Showing papers by "Hospital for Sick Children published in 2007"
TL;DR: This largest longitudinal pediatric neuroimaging study reported to date demonstrates the importance of examining size-by-age trajectories of brain development rather than group averages across broad age ranges when assessing sexual dimorphism and finds robust male/female differences in the shapes of trajectories.
1,208 citations
TL;DR: Pediatric patients responding to an induction regimen of infliximab were more likely to be in clinical response and remission at week 54 without dose adjustment when their maintenance therapy was given every 8 weeks rather than every 12 weeks.
781 citations
TL;DR: New evidence is examined on the association of lipid abnormalities with early atherosclerosis, challenges with previous guidelines, and results of clinical trials with statin therapy in children and adolescents with familial hypercholesterolemia or severe hypercholesterololemia are highlighted.
Abstract: Despite compliance with lifestyle recommendations, some children and adolescents with high-risk hyperlipidemia will require lipid-lowering drug therapy, particularly those with familial hypercholesterolemia. The purpose of this statement is to examine new evidence on the association of lipid abnormalities with early atherosclerosis, discuss challenges with previous guidelines, and highlight results of clinical trials with statin therapy in children and adolescents with familial hypercholesterolemia or severe hypercholesterolemia. Recommendations are provided to guide decision-making with regard to patient selection, initiation, monitoring, and maintenance of drug therapy.
415 citations
TL;DR: A meta-analysis of randomized and quasi-randomized controlled trials involving patients with active Crohn's disease defined by a clinical disease activity index and the importance of formula composition on effectiveness to evaluate the effectiveness of exclusive enteral nutrition as primary therapy to induce remission in Crohn’s disease.
Abstract: Background
The role of enteral nutrition in Crohn's disease is controversial. Increasing research on the mechanisms by which nutritional therapy improves the clinical well being of patients with Crohn's disease has led to novel formula design and trials comparing two different forms of enteral nutrition. This meta-analysis aims to provide an update on the existing effectiveness data for both corticosteroids versus enteral nutrition and for one form of enteral nutrition versus another for inducing remission of active Crohn's disease.
Objectives
To evaluate the effectiveness of exclusive enteral nutrition (EN) as primary therapy to induce remission in Crohn's disease and to examine the importance of formula composition on effectiveness.
Search methods
Studies were selected using a computer-assisted search of the on-line bibliographic databases MEDLINE (1966-2006) and EMBASE (1984-2006), as well as the Science Citation Index on Web of Science. Additional citations were sought by manual search of references of articles retrieved from the computerized search, abstracts submitted to major gastroenterologic meetings and published in the journals: American Journal of Gastroenterology, Gut, Gastroenterology, Journal of Pediatric Gastroenterology and Nutrition, and Journal of Parenteral and Enteral Nutrition, and from the reviewers' personal files or contact with leaders in the field.
Selection criteria
All randomized and quasi-randomized controlled trials involving patients with active Crohn's disease defined by a clinical disease activity index were considered for review. Studies evaluating the administration of one type of enteral nutrition to one group of patients and another type of enteral nutrition or conventional corticosteroids to the other group were selected for review.
Data collection and analysis
Data were extracted independently by two authors and any discrepancies were resolved by rereading and discussion. For the dichotomous variable, achievement of remission, individual and pooled trial statistics were calculated as odds ratios (OR) with 95% confidence intervals (CI); both fixed and random effect models were used. The results for each analysis were tested for heterogeneity using the chi square statistic. The studies were separated into two groups: A. one form of enteral nutrition compared with another form of enteral nutrition and B. one form of enteral nutrition compared with corticosteroids. Subgroup analyses were conducted on the basis of clinical or disease criteria and formula composition. Sensitivity analyses were conducted on the basis of the inclusion of abstract publications, methodologic quality and by random or fixed effects models.
