The use of navigation to achieve soft tissue balance in total knee arthroplasty - a randomised clinical study.

BACKGROUND: Achieving soft tissue balance is an operative goal in total knee arthroplasty. This randomised, prospective study compared computer navigation to conventional techniques in achieving soft tissue balance. METHODS: Forty one consecutive knee arthroplasties were randomised to either a non-navigated or navigated group. In the non-navigated group, balancing was carried out using surgeon judgement. In the navigated group, balancing was carried out using navigation software. In both groups, the navigation software was used as a measuring tool. RESULTS: Balancing of the mediolateral extension gap was superior in the navigation group (p=0.001). No significant difference was found between the two groups in balancing the mediolateral flexion gap or in achieving equal flexion and extension gaps. CONCLUSIONS: Computer navigation offered little advantage over experienced surgeon judgement in achieving soft tissue balance in knee replacement. However, the method employed in the navigated group did provide a reproducible and objective assessment of flexion and extension gaps and may therefore benefit surgeons in training. LEVEL OF EVIDENCE: Level I, RCT.

Toll-like receptor genetic variants are associated with Gram-negative infections in VLBW infants.

OBJECTIVE: To test the hypothesis that single-nucleotide polymorphisms (SNPs) in Toll-like receptor (TLR) genes alter susceptibility to bacterial infections and modulate white blood cell (WBC) counts during infections in very low birth weight (VLBW) infants (birth weight <1500 g). STUDY DESIGN: VLBW infants recruited in a multicenter study were genotyped for nine functional TLR SNPs and associations between SNPs and infection rates examined. WBC counts obtained during infections were compared among infants with and without SNPs. RESULT: In our cohort (n=408), 90 infants developed bacterial infections. Presence of TLR4 (rs4986790 and rs4986791) variants were associated with Gram-negative (G-ve) infections. Female infants heterozygous for the X-linked IRAK1 (rs1059703) SNP had less G-ve infections. In regression models controlling for confounders, the TLR4 (rs4986790) SNP was associated with increased G-ve infections. The TLR5 (rs5744105) variant was associated with elevated WBC counts during infections. CONCLUSION: TLR genetic variants can contribute to increased risk of bacterial infections and altered immune responses in VLBW infants.

Readiness of obstetric professionals to inform parents regarding potential outcome of premature infants.

Parents often regard obstetric professionals as an important source of information regarding prematurity. However, there is no information regarding the readiness of these obstetric professionals to inform expectant parents of the potential outcomes of premature infants. Using a self-report questionnaire, we determined the knowledge of obstetric professionals regarding outcomes of premature infants, and gauged their confidence in providing this information to expectant parents. Some 50% of obstetric professionals reported that they 'struggle to answer parental questions' regarding premature infants. The majority of obstetric professionals correctly identified potential morbidities of prematurity, but compared to neonatal professionals, they were less likely to discuss this information with parents. When they do provide information to parents, obstetric professionals were least likely to discuss neurological morbidities. Our study has identified an important barrier to the effective transfer of neonatal outcomes information to expectant parents. This limitation requires further investigation and intervention.

Evolution of obesity in a low birth weight cohort.

OBJECTIVE: The objective of this study was to determine the evolution of obesity status (OS) in a longitudinal cohort of low birth weight preterm (LBWPT) infants to an age of 8 years, and to determine whether rapid weight gain in the first year of life independently predicts 8-year OS. STUDY DESIGN: In total, 985 infants (birth weight ≤2500 g, gestation age ≤37 weeks) were recruited from the nursery in an eight-site intervention research program and were evaluated at an age of 3, 5, 6.5 and 8 years. Weight and height were measured by standard protocol at each visit and body mass index was calculated. Obesity status is ≥95% for age and sex. Multiple logistic analyses were performed on 8-year OS with predictor variables including infant race, gender, small for gestational age status, birth weight category, neonatal health index, treatment group and first-year weight gain; maternal education and weight status before conception; and HOME Inventory. RESULT: Overall, 2.3% were OS at an age of 3 years, 6.1% at an age of 5 years, 7.7% at age 6.5 years and 8.7% at an age 8 years. OS varied by birth weight category at each visit. The infants born ≤1500 g had the lowest prevalence of OS at each age. In the logistic regression, maternal race (Hispanic) (adjusted odds ratio=2.8, confidence interval=1.2 to 6.8), maternal obese status (adjusted odds ratio 3.4, confidence interval=1.5 to 7.8) and first-year weight gain (adjusted odds ratio=2.7, confidence interval=1.9 to 3.9), significantly predicted 8-year OS. CONCLUSION: OS is common in LBWPT infants during childhood, and prevalence varies by birth weight category. High weight gain in the first year of life is an important predictor of the development of OS in LBWPT children.

