Adjuvant L-arginine treatment in controlled ovarian hyperstimulation: a double-blind, randomized study

BACKGROUND: Enhanced vascularization appears to be important for follicular selection and maturation in both spontaneous and stimulated IVF cycles. Nitric oxide, formed in vivo from L-arginine, may play a key role in follicular maturation and ovulation. METHODS: To evaluate the role of L-arginine supplementation in controlled ovarian hyperstimulation, 37 IVF patients were divided into two groups according to ovarian stimulation protocols: group I, GnRH agonist plus pure (p)FSH plus oral L-arginine (n = 18); and group II, GnRH agonist plus pFSH plus placebo (n = 19). Hormonal, ultrasonographic and Doppler evaluations were performed, and plasma and follicular fluid nitrite/nitrate concentrations were monitored. RESULTS: Thirty-two patients completed the study. In group I (n = 16), plasma L-arginine concentrations increased from (basal) 87 +/- 12 micromol to 279 +/- 31 micromol (P = 0.002) on the day of beta-HCG administration. In this group, pFSH treatment was shorter (P = 0.039) than in group II (n = 16). The number of the follicles > or =17mm was lower (P = 0.038) in group I than group II. The "good quality" embryos were fewer in number (P = 0.034) and pregnancy rate, both per patient (P = 0.024) and per embryo transfer (P = 0.019), was lower in group I. In the L-arginine group, an increased follicular fluid concentration of nitrite/nitrate was observed. On day 8 of the cycle, elevated plasma estradiol levels were associated with decreased blood flow resistances of perifollicular arteries. Follicular fluid concentrations of nitrite/nitrate were inversely correlated with embryo quality (r = -0.613; P = 0.005) and perifollicular artery pulsatility index (r = -0.609; P = 0.021). CONCLUSIONS: L-Arginine supplementation may be detrimental to embryo quality and pregnancy rate during controlled ovarian hyperstimulation cycles.     

Potential use of procalcitonin as a diagnostic criterion in febrile neutropenia: experience from a multicentre study

In order to assess the diagnostic value of procalcitonin, 158 patients with febrile neutropenia from centres across Europe were studied. Patients with fever were diagnosed on the basis of either: (1) clinical, radiological and microbiological criteria; or (2) the procalcitonin value. In the latter case, concentrations of 0.5-1.0 ng/mL were considered diagnostic of localised infection, concentrations of 1.0-5.0 ng/mL of bacteraemia, and concentrations of > 5.0 ng/mL of severe sepsis. Procalcitonin and C-reactive protein were estimated daily in serum by immunochemiluminescence and nephelometry, respectively. Overall, the sensitivity (specificity) of procalcitonin for bacteraemia was 44.2% (64.3%) at concentrations of 1.0-5.0 ng/mL, and 83.3% (100%) for severe sepsis at concentrations of > 5.0 ng/mL. It was concluded that procalcitonin is a marker strongly suggestive of severe sepsis at concentrations of > 5.0 ng/mL. Estimated concentrations of < 0.5 ng/mL indicate that infection is unlikely, but it was observed that bacteraemia associated with coagulase-negative staphylococci may fail to elevate serum procalcitonin levels.     

Impact of antimicrobial treatment duration on outcome of Staphylococcus aureus bacteraemia: a cohort study

ObjectivesTo assess the outcome of Staphylococcus aureus bacteraemia (SAB) according to factors associated with necessity for longer treatment in conjunction with the duration of treatment.MethodsWe prospectively collected the data of patients with SAB consecutively during 12 to 39 months from 11 hospitals. If multiple episodes of SAB occurred in one patient, only the first episode was enrolled. Factors associated with necessity for longer treatment were defined as follows: persistent bacteraemia, metastatic infection, prosthesis and endocarditis. If any of the factors were present, then the case was defined as longer antibiotic treatment warranted (LW) group; those without any factors were defined as shorter antibiotic treatment sufficient (SS) group. Poor outcome was defined as a composite of 90-day mortality or 30-day recurrence. Duration of antibiotic administration was classified as <14 or ≥14 days in the SS group and <28 or ≥28 days in the LW group.ResultsAmong 2098 cases, the outcome was analysed in 1866 cases, of which 591 showed poor outcome. The SS group accounted for 964 cases and the LW group for 852. On multivariate analysis, age over 65 years, pneumonia, higher Sequential Organ Failure Assessment (SOFA) score and chronic liver diseases were risk factors for poor outcome. Administration of antibiotics less than the recommendation was associated with poor outcome, but this significance was observed only in the LW group (adjusted odds ratio = 1.68; 95% confidence interval, 1.00–2.83; p 0.05).ConclusionsInappropriately short antibiotic treatment was associated with poor outcome in the LW group. Vigilant evaluation for risk factors to determine the duration of treatment may improve the outcome among patients with SAB.     

Effects of acetaminophen and ibuprofen monotherapy in febrile children: a meta-analysis of randomized controlled trials

IntroductionWhen a child presents with fever in the clinical encounter, parents are usually concerned about alleviating the fever. However, the indications for selecting an appropriate drug from the most commonly used antipyretic drugs, acetaminophen and ibuprofen, remain unclear. The purpose of this study was to assess the efficacy and safety of acetaminophen and ibuprofen in febrile children through a systematic review with meta-analysis of randomized controlled trials (RCTs).Material and methodsCochrane, Embase, and PubMed databases were searched for the relevant RCTs. Two authors individually extracted information on trial design, demography, rate of fever resolution, body temperature, and overall adverse events. Data were pooled mainly using a random-effects model; however, because of some sparse data, Peto odds ratios (PORs) were used for outcomes of fever resolution and adverse event. 95% confidence intervals (CIs) were also presented.ResultsIn total, 26 RCTs (n = 4137) fulfilled eligibility criteria. Pooled estimates demonstrated that acetaminophen led to significantly lower fever resolution rates than ibuprofen did (POR = 0.91, 95% CI: 0.84–0.98; I ² = 0%) in the subgroup of trials with a mean age of < 2 years. However, the treatment–time interaction model for body temperature demonstrated that the fever resolution effect was mainly from the time factor based on the available data (effect size = –0.20; 95% CI: –0.30 to –0.11; I ² = 6.9%). Acetaminophen demonstrated lower overall adverse event rates than ibuprofen (POR = 0.71; 95% CI: 0.58–0.87; I ² = 0%).ConclusionsThe effects of ibuprofen are similar to acetaminophen even in children with mean age of approximately 5 years. Nevertheless, acetaminophen is safer than ibuprofen, particularly in children approximately 5 years old.     

An observational study on the empiric use of cefpirome in febrile neutropenia.

BACKGROUND AND PURPOSE: The objective of this study was to document the clinical experience of cefpirome use in the treatment of febrile neutropenia in everyday medical practice. METHODS: This was an open, non-controlled multicenter study. Patients with fever and neutropenia were started on cefpirome empirically. Response to therapy was evaluated 72 to 96 h after the beginning of treatment. The primary endpoint, clinical response, was classified as: improvement (disappearance of fever and the other signs and symptoms of infection) or failure (the patient died during the therapy or had no response to the antibiotic regimen; i.e., fever persisted and the patient's clinical condition was not improving, requiring a change in antibiotic therapy). The secondary endpoints were time to the resolution of fever and improvement of neutropenia, and microbiological response evaluated on-treatment or post-treatment. RESULTS: 140 patients were enrolled in this study; clinical response was analyzed on the clinically evaluated population after 72 to 96 h of treatment. Among the 69 evaluated patients, 58 patients (84.1%) were improved and 11 patients (15.9%) failed. Overall, among the enrolled 140 patients, 124 patients' clinical outcomes were improved after treatment and 16 patients failed. The mean time to fever resolution was 3.1 days. Mean temperature reduced from a baseline reading of 38.7 degrees C to 37.2 degrees C (p<0.0001). Moreover, the mean neutrophil count (342.7/mm(3) at baseline) increased significantly to 3664/mm(3) (p<0.0001) after 72 to 96 h of treatment. Twenty five pathogens were isolated from 20 patients (13 Gram-positive and 9 Gram-negative). The eradication rate was 72% on-treatment or post-treatment, and the mean time to eradication was 5 days. CONCLUSIONS: Cefpirome improves clinical signs and symptoms of infection and offers improved coverage against some Gram-positive and Gram-negative pathogens in patients with febrile neutropenia. Thus, cefpirome is likely to be a valuable and cost-effective extended-spectrum agent for the empiric treatment of severe infections.     

