Does childhood experience of attention-deficit hyperactivity disorder symptoms increase sleep/wake cycle disturbances as measured with actigraphy in adult patients with bipolar disorder?

Childhood attention-deficit hyperactivity disorder (ADHD) is a common precursor of adult bipolar disorders (BD). Furthermore, actigraphy studies demonstrate that each disorder may be associated with abnormalities in sleep and activity patterns. This study investigates whether the presence or absence of self-reported childhood experiences of ADHD symptoms is associated with different sleep and activity patterns in adults with BD. A sample of 115 euthymic adult patients with BD was assessed for childhood ADHD symptoms using the Wender Utah Rating Scale (WURS) and then completed 21 days of actigraphy monitoring. Actigraphic measures of sleep quantity and variability and daytime activity were compared between BD groups classified as ADHD+ (n = 24) or ADHD- (n = 91), defined according to established cutoff scores for the WURS; then we examined any associations between sleep-wake cycle parameters and ADHD dimensions (using the continuous score on the WURS). Neither approach revealed any statistically significant associations between actigraphy parameters and childhood ADHD categories or dimensions. We conclude that the sleep and activity patterns of adult patients with BD do not differ according to their self-reported history of ADHD symptoms. We discuss the implications of these findings and suggest how future studies might confirm or refute our findings.

Which actigraphic variables optimally characterize the sleep-wake cycle of individuals with bipolar disorders?

OBJECTIVE: To examine which combination of objectively measured actigraphy parameters best characterizes the sleep-wake cycle of euthymic individuals with bipolar disorder (BD) compared with healthy controls (HC). METHODS: Sixty-one BD cases and 61 matched HC undertook 21 consecutive days of actigraphy. Groups were compared using discriminant function analyses (DFA) that explored dimensions derived from mean values of sleep parameters (Model 1); variability of sleep parameters (2); daytime activity (3); and combined sleep and activity parameters (4). Exploratory within-group analyses examined characteristics associated with misclassification. RESULTS: After controlling for depressive symptoms, the combined model (4) correctly classified 75% cases, while the sleep models (1 and 2) correctly classified 87% controls. The area under the curve favored the combined model (0.86). Age was significantly associated with misclassification among HC, while a diagnosis of BD-II was associated with an increased risk of misclassifications of cases. CONCLUSION: Including sleep variability and activity parameters alongside measures of sleep quantity improves the characterization of cases of euthymic BD and helps distinguish them from HC. If replicated, the findings indicate that traditional approaches to actigraphy (examining mean values for the standard set of sleep parameters) may represent a suboptimal approach to understanding sleep-wake cycles in BD.

ß LACTA testing may not improve treatment decisions made with MALDI-TOF MS-informed antimicrobial stewardship advice for patients with Gram-negative bacteraemia: a prospective comparative study.

PURPOSE: The aim of this study was to assess if use of the ß LACTA test (BLT) for extended-spectrum beta-lactamase (ESBL) detection and/or early bacterial identification by mass spectrometry (MALDI-TOF MS) improves therapeutic decision-making when combined with advice from the antimicrobial stewardship team (AMST) for the management of Gram-negative bacillary (GNB) bacteraemia. METHODS: Prospective observational theoretical study that included patients with GNB bacteraemia during a 6-month period. We compared, against the antimicrobial choice of the local AMST as informed of the Gram-stain result, a hypothetical choice, i.e. one AMST would have made had it been informed of the MALDI-TOF MS results only (option H) with the actual choice AMST made after being informed of the combined MALDI-TOF MS and BLT results (option A).Results/Key findings. A total of 131 episodes of GNB bacteraemia were included. Options H and A led to virtually the same rate of efficient antimicrobial therapy (in 120/131 and 123/131 episodes, respectively, P=0.63). Compared to the gold standard, options H and A did not lead to a significant reduction of carbapenem prescription (9/131, 6/131 and 12/131, P=0.57 and P=0.65, respectively). CONCLUSIONS: Under our test conditions, BLT, when used in conjunction with MALDI-TOF MS and AMST advice, did not allow a significant optimization of the antimicrobial prescription made on the basis AMST advice only. However, the impact of BLT should be evaluated in a population with high prevalence of ESBL-producing Enterobacteriaceae and/or when treatment choices are not made by infectious disease specialists.

