Cardiovascular diseases and stroke in African Americans: a call for action.

Considerable disparities in cardiovascular and stroke mortality and morbidity rates exist between African Americans and other Americans. Increased prevalence and severity of hypertension, with earlier onset and often inadequate therapy, seem to be the major culprits responsible for the differences. There are ominous signs indicating that our recent dramatic progress in the control of cardiovascular disease and stroke is slowing, and in certain areas (stroke incidence and prevalence, hypertensive end-stage renal disease) progress is actually regressing. It is urgent that renewed research and medical interventions be undertaken to address this crisis. The American Heart Association and the National Medical Association have these and many other goals in common. Concerted action by all concerned organizations is essential.     

Psychopharmacology training in clinical psychology: a renewed call for action

Knowledge of psychopharmacology is essential for a clinical psychologist to practice his/her profession, regardless of whether one desires to become licensed to prescribe psychoactive medications. This commentary reiterates a call made almost 20 years ago for all practitioners to gain and utilize this knowledge. Without psychopharmacology knowledge, one is extremely limited in the ability to interact with medical prescribers and to optimally serve their patients as a valued member of the health care team.     

Management and diagnostic guidelines for fungal diseases in infectious diseases and clinical microbiology: critical appraisal

Invasive fungal infections (IFIs) are life-threatening conditions that require rapid diagnostic and optimal management to mitigate their high morbidity and mortality rate. They are also associated with a high economic burden, owing to prolonged hospitalization, the need for intensive supportive care, and the consumption of costly new antifungal agents. To address these issues, several international organizations have proposed guidelines for the management of IFIs. The consistency and reliability of these guidelines have rarely been assessed. This article is a review of the differences between the recommendations of the Infectious Diseases Society of America, the European Conference on Infection in Leukaemia, and the European Society of Clinical Microbiology and Infectious Diseases, and will focus on targeted treatment and diagnostic procedures. Although the conclusions of the three groups of experts are in many points similar we outlined some important differences in the methodology and conclusions of ESCMID. The use of these guidelines has the potential to enhance the management of fungal infections but is probably currently suboptimal.     

Informal consultations in infectious diseases and clinical microbiology practice

Informed consultation between physicians is an important part of medical practice. The aim of the study was to evaluate the nature and frequency of such consultations in infectious diseases and clinical microbiology practice. This study was done in five university hospitals. Twenty-one infectious diseases and clinical microbiology specialists participated in informal ('curbside') consultations. In a written questionnaire, physicians were asked to report the number and nature of the informal consultations (ICs) they were asked to provide. A total three hundred and sixty-two such consultations were carried out during a three-month period. The ICs occurred most frequently in the hospital (82.3%). Most of the ICs from outside the hospital were by telephone. Most of the ICs (54.4%) were requested by fellows of specialists. 78.7% of the ICs were requested during working hours. 58.8% of consultations took less than 5 min, 18.8% took 6–10 min, 15.2% took 11–20 min, and 7.2% took over 20 min. The four most common reasons for obtaining ICs were to: help to select an appropriate treatment plan (41.4%), help to select an appropriate prophylaxis (19.3%), interpret laboratory data (10.2%), and provide information about antibiotics (10.2%). 30.1% of ICs resulted in subsequent formal consultation and only four patients (1.1%) were transferred to the consultants' clinics. Informal consultations are a frequent occurrence in the practice of infectious diseases and clinical microbiology (ID&CM). Physicians use this sort of consultation to select an appropriate treatment plan and obtain medical information. This study confirms the importance of the ID&CM specialists as a resource for medical personnel.     

Biomarkers in clinical trials for neurodegenerative diseases: Regulatory perspectives and requirements

Biomarkers might play comprehensive roles in drug development for neurodegenerative diseases and particularly Alzheimer's disease (AD) and other dementias. Biomarkers can already be used to better define homogeneous study populations (e.g. enriched population at risk for AD) and to select the most promising drug candidates in their effective dosages for phase III clinical trials, so some biomarkers are currently in the process of implementation as primary, co-primary or secondary outcome variables into regulatory guideline documents, e.g. regarding phase II in drug development programs as outcome measures in proof of concept or dose finding studies. There are specific biomarkers available depending on the hypothesized mechanism of action of a medicinal product, e.g. impact on the amyloidogenic cascade or on tau-hyperphosphorylation. However, further validation of specific biomarkers in large-scale international controlled multicenter studies is necessary before they can be accepted as primary outcome measures in pivotal phase III clinical trials. There is an even stronger need for rigorous co-development of biological trait- and state marker candidates to provide evidence that a medicinal product affects the underlying disease process, which, together with clinical improvement, will be a precondition for a label of disease modification. Until now no biomarker has been sufficiently validated to be acceptable as a surrogate endpoint. Establishing of surrogate endpoints is an important goal in neurodegenerative diseases, particularly in their early (preclinical, presymptomatic) stages, as traditional clinical outcome measures might be too insensitive to change or need unfeasible treatment durations for clinical trial conditions. Improvements can only be accomplished by active synergistic collaboration between academic, industrial and regulatory partners.     

