Resolution of organ dysfunction as a predictor of long-term survival in necrotizing soft tissue infections: Analysis of the AB103 Clinical Composite Endpoint Study in Necrotizing Soft Tissue Infections trial and a retrospective claims database-linked chart study.

Background: Necrotizing soft tissue infections (NSTIs) are an acute surgical condition with high morbidity and mortality. Timely identification, resuscitation, and aggressive surgical management have significantly decreased inpatient mortality. However, reduced inpatient mortality has shifted the burden of disease to long-term mortality associated with persistent organ dysfunction.

Estimating the Impact of Necrotizing Soft Tissue Infections in the United States: Incidence and Re-Admissions.

Previous estimates of the incidence of necrotizing soft tissue infections (NSTI) in the United States have substantial limitations and underestimate its occurrence. Improvements in hospital mortality after NSTI have increased the number of survivors at risk for long-term sequelae. This study estimates the incidence of NSTI and the burden of re-admission and associated healthcare spending in patients who survived admission for NSTI.

A Novel Immune Modulator for Patients With Necrotizing Soft Tissue Infections (NSTI): Results of a Multicenter, Phase 3 Randomized Controlled Trial of Reltecimod (AB 103).

Background And Objective: Reltecimod, a CD 28 T-lymphocyte receptor mimetic, inhibits T-cell stimulation by an array of bacterial pathogens. A previous phase 2 trial demonstrated improved resolution of organ dysfunction after NSTI. We hypothesized that early administration of reltecimod would improve outcome in severe NSTI.

Validation of a clinical trial composite endpoint for patients with necrotizing soft tissue infections.

Objective: Our objective was to develop and validate a composite endpoint for patients with necrotizing soft tissue infections that incorporates: local tissue injury, systemic organ dysfunction, and mortality.

Methods: The Necrotizing Infection Clinical Composite Endpoint (NICCE) was defined as follows:(i) alive at day 28, (ii) three or less debridements before day 14, (iii) no amputation beyond first debridement, (iv) modified sequential organ failure assessment score score (mSOFA) at day 14 ≤ 1. To be considered a success, all individual criteria must be met.

Impact and Progression of Organ Dysfunction in Patients with Necrotizing Soft Tissue Infections: A Multicenter Study.

Background: Necrotizing soft tissue infections (NSTI) represent a rare but devastating disease for which the systemic manifestations have been poorly characterized. In an effort to define an optimal endpoint for clinical trials in this condition, the objective of this study was to establish the pattern of organ dysfunction over time and determine the correlation between organ dysfunction and clinical outcome in patients with NSTI.

Methods: We conducted a multicenter, retrospective clinical study of patients with NSTI presenting to 12 academic medical centers in the U.

A randomized, open-label, dose-response study of losartan in hypertensive children.

Background And Objectives: Once-daily losartan reduces BP in a dose-dependent manner and is well tolerated in hypertensive children aged 6-16 years. This study assessed the dose-response relationship, safety, and tolerability of losartan in hypertensive children aged 6 months to 6 years.

Design, Setting, Participants, & Measurements: This was a 12-week, randomized, open-label, dose-ranging study, with a 2-year extension.

Evaluating the efficacy and safety of two doses of the polyclonal anti-tumor necrosis factor-α fragment antibody AZD9773 in adult patients with severe sepsis and/or septic shock: randomized, double-blind, placebo-controlled phase IIb study*.

Objective: This trial compared the efficacy/safety of two IV doses of AZD9773, a polyclonal antibody to tumor necrosis factor-α, in adult patients with severe sepsis/septic shock.

Design: Multicenter, randomized, double-blind, placebo-controlled phase IIb trial.

Setting: ICUs in seven countries (Australia, Belgium, Canada, Czech Republic, Finland, France, and Spain).

Declines in mortality rates and changes in causes of death in HIV-1-infected children during the HAART era.

Context: Introduction of highly active antiretroviral therapy has significantly decreased mortality in HIV-1-infected adults and children. Although an increase in non-HIV-related mortality has been noted in adults, data in children are limited.

Objectives: To evaluate changes in causes and risk factors for death among HIV-1-infected children in Pediatric AIDS Clinical Trials Group 219/219C.

Neurodevelopmental outcomes following ganciclovir therapy in symptomatic congenital cytomegalovirus infections involving the central nervous system.

Background: Ganciclovir protects against hearing deterioration in infants with symptomatic congenital cytomegalovirus (CMV) disease involving the central nervous system (CNS).

Objectives: To assess the neurodevelopmental impact of ganciclovir therapy in this population.

Study Design: 100 neonates were enrolled into a controlled Phase III study of symptomatic congenital CMV involving the CNS, and were randomized to either 6 weeks of intravenous ganciclovir or no treatment.

Virologic and immunologic correlates with the magnitude of antibody responses to the hepatitis A vaccine in HIV-infected children on highly active antiretroviral treatment.