Unravelling the myotonic dystrophy type 1 clinical spectrum: A systematic registry-based study with implications for disease classification.

The broad clinical spectrum of myotonic dystrophy type 1 (DM1) creates particular challenges for both medical care and design of clinical trials. Clinical onset spans a continuum from birth to late adulthood, with symptoms that are highly variable in both severity and nature of the affected organ systems. In the literature, this complex phenotype is divided into three grades (mild, classic, and severe) and four or five main clinical categories (congenital, infantile/juvenile, adult-onset and late-onset forms), according to symptom severity and age of onset, respectively. However, these classifications are still under discussion with no consensus thus far. While some specific clinical features have been primarily reported in some forms of the disease, there are no clear distinctions. As a consequence, no modifications in the management of healthcare or the design of clinical studies have been proposed based on the clinical form of DM1. The present study has used the DM-Scope registry to assess, in a large cohort of DM1 patients, the robustness of a classification divided into five clinical forms. Our main aim was to describe the disease spectrum and investigate features of each clinical form. The five subtypes were compared by distribution of CTG expansion size, and the occurrence and onset of the main symptoms of DM1. Analyses validated the relevance of a five-grade model for DM1 classification. Patients were classified as: congenital (n=93, 4.5%); infantile (n=303, 14.8%); juvenile (n=628, 30.7%); adult (n=694, 34.0%); and late-onset (n=326, 15.9%). Our data show that the assumption of a continuum from congenital to the late-onset form is valid, and also highlights disease features specific to individual clinical forms of DM1 in terms of symptom occurrence and chronology throughout the disease course. These results support the use of the five-grade model for disease classification, and the distinct clinical profiles suggest that age of onset and clinical form may be key criteria in the design of clinical trials when considering DM1 health management and research.

Inhaled nitric oxide for acute chest syndrome in adult sickle cell patients: a randomized controlled study.

PURPOSE: Previous clinical trials suggested that inhaled nitric oxide (iNO) could have beneficial effects in sickle cell disease (SCD) patients with acute chest syndrome (ACS). METHODS: To determine whether iNO reduces treatment failure rate in adult patients with ACS, we conducted a prospective, double-blind, randomized, placebo-controlled clinical trial. iNO (80 ppm, N = 50) gas or inhaled nitrogen placebo (N = 50) was delivered for 3 days. The primary end point was the number of patients with treatment failure at day 3, defined as any one of the following: (1) death from any cause, (2) need for endotracheal intubation, (3) decrease of PaO2/FiO2 ≥ 15 mmHg between days 1 and 3, (4) augmented therapy defined as new transfusion or phlebotomy. RESULTS: The two groups did not differ in age, gender, genotype, or baseline characteristics and biological parameters. iNO was well tolerated, although a transient decrease in nitric oxide concentration was mandated in one patient. There was no significant difference in the primary end point between the iNO and placebo groups [23 (46 %) and 29 (58 %); odds ratio (OR), 0.8; 95 % CI, 0.54-1.16; p = 0.23]. A post hoc analysis of the 45 patients with hypoxemia showed that those in the iNO group were less likely to experience treatment failure at day 3 [7 (33.3 %) vs 18 (72 %); OR = 0.19; 95 % CI, 0.06-0.68; p = 0.009]. CONCLUSIONS: iNO did not reduce the rate of treatment failure in adult SCD patients with mild to moderate ACS. Future trials should target more severely ill ACS patients with hypoxemia. CLINICAL TRIAL REGISTRATION: NCT00748423.

