Traitements de fer: preuves de t'efficacité et bonne pratique clinique [Iron therapy: proof of efficacy and good clinical practice].

Efficacy of iron therapy, whether oral or intravenous, on biological markers of body iron stores is well recognized in medical literature, but current studies are heterogeneous, of sometimes dubious quality, and rarely address clinical outcomes. Precise practical guidelines appear available only for indications related to kidney disease. First-line intravenous use is reserved for situations comprising chronic renal failure, or patients presenting with malabsorption syndromes such as in inflammatory bowel disease. In all other situations, because of the non-negligible risk of hypersensitivity reactions, intravenous iron use is considered justified only in clinically sustained indications, for patients in whom oral administration of iron is unsatisfactory or impossible.

Appropriateness of colonoscopy in Europe (EPAGE II). Functional bowel disorders: pain, constipation and bloating.

BACKGROUND AND STUDY AIMS: To summarize the published literature on assessment of appropriateness of colonoscopy for the investigation of functional bowel symptoms, and report appropriateness criteria developed by an expert panel, the 2008 European Panel on the Appropriateness of Gastrointestinal Endoscopy, EPAGE II. METHODS: A systematic search of guidelines, systematic reviews and primary studies regarding the evaluation and management of functional bowel symptoms was performed. The RAND/UCLA Appropriateness Method was applied to develop appropriateness criteria for colonoscopy for these conditions. RESULTS: Much of the evidence for use of colonoscopy in evaluation of chronic abdominal pain, and/or constipation and/or abdominal bloating is modest. Major limitations include small numbers of patients and lack of adequate characterization of these patients. Large community-based follow-up studies are needed to enable better definition of the natural history of patients with functional bowel disorders. Guidelines stress that alarm features ("red flags"), such as rectal bleeding, anemia, weight loss, nocturnal symptoms, family history of colon cancer, age of onset > 50 years, and recent onset of symptoms should all lead to careful evaluation before a diagnosis of functional bowel disorder is made. EPAGE II assessed these symptoms by means of 12 clinical scenarios, rating colonoscopy as appropriate, uncertain and inappropriate in 42 % (5/12), 25 % (3/12), and 33 % (4/12) of these, respectively. CONCLUSIONS: Evidence to support the use of colonoscopy in the evaluation of patients with functional bowel disorders and no alarm features is lacking. These patients have no increased risk of colon cancer and thus advice on screening for this is not different from that for the general population. EPAGE II criteria, available online (http://www.epage.ch), consider colonoscopy appropriate in patients of > 50 years with chronic or new-onset bowel disturbances, but not in patients with isolated chronic abdominal pain.

Evolutionary comparison provides evidence for pathogenicity of RMRP mutations.

Cartilage-hair hypoplasia (CHH) is a pleiotropic disease caused by recessive mutations in the RMRP gene that result in a wide spectrum of manifestations including short stature, sparse hair, metaphyseal dysplasia, anemia, immune deficiency, and increased incidence of cancer. Molecular diagnosis of CHH has implications for management, prognosis, follow-up, and genetic counseling of affected patients and their families. We report 20 novel mutations in 36 patients with CHH and describe the associated phenotypic spectrum. Given the high mutational heterogeneity (62 mutations reported to date), the high frequency of variations in the region (eight single nucleotide polymorphisms in and around RMRP), and the fact that RMRP is not translated into protein, prediction of mutation pathogenicity is difficult. We addressed this issue by a comparative genomic approach and aligned the genomic sequences of RMRP gene in the entire class of mammals. We found that putative pathogenic mutations are located in highly conserved nucleotides, whereas polymorphisms are located in non-conserved positions. We conclude that the abundance of variations in this small gene is remarkable and at odds with its high conservation through species; it is unclear whether these variations are caused by a high local mutation rate, a failure of repair mechanisms, or a relaxed selective pressure. The marked diversity of mutations in RMRP and the low homozygosity rate in our patient population indicate that CHH is more common than previously estimated, but may go unrecognized because of its variable clinical presentation. Thus, RMRP molecular testing may be indicated in individuals with isolated metaphyseal dysplasia, anemia, or immune dysregulation.

Unlicensed and off-label drug use in a Swiss paediatric university hospital.

BACKGROUND: Many medicines used in newborns, infants, children and adolescents are not licensed ("unlicensed") or are prescribed outside the terms of the marketing authorization ("off-label"). Several studies have shown that this is a common practice in various healthcare settings in the USA, Europe and Australia, but data are scarce in Switzerland. OBJECTIVES: The aim of our prospective study was to determine the proportion of unlicensed or off-label prescriptions in paediatric patients. METHODS: This pilot study was conducted prospectively over a six month period in the department of paediatrics of a university hospital. RESULTS: Sixty patients aged from three days to 14 years were included in the study. A total of 483 prescriptions were written for the patients. More than half of all prescriptions (247; 51%) followed the terms of the marketing authorization. 114 (24%) were unlicensed and 122 (25%) off-label. All patients received at least one unlicensed or offlabel medicine. CONCLUSION: The use of unlicensed or off-label medicines to treat children was found to be common. Co-operation between the pharmaceutical industry, national regulatory authorities, clinical researchers, healthcare professionals and parents is required in order to ensure that children do not remain "therapeutic orphans".

