Using a Modeling-Based Approach to Assess and Optimize HIV Linkage to Care Services.

Evidence-based linkage to care interventions (LTCs) help recently diagnosed HIV+ individuals engage in care in a timely manner yet are heavily impacted by the systems in which they are embedded. We developed a prototype agent-based model informed by data from an established LTC program targeting youth and young adults aged 13-24 in Memphis, Tennessee. We then tested two interventions to improve LTC in a simulated environment: expanding testing sites versus using current testing sites but improving direct referral to LTC staff from organizations providing testing, to understand the impact on timely linkage to care. Improving direct referral to the LTC program decreased days to successful linkage from an average of 30 to 23 days but expanding testing sites increased average days to 31 days unless those sites also made direct referrals. We demonstrated how LTC is impacted by the system and interventions for shortening days to linkage to care.

Multiple endocrine neoplasia syndromes 1 and 2: manifestations and management in childhood and adolescence.

The identification of the genetic causes of the multiple endocrine neoplasia (MEN) syndromes 1 and 2, and associated genotype-phenotype relationships, has revolutionised the clinical care of affected patients. A genetic diagnosis can be made during infancy and careful clinical surveillance, coupled with early intervention, has the potential to improve both morbidity and mortality. These developments have seen the management of patients with MEN move into the arena of paediatric medicine. In this review article, we consider the genetic causes of MEN together with the clinical manifestations and management of these syndromes.

Short-term outcomes after perinatal hypoxic ischemic encephalopathy: a report from the Children's Hospitals Neonatal Consortium HIE focus group.

OBJECTIVE: To characterize infants affected with perinatal hypoxic ischemic encephalopathy (HIE) who were referred to regional neonatal intensive care units (NICUs) and their related short-term outcomes. STUDY DESIGN: This is a descriptive study evaluating the data collected prospectively in the Children's Hospital Neonatal Database, comprised of 27 regional NICUs within their associated children's hospitals. A consecutive sample of 945 referred infants born ⩾36 weeks' gestation with perinatal HIE in the first 3 days of life over approximately 3 years (2010-July 2013) were included. Maternal and infant characteristics are described. Short-term outcomes were evaluated including medical comorbidities, mortality and status of survivors at discharge. RESULT: High relative frequencies of maternal predisposing conditions, cesarean and operative vaginal deliveries were observed. Low Apgar scores, profound metabolic acidosis, extensive resuscitation in the delivery room, clinical and electroencephalographic (EEG) seizures, abnormal EEG background and brain imaging directly correlated with the severity of HIE. Therapeutic hypothermia was provided to 85% of infants, 15% of whom were classified as having mild HIE. Electrographic seizures were observed in 26% of the infants. Rates of complications and morbidities were similar to those reported in prior clinical trials and overall mortality was 15%. CONCLUSION: Within this large contemporary cohort of newborns with perinatal HIE, the application of therapeutic hypothermia and associated neurodiagnostic studies appear to have expanded relative to reported clinical trials. Although seizure incidence and mortality were lower compared with those reported in the trials, it is unclear whether this represented improved outcomes or therapeutic drift with the treatment of milder disease.

Predictors of acquiring a nosocomial bloodstream infection on extracorporeal membrane oxygenation.

PURPOSE: The aim of this study was to identify independent predictors of acquiring a nosocomial bloodstream infection (BSI) during extracorporeal membrane oxygenation (ECMO). METHODS: This retrospective cohort consisted of 202 neonates treated with ECMO from 1989 to 1998 at the author' institution. Data collected included patient demographics, primary and secondary diagnoses, white blood cell counts, antibiotic usage, presence of central lines, operative procedures, and outcome. Surveillance blood cultures were drawn daily from the circuit using sterile technique to identify acquired pathogens. Statistical analyses included logistic regression, Cox proportional regression analysis, and discriminate analysis. RESULTS: There were 1,245 blood cultures drawn on 202 patients (6.2 cultures per patient), and a nosocomial BSI was identified in 7 patients (3.4%) during this 10-year span. These were infections that were neither present nor incubating on admission. Pre-ECMO diagnoses of patients who had a nosocomial BSI while on bypass included group B beta-hemolytic streptococcal sepsis (n = 2), herpes simplex viral sepsis (n = 1), congenital diaphragmatic hernia (n = 2), persistent pulmonary hypertension (n = 1), and congenital heart disease (n = 1). The median time on ECMO before obtaining a positive culture was 390 hours. The infectious agents responsible for these BSIs included Staphylococcus epidermidis (n = 5), Staphylococcus aureus (n = 1), and Escherichia coli (n = 1). The major factor associated with acquiring a nosocomial BSI on ECMO was the duration of bypass (391 v 141 hours, P =.002). Additionally, patients in the BSI group were more likely to have had an arterial catheter in place (16 v 7 days, P =.009) and to have received more screening blood cultures (16 v 6 cultures, P < 001). White blood cell counts, absolute neutrophil counts, and immature/total (I/T) ratios were not useful in predicting a nosocomial BSI. Of the 31 patients who required ECMO for more than 10 days, 7 (23%) had a positive blood culture, and 5 of these 7 infants (71%) died (P =.03). CONCLUSIONS: The only predictor of acquiring a nosocomial BSI on ECMO was the duration of support for greater than 10 days. Because classical predictors of infection are unreliable while the patient is on ECMO, the authors suggest that obtaining daily surveillance blood cultures beginning on the tenth day should be performed with prolonged ECMO courses. The authors confirmed previous reports of the association between a prolonged ECMO course and a high mortality rate. However, the authors speculate that, in actuality, the primary diagnosis leads to the prolonged course of support and is the major factor in the infant' demise.