Main results
In part A, of the 15 included eligible trials (one abstract) comparing different formulations of EN for the treatment of active CD, 11 compared one (or more) elemental formula to a non-elemental one, three compared enteral diets of similar protein composition but different fat composition, and one compared non-elemental diets differing only in glutamine enrichment. Meta-analysis of ten trials comprising 334 patients demonstrated no difference in the efficacy of elemental versus non-elemental formulas (OR 1.10; 95% CI 0.69 to 1.75). Subgroup analyses performed to evaluate the different types of elemental and non-elemental diets (elemental, semi-elemental and polymeric) showed no statistically significant differences. Further analysis of seven trials including 209 patients treated with EN formulas of differing fat content (low fat: 20 g/1000 kCal) demonstrated no statistically significant difference in efficacy (OR 1.13; 95% CI 0.63 to 2.01). Similarly, the effect of very low fat content (< 3 g/1000 kCal) or type of fat (long chain triglycerides) were investigated, but did not demonstrate a difference in efficacy in the treatment of active CD, although a non significant trend was demonstrated favoring very low fat and very low long chain triglyceride content. This result should be interpreted with caution due to statistically significant heterogeneity and small sample size. Sensitivity analyses had no significant effects on the results. The role of specific fatty acids or disease characteristics on response to therapy could not be evaluated. In part B, eight trials (including two abstracts) comparing enteral nutrition to steroid therapy met the inclusion criteria for review. Meta-analysis of six trials that included 192 patients treated with enteral nutrition and 160 treated with steroids yielded a pooled OR of 0.33 favouring steroid therapy (95% CI 0.21 to 0.53). A sensitivity analysis including the abstracts resulted in an increase in the number of participants to 212 in the enteral nutrition group and 179 in the steroid group but the meta-analysis yielded a similar result (OR 0.36; 95% CI 0.23 to 0.56). There were inadequate data from full publications to perform further subgroup analyses by age, disease duration and disease location.
Authors' conclusions
Corticosteroid therapy is more effective than enteral nutrition for inducing remission of active Crohn's disease as was found in previous systematic reviews. Protein composition does not influence the effectiveness of EN in the treatment of active CD. A non significant trend favouring very low fat and/or very low long chain triglyceride content exists but larger trials are required to explore the significance of this finding.
410 citations
TL;DR: In this article, a systematic review on the topic of school feeding is presented, which shows that children who were fed at school attended school more frequently than those in control groups; this finding translated to an average increase of 4 to 6 days a year per child.
Abstract: Early malnutrition and/or micronutrient deficiencies can negatively affect many aspects of child health and development. School feeding programs are designed to provide food to hungry children and to improve their physical, mental and psychosocial health. This is the first systematic review on the topic of school feeding. Eighteen studies were included in this review; nine were performed in higher income countries and nine in lower income countries. In the highest quality studies (randomized controlled trials (RCTs) from low income countries, children who were fed at school gained an average of 0.39 kg more than controls over 19 months; in lower quality studies (controlled before and after trials (CBAs)), the difference in gain was 0.71 kg over 11.3 months. Children who were fed at school attended school more frequently than those in control groups; this finding translated to an average increase of 4 to 6 days a year per child. For educational and cognitive outcomes, children who were fed at school gained more than controls on math achievement, and on some short-term cognitive tasks.
333 citations
TL;DR: In some patients with phenylketonuria who are responsive to BH4, sapropterin treatment to reduce blood phenylalanine could be used as an adjunct to a restrictive low-phenylAlanine diet, and might even replace the diet in some instances.
276 citations
TL;DR: This article describes an atlas, based on a combination of magnetic resonance and computed tomography technology to yield high-resolution volumetric and vasculature data on CBA mouse, which provides an anatomical resource for future mouse studies.
252 citations
TL;DR: The size of the diaphragmatic defect seems to be the major factor influencing outcome in infants with congenital diaphRAGmatic hernia, and it is likely that the defect size is a surrogate marker for the degree of pulmonary hypoplasia.
Abstract: OBJECTIVES Congenital diaphragmatic hernia is a significant cause of neonatal mortality. The objective of this study was to evaluate the clinical factors associated with death in infants with congenital diaphragmatic hernia by using a large multicenter data set. METHODS This was a prospective cohort study of all liveborn infants with congenital diaphragmatic hernia who were cared for at tertiary referral centers belonging to the Congenital Diaphragmatic Hernia Study Group between 1995 and 2004. Factors thought to influence death included birth weight, Apgar scores, size of defect, and associated anomalies. Survival to hospital discharge, duration of mechanical ventilation, and length of hospital stay were evaluated as end points. RESULTS A total of 51 centers in 8 countries contributed data on 3062 liveborn infants. The overall survival rate was 69%. Five hundred thirty-eight (18%) patients did not undergo an operation and died. The defect size was the most significant factor that affected outcome; infants with a near absence of the diaphragm had a survival rate of 57% compared with infants having a primary repair with a survival rate of 95%. Infants without agenesis but who required a patch for repair had a survival rate of 79% compared with primary repair. CONCLUSIONS The size of the diaphragmatic defect seems to be the major factor influencing outcome in infants with congenital diaphragmatic hernia. It is likely that the defect size is a surrogate marker for the degree of pulmonary hypoplasia. Future research efforts should be directed to accurately quantitate the degree of pulmonary hypoplasia or defect size antenatally. Experimental therapies can then be targeted to prospectively identify high-risk patients who are more likely to benefit.
