Hospital Nacional Cayetano Heredia

OBJECTIVE: Retinopathy of prematurity (ROP) is a potentially avoidable cause of blindness in children. The proportion of blindness as a result of ROP varies greatly among countries depending on their level of development, being influenced by the availability of neonatal care, neonatal outcomes, and whether effective screening and treatment programs are in place. The objective of this study was to compare characteristics of premature infants who developed severe ROP between 1996 and 2002 in highly developed countries with less developed countries. METHODS: This was an observational study. A questionnaire was completed by ophthalmologists in countries with low, moderate, and high development rankings (3 highly developed countries and from 10 less well-developed countries) who screen for ROP in which they supplied birth weights and gestational ages (GAs) of infants who were treated for threshold ROP or identified with more advanced stages of the disease. Birth weights and GAs of infants with severe ROP were measured. RESULTS: The mean birth weights of infants from highly developed countries ranged from 737 to 763 g compared with values ranging from 903 to 1527 g in less developed countries. Mean GAs of infants from highly developed countries ranged from 25.3 to 25.6 weeks compared with 26.3 to 33.5 weeks in less developed countries. A total of 13.0% of 1091 infants from poorly developed countries exceeded United Kingdom screening criteria; 3.6% exceeded a criteria of <34 weeks' GA and/or <1750 g birth weight. CONCLUSIONS: These findings suggest that larger, more mature infants are developing severe ROP in countries with low/moderate levels of development compared with highly developed countries. ROP screening programs need to use criteria that are appropriate for their local population.

BACKGROUND: Delamanid (OPC-67683), a nitro-dihydro-imidazooxazole derivative, is a new antituberculosis medication that inhibits mycolic acid synthesis and has shown potent in vitro and in vivo activity against drug-resistant strains of Mycobacterium tuberculosis. METHODS: In this randomized, placebo-controlled, multinational clinical trial, we assigned 481 patients (nearly all of whom were negative for the human immunodeficiency virus) with pulmonary multidrug-resistant tuberculosis to receive delamanid, at a dose of 100 mg twice daily (161 patients) or 200 mg twice daily (160 patients), or placebo (160 patients) for 2 months in combination with a background drug regimen developed according to World Health Organization guidelines. Sputum cultures were assessed weekly with the use of both liquid broth and solid medium; sputum-culture conversion was defined as a series of five or more consecutive cultures that were negative for growth of M. tuberculosis. The primary efficacy end point was the proportion of patients with sputum-culture conversion in liquid broth medium at 2 months. RESULTS: Among patients who received a background drug regimen plus 100 mg of delamanid twice daily, 45.4% had sputum-culture conversion in liquid broth at 2 months, as compared with 29.6% of patients who received a background drug regimen plus placebo (P=0.008). Likewise, as compared with the placebo group, the group that received the background drug regimen plus 200 mg of delamanid twice daily had a higher proportion of patients with sputum-culture conversion (41.9%, P=0.04). The findings were similar with assessment of sputum-culture conversion in solid medium. Most adverse events were mild to moderate in severity and were evenly distributed across groups. Although no clinical events due to QT prolongation on electrocardiography were observed, QT prolongation was reported significantly more frequently in the groups that received delamanid. CONCLUSIONS: Delamanid was associated with an increase in sputum-culture conversion at 2 months among patients with multidrug-resistant tuberculosis. This finding suggests that delamanid could enhance treatment options for multidrug-resistant tuberculosis. (Funded by Otsuka Pharmaceutical Development and Commercialization; ClinicalTrials.gov number, NCT00685360.).