Effects of paralysis with pancuronium bromide on joint mobility in premature infants.

To study the effects of muscle paralysis on joint mobility, we compared eight premature infants treated with pancuronium bromide with a control group. A significant reduction was observed in hip and knee flexion, and in ankle dorsal extension, which tended to resolve in time. We conclude that muscle paralysis reduces the mobility of selected joints; spontaneous activity appears to prevent long-term contractures.

Long-term results of a multicenter SAKK trial on high-dose ifosfamide and doxorubicin in advanced or metastatic gynecologic sarcomas.

BACKGROUND: Dose intensive chemotherapy has not been tested prospectively for the treatment of gynecologic sarcomas. We investigated the antitumor activity and toxicity of high-dose ifosfamide and doxorubicin, in the context of a multidisciplinary strategy for the treatment of advanced and metastatic, not pretreated, gynecologic sarcomas. PATIENTS AND METHODS: Thirty-nine patients were enrolled onto a phase I-II multicenter trial of ifosfamide, 10 g/m2 as a continuous infusion over 5 days, plus doxorubicin intravenously, 25 mg/m2/day for 3 days with Mesna and granulocyte-colony-stimulating factor every 21 days. Salvage therapy was allowed after chemotherapy. RESULTS: Among the 37 evaluable patients, the tumor was locally advanced (n = 11), with concomitant distant metastases (n = 5) or with distant metastases only (n = 21). After a median of three (range 1-7) chemotherapy cycles, six patients experienced a complete response and 12 a partial response for an overall response rate of 49% (95% CI 32% to 66%). The response rate was higher in poorly differentiated tumors (62%) compared with moderately well differentiated ones (18%), but was not different according to histology subtypes. Eleven patients had salvage therapy, either immediately following chemotherapy (n = 7) or at time of progression (n = 4). With a median follow-up time of 5 years, the median overall survival was 30.5 months. Hematological toxicity was as expected neutropenia, thrombopenia and anemia > or = grade 3 at 50%, 34% and 33% of cycles respectively. No toxic death occurred. CONCLUSIONS: High-dose ifosfamide plus doxorubicin is an active regimen for all subtypes of gynecological sarcomas. Its toxicity was manageable in a multicentric setting. The prolonged survival might be due to the multidisciplinary strategy that was possible in one-third of the patients.

Feasibility and efficacy of accelerated weekly concomitant boost postoperative radiation therapy combined with concomitant chemotherapy in patients with locally advanced head and neck cancer.

BACKGROUND: The aim of this study was to assess feasibility and efficacy of weekly concomitant boost accelerated postoperative radiation therapy (PORT) with concomitant chemotherapy (CT) in patients with locally advanced head and neck cancer (LAHNC). METHODS AND MATERIALS: Conformal or intensity-modulated 66-Gy RT was performed in 5.5 weeks in 40 patients. Cisplatin was given at days 1, 22, and 43. Median follow-up was 36 months. RESULTS AND DISCUSSION: Grade 3 mucositis, dysphagia, and erythema was observed in ten (25%), nine (23%), and six (13%) patients, respectively. Grade 3 or more anemia was observed in two (6%) patients, and leukopenia in five (13%) patients. No grade 3 or 4 thrombocytopenia was observed. Grade 3 nephrotoxicity was observed in one patient (3%). No treatment-related mortality was observed. Grade 2 or more xerostomia and edema were observed in ten (25%) and one (3%) patient, respectively. Locoregional relapse occurred in eight patients, and seven patients developed distant metastases. Median time to locoregional relapse was 6 months. Three-year overall, disease-free survival, and locoregional control rates were 63%, 62%, and 81%, respectively. Multivariate analysis revealed that the only prognostic factor was nodal status. CONCLUSION: Reducing overall treatment time using accelerated PORT/CT by weekly concomitant boost (six fractions per week) combined with concomitant cisplatin CT is easily feasible with acceptable morbidity.

Atypical Kawasaki disease with peripheral gangrene and myocardial infarction: therapeutic implications.

