Allied health professional support for children and young adults living in and leaving care: A systematic scoping review.

BACKGROUND: Children and young people living in and leaving care are known to have experienced significant childhood adversity and trauma resulting in potentially deleterious impact on their health and well-being across the life course. Studies point to the complex needs of this population who may benefit from allied health professional (AHP)-related support with limited studies located. This review sought to address this gap by systematically scoping empirical literature focused on the provision of AHP support to this cohort of children and young adults to assist an understanding of the service needs for this vulnerable population. METHODS: This scoping review followed Arskey and O'Malley's five steps framework (2005) to identify and review relevant literature. A focus on identifying the evidence, challenges and gaps in research relating to AHP support for children and young people living in and leaving care was initially agreed, followed by a systematic search using a combination of three key concepts to identify relevant studies in five AHP disciplinary areas to identify best evidence in the past decade (2011-2021). Study inclusion criteria were based on empirical studies of children and young people living in care (0-17 years) and leaving care (18-25 years). A data extraction table was formulated as a means of charting the data, aligned with the scope and objectives of this review. Finally, data were subsequently collated, synthesised and reported based on key thematic areas emerging from included studies regarding AHP support to children and young people living in and leaving care. RESULTS: A total of 13 studies met the review inclusion criteria. Included studies reported specifically on speech and language therapist (SLT; n = 5), occupational therapist (OT; n = 3) and arts-based therapies (n = 5). No studies were identified with regard to the use of physiotherapy and dietetics with this population. Results indicated that children and young people living in and leaving care have high rates of speech, language, communication and sensory needs. More rigorous screening, assessment and early intervention were identified as essential for this vulnerable group. Increased multidisciplinary collaboration and OT support for young adults in preparation for transition to independent living was identified as an urgent requirement. Included studies indicate promising results in relation to access to arts-based therapies with particular reference to identity formation for children and young people living in and leaving care. CONCLUSIONS: Although evidence of effectiveness remains limited, AHP service provision (specifically speech and language therapy, occupational therapy and arts-based therapies) has the potential to contribute positively to addressing the complex and interacting needs of this vulnerable population. As a result, it is recommended that AHP service provision is integrated into the collaborative, multidisciplinary care available to children living in and leaving care. More extensive, higher quality research related to the benefits of AHP provision for this population of children and young people is essential to provide a more robust evidence base across the various professional disciplines that constitute allied health provision.

Trauma Informed Child Welfare Systems-A Rapid Evidence Review.

Trauma informed care (TIC) is a whole system organisational change process which emerged from the seminal Adverse Childhood Experiences (ACE) study, establishing a strong graded relationship between the number of childhood adversities experienced and a range of negative outcomes across multiple domains over the life course. To date, there has been no systematic review of organisation-wide implementation initiatives in the child welfare system. As part of a wider cross-system rapid evidence review of the trauma-informed implementation literature using systematic search, screening and review procedures, twenty-one papers reporting on trauma-informed implementation in the child welfare system at state/regional and organisational/agency levels were identified. This paper presents a narrative synthesis of the various implementation strategies and components used across child welfare initiatives, with associated evidence of effectiveness. Training was the TIC implementation component most frequently evaluated with all studies reporting positive impact on staff knowledge, skills and/or confidence. The development of trauma-informed screening processes, and evidence-based treatments/trauma focused services, where evaluated, all produced positive results. Whilst weaknesses in study design often limited generalisability, there was preliminary evidence for the efficacy of trauma-informed approaches in improving the mental and emotional well-being of children served by community-based child welfare services, as well as their potential for reducing caregiver stress and improving placement stability.

Identification and validation of colorectal neoplasia-specific methylation markers for accurate classification of disease.

