Predicting Intestinal Adaptation in Pediatric Intestinal Failure: A Retrospective Cohort Study.

OBJECTIVE: The primary goal in intestinal failure (IF) is adaptation and enteral autonomy (EA). Our goals were to determine the proportion of patients treated for IF by an established intestinal rehabilitation program who achieved EA and to assess the predictors of EA. BACKGROUND: There have been considerable advancements in the management of IF over the last 15 years, children with short bowel syndrome with a reduction in mortality. Several studies have discussed variables that may influence the ability to attain EA; however, majority were written when mortality rates were considerably higher compared with the current contemporary experience. METHODS: A retrospective analysis of infants <12 months with short bowel syndrome referred between 2006 and 2013 (n = 120). Data was collected on IF-related factors and nutritional intake. The cohort was stratified based on achievement of EA. Statistical testing completed using t test, Chi Square, and Cox Proportional Hazards regression (P < 0.05). RESULTS: EA was achieved in 84 (70.0%) patients. Patients who remained parenteral nutrition dependent were more likely to have volvulus (1.2 vs 22.2%, P < 0.001), shorter percent residual small bowel (29.4 vs 68.6%; P < 0.0001) and colon length (64.6 vs 86.0%; P = 0.001), and no ileocecal valve (61.1 vs 29.8%; P = 0.05). Mortality was also decreased in those who achieved EA (4 vs 22%; P = 0.004). Percent residual small bowel (HR = 1.03; 95% CI 1.02-1.03) and colon (HR = 1.01; 95% CI 1.00-1.02) length were positively associated with EA, while number of septic episodes was negatively associated (HR = 0.95; 95% CI 0.91-0.99). CONCLUSION: Seventy percent of infants with IF achieved EA. Residual small and large bowel length were the most important predictors of EA and septic events had a negative impact.

Persistence of hepatic fibrosis in pediatric intestinal failure patients treated with intravenous fish oil lipid emulsion.

BACKGROUND: Pediatric intestinal failure (PIF) is a life-altering chronic condition with significant morbidity and mortality. Omegaven® therapy has been used to treat children with advanced intestinal failure associated liver disease. Our objective was to determine the evolution of hepatic fibrosis in PIF patients who received Omegaven® and describe their clinical outcome. METHODS: A retrospective review in PIF patients who received Omegaven® was performed. Patients were included if they had liver biopsies completed before Omegaven® therapy and after resolution of hyperbilirubinemia. Biopsy results were evaluated to determine the degree of fibrosis, inflammation, and cholestasis. Clinical and biochemical data was collected. RESULTS: Six patients were identified. Assessment of fibrosis at last follow-up demonstrated improvement in 2 patients and progression or stable fibrosis in 4/6. All patients demonstrated reduction in cholestasis and inflammation. One patient received a liver/intestine transplant and a second is listed, both of them with progressive fibrosis. One patient achieved full enteral nutrition, while the rest remain partially parenteral nutrition dependent. CONCLUSION: Use of Omegaven® is associated with reduced cholestasis and inflammation, but with persistence or worsening of fibrosis in some patients. A subset of patients with progressive fibrosis may develop portal hypertension and progressive liver disease.

Use of balloon dilatation for management of postoperative intestinal strictures in children with short bowel syndrome.

PURPOSE: Children with short bowel syndrome (SBS) often require numerous operations to optimize intestinal function. Postoperative intestinal strictures are a complication that inhibits enteral feeding advancement and prolongs parenteral nutrition dependency, often requiring reoperation. Our objective was to review our experience with fluoroscopic balloon dilatation to treat intestinal strictures. METHODS: A retrospective cohort study of intestinal failure patients with SBS was completed. Patients who had radiologically diagnosed intestinal strictures and treated with fluoroscopic guided balloon dilatation were included [n=6]. Data related to demographics, anatomy, surgical procedures, and dilatation procedures were collected. Descriptive summary statistics were employed. RESULTS: 98 intestinal failure patients were recruited between 2011 and 2015. Five of 98 patients (5.1%) [2 males; median age 4.4months] underwent fluoroscopy guided balloon dilatation of 6 strictures. Balloon dilatation was successful in 4/6 (67%). The median number of dilatations was 2 per patient (range=1-3). Median time to feed initiation postdilatation was 3days. One patient developed an anastomotic leak after dilatation that required antibiotics, but no reoperation. CONCLUSION: Four of six (67%) postoperative bowel strictures in 5 patients with SBS were successfully treated with fluoroscopically guided balloon dilatation. Balloon dilatation is less invasive than reoperation, preserves bowel length and reduces time to reinitiation of enteral feeding. LEVEL OF EVIDENCE: 3.

