Vitamin C requirements in parenteral nutrition.

Some biochemical functions of vitamin C make it an essential component of parenteral nutrition (PN) and an important therapeutic supplement in other acute conditions. Ascorbic acid is a strong aqueous antioxidant and is a cofactor for several enzymes. The average body pool of vitamin C is 1.5 g, of which 3%-4% (40-60 mg) is used daily. Steady state is maintained with 60 mg/d in nonsmokers and 140 mg/d in smokers. Shocked surgical, trauma, and septic patients have a drastic reduction of circulating plasma ascorbate concentrations. These low concentrations require 3-g doses/d to restore normal plasma ascorbate concentrations, questioning the recommended PN dose of 100 mg/d. Determination of intravenous requirements is usually based on plasma concentrations, which are altered during the inflammatory response. There is no clear indicator of deficiency: serum or plasma ascorbate concentrations <0.3 mg/dL (20 micromol/L) indicates inadequate vitamin C status. On the basis of available pharmacokinetic data the 100 mg/d dose for patients receiving home PN and 200 mg/d for stable adult patients receiving PN are adequate, but requirements have been shown to be higher in perioperative, trauma, burn, and critically ill patients, paralleling oxidative stress. One recommendation cannot fit all categories of patients. Large vitamin C supplements may be considered in severe critical illness, major trauma, and burns because of increased requirements resulting from oxidative stress and wound healing. Future research should distinguish therapeutic use of high-dose ascorbic acid antioxidant therapy from nutritional PN requirements.

The effect of treatment with calcitonin on vertebral fracture rate in osteoporosis.

The efficacy of treatments for osteoporosis does not become evident when evaluated by fracture incidence (FI). Vertebral FI decreased in all controlled studies on calcitonin, but not significantly. Small sample sizes and short periods of treatment may have masked a possible therapeutic benefit, but longer, controlled studies with sodium fluoride or etidronate in larger groups of patients also failed to show a decrease in FI. The present analysis of nine published, therapeutic studies which indicate the FI per year and the initial prevalence of vertebral fractures, examines the question of whether the initial prevalence of fractures has an effect on the subsequent incidence of new fractures and whether the therapeutic effects have to be evaluated as a function of the initial prevalence of fractures. Bearing in mind the differences in roentgenological evaluation and in the size and quality of the various studies, the analysis revealed (1) that in the control groups there was a higher FI in patients with more than three vertebral fractures at baseline (estimated odds ratio (OR) = 49, p = 0.011); (2) that a similar trend, although not statistically significant, was observed in treated patients; (3) that the groups of control patients treated for more than 1 year showed in general an increase in FI beyond the first year and that the reverse was true in treated patients. In conclusion, failure to allow for the initial prevalence of vertebral fractures at the individual level in therapeutic trials of calcitonin to treat osteoporosis and prevent new fractures might have contributed to the absence of a demonstrable benefit of the treatment in those studies.

Treating high blood pressure: is reaching the target more important than the means? No, the means are important.

All major antihypertensive drug classes i.e. diuretics, beta-blockers, calcium antagonists and blockers of the renin-angiotensin system have been shown to effectively lower blood pressure and hence to reduce cardiovascular outcomes in hypertensive patients. These drugs decrease cardiovascular complications in hypertension essentially because they reduce systemic blood pressure. Nevertheless, there is growing evidence that the extent of the benefits differed between drug classes suggesting that the various classes of antihypertensive agents are not equivalent in their ability to protect against target organ damages and cardiovascular and renal endpoints. More recently, evidence has also accumulated to demonstrate that even combination therapies are not equally effective in reducing the occurrence of cardiovascular complications in hypertension. These recent observations suggest that the means to lower blood pressure are as important as the achieved target blood pressure in the management of hypertensive patients.

Exacerbations aiguës au cours de la fibrose pulmonaire idiopathique [Acute exacerbations of idiopathic pulmonary fibrosis].

