DRD4 and DAT1 VNTR Genotyping in Children with Attention Deficit Hyperactivity Disorder.

The dopamine receptor-D4 and the dopamine transporter have been investigated for their role in attention deficit hyperactivity disorder (ADHD) in children. Reports of their genetic association with ADHD have shown mixed results. The aim of the study was to evaluate the association of variable number tandem repeats (VNTRs) of the DRD4 and DAT1 genes with ADHD in children. A pilot 1:1 case control study, with 44 clinically confirmed ADHD cases and 44 age/gender matched healthy controls, was conducted at a tertiary care centre in Mumbai. Variable number tandem repeats of DRD4 exon 3, DAT1 intron 8 and 3'UTR were genotyped by PCR-AGE. Several allele repeats of the genes were observed in the screened subjects. Statistical significance was observed for the 10R/10R genotype of the DAT1 3'UTR VNTR between cases and controls.

Molecular Characterization by Using Next-Generation Sequencing of Plasmids Containing blaNDM-7 in Enterobacteriaceae from Calgary, Canada.

Enterobacteriaceae with blaNDM-7 are relatively uncommon and had previously been described in Europe, India, the United States, and Japan. This study describes the characteristics of Enterobacteriaceae (Klebsiella pneumoniae [n = 2], Escherichia coli [n = 2], Serratia marcescens [n = 1], and Enterobacter hormaechei [n = 1] isolates) with blaNDM-7 obtained from 4 patients from Calgary, Canada, from 2013 to 2014. The 46,161-bp IncX3 plasmids with blaNDM-7 are highly similar to other blaNDM-harboring IncX3 plasmids and, interestingly, showed identical structures within the different isolates. This finding may indicate horizontal transmission within our health region, or it may indicate contact with individuals from areas of endemicity within the hospital setting. Patients infected or colonized with bacteria containing blaNDM-7 IncX3 plasmids generate infection control challenges. Epidemiological and molecular studies are required to better understand the dynamics of transmission, the risk factors, and the reservoirs for bacteria harboring blaNDM-7. To the best of our knowledge, this is the first report of S. marcescens and E. hormaechei with blaNDM-7.

Epidemiology and molecular characterization of bacteremia due to carbapenem-resistant Klebsiella pneumoniae in transplant recipients.

We conducted a retrospective study of 17 transplant recipients with carbapenem-resistant Klebsiella pneumoniae bacteremia, and described epidemiology, clinical characteristics and strain genotypes. Eighty-eight percent (15/17) of patients were liver or intestinal transplant recipients. Outcomes were death due to septic shock (18%), cure (24%) and persistent (>7 days) or recurrent bacteremia (29% each). Thirty- and 90-day mortality was 18% and 47%, respectively. Patients who were cured received at least one active antimicrobial agent and underwent source control interventions. Forty-one percent (7/17) of patients had intra-abdominal infections; all except one developed persistent/recurrent bacteremia despite drainage. Two patients tolerated persistent bacteremia for >300 days. All patients except one were infected with sequence type 258 (ST258), K. pneumoniae carbapenemase (KPC)-2-producing strains harboring a mutant ompK35 porin gene; the exception was infected with an ST37, KPC-3-producing strain. Seventy-one percent (12/17) of patients were infected with ST258 ompK36 mutant strains. In two patients, persistent bacteremia was caused by two strains with different ompK36 genotypes. Three ompK36 mutations were associated with significantly higher carbapenem minimum inhibitory concentrations than wild-type ompK36. Pulse-field gel electrophoresis identified a single ST258 lineage; serial strains from individual patients were indistinguishable. In conclusion, KPC-K. pneumoniae bacteremia exhibited highly diverse clinical courses following transplantation, and was caused by clonal ST258 strains with different ompK36 genotypes.

The effect of chronic digitalization on pump function in systolic heart failure.

BACKGROUND: Short- and intermediate-term use of cardiac glycosides promotes inotropy and improves the ejection fraction in systolic heart failure. AIM: To determine whether chronic digitalization alters left ventricular function and performance. METHODS: Eighty patients with mild-to-moderate systolic heart failure (baseline ejection fraction < or =45%) participated from our institution in a multi-center, chronic, randomized, double-blind study of digitalis vs. placebo. Of the 40 survivors, 38 (20 allocated to the digitalis arm and 18 to the placebo arm) were evaluated at the end of follow-up (mean, 48.4 months). Left ventricular systolic function was assessed by both nuclear ventriculography and echocardiography. The ejection fraction was measured scintigraphically, while the ventricular volumes were computed echocardiographically. RESULTS: The groups did not differ, at baseline or end-of-study, with respect to the ejection fraction and the loading conditions (arterial pressure, ventricular volumes and heart rate) by either intention-to-treat or actual-treatment-received analysis. Over the course of the trial, the digitalis arm exhibited no significant increase in the use of diuretics (18%, P=0.33), in distinction from the placebo group (78%, P=0.004), and a longer stay on study drug among those patients who withdrew from double-blind treatment (28.6 vs. 11.4 months, P=0.01). CONCLUSION: Following chronic use of digitalis for mild-to-moderate heart failure, cross-sectional comparison with a control group from the same inception cohort showed no appreciable difference in systolic function or performance. Thus, the suggested clinical benefit cannot be explained by an inotropic effect.

Circadian differences among 4,096 emergency department patients with acute asthma.

