study of pelvic and lower-limb deformity and pathology in adult and pediatric populations; in such a study it has the advantage of allowing the measurement of torsional deformity, which classically requires a CT scan. CONCLUSIONS: The major advantages of EOS(®) are the relatively low dose of radiation (50-80 % less than conventional X-rays) that the patient receives and the possibility of obtaining a 3D reconstruction of the bones. However, this 3D reconstruction is not created automatically; a well-trained operator is required to generate it. The EOS(®) imaging technique has proven itself to be a very useful research and diagnostic tool.

OBJECTIVES: Autophagy constitutes a defense mechanism to overcome aging and apoptosis in osteoarthritic cartilage. Several cytokines and transcription factors are linked to autophagy and play an important role in the degradative cascade in osteoarthritis (OA). Cell therapy such as platelet rich plasma (PRP) has recently emerged as a promising therapeutic tool for many diseases including OA. However, its mechanism of action on improving cartilage repair remains to be determined. The purpose of this study is to investigate the effect of PRP on osteoarthritic chondrocytes and to elucidate the mechanism by which PRP contributes to cartilage regeneration. METHODS: Osteoarthritic chondrocytes were co-cultured with an increasing concentration of PRP obtained from healthy donors. The effect of PRP on the proliferation of chondrocytes was performed using cell counting and WST8 proliferation assays. Autophagy, apoptosis and intracellular level of IL-4, IL-10, and IL-13 were determined using flow cytometry analyses. Autophagy markers BECLIN and LC3II were also determined using quantitative polymerase chain reaction (qPCR). qPCR and ELISA were used to measure the expression of ADAMDTS-5, MMP3, MMP13, TIMP-1-2-3, aggregan, Collagen type 2, TGF-β, Cox-2, Il-6, FOXO1, FOXO3, and HIF-1 in tissues and co-cultured media. RESULTS: PRP increased significantly the proliferation of chondrocytes, decreased apoptosis and increased autophagy and its markers along with its regulators FOXO1, FOXO3 and HIF-1 in osteoarthritic chondrocytes. Furthermore, PRP caused a dose-dependent significant decrease in MMP3, MMP13, and ADAMTS-5, IL-6 and COX-2 while increasing TGF-β, aggregan, and collagen type 2, TIMPs and intracellular IL-4, IL-10, IL-13. CONCLUSION: These results suggest that PRP could be a potential therapeutic tool for the treatment of OA.

Beta-lactamase-producing (Bla+) enterococci have been reported in three state and two countries. Pulsed-field gel electrophoresis was used to compare 14 Bla+ Enterococcus (Streptococcus) faecalis isolated from hospitalized patients in seven states and three continents. The restriction endonuclease digestion patterns of isolates from Connecticut, Massachusetts, Lebanon, and Argentina were all markedly different, indicating that these were different strains. However, isolates from Delaware, Texas, Pennsylvania (Philadelphia and Pittsburgh), Florida, and Virginia were similar, indicating that these isolates were derivatives of a single strain. This conclusion was supported by hybridization using individual fragments as probes. Spread of Bla+ enterococci within the hospital setting was also demonstrated. These findings illustrate the value of pulsed-field gel electrophoresis for epidemiologic analyses and support the importance of identifying and containing organisms with new resistance properties in an effort to decrease their transmission to and from, as well as within, hospitals.

BACKGROUND: Hypocalcemia is a common complication of thyroidectomy. The aim of this study was to evaluate the incidence of hypocalcemia after thyroid operation and its relation to clinical, biologic, and surgical factors. STUDY DESIGN: A retrospective study of 265 patients who underwent unilateral (n = 50) or bilateral (n = 215) thyroidectomy between 1996 and 2000 was done to determine incidence and risk factors for hypocalcemia. Free thyroxine and thyrotropin levels were obtained before operation in 254 patients, together with preoperative and postoperative calcium and phosphorus levels. All patients were examined for age, gender, extent of thyroidectomy, initial versus reoperative neck operation, pathologic characteristics of resected thyroid tissue, substernal thyroid extension, and parathyroid resection and autotransplantation. RESULTS: Hypocalcemia, defined as a calcium level less than 2 mmol/L, occurred in 42 of 265 patients (16%), including 11 (4%) symptomatic patients who required vitamin D, calcium, or both for 2 to 6 weeks. Factors significantly predictive of postoperative hypocalcemia in univariate analysis included elevated free thyroxine level (p = 0.0064), bilateral thyroidectomy (p = 0.00064), parathyroid autotransplantation (p = 0.0128), and female gender (p = 0.0028). Independent risk factors on multivariate analysis were elevated free thyroxine level (p = 0.0476), bilateral thyroidectomy (p = 0.0338), and parathyroid autotransplantation (p = 0.0003). CONCLUSIONS: Bilateral thyroidectomy, elevated free thyroxine level, and parathyroid autotransplantation are independent risk factors for postthyroidectomy hypocalcemia. Oral calcium supplements may be of value in this group of patients to enhance early hospital discharge.

