Devendra K. Amre

SERUM PROCALCITONIN AND C-REACTIVE PROTEIN LEVELS AS MARKERS OF BACTERIAL INFECTION: A SYSTEMATIC REVIEW AND META-ANALYSIS

A meta-analysis was performed to evaluate the accuracy of determination of procalcitonin (PCT) and C-reactive protein (CRP) levels for the diagnosis of bacterial infection. The analysis included published studies that evaluated these markers for the diagnosis of bacterial infections in hospitalized patients. PCT level was more sensitive (88% [95% confidence interval [CI], 80%-93%] vs. 75% [95% CI, 62%-84%]) and more specific (81% [95% CI, 67%-90%] vs. 67% [95% CI, 56%-77%]) than CRP level for differentiating bacterial from noninfective causes of inflammation. The Q value for PCT markers was higher (0.82 vs. 0.73). The sensitivity for differentiating bacterial from viral infections was also higher for PCT markers (92% [95% CI, 86%-95%] vs. 86% [95% CI, 65%-95%]); the specificities were comparable (73% [95% CI, 42%-91%] vs. 70% [95% CI, 19%-96%]). The Q value was higher for PCT markers (0.89 vs. 0.83). PCT markers also had a higher positive likelihood ratio and lower negative likelihood ratio than did CRP markers in both groups. On the basis of this analysis, the diagnostic accuracy of PCT markers was higher than that of CRP markers among patients hospitalized for suspected bacterial infections.

Imbalances in Dietary Consumption of Fatty Acids, Vegetables, and Fruits Are Associated With Risk for Crohn's Disease in Children

BACKGROUND AND OBJECTIVES:The role of dietary factors in the etiology of Crohns disease (CD) is inconsistent largely due to difficulties in acquiring valid information on consumption habits. We examined the impact of diet on new onset CD in children using a validated food-frequency questionnaire (FFQ).METHODOLOGY:A case-control study was carried out. Children ≤20 yr, newly diagnosed with CD, were recruited from 3 pediatric gastroenterology clinics across Canada. Population or hospital controls were selected matched to cases for time of diagnosis (±6 months) and area of residence. Dietary consumption 1 yr prior to disease diagnosis was evaluated using a validated FFQ, administered within 1 month of diagnosis. Conditional logistic regression analysis adjusting for potential confounding variables (energy intake, age, gender, body mass index) was carried out.RESULTS: A total of 130 CD patients and 202 controls were studied. Mean age at diagnosis (±SD) was 14.2 (2.7). There were more male patients (59%). Comparing the highest to the lowest levels of consumption, higher amounts of vegetables (OR 0.69, 95% CI 0.33–1.44, P = 0.03), fruits (OR 0.49, 95% CI 0.25–0.96, P = 0.02), fish (OR 0.46, 95% CI 0.20–1.06, P = 0.02), and dietary fiber (OR 0.12, 95% CI 0.04–0.37, P < 0.001) protected from CD. Consumption of long-chain omega-3 fatty acids (LCN-ω-3) was negatively associated with CD (OR 0.44, 95% CI 0.19–1.00, P < 0.001). A higher ratio of LCN-ω-3/ω-6 fatty acids was significantly associated with lower risks for CD (OR 0.32, 95% CI 0.14–0.71, P = 0.02).CONCLUSIONS: Our findings indicate that an imbalance in consumption of fatty acids, vegetables, and fruits is associated with increased risks for CD among Canadian children.

The three-gene paraoxonase family: Physiologic roles, actions and regulation

The paraoxonase (PON) gene family is composed of three members (PON1, PON2, PON3) that share considerable structural homology and are located adjacently on chromosome 7 in humans. By far the most-studied member is PON1, a high-density lipoprotein-associated esterase/lactonase, also endowed with the capacity to hydrolyze organophosphates, but all the three proteins prevent oxidative stress and fight inflammation. They therefore seem central to a wide variety of human illnesses, including atherosclerosis, diabetes mellitus, mental disorders and inflammatory bowel disease. The major goal of this review is to highlight the regulation of each of the paraoxonase components by diverse nutritional molecules and pharmacological agents as well as a number of pathophysiological events, such as oxidative stress and inflammation. Considerable and detailed cell-based studies and animal model experiments have been provided to allow a thorough scrutiny of PON modulation, which will increase our understanding and ability to target these genes in order to efficiently increase their transcriptional activity and decrease the risks of developing different disorders.