Editor's Choice - ECAR (Endovasculaire ou Chirurgie dans les Anévrysmes aorto-iliaques Rompus): A French Randomized Controlled Trial of Endovascular Versus Open Surgical Repair of Ruptured Aorto-iliac Aneurysms.

OBJECTIVES/BACKGROUND: ECAR (Endovasculaire ou Chirurgie dans les Anévrysmes aorto-iliaques Rompus) is a prospective multicentre randomized controlled trial including consecutive patients with ruptured aorto-iliac aneurysms (rAIA) eligible for treatment by either endovascular (EVAR) or open surgical repair (OSR). Inclusion criteria were hemodynamic stability and computed tomography scan demonstrating aorto-iliac rupture. METHODS: Randomization was done by week, synchronously in all centers. The primary end point was 30 day mortality. Secondary end points were post-operative morbidity, length of stay in the intensive care unit (ICU), amount of blood transfused (units) and 6 month mortality. RESULTS: From January 2008 to January 2013, 107 patients (97 men, 10 women; median age 74.4 years) were enrolled in 14 centers: 56 (52.3%) in the EVAR group and 51 (47.7%) in the OSR group. The groups were similar in terms of age, sex, consciousness, systolic blood pressure, Hardman index, IGSII score, type of rupture, use of endoclamping balloon, and levels of troponin, creatinine, and hemoglobin. Delay to treatment was higher in the EVAR group (2.9 vs. 1.3 hours; p < .005). Mortality at 30 days and 1 year were not different between the groups (18% in the EVAR group vs. 24% in the OSR group at 30 days, and 30% vs. 35%, respectively, at 1 year). Total respiratory support time was lower in the EVAR group than in the OSR group (59.3 hours vs. 180.3 hours; p = .007), as were pulmonary complications (15.4% vs. 41.5%, respectively; p = .050), total blood transfusion (6.8 vs. 10.9, respectively; p = .020), and duration of ICU stay (7 days vs. 11.9 days, respectively; p = .010). CONCLUSION: In this study, EVAR was found to be equal to OSR in terms of 30 day and 1 year mortality. However, EVAR was associated with less severe complications and less consumption of hospital resources than OSR.

Early initiation of combined antiretroviral therapy preserves immune function in the gut of HIV-infected patients.

Massive loss of lamina propria CD4(+) T cells, changes in the lymphatic architecture, and altered intestinal epithelial barrier leading to microbial translocation are the common features of HIV-1 infection and are not fully restored under combined antiretroviral therapy (cART). To better understand determinants of gut mucosal restoration, we have performed phenotypic and gene expression analyses of the gut from HIV-infected patients, naive or treated with cART initiated either at the early phase of the primary infection or later during the chronic phase. We found a depletion of T helper type 22 (Th22) and interleukin-17-producing cells in naive patients. These populations, except Th22 cells, were not restored under cART. Regulatory T cells/Th17 ratio was significantly increased in HIV-infected patients and was inversely correlated to the restoration of CD4(+) T cells but not to gut HIV DNA levels. Gene profile analysis of gut mucosal distinguished two groups of patients, which fitted with the timing of cART initiation. In their majority early, but not later treated patients, exhibited conserved intestinal lymphoid structure, epithelial barrier integrity and dendritic cell maturation pathways. Our data demonstrate that early initiation of cART helps to preserve and/or restore lymphoid gut mucosal homeostasis and provide a rationale for initiating cART during the acute phase of HIV infection.

Extensive chronic GVHD is associated with donor blood CD34+ cell count after G-CSF mobilization in non-myeloablative allogeneic PBSC transplantation.