244 citations
TL;DR: This review summarizes key factors that must be considered to support this critical clinical transition and sets the foundation for future research to apply prospective study designs to evaluate transition interventions and determine long-term health outcomes.
241 citations
TL;DR: It is demonstrated that L. monocytogenes utilizes multiple mechanisms to avoid destruction by the autophagy system during colonization of macrophages, as well as a role for the bacterial phospholipases, PI-PLC and PC-P LC, in autophile evasion, as bacteria lacking phospholIPase expression were targeted by autophagic at later times in infection.
Abstract: Listeria monocytogenes is an intracellular pathogen that is able to colonize the cytosol of macrophages. Here we examined the interaction of this pathogen with autophagy, a host cytosolicdegradative pathway that constitutes an important component of innate immunity towards microbial invaders. L. monocytogenes infection induced activation of the autophagy system in macrophages. At 1 h post infection (p.i.), a population of intracellular bacteria (~37%) colocalized with the autophagy marker LC3. These bacteria were within vacuoles and were targeted by autophagy in an LLO-dependent manner. At later stages in infection (by 4 h p.i.), the majority of L. monocytogenes escaped into the cytosol and rapidly replicated. At these times, less than 10% of intracellular bacteria colocalized with LC3. We found that ActA expression was sufficient to prevent autophagy of bacteria in the cytosol of macrophages. Surprisingly, ActA expression was not strictly necessary, indicating that other virulence factors were involved. ...
231 citations
TL;DR: A simple labeling approach is presented based on protein expression in glucose containing media that produces molecules enriched at methyl carbon positions or backbone Cα sites, facilitating studies of dynamics through the use of spin-spin relaxation experiments without artifacts introduced by evolution due to large homonuclear scalar couplings.
Abstract: A simple labeling approach is presented based on protein expression in [1-(13)C]- or [2-(13)C]-glucose containing media that produces molecules enriched at methyl carbon positions or backbone C(alpha) sites, respectively. All of the methyl groups, with the exception of Thr and Ile(delta1) are produced with isolated (13)C spins (i.e., no (13)C-(13)C one bond couplings), facilitating studies of dynamics through the use of spin-spin relaxation experiments without artifacts introduced by evolution due to large homonuclear scalar couplings. Carbon-alpha sites are labeled without concomitant labeling at C(beta) positions for 17 of the common 20 amino acids and there are no cases for which (13)C(alpha)-(13)CO spin pairs are observed. A large number of probes are thus available for the study of protein dynamics with the results obtained complimenting those from more traditional backbone (15)N studies. The utility of the labeling is established by recording (13)C R (1rho) and CPMG-based experiments on a number of different protein systems.
TL;DR: The current scientific evidence supporting the cancer stem cell hypothesis is presented and the experimental and therapeutic implications of the discovery of human cancer stem cells are discussed.
Abstract: According to the cancer stem cell hypothesis, only a subpopulation of cells within a cancer has the capacity to sustain tumor growth. This subpopulation of cells is made up of cancer stem cells, which are defined simply as the population of cells within a tumor that can self-renew, differentiate, and regenerate a phenocopy of the cancer when injected in vivo. Cancer stem cells have now been prospectively isolated from human cancers of the blood, breast, and brain, and putative cancer stem cells have been identified from human skin, bone, and prostate tumors and from multiple established mammalian cancer cell lines. Furthermore, researchers are actively seeking cancer stem cells in every human cancer type. We present the current scientific evidence supporting the cancer stem cell hypothesis and discuss the experimental and therapeutic implications of the discovery of human cancer stem cells.
TL;DR: These provisional classification criteria for juvenile SSc will help standardize the conduct of clinical research, epidemiologic and outcome studies, and therapeutic trials.
Abstract: Objective
To develop criteria for the classification of systemic sclerosis (SSc) in children (juvenile SSc).
Methods
The study consisted of 3 phases: 1) collection of data on the signs and symptoms of actual patients with juvenile SSc that are useful for defining involvement of a particular organ; 2) selection of the parameters essential for the classification of juvenile SSc and preparation of a set of provisional classification criteria (PCC) using 2 Delphi surveys; 3) consensus conference consisting of 2 steps: discussion and rating of clinical profiles of 160 patients with definite juvenile SSc, possible juvenile SSc, or other fibrosing diseases as “having or not having juvenile SSc,” using nominal group technique, and defining those PCC with the best statistical performance and highest face validity by using the clinical profiles of patients with definite juvenile SSc as the gold standard.
