A fully degradable tracheal stent: in vitro and in vivo characterization of material degradation.

We report on the testing of materials for a fully degradable tracheal stent. Such a stent has several advantages over currently used permanent stents made of metal or silicone polymers. However, the mode of degradation in the trachea is expected to be different from a fully submerged device, because of the uniqueness of the tracheal environment. A physical model was developed to allow an in-depth study of degradation of bioabsorbable polymers exposed to two differing media; namely 70 wt % water (gel) on one side and humidified air on the other, simulating conditions in a tracheal passage. Longitudinal microtome slices were obtained from both polymer surfaces and degradation kinetics data were derived from size exclusion chromatography. On the basis of the data obtained, it is observed that well-studied bulk-degrading polymers might show surface-eroding properties in such an environment. Generally, hydrophobic polymers retard the formation of a water concentration gradient and exhibit bulk-degradation kinetics. However, addition of specific plasticizers can influence the water uptake gradient, and force the polymer towards a pseudo "surface-eroding" behavior. In vivo studies in a rabbit model of degradable stents made from a selected polymer, demonstrate the feasibility of a fully bioabsorbable tracheal stent. This study aims to improve understanding of degradation of polymers under heterogeneous environments.

Pediatric gastroesophageal reflux disease and acid-related conditions: trends in incidence of diagnosis and acid suppression therapy.

OBJECTIVE: To describe the incidence of diagnosis of gastroesophageal reflux disease and acid-related conditions (GERD/ARC) throughout childhood and characterize patterns of diagnosis and treatment with proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H(2)RAs). METHODS: Cohorts of GERD/ARC children (age 0-18 years) were identified from a large US administrative claims database covering 1999-2005 using ICD-9 codes. Incidence, healthcare utilization (HCU), costs, therapy discontinuation and switching rates were compared between various age and patient groups. RESULTS: Between 2000 and 2005 annual incidence of GERD/ARC diagnosis among infants (age ≤1 year) more than tripled (from 3.4 to 12.3%) and increased by 30% to 50% in other age groups. Patients diagnosed by GI specialists (9.2%) were more likely to be treated with PPIs compared to patients diagnosed by primary care physician (PCP). PPI-initiated patients doubled (from 31.5% in 1999 to 62.6% in 2005) and, when compared with H(2)RA-initiated patients, were associated with 30% less discontinuation and 90% less therapy switching in the first month, and with higher comorbidity burden and pre-treatment total HCU and costs when diagnosed by GI specialists. LIMITATIONS: The use of an exploratory definition for GERD/ARC, administrative claims data and potential coding errors in diagnosis codes used in selection process may limit the generalizability of the results. CONCLUSIONS: GERD/ARC incidence increased for children of all ages between 2000 and 2005. PCPs made the majority of diagnoses. PPI initiations have now surpassed H(2)RA initiations.

Healthcare costs of GERD and acid-related conditions in pediatric patients, with comparison between histamine-2 receptor antagonists and proton pump inhibitors.