We describe a 2-month-old girl with atypical Kawasaki disease (KD) complicated by peripheral gangrene and myocardial infarction. Peripheral ischaemia leading to gangrene is a rare but serious complication of KD in infants younger than 7 months of age. Treatment has been targeted at reducing arterial inflammation, arteriospasm and thrombosis. We report the first patient with incomplete KD and peripheral ischaemia in whom therapy with prostaglandin E1 (PGE1) as vasodilating and antithrombotic agent appeared successful, restoring hand and foot perfusion without significant long-term sequelae. However, PGE1 could have supported development of myocardial infarction by shunting blood away from ischaemic areas distal to a giant coronary artery aneurysm with beginning thrombosis. CONCLUSION. Atypical KD with peripheral gangrene appears to react favourably to treatment with PGE1, but needs careful monitoring to detect early signs of cardiac ischaemia.

Marqueurs diagnostiques de la carence en fer: lequel choisir [Diagnostic markers of iron deficiency: which should we choose?].

Iron deficiency is generally investigated when faced with anemia, or with symptoms that could be related to iron deficiency without anemia. This simple disorder is easy to treat, provided that the diagnosis is correct. Several biological tests are available, but their interpretation is oftentimes problematic. Pre-analytical factors can interfere with measurements, normal values can change depending on suppliers, and, above all, results from different markers can be contradictory in some clinical situations. The aim of this article is to evaluate how the evolution of scientific knowledge and clinical trials can contribute to a better understanding and greater reliability in the diagnosis of iron deficiency.

Salmonella epidural abscess in sickle cell disease: failure of the nonsurgical treatment.

In patients suffering from sickle cell disease (SCD), bone is a preferred site of infection. We report the case of a five-year-and-eight-month-old black African boy with homozygous-SS disease who developed a cranial epidural abscess. This intracranial infectious complication originated from a Salmonella enteritidis osteitis of the frontal bone. Antibiotic treatment alone did not control the disease, so surgery was necessary to remove the necrotic bone and to evacuate the epidural pus. The numerous factors interfering with normal healing of a septic focus in sickle cell anemia, particularly in this previously undescribed intracranial complication, emphasize the need for a primary and early surgical treatment in similar situations.

Diagnostic potential of neutrophil elastase inhibitor complex in the routine care of critically ill newborn infants.

It has been suggested that determination of the neutrophil elastase alpha1-proteinase inhibitor complex (E-alpha1PI) improves the diagnosis of bacterial infection in newborns. We evaluated the use of E-alpha1PI measurements in 143 newborns, consecutively admitted to a tertiary intensive care unit, employing a new random access assay and a sampling procedure that minimises post-collection artefacts. The 95% range for noninfected newborns was 20-110 microg/l up to the 5th day of life and 20-85 microg/l thereafter. The sensitivity as to the diagnosis of culture-proven bloodstream infection was 80% for E-alpha1PI, 86% for the immature to total neutrophil ratio, 64% for C-reactive protein and 37% for the total white blood cell count. The corresponding specificity amounted to 97%, 85%, 85% and 86%, respectively. E-alpha1PI increases preceded elevations of C-reactive protein by 18 h. Like C-reactive protein, E-alpha1PI levels did not distinguish between bloodstream infection and non-bacterial inflammatory responses. Results of E-alpha1PI became available within 1 h of collection and usually 2-3 h before manual leucocyte counts. CONCLUSION: Determination of neutrophil elastase alpha1-proteinase inhibitor levels yields diagnostic advantages comparable to those of manual differential counts but provide faster turnaround times.

The release of antidiuretic hormone is appropriate in response to hypovolemia and/or sodium administration in children with severe head injury: a trial of lactated Ringer's solution versus hypertonic saline.

We conducted an open, randomized, and prospective study to determine the effect of hypertonic saline on the secretion of antidiuretic hormone (ADH) and aldosterone in children with severe head injury (Glasgow coma scale <8). Thirty-one consecutive patients at a level III pediatric intensive care unit at a children's hospital received either lactated Ringer's solution (Ringer's group, n = 16) or hypertonic saline (Hypertonic Saline group, n = 15) over a 3-day period. Serum ADH levels were significantly larger in the Hypertonic Saline group as compared with the Ringer's group (P = 0.001; analysis of variance) and were correlated to sodium intake (Ringer's group: r = 0.39, R(2) = 0.15, P = 0.02; Hypertonic Saline group: r = 0.42, R(2) = 0.18, P = 0.02) and volume of fluids given IV (Ringer's group: r = 0.38, R(2) = 0.15, P = 0.02; Hypertonic Saline group: r = 0.32, R(2) = 0.1, P = not significant). Correlation of ADH to plasma osmolality was significant if plasma osmolality was >280 mOsm/kg (r = 0.5, R(2) = 0.25, P = 0.06), indicating an osmotic threshold for ADH release. Serum aldosterone levels were larger on the first day than during Days 2 and 3 in both groups and inversely correlated to serum sodium levels only in the Ringer's group (r = -0.55, R(2) = 0.3, P < 0.001). This group received a significantly larger fluid volume on Day 1 (P = 0.05, Mann-Whitney U-test) than did patients in the Hypertonic Saline group, indicating hypovolemia during the first day. Head-injured children have appropriate levels of ADH. They may be hypovolemic during the first day of treatment, especially if they receive lactated Ringer's solution. IMPLICATIONS: In head-injured patients, we recommend fluid restriction to avoid inappropriate secretion of antidiuretic hormone. In a prospective, randomized, and controlled study in 31 children, we were able to show that the antidiuretic hormone levels are appropriate in response to hypovolemia, sodium load, or both.