Clostridium difficile in patients undergoing primary hip and knee replacement.

Antibiotic prophylaxis is routinely administered during joint replacement surgery and may predispose patients to Clostridium difficile-associated disease (CDAD). The primary aim of this study was to determine the incidence of this following joint replacement, using a cefuroxime-based regimen. Patients developing CDAD were compared with a control group of patients without CDAD. The incidence of the former was 1.7 per 1000 primary joint replacements. Those patients prescribed additional antibiotics had a higher incidence of CDAD (p = 0.047), but there was no difference between the two groups in relation to the use of gastroprotective agents (p = 0.703). A trial of a new prophylaxis regimen would require 43 198 patients in each arm to show a reduction of one case per 1000 procedures. Cefuroxime-based antibiotic prophylaxis is safe in patients undergoing primary elective joint replacement.

Acetaminophen-associated hepatic injury: evaluation of acetaminophen protein adducts in children and adolescents with acetaminophen overdose.

Acetaminophen protein adducts (APAP adducts) were quantified in 157 adolescents and children presenting at eight pediatric hospitals with the chief complaint of APAP overdose. Two of the patients required liver transplantation, whereas all the others recovered spontaneously. Peak APAP adducts correlated with peak hepatic transaminase values, time-to-treatment with N-acetylcysteine (NAC), and risk determination per the Rumack-Matthews nomogram. A population pharmacokinetic analysis (NONMEM) was performed with post hoc empiric Bayesian estimates determined for the elimination rate constants (k(e)), elimination half-lives (t(1/2)), and maximum concentration of adducts (C(max)) of the subjects. The mean (+/-SD)k(e) and half-life were 0.486 +/- 0.084 days(-1) and 1.47+/- 0.30 days, respectively, and the C(max) was 1.2 (+/-2.92) nmol/ml serum. The model-derived, predicted adduct value at 48 h (Adduct 48) correlated with adductC(max), adduct T(max), Rumack-Matthews risk determination, peak aspartate aminotransferase (AST), and peak alanine aminotransferase (ALT). The pharmacokinetics and clinical correlates of APAP adducts in pediatric and adolescent patients with APAP overdose support the need for a further examination of the role of APAP adducts as clinically relevant and specific biomarkers of APAP toxicity.

[In vitro elution and mechanical properties of antibiotic-loaded SmartSet HV and Palacos R acrylic bone cements]. / In-vitro-Freisetzung von Antibiotika aus SmartSet HV- und Palacos R-Knochenzement und deren Einfluss auf die mechanischen Eigenschaften.

BACKGROUND: The continuing emergence of new bone cements with additional antibiotics makes it important to establish which one will provide the most favourable antibiotic elution. An in vitro antibiotic elution and mechanical study was therefore carried out to compare a newer bone cement, SmartSet, with the established Palacos R cement. METHODS: Samples were prepared with each cement adding 1 g gentamicin, 1 g of vancomycin, or 1 g of gentamicin and vancomycin. The samples were analysed using fluorescence polarisation immunoassay. Mechanical tests were performed to determine whether any significant degradation in the cement strength occurred following addition of the antibiotic. RESULTS: With regards to gentamicin release Palacos R eluted significantly more antibiotic over the study period than SmartSet (p<0.001). Both cements eluted significantly more gentamicin when two antibiotics were added. With respect to vancomycin release there was no significant difference. Palacos R was significantly stronger than SmartSet in the 4-point bending test when the gentamicin + vancomycin antibiotic groups were compared (p=0.01). Palacos R also demonstrated a higher elastic modulus than SmartSet when the gentamicin and gentamicin + vancomycin groups were compared (p=0.03, p=0.005). CONCLUSIONS: Gentamcin shows better release characteristics from Palacos R. Both cements exhibited synergistic release of combined antibiotics.