Prevention and treatment of post-partum depression: a controlled randomized study on women at risk

BACKGROUND: Research is needed to evaluate the efficacy of prevention and treatment for post-partum depression. METHOD: Subjects were screened with the Edinburgh Post-natal Depression Scale (EPDS) at the obstetric clinic. Mothers at risk (N = 258) (EPDS scores > or = 9) were randomly assigned to a prevention/treatment group or a control group. The prevention group received one cognitive-behavioural prevention session during hospitalization. At 4 to 6 weeks post-partum, subjects were screened again with the EPDS, after drop-out rates (refusals plus no return of the second EPDS) of 25.4% (33/130) in the intervention group and 10.9% (14/128) in the control group. Mothers with probable depression (EPDS scores > or = 11) were assessed using the Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory (BDI). Mothers with major depression continued in the treatment group (N = 18) or in the control group (N = 30). Treated subjects received a cognitive-behavioural programme of between five and eight weekly home-visits. RESULTS: Compared with the control group, women in the prevention group had significant reductions in the frequency of probable depression (30.2 % v. 48.2%). Recovery rates based on HDRS scores of < 7 and BDI scores of < 4 were also significantly greater in the treated group than in the control group. CONCLUSIONS: The study suggests that this programme for prevention and treatment of post-partum depression is reasonably well-accepted and efficacious.     

Topical treatment of chronic venous ulcers with sucralfate: a placebo controlled randomized study

Venous leg ulcers are an important medical issue due to their high incidence in the elderly and the lack of a standard curative approach. Apart from surgical therapy, different medical treatments to effect ulcer wound repair and regeneration are currently being investigated. Sucralfate is a cytoprotective agent employed to prevent or treat several gastrointestinal diseases such as gastroesophageal reflux, gastritis, peptic ulcer, stress ulcer and dyspepsia. In this study we evaluated the efficacy, safety and tolerability of topical sucralfate (SUC-LIS 95) on the healing of chronic venous leg ulcers in 50 patients by a double-blind, placebo-controlled, randomized study. Our results indicated that the daily application of SUC-LIS 95 to non-infected post-phlebitis/vascular ulcers, for a median period of 42.0 days, led to complete healing in 95.6% of patients, against only 10.9% of cases with a matched placebo. A significant improvement was obtained in the SUC-LIS 95-treated patient group with regard to local tissue inflammation as well as pain and burning, and consequently, in ulcer size and the evolution of granulation tissue. Our findings were corroborated for selected patients by the morphological analysis of biopsies obtained before and after treatment. Using ultrastructural analysis we demonstrated that the topical use of SUC-LIS 95 was able to affect neoangiogenesis, increase wound contraction, promote re-epithelialization of the wound area and diminish the inflammatory reaction. Overall, our results indicated that patients with chronic venous ulcers show improvement after the use of topical sucralfate.     

