Regional Anesthesia as an Alternative to Moderate Sedation for Perioperative Pain Control for Percutaneous Gastrostomy Tube Placement.

Percutaneous gastrostomy tube placement is typically performed under moderate sedation. However, some patients are not ideal candidates for moderate sedation because of respiratory compromise, difficult airways, or other factors. The purpose of this study was to evaluate regional anesthesia as an alternative to moderate sedation. A retrospective review of patients who underwent percutaneous gastrostomy tube placement between March 2014 and September 2020 was performed. Data on patient demographics, anesthesia type, pain scores, and opiate usage were collected. A total of 189 patients were included in the study; 35 (18.5%) received regional anesthesia and 154 received moderate sedation. Patients in the regional anesthesia group tolerated the procedure well, with lower mean immediate postprocedural and maximal pain scores of 0.7 vs 2.2 (P = .011) and 4.3 vs 6.5 (P = .003), respectively. Regional anesthesia is effective at controlling perioperative pain and is an alternative with a low complication rate for patients who cannot tolerate moderate sedation.

Developing a mHealth Routine Outcome Monitoring and Feedback App ("SMART Track") to Support Self-Management of Addictive Behaviours.

Background: Routine outcome monitoring (ROM) has been implemented across a range of addiction treatment services, settings and organisations. Mutual support groups are a notable exception. Innovative solutions are needed. SMART Track is a purpose built smartphone app designed to capture ROM data and provide tailored feedback to adults attending Australian SMART Recovery groups for addictive behaviour(s). Objective: Details regarding the formative stage of app development is essential, but often neglected. Improved consideration of the end-user is vital for curtailing app attrition and enhancing engagement. This paper provides a pragmatic example of how principles embedded in published frameworks can be operationalised to address these priorities during the design and development of the SMART Track app. Methods: Three published frameworks for creating digital health technologies ("Person-Based Approach," "BIT" Model and IDEAS framework) were integrated and applied across two stages of research to inform the development, design and content of SMART Track. These frameworks were chosen to ensure that SMART Track was informed by the needs and preferences of the end-user ("Person-Based"); best practise recommendations for mHealth development ("BIT" Model) and a collaborative, iterative development process between the multi-disciplinary research team, app developers and end-users (IDEAS framework). Results: Stage one of the research process generated in-depth knowledge to inform app development, including a comprehensive set of aims (clinical, research/organisation, and usage); clear articulation of the target behaviour (self-monitoring of recovery related behaviours and experiences); relevant theory (self-determination and social control); appropriate behavioural strategies (e.g., behaviour change taxonomy and process motivators) and key factors that may influence engagement (e.g., transparency, relevance and trust). These findings were synthesised into guiding principles that were applied during stage two in an iterative approach to app design, content and development. Conclusions: This paper contributes new knowledge on important person-centred and theoretical considerations that underpin a novel ROM and feedback app for people with addictive behaviour(s). Although person-centred design and best-practise recommendations were employed, further research is needed to determine whether this leads to improved usage outcomes. Clinical Trial Registration: Pilot Trial: http://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377336.

F-18 FDG perfusion PET: intraprocedural assessment of the liver tumor ablation margin.

PURPOSE: To evaluate 18F-fluorodeoxyglucose (FDG) perfusion PET during FDG PET/CT-guided liver tumor microwave ablation procedures for assessing the ablation margin and correlating minimum margin measurements with local progression. METHODS: This IRB-approved, HIPAA-compliant study included 20 adult patients (11 M, 9 F; mean age 65) undergoing FDG PET/CT-guided liver microwave ablation to treat 31 FDG-avid tumors. Intraprocedural FDG perfusion PET was performed to assess the ablation margin. