Is it worth treating fever in intensive care unit patients? Preliminary results from a randomized trial of the effect of external cooling.

BACKGROUND: Antipyresis is a common clinical practice in intensive care, although it is unknown if fever is harmful, beneficial, or a negligible adverse effect of infection and inflammation. METHODS: In a randomized study, rectal temperature and discomfort were assessed in 38 surgical intensive care unit patients without neurotrauma or severe hypoxemia and with fever (temperature >/=38.5 degrees C) and systemic inflammatory response syndrome. Eighteen patients received external cooling while 20 received no antipyretic treatment. RESULTS: Temperature and discomfort decreased similarly in both groups after 24 hours. No significant differences in recurrence of fever, incidence of infection, antibiotic therapy, intensive care unit and hospital length of stay, or mortality were noted between the groups. CONCLUSIONS: These results suggest that the systematic suppression of fever may not be useful in patients without severe cranial trauma or significant hypoxemia. Letting fever take its natural course does not seem to harm patients with systemic inflammatory response syndrome or influence the discomfort level and may save costs.

Feasibility and clinical outcomes when using practice guidelines for evaluation of fever in returning travelers and migrants : a validation study.

BACKGROUND: Practice guidelines for examining febrile patients presenting upon returning from the tropics were developed to assist primary care physicians in decision making. Because of the low level of evidence available in this field, there was a need to validate them and assess their feasibility in the context they have been designed for. OBJECTIVES: The objectives of the study were to (1) evaluate physicians' adherence to recommendations; (2) investigate reasons for non-adherence; and (3) ensure good clinical outcome of patients, the ultimate goal being to improve the quality of the guidelines, in particular to tailor them for the needs of the target audience and population. METHODS: Physicians consulting the guidelines on the Internet (www.fevertravel.ch) were invited to participate in the study. Navigation through the decision chart was automatically recorded, including diagnostic tests performed, initial and final diagnoses, and clinical outcomes. The reasons for non-adherence were investigated and qualitative feedback was collected. RESULTS: A total of 539 physician/patient pairs were included in this study. Full adherence to guidelines was observed in 29% of the cases. Figure-specific adherence rate was 54.8%. The main reasons for non-adherence were as follows: no repetition of malaria tests (111/352) and no presumptive antibiotic treatment for febrile diarrhea (64/153) or abdominal pain without leukocytosis (46/101). Overall, 20% of diversions from guidelines were considered reasonable because there was an alternative presumptive diagnosis or the symptoms were mild, which means that the corrected adherence rate per case was 40.6% and corrected adherence per figure was 61.7%. No death was recorded and all complications could be attributed to the underlying illness rather than to adherence to guidelines. CONCLUSIONS: These guidelines proved to be feasible, useful, and leading to good clinical outcomes. Almost one third of physicians strictly adhered to the guidelines. Other physicians used the guidelines not to forget specific diagnoses but finally diverged from the proposed attitudes. These diversions should be scrutinized for further refinement of the guidelines to better fit to physician and patient needs.

Hindsight judgement on ambiguous episodes of suspected infection in critically ill children: poor consensus amongst experts?

Few episodes of suspected infection observed in paediatric intensive care are classifiable without ambiguity by a priori defined criteria. Most require additional expert judgement. Recently, we observed a high variability in antibiotic prescription rates, not explained by the patients' clinical data or underlying diseases. We hypothesised that the disagreement of experts in adjudication of episodes of suspected infection could be one of the potential causes for this variability. During a 5-month period, we included all patients of a 19-bed multidisciplinary, tertiary, neonatal and paediatric intensive care unit, in whom infection was clinically suspected and antibiotics were prescribed ( n=183). Three experts (two senior ICU physicians and a specialist in infectious diseases) were provided with all patient data, laboratory and microbiological findings. All experts classified episodes according to a priori defined criteria into: proven sepsis, probable sepsis (negative cultures), localised infection and no infection. Episodes of proven viral infection and incomplete data sets were excluded. Of the remaining 167 episodes, 48 were classifiable by a priori criteria ( n=28 proven sepsis, n= 20 no infection). The three experts only achieved limited agreement beyond chance in the remaining 119 episodes (kappa = 0.32, and kappa = 0.19 amongst the ICU physicians). The kappa is a measure of the degree of agreement beyond what would be expected by chance alone, with 0 indicating the chance result and 1 indicating perfect agreement. CONCLUSION: agreement of specialists in hindsight adjudication of episodes of suspected infection is of questionable reliability.