Immediate versus deferred empirical antifungal (IDEA) therapy in high-risk patients with febrile neutropenia: a randomized, double-blind, placebo-controlled, multicenter study

Empirical antifungal therapy is widely used in high-risk neutropenic hematology patients with fever persisting for more than 4 days. This clinical trial assessed whether immediate empirical therapy with voriconazole could lower the rates of invasive fungal infections (IFIs) compared with this approach. In a double-blind, placebo-controlled, multicenter study, patients with acute leukemia undergoing chemotherapy or allogeneic hematopoietic stem cell transplantation (HSCT) recipients were randomized to broad-spectrum antibacterial therapy plus voriconazole (immediate) or placebo (deferred) after the onset of neutropenic fever. If fever persisted for 96 h, patients were switched to open-label intravenous voriconazole; oral treatment was permitted after 96 h. The primary endpoint was the rate of proven/probable IFIs between Days 2 and 28 after fever onset in the modified intent-to-treat (mITT) complete-case population. One hundred and forty-seven patients were randomized to immediate (n?=?81) or deferred (n?=?66) voriconazole. In the mITT population, six patients in the immediate group and nine in the deferred group developed proven/probable IFI between Days 2 and 28 (p?=?0.258). The safety profiles were similar in both groups. While immediate empirical therapy with voriconazole appears to be safe in febrile neutropenic high-risk patients, it was not associated with a significant reduction in IFIs compared with therapy deferred for 96 h after fever onset.     

Self-help treatment for insomnia: a randomized controlled trial

STUDY OBJECTIVES: Insomnia is a prevalent health complaint that often remains untreated. Several interventions are efficacious but they are not widely available. This study evaluated the efficacy of a self-help behavioral intervention for insomnia. DESIGN: The study used a 2 (conditions; self-help treatment, no treatment control) x 3 (assessments; pretreatment, posttreatment, 6-month follow-up) mixed factorial design. SETTING: This study was part of a larger epidemiologic study conducted with a randomly selected sample of 2001 adults of the province of Quebec in Canada. PARTICIPANTS: One-hundred ninety-two adults (n = 127 women, 65 men; mean age, 46 years) with insomnia, selected from a larger community-based epidemiologic sample, were randomly assigned to self-help treatment (n = 96) or no-treatment control (n = 96). INTERVENTIONS: The self-help intervention included 6 educational booklets mailed weekly to participants and providing information about insomnia, healthy sleep practices, and behavioral sleep scheduling and cognitive strategies. MEASUREMENTS AND RESULTS: Participants completed sleep diaries and questionnaires at pretreatment, posttreatment, and 6-month follow-up. Significant but modest improvements were obtained on subjective sleep parameters for treatment but not control participants. Treated participants averaged nightly gains of 21 minutes of sleep and a reduction of 20 minutes of wakefulness, with a corresponding increase of 4% in sleep efficiency. Improvements were also obtained on measures of insomnia severity (Insomnia Severity Index) and of sleep quality (Pittsburgh Sleep Quality Index), and those changes were maintained at follow-up. CONCLUSIONS: A self-help behavioral intervention was effective in alleviating a broad range of insomnia symptomatology in a community sample. Self-help may be a promising approach to make effective intervention more widely available.     

Role of Abelcet in children with febrile neutropenia

AIM OF STUDY: In order to optimise the use of new forms of Amphotericine B (Ampho B), a decisional tree was created at the end of 2001 in the paediatric hemato-oncology unit for the empirical antifungal treatment in febrile neutropenic children: the standard remained conventional Ampho B and Abelcet was proposed in case of antecedent or occurrence of a deterioration of the renal function (DRF). In order to validate the place of Abelcet we initiated a retrospective study over year 2002. RESULTS: 21 treatments were begun in 14 children for a median duration of 8 days (1-48 days). Three kind of indications were found: DRF antecedent (10 episodes: A group), DRF occurrence during a treatment with conventional Ampho B (7 episodes: B group), age lower than 1 year (3 episodes). 81% of the children were thus treated according to the decisional tree. The clinical tolerance was good in 90% of the cases, with a premedication in half of the cases. The study of the renal function showed a good renal tolerance for 6 episodes out of 9 evaluable in A group, 3 resolutions and 2 stabilisation of the renal failure for the 5 evaluable episodes of the B group. Seven to ten days of treatment by Abelcet were necessary to obtain the renal failure resolved. CONCLUSION: This study confirms the interest of Abelcet in the empirical antifungal treatment in febrile neutropenic children and specially in children having antecedents of DRF related or not to a treatment with conventional Ampho B.     

