BK virus infection in hematopoietic stem cell transplant recipients: frequency, risk factors, and association with postengraftment hemorrhagic cystitis.

Blood samples from 132 consecutive hematopoietic stem cell transplant recipients were obtained and tested weekly for BK virus DNA by use of quantitative real-time PCR. Forty-four patients (33%) developed BK viremia at a median of 41 days (range, 9-91 days) after transplantation. Patients with hemorrhagic cystitis that occurred after platelet engraftment had higher levels of viremia than did patients without hemorrhagic cystitis (median, 9.7x10(3) vs. 0 copies/mL; P=.008) and patients with hemorrhagic cystitis that occurred before platelet engraftment (median, 9.7x10(3) vs. 0 copies/mL; P=.0006). BK viremia also was strongly associated with postengraftment hemorrhagic cystitis in a time-dependent analysis (P=.004).

Cardiorenal end points in a trial of aliskiren for type 2 diabetes.

BACKGROUND: This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both. METHODS: In a double-blind fashion, we randomly assigned 8561 patients to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failure; end-stage renal disease, death attributable to kidney failure, or the need for renal-replacement therapy with no dialysis or transplantation available or initiated; or doubling of the baseline serum creatinine level. RESULTS: The trial was stopped prematurely after the second interim efficacy analysis. After a median follow-up of 32.9 months, the primary end point had occurred in 783 patients (18.3%) assigned to aliskiren as compared with 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence interval [CI], 0.98 to 1.20; P=0.12). Effects on secondary renal end points were similar. Systolic and diastolic blood pressures were lower with aliskiren (between-group differences, 1.3 and 0.6 mm Hg, respectively) and the mean reduction in the urinary albumin-to-creatinine ratio was greater (between-group difference, 14 percentage points; 95% CI, 11 to 17). The proportion of patients with hyperkalemia (serum potassium level, ≥6 mmol per liter) was significantly higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%), as was the proportion with reported hypotension (12.1% vs. 8.3%) (P<0.001 for both comparisons). CONCLUSIONS: The addition of aliskiren to standard therapy with renin-angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful. (Funded by Novartis; ALTITUDE ClinicalTrials.gov number, NCT00549757.).

Enhanced kangaroo mother care for heel lance in preterm neonates: a crossover trial.

OBJECTIVE: To test if enhancing maternal skin-to-skin contact, or kangaroo mother care (KMC) by adding rocking, singing and sucking is more efficacious than simple KMC for procedural pain in preterm neonates. STUDY DESIGN: Preterm neonates (n=90) between 32 0/7 and 36 0/7 weeks' gestational age participated in a single-blind randomized crossover design. The infant was held in KMC with the addition of rocking, singing and sucking or the infant was held in KMC without additional stimulation. The Premature Infant Pain Profile was the primary outcome with time to recover as the secondary outcome. A repeated-measures analysis of covariance was employed for analyses. RESULT: There were no significant differences in any of the 30 s time periods over the 2 min of blood sampling nor in time to return to baseline. Compared to historical controls of the same age in incubator, the pain scores were lower and comparable to other studies of KMC. There were site differences related to lower scores with the use of sucrose in one site and higher scores in younger, sicker infants in another site. CONCLUSION: The sensorial stimulations from skin-to-skin contact that include tactile, olfactory sensations from the mother are sufficient to decrease pain response in premature neonates. Other studies showing that rocking, sucking and music were efficacious were independent of skin-to-skin contact, which, when used alone has been shown to be effective as reported across studies.

Intrathecal administration of Ziconotide: does single-shot injection predict efficacy?

