Quantitative antibiogram as a typing method for the prospective epidemiological surveillance and control of MRSA: comparison with molecular typing.

OBJECTIVE: Evaluation of the quantitative antibiogram as an epidemiological tool for the prospective typing of methicillin-resistant Staphylococcus aureus (MRSA), and comparison with ribotyping. METHODS: The method is based on the multivariate analysis of inhibition zone diameters of antibiotics in disk diffusion tests. Five antibiotics were used (erythromycin, clindamycin, cotrimoxazole, gentamicin, and ciprofloxacin). Ribotyping was performed using seven restriction enzymes (EcoRV, HindIII, KpnI, PstI, EcoRI, SfuI, and BamHI). SETTING: 1,000-bed tertiary university medical center. RESULTS: During a 1-year period, 31 patients were found to be infected or colonized with MRSA. Cluster analysis of antibiogram data showed nine distinct antibiotypes. Four antibiotypes were isolated from multiple patients (2, 4, 7, and 13, respectively). Five additional antibiotypes were isolated from the remaining five patients. When analyzed with respect to the epidemiological data, the method was found to be equivalent to ribotyping. Among 206 staff members who were screened, six were carriers of MRSA. Both typing methods identified concordant of MRSA types in staff members and in the patients under their care. CONCLUSIONS: The quantitative antibiogram was found to be equivalent to ribotyping as an epidemiological tool for typing of MRSA in our setting. Thus, this simple, rapid, and readily available method appears to be suitable for the prospective surveillance and control of MRSA for hospitals that do not have molecular typing facilities and in which MRSA isolates are not uniformly resistant or susceptible to the antibiotics tested.

Pulse pressure variation-guided fluid therapy after cardiac surgery: A pilot before-and-after trial.

PURPOSE: The aim of this study is to study the feasibility, safety, and physiological effects of pulse pressure variation (PPV)-guided fluid therapy in patients after cardiac surgery. MATERIALS AND METHODS: We conducted a pilot prospective before-and-after study during mandatory ventilation after cardiac surgery in a tertiary intensive care unit. We introduced a protocol to deliver a fluid bolus for a PPV ≥13% for at least >10 minutes during the intervention period. RESULTS: We studied 45 control patients and 53 intervention patients. During the intervention period, clinicians administered a fluid bolus on 79% of the defined PPV trigger episodes. Median total fluid intake was similar between 2 groups during mandatory ventilation (1297 mL [interquartile range 549-1968] vs 1481 mL [807-2563]; P = .17) and the first 24 hours (3046 mL [interquartile range 2317-3982] vs 3017 mL [2192-4028]; P = .73). After adjusting for several baseline factors, PPV-guided fluid management significantly increased fluid intake during mandatory ventilation (P = .004) but not during the first 24 hours (P = .47). Pulse pressure variation-guided fluid therapy, however, did not significantly affect hemodynamic, renal, and metabolic variables. No serious adverse events were noted. CONCLUSIONS: Pulse pressure variation-guided fluid management was feasible and safe during mandatory ventilation after cardiac surgery. However, its advantages may be clinically small.

A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control.

HIV-1 sequence diversity is affected by selection pressures arising from host genomic factors. Using paired human and viral data from 1071 individuals, we ran >3000 genome-wide scans, testing for associations between host DNA polymorphisms, HIV-1 sequence variation and plasma viral load (VL), while considering human and viral population structure. We observed significant human SNP associations to a total of 48 HIV-1 amino acid variants (p<2.4 × 10(-12)). All associated SNPs mapped to the HLA class I region. Clinical relevance of host and pathogen variation was assessed using VL results. We identified two critical advantages to the use of viral variation for identifying host factors: (1) association signals are much stronger for HIV-1 sequence variants than VL, reflecting the 'intermediate phenotype' nature of viral variation; (2) association testing can be run without any clinical data. The proposed genome-to-genome approach highlights sites of genomic conflict and is a strategy generally applicable to studies of host-pathogen interaction. DOI:http://dx.doi.org/10.7554/eLife.01123.001.

Alpha1b-adrenergic receptors control locomotor and rewarding effects of psychostimulants and opiates.

Drugs of abuse, such as psychostimulants and opiates, are generally considered as exerting their locomotor and rewarding effects through an increased dopaminergic transmission in the nucleus accumbens. Noradrenergic transmission may also be implicated because most psychostimulants increase norepinephrine (NE) release, and numerous studies have indicated interactions between noradrenergic and dopaminergic neurons through alpha1-adrenergic receptors. However, analysis of the effects of psychostimulants after either destruction of noradrenergic neurons or pharmacological blockade of alpha1-adrenergic receptors led to conflicting results. Here we show that the locomotor hyperactivities induced by d-amphetamine (1-3 mg/kg), cocaine (5-20 mg/kg), or morphine (5-10 mg/kg) in mice lacking the alpha1b subtype of adrenergic receptors were dramatically decreased when compared with wild-type littermates. Moreover, behavioral sensitizations induced by d-amphetamine (1-2 mg/kg), cocaine (5-15 mg/kg), or morphine (7.5 mg/kg) were also decreased in knock-out mice when compared with wild-type. Ruling out a neurological deficit in knock-out mice, both strains reacted similarly to novelty, to intraperitoneal saline, or to the administration of scopolamine (1 mg/kg), an anti-muscarinic agent. Finally, rewarding properties could not be observed in knock-out mice in an oral preference test (cocaine and morphine) and conditioned place preference (morphine) paradigm. Because catecholamine tissue levels, autoradiography of D1 and D2 dopaminergic receptors, and of dopamine reuptake sites and locomotor response to a D1 agonist showed that basal dopaminergic transmission was similar in knock-out and wild-type mice, our data indicate a critical role of alpha1b-adrenergic receptors and noradrenergic transmission in the vulnerability to addiction.

Precision of tibial tunnel placement under arthroscopic control alone in posterior cruciate ligament reconstruction: A radiological study

Introduction: Accurate and reproducible tibial tunnel placement minimizing the risk of neurovascular damage is a crucial condition for successful arthroscopic reconstruction of the posterior cruciate ligament (PCL). This step is commonly performed under fluoroscopic control. Hypothesis: Performing the tibial tunnel under exclusive arthroscopic control allows accurate and reliable tunnel placement according to recommendations in the literature. Materials and Methods: Between February 2007 and December 2009, 108 arthroscopic single bundle PCL reconstructions in tibial tunnel technique were performed. The routine postoperative radiographs were screened according to previously defined quality criterions. After critical analysis, the radiographs of 48 patients (48 knees) were enrolled in the study. 10 patients had simultaneous ACL reconstruction and 7 had PCL revision surgery. The tibial tunnel was placed under direct arthroscopic control through a posteromedial portal using a standard tibial aming device. Key anatomical landmarks were the exposed tibial insertion of the PCL and the posterior horn of the medial meniscus. First, the centre of the posterior tibial tunnel outlet on the a-p view was determined by digital analysis of the postoperative radiographes. Its distance to the medial tibial spine was measured parallel to the tibia plateau. The mediolateral position was expressed by the ratio between the distance of the tunnel outlet to the medial border and the total width of the tibial plateau. On the lateral view the vertical tunnel position was measured perpendicularly to a tangent of the medial tibial plateau. All measurement were repeated at least twice and carried out by two examiners. Results: The mean mediolateral tunnel position was 49.3 ± 4.6% (ratio), 6.7 ± 3.6 mm lateral to the medial tibial spine. On the lateral view the tunnel centre was 10.1 ± 4.5 mm distal to the bony surface of the medial tibial plateau. Neurovascular damage was observed in none of our patients. Conclusion: The results of this radiological study confirm that exclusive arthroscopic control for tibial tunnel placement in PCL reconstruction yields reproducible and accurate results according to the literature. Our technique avoids radiation, facilitates the operation room setting and enables the surgeon to visualize the anatomic key landmarks for tibial tunnel placement.

Optimal and continuous anaemia control in a cohort of dialysis patients in Switzerland.

BACKGROUND: Guidelines for the management of anaemia in patients with chronic kidney disease (CKD) recommend a minimal haemoglobin (Hb) target of 11 g/dL. Recent surveys indicate that this requirement is not met in many patients in Europe. In most studies, Hb is only assessed over a short-term period. The aim of this study was to examine the control of anaemia over a continuous long-term period in Switzerland. METHODS: A prospective multi-centre observational study was conducted in dialysed patients treated with recombinant human epoetin (EPO) beta, over a one-year follow-up period, with monthly assessments of anaemia parameters. RESULTS: Three hundred and fifty patients from 27 centres, representing 14% of the dialysis population in Switzerland, were included. Mean Hb was 11.9 +/- 1.0 g/dL, and remained stable over time. Eighty-five % of the patients achieved mean Hb &gt;or= 11 g/dL. Mean EPO dose was 155 +/- 118 IU/kg/week, being delivered mostly by subcutaneous route (64-71%). Mean serum ferritin and transferrin saturation were 435 +/- 253 microg/L and 30 +/- 11%, respectively. At month 12, adequate iron stores were found in 72.5% of patients, whereas absolute and functional iron deficiencies were observed in only 5.1% and 17.8%, respectively. Multivariate analysis showed that diabetes unexpectedly influenced Hb towards higher levels (12.1 +/- 0.9 g/dL; p = 0.02). One year survival was significantly higher in patients with Hb &gt;or= 11 g/dL than in those with Hb &lt;11 g/dL (19.7% vs 7.3%, p = 0.006). CONCLUSION: In comparison to European studies of reference, this survey shows a remarkable and continuous control of anaemia in Swiss dialysis centres. These results were reached through moderately high EPO doses, mostly given subcutaneously, and careful iron therapy management.

Impact of electronic monitoring of drug adherence on blood pressure control in primary care: a cluster 12-month randomised controlled study.

BACKGROUND: Poor long-term adherence is an important cause of uncontrolled hypertension. We examined whether monitoring drug adherence with an electronic system improves long-term blood pressure (BP) control in hypertensive patients followed by general practitioners (GPs). METHODS: A pragmatic cluster randomised controlled study was conducted over one year in community pharmacists/GPs' networks randomly assigned either to usual care (UC) where drugs were dispensed as usual, or to intervention (INT) group where drug adherence could be monitored with an electronic system (Medication Event Monitoring System). No therapy change was allowed during the first 2 months in both groups. Thereafter, GPs could modify therapy and use electronic monitors freely in the INT group. The primary outcome was a target office BP<140/90 mmHg. RESULTS: Sixty-eight treated uncontrolled hypertensive patients (UC: 34; INT: 34) were enrolled. Over the 12-month period, the likelihood of reaching the target BP was higher in the INT group compared to the UC group (p<0.05). At 4 months, 38% in the INT group reached the target BP vs. 12% in the UC group (p<0.05), and 21% vs. 9% at 12 months (p: ns). Multivariate analyses, taking account of baseline characteristics, therapy modification during follow-up, and clustering effects by network, indicate that being allocated to the INT group was associated with a greater odds of reaching the target BP at 4 months (p<0.01) and at 12 months (p=0.051). CONCLUSION: GPs monitoring drug adherence in collaboration with pharmacists achieved a better BP control in hypertensive patients, although the impact of monitoring decreased with time.

Interleukin-17 is a critical mediator of vaccine-induced reduction of Helicobacter infection in the mouse model.

BACKGROUND &amp; AIMS: Despite the proven ability of immunization to reduce Helicobacter infection in mouse models, the precise mechanism of protection has remained elusive. This study explores the possibility that interleukin (IL)-17 plays a role in the reduction of Helicobacter infection following vaccination of wild-type animals or in spontaneous reduction of bacterial infection in IL-10-deficient mice. METHODS: In mice, reducing Helicobacter infection, the levels and source of IL-17 were determined and the role of IL-17 in reduction of Helicobacter infection was probed by neutralizing antibodies. RESULTS: Gastric IL-17 levels were strongly increased in mice mucosally immunized with urease plus cholera toxin and challenged with Helicobacter felis as compared with controls (654 +/- 455 and 34 +/- 84 relative units for IL-17 messenger RNA expression [P &lt; .01] and 6.9 +/- 8.4 and 0.02 +/- 0.04 pg for IL-17 protein concentration [P &lt; .01], respectively). Flow cytometry analysis showed that a peak of CD4(+)IL-17(+) T cells infiltrating the gastric mucosa occurred in immunized mice in contrast to control mice (4.7% +/- 0.3% and 1.4% +/- 0.3% [P &lt; .01], respectively). Gastric mucosa-infiltrating CD4(+)IL-17(+) T cells were also observed in IL-10-deficient mice that spontaneously reduced H felis infection (4.3% +/- 2.3% and 2% +/- 0.6% [P &lt; .01], for infected and noninfected IL-10-deficient mice, respectively). In wild-type immunized mice, intraperitoneal injection of anti-IL-17 antibodies significantly inhibited inflammation and the reduction of Helicobacter infection in comparison with control antibodies (1 of 12 mice vs 9 of 12 mice reduced Helicobacter infection [P &lt; .01], respectively). CONCLUSIONS: IL-17 plays a critical role in the immunization-induced reduction of Helicobacter infection from the gastric mucosa.

Impact of tight glycemic control on cerebral glucose metabolism after severe brain injury: a microdialysis study.

OBJECTIVES: To analyze the effect of tight glycemic control with the use of intensive insulin therapy on cerebral glucose metabolism in patients with severe brain injury. DESIGN: Retrospective analysis of a prospective observational cohort. SETTING: University hospital neurologic intensive care unit. PATIENTS: Twenty patients (median age 59 yrs) monitored with cerebral microdialysis as part of their clinical care. INTERVENTIONS: Intensive insulin therapy (systemic glucose target: 4.4-6.7 mmol/L [80-120 mg/dL]). MEASUREMENTS AND MAIN RESULTS: Brain tissue markers of glucose metabolism (cerebral microdialysis glucose and lactate/pyruvate ratio) and systemic glucose were collected hourly. Systemic glucose levels were categorized as within the target "tight" (4.4-6.7 mmol/L [80-120 mg/dL]) vs. "intermediate" (6.8-10.0 mmol/L [121-180 mg/dL]) range. Brain energy crisis was defined as a cerebral microdialysis glucose <0.7 mmol/L with a lactate/pyruvate ratio >40. We analyzed 2131 cerebral microdialysis samples: tight systemic glucose levels were associated with a greater prevalence of low cerebral microdialysis glucose (65% vs. 36%, p < 0.01) and brain energy crisis (25% vs.17%, p < 0.01) than intermediate levels. Using multivariable analysis, and adjusting for intracranial pressure and cerebral perfusion pressure, systemic glucose concentration (adjusted odds ratio 1.23, 95% confidence interval [CI] 1.10-1.37, for each 1 mmol/L decrease, p < 0.001) and insulin dose (adjusted odds ratio 1.10, 95% CI 1.04-1.17, for each 1 U/hr increase, p = 0.02) independently predicted brain energy crisis. Cerebral microdialysis glucose was lower in nonsurvivors than in survivors (0.46 +/- 0.23 vs. 1.04 +/- 0.56 mmol/L, p < 0.05). Brain energy crisis was associated with increased mortality at hospital discharge (adjusted odds ratio 7.36, 95% CI 1.37-39.51, p = 0.02). CONCLUSIONS: In patients with severe brain injury, tight systemic glucose control is associated with reduced cerebral extracellular glucose availability and increased prevalence of brain energy crisis, which in turn correlates with increased mortality. Intensive insulin therapy may impair cerebral glucose metabolism after severe brain injury.

Drinking Patterns and Their Predictive Factors in CONTROL: a 12-Month Prospective Study in a Sample of Alcohol-Dependent Patients Initiating Treatment.

Aims: To describe the drinking patterns and their baseline predictive factors during a 12-month period after an initial evaluation for alcohol treatment. Methods CONTROL is a single-center, prospective, observational study evaluating consecutive alcohol-dependent patients. Using a curve clustering methodology based on a polynomial regression mixture model, we identified three clusters of patients with dominant alcohol use patterns described as mostly abstainers, mostly moderate drinkers and mostly heavy drinkers. Multinomial logistic regression analysis was used to identify baseline factors (socio-demographic, alcohol dependence consequences and related factors) predictive of belonging to each drinking cluster. ResultsThe sample included 143 alcohol-dependent adults (63.6% males), mean age 44.6 ± 11.8 years. The clustering method identified 47 (32.9%) mostly abstainers, 56 (39.2%) mostly moderate drinkers and 40 (28.0%) mostly heavy drinkers. Multivariate analyses indicated that mild or severe depression at baseline predicted belonging to the mostly moderate drinkers cluster during follow-up (relative risk ratio (RRR) 2.42, CI [1.02-5.73, P = 0.045] P = 0.045), while living alone (RRR 2.78, CI [1.03-7.50], P = 0.044) and reporting more alcohol-related consequences (RRR 1.03, CI [1.01-1.05], P = 0.004) predicted belonging to the mostly heavy drinkers cluster during follow-up. Conclusion In this sample, the drinking patterns of alcohol-dependent patients were predicted by baseline factors, i.e. depression, living alone or alcohol-related consequences and findings that may inform clinicians about the likely drinking patterns of their alcohol-dependent patient over the year following the initial evaluation for alcohol treatment.

Nervous glucose sensing regulates postnatal β cell proliferation and glucose homeostasis.

How glucose sensing by the nervous system impacts the regulation of β cell mass and function during postnatal development and throughout adulthood is incompletely understood. Here, we studied mice with inactivation of glucose transporter 2 (Glut2) in the nervous system (NG2KO mice). These mice displayed normal energy homeostasis but developed late-onset glucose intolerance due to reduced insulin secretion, which was precipitated by high-fat diet feeding. The β cell mass of adult NG2KO mice was reduced compared with that of WT mice due to lower β cell proliferation rates in NG2KO mice during the early postnatal period. The difference in proliferation between NG2KO and control islets was abolished by ganglionic blockade or by weaning the mice on a carbohydrate-free diet. In adult NG2KO mice, first-phase insulin secretion was lost, and these glucose-intolerant mice developed impaired glucagon secretion when fed a high-fat diet. Electrophysiological recordings showed reduced parasympathetic nerve activity in the basal state and no stimulation by glucose. Furthermore, sympathetic activity was also insensitive to glucose. Collectively, our data show that GLUT2-dependent control of parasympathetic activity defines a nervous system/endocrine pancreas axis that is critical for β cell mass establishment in the postnatal period and for long-term maintenance of β cell function.

How important are interview methods and questionnaire designs in research on self-reported juvenile delinquency? An experimental comparison of internet vs. paper-and-pencil questionnaires and different definitions of the reference period