Léon-Velarde, Fabiola, Marco Maggiorini, John T. Reeves, Almaz Aldashev, Ingrid Asmus, Luciano Bernardi, Ri-Li Ge, Peter Hackett, Toshio Kobayashi, Lorna G. Moore, Dante Penaloza, Jean-Paul Richalet, Robert Roach, Tianyi Wu, Enrique Vargas, Gustavo Zubieta-Castillo, and Gustavo Zubieta-Calleja. Consensus on high altitude diseases. High Alt Med Biol 6:147–157, 2005.—This is an international consensus statement of an ad hoc committee formed by the International Society for Mountain Medicine (ISMM) at the VI World Congress on Mountain Medicine and High Altitude Physiology (Xining, China; 2004) and represents the committee's interpretation of the current knowledge with regard to the most common chronic and subacute high altitude diseases. It has been developed by medical and scientific authorities from the committee experienced in the recognition and prevention of high altitude diseases and is based mainly on published, peer-reviewed articles. It is intended to include all legitimate criteria for choosing to use a specific method or procedure to diagnose or manage high altitude diseases. However, the ISMM recognizes that specific patient care decisions depend on the different geographic circumstances involved in the development of each chronic high altitude disease. These guidelines are established to inform the medical services on site who are directed to solve high altitude health problems about the definition, diagnosis, treatment, and prevention of the most common hychronic high altitude diseases. The health problems associated with life at high altitude are well documented, but health policies and procedures often do not reflect current state-of-the-art knowledge. Most of the cases of high altitude diseases are preventable if on-site personnel identify the condition and implement appropriate care.

Since their discovery in patients with autosomal dominant (AD) chronic mucocutaneous candidiasis (CMC) in 2011, heterozygous STAT1 gain-of-function (GOF) mutations have increasingly been identified worldwide. The clinical spectrum associated with them needed to be delineated. We enrolled 274 patients from 167 kindreds originating from 40 countries from 5 continents. Demographic data, clinical features, immunological parameters, treatment, and outcome were recorded. The median age of the 274 patients was 22 years (range, 1-71 years); 98% of them had CMC, with a median age at onset of 1 year (range, 0-24 years). Patients often displayed bacterial (74%) infections, mostly because of Staphylococcus aureus (36%), including the respiratory tract and the skin in 47% and 28% of patients, respectively, and viral (38%) infections, mostly because of Herpesviridae (83%) and affecting the skin in 32% of patients. Invasive fungal infections (10%), mostly caused by Candida spp. (29%), and mycobacterial disease (6%) caused by Mycobacterium tuberculosis, environmental mycobacteria, or Bacille Calmette-Guérin vaccines were less common. Many patients had autoimmune manifestations (37%), including hypothyroidism (22%), type 1 diabetes (4%), blood cytopenia (4%), and systemic lupus erythematosus (2%). Invasive infections (25%), cerebral aneurysms (6%), and cancers (6%) were the strongest predictors of poor outcome. CMC persisted in 39% of the 202 patients receiving prolonged antifungal treatment. Circulating interleukin-17A-producing T-cell count was low for most (82%) but not all of the patients tested. STAT1 GOF mutations underlie AD CMC, as well as an unexpectedly wide range of other clinical features, including not only a variety of infectious and autoimmune diseases, but also cerebral aneurysms and carcinomas that confer a poor prognosis.

BACKGROUND: Neurocysticercosis is the main cause of adult-onset seizures in the developing world. Whether therapy with antiparasitic agents results in improved seizure control has been questioned because of the lack of adequate, controlled studies. METHODS: We conducted a double-blind, placebo-controlled trial in which 120 patients who had living cysticerci in the brain and seizures treated with antiepileptic drugs were randomly assigned to receive either 800 mg of albendazole per day and 6 mg of dexamethasone per day for 10 days (60 patients) or two placebos (60 patients). The patients were followed for 30 months or until they had been seizure-free for 6 months after the doses of the antiepileptic drugs had been tapered. The efficacy of treatment was measured as the decrease in the number of seizures after treatment. RESULTS: In the albendazole group, there was a 46 percent reduction in the number of seizures (95 percent confidence interval, -74 to 83 percent) during months 2 to 30 after treatment. This reduction, which was not statistically significant, was composed of a nonsignificant reduction of 41 percent in the number of partial seizures (95 percent confidence interval, -124 to 84 percent) and a significant 67 percent reduction in the number of seizures with generalization (95 percent confidence interval, 20 to 86 percent). Most of the difference in the number of partial seizures was attributable to a few patients who had many seizures during follow-up. The proportions of patients who had partial seizures during follow-up were similar in the two groups (19 of 57 in the albendazole group and 16 of 59 in the placebo group), but the patients in the placebo group had a greater tendency to have seizures with generalization (22 of 59, vs. 13 of 57 in the albendazole group; risk ratio, 1.63; 95 percent confidence interval, 0.91 to 2.92). More of the intracranial cystic lesions resolved in the albendazole group than in the placebo group. With the sole exception of abdominal pain, side effects did not differ significantly between the two groups. CONCLUSIONS: In patients with seizures due to viable parenchymal cysts, antiparasitic therapy decreases the burden of parasites and is safe and effective, at least in reducing the number of seizures with generalization.