Background: HIV-infected individuals mount poor antibody responses to vaccines. We sought to identify the immunologic and virologic factors associated with a robust response to hepatitis A virus (HAV) vaccine in children on highly active antiretroviral treatment.

Methods: One hundred fifty-two pediatric highly active antiretroviral treatment recipients immunized against HAV at weeks 0 and 24 had anti-HAV antibodies, CD4+, CD8+, and CD19+ cell percent assessed at weeks 0 and 32.

Incidence of noninfectious conditions in perinatally HIV-infected children and adolescents in the HAART era.

Objective: To estimate highly active antiretroviral therapy (HAART)-era incident rates for the first episode of noninfectious conditions in human immunodeficiency virus (HIV)-infected youth in order to identify HAART-era changes in the natural history of perinatal HIV infection.

Design: Multicenter prospective cohort study.

Setting: More than 80 sites in the United States including Puerto Rico.

The Pediatric AIDS Severity Score (PASS): a multidimensional AIDS-severity adjustment for pediatric HIV infection.

Background: A severity staging system predictive of mortality for perinatally HIV-infected children is needed for clinical and research purposes.

Methods: A pediatric AIDS severity score (PASS) was developed using baseline sociodemographic, clinical, immunologic, and functional measures obtained from 786 perinatally HIV-infected children enrolled into a prospective cohort study (PACTG 219) in the pre-highly active antiretroviral therapy (HAART) era (pre-1996). PASS was then validated among 392 perinatally HIV-infected children randomly sampled from the original source population (n = 1178).

Simple Pediatric AIDS Severity Score (PASS): a pediatric severity score for resource-limited settings.

Background: A multidimensional pediatric AIDS severity score (PASS) has been developed for severity adjustment and as a predictive model for mortality in a pediatric HIV-infected population. While the prognostic value of PASS is relevant in the US setting, there is a need to develop a simpler model of PASS for use in resource-limited settings where CD4% values and HIV RNA levels may not be available to assess prognosis and guide treatment decisions.

Methods: A Simple PASS model was developed including baseline weight percentile, WHO stage, symptoms, a general health rating, total lymphocyte count, packed-cell volume, and albumin measures from 1178 perinatally HIV-infected children enrolled into a prospective cohort study (PACTG 219).

Risk factors for opportunistic illnesses in children with human immunodeficiency virus in the era of highly active antiretroviral therapy.

Objective: To examine the relationship between the use of highly active antiretroviral treatment (HAART) and the occurrence of opportunistic illnesses (OIs) among children perinatally infected with human immunodeficiency virus.

Design: Prospective cohort study.

Setting: Pediatric AIDS Clinical Trials Group 219C cohort.

Incidence of opportunistic and other infections in HIV-infected children in the HAART era.

Context: Combination anti-retroviral therapy or highly active antiretroviral therapy (HAART) has resulted in a dramatic decline in the incidence of opportunistic and other infections in human immunodeficiency virus (HIV)-infected adults and children.

Objectives: To estimate the incidence of 29 targeted opportunistic and other infections occurring in the era of HAART-between January 1, 2001, and December 31, 2004-in HIV-infected infants, children, and adolescents followed up in Pediatric AIDS Clinical Trials Group (PACTG) 219C; to compare incidence rates in the HAART era to those of the pre-HAART era; and to test for linear trends over time in the HAART era.

Design, Setting, And Participants: Ongoing, multicenter, prospective cohort study designed to examine long-term outcomes in HIV-infected children.

Antibody responses to hepatitis A virus vaccine in HIV-infected children with evidence of immunologic reconstitution while receiving highly active antiretroviral therapy.

Background: Human immunodeficiency virus (HIV)-infected patients have weak responses to vaccines and may require revised immunization regimens. We investigated the safety and immunogenicity of 2 doses of hepatitis A virus (HAV) vaccine followed by a booster dose in HIV-infected children receiving stable highly active antiretroviral therapy.

Methods: A total of 235 children with CD4+ T cell percentages > or = 20% received 2 vaccine doses 24 weeks apart, and 117 received a third vaccine dose after 104 weeks.

GB virus C infection in children with perinatal human immunodeficiency virus infection.

Background: GB virus C (GBV-C) infection occurs in 20-40% of human immunodeficiency virus (HIV)-infected adults, and coinfection is associated with improved HIV disease outcome.

Methods: To determine the prevalence of GBV-C infection in children who were perinatally infected with HIV, we conducted a cross-sectional prevalence survey in a cohort of perinatally infected HIV-positive children selected from a large, multicenter observational protocol. A blood specimen was obtained and tested for GBV-C viremia with the use of a qualitative GBV-C RNA assay and screened for past GBV-C infection with enzyme-linked immunosorbent assay to detect antibodies to the GBV-C envelope protein E2 (E2 Ab).

The rate of serious bacterial infections among HIV-infected children with immune reconstitution who have discontinued opportunistic infection prophylaxis.