Although generally considered as a slowly evolving disease, idiopathic pulmonary fibrosis (IPF) is also characterized by episods of rapid deterioration with worsening of dyspnea and hypoxemia, and new ground glass opacities at imaging. These events called "acute exacerbations" (AE) are responsible for half of all deaths in IPF. Pathophysiologic mechanisms of AE are poorly understood. The effectiveness of corticosteroids and immunosuppressive agents appears limited. The mortality of AE is 60-70%. Preventing or controlling AE could improve the overall prognosis of IPF. AE also exist in other interstitial lung diseases.

Effects of a treatment gap during adjuvant chemotherapy in node-positive breast cancer: results of International Breast Cancer Study Group (IBCSG) Trials 13-93 and 14-93.

BACKGROUND: The International Breast Cancer Study Group (IBCSG) conducted two complementary randomized trials to assess whether a treatment-free gap during adjuvant chemotherapy influenced outcome. PATIENTS AND METHODS: From 1993 to 1999, IBCSG Trials 13-93 and 14-93 enrolled 2215 premenopausal and postmenopausal women with axillary node-positive, operable breast cancer. All patients received cyclophosphamide (Cytoxan, C) plus either doxorubicin (Adriamycin, A) or epirubicin (E) for four courses followed immediately (No Gap) or after a 16-week delay (Gap) by classical cyclophosphamide, methotrexate, and fluorouracil (CMF) for three courses. The median follow-up was 7.7 years. RESULTS: The Gap and No-Gap groups had similar disease-free survival (DFS) and overall survival (OS). No identified subgroup showed a statistically significant difference, but exploratory subgroup analysis noted a trend towards decreased DFS for Gap compared with No Gap for women with estrogen receptor (ER)-negative tumors not receiving tamoxifen, especially evident during the first 2 years. CONCLUSIONS: A 16-week gap between adjuvant AC/EC and CMF provided no benefit and may have increased early recurrence rates in patients with ER-negative tumors.

Médecine d'urgence [Emergency medicine: updates 2011].

Emergency medicine physicians aim to stabilize or restore vital functions, establish diagnosis, initiate specific treatments and adequately orientate patients. This year, new evidences have improved our knowledge about diagnostic strategy for patients with acute non traumatic headache, treatment of acute atrial fibrillation and outpatient management of acute pulmonary embolism. Reducing injection pain of local anesthetics, reducing irradiation by using alternative diagnostic tools in appendicitis suspicion, and identification of trauma patients who benefit from tranexamic acid administration are other illustrations of the efforts to improve efficacy, safety and comfort in the management of emergency patients.

Traitements des facteurs de risque cardiovasculaire et dépistage de la maladie coronarienne dans le diabète de type 2 [Treatments for cardiovascular risk factors and screening for coronary artery disease in type 2 diabetes mellitus]

The recent ACCORD and DIAD studies revealed results which could modify treatments and the screening of diabetes vascular complications. Indeed, ACCORD shows no benefit on the prevention of diabetes vascular complications by aggressive treatment of hypertension or the combined treatment of the dyslipidemia. The intensive treatment of the blood glucose, if associated with severe hypoglycemias, increases mortality. DIAD revealed 20% of silent myocardial ischaemia in diabetic patients but no beneficial effect on the cardiovascular mortality. A careful reading of these studies in the light of long term studies such as UKPDS and STENO reveals that these negative results are generated by a too short follow-up and too aggressive objectives. The long term studies reveal that more realistic objectives remain beneficial.

Adverse events to antiretrovirals in the Swiss HIV Cohort Study: effect on mortality and treatment modification.