BACKGROUND: Raltegravir is an HIV-1 integrase strand-transfer inhibitor with potent in vitro activity. This study explored the antiretroviral activity and safety of raltegravir in treatment-naive patients with plasma HIV-1 RNA levels > or = 5000 copies/mL and CD4 T-cell counts > or = 100 cells/mm. METHODS: Multicenter, double-blind, randomized, controlled study of raltegravir at doses of 100, 200, 400, and 600 mg twice daily versus efavirenz at a dose of 600 mg/d, all in combination with tenofovir at a dose of 300 mg/d and lamivudine at a dose of 300 mg/d (clinicaltrials.gov identifier: NCT00100048). RESULTS: In the 198 patients treated (160 on raltegravir and 38 on efavirenz), the mean HIV-1 RNA level ranged from 4.6 to 4.8 log10 copies/mL at baseline. At weeks 2, 4, and 8, the proportion of patients achieving an HIV-1 RNA level <50 copies/mL was greater in each of the raltegravir treatment groups than in the efavirenz group. By week 24, all treatment groups appeared similar, with plasma HIV-1 RNA levels <400 copies/mL in 85% to 98% of patients and <50 copies/mL in 85% to 95% of patients. These reductions were maintained through week 48 in 85% to 98% of patients and in 83% to 88% of patients, respectively. Five (3%) patients on raltegravir and 1 (3%) on efavirenz experienced virologic failure before week 48. Drug-related clinical adverse events were less common with raltegravir than with efavirenz. After 24 and 48 weeks of treatment, raltegravir did not result in increased serum levels of total cholesterol, low-density lipoprotein cholesterol, or triglycerides. CONCLUSIONS: Raltegravir at all doses studied was generally well tolerated in combination with tenofovir and lamivudine. Raltegravir exhibited potent and durable antiretroviral activity similar to that of efavirenz at 24 and 48 weeks but achieved HIV-1 RNA levels below detection at a more rapid rate.

OBJECTIVE: To compare the performance of the direct agglutination test and rK39 dipstick for the diagnosis of visceral leishmaniasis. DATA SOURCES: Medline, citation tracking, January 1986 to December 2004. Selection criteria Original studies evaluating the direct agglutination test or the rK39 dipstick with clinical visceral leishmaniasis as target condition; adequate reference classification; and absolute numbers of true positive, true negative, false positive, and false negative observations available or derivable from the data presented. RESULTS: 30 studies evaluating the direct agglutination test and 13 studies evaluating the rK39 dipstick met the inclusion criteria. The combined sensitivity estimates of the direct agglutination test and the rK39 dipstick were 94.8% (95% confidence interval 92.7% to 96.4%) and 93.9% (87.7% to 97.1%), respectively. Sensitivity seemed higher and more homogenous in the studies carried out in South Asia. Specificity estimates were influenced by the type of controls. In phase III studies carried out on patients with clinically suspected disease, the estimated specificity of the direct agglutination test was 85.9% (72.3% to 93.4%) and of the rK39 dipstick was 90.6% (66.8% to 97.9%). CONCLUSION: The diagnostic performance of the direct agglutination test and the rK39 dipstick for visceral leishmaniasis is good to excellent and seem comparable.