BACKGROUND: Gastroesophageal reflux disease and acid-related conditions (GERD/ARC) are common in pediatric practice but their costs have not been well characterized. AIM: To compare healthcare costs (HCC) and healthcare utilization (HCU) of pediatric GERD/ARC between groups of GERD/ARC patients initiated on histamine-2 receptor antagonists (H(2)RAs) or proton pump inhibitors (PPIs) and matched controls. PATIENTS AND METHODS: Children (age < 18 years) diagnosed with GERD or ARC (exploratory category) were identified from a large US claims database (1999-2005) using ICD-9 codes. Costs of pediatric GERD/ARC were estimated by comparing 6-month post-diagnosis HCC between cases and matched controls. GERD/ARC-related HCC and HCU for the year 2005 were further compared between GERD/ARC patients initiated with PPIs vs. H(2)RAs in terms of the cost differences relative to pre-initiation (difference-in-difference) and using multivariate regression to adjust for demographics, pre-treatment health status and pre-treatment costs. RESULTS: A total of 27 865 matched pairs were identified. GERD/ARC patients incurred on average more 6-month total HCC than controls ($2386). In 2005, 1010 pediatric patients were initiated on H(2)RAs or PPIs. About 61% were initiated on PPIs and incurred 1.8 times higher 6-month post-initiation GERD/ARC-related HCC than H(2)RA-initiated patients ($661 vs. $372, p < 0.001). Although total 6-month GERD/ARC-related HCC increased for both PPI- and H(2)RA-treated patients, the increase was 30% less for PPI-treated patients ($173 vs. $246, p = 0.521) in the difference-in-difference analysis and 69% less in the multivariate analysis ($109 vs. $347, p = 0.040). LIMITATIONS: The use of an exploratory definition for GERD/ARC, administrative claims data and potential coding errors in diagnosis codes used in selection process may limit the generalizability of the results. CONCLUSION: Pediatric GERD/ARC patients incurred significantly higher healthcare costs compared to similar children without GERD/ARC. Compared to patients initiated with H(2)RAs, patients initiated with PPIs had more baseline comorbidities, and lower GERD/ARC-related HCC after beginning treatment.

The comparative effectiveness of rosuvastatin vs. other statins in patients with an increased risk of failure to reach NCEP ATP III goal.

BACKGROUND: Previous studies have demonstrated that failure to reach National Cholesterol Education Program (NCEP) target low-density lipoprotein cholesterol (LDL-C) goal increases the risk of cardiovascular events. Ability to meet goal may be impacted by the choice of statin therapy. PURPOSE: This study compares rosuvastatin to other statin therapies among patients presenting with risk factors associated with failure to reach NCEP goal. METHODS: Retrospective analysis using medical and pharmacy claims linked to laboratory results from a national health plan encompassing private and MedicareAdvantage enrollees age > or = 18 years and newly treated with statins from 1 August 2003 to 28 February 2005. Predictors of failure to reach goal were statin treatment group, age, gender, NCEP risk level, per cent reduction required to attain goal and days from index to LDL-C measurement. RESULTS: Of 11,814 eligible patients, 9.6% were initiated on rosuvastatin, 54.2% atorvastatin, 17.9% simvastatin, 7.1% pravastatin, 2.0% fluvastatin and 9.3% lovastatin. Independent predictors of failure to reach goal included > or = 15% LDL-C reduction required to reach goal, and high and moderate NCEP risk status. In the subset of patients at higher risk of failure to reach goal, rosuvastatin demonstrated a significantly lower rate of failure to achieve goal than atorvastatin, simvastatin, pravastatin, fluvastatin or lovastatin. CONCLUSIONS: Real-world factors associated with high risk of failure to reach goal may be used in identifying patients more likely to succeed on rosuvastatin compared with other statins. Low-risk patients needing < 15% LDL-C reduction would be suitable candidates for initiation of most other statins, specifically simvastatin, which has recently become available in the generic form.

Prevalence of symptoms of gastroesophageal reflux during childhood: a pediatric practice-based survey. Pediatric Practice Research Group.