Enhanced antimicrobial stewardship based on rapid phenotypic antimicrobial susceptibility testing for bacteraemia in patients with haematological malignancies: a randomized controlled trial

ObjectivesRecently, rapid phenotypic antimicrobial susceptibility testing (AST) based on microscopic imaging analysis has been developed. The aim of this study was to determine whether implementation of antimicrobial stewardship programmes (ASP) based on rapid phenotypic AST can increase the proportion of patients with haematological malignancies who receive optimal targeted antibiotics during early periods of bacteraemia.MethodsThis randomized controlled trial enrolled patients with haematological malignancies and at least one positive blood culture. Patients were randomly assigned 1:1 to conventional (n = 60) or rapid phenotypic (n = 56) AST. The primary outcome was the proportion of patients receiving optimal targeted antibiotics 72 hr after blood collection for culture.ResultsThe percentage receiving optimal targeted antibiotics at 72 hr was significantly higher in the rapid phenotypic AST group (45/56, 80.4%) than in conventional AST group (34/60, 56.7%) (relative risk (RR) 1.42, 95% confidence interval (CI) 1.09–1.83). The percentage receiving unnecessary broad-spectrum antibiotics at 72 hr was significantly lower (7/26, 12.5% vs 18/60, 30.0%; RR 0.42, 95% CI 0.19–0.92) and the mean time to optimal targeted antibiotic treatment was significantly shorter (38.1, standard deviation (SD) 38.2 vs 72.8, SD 93.0 hr; p < 0.001) in the rapid phenotypic AST group. The mean time from blood collection to the AST result was significantly shorter in the rapid phenotypic AST group (48.3, SD 17.6 vs 83.1, SD 22.2 hr).DiscussionASP based on rapid phenotypic AST can rapidly optimize antibiotic treatment for bacteraemia in patients with haematological malignancy. Rapid phenotypic AST can improve antimicrobial stewardship in immunocompromised patients.     

Successful treatment with Protein C of febrile neutropenia in pediatric patients during cancer therapy

Febrile Neutropenia (FN) is a complication of chemotherapy in childhood cancer and at the same time secondary deficit of Protein C (PC) is often present during sepsis in children with cancer. In this study we have compared the clinical outcome of two different groups. At the onset of FN during chemotherapy the first group (patients with a secondary deficit of PC) received Protein C Concentrate (PCC) replacement while the other group without PC deficiency received only symptomatic therapies. We report that PC replacement could shorten duration of FN and improve the clinical outcome. The administration of PCC was safe and without any complications.     

No effect of vitamin B-12 treatment on cognitive function and depression: a randomized placebo controlled study

BACKGROUND: Associations between vitamin B-12 deficiency and impaired cognitive function and depression have been reported. METHODS: A randomized placebo controlled study including 140 individuals with an increased plasma methylmalonic acid (0.40-2.00 micromol/l) not previously treated with vitamin B-12. Cognitive function was assessed by the Cambridge Cognitive Examination (CAMCOG), Mini-Mental State Examination (MMSE), and a 12-words learning test. Symptoms of depression were evaluated by the Major Depression Inventory. The main outcome measure was change in cognitive function and depression score from baseline to follow-up 3 months later. RESULTS: At baseline 78 (56%) individuals had cognitive impairment judged from the CAMCOG score and 40 (29%) according to the MMSE; 18 (13%) individuals had symptoms of depression. No improvement was found in cognitive function comparing the treatment and placebo group (total CAMCOG score: P = 0.43), nor among individuals with only slightly impaired cognitive function (n = 44, total CAMCOG score: P = 0.42). The treatment group did not improve in depression score as compared to the placebo group (P = 0.18). LIMITATIONS: The duration of impaired cognitive function was unknown. CONCLUSIONS: A high proportion of individuals with an increased plasma methylmalonic acid had impaired cognitive function, and a rather high prevalence of depression was observed. However, vitamin B-12 treatment did not improve cognitive function or symptoms of depression within the 3-months study period.     