INTRODUCTION: In patients with asthma, airways narrow during the night. The clinical implications of a nocturnal presentation of patients with acute asthma to the emergency department (ED) are uncertain. OBJECTIVE: Our objective was to determine whether patients with asthma who had ED visits during the night (midnight to 7:59 am) vs. other times were more severe, responded less well to ED therapy, and had worse clinical outcomes. DESIGN AND SETTING: We performed a cohort study, as part of the Multicenter Airway Research Collaboration (n = 77 sites). ED patients with acute asthma, ages 2-54 yrs, underwent a structured interview in the ED. Chart review of missed/refusal patients created a truly consecutive case series. MEASUREMENTS AND MAIN RESULTS: Among 1,602 children, 19% presented at night Nighttime patients were more likely to be younger, male, and have a shorter duration of symptoms; there were no other clinical differences noted. Among 2,494 adults, 20% presented at night, and they were more likely to be female and to have a history of steroid use for asthma. Nighttime adults also had a shorter duration of symptoms and slightly lower peak flows (mean, 45% vs. 49% of predicted; p = .006) and were more likely to receive steroids. They were more likely to be intubated (2.0% vs. 0.2%; p < .001), but, overall, they were equally likely to be admitted or relapse after ED discharge. In contrast to objective measures of acute asthma severity, both nighttime children and adults were significantly less likely to report their asthma symptoms as severe. CONCLUSION: Except for endotracheal intubation (in adults only), circadian differences minimally affect ED presentation, therapy, or the outcomes of acute asthma. Nighttime asthmatics may be relatively insensitive to the symptoms of severe asthma.

Randomized trial of inhaled flunisolide versus placebo among asthmatic patients discharged from the emergency department.

STUDY OBJECTIVE: Inhaled corticosteroids (ICs) improve airflow and decrease symptoms in patients with chronic asthma. We examined whether high-dose inhaled flunisolide would have similar benefits after an emergency department visit for acute asthma. METHODS: Over a 16-month period at one inner-city ED, we documented 551 eligible patients (acute asthma; age 18 to 50 years; no ICs in past week; no oral corticosteroids in past month; and peak expiratory flow rate [PEFR] <70% of predicted value after first beta-agonist treatment); 104 patients agreed to participate. At ED discharge, all patients were given prednisone 40 mg/d for 5 days and inhaled beta-agonists as needed and were randomly assigned to receive high-dose inhaled flunisolide 2 mg/d (n=51) or placebo (n=53). Patients were telephoned daily and asked to return for PEFR measurement at 3, 7, 12, 21, and 24 days. RESULTS: Despite precautions, 28% (16 receiving flunisolide and 13 receiving placebo) of patients were completely lost to follow-up, 2 patients had only one follow-up (day 3), 2 patients receiving flunisolide withdrew because of medication-related bronchospasm, and 4 patients in each group experienced relapse. Among the 63 remaining patients, we found no difference between flunisolide and placebo at day 24 follow-up in percent predicted PEFR (87% versus 83% on day 24, P =.36; difference 4%, 95% confidence interval [CI] -5% to 13%). Nocturnal wheezing and nocturnal albuterol inhaler use was higher among patients receiving flunisolide than those receiving placebo on day 24 (48% versus 18% for nocturnal wheezing, P =.01; mean difference 30%, 95% CI 11% to 49%; 3.8 versus 1.4 nocturnal albuterol puffs, P =.03; mean difference 2.4 puffs, (95% CI 0.2 to 4). Levels of dyspnea, cough, and overall well-being were similar between the flunisolide and placebo groups. CONCLUSION: Addition of high-dose inhaled flunisolide to standard therapy does not benefit inner-city patients with acute asthma in the first 24 days after ED discharge. Airway inflammation during acute asthma may require higher doses or more potent anti-inflammatory agents.

A multi-centre comparative study of diclofenac sodium and a dipyrone/spasmolytic combination, and a single-centre comparative study of diclofenac sodium and pethidine in renal colic patients in India.

A single-blind, randomized clinical trial was carried out to compare the analgesic effectiveness in patients with renal colic of single intramuscular doses of diclofenac sodium (75 mg) versus a dipyrone (1 g)/spasmolytics combination, and diclofenac sodium (75 mg) versus pethidine (75 mg). The first study involved three centres, the second study one centre. In total, 107 patients were treated with diclofenac sodium, 85 with dipyrone/spasmolytics, and 25 with pethidine. Assessments were made during the first hour after drug administration of the degree of pain relief, the severity of pain using a visual analogue scale, and the duration of analgesia. A global assessment of treatment efficacy was made by the participating physicians at the end of the study period. Patients treated with diclofenac sodium showed an earlier onset of analgesia and a higher incidence of total pain relief compared to those treated with dipyrone/spasmolytics or pethidine. Although the mean duration of analgesia was only slightly greater in the diclofenac sodium group than in the dipyrone/spasmolytics group, a significantly longer effect was seen when diclofenac sodium was compared with pethidine (p less than 0.01). Pain severity assessments revealed that diclofenac sodium caused a significantly greater improvement in pain after 60 minutes compared to dipyrone/spasmolytics (p less than 0.05) and after 30 minutes compared to pethidine (p less than 0.05). Global efficacy assessments by the physician rated diclofenac sodium as significantly superior to dipyrone/spasmolytics (p less than 0.01) and pethidine (p less than 0.001). Moreover, diclofenac sodium was better tolerated than either of the comparative treatments. The results indicate that intramuscular diclofenac sodium is a useful alternative to the drugs commonly used in India in the treatment of renal colic.