Cumulative frequency-dependent selective episodes allow for rapid morph cycles and rock-paper-scissors dynamics in species with overlapping generations.

Rock-paper-scissors (RPS) dynamics, which maintain genetic polymorphisms over time through negative frequency-dependent (FD) selection, can evolve in short-lived species with no generational overlap, where they produce rapid morph frequency cycles. However, most species have overlapping generations and thus, rapid RPS dynamics are thought to require stronger FD selection, the existence of which yet needs to be proved. Here, we experimentally demonstrate that two cumulative selective episodes, FD sexual selection reinforced by FD selection on offspring survival, generate sufficiently strong selection to generate rapid morph frequency cycles in the European common lizard Zootoca vivipara, a multi-annual species with major generational overlap. These findings show that the conditions required for the evolution of RPS games are fulfilled by almost all species exhibiting genetic polymorphisms and suggest that RPS games may be responsible for the maintenance of genetic diversity in a wide range of species.

Fever in neutropenic cancer patients : a structured approach

Infectious complications related to acquired neutropenia have become a major medical issue, often requiring intensive care management. These infections may be lethal if empirical broad-spectrum treatment is not rapidly started at the first sign of infection (i.e., fever), and this concept is now widely recognized a standard practice. However, the choice of antibiotics has generated considerable controversy for nearly 25 years. After reviewing some particularities of infection in neutropenic patients, this paper will discuss the options and present comprehensive algorithm for non-infectious diseases specialist, including recent advances about early IV-oral switch and the selection of low risk patients for outpatient management.

Oral Antibiotics for Fever in Low-Risk Neutropenic Patients With Cancer: A Double-Blind, Randomized, Multicenter Trial Comparing Single Daily Moxifloxacin With Twice Daily Ciprofloxacin Plus Amoxicillin/Clavulanic Acid Combination Therapy--EORTC Infectious Diseases Group Trial XV.

PURPOSE This double-blind, multicenter trial compared the efficacy and safety of a single daily oral dose of moxifloxacin with oral combination therapy in low-risk febrile neutropenic patients with cancer. PATIENTS AND METHODS Inclusion criteria were cancer, febrile neutropenia, low risk of complications as predicted by a Multinational Association for Supportive Care in Cancer (MASCC) score > 20, ability to swallow, and ≤ one single intravenous dose of empiric antibiotic therapy before study drug treatment initiation. Early discharge was encouraged when a set of predefined criteria was met. Patients received either moxifloxacin (400 mg once daily) monotherapy or oral ciprofloxacin (750 mg twice daily) plus amoxicillin/clavulanic acid (1,000 mg twice daily). The trial was designed to show equivalence of the two drug regimens in terms of therapy success, defined as defervescence and improvement in clinical status during study drug treatment (< 10% difference). Results Among the 333 patients evaluated in an intention-to-treat analysis, therapy success was observed in 80% of the patients administered moxifloxacin and in 82% of the patients administered combination therapy (95% CI for the difference, -10% to 8%, consistent with equivalence). Minor differences in tolerability, safety, and reasons for failure were observed. More than 50% of the patients in the two arms were discharged on protocol therapy, with 5% readmissions among those in either arm. Survival was similar (99%) in both arms. CONCLUSION Monotherapy with once daily oral moxifloxacin is efficacious and safe in low-risk febrile neutropenic patients identified with the help of the MASCC scoring system, discharged early, and observed as outpatients.