OBJECTIVES: To determine the prevalence of symptoms associated with gastroesophageal reflux (GER) in 3- to 17-year-old children, to describe the prevalence of factors associated with GER in these children, and to determine the percentage of symptomatic children who have been treated. DESIGN: A cross-sectional survey. SETTING: Sixteen pediatric practice research group practices in the Chicago, Ill, area (urban, suburban, and semirural). PARTICIPANTS: A total of 566 parents of 3- to 9-year-old children, 584 parents of 10- to 17-year-old children, and 615 children aged 10 to 17 years. INTERVENTION: None. MAIN OUTCOME MEASURE: Reported frequency of symptoms associated with GER. RESULTS: Parents of 3- to 9-year-old children reported that their children experienced a sensation of heartburn ("burning/painful feeling in middle of chest"), epigastric pain ("stomachache above belly button"), and regurgitation ("sour taste or taste of throw up") 1.8%, 7.2%, and 2.3% of the time, respectively. Parents of 10- to 17-year-old children reported that their children experienced the same symptoms 3.5%, 3.0%, and 1.4% of the time, while children aged 10 to 17 years reported the symptoms 5.2%, 5.0%, and 8.2% of the time, respectively. Complaints of abdominal pain ("stomachache") were most common, reported by 23.9% and 14.7% of parents of 3- to 9-year-old and 10- to 17-year-old children and by 27.9% of children aged 10 to 17 years. In those aged 10 to 17 years, heartburn reported by the children was associated with reported cigarette use (odds ratio, 6.5; 95% confidence interval, 2-21); no other complaint was associated with cigarette, alcohol, or caffeine consumption or passive smoking exposure. In 3- to 9-year-old children, no complaint was associated with caffeine consumption or passive smoking exposure. Reported treatment in the past week with antacids was 0.5% according to parents of children aged 3 to 9 years and 1.9% and 2.3% according to parents of children aged 10 to 17 years and children aged 10 to 17 years, respectively. Treatment with over-the-counter histamine receptor blockers was 0% for children aged 3 to 9 years and 10 to 17 years, as reported by their parents, and 1.3% for those aged 10 to 17 years, as reported by themselves. CONCLUSIONS: Symptoms suggestive of GER are not rare in childhood, yet only a fraction of children with symptoms are treated with over-the-counter antacids or histamine2 antagonists. Prospective longitudinal data are needed to determine which children with symptoms of GER actually have GER disease and are at risk of developing complications.

One-year follow-up of symptoms of gastroesophageal reflux during infancy. Pediatric Practice Research Group.

OBJECTIVES: 1) Determine what percentage of infants outgrow regurgitation over 1 year. 2) Determine whether they develop feeding or mealtime problems. 3) Determine whether they develop frequent respiratory illnesses, including ear, sinus, and upper respiratory infections, or wheezing episodes. DESIGN: One-year follow-up survey of parents of children identified at 6 to 12 months of age as those who regurgitate (case subjects) and matched control subjects. PARTICIPANTS: Sixty-three case subjects and 92 control subjects attending 12 different (urban, suburban, and rural) practices in the Pediatric Practice Research Group in the Chicago area. PRIMARY OUTCOME MEASURES: The Infant Gastroesophageal Reflux Questionnaire-Shortened and Revised Form and the Children's Eating Behavior Inventory (CEBI). RESULTS: At 1-year follow-up, no parents of case or control subject described spitting up as currently a problem. The parent of only one control subject (and no case subject) reported spitting up one or more times a day. Parents of subjects were more likely than those of control subjects to report frequent feeding refusal: odds ratio = 4.2, adjusted by age (95% confidence interval: 1.4-12.0). Case and control subjects had comparable average total CEBI scores (case subjects, = 83 +/- 10 vs control subjects, = 82 +/- 11) and comparable average proportion of items identified as a problem (8% +/- 11% case subjects vs 6% +/- 9% control subjects). Case subjects were more likely to respond positively to two CEBI questions indicating specific feeding problems: 1) "my child takes more than an hour to eat his/her meals" (8% case subjects vs 0% control subjects) and 2) "I get upset when I think about our meals" (14% case subjects vs 4% control subjects). The frequencies of ear, sinus, and upper respiratory infections and of episodes of wheezing were comparable in both groups. CONCLUSIONS: 1) Infants with daily or problematic regurgitation at 6 to 12 months of age outgrew this within the following year. 2) Infants with daily or problematic regurgitation were more likely to develop feeding problems. 3) There was no increase in respiratory illnesses in infants with a history of regurgitation.

Histopathology of the liver in children with chronic hepatitis C viral infection.