Comparing methods to estimate treatment effects on a continuous outcome in multicentre randomized controlled trials: A simulation study

Background  

Multicentre randomized controlled trials (RCTs) routinely use randomization and analysis stratified by centre to control for differences between centres and to improve precision. No consensus has been reached on how to best analyze correlated continuous outcomes in such settings. Our objective was to investigate the properties of commonly used statistical models at various levels of clustering in the context of multicentre RCTs.     

Internet-based support for infertile patients: a randomized controlled study

This study aimed to evaluate the efficacy and patient acceptance of the first German-language Internet-based treatment for infertile patients. Infertile patients (N = 124) were randomly assigned to either an 8-week Internet-based cognitive-behavioral treatment, or to a waiting-list control group. Participants were assessed at treatment start, post-treatment, and at a 5-month follow-up. Outcome measures included mental health and pregnancy rate. From pre- to posttest, treated participants in contrast to controls did not show significant improvement, although between-group effect sizes were in favor of the intervention group on all mental health measures (Cohen’s d ranged from 0.16 to 0.38). The intervention significantly reduced the depression level of clinically distressed and depressed participants. No effects were found regarding pregnancy rate. The treatment was assessed as positive or very positive by 80% of the participants; this finding coupled with the high demand for such support confirm that Internet-based interventions are a promising new approach for infertile patients that needs more development and testing.     

Vaginoscopic versus traditional office hysteroscopy: a randomized controlled study

BACKGROUND: A randomized, controlled study was performed to compare vaginoscopic versus traditional (speculum with or without tenaculum) hysteroscopy in terms of pain score and procedure time. METHODS: Three hundred patients were randomized in two groups: Group A, diagnostic hysteroscopy with vaginoscopic approach (150 patients) and Group B, diagnostic hysteroscopy with traditional approach (150 patients). All procedures were performed using a semi-rigid 3.5-mm minihysteroscope with a 0 degrees grade optic. Patients of each group were divided into three subgroups according to their reproductive status: fertile nulliparous (FN), fertile multiparous (FM) and post-menopausal (MEN) women. Women were asked to rate their degree of pain during four phases of the procedure: introduction of hysteroscope (Group A) or speculum (Group B) into the vagina (Phase I) and progression through cervical canal up to internal uterine orifice (IUO) (Phase II), inspection of uterine cavity (Phase III) and performing of endometrial biopsy (Phase IV). A total pain score was calculated for each group. For each patient, the duration of hysteroscopy was recorded from the introduction to the extraction of the scope (Group A) or of the speculum (Group B). RESULTS: Although the median total pain scores were 2 in each group, the 95% confidence interval for vaginoscopic hysteroscopy (1.86-2.01) was significantly (P < 0.05) lower than that for traditional hysteroscopy (2.10-2.26). Comparison between the corresponding phases of the procedure showed the only significant difference during Phase I of the procedure [Group A: 1 (95% CI 1.0-1.18) versus Group B: 2 (95% CI 2.3-2.8); P < 0.05]. No significant differences in terms of duration of the procedure were observed between the two approaches. CONCLUSIONS: When surgeons using vaginoscopic hysteroscopy with a semi-rigid minihysteroscope were compared with those using traditional approach and the same instrumentation, the operating times and the patients' pain scores were similar.