Decreased antitoxic activities among children with clinical episodes of malaria.

Healthy Gambian children, children with clinical Plasmodium falciparum malaria, and children with asymptomatic P. falciparum infections were studied to investigate whether antitoxic activities may contribute to protection against malarial symptoms. Markers of inflammatory reactions, soluble tumor necrosis factor receptor I, and C-reactive protein were found in high concentrations in children with symptomatic P. falciparum malaria compared with levels in children with asymptomatic P. falciparum infections or in healthy children, indicating that inflammatory reactions are induced only in children with clinical symptoms. Concentrations of soluble tumor necrosis factor receptor I and C-reactive protein were associated with levels of parasitemia. We detected antitoxic activities in sera as measured by their capacity to block toxin-induced Limulus amoebocyte lysate (LAL) activation. Symptomatic children had decreased capacity to block induction of LAL activation by P. falciparum exoantigen. The decreased blocking activity was restored in the following dry season, when the children had no clinical malaria. Symptomatic children also had the highest immunoglobulin G (IgG) reactivities to conserved P. falciparum erythrocyte membrane protein 1 and "Pfalhesin" (band #3) peptides, indicating that such IgG antibodies are stimulated by acute disease but are lost rapidly after the disease episode. Half of the children with symptomatic infections had low levels of haptoglobin, suggesting that these children had chronic P. falciparum infections which may have caused symptoms previously. Only a few of the children with asymptomatic P. falciparum infections had high parasite counts, and antitoxic immunity in the absence of antiparasite immunity appears to be rare among children in this community.

Retaining extracorporeal membrane oxygenation cannulae after extracorporeal support in the neonate: is it safe?

The retention of extracorporeal membrane oxygenation (ECMO) cannulae of ECMO is discontinued was originally developed to avoid reexploration of the neck in patients who may require a second course of ECMO. Because of the incidence, at the authors' institution, of thrombi noted on the ends of retained cannulae and their potential to cause significant morbidity, a critical review of this procedure was initiated. A telephone survey of 72 Extracorporeal Life Support Organization (ELSO) centers was conducted, and ELSO registry forms were requested for patients who had their cannulae retained. Twenty-four of these centers had performed the procedure of retaining ECMO cannulae. There were 324 neonatal and pediatric patients who had their cannulae retained, with 41 patients (12%) requiring a second course of ECMO and 17 of 41 (41%) surviving the second course. Twelve of the 24 ELSO centers that retain cannulae have reported complications. Analyses of the patients who had their cannulae retained showed that the three best predictors for requiring a second course of ECMO were the diagnosis of congenital diaphragmatic hernia (CDH) a high oxygenation index just before the initiation of ECMO, and a lengthy first ECMO course. The only difference between the survivors and nonsurvivors of the second course of ECMO was the length of the first ECMO course (P < .05). Five of the 25 patients who required two courses of ECMO had serious complications from their retained cannulae and all were nonsurvivors. The authors conclude that patients with retained ECMO cannulae are at high risk for developing thrombi, which can lead to severe embolic events. Therefore, the procedure of retaining cannulae should only be used in patients at high risk for requiring a second course of ECMO and not for the convenience of surgical availability to remove the cannulae.

Preoperative versus postoperative extracorporeal life support in neonatal cardiac patients.

