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PURPOSE: Patients with the autosomal recessive disorder of familial dysautonomia typically exhibit exacerbated adverse side effects to many common drugs. We aimed to catalog these adverse effects - with a focus on common drugs that are frequently administered to FD patients and compare their incidences to those within the general population. METHODS: We used data of 595 FD patients from an international database with information on drugs received and adverse effects. To investigate the molecular causes of reported differences in drug responses in FD patients, we used expression microarrays to compare the mRNA expression profiles in peripheral blood leukocytes of FD patients (n = 12) and healthy individuals (n = 10). RESULTS: Several drug classes, including cholinergics, anti-cholinergics, anti-convulsants, methylxanthines, SSRIs, and antibiotics caused either unreported symptoms or elevated rates of adverse events in FD patients. FD patients experienced different or more frequent adverse side effects than the general population in 31/123 drugs. These side effects included blood cell dyscrasias, amenorrhea, gastrointestinal bleeding, and bronchospasm. New findings include enhanced reaction of FD patients to H2 antagonist agents and to serotonin receptor agonists. We also detected eight genes differentially expressed between FD patients and healthy individuals that may underlie the differential drug responses of FD patients. CONCLUSION: We provide evidence that suggests the use of several common drugs should be discontinued or reduced in FD patients.
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Disautonomia Familiar , Preparações Farmacêuticas , Proteínas de Transporte , Disautonomia Familiar/epidemiologia , Disautonomia Familiar/genética , Feminino , Humanos , Fatores de Elongação da TranscriçãoRESUMO
PURPOSE OF REVIEW: Postoperative sepsis is a major cause of surgical associated morbidity and mortality. Our goal is to describe its incidence, pathophysiology, and contributing factors. In addition, we will review preventive measures and treatment options that may possibly reduce its healthcare burden. RECENT FINDINGS: We review epidemiologic data and clinical tools presented in multiple current studies, which may help lower incidence and improve outcome of postoperative sepsis. SUMMARY: The incidence of postoperative sepsis has not declined over the past years, although mortality is trending downwards. Several biochemical and genetic markers may allow early diagnosis. Prevention and prompt treatment may lower mortality.
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Complicações Pós-Operatórias , Sepse/etiologia , Marcadores Genéticos , Humanos , Incidência , Cuidados Pós-Operatórios , Cuidados Pré-Operatórios , Prevalência , Fatores de Risco , Sepse/epidemiologia , Sepse/patologia , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
Faced with increased demands for critical care services as a result of the novel H1N1 pandemic, hospitals must prepare a surge response in an attempt to manage these needs. In preparing for a surge response, factors to consider are staff, stuff (supplies and equipment), space, and systems necessary to respond to the event. This article uses this general framework to discuss surge issues in the context of H1N1 challenges that we are facing currently and to provide specific advice for hospitals. Particular attention is given to how hospitals can estimate the potential impact of H1N1 and pharmaceutical stockpiling.
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Planejamento em Desastres/organização & administração , Surtos de Doenças , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/epidemiologia , Influenza Humana/terapia , Unidades de Terapia Intensiva/organização & administração , Necessidades e Demandas de Serviços de Saúde/organização & administração , Humanos , Modelos Teóricos , Admissão e Escalonamento de PessoalRESUMO
A 17-year-old patient with GSD type 1a (von Gierke disease) was hospitalized with an extremely elevated serum lactate following an intercurrent infection and interruption of his frequent intake of carbohydrates. The patient developed shock, oliguric renal failure, and cardiorespiratory failure requiring mechanical ventilation and inotropes. At the peak of metabolic decompensation and clinical instability, serum lactate reached a level of 47.6 mmol/L which was accompanied by a severe anion gap metabolic acidosis with a pH of 6.8 and bicarbonate of 4 meq/L. The patient was stabilized with massive infusions of sodium bicarbonate (45 meq/h) and glucose and recovered without the need for dialysis. This patient illustrates pathophysiologic mechanisms involved in the development of extreme mixed type A and type B lactic acidemia, reflecting altered metabolic pathways in GSD type 1, combined with tissue hypoperfusion. The rationale for the specific interventions in this case is outlined.
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Intravenous cannula and administration set fixation is crucial for fluid resuscitation and intravenous administration of medications. Because conventional hospital fixations are insufficient for the military field scenario, two consecutive, prospective, randomized, clinical trials were performed in the Israel Defense Forces Medical School, to determine the most effective fixation method in the military arena. Gauze bandage, adhesive bandage, Coban wrap, and plastic wrap fixation methods were tested for field conditions and intravenous fluid flow. The results showed that plastic wrap is the fastest fixation method, withstands field conditions with minimal negative effects on the intravenous fluid flow, and is the most cost-effective.