Myocardial impairment in chronic hypoxia is abolished by short aeration episodes: involvement of K+ATP channels.

In vivo exposure to chronic hypoxia is considered to be a cause of myocardial dysfunction, thereby representing a deleterious condition, but repeated aeration episodes may exert some cardioprotection. We investigated the possible role of ATP-sensitive potassium channels in these mechanisms. First, rats (n = 8/group) were exposed for 14 days to either chronic hypoxia (CH; 10% O(2)) or chronic hypoxia with one episode/day of 1-hr normoxic aeration (CH+A), with normoxia (N) as the control. Second, isolated hearts were Langendorff perfused under hypoxia (10% O(2), 30 min) and reoxygenated (94% O(2), 30 min) with or without 3 microM glibenclamide (nonselective K(+)(ATP) channel-blocker) or 100 microM diazoxide (selective mitochondrial K(+)(ATP) channel-opener). Blood gasses, hemoglobin concentration, and plasma malondialdehyde were similar in CH and CH+A and in both different from normoxic (P < 0.01), body weight gain and plasma nitrate/nitrite were higher in CH+A than CH (P < 0.01), whereas apoptosis (number of TUNEL-positive nuclei) was less in CH+A than CH (P < 0.05). During in vitro hypoxia, the efficiency (ratio of ATP production/pressure x rate product) was the same in all groups and diazoxide had no measurable effects on myocardial performance, whereas glibenclamide increased end-diastolic pressure more in N and CH than in CH+A hearts (P < 0.05). During reoxgenation, efficiency was markedly less in CH with respect to N and CH+A (P < 0.0001), and ratex pressure product remained lower in CH than N and CH+A hearts (P < 0.001), but glibenclamide or diazoxide abolished this difference. Glibenclamide, but not diazoxide, decreased vascular resistance in N and CH (P < 0.005 and < 0.001) without changes in CH+A. We hypothesize that cardioprotection in chronically hypoxic hearts derive from cell depolarization by sarcolemmal K(+)(ATP) blockade or from preservation of oxidative phosphorylation efficiency (ATP turnover/myocardial performance) by mitochondrial K(+)(ATP) opening. Therefore K(+)(ATP) channels are involved in the deleterious effects of chronic hypoxia and in the cardioprotection elicited when chronic hypoxia is interrupted with short normoxic aeration episodes.

Incidence and types of illness when traveling to the tropics: a prospective controlled study of children and their parents.

Increasingly, families travel to tropical destinations exposing them to infectious agents and tropical diseases not encountered at home. We studied 157 children (0-16 years) and their adult relatives traveling to the tropics, who attended a pretravel clinic and were generally adherent to prescribed advice. Incidence rates of common illness in children and adults were respectively 16.9 (14.3-19.7) and 15.1 (12.7-17.8) episodes/100 person-weeks. Diarrhea, abdominal pain, and fever were the most frequent complaints. There was no significant difference in the incidence of morbid episodes between children and adults, except for fever (more frequent in children). Most episodes occurred in the first 10 days of travel. The similar incidence of morbidity in children and adults and the episodes' mildness challenge the view that it is unwise to travel with small children.

Recurrent paroxysmal fever revealing ocular syphilis.

An increased prevalence of ocular syphilis has been reported in recent years reflecting a trend towards liberalisation of sexual practices in the era of Highly Active Anti-retroviral Treatment for HIV infection [1][2]. In view of the protean nature of the disease, pathognomonic features that could guide differential diagnosis of ocular inflammation towards syphilis are lacking. Ocular involvement can antedate or follow systemic manifestations of syphilitic infection, ranging widely and potentially involving all ocular tissue [3][4]. We report here an unusual case of chronic fever and fatigue the cause of which remained elusive for a period of three years, despite extensive investigations, until the development of bilateral panuveitis, raising the suspicion of syphilitc infection.

Pédiatrie 4. Comment traiter la fièvre de l'enfant en 2013 avec un peu d'évidence [How to treat pediatric fever in 2013 with little evidence-based?].