Aberrant DNA methylation occurs early in oncogenesis, is stable, and can be assayed in tissues and body fluids. Therefore, genes with aberrant methylation can provide clues for understanding tumor pathways and are attractive candidates for detection of early neoplastic events. Identification of sequences that optimally discriminate cancer from other diseased and healthy tissues is needed to advance both approaches. Using well-characterized specimens, genome-wide methylation techniques were used to identify candidate markers specific for colorectal neoplasia. To further validate 30 of these candidates from genome-wide analysis and 13 literature-derived genes, including genes involved in cancer and others with unknown functions, a high-throughput methylation-specific oligonucleotide microarray was used. The arrays were probed with bisulfite-converted DNA from 89 colorectal adenocarcinomas, 55 colorectal polyps, 31 inflammatory bowel disease, 115 extracolonic cancers, and 67 healthy tissues. The 20 most discriminating markers were highly methylated in colorectal neoplasia (area under the receiver operating characteristic curve > 0.8; P < 0.0001). Normal epithelium and extracolonic cancers revealed significantly lower methylation. Real-time PCR assays developed for 11 markers were tested on an independent set of 149 samples from colorectal adenocarcinomas, other diseases, and healthy tissues. Microarray results could be reproduced for 10 of 11 marker assays, including eight of the most discriminating markers (area under the receiver operating characteristic curve > 0.72; P < 0.009). The markers with high specificity for colorectal cancer have potential as blood-based screening markers whereas markers that are specific for multiple cancers could potentially be used as prognostic indicators, as biomarkers for therapeutic response monitoring or other diagnostic applications, compelling further investigation into their use in clinical testing and overall roles in tumorigenesis.

Much More Than PTSD: Mothers' Narratives of the Impact of Trauma on Child Survivors and Their Families.

This study examined the narratives of ten Caucasian mothers whose children had been impacted by 'traumatic' events and referred to a specialist trauma service in N. Ireland. The research question was whether the PTSD construct adequately represented the broad 'lived' experience of the impact of trauma on survivors' wellbeing and their family relationships as articulated by mothers post trauma. Narrative Interviewing methodology was employed and the resulting data inductively organised into an evolving thematic framework. A quantitative analysis of the prevalence of particular themes is presented supplemented by qualitative quotations to illustrate the complexity of reported impact. The major components of the mothers' narratives included family and relational distress (35.7%), non-pathological individual distress (24.4%), resilience (16.7%) and a prior history of adversity (16.6%). Prior history of adversity was resent in 8 out the 10 cases including a high level of suicide. PTSD symptomatology constituted a small proportion of the narratives (6.6%) and this suggests that the PTSD construct does not adequately represent the broad 'lived' experience of the impact of trauma. Although a small and heterogeneous study sample, the findings are sufficiently robust to suggest further investigation is required to understand the phenomenological experience of trauma of child victims/survivors and their families.

A real-time PCR assay for DNA-methylation using methylation-specific blockers.

DNA methylation-based biomarkers have been discovered that could potentially be used for the diagnosis of cancer by detection of circulating, tumor-derived DNA in bodily fluids. Any methylation detection assay that would be applied to these samples must be capable of detecting small amounts of tumor DNA in the presence of background normal DNA. We have developed a real-time PCR assay, called HeavyMethyl, that is well suited for this application. HeavyMethyl uses methylation-specific oligonucleotide blockers and a methylation-specific probe to achieve methylation-specific amplification and detection. We tested the assays on unmethylated and artificially methylated DNA in order to determine the limit of detection. After careful optimization, our glutathione-S-transferase pi1 and Calcitonin assays can amplify as little as 30 and 60 pg of methylated DNA, respectively, and neither assay amplifies unmethylated DNA. The Calcitonin assay showed a highly significant methylation difference between normal colon and colon adenocarcinomas, and methylation was also detected in serum DNA from colon cancer patients. These assays show that HeavyMethyl technology can be successfully employed for the analysis of very low concentrations of methylated DNA, e.g. in serum of patients with tumors.

Hypermethylation of the TPEF/HPP1 gene in primary and metastatic colorectal cancers.