Introduction: Though a trial of intrathecal (IT) therapy should always be performed before implantation of a definitive intrathecal pump, there is no agreement as to how this test should be performed. Ziconotide is trialed in most of cases with continuous IT administration using implanted catheters. Unlike other intrathecal drugs, there is little experience with single bolus IT injections of ziconotide. The aim of the study is to assess the feasibility of single-shot IT trialing with ziconotide. Patients and methods: Eleven consecutive patients with chronic neuropathic intractable pain were trialed with a single IT bolus of 2.5 mcg of ziconotide. Pain and side effects are monitored for at least 72 hours after the injection. Depending on the response, a second injection is given a week later, with either the same dose (if VAS decreased ≥50% without side effects), a higher dose of 3.75 mcg (if VAS decreased <50% without side effects) or a lower dose of 1.25 mcg (if VAS decreased ≥50% but with side effects). If VAS decreased less than 50% and side effects occurred, no further injection was performed. When VAS decreased >50% without side effects after the first or the second dose, the result is confirmed by one more injection of the same dose one week later. The trial is considered positive if two successive injections provide a VAS decreased more than 50% without side effects. Results: Eleven patients (6 females and 5 males) were included. Nine patients experienced modest or no pain relief. Four of these had significant side effects (dizziness, nausea, vomiting or abdominal pain) and had no further injection. In the others 5, one patient retired from study and four received a second injection of 3.75 mcg. The trial was negative in all 5 cases because of side effects (dizziness, drowsiness, weakness, muscle cramps), the pain decreased in only 2 patients. Two patients experienced profound pain relief with an IT injection of 2.5 mcg. One patient had no side effects and the other had dizziness and drowsiness that disappeared with an injection of 1.25 mcg. Pain relief without adverse effects was confirmed with the second injection. The trial was considered positive for those two patients. Discussion and conclusion: The response rate of 18% (2/11) is consistent with the success rate of a continuous infusion trialing with an implanted catheter. Single-shot injection of ziconotide may therefore predict efficacy.

Consommation d'alcool et de benzodiozépines au troisième âge [Consumption of alcohol and benzodiazepines in the elderly]

In Switzerland, 9.1% of the general population accept regular consumption of BZD. In 65-74 years age group, 2% of cases display a high-risk alcohol consumption. Moderate risk consumption is present in 5% of cases. For the BZD, the cognitive difficulties settle in an insidious way; for alcohol, the daily consumption of fairly high quantities may lead to cognitive deterioration. At early stages, alcohol abusers show preserved neuropsychological performances. Gradually, the deficits will affect the remaining cognitive functions and become irreversible. This review indicates that the chronic consumption of alcohol and BZD in old age is at the origin of major clinical difficulties that need ad hoc training both for psychiatrists and general practitioners.

Home versus in-hospital treatment of outpatients with acute deep venous thrombosis of the lower limbs.

BACKGROUND: Some physicians are still concerned about the safety of treatment at home of patients with acute deep venous thrombosis (DVT). METHODS: We used data from the RIETE (Registro Informatizado de la Enfermedad TromboEmbólica) registry to compare the outcomes in consecutive outpatients with acute lower limb DVT according to initial treatment at home or in the hospital. A propensity score-matching analysis was carried out with a logistic regression model. RESULTS: As of December 2012, 13,493 patients had been enrolled. Of these, 4456 (31%) were treated at home. Patients treated at home were more likely to be male and younger and to weigh more; they were less likely than those treated in the hospital to have chronic heart failure, lung disease, renal insufficiency, anemia, recent bleeding, immobilization, or cancer. During the first week of anticoagulation, 27 patients (0.20%) suffered pulmonary embolism (PE), 12 (0.09%) recurrent DVT, and 51 (0.38%) major bleeding; 80 (0.59%) died. When only patients treated at home were considered, 12 (0.27%) had PE, 4 (0.09%) had recurrent DVT, 6 (0.13%) bled, and 4 (0.09%) died (no fatal PE, 3 fatal bleeds). After propensity analysis, patients treated at home had a similar rate of venous thromboembolism recurrences and a lower rate of major bleeding (odds ratio, 0.4; 95% confidence interval, 0.1-1.0) or death (odds ratio, 0.2; 95% confidence interval, 0.1-0.7) within the first week compared with those treated in the hospital. CONCLUSIONS: In outpatients with DVT, home treatment was associated with a better outcome than treatment in the hospital. These data may help safely treat more DVT patients at home.