Treatment of pediatric fever is based on two main molecules, paracetamol and ibuprofen. Fever should be treated when associated with discomfort. The two molecules have almost similar efficacy and safety. Monotherapy should be preferred to a combined or alternating treatment. Antipyretics do not seem to prevent febrile seizures.

Immune activation alters cellular and humoral responses to yellow fever 17D vaccine.

Background. Defining the parameters that modulate vaccine responses in African populations will be imperative to design effective vaccines for protection against HIV, malaria, tuberculosis, and dengue virus infections. This study aimed to evaluate the contribution of the patient-specific immune microenvironment to the response to the licensed yellow fever vaccine 17D (YF-17D) in an African cohort. Methods. We compared responses to YF-17D in 50 volunteers in Entebbe, Uganda, and 50 volunteers in Lausanne, Switzerland. We measured the CD8+ T cell and B cell responses induced by YF-17D and correlated them with immune parameters analyzed by flow cytometry prior to vaccination. Results. We showed that YF-17D-induced CD8+ T cell and B cell responses were substantially lower in immunized individuals from Entebbe compared with immunized individuals from Lausanne. The impaired vaccine response in the Entebbe cohort associated with reduced YF-17D replication. Prior to vaccination, we observed higher frequencies of exhausted and activated NK cells, differentiated T and B cell subsets and proinflammatory monocytes, suggesting an activated immune microenvironment in the Entebbe volunteers. Interestingly, activation of CD8+ T cells and B cells as well as proinflammatory monocytes at baseline negatively correlated with YF-17D-neutralizing antibody titers after vaccination. Additionally, memory T and B cell responses in preimmunized volunteers exhibited reduced persistence in the Entebbe cohort but were boosted by a second vaccination. Conclusion. Together, these results demonstrate that an activated immune microenvironment prior to vaccination impedes efficacy of the YF-17D vaccine in an African cohort and suggest that vaccine regimens may need to be boosted in African populations to achieve efficient immunity. Trial registration. Registration is not required for observational studies. Funding. This study was funded by Canada's Global Health Research Initiative, Defense Threat Reduction Agency, National Institute of Allergy and Infectious Diseases, Bill & Melinda Gates Foundation, and United States Agency for International Development.

Beyond malaria--causes of fever in outpatient Tanzanian children.

BACKGROUND: As the incidence of malaria diminishes, a better understanding of nonmalarial fever is important for effective management of illness in children. In this study, we explored the spectrum of causes of fever in African children. METHODS: We recruited children younger than 10 years of age with a temperature of 38°C or higher at two outpatient clinics--one rural and one urban--in Tanzania. Medical histories were obtained and clinical examinations conducted by means of systematic procedures. Blood and nasopharyngeal specimens were collected to perform rapid diagnostic tests, serologic tests, culture, and molecular tests for potential pathogens causing acute fever. Final diagnoses were determined with the use of algorithms and a set of prespecified criteria. RESULTS: Analyses of data derived from clinical presentation and from 25,743 laboratory investigations yielded 1232 diagnoses. Of 1005 children (22.6% of whom had multiple diagnoses), 62.2% had an acute respiratory infection; 5.0% of these infections were radiologically confirmed pneumonia. A systemic bacterial, viral, or parasitic infection other than malaria or typhoid fever was found in 13.3% of children, nasopharyngeal viral infection (without respiratory symptoms or signs) in 11.9%, malaria in 10.5%, gastroenteritis in 10.3%, urinary tract infection in 5.9%, typhoid fever in 3.7%, skin or mucosal infection in 1.5%, and meningitis in 0.2%. The cause of fever was undetermined in 3.2% of the children. A total of 70.5% of the children had viral disease, 22.0% had bacterial disease, and 10.9% had parasitic disease. CONCLUSIONS: These results provide a description of the numerous causes of fever in African children in two representative settings. Evidence of a viral process was found more commonly than evidence of a bacterial or parasitic process. (Funded by the Swiss National Science Foundation and others.).