Tracheostomy in children.

We reviewed the records of 108 patients who had a tracheostomy performed over a 10-year period from July 1979 to April 1989. Median age at tracheostomy was 6 months (1 week-15 years). Indications for surgery were acquired subglottic stenosis (31.4%), bilateral vocal cord paralysis (22.2%), congenital airway malformations (22.2%) and tumours (11.1%). No epiglottis and no emergency situation had to be managed by tracheostomy. Operation was uneventful in all, but 8 patients (7.4%) developed a pneumothorax in the postoperative period. Twenty-one (19.5%) had severe complications during the cannulation period (tube obstruction in 11 patients with cardiorespiratory arrest in 4; dislocation of the tube in 6 patients). Fifteen patients (13.8%) had severe complications after decannulation (2 had a cardiorespiratory arrest); all 15 had to be recannulated. At the end of the study period 85 patients (78.7%) were successfully decannulated with a median period of tracheostomy of 486 days (8 days-6.6 years). The median hospital stay was 159 days (13 days-2.7 years). All patients could be discharged. Eight patients (7.4%) died but no death was related to tracheostomy. In summary the mortality rate is lower than reported in previous reviews and tracheostomy is a safe operation even in small children but cannula-related complications may lead to life-threatening events. The management of tracheostomized small children and infants in a highly staffed and monitored intensive care unit has allowed better handling of complications and has resulted in a reduction in cannula-related deaths.

Squamous-cell carcinoma arising in a non-irradiated child with recurrent respiratory papillomatosis.

We describe a patient with recurrent respiratory papillomatosis (RRP) associated with human papilloma virus (HPV), who developed a fatal squamous cell carcinoma of the lung. At the age of 1 year he presented with hoarseness, dyspnoea and inspiratory stridor but the diagnosis of RRP was made only 1 year later. At the age of 4 years he was tracheostomized because of upper airway obstruction. In spite of multiple surgical excisions and topic treatment with 5-fluorouracil the papillomata extended to the lung parenchyma. At the age of 16 years he developed a squamous-cell carcinoma of the lung and died 4 months later. Transformation to pulmonary carcinoma is a rare complication in non-irradiated patients with lung papillomatosis. We found only 11 similar cases in the literature.

Experience and endocrine stress responses in neonatal and pediatric critical care nurses and physicians.

OBJECTIVE: Critical care is a working environment with frequent exposure to stressful events. High levels of psychological stress have been associated with increased prevalence of burnout. Psychological distress acts as a potent trigger of cortisol secretions. We attempted to objectify endocrine stress reactivity. DESIGN: Observational cohort study during two 12-day periods in successive years. SETTING: A tertiary multidisciplinary neonatal and pediatric intensive care unit (33 beds). SUBJECTS: One hundred and twelve nurses and 27 physicians (94% accrual rate). INTERVENTIONS AND MEASUREMENTS: Cortisol determined from salivary samples collected every 2 hrs and after stressful events. Participants recorded the subjective perception of stress with every sample. Endocrine reactions were defined as transient surges in cortisol of &gt;50% and 2.5 nmol/L over the baseline. MAIN RESULTS: During 7,145 working hours, we observed 474 (12.5%) endocrine reactions from 3,781 samples. The mean cortisol increase amounted to 10.6 nmol/L (219%). The mean occurrence rate of endocrine reactions per subject and sample was 0.159 (range, 0-0.43). Although the mean raw cortisol levels were lower in experienced team members (&gt;3 yrs of intensive care vs. &lt;3 yrs, 4.1 vs. 4.95 nmol/L, p &lt; .001), professional experience failed to attenuate the frequency and magnitude of endocrine reactions, except for the subgroup of nurses and physicians with &gt;8 yrs of intensive care experience. A high proportion (71.3%) of endocrine reactions occurred without conscious perception of stress. Unawareness of stress was higher in intensive care nurses (75.1%) than in intermediate care nurses (51.8%, p &lt; .01). CONCLUSIONS: Stress-related cortisol surges occur frequently in neonatal and pediatric critical care staff. Cortisol increases are independent of subjective stress perception. Professional experience does not abate the endocrine stress reactivity.