Background
Racial and ethnic disparities in health status are pervasive at all stages of the life cycle. One approach to reducing health disparities involves mobilizing community coalitions that ...include representatives of target populations to plan and implement interventions for community level change. A systematic examination of coalition‐led interventions is needed to inform decision making about the use of community coalition models.
Objectives
To assess effects of community coalition‐driven interventions in improving health status or reducing health disparities among racial and ethnic minority populations.
Search methods
We searched MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, Social Science Citation Index, Dissertation s, System for Information on Grey Literature in Europe (SIGLE) (from January 1990 through September 30, 2013), and Global Health Library (from January 1990 through March 31, 2014).
Selection criteria
Cluster‐randomized controlled trials, randomized controlled trials, quasi‐experimental designs, controlled before‐after studies, interrupted time series studies, and prospective controlled cohort studies. Only studies of community coalitions with at least one racial or ethnic minority group representing the target population and at least two community public or private organizations are included. Major outcomes of interest are direct measures of health status, as well as lifestyle factors when evidence indicates that these have an effect on the direct measures performed.
Data collection and analysis
Two review authors independently extracted data and assessed risk of bias for each study.
Main results
Fifty‐eight community coalition‐driven intervention studies were included. No study was considered to be at low risk of bias. Behavioral change outcomes and health status change outcomes were analyzed separately. Outcomes are grouped by intervention type. Pooled effects across intervention types are not presented because the diverse community coalition‐led intervention studies did not examine the same constructs or relationships, and they used dissimilar methodological designs. Broad‐scale community system level change strategies led to little or no difference in measures of health behavior or health status (very low‐certainty evidence). Broad health and social care system level strategies leds to small beneficial changes in measures of health behavior or health status in large samples of community residents (very low‐certainty evidence). Lay community health outreach worker interventions led to beneficial changes in health behavior measures of moderate magnitude in large samples of community residents (very low‐certainty evidence). Lay community health outreach worker interventions may lead to beneficial changes in health status measures in large samples of community residents; however, results were not consistent across studies (low‐certainty evidence). Group‐based health education led by professional staff resulted in moderate improvement in measures of health behavior (very low‐certainty evidence) or health status (low‐certainty evidence). Adverse outcomes of community coalition‐led interventions were not reported.
Authors' conclusions
Coalition‐led interventions are characterized by connection of multi‐sectoral networks of health and human service providers with ethnic and racial minority communities. These interventions benefit a diverse range of individual health outcomes and behaviors, as well as health and social care delivery systems. Evidence in this review shows that interventions led by community coalitions may connect health and human service providers with ethnic and racial minority communities in ways that benefit individual health outcomes and behaviors, as well as care delivery systems. However, because information on characteristics of the coalitions themselves is insufficient, evidence does not provide an explanation for the underlying mechanisms of beneficial effects. Thus, a definitive answer as to whether a coalition‐led intervention adds extra value to the types of community engagement intervention strategies described in this review remains unattainable.
Glycogen storage disease (GSD) types VI and IX are rare diseases of variable clinical severity affecting primarily the liver. GSD VI is caused by deficient activity of hepatic glycogen phosphorylase, ...an enzyme encoded by the PYGL gene. GSD IX is caused by deficient activity of phosphorylase kinase (PhK), the enzyme subunits of which are encoded by various genes: ɑ (PHKA1, PHKA2), β (PHKB), ɣ (PHKG1, PHKG2), and δ (CALM1, CALM2, CALM3). Glycogen storage disease types VI and IX have a wide spectrum of clinical manifestations and often cannot be distinguished from each other, or from other liver GSDs, on clinical presentation alone. Individuals with GSDs VI and IX can present with hepatomegaly with elevated serum transaminases, ketotic hypoglycemia, hyperlipidemia, and poor growth. This guideline for the management of GSDs VI and IX was developed as an educational resource for health-care providers to facilitate prompt and accurate diagnosis and appropriate management of patients.
A national group of experts in various aspects of GSDs VI and IX met to review the limited evidence base from the scientific literature and provided their expert opinions. Consensus was developed in each area of diagnosis, treatment, and management. Evidence bases for these rare disorders are largely based on expert opinion, particularly when targeted therapeutics that have to clear the US Food and Drug Administration (FDA) remain unavailable.
This management guideline specifically addresses evaluation and diagnosis across multiple organ systems involved in GSDs VI and IX. Conditions to consider in a differential diagnosis stemming from presenting features and diagnostic algorithms are discussed. Aspects of diagnostic evaluation and nutritional and medical management, including care coordination, genetic counseling, and prenatal diagnosis are addressed.
A guideline that will facilitate the accurate diagnosis and optimal management of patients with GSDs VI and IX was developed. This guideline will help health-care providers recognize patients with GSDs VI and IX, expedite diagnosis, and minimize adverse sequelae from delayed diagnosis and inappropriate management. It will also help identify gaps in scientific knowledge that exist today and suggest future studies.
Introduction
Ketone formation is a normal response when hypoglycemia occurs. Since the majority of children with recurrent hypoglycemia cannot be diagnosed with a known endocrine or metabolic ...disorder on a critical sample, ketotic hypoglycemia has been described as the most common cause of low blood glucose concentrations in children. Critical samples, however, will miss the ketotic forms of glycogen storage disease (GSD), which present with elevated ketones, hypoglycemia, and normal hormonal concentrations.
Results
A total of 164 children (96 boys, 68 girls) were enrolled in the study. Prediction of pathogenicity of DNA changes using computer modeling confirmed pathology in 20 individuals four GSD 0, two GSD VI, 12 GSD IX alpha, one GSD IX beta, one GSD IX gamma (12 %). Boys were most likely to have changes in the
PHKA2
gene, consistent with GSD IX alpha, an X-linked disorder.
Conclusions
Mutations in genes involved in glycogen synthesis and degradation were commonly found in children with idiopathic ketotic hypoglycemia. GSD IX is likely an unappreciated cause of ketotic hypoglycemia in children, while GSD 0 and VI are relatively uncommon. GSD IX alpha should particularly be considered in boys with unexplained hypoglycemia.
The onset of microalbuminuria (MA) heralds the onset of glomerulopathy in patients with glycogen storage disease (GSD) type I. Unlike tubulopathy, which responds to improved metabolic control, ...glomerulopathy in GSD I is considered refractory to medical intervention, and it is thought to inexorably progress to overt proteinuria and renal failure. Recent reports of reduced microalbuminuria following strict adherence to therapy counter this view. In contrast to type Ia, little is known regarding the prevalence of kidney disease in GSD Ib, 0, III, VI, and IX. Subjects were evaluated with 24-h urine collections between 2005 and 2014 as part of a longitudinal study of the natural history of GSD. ACE inhibitor therapy (AIT) was commenced after documentation of microalbuminuria. Elevated urine albumin excretion was detected in 23 of 195 GSD Ia patients (11.7%) and six of 45 GSD Ib (13.3%). The median age of onset of microalbuminuria in GSD Ia was 24 years (range 9–56); in GSD Ib it was 25 years (range 20–38). Of 14 with GSD Ia who complied with dietary and AIT during the study period, microalbuminuria decreased in 11, in whom metabolic control improved. All 135 patients with the ketotic forms of GSD (0, III, VI and IX) consistently had normal microalbumin excretion. Strict adherence to dietary therapy and maintenance of optimal metabolic control is necessary to halt the progression of GSD Ia glomerulopathy in patients treated with AIT. With optimal care, protein excretion can be reduced and even normalize.
Mutations in the liver glycogen phosphorylase (Pygl) gene are associated with the diagnosis of glycogen storage disease type VI (GSD‐VI). To understand the pathogenesis of GSD‐VI, we generated a ...mouse model with Pygl deficiency (Pygl−/−). Pygl−/− mice exhibit hepatomegaly, excessive hepatic glycogen accumulation, and low hepatic free glucose along with lower fasting blood glucose levels and elevated blood ketone bodies. Hepatic glycogen accumulation in Pygl−/− mice increases with age. Masson's trichrome and picrosirius red staining revealed minimal to mild collagen deposition in periportal, subcapsular, and/or perisinusoidal areas in the livers of old Pygl−/− mice (>40 weeks). Consistently, immunohistochemical analysis showed the number of cells positive for alpha smooth muscle actin (α‐SMA), a marker of activated hepatic stellate cells, was increased in the livers of old Pygl−/− mice compared with those of age‐matched wild‐type (WT) mice. Furthermore, old Pygl−/− mice had inflammatory infiltrates associated with hepatic vessels in their livers along with up‐regulated hepatic messenger RNA levels of C‐C chemokine ligand 5 (Ccl5/Rantes) and monocyte chemoattractant protein 1 (Mcp‐1), indicating inflammation, while age‐matched WT mice did not. Serum levels of aspartate aminotransferase and alanine aminotransferase were elevated in old Pygl−/− mice, indicating liver damage. Conclusion: Pygl deficiency results in progressive accumulation of hepatic glycogen with age and liver damage, inflammation, and collagen deposition, which can increase the risk of liver fibrosis. Collectively, the Pygl‐deficient mouse recapitulates clinical features in patients with GSD‐VI and provides a model to elucidate the mechanisms underlying hepatic complications associated with defective glycogen metabolism.
Pygl‐deficient mice exhibit hepatomegaly and fasting hypoglycemia. Moreover, hepatic glycogen accumulation increases with age. Thus, Pygl‐deficient mice at old age display excessive buildup of hepatic glycogen and at risk of liver damage, inflammation and fibrosis.
