Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria.

Invasive fungal diseases (IFDs) have become major causes of morbidity and mortality among highly immunocompromised patients. Authoritative consensus criteria to diagnose IFD have been useful in establishing eligibility criteria for antifungal trials. There is an important need for generation of consensus definitions of outcomes of IFD that will form a standard for evaluating treatment success and failure in clinical trials. Therefore, an expert international panel consisting of the Mycoses Study Group and the European Organization for Research and Treatment of Cancer was convened to propose guidelines for assessing treatment responses in clinical trials of IFDs and for defining study outcomes. Major fungal diseases that are discussed include invasive disease due to Candida species, Aspergillus species and other molds, Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. We also discuss potential pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or mycological data and gaps in knowledge.

Intracerebellar hemorrhage caused by developmental venous anomaly, from diagnosis to treatment.

BACKGROUND: Developmental venous anomaly (DVA) is considered a benign and asymptomatic cerebrovascular malformation, and only isolated cases of symptomatic DVAs are described in the literature. Even more rarely will these symptoms come from an intraparenchymal hemorrhage caused by the DVA. METHODS AND RESULTS: We present two symptomatic DVAs by intracerebellar hemorrhage. CONCLUSION: The diagnostic steps regarding the pathophysiology of DVA hemorrhage and the treatment options are discussed.

Consultation d'urgence/crise pour couples et families: motifs d'urgence et évaluation du traitement [Couples and families emergency/crisis consultation: emergency patterns and treatment assessment]

Since the opening in 2003 of the Couple & Family Consultation Unit (UCCF) at Prangins Hospital, we have met urgent demands and observed that the suffering systems (i.e., couples and families) couldn't face any waiting period. So in 2007 an Emergency/Crisis Facility was created, based on the hypothesis that there is no contra-indication to systemic emergency care, if one understands and structures both crisis and treatment. We studied the suffering population in demand and the emergency/crisis issues and assessed therapy efficiency. Then we observed that treating suffering systems in emergency does produce therapeutic gain in terms of crisis resolution and patients' satisfaction. Those treatments refer to public health issues, as considered the human, social and financial cost of couples/families dysfunctions.

Language lateralization in early and late bilinguals using an international vocabulary

In lateralized Lexical Decision Tasks (LDT), accuracy is commonly higher and reaction times are commonly faster for right visual field (RVF) than left visual field (LVF) presentations. This visual field differences are thought to demonstrate the left hemisphere's dominance for language. Unfortunately, different tasks and words are used between studies and languages making direct comparisons difficult. For example, high frequency words show a performance advantage over low frequency words. Moreover, demographic variables impact on lateralized behavior such as language knowledge (one versus several, early acquired versus late acquired). We here aim to alleviate some of these obstacles by presenting results from a lateralized LDT for which we selected words between 4 and 6 letters used in five different languages, i.e. English, French, German, Dutch and Italian. In this first study using these words, we compared performance of right- and left-handed students being either early or late bilinguals (acquired before or after the age of 6 years) from a French-speaking University in Switzerland. Results showed a left hemispheric advantage (accuracy, reaction times) for all groups, with a trend for early as compared to late bilinguals to be less accurate and taking longer in lexical decisions. These results show that the current words result in solid visual field differences, and do so irrespective of how many languages are spoken. While early bilinguals might experience a slight performance disadvantage, it was not affecting visual field differences.

Prevalence, pathophysiology, health consequences and treatment options of obesity in the elderly: a guideline.