BACKGROUND: Racecadotril (acetorphan), an enkephalinase inhibitor with antisecretory and antidiarrheal actions, is an effective and safe treatment for acute diarrhea in adults and children. Whether treatment with racecadotril and oral rehydration therapy is more effective than treatment with oral rehydration alone in hospitalized children with acute watery diarrhea is not known. METHODS: We treated 135 boys 3 to 35 months of age who had watery diarrhea of five days' duration or less with racecadotril (1.5 mg per kilogram of body weight orally every eight hours) or placebo, in addition to oral rehydration solution. The primary end point was the 48-hour stool output (measured in grams); the total stool output, duration of diarrhea, and total intake of oral rehydration solution were also measured. RESULTS: The mean (+/-SE) 48-hour stool output was 92+/-12 g per kilogram in the racecadotril group and 170+/-15 g per kilogram in the placebo group (P<0.001), a 46 percent reduction with racecadotril. The results were similar among the 73 boys with rotavirus infections. The total stool output was 157+/-27 g per kilogram in the racecadotril group and 331+/-39 g per kilogram in the placebo group (P<0.001). The median duration of diarrhea was significantly less (P<0.001) in the racecadotril group (28 hours regardless of rotavirus status) than in the placebo group (72 and 52 hours, respectively, for rotavirus-positive and rotavirus-negative patients). The intake of oral rehydration solution was significantly lower in the racecadotril group than in the placebo group (P<0.001). Racecadotril was well tolerated; only seven patients taking racecadotril had adverse effects, which were all mild and transient. CONCLUSIONS: In young boys with acute watery diarrhea, racecadotril is an effective and safe treatment.

BACKGROUND: Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. METHODS: In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 μg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. RESULTS: A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P = 0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P = 0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. CONCLUSIONS: In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778.).

BACKGROUND: Allogeneic hematopoietic stem-cell transplantation for X-linked severe combined immunodeficiency (SCID-X1) often fails to reconstitute immunity associated with T cells, B cells, and natural killer (NK) cells when matched sibling donors are unavailable unless high-dose chemotherapy is given. In previous studies, autologous gene therapy with γ-retroviral vectors failed to reconstitute B-cell and NK-cell immunity and was complicated by vector-related leukemia. METHODS: complementary DNA to bone marrow stem cells after low-exposure, targeted busulfan conditioning in eight infants with newly diagnosed SCID-X1. RESULTS: Eight infants with SCID-X1 were followed for a median of 16.4 months. Bone marrow harvest, busulfan conditioning, and cell infusion had no unexpected side effects. In seven infants, the numbers of CD3+, CD4+, and naive CD4+ T cells and NK cells normalized by 3 to 4 months after infusion and were accompanied by vector marking in T cells, B cells, NK cells, myeloid cells, and bone marrow progenitors. The eighth infant had an insufficient T-cell count initially, but T cells developed in this infant after a boost of gene-corrected cells without busulfan conditioning. Previous infections cleared in all infants, and all continued to grow normally. IgM levels normalized in seven of the eight infants, of whom four discontinued intravenous immune globulin supplementation; three of these four infants had a response to vaccines. Vector insertion-site analysis was performed in seven infants and showed polyclonal patterns without clonal dominance in all seven. CONCLUSIONS: Lentiviral vector gene therapy combined with low-exposure, targeted busulfan conditioning in infants with newly diagnosed SCID-X1 had low-grade acute toxic effects and resulted in multilineage engraftment of transduced cells, reconstitution of functional T cells and B cells, and normalization of NK-cell counts during a median follow-up of 16 months. (Funded by the American Lebanese Syrian Associated Charities and others; LVXSCID-ND ClinicalTrials.gov number, NCT01512888.).