Results
In phase 1, 55 centers submitted clinical data on 153 patients with juvenile SSc. A total of 48 signs and symptoms were derived from these patient data and were used to define 9 organ system categories (cutaneous, vascular, gastrointestinal, respiratory, renal, cardiac, neurologic, musculoskeletal, and serologic). During phase 2, these were reduced to 21 criteria (3 major criteria [Raynaud's phenomenon, proximal skin sclerosis/induration of the skin, and sclerodactyly] and 18 minor criteria) and combined to generate 86 different PCC. At the consensus conference, these 86 definitions were tested on the case profiles of 127 patients with juvenile SSc. The PCC with the highest ranking were proximal sclerosis/induration and at least 2 minor criteria.
Conclusion
These provisional classification criteria for juvenile SSc will help standardize the conduct of clinical research, epidemiologic and outcome studies, and therapeutic trials.
TL;DR: Results showed that significant improvements in children’s externalizing behavior were associated with increases in parent–child emotional flexibility during the problem-solving discussion, and dyads who improved still expressed negative emotions, but they acquired the skills to repair conflicts, shifting out of their negative interactions to mutually positive patterns.
Abstract: Studies have shown that improved parenting mediates treatment outcomes for aggressive children, but we lack fine-grained descriptions of how parent-child interactions change with treatment. The current study addresses this gap by applying new dynamic systems methods to study parent-child emotional behavior patterns. These methods tap moment-to-moment changes in interaction processes within and across sessions and quantify previously unmeasured processes of change related to treatment success. Aggressive children and their parents were recruited from combined Parent Management Training and Cognitive-behavioral programs in "real world" clinical settings. Behavioral outcomes were assessed by reports from parents and clinicians. At pre- and post-treatment, home visits were videotaped while parents and children discussed consecutively: a positive topic, a mutually unresolved problem, and another positive topic. Results showed that significant improvements in children's externalizing behavior were associated with increases in parent-child emotional flexibility during the problem-solving discussion. Also, dyads who improved still expressed negative emotions, but they acquired the skills to repair conflicts, shifting out of their negative interactions to mutually positive patterns.
TL;DR: The results are consistent with Bowlby's (1969/1982) original conceptualization of the explanatory role of the attachment relationship in the development and manifestation of behavioral maladaptation.
Abstract: Background: Attachment theory’s original formulation was substantially driven by Bowlby’s (1969/ 1982) quest for a meaningful model of the development of psychopathology Bowlby posited that aberrant experiences of parenting increase the child’s risk of psychopathological outcomes, and that these risks are mediated by the quality of the attachment relationship To empirically examine this hypothesis, the current study explores the associations between the development of toddler behavior problems and a) maternal unresolved attachment representations, b) maternal interactive behavior, and c) infant attachment relationships Second, we test the mediating role of disorganized attachment in the association between disruptive behavior and toddler behavior problems, as well as unresolved attachment and behavior problems Method: Sixty-four adolescent mother–infant dyads participated in this longitudinal study The Adult Attachment Interview was administered at 6 months, the Strange Situation procedure was conducted at 12 months, disrupted behavior was assessed during play interactions at 12 months using the AMBIANCE measure, and the Child Behavior Checklist (CBCL) was used to assess behavior problems at 24 months of age Results: Maternal reports of externalizing problems were significantly associated with unresolved representations of attachment, disrupted maternal behavior, and disorganized attachment Inclusion of these variables in a path analytic model suggested that disorganized attachment mediated the associations between disrupted maternal behavior and externalizing problems Although the association between unresolved attachment representations and externalizing problems was no longer significant when mediation by disrupted behavior and disorganized attachment was taken into account, this indirect pathway was not significant Conclusions: The results are consistent with Bowlby’s (1969/1982) original conceptualization of the explanatory role of the attachment relationship in the development and manifestation of behavioral maladaptation Effects of unresolved attachment on externalizing problems await further explanation Keywords: Attachment, parent–child interaction, behavior problems
TL;DR: ERT of LSDs represents the most important advance in the treatment of this class of diseases and the information that is currently being collected as part of large-scale observational studies will help to establish the full potential of the treatment.
Abstract: Enzyme replacement therapy (ERT) as treatment for lysosomal storage diseases (LSDs) was suggested as long ago as 1966 by De Duve and Wattiaux. However, it took >35 years to demonstrate the safety and effectiveness of ERT for type 1 Gaucher's disease. An important breakthrough was certainly the enactment of legislation in the US, designed to encourage commercialisation of products developed in academic institutions for pharmaceutical companies to invest in treatments for rare diseases. The principles elaborated in the development of the treatment of Gaucher's disease were subsequently applied to the development of ERT of other LSDs. The safety and effectiveness of ERT for Fabry's disease, mucopolysaccharidoses (MPS) I, MPS II and MPS VI, as well as for Pompe's disease have been demonstrated in well designed clinical trials, and the treatments are now commercially available throughout the world. Several questions remain to be answered. The long-term effectiveness of most of the treatments has not yet been established. What is reversible by ERT and what may not be reversible but is preventable, is not yet clear. The pathology in some tissues, such as the brain, is inaccessible to ERT, indicating that some manifestations of the LSD will not respond to the treatment. The extent of this problem is still unclear. The cost of ERT is very high, creating problems for third-party payers, which has strained reimbursement schemes based on the demonstration of acceptable cost effectiveness. ERT of LSDs represents the most important advance in the treatment of this class of diseases. The information that is currently being collected as part of large-scale observational studies will help to establish the full potential of the treatment.