Fulminant hepatic failure secondary to acetaminophen poisoning: a systematic review and meta-analysis of prognostic criteria determining the need for liver transplantation.

ObjectivesTo summarize and compare different prognostic criteria used to determine need for liver transplantation in patients with fulminant hepatic failure secondary to acetaminophen poisoning. Data SourcesStudies published in the literature that investigated criteria for hepatic transplantation secondary to acetaminophen-induced liver failure as identified by a preestablished MEDLINE strategy (1966 through October 2001). Study SelectionStudies were included if 2 × 2 tables could be reconstructed and if they did not assume that patients undergoing transplantation would have eventually died had they not received the transplant. Data ExtractionRelevant articles were reviewed by two authors independently. Discrepancies or disagreements, if any, on the inclusion or exclusion of studies were resolved by consulting the third author. Data SynthesisKing’s criteria (pH < 7.30 or prothrombin time of >100 secs plus creatinine of >300 &mgr;mol/L plus encephalopathy grade of ≥3) were evaluated in nine studies, pH < 7.30 in four, prothrombin time of >100 secs in three, prothrombin time of >100 secs plus creatinine of >300 &mgr;mol/L plus encephalopathy grade of ≥3 in three, creatinine of >300 &mgr;mol/L in two, and one each for increase in prothrombin time day 4, factor V of <10%, Acute Physiology and Chronic Health Evaluation (APACHE) II score of >15, and Gc-globulin of <100 mg/L. King’s criteria were more sensitive than pH: 69% (95% confidence interval, 63–75) vs. 57% (95% confidence interval, 44–68). Their specificities were, however, comparable: 92% (95% confidence interval, 81–97) vs. 89% (95% confidence interval, 62–97). APACHE II score of >15 had the highest positive likelihood ratio (16.4) and the lowest negative likelihood ratio (0.19) but was evaluated in only one study. The accuracy measures of all other criteria were lower than that of King’s criteria or pH < 7.30. ConclusionsPresently, available criteria are not very sensitive and may miss patients requiring transplantation. Future studies should further evaluate the efficacy of the APACHE II criteria.

Investigating the Hygiene Hypothesis as a Risk Factor in Pediatric Onset Crohn's Disease: A Case-Control Study

BACKGROUND AND OBJECTIVES:Evidence for the hygiene hypothesis in the etiology of Crohns disease (CD) is unclear. We investigated the relationship between infection-related exposures and risk for CD in children.METHODS:A hospital-based case-control was carried out. Newly-diagnosed cases of CD (n = 194), less than 20 yr of age were recruited from the gastroenterology clinic of a large-pediatric inflammatory bowel disease (IBD) center in Montreal, Canada. Orthopedic patients pair-matched (n = 194) for timing of diagnosis and area of residence were recruited as controls. Information on infection-related exposures between birth and disease diagnosis was ascertained by administering a structured questionnaire to the mother and the index subject. The relationship between the frequency and timing of infection-related exposures with CD was studied.RESULTS:The mean age (SD) at diagnosis was 12.3 (5.1). CD was more common after 10 yr of age. Gender distribution was similar between comparison groups. In multivariate conditional logistic regression, family history of IBD (odds ratio (OR) = 4.6; 95% confidence interval (CI) = 1.6–13.3), age (OR = 1.2; 95% CI = 1.1–1.3), and owning a pet (OR = 2.0; 95% CI = 0.9–4.5) were associated with risk for CD, whereas regular use of a personal towel (OR = 0.5; 95% CI = 0.2–0.9) and lesser crowding in homes (OR = 0.3; 95% CI = 0.1–0.8) were protective. Day-care attendance during the first 6 months of life and “physician-diagnosed infections” between 5 and 10 yr of age were associated with increased risks for CD.CONCLUSIONS:Infection-related exposures seem to enhance risk for CD in children. The timing of these exposures during early childhood may be relevant to the etiology of pediatric CD.