Although the epidemiology, natural history, and pathological aspects of chronic hepatitis C are well-defined in the adult population, little is known about the characteristics of chronic hepatitis C infection in children. Reports on the histological features and progression of hepatitis C in children are scarce, and consist primarily of multicenter studies in Japanese and European children. Given the geographic variations in viral genotype and the association of pathology with genotype, whether the Japanese and European studies can be extended to the North American populations is unclear. We report the histopathology of the liver in 40 children with chronic hepatitis C infection treated in a single North American institution. The children included 19 males and 21 females ranging in age from 2.0 to 18.6 years at the time of liver biopsy (mean +/- SD: 11.4 +/- 4.3 years). Our findings indicate that the characteristic histopathological lesions of chronic hepatitis C infection, including sinusoidal lymphocytosis, steatosis, portal lymphoid aggregates/follicles, and bile duct epithelial damage, occur with approximately the same frequencies in children as have been reported in adults. Necroinflammatory activity was generally mild. Portal fibrosis was present in 78% of the specimens, including fibrous portal expansion (26%), bridging fibrosis (22%), bridging fibrosis with architectural distortion (22%), and cirrhosis (8%). Centrilobular pericellular fibrosis, which has not been previously reported in the context of chronic hepatitis C infection in adults or children, was also a prominent feature in our series, occurring with a similar frequency as steatosis or portal lymphoid aggregates/follicles. Our data suggest that in spite of mild histological necroinflammatory activity in general, the stage of fibrosis in children can be severe in spite of relatively short duration of infection.

Interferon-alpha treatment of chronic hepatitis C virus infection in children.

OBJECTIVES: To determine the safety and efficacy of interferon-alpha therapy of chronic hepatitis C virus (HCV) infection in children. STUDY DESIGN: This was an open-labeled prospective trial of interferon-alpha-2a (IFN-alpha) in children with evidence of HCV infection for at least 6 months. Twenty-three children were enrolled and treated with IFN-alpha at a dosage of 3 million units/m2 three times weekly. Beginning in 1995 patients defined as complete or partial responders after 6 months were offered an additional 6 months of treatment. Endpoints were alanine aminotransferase normalization and loss of hepatitis C viral ribonucleic acid from serum. Responders were compared with nonresponders for age, gender, duration of infection, pretreatment alanine aminotransferase and hepatitis C viral ribonucleic acid levels, saturation of serum iron-binding capacity, histologic score of chronic hepatitis and viral genotype. Statistical methods used for these comparisons included the Kruskal-Wallis test, the Mann-Whitney two-sample test and the Fisher exact test. RESULTS: Of the 21 children who completed at least 6 months of treatment, 4 (19%) had complete response, 8 (38%) had partial response and 9 (43%) had no response. Three of the 4 complete responders had prolonged treatment; in 2 the response was maintained. One responder relapsed but responded to a second, longer course of treatment. Four of the 8 partial responders had prolonged therapy and 3 of them became complete responders. One child who was originally a nonresponder lost HCV RNA within the first year after therapy. Thus eventually 7 (33%) of 21 patients were complete responders. After at least 12 months of follow-up on most of these children, no relapses have been observed. No differences in any of the variables tested could be demonstrated between responders and nonresponders, but small sample size limits power. IFN-alpha was discontinued in only one child because of side effects, and temporary dosage adjustments were needed in 4 children. CONCLUSIONS: IFN-alpha is of some efficacy in the treatment of chronic HCV infection in children. Complete or partial responders at 6 months should undergo prolonged treatment.

Prevalence of symptoms of gastroesophageal reflux during infancy. A pediatric practice-based survey. Pediatric Practice Research Group.