TL;DR: The etiology and underlying pathophysiological process responsible for perioperative reactions reported in muscular dystrophy patients is discussed, and recommendations are proposed for the safe anesthetic management of these patients.
Abstract: Patients with Duchenne and Becker muscular dystrophy suffer from a progressive deterioration in muscle secondary to a defect in the dystrophin gene. As such, they are susceptible to perioperative respiratory, cardiac and other complications, such as rhabdomyolysis. Inhalational anesthetic agents have been implicated as a cause of acute rhabdomyolysis that can resemble malignant hyperthermia (MH). This article reviews perioperative 'MH-like' reactions reported in muscular dystrophy patients and groups them into three categories according to clinical presentation. The etiology and underlying pathophysiological process responsible for these reactions is discussed and recommendations are proposed for the safe anesthetic management of these patients.
TL;DR: Clinical assessments need to consider the experiences and perceptions of children as they manage their IBD, and a positive attitude and other strategies were described as strengths contributing to quality of life.
Abstract: The aims of this study were to understand the lived experience and elements of quality of life as depicted by children and adolescents with inflammatory bowel disease (IBD). Eighty participants with IBD, ranging in age from 7 to 19 years, were interviewed about the impact of IBD on their daily lives. Findings demonstrated that IBD profoundly affects children and adolescents. These young patients experience concerns and discomfort as a result of IBD symptoms and treatments. They commonly feel, in varying degrees, a sense of vulnerability and diminished control over their lives and future, and perceive themselves as "different" from healthy peers and siblings. Despite these negative impacts, participants also described effective means of coping with IBD, and reported that support from family members and friends contributes to coping. A positive attitude and other strategies were also described as strengths contributing to quality of life. Clinical assessments need to consider the experiences and perceptions of children as they manage their IBD. Implications for clinical practice are discussed.
TL;DR: No evidence was found that supports the use of omega 3 fatty acids for maintenance of remission in UC and further studies using enteric coated capsules may be justified.
Abstract: Background Omega-3 fatty acids (n-3, fish oil) have been shown to have anti-inflammatory properties. Therefore, n-3 therapy may be beneficial in chronic inflammatory disorders such as ulcerative colitis. Objectives To systematically review the efficacy and safety of n-3 for maintaining remission in ulcerative colitis (UC). Search strategy The following databases were searched from their inception without language restriction: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Healthstar, PubMed, and ACP journal club. Experts were contacted for unpublished data. Selection criteria Randomized placebo-controlled trials (RCT) of fish oil for maintenance of remission in UC were included. Studies must have enrolled patients (of any age group) who were in remission at the time of recruitment, and were followed for at least six months. The intervention must have been fish oil given in pre-defined dosage. Co-interventions were allowed only if they were balanced between the study groups. The primary outcome was relapse rate and the secondary outcome was frequency of adverse events. Other outcomes to assess efficacy were change in disease activity scores and time to first relapse. Data collection and analysis Two independent investigators reviewed studies for eligibility, extracted the data and assessed study quality. Meta-analysis weighted by the Mantel-Haenszel method was performed using RevMan 4.2.8 software. Random or fixed effect models were used according to degree of heterogeneity and subgroup analyses were performed to explore heterogeneity. A sensitivity analysis was performed excluding a study of questionable quality . Main results The three studies that were included used different formulation and dosing of n-3 but none used enteric coated capsules. The pooled analysis showed a similar relapse rate in the n-3 treated patients and controls (RR 1.02; 95% CI 0.51 to 2.03; P = 0.96). Combining the studies resulted in virtually no statistical heterogeneity (P = 0.93, I(2) = 0%). Various subgroup and sensitivity analyses showed similar results. However, the total number of patients enrolled in these studies was small (n = 138). No significant adverse events were recorded in any of the studies and not enough data were available to pool the other secondary outcomes for meta-analysis. Authors' conclusions No evidence was found that supports the use of omega 3 fatty acids for maintenance of remission in UC. Further studies using enteric coated capsules may be justified.
TL;DR: Assessment of neural mechanisms of emotion regulation that might distinguish subtypes of externalizing children from each other and from their normal age mates highlights different mechanisms of self-regulation underlying externalizing subtypes and point toward distinct developmental pathways and treatment strategies.
Abstract: Children referred for externalizing behavior problems may not represent a homogeneous population. Our objective was to assess neural mechanisms of emotion regulation that might distinguish subtypes of externalizing children from each other and from their normal age mates. Children with pure externalizing (EXT) problems were compared with children comorbid for externalizing and internalizing (MIXED) problems and with age-matched controls. Only boys were included in the analysis because so few girls were referred for treatment. We used a go/no-go task with a negative emotion induction, and we examined dense-array EEG data together with behavioral measures of performance. We investigated two event-related potential (ERP) components tapping inhibitory control or self-monitoring—the inhibitory N2 and error-related negativity (ERN)—and we constructed source models estimating their cortical generators. The MIXED children's N2s increased in response to the emotion induction, resulting in greater amplitudes than EXT children in the following trial block. ERN amplitudes were greatest for control children and smallest for EXT children with MIXED children in between, but only prior to the emotion induction. These results were paralleled by behavioral differences in response time and performance monitoring. ERP activity was localized to cortical sources suggestive of the dorsal anterior cingulate for control children, posterior cingulate areas for the EXT children, and both posterior cingulate and ventral cingulate/prefrontal regions for the MIXED children. These findings highlight different mechanisms of self-regulation underlying externalizing subtypes and point toward distinct developmental pathways and treatment strategies.We gratefully acknowledge the financial support provided by Grant 1 R21 MH67357-01 from the Developmental Psychopathology and Prevention Research branch of the National Institute of Mental Health (NIMH), as well as support from the Canadian Institutes for Health Research (CIHR). We are also grateful for support provided (to P.D.Z.) by the Canadian Foundation for Innovation.
TL;DR: Differential patterns of parental bereavement and related factors, information that has important implications for identifying at-risk parents for complicated bereavement, are illustrated.
Abstract: This study investigated the patterns of parental bereavement in 20 parents who have lost a child to cancer, congenital heart disease, meningitis, or drowning in the last 19 months, using semi-structured interviews and standardized questionnaires of depression and grief. Qualitative content analysis of interviews identified three bereavement patterns: The majority of parents (65%) presented uncomplicated, Integrated Grief five mothers were Consumed by Grief and one mother and one father expressed Minimal Grief. Quotes from parents exemplified these patterns. Parental gender, symptoms of depression, and pre-death relationship between parents and their deceased child differentially related to these patterns. Having surviving children, social support, and being active appeared to help to integrate grief into daily life. These findings illustrate differential patterns of parental bereavement and related factors, information that has important implications for identifying at-risk parents for complicated bereavement.
TL;DR: The rate of spontaneous clearance of childhood HCV infection was comparable between transfusional and nontransfusional cases, and tends to occur early in infection, at a younger age.
Abstract: To describe the spontaneous clearance rate of childhood hepatitis C virus (HCV) infection, to determine whether route of transmission affects the clearance rate and to identify other predictors of clearance. Children with chronic hepatitis C were identified between 1990 and 2001. The rate of spontaneous clearance (defined as >or=2 positive anti-HCV antibody test but negative HCV RNA) was calculated using survival analysis. Univariate and multivariate predictor variables [route of transmission, age at infection, age at last follow-up, alanine aminotransferase (ALT) and gender] for clearance were evaluated. Of 157 patients, 28% of children cleared infection (34 transfusional and 10 nontransfusional cases). The 123 transfusional cases were older at time of infection and at follow-up, compared with the 34 nontransfusional cases. Younger age at follow-up (p < 0.0001) and normal ALT levels (p < 0.0001) favoured clearance. Among cases of neonatal infection, 25% demonstrated spontaneous clearance by 7.3 years. The rate of spontaneous clearance of childhood HCV infection was comparable between transfusional and nontransfusional cases. If clearance occurs, it tends to occur early in infection, at a younger age.
TL;DR: Based on a literature review and collective experience in reviewing adverse event case reports in regulatory, academic, and industry settings, information that is proposed should always be considered for inclusion in a report submitted for publication is identified.