Objective: Receipt of highly active antiretroviral therapy is associated with a decrease in the incidence of opportunistic infections (OIs) among HIV-infected adults. The goal of Pediatric AIDS Clinical Trials Group protocol 1008 was to evaluate prospectively the incidence of serious bacterial infections (SBIs) and other OIs after discontinuation of OI and/or Pneumocystis jiroveci pneumonia (PCP) prophylaxis among HIV-infected pediatric subjects who experienced immune reconstitution while receiving stable antiretroviral therapy.

Methods: HIV-infected children and adolescents, 2 to 21 years of age, who had received OI and/or PCP prophylaxis for > or =6 months were enrolled if they had sustained responses (>16 weeks before study entry) to antiretroviral therapy, with CD4+ cell percentages of > or =20% for patients >6 years of age or > or =25% for patients 2 to 6 years of age.

Comparison of atovaquone and azithromycin with trimethoprim-sulfamethoxazole for the prevention of serious bacterial infections in children with HIV infection.

Background: Trimethoprim-sulfamethoxazole (TMP-SMZ) has been used extensively for the prevention of Pneumocystis carinii (also referred to as "Pneumocystis jiroveci") pneumonia (PCP) and other opportunistic infections in human immunodeficiency virus (HIV)-infected children. Because the efficacy of TMP-SMZ for treatment of bacterial infections is limited, it is sometimes poorly tolerated, and there is risk of emergence of drug-resistant strains associated with widespread use, we evaluated a regimen that included atovaquone and azithromycin.

Methods: A randomized, double-blind, placebo-controlled trial was designed to determine whether atovaquone-azithromycin had equivalent efficacy to TMP-SMZ for the prevention of serious bacterial infections and to compare the long-term tolerance, PCP breakthrough rates, and nonserious bacterial infection rates among HIV-infected children aged 3 months to 19 years.

Hepatitis C prevalence in children with perinatal human immunodeficiency virus infection enrolled in a long-term follow-up protocol.

Objective: To evaluate the prevalence of hepatitis C virus (HCV) infection in children with perinatal human immunodeficiency virus (HIV) infection.

Design: Cross-sectional substudy.

Setting: Multicenter study from 41 sites in the United States.

A new respiratory fluoroquinolone, oral gemifloxacin: a safety profile in context.

Gemifloxacin is a broad-spectrum quinolone antibacterial with enhanced potency against Gram-positive bacteria, including multi-drug resistant Streptococcus pneumoniae, and retained potency against Gram-negative bacilli and bacterial strains resistant to other antibiotics. It has proven particularly effective in respiratory and urinary tract infection. This review presents safety data from 6775 patients included in clinical trials, receiving either the recommended 320 mg once daily oral dose of gemifloxacin, or standard dose of other quinolones, macrolides or beta-lactams (n = 5248).

Long-term effects of protease-inhibitor-based combination therapy on CD4 T-cell recovery in HIV-1-infected children and adolescents.

Background: There is limited evidence about longer-term effects of combination antiretroviral therapy that includes protease inhibitors (PIs) on the immunological status of HIV-1-infected children. Better understanding might help to resolve questions on when to initiate treatment.

Methods: The change in percentage of CD4-positive T lymphocytes (CD4%) was investigated in 1012 previously treated HIV-1-infected children (aged 0-17 years) who were enrolled in research clinics in the USA before 1996 and followed up to 2000.

Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial.

Objective: To evaluate the efficacy and safety of ganciclovir therapy in neonates with congenital cytomegalovirus (CMV) disease.

Study Design: Neonates with symptomatic CMV disease involving the central nervous system were randomly assigned to receive 6 weeks of intravenous ganciclovir versus no treatment. The primary end point was improved brainstem-evoked response (BSER) between baseline and 6-month follow-up (or, for patients with normal baseline hearing, normal BSER at both time points).

Pharmacokinetics and tolerance of zidovudine in preterm infants.

Objective: To determine zidovudine pharmacokinetics and tolerance in premature human human immunodeficiency virus-exposed infants.

Study Design: Pediatric AIDS Clinical Trials Group Study 331 was a multicentered prospective, open-label study of the use of zidovudine in premature infants. Thirty-eight infants <35 weeks' gestational age (GA) were studied while receiving zidovudine 1.

Effect of combination therapy including protease inhibitors on mortality among children and adolescents infected with HIV-1.

Background: Combination therapy including protease inhibitors has been shown to be effective in treating adults infected with human immunodeficiency virus type 1 (HIV-1), but there are only limited data regarding the treatment of children and adolescents.

Methods: A cohort of 1028 HIV-1-infected children and adolescents, from birth through 20 years of age, who were enrolled in research clinics in the United States before 1996 was followed prospectively through 1999. We used proportional-hazards regression models to estimate the effect on mortality of combination therapy including protease inhibitors.