OBJECTIVES: To report available information in the literature regarding frequency, indications, types of antibiotic usage, duration, and their efficacy in Covid-19 infected patients. METHODS: The search was conducted on April 30 and May 7, 2020, using Ovid database and Google search. Patients' characteristics, clinical outcomes, as well as selected characteristics regarding antibiotic use (indication, class used, rates and types of bacterial secondary and co-infection, and duration of treatment) were analyzed. RESULTS: Nineteen clinical studies reporting data from 2834 patients were included. Mean rate of antibiotic use was 74.0 % of cases. Half the studies reported occurrence of a bacterial co-infection or complication (10 studies). Amongst the latter, at least 17.6 % of patients who received antibiotics had secondary infections. Pooled data of 4 studies show that half of patients receiving antibiotics were not severe nor critical. Detailed data on antibiotic use lack in most articles. CONCLUSIONS: The present review found a major use of antibiotics amongst Covid-19 hospitalized patients, mainly in an empirical setting. There is no proven efficacy of this practice. Further research to determine relevant indications for antibiotic use in Covid-19 patients is critical in view of the significant mortality associated with secondary infections in these patients, and the rising antimicrobial resistance.

Waterpipe smoking is becoming fashionable in Lebanon, but no studies have studied nicotine dependence related to waterpipe smoking. A score was constructed from 21 items and subsequently submitted to two factor analyses, which led to the extraction of four factors. Reliability and test-retest reproducibility were measured. Convergent construct validity and discriminant validity also were assessed for different smokers' samples. The Lebanon Waterpipe Dependence Scale-11 (LWDS-11) was composed of four subscales, the first representing nicotine dependence, the second negative reinforcement, the third psychological craving, and the fourth positive reinforcement. Internal consistency and test-retest reproducibility were adequate, and the subscales correlated adequately with measurements of nicotine metabolites, exhaled carbon monoxide levels, and the frequency of waterpipe smoking. The LWDS-11 discriminated between mild, moderate, and heavy waterpipe smokers, based on a threshold score of 10. Results were biologically and psychologically sound. This is the first scale to characterize waterpipe dependence. With further improvement and confirmation, it could become a useful clinical and epidemiological tool.

IMPORTANCE: Gaucher disease type 1 is characterized by hepatosplenomegaly, anemia, thrombocytopenia, and skeletal disease. A safe, effective oral therapy is needed. OBJECTIVE: To determine whether eliglustat, a novel oral substrate reduction therapy, safely reverses clinical manifestations in untreated adults with Gaucher disease type 1. DESIGN, SETTING, AND PARTICIPANTS: Phase 3, randomized, double-blind, placebo-controlled trial conducted at 18 sites in 12 countries from November 2009 to July 2012 among eligible patients with splenomegaly plus thrombocytopenia and/or anemia. Of 72 patients screened, 40 were enrolled. INTERVENTIONS: Patients were stratified by spleen volume and randomized 1:1 to receive eliglustat (50 or 100 mg twice daily; n = 20) or placebo (n = 20) for 9 months. MAIN OUTCOMES AND MEASURES: The primary efficacy end point was percentage change in spleen volume in multiples of normal from baseline to 9 months; secondary efficacy end points were change in hemoglobin level and percentage changes in liver volume and platelet count. RESULTS: All patients had baseline splenomegaly and thrombocytopenia (mostly moderate or severe), most had mild or moderate hepatomegaly, and 20% had mild anemia. Least-square mean spleen volume decreased by 27.77% (95% CI, -32.57% to -22.97%) in the eliglustat group (from 13.89 to 10.17 multiples of normal) vs an increase of 2.26% (95% CI, -2.54% to 7.06%) in the placebo group (from 12.50 to 12.84 multiples of normal) for an absolute treatment difference of -30.03% (95% CI, -36.82% to -23.24%; P < .001). For the secondary end points, the least-square mean absolute differences between groups all favored eliglustat, with a 1.22-g/dL increase in hemoglobin level (95% CI, 0.57-1.88 g/dL; P < .001), 6.64% decrease in liver volume (95% CI, -11.37% to -1.91%; P = .007), and 41.06% increase in platelet count (95% CI, 23.95%-58.17%; P < .001). No serious adverse events occurred. One patient in the eliglustat group withdrew (non-treatment related); 39 of the 40 patients transitioned to an open-label extension study. CONCLUSIONS AND RELEVANCE: Among previously untreated adults with Gaucher disease type 1, treatment with eliglustat compared with placebo for 9 months resulted in significant improvements in spleen volume, hemoglobin level, liver volume, and platelet count. The clinical significance of these findings is uncertain, and more definitive conclusions about clinical efficacy and utility will require comparison with the standard treatment of enzyme replacement therapy as well as longer-term follow-up. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00891202.

PURPOSE OF REVIEW: Osteoid osteoma is a benign painful bone tumor usually found in the lower extremities of children and young adults. It has been traditionally treated by surgical excision. Despite the small size of the lesion, the operative procedure for its removal can be extensive, but still sometimes remains incomplete. The purpose of this review is to highlight and discuss current developments in the management of osteoid osteoma. RECENT FINDINGS: During the past decade, efforts were deployed to minimize bone removal, lessen the risk of pathologic fracture and the need for bone grafting, and thereby shorten the period of convalescence. Improved methods for the precise localization of an osteoid osteoma with use of radioisotope scanning or computed tomography scan have made it possible to treat this lesion with more limited and effective operations, mainly in deep and non-easily accessible osteoid osteomas. SUMMARY: Although they bear the criticism of lacking histological proof for diagnosis of osteoid osteoma, minimally invasive techniques, such as computed tomography-guided percutaneous radiofrequency thermal ablation and laser photocoagulation have become the methods of choice for the treatment of all localizations except those in contact with neural structures (awaiting further research and experience), provided that the diagnosis is based on a typical clinical, scintigraphic and computed tomography presentation.