The prevalence of obesity is rising progressively, even among older age groups. By the year 2030-2035 over 20% of the adult US population and over 25% of the Europeans will be aged 65 years and older. The predicted prevalence of obesity in Americans, 60 years and older was 37% in 2010. The predicted prevalence of obesity in Europe in 2015 varies between 20 and 30% dependent on the model used. This means 20.9 million obese 60+ people in the USA in 2010 and 32 million obese elders in 2015 in the EU. Although cut-off values of BMI, waist circumference and percentages of fat mass have not been defined for the elderly (nor for the elderly of different ethnicity), it is clear from several meta-analyses that mortality and morbidity associated with overweight and obesity only increases at a BMI above 30 kg/m(2). Thus, treatment should only be offered to patients who are obese rather than overweight and who also have functional impairments, metabolic complications or obesity-related diseases, that can benefit from weight loss. The weight loss therapy should aim to minimize muscle and bone loss but also vigilance as regards the development of sarcopenic obesity - a combination of an unhealthy excess of body fat with a detrimental loss of muscle and fat-free mass including bone - is important in the elderly, who are vulnerable to this outcome. Life-style intervention should be the first step and consists of a diet with a 500 kcal (2.1 MJ) energy deficit and an adequate intake of protein of high biological quality together with calcium and vitamin D, behavioural therapy and multi-component exercise. Multi-component exercise includes flexibility training, balance training, aerobic exercise and resistance training. The adherence rate in most studies is around 75%. Knowledge of constraints and modulators of physical inactivity should be of help to engage the elderly in physical activity. The role of pharmacotherapy and bariatric surgery in the elderly is largely unknown as in most studies people aged 65 years and older have been excluded.

Postoperative delirium. Part 2: detection, prevention and treatment.

To target pharmacological prevention, instruments giving an approximation of an individual patient's risk of developing postoperative delirium are available. In view of the variable clinical presentation, identifying patients in whom prophylaxis has failed (that is, who develop delirium) remains a challenge. Several bedside instruments are available for the routine ward and ICU setting. Several have been shown to have a high specificity and sensitivity when compared with the standard definitions according to DSM-IV-TR and ICD-10. The Confusion Assessment Method (CAM) and a version specifically developed for the intensive care setting (CAM-ICU) have emerged as a standard. However, alternatives allowing grading of the severity of delirium are also available. In many units, the approach to delirium follows a three-step strategy. Initially, non-pharmacological multicomponent strategies are used for primary prevention. As a second step, pharmacological prophylaxis may be added. Perioperative administration of haloperidol has been shown to reduce the severity, but not the incidence, of delirium. Perioperative administration of atypical antipsychotics has been shown to reduce the incidence of delirium in specific groups of patients. In patients with delirium, both symptomatic and causal treatment of delirium need to be considered. So far symptomatic treatment of delirium is primarily based on antipsychotics. Currently, cholinesterase inhibitors cannot be recommended and the data on dexmedetomidine are inconclusive. With the exception of alcohol-withdrawal delirium, there is no role for benzodiazepines in the treatment of delirium. It is unclear whether treating delirium prevents long-term sequelae.

Presentation and treatment outcome of diverticulitis in younger adults: a different disease than in older patients?

PURPOSE: The severity and most appropriate treatment of diverticulitis in young patients are still controversial. The aim of this study is to compare young patients (<or=50 years) with older patients (>50 years) regarding clinical and radiologic parameters of acute left colonic diverticulitis and to determine whether differences exist in presentation and treatment. METHODS: We reviewed medical records of 271 consecutive patients with left colonic acute diverticulitis admitted to our institution from 2001 through 2004: 71 patients were aged 50 years or younger and 200 patients were older than 50. Clinical and radiologic parameters were analyzed. Conservative treatment was standardized, and included antibiotic therapy and bowel rest. Criteria for emergency surgical treatment were diffuse peritonitis, pneumoperitoneum, and septic shock. RESULTS: Conservative treatment alone was successful in 64 patients (90.1%) in the younger group and in 152 patients (76%) in the older group (P = .017). The percentage of patients requiring surgery at admission or during the hospital stay was significantly lower in younger than in older patients (5.6% vs 20.5%, P = .007), and the percentage of patients requiring emergency end colostomy was higher (although not significantly) in the older group (1.4% vs 9.0%, P = .059). No differences in rate of successful conservative treatment were observed between patients with a first episode and those with recurrence in either age group (P = .941 in the younger group; P = .227 in the older group). CONCLUSION: Young age is not a predictive factor of poor outcome in the management of first or recurrent episodes of acute diverticulitis. Patients older than 50 years more frequently need emergency surgical treatment.