The role of promoter methylation in the process of cancer cell metastasis has, however, not yet been studied. Recently, methylation of the TPEF (transmembrane protein containing epidermal growth factor and follistatin domain) gene was reported in human colon, gastric, and bladder cancer cells. Using the Methylight assay, TPEF/HPP1 gene methylation was assessed in primary colorectal cancers (n = 47), matched normal colon mucosa, as well as in the liver metastasis of 24 patients with colorectal cancer, and compared to the methylation status of the TIMP-3, APC, DAPK, caveolin-2, and p16 genes. TPEF was frequently methylated in primary colorectal cancers (36 of 47) compared to the normal colon mucosa (1 of 21) (P < .0001), and TPEF mRNA expression in colon cancer cell lines was restored after treatment with 5-aza-2'-deoxycytidine. The p16 and APC genes were also frequently methylated in primary colorectal cancers (P < .02) compared to the normal colon mucosa. Interestingly, promoter methylation was significantly more frequent in proximal, nonrectal cancers (P < .05). Furthermore, a high degree of methylation of the TPEF gene was also observed in liver metastasis (19 of 24). In summary, we observed frequent TPEF methylation in primary colorectal cancers and liver metastases, indicating that epigenetic alterations are not only present in the early phases of carcinogenesis, but are also common in metastatic lesions. The high frequency of TPEF methylation in this series of colorectal cancers underscores the importance of epigenetic changes as targets for the development of molecular tests for cancer diagnosis.

Defective C-propeptides of the proalpha2(I) chain of type I procollagen impede molecular assembly and result in osteogenesis imperfecta.

Type I procollagen is a heterotrimer composed of two proalpha1(I) chains and one proalpha2(I) chain, encoded by the COL1A1 and COL1A2 genes, respectively. Mutations in these genes usually lead to dominantly inherited forms of osteogenesis imperfecta (OI) by altering the triple helical domains, but a few affect sequences in the proalpha1(I) C-terminal propeptide (C-propeptide), and one, which has a phenotype only in homozygotes, alters the proalpha2(I) C-propeptide. Here we describe four dominant mutations in the COL1A2 gene that alter sequences of the proalpha2(I) C-propeptide in individuals with clinical features of a milder form of the disease, OI type IV. Three of the four appear to interfere with disulfide bonds that stabilize the C-propeptide conformation and its interaction with other chains in the trimer. Cultured cells synthesized proalpha2(I) chains that were slow to assemble with proalpha1(I) chains to form heterotrimers and that were retained intracellularly. Some alterations led to the uncharacteristic formation of proalpha1(I) homotrimers. These findings show that the C-propeptide of proalpha2(I), like that of the proalpha1(I) C-propeptide, is essential for efficient assembly of type I procollagen heterotrimers. The milder OI phenotypes likely reflect a diminished amount of normal type I procollagen, small populations of overmodified heterotrimers, and proalpha1(I) homotrimers that are compatible with normal skeletal growth.

Aristaless-like homeobox-4 gene methylation is a potential marker for colorectal adenocarcinomas.

BACKGROUND & AIMS: The identification of novel genetic and epigenetic markers indicative of changes in the pathogenesis of colon cancer, along with easier-to-use, more sensitive assay methods, may improve the detection, treatment, and overall prognosis of this malignancy. METHODS: Using methylation-specific arbitrarily primed polymerase chain reaction, a fragment of the Aristaless-like homeobox-4 (ALX4) gene that was highly methylated in colon adenomas and cancer was identified. Methylation of ALX4 was analyzed in colorectal adenomas and cancers, in the liver metastases of patients with colorectal cancer, and in 61 other neoplasias, including gastric, esophageal, and hepatocellular cancer and cholangiocarcinoma. ALX4 methylation was also analyzed in the serum of 30 patients with colon cancer. RESULTS: ALX4 gene methylation was confirmed in colon adenomas (11/13) and more frequently present in primary colorectal cancers (30/47) compared with the normal colon mucosa (0/21) (P < .0001). In addition, ALX4 methylation was frequently observed in adenocarcinomas of the esophagus (12/14), stomach (11/15), and bile ducts (4/5) compared with all other cancers (P < .001). ALX4 gene methylation was also more frequently found in sera of patients with colon cancer compared with noncancer controls (P < .0001). Using a cutoff of 41.4 pg/mL, sensitivity and specificity were 83.3% and 70%, respectively. CONCLUSIONS: Apart from colon adenomas and primary and metastatic colorectal cancers, ALX4 is frequently methylated in adenocarcinomas of the gastrointestinal tract. ALX4 gene methylation in sera of patients with cancer may thus serve as a methylation-specific test for colon and other gastrointestinal cancers.