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Cateterismo/métodos , Bombas de Infusão , Medicina Militar , Humanos , Israel , Estudos ProspectivosRESUMO
BACKGROUND: The sterile conditions used when inserting a central venous catheter (CVC) might be thought to decrease the contamination rate of blood cultures taken at CVC insertion; however, a previous retrospective study showed the opposite, that such blood cultures are contaminated more frequently than peripheral venipuncture blood cultures. The current study explored whether use of the CVC nonwire hub as a source of blood cultures decreased contamination while maintaining detection of true pathogens. METHODS: A prospective, observational study was performed from June 2010 to May 2011 in the general ICU of an academic, tertiary referral center. The proportions of blood cultures taken from wire and nonwire CVC hubs growing contaminants and true pathogens were compared. Risk factors for blood culture contamination were identified, and multivariate analysis was used to identify independent predictors of blood culture contamination. RESULTS: Among 313 blood cultures taken from 227 CVCs in 139 patients, 27 of 141 wire hub (19%) vs nine of 172 nonwire hub (5%) cultures were contaminated (P < .001). Only hub of blood culture origin was associated with contamination on multivariate analysis (OR, 4.3; 95% CI, 1.9-9.5; P < .001). True pathogens grew in 19 of 141 wire hub (13%) vs 27 of 172 nonwire hub (16%) cultures (P = .581). CONCLUSIONS: A higher proportion of blood cultures taken from the CVC lumen exposed to the guidewire were contaminated when compared with nonwire hub cultures; detection of true pathogens was equivalent. To limit detrimental sequelae of blood culture contamination, blood cultures obtained at CVC insertion should be taken from the nonwire hub.
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Coleta de Amostras Sanguíneas/métodos , Cateterismo Venoso Central/métodos , Sepse/prevenção & controle , Infecções Relacionadas a Cateter/epidemiologia , Cateterismo Venoso Central/efeitos adversos , Cateterismo Periférico/efeitos adversos , Humanos , Análise Multivariada , Estudos ProspectivosRESUMO
OBJECTIVE: N-terminal pro-B-type natriuretic peptide has been shown to be a marker for cardiac dysfunction. The peptide level is also elevated in patients with sepsis. The purpose of this study was to assess whether N-terminal pro-B-type natriuretic peptide levels can differentiate pediatric patients with sepsis from patients with acute left ventricular dysfunction. PATIENTS AND METHODS: Pediatric patients admitted to an ICU with sepsis or acute left ventricular dysfunction were evaluated clinically, and the grade of systemic inflammatory-response syndrome was determined. Echocardiography was performed, and their levels of N-terminal pro-B-type natriuretic peptide were measured. The N-terminal pro-B-type natriuretic peptide level was also measured in patients with simple febrile illness. RESULTS: There were 10 patients with sepsis and 10 with acute left ventricular dysfunction. The age of the patients was similar, and systemic inflammatory-response syndrome grading was not different (sepsis: 2.8 +/- 0.4; acute left ventricular dysfunction: 2.6 +/- 0.7). N-terminal pro-B-type natriuretic peptide levels were elevated in patients with sepsis (median: 6064 pg/mL; range: 495-60,417 pg/mL) but were significantly higher in patients with acute left ventricular dysfunction (median: 65,630 pg/mL; range: 15,125-288,000). The area under the receiver operating characteristics curve for the diagnosis of acute left ventricular dysfunction was 0.9. N-terminal pro-B-type natriuretic peptide levels of patients with sepsis and impaired systolic function were not different from those of patients with sepsis and normal systolic function. The N-terminal pro-B-type natriuretic peptide levels of 20 patients with simple febrile illness were significantly lower. CONCLUSIONS: N-terminal pro-B-type natriuretic peptide levels are elevated in pediatric patients with sepsis but are higher in some, but not all, patients with acute left ventricular dysfunction. The overlap between N-terminal pro-B-type natriuretic peptide levels in sepsis and acute left ventricular dysfunction precludes the use of the peptide's level as a sole means to differentiate between these conditions. Excessive elevation in N-terminal pro-B-type natriuretic peptide levels, however, suggests cardiac etiology for acute hemodynamic deterioration in infants and children.