Usage of Calendula officinalis in the prevention and treatment of radiodermatitis: a randomized double-blind controlled clinical trial

OBJECTIVE To evaluate the efficacy of Calendula officinalis in relation to Essential Fatty Acids for the prevention and treatment of radiodermatitis. METHOD This is a randomized double-blind controlled clinical trial with 51 patients with head and neck cancer in radiotherapy treatment divided into two groups: control (27) and experimental (24). RESULTS There is statistically significant evidence (p-value = 0.0120) that the proportion of radiodermatitis grade 2 in Essential Fatty Acids group is higher than Calendula group. Through the Kaplan-Meier survival curve we observed that Essential Fatty Acids group has always remained below the Calendula group survival curve, due to the lower risk of developing radiodermatitis grade 1, which makes the usage of Calendula more effective, with statistical significance (p-value = 0.00402). CONCLUSION Calendula showed better therapeutic response than the Essential Fatty Acids in the prevention and treatment of radiodermatitis. Brazilian Registry of Clinical Trials: RBR-237v4b.

Low-Income Home Energy Assistance Program and Weatherization Program Interim Study Committee, 2007

The Low-Income Home Energy Assistance Program (LIHEAP) and Weatherization Program Interim Study Committee was created by the Legislative Council and charged to review issues involving the Low-Income Home Energy Assistance Program (LIHEAP) and Weatherization Program including financial assistance, the application and intake processes, the community action agencies' assessment and resolution proposal, and whether to involve the Department of Human Services in the administration of the programs to enable low-income persons to access additional assistance programs through a single location.

An European Organisation for Research and Treatment of Cancer phase I study of lapatinib and docetaxel as neoadjuvant treatment for Human Epidermal Growth Factor Receptor 2 (HER2) positive locally-advanced/inflammatory or large operable breast cancer.

BACKGROUND: Lapatinib is an effective anti-HER2 therapy in advanced breast cancer and docetaxel is one of the most active agents in breast cancer. Combining these agents in pre-treated patients with metastatic disease had previously proved challenging, so the primary objective of this study aimed to determine the maximum tolerated dose (MTD) in treatment-naive patients, by identifying acute dose-limiting toxicities (DLT) during cycle 1 in the first part of a phases 1-2 neoadjuvant European Organisation for Research and Treatment of Cancer (EORTC) trial. PATIENTS AND METHODS: Patients with large operable or locally-advanced HER2 positive breast cancer were treated with continuous lapatinib, and docetaxel every 21days for 4 cycles. Dose levels (DLs) were: 1000/75, 1250/75, 1000/85, 1250/85, 1000/100 and 1250/100 (mg/day)/(mg/m(2)). RESULTS: Twenty-one patients were included. Two DLTs occurred at dose level 5 (1000/100); one grade 4 neutropenia ⩾7days and one febrile neutropenia. A further 3 patients were therefore treated at the same dose with prophylactic granulocyte-colony stimulating factor (G-CSF), and 3 patients at dose level 6. No further DLTs were observed. CONCLUSIONS: Our recommended dose for phase II is lapatinib 1000mg/day and docetaxel 100mg/m(2) with G-CSF in HER2 positive non-metastatic breast cancer. The dose of lapatinib should have been 1250mg/day but we were mindful of the high rate of treatment discontinuation in GeparQuinto with lapatinib 1250mg/day combined with docetaxel. No grade 3-4 diarrhoea was observed. Pharmacodynamics analysis suggests that concomitant medications altering P-glycoprotein activity (in addition to lapatinib) can modify toxicity, including non-haematological toxicities. This needs verification in larger trials, where it may contribute to understanding the sources of variability in clinical toxicity and treatment discontinuation.

Iowa Department of Transportation report on funds received from the Rebuild Iowa Infrastructure Fund, the State Recreational Trails Fund, the Health Restricted Capitals and the Rail Revolving Loan and Grant Program in fiscal year 2007

House file 2782 (2007 Infrastructure Appropriations Act) requires state agencies that receive appropriations from specific funds to report that information. The Iowa Department of Transportation received funds from the Rebuild Iowa Infrastructure Fund, the State Recreational Trails Fund, the Health Restricted Capitals, and the Rail Revolving Loan and Grant Program in FY 2007. These are the status reports for those funds and the status of the FY2006 funds received from the State Recreational Trails Fund, the Rebuild Iowa Infrastructure Fund and the Tobacco Settlement Trust Fund.