BACKGROUND: Once-daily atazanavir/ritonavir demonstrated similar antiviral efficacy to twice-daily lopinavir/ritonavir over 48 weeks, with less gastrointestinal disturbance and a better lipid profile, in treatment-naive patients. METHODS: International, multicenter, open-label, 96-week noninferiority randomized trial of atazanavir/ritonavir 300/100 mg once daily vs lopinavir/ritonavir 400/100 mg twice daily, each in combination with fixed-dose tenofovir/emtricitabine 300/200 mg once daily, in antiretroviral-naive, HIV-1-infected patients. The primary end point was the proportion of patients with HIV RNA <50 copies/mL at 48 weeks. Results through 96 weeks are reported. RESULTS: Of 883 patients enrolled, 440 were randomized to atazanavir/ritonavir and 443 to lopinavir/ritonavir. At week 96, more patients receiving atazanavir/ritonavir achieved HIV RNA <50 copies/mL (74% vs 68%, P < 0.05) in the intent-to-treat analysis. On both regimens, 7% of subjects were virologic failures by 96 weeks. Bilirubin-associated disorders were greater in patients taking atazanavir/ritonavir. Treatment-related gastrointestinal adverse events were greater in patients taking lopinavir/ritonavir. Mean changes from baseline in fasting total cholesterol, non-high-density lipoprotein cholesterol, and triglycerides at week 96 were significantly higher with lopinavir/ritonavir (P < 0.0001). CONCLUSIONS: Noninferiority of atazanavir/ritonavir to lopinavir/ritonavir was confirmed at 96 weeks. Atazanavir/ritonavir had a better lipid profile and fewer gastrointestinal adverse events than lopinavir/ritonavir.

Caspofungin is an antifungal agent of the novel echinocandin class. We investigated its efficacy, safety, and tolerability as therapy for oropharyngeal and/or esophageal candidiasis in a phase II dose-ranging study. Patients were randomized in a double-blind manner to receive either caspofungin acetate (35, 50, or 70 mg) or amphotericin B (0.5 mg/kg of body weight) intravenously once daily for 7 to 14 days. A favorable response required both complete resolution of symptoms and quantifiable improvement of mucosal lesions 3 to 4 days after discontinuation of study drug. Efficacy was assessed using a modified intent-to-treat analysis. No hypothesis testing of efficacy was planned or performed. Of 140 enrolled patients, 63% had esophageal involvement and 98% were infected with the human immunodeficiency virus (HIV) (median CD4 count, 30/mm(3)). A modestly higher proportion of patients in each of the caspofungin groups (74 to 91%) achieved favorable responses compared to amphotericin B recipients (63%), but there was considerable overlap in the 95% confidence intervals surrounding these point estimates. Similar trends were found in the subgroups with esophageal involvement, a history of fluconazole failure, and CD4 counts of < or =50/mm(3). A smaller proportion of patients receiving any dose of caspofungin experienced drug-related adverse events compared to patients given standard doses of conventional amphotericin B (P < 0.01). Caspofungin provided a generally well-tolerated parenteral therapeutic option for HIV-infected patients with oropharyngeal and/or esophageal candidiasis in this study.

En la lucha contra la epidemia del Coronavirus (COVID-19), el personal de salud puede experimentar problemas de salud mental tales como estrés, ansiedad, síntomas depresivos, insomnio, negación, ira y temor. En un estudio en China se observó que la tasa de ansiedad del personal de salud fue del 23,04%, mayor en mujeres que en hombres y mayor entre las enfermeras que entre los médicos. Asimismo, en la población general de China se observó un 53,8% de impacto psicológico moderado a severo; un 16,5% de síntomas depresivos, un 28,8% de síntomas ansiosos y un 8,1% de estrés, todos entre moderados y severos. Los factores asociados con un alto impacto psicológico y niveles elevados de estrés, síntomas de ansiedad y depresión fueron sexo femenino, ser estudiante, tener síntomas físicos específicos y una percepción pobre de la propia salud. Otro estudio en el mismo país detectó un 35% de distrés psicológico en la población general, con las mujeres presentando mayores niveles que los varones, al igual que los sub-grupos de 18-30 años y los mayores de 60 años. La pandemia plantea pues el desafío de cuidar la salud mental del personal de salud tanto como la de la población general. Así, el uso de instrumentos breves de detección de problemas de salud mental, validados en nuestra población, sería de mucha utilidad para los retos de salud pública que afronta el país.