Use of a Loading Dose of Vitamin D for Treatment of Vitamin D Deficiency in Patients With Intestinal Failure.

Vitamin D deficiency is common in patients with intestinal failure and short bowel syndrome who have been weaned of parenteral nutrition. Dietary supplementation with vitamin D is necessary to correct this deficiency. In certain cases, routine supplementation strategy may be ineffective. We report 3 cases of vitamin D deficiency in patients with intestinal failure who showed improvement in serum 25-hydroxyvitamin D levels after supplementation with a loading dose of 20,000-40,000 IU vitamin D provided weekly.

Cost of ambulatory care for the pediatric intestinal failure patient: One-year follow-up after primary discharge.

BACKGROUND: Survival of children with intestinal failure has improved over the last decade, resulting in increased health care expenditures. Our objective was to determine outpatient costs for the first year after primary discharge. METHODS: A retrospective analysis was performed in pediatric intestinal failure (PIF) patients between 2010 and 2012. Patients were stratified into 3 groups (1=enteral support with no devices [7 patients], 2=enteral support with devices (gastrostomy and/or ostomy) [19 patients], 3=home parenteral nutrition (HPN) [22 patients]). Data abstraction included clinical characteristics and costs related to medication, enteral/parenteral nutrition, and supplies were calculated. Data were analyzed using one way ANOVA. RESULTS: Forty-eight patients (mean age 7.6months; 31 males [65%]) were studied. See attached table for results. HPN patients had significantly more ambulatory visits (p<0.0001), number of admitted days (p=0.01), and productive days lost (p<0.0001). Total cost of care was significantly higher for HPN patients (mean=$320,368.50, p<0.0001) when compared to other groups. Costs covered by the health care system were significantly higher for patients on HPN (mean=$316,101.56, p<0.0001). CONCLUSION: The outpatient expenditures to care for PIF patients in the first year post primary discharge are significant. Our single payer health care system supports the majority of costs, but families are also incurring expenses related to travel and lost productivity. Children on HPN have more visits to hospital, but have access to more funding options. Children solely on gastrostomy or stoma therapy, however, have a significantly greater personal financial burden.

Prevalence of renal abnormality in pediatric intestinal failure.

BACKGROUND: Outcomes of children with intestinal failure have improved over the last decade. However, with improved survival, other co-morbidities have become evident. The goal of our study was to evaluate the presence of renal nephrocalcinosis or increased echogenicity in a cohort of patients with pediatric intestinal failure (PIF). METHODS: A cross-sectional prevalence design was performed in PIF patients followed by our intestinal rehabilitation program between 2013 and 2014. Renal function was evaluated using serum creatinine and urea, urine oxalate, creatinine, calcium, and calcium/creatinine ratios. Renal ultrasounds were performed to assess for echogenicity. Data was collected on intestinal failure related factors and nutritional intake. Data was analyzed using medians and Mann-Whitney U or proportions and chi square. RESULTS: Fifty-four patients (median age 48months; 33 males (61%) were studied. Twenty-two patients (41%) had increased echogenicity or nephrocalcinosis on ultrasound. There were no differences in serum Creatinine or urea, but patients with nephrocalcinosis had statistically different calcium:creatinine ratio (1.69 vs 0.74; p=0.043), urine oxalate (108 vs 219; p=0.06), and serum phosphate (1.55 vs 1.75; p=0.044). Patients with echogenicity had a shorter colonic remnant (25cm vs 31cm; p=0.01), a history of longer PN exposure (928 vs 483days; p=0.05), percent PN calories (37 vs 0; p=0.05), PN h/day (13 vs 0; p=0.05), but no difference in PN Ca/phosphate/magnesium content (mmol/kg). CONCLUSION: A large proportion of PIF patients have increased echogenicity/nephrocalcinosis on ultrasound that is associated with prolonged PN exposure. This has implications for long-term management. Regular surveillance is required, and further study is warranted to determine specific risk factors.

Plasma Aluminum Concentrations in Pediatric Patients Receiving Long-Term Parenteral Nutrition.