Utility of serological markers in predicting the early occurrence of complications and surgery in pediatric Crohn's disease patients.

BACKGROUND AND OBJECTIVES:Many Crohns disease (CD) patients develop complications (fistulae and abscesses), and require surgery, often repeatedly and at variable instances. Identifying serological markers that determine their early or repeated manifestation can enable implementing more aggressive preventive strategies. Our objective was to study the ability of serological markers for predicting development of early (first) and recurrent complications or requirement for surgery.METHODS:Serum anti-Saccharomyces cervisiae (ASCA) (IgA & IgG) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) were assayed close to diagnosis in a pediatric cohort of CD patients identified between 1996 and 1998. At diagnosis and follow-up, information was acquired on demographic and clinical features of disease. Relation between ASCA and clinical events was studied using adjusted Cox-proportional hazards modeling. The relative rates of recurrent clinical events according to the marker measures were compared.RESULTS:The mean age (SD) at diagnosis was 11.2 (3.4) yr. Among 139 patients, 35 (25.9%) and 31 (22.3%) acquired one or more CD related surgery or complication, respectively. Time to occurrence of the first complication was lower among patients ASCA+ (IgA or IgG) (hazards ratio (HR) = 2.33; 95% confidence interval (CI) = 0.99–5.50) and among those with higher ASCA-IgA titers (HR = 1.20; 95% CI = 1.08–1.34). The rates of recurrent complications were higher among those positive or with higher ASCA titers. ASCA did not predict time to undergoing surgery independent of complications, and was unrelated to the occurrence of recurrent surgeries.CONCLUSIONS:Our study shows that serum ASCA measured close to diagnosis can determine the occurrence of early complications in pediatric CD. Preventive treatment targeted toward these susceptible patients could potentially modify the disease course.

Dietary Patterns and Risk for Crohn's Disease in Children

Background: Some dietary foods are considered protective (vegetables and fruits), whereas others (fatty foods) are thought to enhance the risk for Crohns disease (CD). The evidence, however, is inconsistent. Methods: We postulated that specific dietary patterns may influence the risk for CD. A case‐control study was carried out. Newly diagnosed CD cases with population and/or hospital‐based controls ≤20 years were selected from 3 tertiary hospitals across Canada. Predisease diet was assessed using a validated food frequency questionnaire (FFQ) administered within 1 month of diagnosis. Factor analyses and unconditional logistic regression (adjusted) was used to determine gender‐specific dietary patterns and assess associated risks for CD. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were estimated. Results: A total of 149 cases and 251 controls were included. The mean age (range) of the cases was 13.3 (2.6‐20 years). There were more boys (61.1%). Four dietary patterns each were observed among both boys and girls. Pattern 1 in girls, characterized by meats, fatty foods, and desserts, was positively associated with CD (OR 4.7, 95% CI 1.6–14.2). Pattern 2, common to both boys and girls, was characterized by vegetables, fruits, olive oil, fish, grains, and nuts and was inversely associated with CD in both genders (girls: OR 0.3, 95% CI 0.1–0.9; boys: OR 0.2, 95% CI 0.1–0.5). Conclusions: Our results suggest that specific dietary patterns could be associated with higher or lower risks for CD in children. Larger prospective studies are required to confirm these findings.

Utility of serum antibodies in determining clinical course in pediatric Crohn's disease.