Official Positions for FRAX® clinical regarding smoking from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®.

The worldwide prevalence of smoking has been estimated at about 50% in men, and 10% in women, with larger variations among different populations studied. Smoking has been shown to affect many organ systems resulting in severe morbidity and increased mortality. In addition, smoking has been identified as a predictor of ten-year fracture risk in men and women, largely independent of an individual's bone mineral density. This finding has eventually lead to incorporation of this risk factor into FRAX®, an algorithm that has been developed to calculate an individual's ten-year fracture risk. However, only little, or conflicting data is available on a possible association between smoking dose, duration, length of time after cessation, type of tobacco and fracture risk, limiting this risk factor's applicability in the context of FRAX®.

Urinary D-lactate excretion in infants receiving Lactobacillus johnsonii with formula.

BACKGROUND/AIMS: Supplementation with certain probiotics can improve gut microbial flora and immune function but should not have adverse effects. This study aimed to assess the risk of D-lactate accumulation and subsequent metabolic acidosis in infants fed on formula containing Lactobacillus johnsonii (La1). METHODS: In the framework of a double-blind, randomized controlled trial enrolling 71 infants aged 4-5 months, morning urine samples were collected before and 4 weeks after being fed formulas with or without La1 (1 x 10(8)/g powder) or being breastfed. Urinary D- and L-lactate concentrations were assayed by enzymatic, fluorimetric methods and excretion was normalized per mol creatinine. RESULTS: At baseline, no significant differences in urinary D-/L-lactate excretion among the formula-fed and breastfed groups were found. After 4 weeks, D-lactate excretion did not differ between the two formula groups, but was higher in both formula groups than in breastfed infants. In all infants receiving La1, urinary D-lactate concentrations remained within the concentration ranges of age-matched healthy infants which had been determined in an earlier study using the same analytical method. Urinary L-lactate also did not vary over time or among groups. CONCLUSIONS: Supplementation of La1 to formula did not affect urinary lactate excretion and there is no evidence of an increased risk of lactic acidosis.

Frequent accesses to totally implanted vascular ports in pediatric oncology patients are associated with higher infection rates.

PURPOSE: Totally implanted vascular (TIVA) ports are used in children for repeated blood samples or intravenous treatments. We have recently published a prospective evaluation of surgical incidents and early complications associated with these devices. This work is the final part of the same study, assessing late complications over a follow-up of 2 yrs. METHODS: From January 2006 to January 2008, children older than 1 yr of age with a diagnosis of solid or blood cell malignancy were included. Insertion technique and care of the device were standardized. Every manipulation was prospectively recorded by specialized nurses. Obstruction was documented clinically. When bacteremia was suspected, routine central and peripheral blood cultures were drawn. RESULTS: Forty-five consecutive patients were enrolled in the study. Mean age at the time of the procedure was 8.5 yrs. There was no catheter-related infection within the first 4 weeks post-surgery. No device had to be removed because of infection or obstruction during follow-up. Frequent accesses to the port (=3 per day over a 10-day period) were associated with an 8-fold risk of infection. CONCLUSION: Insertion and use of TIVA devices were frequently associated with complications. No device had to be removed because of infection or obstruction over the follow-up period, although no prophylactic antibiotic agent was used. Restrictive use of antibiotics may prevent opportunistic infection. Frequent access to the device was significantly associated with line infection (odds ratio=8.43). No risk factor was identified for obstruction which occurred at a rate of 5.3 per 10,000 accesses.