BACKGROUND: Patients receiving long-term parenteral nutrition (PN) are at increased risk of aluminium (Al) toxicity because of bypass of the gastrointestinal tract during PN infusion. Complications of Al toxicity include metabolic bone disease (MBD), Al-associated encephalopathy in adults, and impaired neurological development in preterm infants. Unlike the United States, there are no regulations regarding Al content of large- and small-volume parenterals in Canada. We, therefore, aimed to present our data on plasma Al concentration and Al intake from our cohort of pediatric patients receiving long-term PN. METHODS: Plasma Al concentration was retrospectively gathered from the patient charts of all 27 patients with intestinal failure (IF) receiving long-term PN at The Hospital for Sick Children, Toronto, Canada, and compared with age- and sex-matched controls recruited for comparison. In addition, Al concentration was measured in PN samples collected from 10 randomly selected patients with IF and used to determine their Al intake. RESULTS: The plasma Al concentration of patients with IF receiving long-term PN was significantly higher than that of control participants (1195 ± 710 vs 142 ± 63 nmol/L; P < .0001). In the subgroup of 10 patients for whom Al intake from their PN solution was determined, mean ± SD Al intake from PN was 15.4 ± 15 µg/kg, 3 times the Food and Drug Administration upper recommended intake level, and Al intake was significantly related to plasma Al concentration (P = .02, r (2) = 0.52). CONCLUSION: Pediatric patients receiving long-term PN for IF in Canada are at risk for Al toxicity.

Randomized trial comparison of emotion regulation and relational psychotherapies for PTSD with girls involved in delinquency.

Posttraumatic stress disorder (PTSD) is prevalent in youth involved in delinquency, but it is often not effectively treated. A randomized clinical trial was conducted comparing the outcomes of an emotion regulation therapy (Trauma Affect Regulation: Guide for Education and Therapy, or TARGET) with a relational supportive therapy (Enhanced Treatment as Usual, or ETAU) with 59 delinquent girls (age 13-17 years) who met criteria for full or partial PTSD. Mixed model regression analyses demonstrated generally large effects for pre-post change in PTSD symptoms for both therapies but not in emotion regulation. Both therapies had small to medium effect size changes in anxiety, anger, depression, and posttraumatic cognitions. Treatment × Time interactions showed small to medium effects favoring TARGET for change in PTSD (intrusive reexperiencing and avoidance) and anxiety symptoms, posttraumatic cognitions, and emotion regulation, and favoring ETAU for change in hope and anger. Results provide preliminary support for TARGET as a potentially efficacious therapy for PTSD with delinquent girls. Relational therapies such as ETAU also may be beneficial for delinquent girls with PTSD, particularly to enhance optimism and self-efficacy and reduce anger.

A randomized clinical trial comparing affect regulation and social problem-solving psychotherapies for mothers with victimization-related PTSD.

Addressing affect dysregulation may provide a complementary alternative or adjunctive approach to the empirically supported trauma memory processing models of cognitive behavior therapy (CBT) for posttraumatic stress disorder (PTSD). A CBT designed to enhance affect regulation without trauma memory processing--trauma affect regulation: guide for education and therapy (TARGET)--was compared to present centered therapy (PCT) and wait-list (WL) conditions in a randomized clinical trial with 146 primarily low-income and ethnoracial minority mothers with PTSD. TARGET achieved statistically and clinically significant improvement on PTSD and affect regulation measures compared to WL, with more consistent and sustained (over a 6-month follow-up period) evidence of improvement than PCT. Drop-out rates (~25%) were comparable in TARGET and PCT, similar to those previously reported for trauma memory processing CBTs. Symptom worsening was rare (2-8%) and transient. Affect regulation-based CBT without trauma memory processing warrants further research as a potentially efficacious therapy for victimization-related PTSD.

Treatment process, alliance and outcome in brief versus extended treatments for marijuana dependence.

AIMS: The Marijuana Treatment Project, a large multi-site randomized clinical trial, compared a delayed treatment control condition with a brief (two-session) and extended (nine-session) multi-component treatment among 450 marijuana-dependent participants. In this report we present treatment process data, including the fidelity of treatment delivery in the three community-based treatment settings as well as the relationships between treatment process and outcome. DESIGN: Independent evaluations of clinician adherence and competence ratings were made based on 633 videotaped sessions from 163 participants. Relationships between clinician adherence and competence, ratings of the working alliance and marijuana treatment outcomes were evaluated. FINDINGS: Protocol treatments were implemented with strong fidelity to manual specifications and with few significant differences in adherence and competence ratings across sites. In the brief two-session treatment condition, only the working alliance was associated significantly with frequency of marijuana use, but in the extended treatment therapist ratings of working alliance predicted outcomes, as did the interaction of alliance and curvilinear adherence. CONCLUSIONS: Behavioral treatments for marijuana use were delivered in community settings with good fidelity. Participant and therapist working alliance scores were associated significantly with improved marijuana use outcomes in a brief behavioral treatment for adults with marijuana dependence. In extended treatment the therapist ratings of working alliance were associated with more positive outcome. However, in that treatment there was also a significant interaction between alliance and curvilinear adherence.