Continuing with previous research by our group in an ESF system, four types of enrichment treatments were assessed in gestating sows housed in Free Access Stalls: (1) Constant: constant provision of ...wood on chain; (2) Rotate: rotation of rope, straw and wood; (3) Stimulus: rotation of enrichments with an acoustic cue; and (4) Control: no enrichment. Treatments had a 12 day-duration. Four groups (28 ± 2 sows) were studied from weeks 6 to 14 of gestation. Groups received all treatments in random order. Three dominant and 3 subordinates per pen were selected using a feed competition test. Digital photos were collected at 10 min intervals for 8 h on days 1, 8, 10 and 12 to record interactions with enrichment. Skin lesions were assessed on days 1 and 12, and salivary cortisol was assessed in weeks 6, 10 and 14 of gestation. More enrichment use was observed in Rotate and Stimulus treatments compared to Constant, and more sows contacted enrichment when straw was provided in the Rotate and Stimulus treatments. There was no difference in the amount of enrichment use by dominants and subordinates, no cortisol concentration elevation in subordinate sows nor any difference in lesion scores. In conclusion, social status had little impact and feeding system is important to reduce stress and aggression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The goal of this study was to identify practical enrichments for sows in partially or fully slatted pen systems. Four treatments were applied: (1) Constant: constant provision of wood on chain; (2) ...Rotate: rotation of rope, straw and wood enrichments; (3) Stimulus: rotation of enrichments (as in Rotate) with an associative stimulus (bell or whistle); and (4) Control: no enrichment, with each treatment lasting 12 days. Six groups of 20 ± 2 sows were studied from weeks 6 to 14 of gestation in pens with one electronic sow feeder. Each group received all treatments in random order. Six focal animals (3 dominant and 3 subordinate) were selected per pen using a feed competition test. Digital photos were collected at 10 min intervals for 8 h (between 8 a.m. and 4 p.m.) on 4 days/treatment (d 1, 8, 10 and 12) to record interactions with enrichment. Skin lesions were assessed on days 1 and 12, and saliva cortisol samples collected in weeks 6, 10 and 14 of gestation on focal pigs. Sows spent more time in contact with enrichments in Rotate and Stimulus treatments than Constant. Enrichment treatments did not influence lesion scores. Subordinate sows spent more time standing and near enrichments than dominants. Subordinate sows also received more skin lesions and had higher salivary cortisol concentrations than dominants. These results indicate that access to enrichment is valued by sows but can result in greater aggression directed towards subordinates.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
BCR‐ABL1‐like B‐Acute Lymphoblastic Leukemia (B‐ALL) is a subset of B‐ALL with a poor prognosis that is found in all age groups. Definitive identification of these patients is difficult in routine ...clinical practice as gene expression profiling, the gold standard test, is not widely available. Comprehensive genomic profiling performed on 450 patients with extensive fusion profiling revealed a wide range of genomic alterations which were consistent with a classification of BCR‐ABL1‐like B‐ALL in 29% of cases. This manuscript highlights a clinically available alternative method for identifying a large subset of patients with BCR‐ABL1‐like B‐ALL.
BCR‐ABL1‐like B‐lymphoblastic leukemia, also termed Philadelphia‐like B‐acute lymphoblastic leukemia (Ph‐like B‐ALL), shares a gene expression profile similar to BCR‐ABL1‐positive B‐ALL1 but lacks BCR‐ABL1 fusion. Because Ph‐like status confers a poor prognosis, identification of Ph‐like B‐ALL cases is important. This brief communication reports 450 cases of B‐ALL evaluated by genomic profiling.
Background
Viral mediated gene therapy has progressed after overcoming early failures, and gene therapy has now been approved for several conditions in Europe and the USA. Glycogen storage disease ...(GSD) type Ia, caused by a deficiency of glucose-6-phosphatase-α, has been viewed as an outstanding candidate for gene therapy. This follow-up report describes the long-term outcome for the naturally occurring GSD-Ia dogs treated with rAAV-GPE-hG6PC-mediated gene therapy.
Methods
A total of seven dogs were treated with rAAV-GPE-hG6PC-mediated gene therapy. The first four dogs were treated at birth, and three dogs were treated between 2 and 6 months of age to assess the efficacy and safety in animals with mature livers. Blood and urine samples, radiographic studies, histological evaluation, and biodistribution were assessed.
Results
Gene therapy improved survival in the GSD-Ia dogs. With treatment, the biochemical studies normalized for the duration of the study (up to 7 years). None of the rAAV-GPE-hG6PC-treated dogs had focal hepatic lesions or renal abnormalities. Dogs treated at birth required a second dose of rAAV after 2–4 months; gene therapy after hepatic maturation resulted in improved efficacy after a single dose.
Conclusion
rAAV-GPE-hG6PC treatment in GSD-Ia dogs was found to be safe and efficacious. GSD-Ia is an attractive target for human gene therapy since it is a monogenic disorder with limited tissue involvement. Blood glucose and lactate monitoring can be used to assess effectiveness and as a biomarker of success. GSD-Ia can also serve as a model for other hepatic monogenic disorders.
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