Impact of a waiting room videotape message on parent attitudes toward pediatric antibiotic use.

OBJECTIVE: To reduce the injudicious use of antibiotics, we developed an educational strategy that focused on parents of pediatric patients and their physicians. METHODS: This intervention was conducted in 5 pediatric practices in Arkansas during a 9-month period. Baseline data on parent attitudes about antibiotics and physician practice habits were measured by questionnaire. During the following 36 weeks, an educational videotape about the judicious use of antibiotics was played in waiting rooms. The videotape on antibiotics used a standard script based on the recommendations of the American Academy of Pediatrics. The physicians and staff at each site were actors in the videotape. During week 2 and week 36 of videotape use, parent attitudes were measured again. After the baseline week, the physicians and staff in each site were provided a standard in-service review of the American Academy of Pediatrics recommendations for judicious use of antibiotics. A study nurse recruited patients, administered questionnaires, and reviewed charts on-site. RESULTS: Parents who were exposed to the videotape were significantly less inclined to seek antibiotics for viral infections. Passively provided pamphlets were not read. No significant change in antibiotic prescribing by physicians was seen. CONCLUSION: Parent-focused passive education tools are effective at changing parent attitudes toward the use of antibiotics. Although physicians have blamed parent attitudes and demands for the overuse of antibiotics, changes in parent attitudes in this study were not associated with changes in prescribing rates. Changes in parent attitudes may be necessary but do not seem sufficient for changes in antimicrobial prescribing patterns.

Elevation of serum interleukin 8 levels in acetaminophen overdose in children and adolescents.

BACKGROUND: Elevations of inflammatory cytokines have been reported in animal models of acetaminophen (INN, paracetamol) toxicity. In addition, interleukin 8, a chemokine, has been found to be elevated in toxin-associated hepatic disease (ie, acute alcoholic hepatitis). The purpose of this study was to measure serum cytokine levels in children and adolescents with acetaminophen overdose and to evaluate relationships between cytokine elevation and hepatotoxicity. METHODS: Serum levels of tumor necrosis factor alpha, interleukin 1beta, interleukin 6, interleukin 8, and interleukin 10 were measured by ELISA in children and adolescents (n = 35) with acetaminophen overdose. Peak cytokine levels were examined relative to biochemical evidence of hepatocellular injury, nomogram risk assessment, and prothrombin time. RESULTS: Five patients had aspartate aminotransferase or alanine aminotransferase levels >1000 IU/L, and 4 patients had aspartate aminotransferase or alanine aminotransferase levels > or =100 IU/L and < or =1000 IU/L. No elevations of tumor necrosis factor alpha or interleukin 1beta were detected. Peak interleukin 8, but not interleukin 6 or interleukin 10, correlated with hepatotoxicity (Mann-Whitney exact test, P <.001). The peak interleukin 8 level was greater in patients at high risk by the nomogram combined with those presenting at >15 hours, as compared with other patients (Mann-Whitney U test, P <.01). The interleukin 8 level peaked before aspartate aminotransferase or alanine aminotransferase in 5 of the 9 patients with hepatotoxicity. In addition, interleukin 8 concentrations of >20 pg/mL were associated with peak prothrombin time values (Mann-Whitney exact test, P <.015). CONCLUSIONS: Interleukin 8 elevation in patients with acetaminophen hepatotoxicity corresponds with other common clinical measures that are predictive of hepatocellular injury. Further study is warranted to evaluate possible mechanistic relationships between inflammatory cytokines and acetaminophen hepatotoxicity in children and adults.

Nosocomial infections during extracorporeal membrane oxygenation.