Abstract: Publication of case reports describing suspected adverse effects of drugs and medical products that include herbal and complementary medicines, vaccines, and other biologicals and devices is important for postmarketing surveillance. Publication lends credence to important signals raised in these adverse event reports. Unfortunately, deficiencies in vital information in published cases can often limit the value of such reports by failing to provide enough details for either (i) a differential diagnosis or provisional assessment of cause-effect association, or (ii) a reasonable pharmacological or biological explanation. Properly described, a published report of one or more adverse events can provide a useful signal of possible risks associated with the use of a drug or medical product which might warrant further exploration. A review conducted by the Task Force authors found that many major journals have minimal requirements for publishing adverse event reports, and some have none at all. Based on a literature review and our collective experience in reviewing adverse event case reports in regulatory, academic, and industry settings, we have identified information that we propose should always be considered for inclusion in a report submitted for publication. These guidelines have been endorsed by the International Society for Pharmacoepidemiology (ISPE) and the International Society of Pharmacovigilance (ISoP) and are freely available on the societies’ websites. Their widespread distribution is encouraged. ISPE and ISoP urge biomedical journals to adopt these guidelines and apply them to case reports submitted for publication. They also encourage schools of medicine, pharmacy, and nursing to incorporate them into the relevant curricula that address the detection, evaluation, and reporting of suspected drug or other medical product adverse events.
TL;DR: The type of monosaccharide sugar or polyols, CPA molarity, and combination of permeating and nonpermeating cryoprotectant are significant factors for improving progressive motility, plasma membrane integrity, DNA integrity, in vitro fertilization rate, and in vitro embryo development rate to blastocyst in cryopreserved mouse sperm.
Abstract: Efficient freezing, archiving, and thawing of sperm are essential techniques to support large scale research programs using mouse models of human disease. The purpose of this study was to investigate the effects of variable combinations and concentrations of cryoprotectants on sperm-assessment parameters of frozen-thawed mouse sperm in order to optimize cryopreservation protocols. Sperm was frozen using combinations of 3% skim milk + 0.2 or 0.3 M nonpermeating raffinose with either permeating glucose, fructose, propylene glycol, ethylene glycol, glycerol, or sodium pyruvate in CD-1, C3FeB6F1/J, B6129SF1, C57BL/6NCrIBR, 129S/SvPaslco, and DBA/2NCrIBR mice. Sperm-assessment parameters included progressive motility, plasma membrane integrity (SYBR-14 + PI), in vitro fertilization rate, and in vitro embryo development rate to blastocyst. DNA content analysis of sperm was measured by the sperm chromatin structure assay (SCSA). 0.3 M raffinose with 0.1 M fructose significantly improved post-thaw sperm-assessment parameters for CD-1, C3B6F1, B6129SF1 mice (P < 0.05-0.01), whereas 0.2 M raffinose with 0.1 M glycerol or 0.1 M fructose enhanced sperm assessment values for C57BL/6 and 129S mice (P < 0.01), compared to 0.3 M raffinose alone. DNA fragmentation during cryopreservation was significantly increased in all strains evaluated when compared with fresh control sperm in a strain-dependent manner (P < 0.01). Supplementation with permeating glycerol or fructose to the cryoprotectant (CPA) solution showed a significant protective effect to DNA integrity when cryopreserving sperm from C57BL/6 and 129S mice. Damage to sperm DNA significantly decreased the rate of in vitro embryo development to blastocyst in C57BL/6 mice. The type of monosaccharide sugar or polyols, CPA molarity, and combination of permeating and nonpermeating cryoprotectant are significant factors for improving progressive motility, plasma membrane integrity, DNA integrity, in vitro fertilization rate, and in vitro embryo development rate to blastocyst in cryopreserved mouse sperm.
TL;DR: In this article, a method of reducing blur in an optical projection tomography (OPT) image comprises filtering the frequency space information of OPT image data to reduce the effects of out-of-focus data and defocused in-focus.
Abstract: A method of reducing blur in an optical projection tomography (OPT) image comprises filtering the frequency space information of OPT image data to reduce the effects of out-of-focus data and defocused in-focus data and reconstructing the filtered OPT data.
Journal Article•
TL;DR: Functional magnetic resonance imaging shows a discordant pattern of activation when compared with EEG or electrocorticography, which could be due to complex epileptic networks.
Abstract: Functional magnetic resonance imaging (fmri) is a non-invasive functional brain mapping technique ased on blood oxygenated level dependent signal (BOLD). It is obtained during T2* weighted imaging MRI studies. fmri aids in the localization of language and motor function for patients candidates for epilepsy surgery, and has up to a 90% concordance with WADA test. Even though synchronous recording of fmri and EEG is technically challenging, it shows a discordant pattern of activation when compared with EEG or electrocorticography. This finding could be due to complex epileptic networks, and overall this study technique has the potential to contribute to further research into epileptic network and epilepsy physiopathology.
TL;DR: The methodological implications of conducting a secondary analysis of qualitative data focusing on parents’ narratives of help-seeking activities in the prodrome to psychosis in children’s mental health services and research are reported on.