OBJECTIVES: A multinational, multicentre, open-label clinical trial was conducted to evaluate the safety and efficacy of posaconazole, an extended-spectrum triazole antifungal agent, in subjects with invasive fungal infections who had refractory disease or who were intolerant of standard antifungal therapy. In this subanalysis, we report on those subjects in this trial who had a fungal infection that involved the CNS. METHODS: Subjects received posaconazole oral suspension 800 mg/day in divided doses for up to 1 year; however, subjects could receive additional therapy as part of a treatment-use extension protocol. A blinded, third-party data review committee determined subject eligibility and outcome. RESULTS: Of the 330 subjects who enrolled in the study, 53 had infections of the CNS, of which 39 were considered evaluable for efficacy. Most had refractory disease (37 of 39) and underlying HIV infection (29 of 39). Twenty-nine subjects had cryptococcal infections, and 10 had infections caused by other fungal pathogens [Aspergillus spp. (four), Pseudallescheria boydii (two), Coccidioides immitis (one), Histoplasma capsulatum (one), Ramichloridium mackenziei (one), and Apophysomyces elegans plus a Basidiomycetes sp. (one)]. Successful outcomes were observed in 14 of 29 (48%) subjects with cryptococcal meningitis and five of 10 (50%) subjects with CNS infections due to other fungal pathogens. Posaconazole was well tolerated. CONCLUSIONS: These data suggest that posaconazole, as an oral medication, has clinical activity against fungal infections of the CNS and may provide a valuable alternative to parenteral therapy in patients failing existing antifungal agents.

RATIONALE: Esophageal manometry is the clinically available method to estimate pleural pressure, thus enabling calculation of transpulmonary pressure (Pl). However, many concerns make it uncertain in which lung region esophageal manometry reflects local Pl. OBJECTIVES: To determine the accuracy of esophageal pressure (Pes) and in which regions esophageal manometry reflects pleural pressure (Ppl) and Pl; to assess whether lung stress in nondependent regions can be estimated at end-inspiration from Pl. METHODS: In lung-injured pigs (n = 6) and human cadavers (n = 3), Pes was measured across a range of positive end-expiratory pressure, together with directly measured Ppl in nondependent and dependent pleural regions. All measurements were obtained with minimal nonstressed volumes in the pleural sensors and esophageal balloons. Expiratory and inspiratory Pl was calculated by subtracting local Ppl or Pes from airway pressure; inspiratory Pl was also estimated by subtracting Ppl (calculated from chest wall and respiratory system elastance) from the airway plateau pressure. MEASUREMENTS AND MAIN RESULTS: In pigs and human cadavers, expiratory and inspiratory Pl using Pes closely reflected values in dependent to middle lung (adjacent to the esophagus). Inspiratory Pl estimated from elastance ratio reflected the directly measured nondependent values. CONCLUSIONS: These data support the use of esophageal manometry in acute respiratory distress syndrome. Assuming correct calibration, expiratory Pl derived from Pes reflects Pl in dependent to middle lung, where atelectasis usually predominates; inspiratory Pl estimated from elastance ratio may indicate the highest level of lung stress in nondependent "baby" lung, where it is vulnerable to ventilator-induced lung injury.

OBJECTIVES: The aims of this survey were (1) to assess the quality of asthma treatment and control in Latin America, (2) to determine how closely asthma management guidelines are being followed, and (3) to assess perception, knowledge and attitudes related to asthma in Latin America. METHODS: We surveyed a household sample of 2,184 adults or parents of children with asthma in 2003 in 11 countries in Latin America. Respondents were asked about healthcare utilization, symptom severity, activity limitations and medication use. RESULTS: Daytime asthma symptoms were reported by 56% of the respondents, and 51% reported being awakened by their asthma at night. More than half of those surveyed had been hospitalized, attended a hospital emergency service or made unscheduled emergency visits to other healthcare facilities for asthma during the previous year. Patient perception of asthma control did not match symptom severity, even in patients with severe persistent asthma, 44.7% of whom regarded their disease as being well or completely controlled. Only 2.4% (2.3% adults and 2.6% children) met all criteria for asthma control. Although 37% reported treatment with prescription medications, only 6% were using inhaled corticosteroids. Most adults (79%) and children (68%) in this survey reported that asthma symptoms limited their activities. Absence from school and work was reported by 58% of the children and 31% of adults, respectively. CONCLUSIONS: Asthma control in Latin America falls short of goals in international guidelines, and in many aspects asthma care and control in Latin America suffer from the same shortcomings as in other areas of the world.