The correlation between the incidence of GVHD and the number of infused CD34(+) cells remains controversial for PBSC transplantation after a reduced-intensity-conditioning (RIC) regimen. We evaluated 99 patients transplanted with an HLA-identical sibling after the same RIC (2-Gy-TBI/fludarabine). Donor and recipient characteristics, donor's blood G-CSF-mobilized CD34(+) cell count, and number of infused CD34(+) and CD3(+) cells were analyzed as risk factors for acute and chronic GVHD There was a trend for an increased incidence of extensive chronic GVHD in the quartile of patients receiving more than 10 × 10(6) CD34(+) cells/kg (P = 0.05). Interestingly, the number of donor's blood CD34(+) cells at day 5 of G-CSF mobilization was closely associated with the incidence of extensive chronic GVHD, that is, 48% (95% CI: 28-68) at 24-months in the quartile of patients whose donors had the highest CD34(+) cell counts versus 24.3% (95% CI: 14-34) in the other patients (P = 0.007). In multivariate analysis, the only factor correlating with extensive chronic GVHD (cGVHD) was the donor's blood CD34(+) cell count after G-CSF (HR 2.49; 95% CI: 1.16-5.35, P = 0.019). This study shows that the incidence of cGVHD is more strongly associated with the donor's ability to mobilize CD34(+) cells than with the number of infused CD34(+) cells.

The Eigenfactor™ Score in highly specific medical fields: the dental model.

We sought to compare the Eigenfactor Score™ journal rank with the journal Impact Factor over five years, and to identify variables that may influence the ranking differences between the two metrics. Datasets were retrieved from the Thomson Reuters(®) and Eigenfactor Score™ Web sites. Dentistry was identified as the most specific medical specialty. Variables were retrieved from the selected journals to be included in a regression linear model. Among the 46 dental journals included in the analysis, striking variations in ranks were observed according to the metric used. The Bland-Altman plot showed a poor agreement between the metrics. The multivariate analysis indicates that the number of original research articles, the number of reviews, the self-citations, and the citing time may explain the differences between ranks. The Eigenfactor Score™ seems to better capture the prestige of a journal than the Impact Factor. In medicine, the bibliometric indicators should focus not only on the overall medical field but also on specialized disciplinary fields. Distinct measures are needed to better describe the scientific impact of specialized medical publications.

Liver stiffness measurement as a predictive tool of clinically significant portal hypertension in patients with compensated hepatitis C virus or alcohol-related cirrhosis.

BACKGROUND: Hepatic venous pressure gradient (HVPG) is the gold standard for assessing the presence and the severity of portal hypertension (PHT). Liver stiffness measurement (LSM) is a non-invasive method for liver fibrosis assessment. AIMS: To assess the relationship between LSM and HVPG in patients with compensated cirrhosis related to hepatitis C virus (HCV) or alcohol and to define the performance and the best cut-off of LSM for the diagnosis of PHT in these patients. METHODS: Between January 2004 and September 2006, we studied all the consecutive patients with compensated HCV or alcohol-related-cirrhosis referred for transjugular liver biopsy with HVPG measurement and LSM performed the same day. RESULTS: Ninety-two patients were eligible, 44 had HCV related-cirrhosis and 48 alcoholic cirrhosis. LSM was positively correlated to HVPG in both groups. The area under the receiver operating characteristic curve for the diagnosis of significant PHT was 0.76 +/- 0.07 in HCV patients (best cut-off at 20.5 kPa) and 0.94 +/- 0.03 (best cut-off at 34.9 kPa) in alcoholic patients. CONCLUSIONS: Liver stiffness measurement and HVPG were significantly correlated in patients with compensated cirrhosis because of HCV infection or alcohol. LSM could predict significant PHT in both these groups of patients with a higher cut-off and a better performance in alcoholic patients.

[Morbi-mortality after Hartmann procedure for peritonitis complicating sigmoid diverticulitis. A retrospective analysis of 85 cases]. / Morbimortalité de l'intervention de Hartmann pour péritonite diverticulaire. Etude rétrospective multicentrique à propos de 85 patients.