The aim of this study is to document our experience with the use of extracorporeal life support (ECLS) in the neonatal cardiac patient, to detect differences in the morbidity and mortality between patients who required ECLS preoperatively and those who required ECLS postoperatively, and to determine the long-term effects of these morbidities. A chart review was undertaken of all neonatal cardiac patients who required ECLS between May 1985 and July 1994 at Kosair Children's Hospital, Louisville, Kentucky. Twenty-three neonatal cardiac patients had received preoperative or postoperative ECLS with an overall survival rate of 35%. Our preoperative and postoperative patients had similar demographics, diagnoses, decannulation rates and survival rates. However, patients receiving postoperative ECLS more frequently required more than two inotropes (p < 0.001), had an increased incidence of renal failure (p < 0.02), had more central nervous system abnormalities on brain imaging studies (p < 0.004), and had a longer hospital stay (p < 0.05). Follow-up testing of survivors yielded normal Bayley Scale of Infant Development (BSID) scores in half of the patients. Survival in the two groups was similar, but a significant difference in morbidity was found. Except for severe intracranial abnormalities, the morbidity was shown to be reversible on follow-up examination. We recommend the continued use of ECLS for neonatal cardiac patients who require preoperative or postoperative support even when severe renal failure ensues or minor abnormalities are detected on brain imaging studies.

Discharge of elderly people from an accident and emergency department: evaluation of health visitor follow-up.

Elderly people discharged directly home from an accident and emergency department are known to be a vulnerable group. The value of health visitor follow-up in patients aged 75 years and over was assessed in a random controlled trail; 222 intervention patients were seen at home by a research health visitor shortly after discharge and screened for new dependency and support needs, appropriate community services then being offered. These patients, and 192 controls for whom no special arrangements were made, were followed up four weeks later by a research occupational therapist. New dependency, most commonly trauma-related, was found in approximately 50%, and in the majority proved transient. Advice and/or referral to a wide range of services was offered to 92% of the intervention group. Service refusal rates were high in both groups. Compared to controls, intervention patients received more services and were significantly more independent at four weeks. Health visitor assessment was seen as helpful. In order to identify elderly accident and emergency department patients at risk following discharge, study data were used to derive a short questionnaire. In follow-up visits to 48 patients the use of this questionnaire was piloted, and its validity demonstrated. A number of study limitations and areas for development of discharge planning are discussed.

Soluble products of inflammatory reactions are not induced in children with asymptomatic Plasmodium falciparum infections.

A proportion of children with Plasmodium falciparum infection have a high parasitaemia without accompanying fever, indicative of different clinical thresholds of parasitaemia. Higher levels of IL-10, IL-1Ra and sIL-4R but not sIL-2R were found in children with P. falciparum malaria, compared with levels in children with asymptomatic P. falciparum infections and in healthy children. Concentrations of IL-10 and IL-1Ra were correlated with levels of parasitaemia, but the association of cytokine levels with disease was independent of the association with parasitaemia. Children may tolerate a high parasitaemia by neutralizing the parasite-derived toxins. When studying potential anti-toxic molecules we found that children with symptomatic infections had lower concentrations of a phospholipid-binding molecule, beta 2-glycoprotein I (beta 2-GPI), compared with children with asymptomatic infections or healthy children. In conclusion, cytokines were found in much higher concentrations in children with symptomatic P. falciparum malaria than in children with asymptomatic infections, whilst the former had lower concentrations of beta 2-GPI.

Increased concentrations of interleukin-6 and interleukin-1 receptor antagonist and decreased concentrations of beta-2-glycoprotein I in Gambian children with cerebral malaria.

To investigate the pathogenic versus the protective role of cytokines and toxin-binding factors in Plasmodium falciparum infections, we measured the concentrations of tumor necrosis factor alpha, interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor antagonist, and IL-6, as well as soluble receptors of tumor necrosis factor and IL-6 (sIL-6R) in serum of Gambian children with cerebral malaria, mild or asymptomatic malaria, or other illnesses unrelated to malaria. Because cytokine secretion may be triggered by toxic structures containing phosphatidylinositol (PI), we also measured concentrations of anti-PI antibodies and the PI-binding serum protein beta-2-glycoprotein I. We found increased concentrations of IL-6, sIL-6R, IL-1ra, and some immunoglobulin M antibodies against PI in children with cerebral malaria, but those who died had decreased concentrations of beta-2-glycoprotein I. We conclude that increased concentrations of cytokines and soluble cytokine receptors represent a normal host response to P. falciparum infections but that excessive secretion of cytokines like IL-6 may predispose to cerebral malaria and a fatal outcome while beta-2-glycoprotein I may protect against a fatal outcome of cerebral malaria.