Phase II study of imatinib in patients with recurrent gliomas of various histologies: a European Organisation for Research and Treatment of Cancer Brain Tumor Group Study.

PURPOSE: To evaluate the safety and the efficacy of imatinib in recurrent malignant gliomas. PATIENTS: AND METHODS: This was a single-arm, phase II study. Eligible patients had recurrent glioma after prior radiotherapy with an enhancing lesion on magnetic resonance imaging. Three different histologic groups were studied: glioblastomas (GBM), pure/mixed (anaplastic) oligodendrogliomas (OD), and low-grade or anaplastic astrocytomas (A). Imatinib was started at a dose of 600 mg/d with dose escalation to 800 mg in case of no toxicity; during the trial this dose was increased to 800 mg/d with escalation to 1,000 mg/d. Trial design was one-stage Fleming; both an objective response and 6 months of progression-free survival (PFS) were considered a successful outcome to treatment. RESULTS: A total of 112 patients (51 patients with GBM, 25 patients with A, and 36 patients with OD) were enrolled. Imatinib was in general well tolerated. The median number of cycles was 2.0 (range, 1 to 43 cycles). Five patients had an objective partial response, including three patients with GBM; all had 6 months of PFS. The 6-month PFS rate was 16% (95% CI, 8.0% to 34.0%) in GBM, 4.0% (95% CI, 0.3% to 15.0%) in OD, and 9% (95% CI, 2.0% to 25.0%) in A. The exposure to imatinib was significantly lower in patients using enzyme-inducing antiepileptic drugs. The presence of ABCG2 point mutations were not correlated with pharmacokinetic findings. No somatic activating mutations of KIT or platelet-derived growth factor receptor-A or -B were found. CONCLUSION: In the dose range of 600 to 1,000 mg/d, single-agent imatinib is well tolerated but has limited antitumor activity in patients with recurrent gliomas.

Application of the 2008 definitions for invasive fungal diseases to the trial comparing voriconazole versus amphotericin B for therapy of invasive aspergillosis: a collaborative study of the Mycoses Study Group (MSG 05) and the European Organization for Research and Treatment of Cancer Infectious Diseases Group.

BACKGROUND: Strict definition of invasive aspergillosis (IA) cases is required to allow precise conclusions about the efficacy of antifungal therapy. The Global Comparative Aspergillus Study (GCAS) compared voriconazole to amphotericin B (AmB) deoxycholate for the primary therapy of IA. Because predefined definitions used for this trial were substantially different from the consensus definitions proposed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group in 2008, we recategorized the 379 episodes of the GCAS according to the later definitions. METHODS: The objectives were to assess the impact of the current definitions on the classification of the episodes and to provide comparative efficacy for probable/proven and possible IA in patients treated with either voriconazole or AmB. In addition to original data, we integrated the results of baseline galactomannan serum levels obtained from 249 (65.7%) frozen samples. The original response assessment was accepted unchanged. RESULTS: Recategorization allowed 59 proven, 178 probable, and 106 possible IA cases to be identified. A higher favorable 12-week response rate was obtained with voriconazole (54.7%) than with AmB (29.9%) (P < .0001). Survival was higher for voriconazole for mycologically documented (probable/proven) IA (70.2%) than with AmB (54.9%) (P = .010). Higher response rates were obtained in possible IA treated with voriconazole vs AmB with the same magnitude of difference (26.2%; 95% confidence interval [CI], 7.2%-45.3%) as in mycologically documented episodes (24.3%; 95% CI, 11.9%-36.7%), suggesting that possible cases are true IA. CONCLUSIONS: Recategorization resulted in a better identification of the episodes and confirmed the higher efficacy of voriconazole over AmB deoxycholate in mycologically documented IA.

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.