Biomarkers in clinical trials for neurodegenerative diseases: regulatory perspectives and requirements

Biomarkers might play comprehensive roles in drug development for neurodegenerative diseases and particularly Alzheimer's disease (AD) and other dementias. Biomarkers can already be used to better define homogeneous study populations (e.g. enriched population at risk for AD) and to select the most promising drug candidates in their effective dosages for phase III clinical trials, so some biomarkers are currently in the process of implementation as primary, co-primary or secondary outcome variables into regulatory guideline documents, e.g. regarding phase II in drug development programs as outcome measures in proof of concept or dose finding studies. There are specific biomarkers available depending on the hypothesized mechanism of action of a medicinal product, e.g. impact on the amyloidogenic cascade or on tau-hyperphosphorylation. However, further validation of specific biomarkers in large-scale international controlled multicenter studies is necessary before they can be accepted as primary outcome measures in pivotal phase III clinical trials. There is an even stronger need for rigorous co-development of biological trait- and state marker candidates to provide evidence that a medicinal product affects the underlying disease process, which, together with clinical improvement, will be a precondition for a label of disease modification. Until now no biomarker has been sufficiently validated to be acceptable as a surrogate endpoint. Establishing of surrogate endpoints is an important goal in neurodegenerative diseases, particularly in their early (preclinical, presymptomatic) stages, as traditional clinical outcome measures might be too insensitive to change or need unfeasible treatment durations for clinical trial conditions. Improvements can only be accomplished by active synergistic collaboration between academic, industrial and regulatory partners.     

Childhood injury: call for action

We aim to raise awareness of the burden of avoidable death and disability attributable to childhood injury in Europe in general and Croatia in particular. As formerly common causes of childhood death have declined, injuries have become the most important single cause of death in childhood in European countries. Yet, there are large differences between countries, and especially between the eastern and western parts of Europe. The existence of these differences, reflecting rapid declines in some countries, indicate the scope for prevention. But injuries are low on the policy agenda for various reasons, including their lack of visibility. We advocated the development of integrated intersectoral policies underpinned by an effective public health structure.     

Bloodstream infection surveillance in a cancer centre: a prospective look at clinical microbiology aspects

A prospective clinical and microbiological surveillance study was conducted during a 26-month period to evaluate consecutive malignancy or post-bone marrow transplant patients with positive blood cultures. The study included 859 episodes of bloodstream infection (BSI) in 719 patients. There were 6.9 BSI episodes/1000 patient-days. Overall mortality was 25%. The median age of patients was 43 years, with 71% of episodes occurring in patients aged > 18 years. Patients with underlying haematology malignancies accounted for 38.2% of the episodes. An indwelling central vein catheter was present in 61% of episodes. BSI origin was unknown in 27% of episodes, associated with other sites in 49.6%, and catheter-related in 23.4%. There were 638 concomitant infection sites, of which the most common were pulmonary (28.4%), urinary tract (14.8%), and non-surgical skin or soft tissue (9.7%). In total, 1039 microorganisms were isolated within 48 h of the first blood culture, of which Gram-negative bacilli accounted for 56%. Among Klebsiella pneumoniae and Escherichia coli isolates, 37.8% and 8.9%, respectively, produced extended-spectrum beta-lactamases. High rates of ceftazidime resistance were detected among Acinetobacter spp. (40%) and Enterobacter spp. (51.2%). E. coli and K. pneumoniae were isolated frequently from haematology patients, and Enterobacter spp. from solid tumour patients. E. coli, K. pneumoniae and Pseudomonas aeruginosa were isolated more often from neutropenic than from non-neutropenic patients. Oxacillin resistance was detected in 18.7% of Staphylococcus aureus isolates. It was concluded that continuous multidisciplinary surveillance of BSI is warranted in this high-risk group of patients in order to develop strategies for antimicrobial resistance control and treatment of infectious complications.     

Guidelines for assessing immunocompetency in clinical trials for autoimmune diseases

Clinical trials testing the safety and efficacy of immunosuppressive agents for the treatment of autoimmune diseases should also be designed to evaluate immunocompetency. The most clinically relevant outcome for assessing immunocompetency is the infection rate. Therefore, a systematic approach to screening, monitoring, and reporting infections, modeled after the recommendations of the American Society of Transplantation, is presented. However, because the baseline infection rate in most autoimmune diseases is low, additional tests for immunocompetency should be considered. Evaluation of vaccine responses, an alternative clinically relevant approach, may be particularly useful. Other adjunctive approaches to evaluation of immunocompetency are discussed including immunization with non-vaccine neoantigens, surveillance of chronic viral infections, in vivo or in vitro assessment of cellular immunity, and analysis of innate immunity. Banking genetic material to allow genotyping should be considered particularly if a central repository for samples from different trials can be established.