Relationship between cigarette smoking and abdominal obesity

BACKGROUND: Although smokers tend to have a lower body-mass index (BMI) than non-smokers, smoking may affect body fat (BF) distribution. Some studies have assessed the association between smoking, BMI and waist circumference (WC), but, to our knowledge, no population-based studies assessed the relation between smoking and BF composition. We assessed the association between amount of cigarette smoking, BMI, WC and BF composition. METHODS: Data was analysed from a cross-sectional population-based study including 6187 Caucasians aged 32-76 and living in Switzerland. Height, weight and WC were measured. BF, expressed in percent of total body weight, was measured by electrical bioimpedance. Obesity was defined as a BMI>=30 kg/m2 and normal weight as a BMI<25 kg/m2. Abdominal obesity was defined as a WC>=102 cm for men and >=88 cm for women and normal WC as <94 cm for men and <80 cm for women. In men, excess BF was defined as %BF >=28.1, 28.7, 30.6 and 32.6 for age groups 32-44, 45-54, 55-64 and 65-76, respectively; the corresponding values for women were 35.9, 36.5, 40.5 and 44.4. Cigarette smoking was assessed using a self-reported questionnaire. RESULTS: 29.3% of men and 25.0% of women were smokers. Prevalence of obesity, abdominal obesity, and excess of BF was 16.9% and 26.6% and 14.2% in men and 15.0%, 33.0% and 27.5% in women, respectively. Smokers had lower age-adjusted mean BMI, WC and percent of BF compared to non-smokers. However, among smokers,mean age-adjusted BMI,WC and BF increased with the number of cigarettes smoked per day: among light (1-10 cig/day), moderate (11-20) and heavy smokers (>20), mean +/-SE %BF was 22.4 +/−0.3, 23.1+/−0.3 and 23.5+/−0.4 for men, and 31.9+/−0.3, 32.6+/−0.3 and 32.9+/−0.4 for women, respectively. Mean WC was 92.9+/−0.6, 94.0+/−0.5 and 96.0+/−0.6 cm for men, and 80.2+/−0.5, 81.3+/−0.5 and 83.3+/−0.7 for women, respectively. Mean BMI was 25.7+/−0.2, 26.0+/−0.2, and 26.1+/−0.2 kg/m2 for men; and 23.6+/−0.2, 24.0+/−0.2 and 24.1+/−0.3 for women, respectively. Compared with light smokers, the age-adjusted odds ratio (95% Confidence Interval) for excess of BF was 1.04 (0.58 to 1.85) formoderatesmokers and 1.06 (0.57 to 1.99) for heavy smokers in men (p-trend = 0.9), and 1.35 (0.92 to 1.99) and 2.26 (1.38 to 3.72), respectively, in women (p-trend = 0.04). Odds ratio for abdominal obesity vs. normal WC was 1.32 (0.81 to 2.15) for moderate smokers and 1.95 (1.16 to 3.27) for heavy smokers in men (p-trend < 0.01), and 1.15 (0.79 to 1.69) and 2.36 (1.41 to 3.93) in women (p-trend = 0.03). Odds ratio for obesity vs. normal weight was 1.35 (0.76 to 2.41) for moderate smokers and 1.33 (0.71 to 2.49) for heavy smokers in men (p-trend = 0.9) and 0.78 (0.45 to 1.35) and 1.44 (0.73 to 2.85), in women (p-trend = 0.08). CONCLUSIONS: WC and BF were positively and dose-dependently associated with the number of cigarettes smoked per day in women, whereas onlyWC was dose dependently and significantly associated with the amount of cigarettes smoked per day in men. This suggests that heavy smokers, especially women, are more likely to have an excess of BF and to accumulate BF in the abdomen compared to lighter smokers.

Prospective monitoring of cefepime in intensive care unit adult patients.