Prevalence and effects of gene-gene and gene-nutrient interactions on serum folate and serum total homocysteine concentrations in the United States: findings from the third National Health and Nutrition Examination Survey DNA Bank.

BACKGROUND: Abnormalities of folate and homocysteine metabolism are associated with a number of pediatric and adult disorders. Folate intake and genetic polymorphisms encoding folate-metabolizing enzymes influence blood folate and homocysteine concentrations, but the effects and interactions of these factors have not been studied on a population-wide basis. OBJECTIVE: The objective was to assess the prevalence of these genetic polymorphisms and their relation to serum folate and homocysteine concentrations. DESIGN: DNA samples from 6793 participants in the third National Health and Nutrition Examination Survey (NHANES III) during 1991-1994 were genotyped for polymorphisms of genes coding for folate pathway enzymes 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C-->T and 1298A-->C, methionine synthase reductase (MTRR) 66A-->G, and cystathionine-beta-synthase 844ins68. The influence of these genetic variants on serum folate and homocysteine concentrations was analyzed by age, sex, and folate intake in 3 race-ethnicity groups. RESULTS: For all race-ethnicity groups, serum folate and homocysteine concentrations were significantly related to the MTHFR 677C-->T genotype but not to the other polymorphisms. Persons with the MTHFR 677 TT genotype had a 22.1% (95% CI: 14.6%, 28.9%) lower serum folate and a 25.7% (95% CI: 18.6%, 33.2%) higher homocysteine concentration than did persons with the CC genotype. Moderate daily folic acid intake (mean: 150 microg/d; 95% CI: 138, 162) significantly reduced the difference in mean homocysteine concentrations between those with the MTHFR 677 CC and TT genotypes. We found a significant interaction between MTHFR 677C-->T and MTRR 66A-->G on serum homocysteine concentrations among non-Hispanic whites. CONCLUSIONS: The MTHFR 677C-->T polymorphism was associated with significant differences in serum folate and homocysteine concentrations in the US population before folic acid fortification. The effect of MTHFR 677C-->T on homocysteine concentrations was reduced by moderate daily folic acid intake.

Investigating childhood leukemia in Churchill County, Nevada.

BACKGROUND: Sixteen children diagnosed with acute leukemia between 1997 and 2002 lived in Churchill County, Nevada, at the time of or before their illness. Considering the county population and statewide cancer rate, fewer than two cases would be expected. OBJECTIVES: In March 2001, the Centers for Disease Control and Prevention led federal, state, and local agencies in a cross-sectional, case-comparison study to determine if ongoing environmental exposures posed a health risk to residents and to compare levels of contaminants in environmental and biologic samples collected from participating families. METHODS: Surveys with more than 500 variables were administered to 205 people in 69 families. Blood, urine, and cheek cell samples were collected and analyzed for 139 chemicals, eight viral markers, and several genetic polymorphisms. Air, water, soil, and dust samples were collected from almost 80 homes to measure more than 200 chemicals. RESULTS: The scope of this cancer cluster investigation exceeded any previous study of pediatric leukemia. Nonetheless, no exposure consistent with leukemia risk was identified. Overall, tungsten and arsenic levels in urine and water samples were significantly higher than national comparison values; however, levels were similar among case and comparison groups. CONCLUSIONS: Although the cases in this cancer cluster may in fact have a common etiology, their small number and the length of time between diagnosis and our exposure assessment lessen the ability to find an association between leukemia and environmental exposures. Given the limitations of individual cancer cluster investigations, it may prove more efficient to pool laboratory and questionnaire data from similar leukemia clusters.

Genetic studies of a cluster of acute lymphoblastic leukemia cases in Churchill County, Nevada.