BACKGROUND: Antiretroviral therapy (ART) decreases morbidity and mortality in HIV-infected patients but is associated with considerable adverse events (AEs). METHODS: We examined the effect of AEs to ART on mortality, treatment modifications and drop-out in the Swiss HIV Cohort Study. A cross-sectional evaluation of prevalence of 13 clinical and 11 laboratory parameters was performed in 1999 in 1,078 patients on ART. AEs were defined as abnormalities probably or certainly related to ART. A score including the number and severity of AEs was defined. The subsequent progression to death, drop-out and treatment modification due to intolerance were evaluated according to the baseline AE score and characteristics of individual AEs. RESULTS: Of the 1,078 patients, laboratory AEs were reported in 23% and clinical AEs in 45%. During a median follow up of 5.9 years, laboratory AEs were associated with higher mortality with an adjusted hazard ratio (HR) of 1.3 (95% confidence interval [CI] 1.2-1.5; P < 0.001) per score point. For clinical AEs no significant association with increased mortality was found. In contrast, an increasing score for clinical AEs (HR 1.11,95% CI 1.04-1.18; P = 0.002), but not for laboratory AEs (HR 1.07, 95% CI 0.97-1.17; P = 0.17), was associated with antiretroviral treatment modification. AEs were not associated with a higher drop-out rate. CONCLUSIONS: The burden of laboratory AEs to antiretroviral drugs is associated with a higher mortality. Physicians seem to change treatments to relieve clinical symptoms, while accepting laboratory AEs. Minimizing laboratory drug toxicity seems warranted and its influence on survival should be further evaluated.

Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in intensive care unit study.

OBJECTIVES: To provide a global, up-to-date picture of the prevalence, treatment, and outcomes of Candida bloodstream infections in intensive care unit patients and compare Candida with bacterial bloodstream infection. DESIGN: A retrospective analysis of the Extended Prevalence of Infection in the ICU Study (EPIC II). Demographic, physiological, infection-related and therapeutic data were collected. Patients were grouped as having Candida, Gram-positive, Gram-negative, and combined Candida/bacterial bloodstream infection. Outcome data were assessed at intensive care unit and hospital discharge. SETTING: EPIC II included 1265 intensive care units in 76 countries. PATIENTS: Patients in participating intensive care units on study day. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Of the 14,414 patients in EPIC II, 99 patients had Candida bloodstream infections for a prevalence of 6.9 per 1000 patients. Sixty-one patients had candidemia alone and 38 patients had combined bloodstream infections. Candida albicans (n = 70) was the predominant species. Primary therapy included monotherapy with fluconazole (n = 39), caspofungin (n = 16), and a polyene-based product (n = 12). Combination therapy was infrequently used (n = 10). Compared with patients with Gram-positive (n = 420) and Gram-negative (n = 264) bloodstream infections, patients with candidemia were more likely to have solid tumors (p < .05) and appeared to have been in an intensive care unit longer (14 days [range, 5-25 days], 8 days [range, 3-20 days], and 10 days [range, 2-23 days], respectively), but this difference was not statistically significant. Severity of illness and organ dysfunction scores were similar between groups. Patients with Candida bloodstream infections, compared with patients with Gram-positive and Gram-negative bloodstream infections, had the greatest crude intensive care unit mortality rates (42.6%, 25.3%, and 29.1%, respectively) and longer intensive care unit lengths of stay (median [interquartile range]) (33 days [18-44], 20 days [9-43], and 21 days [8-46], respectively); however, these differences were not statistically significant. CONCLUSION: Candidemia remains a significant problem in intensive care units patients. In the EPIC II population, Candida albicans was the most common organism and fluconazole remained the predominant antifungal agent used. Candida bloodstream infections are associated with high intensive care unit and hospital mortality rates and resource use.

Allergo-immunologie. 1. Nouveautés dans le traitement des crises aiguës d'angioedème héréditaire [Allergy-immunology. New therapies for acute attacks in hereditary angioedema].

Hereditary angioedema is a disease which develops as a result of a deficiency or dysfonction of C1-inhibitor, a key regulator of the complement, coagulation and contact cascades, resulting among others in excessive release of bradykinin. This disease mortality rate is high in absence of immediate and effective treatment, in particular in presence of acute attacks of the upper respiratory tract (laryngeal edema). Until now only administration of a purified C1-inhibitor extract was effective against these symptoms. This paper aims to synthesise essentials knowledge concerning news drugs, in particular icatibant, a selective bradykinin B2- receptor antagonist whose use should be widened to the treatment of angioedema with ACE-inhibitors intolerance.