OBJECTIVE: To examine trends in nosocomial infection associated with Extracorporeal Membrane Oxygenation (ECMO). DESIGN: Retrospective review of all patients who underwent ECMO over a 4-year period at our institution; specifically, examining reasons for placement and duration of time on ECMO, as well as nosocomial infections incurred while on or shortly after discontinuation of support. Infections were considered ECMO-related if the organism was recovered on support or within 7 days from decannulation. Analyses were performed utilizing Pearson's chi-square for dichotomous factors and t-tests for continuous factors. RESULTS: Of 141 patients requiring ECMO support, 90 (64%) survived to hospital discharge. Indication for support included circulatory failure (53%) and non-cardiac (47%). Twenty-six percent of patients developed infections on ECMO. Organisms isolated included: bacterial 20 (54%), fungal 10 (27%), mixed five (14%) and viral two (5%). Infection sites included: blood 13 (35%), urine nine (24%), mixed eight (22%), wound five (14%) and lung two (5%). Seventy-eight percent of infections noted occurred in cardiac patients. Patients with nosocomial infections were supported for a median of 169 h (range, 84-936 h), versus those without nosocomial infection [146 h (range, 50-886 h); P<0.001]. Procedures on ECMO were associated with an increased risk of infection (P<0.001) as was the presence of an open chest (P<0.025). CONCLUSIONS: The incidence of infection in ECMO patients at our institution has not increased significantly since our previous study. Cardiac patients have increased risk for nosocomial infection while on ECMO, which may be in part due to longer cannulation times, as well as increased likelihood of undergoing major procedures or having an open chest.

Interactions of inflammatory pain and morphine in infant rats: long-term behavioral effects.

Neonatal rat pups exposed to repetitive acute pain show decreases in pain threshold and altered behavior during adulthood. A model using prolonged inflammatory pain in neonatal rats may have greater clinical relevance for investigating the long-term behavioral effects of neonatal pain in ex-preterm neonates. Neonatal rat pups were exposed to repeated formalin injections on postnatal (P) days 1-7 (P1-P7), with or without morphine pretreatment, and were compared with untreated controls. Behavioral testing during adulthood assessed pain thresholds using hot-plate (HP) and tail-flick (TF) tests, alcohol preference, and locomotor activity (baseline and postamphetamine). Adult rats exposed to neonatal inflammatory pain exhibited longer HP latencies than controls and male rats had longer HP thresholds compared to females. Male rats exposed to neonatal morphine alone exhibited longer TF latencies than controls. Both neonatal morphine treatment and neonatal inflammatory pain decreased ethanol preference, but their effects were not additive. During adulthood, male rats exposed to neonatal inflammatory pain exhibited less locomotor activity than untreated controls. We conclude that neonatal formalin and morphine treatment have specific patterns of long-term behavioral effects in adulthood, some of which are attenuated when the two treatments are combined.

Evaluation of occult acetaminophen hepatotoxicity in hospitalized children receiving acetaminophen. Pediatric Pharmacology Research Unit Network.

The safety of repeated doses of acetaminophen in ill children with the potential of reduced glutathione stores has been questioned. This study measured hepatic transaminases in children and adolescents (n=100) who received > or = 6 therapeutic doses of acetaminophen over a 48-hour period of hospitalization. Acetaminophen-protein adducts were measured in a cohort of subjects with hepatic transaminase elevation (n=8) and in those (n=10) receiving concurrent drug therapy with agents that induce the cytochrome P450 enzymes involved in acetaminophen metabolism. Acetaminophen-protein adducts were not detected in this cohort of 18 subjects. Based on this pilot study, the routine use of acetaminophen at therapeutic doses in ill, hospitalized children and adolescents appears safe.

Variation in therapy and outcome for pediatric head trauma patients.

OBJECTIVE: This study was undertaken to examine variation in therapies and outcome for pediatric head trauma patients by patient characteristics and by pediatric intensive care unit. Specifically, the study was designed to examine severity of illness on admission to the pediatric intensive care unit, the therapies used during the pediatric intensive care unit stay, and patient outcomes. DATA SOURCES AND SETTING: Consecutive admissions from three pediatric intensive care units were recorded prospectively (n = 5,749). For this study, all patients with an admitting diagnosis of head trauma were included (n = 477). Data collection occurred during an 18-month period beginning in June 1996. All of the pediatric intensive care units were located in children's hospitals, had residency and fellowship training programs, and were headed by a pediatric intensivist. METHODS: Admission severity was measured as the worst recorded physiological derangement during the period 1 yr old (16.1% vs. 6.1%; p = .002). Comparisons by insurance status indicated that observed mortality rates were highest for self-paying patients. However, patient characteristics were not associated with use of therapies or standardized mortality rates after adjustment for patient severity. There was significant variation in the use of paralytic agents, seizure medications, induced hypothermia, and intracranial pressure monitoring on admission across the three pediatric intensive care units. In multivariate models, only the use of seizure medications was associated significantly with reduced mortality risk (odds ratio = 0.17; 95% confidence interval = 0.04-0.70; p = .014). CONCLUSIONS: Therapies and outcomes vary across pediatric intensive care units that care for children with head injuries. Increased use of seizure medications may be warranted based on data from this observational study. Large randomized controlled trials of seizure prophylaxis in children with head injury have not been conducted and are needed to confirm the findings presented here.