BACKGROUND AND AIMS The utility of serial measurements of anti-Saccharomyces cerevisiae (ASCA) and perinuclear antineutrophil cytoplasmic (p-ANCA) antibodies in Crohns disease (CD) evolution is unknown. We aimed to study the pattern of antibody change and the prognosis of selected outcomes by baseline (at time of diagnosis) and serial antibody measurements in pediatric CD patients. METHODS Serum ASCA and p-ANCA antibodies were measured at baseline (n = 154) and repeated during follow-up (n = 61) using standard techniques in a cohort of patients identified at Hôpital Sainte-Justine between 1996 and 1998. Clinical information was abstracted from medical charts. Antibody patterns were examined using mixed modeling techniques. The prognostic ability of antibodies for selected outcomes was evaluated using logistic regression. RESULTS Fifteen (24.5%), 18 (29.5%), and 11 (18%) patients with serial antibody measurements changed their ASCA-IgA, ASCA-IgG, and p-ANCA status (positivity), respectively. No distinct patterns in the evolution of antibody titers were noted. Baseline ASCA-IgA positivity significantly predicted relapses during disease course (IgA: odds ratio [OR], 2.9; 95% confidence interval [CI], 1.33-6.35). Serial antibody measurements did not predict the occurrence of clinical outcomes. CONCLUSIONS Baseline serum antibodies were predictive of a more relapsing disease course in pediatric CD. However, the limited variability in the antibodies over time and the inability of serial measurements to predict clinical outcomes may limit their use in the establishment of intervention strategies.

Procalcitonin and c-reactive protein as markers of bacterial infection in critically ill children at onset of systemic inflammatory response syndrome

Objective: To compare the accuracy of procalcitonin and C-reactive protein as diagnostic markers of bacterial infection in critically ill children at the onset of systemic inflammatory response syndrome (SIRS). Design: Prospective cohort study. Setting: Tertiary care, university-affiliated pediatric intensive care unit (PICU). Patients: Consecutive patients with SIRS. Interventions: From June to December 2002, all PICU patients were screened daily to include cases of SIRS. At inclusion (onset of SIRS), procalcitonin and C-reactive protein levels as well as an array of cultures were obtained. Diagnosis of bacterial infection was made a posteriori by an adjudicating process (consensus of experts unaware of the results of procalcitonin and C-reactive protein). Baseline and daily data on severity of illness, organ dysfunction, and outcome were collected. Measurements and Main Results: Sixty-four patients were included in the study and were a posteriori divided into the following groups: bacterial SIRS (n = 25) and nonbacterial SIRS (n = 39). Procalcitonin levels were significantly higher in patients with bacterial infection compared with patients without bacterial infection (p = .01). The area under the receiver operating characteristic curve for procalcitonin was greater than that for C-reactive protein (0.71 vs. 0.65, respectively). A positive procalcitonin level (≥2.5 ng/mL), when added to bedside clinical judgment, increased the likelihood of bacterial infection from 39% to 92%, while a negative C-reactive protein level (<40 mg/L) decreased the probability of bacterial infection from 39% to 2%. Conclusions: Procalcitonin is better than C-reactive protein for differentiating bacterial from nonbacterial SIRS in critically ill children, although the accuracy of both tests is moderate. Diagnostic accuracy could be enhanced by combining these tests with bedside clinical judgment.

Maternal and obstetric risk factors for sudden infant death syndrome in the United States.

OBJECTIVE: The objectives of this study were to 1) study the incidence of sudden infant death syndrome (SIDS) among singleton births in the United States and 2) identify maternal and obstetric risk factors for SIDS. METHODS: A cohort of all live births in the United States from 1995 to 1998, formed the source population (n = 15,627,404). The data were obtained from the National Centers for Health Statistics Linked Births and Infant Deaths File. A nested case-control study was used to examine risk factors for SIDS. From this birth cohort, all SIDS deaths (n = 12,404) were first identified (case group). From the remaining non-SIDS births, a 4-fold larger sample (n = 49,616) was randomly selected as a control group. RESULTS: The overall incidence of SIDS was 81.7 per 100,000 live births. More mothers in the case group than in the control group were reported to have placenta previa (odds ratio [OR]: 1.70; 95% confidence interval [CI] 1.24, 2.33), abruptio placentae (OR 1.57; 95% CI 1.24, 1.98), premature rupture of membranes (OR 1.48; 95% CI 1.33, 1.66), or small for gestational age (OR 1.40; 95% CI 1.30, 1.50 for the 10th percentile). SIDS cases were also more likely to be male. Mothers of cases were more likely to be younger, less educated, and nonwhite, and more of them smoked during pregnancy and did not attend prenatal care. CONCLUSION: This analysis confirms the importance of several well known demographic and lifestyle risk factors for SIDS. In addition, placental abnormalities were risk factors for SIDS. LEVEL OF EVIDENCE: II-2