INTRODUCTION: Cefepime has been associated with a greater risk of mortality than other beta-lactams in patients treated for severe sepsis. Hypotheses for this failure include possible hidden side-effects (for example, neurological) or inappropriate pharmacokinetic/pharmacodynamic (PK/PD) parameters for bacteria with cefepime minimal inhibitory concentrations (MIC) at the highest limits of susceptibility (8 mg/l) or intermediate-resistance (16 mg/l) for pathogens such as Enterobacteriaceae, Pseudomonas aeruginosa and Staphylococcus aureus. We examined these issues in a prospective non-interventional study of 21 consecutive intensive care unit (ICU) adult patients treated with cefepime for nosocomial pneumonia. METHODS: Patients (median age 55.1 years, range 21.8 to 81.2) received intravenous cefepime at 2 g every 12 hours for creatinine clearance (CLCr) >or= 50 ml/min, and 2 g every 24 hours or 36 hours for CLCr < 50 ml/minute. Cefepime plasma concentrations were determined at several time-points before and after drug administration by high-pressure liquid chromatography. PK/PD parameters were computed by standard non-compartmental analysis. RESULTS: Seventeen first-doses and 11 steady states (that is, four to six days after the first dose) were measured. Plasma levels varied greatly between individuals, from two- to three-fold at peak-concentrations to up to 40-fold at trough-concentrations. Nineteen out of 21 (90%) patients had PK/PD parameters comparable to literature values. Twenty-one of 21 (100%) patients had appropriate duration of cefepime concentrations above the MIC (T>MIC >or= 50%) for the pathogens recovered in this study (MIC <or= 4 mg/l), but only 45 to 65% of them had appropriate coverage for potential pathogens with cefepime MIC >or= 8 mg/l. Moreover, 2/21 (10%) patients with renal impairment (CLCr < 30 ml/minute) demonstrated accumulation of cefepime in the plasma (trough concentrations of 20 to 30 mg/l) in spite of dosage adjustment. Both had symptoms compatible with non-convulsive epilepsy (confusion and muscle jerks) that were not attributed to cefepime-toxicity until plasma levels were disclosed to the caretakers and symptoms resolved promptly after drug arrest. CONCLUSIONS: These empirical results confirm the suspected risks of hidden side-effects and inappropriate PK/PD parameters (for pathogens with upper-limit MICs) in a population of ICU adult patients. Moreover, it identifies a safety and efficacy window for cefepime doses of 2 g every 12 hours in patients with a CLCr >or= 50 ml/minute infected by pathogens with cefepime MICs <or= 4 mg/l. On the other hand, prompt monitoring of cefepime plasma levels should be considered in case of lower CLCr or greater MICs.

Le QT long acquis [Acquired long QT syndrome].

The long QT syndrome may be acquired or genetically determined. The syndrome is characterized by a prolonged QT interval and is associated with an increased risk of cardiac arrhythmia such as a torsade de pointe and death. Electrolytes disorders such as hypomagnesemia and hypokaliemia and several drugs may increase the risk to develop a long QT syndrome. The epidemiology, the aetiology, the diagnostic approach as well as the management options of an acquired QT prolongation is discussed and reviewed herein.

Interventions motivationnelles: psychose et cannabis [Motivational interventions: psychosis and cannabis]

Cannabis use by people suffering from schizophrenia increase relapse rate and reduce adhesion to treatment. Motivational interventions could reduce cannabis misuse. The motivational interviewing principles and techniques are presented in a concrete way as well as the required adaptations to bypass cognitive deficits associated with schizophrenia.

Antagonistes de l'angiotensine II et cancer: un bilan rassurant [Angiotensin II receptor blockers (ARBs) and cancer: a reassuring balance].

The effects of drugs on new cancer and cancer-related death are a major concern. Recently, a meta-analysis raised the possibility that ARBs might have an adverse impact in this respect. This point of view was highly debated until the publication of two other meta-analyses which did not demonstrate any increased risk of new cancer occurrence as well as of cancer related-death with the use of ARBs in patients with hypertension, heart failure and/or nephropathy. This illustrates that the results of meta-analyses should be interpreted cautiously and critically in order to avoid biased conclusions. Overall the bulk of evidence today indicates that ARBs are not associated with an increased cancer risk.