Encouraging physicians to respond to surveys through the use of fax technology.

High response rates in surveys of physicians are difficult to achieve. One possible strategy to improve physicians' survey participation is to offer the option of receiving and returning the survey by fax. This study describes the success of the option of fax communication in a survey of general practitioners, family physicians, and pediatricians in Arkansas with regard to pediatric asthma. Eligible physicians were given the choice of receiving the survey by telephone, mail, or fax. In this observational study, physicians' preferences, response rates, and biases for surveys administered by fax were compared with mail and telephone surveys. The overall survey response rate was 59%. For the 96 physicians completing an eligibility screener survey, the largest percentage requested to be surveyed by fax (47%) rather than by telephone (28%) or mail (25%). Faxing may be one strategy to add to the arsenal of tools to increase response rates in surveying physicians.

Volume-outcome relationships in pediatric intensive care units.

CONTEXT: Pediatric intensive care units (PICUs) have expanded nationally, yet few studies have examined the potential impact of regionalization and no study has demonstrated whether a relationship between patient volume and outcome exists in these units. Documentation of an inverse relationship between volume and outcome has important implications for regionalization of care. OBJECTIVES: This study examines relationships between the volume of patients and other unit characteristics on patient outcomes in PICUs. Specifically, we investigate whether an increase in patient volume improves mortality risk and reduces length of stay. DESIGN AND SETTING: A prospective multicenter cohort design was used with 16 PICUs. All of the units participated in the Pediatric Critical Care Study Group. Participants. Data were collected on 11 106 consecutive admissions to the 16 units over a 12-month period beginning in January 1993. MAIN OUTCOME MEASURES: Risk-adjusted mortality and length of stay were examined in multivariate analyses. The multivariate models used the Pediatric Risk of Mortality score and other clinical measures as independent variables to risk-adjust for illness severity and case-mix differences. RESULTS: The average patient volume across the 16 PICUs was 863 with a standard deviation of 341. We found significant effects of patient volume on both risk-adjusted mortality and patient length of stay. A 100-patient increase in PICU volume decreased risk-adjusted mortality (adjusted odds ratio:.95; 95% confidence interval:.91-.99), and reduced length of stay (incident rate ratio:.98; 95% confidence interval:.975-.985). Other PICU characteristics, such as fellowship training program, university hospital affiliation, number of PICU beds, and children's hospital affiliation, had no effect on risk-adjusted mortality or patient length of stay. CONCLUSIONS: The volume of patients in PICUs is inversely related to risk-adjusted mortality and patient length of stay. A further understanding of this relationship is needed to develop effective regionalization and referral policies for critically ill children.

Phenothiazine, butyrophenone, and other psychotropic medication poisonings in children and adolescents.