Abstract: Primary data are rarely used explicitly as a source of data outside of the original research purpose for which they were collected. As a result, qualitative secondary analysis (QSA) has been described as an "invisible enterprise" for which there is a "notable silence" amongst the qualitative research community. In this paper, we report on the methodological implications of conducting a secondary analysis of qualitative data focusing on parents' narratives of help-seeking activities in the prodrome to psychosis. We review the literature on QSA, highlighting the main characteristics of the approach, and discuss issues and challenges encountered in conducting a secondary analysis. We conclude with some thoughts on the implications for conducting a QSA in children's mental health services and research.
TL;DR: The CCN family of genes currently comprises six secreted proteins that are involved in mitosis, adhesion, apoptosis, extracellular matrix production, growth arrest and migration of multiple cell types.
Abstract: The CCN family of genes currently comprises six secreted proteins (designated CCN1–6 after Cyr61/CCN1; ctgf/CCN2; Nov/CCN3; WISP1/CCN4; WISP2/CCN5, WISP3/CCN6) with a similar mosaic primary structure. It is now well accepted that CCN proteins are not growth factors but matricellular proteins that modify signaling of other molecules, in particular those associated with the extracellular matrix. CCN proteins are involved in mitosis, adhesion, apoptosis, extracellular matrix production, growth arrest and migration of multiple cell types. Since their first identification as matricellular factors, the CCN proteins now figure prominently in a variety of major diseases and are now considered valid candidates for therapeutic targeting. Dissection of the molecular mechanisms governing the biological properties of these proteins is being actively pursued by an expanding network of scientists around the globe who will meet this year at the 5th International Workshop on the CCN family of Genes, organized by the International CCN Society (http://ccnsociety.com), home for an international cadre of collaborators working in the CCN field.
TL;DR: The most important and best described clinical context for pulmonary regurgitation occurs in patients with repaired Tetralogy of Fallot, which is dominated by the primary lung disease or the high pulmonary vascular resistance rather than the volume load.
Abstract: The most important and best described clinical context for pulmonary regurgitation occurs in patients with repaired Tetralogy of Fallot. The first section deals briefly with pulmonary regurgitation in other situations; the remainder of the article deals with tetralogy of Fallot.
Isolated pulmonary regurgitation, in an otherwise normal heart, is well tolerated for decades. However, in a meta-analysis reported in the literature, 29% of patients had developed symptoms within 40 years.1 Many patients with a right ventricle to pulmonary artery conduit develop a mixture of obstruction and regurgitation across the conduit. However, some of these patients have regurgitation as the dominant lesion, and feature in pulmonary valve replacement series.2,3
Even valvar pulmonary stenosis treated surgically or by balloon dilatation can lead to significant pulmonary regurgitation requiring valve replacement. Fiftyseven per cent of patients had moderate to severe pulmonary regurgitation in a balloon dilatation series,w1 and in a surgical pulmonary valvotomy series 9% of patients required pulmonary valve replacement.w2
In pulmonary regurgitation secondary to pulmonary hypertension, the clinical picture is dominated by the primary lung disease or the high pulmonary vascular resistance rather than the volume load.
Severe acute pulmonary regurgitation driven by a large duct can occur in neonatal Ebstein’s anomaly,4 or following balloon dilation of critical pulmonary stenosis or perforation of valvar pulmonary atresia. If this torrential pulmonary regurgitation is accompanied by tricuspid regurgitation, a circular shunt may occur, due to righttoleft shunting across the atrial communication and lefttoright shunting at the duct resulting in poor systemic blood flow. Prostaglandins are stopped and in the most unstable patients, urgent duct ligation may be required. Attempts to decrease pulmonary regurgitation by pulmonary vasodilatation (increased ventilation, oxygen, nitric oxide) may be more successful if the tricuspid valve is competent.
Repair of tetralogy of Fallot is one …
TL;DR: These guidelines have been endorsed by the International Society for Pharmacoepidemiology (ISPE) and the International society of Pharmacovigilance (ISoP) and are freely available on the societies' web sites and widespread distribution is encouraged.
Abstract: medical products that include herbal and complementary medicines, vaccines, and other biologicals and devices is important for postmarketing surveillance. Publication lends credence to important signals raised in these adverse event reports. Unfortunately, deficiencies in vital information in published cases can often limit the value of such reports by failing to provide enough details for either (i) a differential diagnosis or provisional assessment of cause-effect association, or (ii) a reasonable pharmacological or biological explanation. Properly described, a published report of one or more adverse events can provide a useful signal of possible risks associated with the use of a drug or medical product which might warrant further exploration. A review conducted by the Task Force authors found that many major journals have minimal requirements for publishing adverse event reports, and some have none at all. Based on a literature review and our collective experience in reviewing adverse event case reports in regulatory, academic, and industry settings, we have identified information that we propose should always