BACKGROUND: Invasive fungal infections are found most frequently in immunosuppressed and critically ill hospitalized patients. Antifungal therapy is often required for long periods. Safety data from the clinical development program of the triazole antifungal agent, posaconazole, were analyzed. METHODS: A total of 428 patients with refractory invasive fungal infections (n = 362) or febrile neutropenia (n = 66) received posaconazole in 2 phase II/III open-label clinical trials. Also, 109 of these patients received posaconazole therapy for > or = 6 months. Incidences of treatment-emergent, treatment-related, and serious adverse events and abnormal laboratory parameters were recorded during these studies. RESULTS: Treatment-emergent, treatment-related adverse events were reported in 38% of the overall patient population. The most common treatment-related adverse events were nausea (8%) and vomiting (6%). Treatment-related serious adverse events occurred in 8% of patients. Low rates of treatment-related corrected QT interval and/or QT interval prolongation (1%) and elevation of hepatic enzymes (2%) were reported as adverse events. Treatment-emergent, treatment-related adverse events occurred at similar rates in patients who received posaconazole therapy for < 6 months and > or = 6 months. CONCLUSIONS: Prolonged posaconazole treatment was associated with a generally favorable safety profile in seriously ill patients with refractory invasive fungal infections. Long-term therapy did not increase the risk of any individual adverse event, and no unique adverse event was observed with longer exposure to posaconazole.

Human neurocysticercosis, the infection of the nervous system by the larvae of Taenia solium, is a major cause of epileptic seizures and other neurologic morbidity worldwide. The diagnosis and treatment of neurocysticercosis have been considerably improved in recent years. This improvement includes identification and sequencing of specific antigens and development of new assays for laboratory diagnosis, recognition of the frequency and significance of edema around old, calcified cysts (associated to symptomatic episodes), results of a randomized blinded control treatment trial on treatment efficacy for intraparenchymal disease showing a clinical benefit of decreased seizures, and a much better assessment of the frequency and spectrum of cerebrovascular complications. These advances now permit a much better integration of clinical, serologic, and imaging data for diagnosis and therapeutic purposes.

PURPOSE OF REVIEW: Hepatobiliary flukes--Fasciola, Opisthorchis, Clonorchis- are a major public health problem in east Asia, east Europe, Africa and Latin America. The present review focuses on current knowledge of clinical, diagnostic and treatment aspects caused by hepatobiliary flukes that can be applied to current protocols in endemic areas. RECENT FINDINGS: Specific risk factors and geographic areas for these flukes have been heavily reported recently, with millions of people infected worldwide. Human cases in nonendemic areas, related to immigration and the international food trade (i.e. raw vegetables and fish), have also been reported. Diagnostic imaging changes include track-like lesions that are a characteristic feature of acute fascioliasis on computed tomography scanning of the liver. Newly available diagnostic serological tests may detect early infection and, therefore, help reduce severe clinical complications such as recurrent cholangitis, cholecystitis, hepatic tumours, cysts, calcification, cholelithiasis, pancreatitis, most importantly, cholangiocarcinoma related to Opisthorchis viverrini and possibly Clonorchis sinensis, and liver fibrosis associated with Fasciola hepatica infections. Highly effective antiparasitic treatment is available for all flukes. SUMMARY: There is a better understanding of risk factors, clinical manifestations and complications, novel diagnosis tests and effective treatment, which together should help reduce the morbidity and mortality of these infections.

< .05). Differences in survival did not correlate with genetic profile or extent of therapy. HLH should be conceptualized as a phenotype of critical illness characterized by toxic activation of immune cells from different underlying mechanisms. In most patients with HLH, targeted sequencing of fHLH genes remains insufficient for identifying pathogenic mechanisms. Whole-exome sequencing, however, may identify specific therapeutic opportunities and affect hematopoietic stem cell transplantation options for these patients.