OBJECTIVE: To describe the presentation, epidemiology, management, and outcome of phenothiazine and butyrophenone ingestions in children requiring hospitalization. METHOD: Retrospective case series in two pediatric hospitals. RESULTS: Eighty-six cases were identified among 83 patients. The majority (69.7%) of ingestions occurred in children <6 years of age and there was no gender predominance. These ingestions were more common in African Americans (65.1%). They occurred more commonly in the patient's (64.0%) or a relative's (22.1%) home and haloperidol and thioridazine accounted for 58.1% of exposures. Depressed levels of consciousness and dystonia were the most common presenting signs, present in 90.7% and 51.2% of patients, respectively. Miosis occurred in only 13.9% of the patients. Fluid boluses were administered to 28.7% of the patients but about a quarter of these had coingested potentially cardiotoxic drugs. In addition, 2 of the 12 (13.9%) patients with abnormal electrocardiograms had also ingested potentially cardiotoxic drugs. Numerous diagnostic tests were performed in these patients including electrolyte panels (80.2%), complete blood counts (69.8%), liver function tests (31.4%), serum osmolality (20.9%), blood cultures (10.5%), lumbar punctures (17.4%), head computed tomographies (15.1%), and electroencephalograms (3.5%). The median length of hospitalization was 1.78 (range 1-9) days and there were no deaths. Patients presenting with dystonias were more likely to have extensive diagnostic testing for neurologic disease than those presenting without dystonias. CONCLUSION: The presentation of phenothiazine and butyrophenone ingestions in children and adolescents may be nonspecific and confounded by coingestants. Patients with dystonias had more extensive neurologic testing than patients without dystonias, suggesting that physicians may not recognize dystonias as a clinical finding characteristic of phenothiazine or butyrophenone exposure.

The role of transthoracic echocardiography in the diagnosis of infective endocarditis in children.

BACKGROUND: Infective endocarditis (IE) is frequently suspected but infrequently diagnosed in children. Clinicians often order echocardiograms to "rule out" IE. In an era of cost constraint, clinically efficient strategies must be developed to eliminate unnecessary tests. We hypothesized that transthoracic echocardiography (TTE) is only useful in children in whom there is a high clinical suspicion of IE based on history, physical examination, and persistently positive blood cultures. OBJECTIVE: To determine the role of TTE as a screening test for suspected IE in children. METHODS: Echocardiographic reports and medical records were reviewed retrospectively for 173 consecutive patients who underwent TTE to rule out IE from January 1993 to August 1996. RESULTS: Persistent fever was the predominant symptom leading to a suspicion of IE (120 patients [69.4%]). Fifty-seven (32.9%) of the 173 patients had congenital heart disease and 95 patients (54.9%) had indwelling venous catheters. Twenty-six patients (15.0%) were diagnosed and treated for IE. Twelve (46.2%) of these 26 patients had vegetations seen on TTE. The conditions of the remaining 14 patients were diagnosed clinically and these patients had persistently positive blood cultures. By univariate analysis, the risk factors associated with the diagnosis of IE were malaise, congestive heart failure, new or changing heart murmur, leukocytosis, hematuria, and the presence of 2 or more positive blood cultures for the same organism. The risk factors associated with positive TTE were malaise, congestive heart failure, new or changing heart murmur, leukocytosis, hematuria, and 2 or more positive blood cultures. The presence of an indwelling catheter or immunocompromised status were not predictive of vegetation or IE. CONCLUSIONS: Transthoracic echocardiography has poor sensitivity as a screening test for IE in patients with low clinical probability of the disease. A diagnostic algorithm for IE is suggested based on these data.

Increased colonic ornithine decarboxylase activity in inflammatory bowel disease in children.

The risk of colorectal carcinoma is increased in pediatric-onset inflammatory bowel disease (IBD). There is little information available regarding the colonic mucosal proliferative state in children with IBD. The aim of this study was to assess colonic ornithine decarboxylase (ODC) activity, a marker of cell proliferation, in pediatric IBD patients. ODC activity was assessed in colonic mucosa from 23 children (7 with ulcerative colitis, 9 with Crohn's disease, and 7 controls) undergoing colonoscopic examination. ODC activities were then compared with degree of inflammation of biopsied samples. ODC activities in patients with and without corticosteroid treatment were also analyzed. The mucosal ODC activities of sigmoid colon and rectum were significantly higher (2.5- to 4-fold) in both ulcerative colitis and Crohn's disease. The higher ODC activity was associated with increased mucosal inflammation. Moreover, treatment with corticosteroids decreased the ODC activity. In conclusion, using ODC activities as a marker of cell proliferation, our results suggest that there is a higher colonic mucosal proliferative state in children with IBD. The increased ODC activities were associated with increased colonic mucosal inflammation. Colonic mucosal ODC activity may provide an additional parameter to access the therapeutic efficacy of corticosteroid treatment in pediatric IBD patients.