OBJECTIVE: In a study to identify exposures associated with 15 cases of childhood leukemia, we found levels of tungsten, arsenic, and dichlorodiphenyldichloroethylene in participants to be higher than mean values reported in the National Report on Human Exposure to Environmental Chemicals. Because case and comparison families had similar levels of these contaminants, we conducted genetic studies to identify gene polymorphisms that might have made case children more susceptible than comparison children to effects of the exposures. DESIGN: We compared case with comparison children to determine whether differences existed in the frequency of polymorphic genes, including genes that code for enzymes in the folate and purine pathways. We also included discovery of polymorphic forms of genes that code for enzymes that are inhibited by tungsten: xanthine dehydrogenase, sulfite oxidase (SUOXgene), and aldehyde oxidase. PARTICIPANTS: Eleven case children were age- and sex-matched with 42 community comparison children for genetic analyses. Twenty parents of case children also contributed to the analyses. RESULTS: One bilalleleic gene locus in SUOX was significantly associated with either case or comparison status, depending on which alleles the child carried (without adjusting for multiple comparisons). CONCLUSIONS: Although genetic studies did not provide evidence that a common agent or genetic susceptibility factor caused the leukemias, the association between a SUOXgene locus and disease status in the presence of high tungsten and arsenic levels warrants further investigation. RELEVANCE: Although analyses of community clusters of cancer have rarely identified causes, these findings have generated hypotheses to be tested in subsequent studies.

Laboratory science and public health at CDC.

Laboratory technology is as essential to public health practitioners for monitoring threats to public health as it is to clinical practitioners who depend on laboratory technology to diagnose and monitor disease in individuals. Laboratory technology provides essential information for effective public health interventions, whether monitoring emerging infectious diseases, such as avian influenza globally; identifying pathogens, such as Escherichia coli in the U.S. food supply and pinpointing its source; screening newborns for devastating disorders, such as phenylketonuria, that can be prevented by early intervention; or developing the capacity to quickly screen for exposure to chemical and biologic agents.

Systematic review of the efficacy of meditation techniques as treatments for medical illness.

BACKGROUND: Meditative techniques are sought frequently by patients coping with medical and psychological problems. Because of their increasingly widespread appeal and use, and the potential for use as medical therapies, a concise and thorough review of the current state of scientific knowledge of these practices as medical interventions was conducted. PURPOSE: To systematically review the evidence supporting efficacy and safety of meditative practices in treating illnesses, and examine areas warranting further study. Studies on normal healthy populations are not included. METHODS: Searches were performed using PubMed, PsycInfo, and the Cochrane Database. Keywords were Meditation, Meditative Prayer, Yoga, Relaxation Response. Qualifying studies were reviewed and independently rated based on quality by two reviewers. Mid-to-high-quality studies (those scoring above 0.65 or 65% on a validated research quality scale) were included. RESULTS: From a total of 82 identified studies, 20 randomized controlled trials met our criteria. The studies included 958 subjects total (397 experimentally treated, 561 controls). No serious adverse events were reported in any of the included or excluded clinical trials. Serious adverse events are reported in the medical literature, though rare. The strongest evidence for efficacy was found for epilepsy, symptoms of the premenstrual syndrome and menopausal symptoms. Benefit was also demonstrated for mood and anxiety disorders, autoimmune illness, and emotional disturbance in neoplastic disease. CONCLUSIONS: The results support the safety and potential efficacy of meditative practices for treating certain illnesses, particularly in nonpsychotic mood and anxiety disorders. Clear and reproducible evidence supporting efficacy from large, methodologically sound studies is lacking.

Cognitive-behavioral therapy for pathological gamblers.

Few studies have evaluated efficacy of psychotherapies for pathological gambling. Pathological gamblers (N = 231) were randomly assigned to (a) referral to Gamblers Anonymous (GA), (b) GA referral plus a cognitive- behavioral (CB) workbook, or (c) GA referral plus 8 sessions of individual CB therapy. Gambling and related problems were assessed at baseline, 1 month later, posttreatment, and at 6- and 12-month follow-ups. CB treatment reduced gambling relative to GA referral alone during the treatment period and resulted in clinically significant improvements, with some effects maintained throughout follow-up ( ps = .05). Individual CB therapy improved some outcomes compared with the CB workbook. Attendance at GA and number of CB therapy sessions or workbook exercises completed were associated with gambling abstinence. These data suggest the efficacy of this CB therapy approach.

Childhood maltreatment in male and female treatment-seeking pathological gamblers.

Little empirical research has evaluated childhood abuse in pathological gamblers. This study describes results of an analysis of childhood maltreatment histories among 149 pathological gamblers being treated at 1 of 7 gambling treatment programs. Measurements included instruments assessing gambling behavior and the Childhood Trauma Questionnaire (CTQ; D. P. Bernstein et al., 1994). Women scored higher than men on the overall CTQ scale and subscales measuring childhood physical neglect, emotional abuse, and sexual abuse. Severity of childhood maltreatment was significantly and independently associated with lower age of onset of gambling and increased severity of gambling problems. This study suggests that childhood maltreatment is prevalent in pathological gamblers, especially female gamblers. These results warrant further investigation of the role of childhood maltreatment in the etiology of pathological gambling and its treatment.