OBJECTIVES: To determine the prevalence of symptoms associated with overt gastroesophageal reflux (GER) during the first year of life, to describe when most infants outgrow these symptoms, and to assess the prevalence of parental reports of various symptoms associated with GER and the percentages of infants who have been treated for GER. DESIGN: Cross-sectional survey. SETTING: Nineteen Pediatric Practice Research Group practices in the Chicago, Ill, area (urban, suburban, and semirural). PARTICIPANTS: A total of 948 parents of healthy children 13 months old and younger. INTERVENTION: None. MAIN OUTCOME MEASURE: Reported frequency of regurgitation. RESULTS: Regurgitation of at least 1 episode a day was reported in half of 0- to 3-month-olds. This symptom decreased to 5% at 10 to 12 months of age (P < .001). Peak reported regurgitation was 67% at 4 months; the prevalence of symptoms decreased dramatically from 61% to 21% between 6 and 7 months of age. Infants with at least 4 episodes daily of regurgitation showed a similar pattern (P < .001). Peak regurgitation reported as a "problem" was most often seen at 6 months (23%); this prevalence decreased to 14% at 7 months of age. Parental perception that regurgitation was a problem was associated with the frequency and volume of regurgitation, increased crying or fussiness, reported discomfort with spitting up, and frequent back arching. Reported treatment for regurgitation included a change in formula in 8.1%, thickened feedings in 2.2%, termination of breast-feeding in 1.1%, and medication in 0.2%. CONCLUSIONS: Complaints of regurgitation are common during the first year of life, peaking at 4 months of age. Many infants "outgrow" overt GER by 7 months and most by 1 year. Parents view this symptom as a problem more often than medical intervention is given.

The implementation of a pharmaceutical care practice system.

The growing emphasis on a well-rounded clinical pharmacy practitioner, combined with the implementation of the six-year Doctor of Pharmacy degree requires innovative training strategies. A method to integrate clinical practice and training missions is described in Development of a Patient Care Unit(PCU). Pharmacist practice is described.

Hepatitis C infection in children who received extracorporeal membrane oxygenation.

OBJECTIVE: To determine the prevalence of antibody to hepatitis C virus (HCV) in a cohort of neonates who received extracorporeal membrane oxygenation (ECMO) therapy, and to determine risk factors associated with seropositivity. DESIGN: Eighty-three patients who had been treated with ECMO as neonates (from August 1986 through January 1992) at Children's Hospital, Boston, were tested for antibodies to HCV. The medical records were reviewed, and information regarding neonatal history was obtained. Anti-HCV seronegative and seropositive children were compared using univariate and multivariate analyses. RESULTS: Seven patients (8%) were anti-HCV seropositive of the seven seropositive children, four (57%) currently have ALT values of more than 1.5 times the upper limit of normal; only five of the 52 (9.6%) seronegative patients have values this high (P < .001). Patients in the seropositive group had received blood screened by "surrogate markers" (6 of 50) or by ELISA-1 anti-HCV testing (1 of 33). Significant differences between the seropositive and seronegative patients were found with respect to the aminotransferase and bilirubin levels during the initial ECMO hospitalization. The last ALT value before discharge was the only significant predictor of HCV infection in the multivariate model. CONCLUSION: Neonates treated with ECMO are at risk for the development of HCV infection. Neonates who received blood products from donors screened by surrogate markers or ELISA-1 anti-HCV testing should be considered at risk. Neonates who had an abnormal ALT value at the time of discharge are most likely to be anti-HCV seropositive.

A foregut carcinoid tumor causing Zollinger-Ellison syndrome.

A patient had severe peptic ulcer disease complicated by gastric outlet obstruction and choledochoduodenal fistula. Serum gastrin levels were elevated preoperatively to 340 ng/L. A 1.5-cm histologically benign carcinoid tumor of the antrum of the stomach was found at surgery, and surgical resection of the tumor resulted in normalization of serum gastrin levels and amelioration of the peptic acid diathesis. The patient remains asymptomatic at one year. Immunohistochemical staining demonstrated that the carcinoid indeed contained gastrin along with chromogranin, cholecystokinin, and neuron-specific enolase. This is a case of Zollinger-Ellison syndrome caused by a benign foregut carcinoid (gastric carcinoid-gastrinoma).