INTRODUCTION: Hartmann's procedure (HP) is a simple operation, which can be performed by all the surgeons. However, it remains criticized (high morbimortality, low rate of intestinal continuity restoration). The aim of this study was to analyse natural history of HP and intestinal continuity restoration for sigmoid diverticulitis, and to assess risk factors for mortality, morbidity and absence of intestinal continuity restoration. PATIENTS AND METHODS: In three centers, from 1992 to 2002, 85 patients underwent HP. A retrospective analysis was performed on mortality, early and late morbidity of HP and intestinal continuity restoration. RESULTS: 22% of patients (mean age, 68 years) presented comorbidity, 17% of them, an altered immunity, and 3 or 4 Hinchey score for 64%. ASA score was > or =3 in 49% of the cases. Mean AFC and Mannheim scores were 2 and 21 respectively. Mortality rate was 14% and in-hospital morbidity, 50%. Main complications were: cardiorespiratory (18%), wound abcess (14%) and stomal (6%). No rectal stump fistula was noted. Mean hospital stay was 19+/-13 days. Late morbidity rate was 29%, mainly due to stomal complications (12%) and small bowel obstruction (7%). Intestinal continuity restoration was done in 77% of the cases, followed by only 1 fistula. Mortality rate for intestinal continuity restoration was 0% and morbidity was 13%. Mean hospital stay was 10+/-3 days. Age >75 years, ASA score > or =3 and comorbidity were risk factors for morbidity and mortality and for absence of intestinal continuity restoration. CONCLUSIONS: HP is associated with a high morbidity and mortality rates. Intestinal continuity restoration rate was high in this series. HP is a simple operation in high-risk patients with advanced peritonitis. This study allows to precise natural history of HP. Knowledge of this history is crucial for choosing the best operation (between HP and anastomosis) for patient with peritonitis complications sigmoid diverticuitis.

Evaluating high dose therapy in Multiple Myeloma: use of quality-adjusted survival analysis.

PURPOSE: To incorporate quality-of-life considerations in assessing high dose therapy (HDT) for patients with Multiple Myeloma (MM). PATIENTS AND METHODS: A quality-adjusted survival analysis. using the quality-adjusted time without symptoms or toxicity (Q-TWiST) method, was applied to two randomized clinical trials conducted in patients with MM which compared randomized assignment to HDT vs. conventional chemotherapy (CCT) alone (MAG91) or followed by HDT (MAG90). Treatment benefit in terms of mean Q-TWiST was assessed through threshold utility analyses, i.e., sensitivity analyses of the choice of the utility coefficients over all possible values of utility weights. RESULTS: In both trials, results slightly favored the first-line HDT group over the first-line CCT group, with an average gain in TWiST of about 5.5 months over the 58 month-median follow-up period (27.8 vs. 22.3 months, respectively) in the MAG90 trial and 5.8 months over the 56 month-median follow-up period (19.1 vs. 13.3 months, respectively) in the MAG91 trial. The utility threshold analyses revealed that the first-line HDT group had a statistically increased mean quality-of-life adjusted time compared to the other group for a broad range of utility coefficient values. CONCLUSION: The development of such understandable and intuitive measures of expressing the relative benefit of complex treatment strategies is expected to be used in clinical decision making in the near future.

Descriptive epidemiology of non-Hodgkin lymphomas in a southwestern French hematology center: absence of significant relationship with hepatitis C virus infection.

From January 1995 to June 1998, 136 new cases of non-Hodgkin lymphomas (NHLs) were seen in our center which serves all the French Basque Country (300000 inhabitants). The crude and standardized incidence rates were respectively 13.2 and 7.6 cases/100000/year. The distribution of histologic subtypes according to the REAL classification showed a good correlation with the previous published data. Eleven patients (8%) were HIV-positive and two (1.4%) were HCV carriers. Hence, in our region, contrary to Italy, there is no evidence of relationship between HCV and NHLs.