There has been relatively little change over recent decades in the methods used in research on self-reported delinquency. Face-to-face interviews and selfadministered interviews in the classroom are still the predominant alternatives envisaged. New methods have been brought into the picture by recent computer technology, the Internet, and an increasing availability of computer equipment and Internet access in schools. In the autumn of 2004, a controlled experiment was conducted with 1,203 students in Lausanne (Switzerland), where "paper-and-pencil" questionnaires were compared with computer-assisted interviews through the Internet. The experiment included a test of two different definitions of the (same) reference period. After the introductory question ("Did you ever..."), students were asked how many times they had done it (or experienced it), if ever, "over the last 12 months" or "since the October 2003 vacation". Few significant differences were found between the results obtained by the two methods and for the two definitions of the reference period, in the answers concerning victimisation, self-reported delinquency, drug use, failure to respond (missing data). Students were found to be more motivated to respond through the Internet, take less time for filling out the questionnaire, and were apparently more confident of privacy, while the school principals were less reluctant to allow classes to be interviewed through the Internet. The Internet method also involves considerable cost reductions, which is a critical advantage if self-reported delinquency surveys are to become a routinely applied method of evaluation, particularly so in countries with limited resources. On balance, the Internet may be instrumental in making research on self-reported delinquency far more feasible in situations where limited resources so far have prevented its implementation.

Long-distance wolf recolonization of France and Switzerland inferred from non-invasive genetic sampling over a period of 10 years

In the early 1900s, the wolf (Canis lupus) was extirpated from France and Switzerland. There is growing evidence that the species is presently recolonizing these countries in the western Alps. By sequencing the mitochondrial DNA (mtDNA) control region of various samples mainly collected in the field (scats, hairs, regurgitates, blood or tissue; n = 292), we could (1) develop a non-invasive method enabling the unambiguous attribution of these samples to wolf, fox (Vulpes vulpes) or dog (Canis familiaris), among others; (2) demonstrate that Italian, French and Swiss wolves share the same mtDNA haplotype, a haplotype that has never been found in any other wolf population world-wide. Combined together, field and genetic data collected over 10 years corroborate the scenario of a natural expansion of wolves from the Italian source population. Furthermore, such a genetic approach is of conservation significance, since it has important consequences for management decisions. This first long-term report using non-invasive sampling demonstrates that long-distance dispersers are common, supporting the hypothesis that individuals may often attempt to colonize far from their native pack, even in the absence of suitable corridors across habitats characterized by intense human activities.

2 years' review of pediatric emergencies admitted in the resuscitation room of a Swiss university hospital

Introduction: Paediatric resuscitation is an intense, stressful andchallenging process performed in a specific surrounding. In theresuscitation room (RR), a dedicated pediatric team is not alwaysavailable and its composition varies according to local resources. Aregular review of the children admitted in the resuscitation room andthe assessment of various outcome measures are the basis of qualitycontrol (QC). The epidemiology of Potentially Life ThreateningPaediatric (LTP) emergencies admitted in a Swiss university hospitalhas never been reported. The aims of this study were to review theLTP emergency population with regards to origin, patients'demographics, reason for admission and final diagnosis, treatmentmodalities, critical events and outcome.Methods: A retrospective observational cohort study of prospectivelycollected data was conducted, including all LTP emergencies admittedover a period of 2 years in the RR of a Swiss university hospitalfunctioning as a tertiary level referral centre. Multiple variablesincluding indication for transfer, mode of pre-hospital transportation,diagnosis and the time spent in RR were assessed. Data assessmenttook place 2 years after the implementation of a quality control (QC)team assessing the pediatric resuscitations occurring within theinstitution on a monthly basis.Results: Out of 60 939 pediatric emergencies treated in LausanneUniversity Medical center over 2 years, a total of 277 LTP emergencies(0.46%) were admitted to the RR, including 160 boys and 117 girls,aged 6 days to 15.95 years (mean 6.69 years, median 5.06). The tablebelow illustrates in more details the identified problems, average age,time in hospital and outcome of both surgical and medical groups ofpatients.Conclusions: With the need for health care quality improvement andfinancial restrictions, an excellent knowledge of the characteristics ofLTP emergencies is unavoidable. A thorough understanding of theresuscitation process and humans resources involved can be achievedwith a systematic review of the cases. A dedicated quality control teamevaluating LTP emergencies in a hospital will identify areas forimprovement. A LTP registry at the national level would be of greatvalue in Switzerland.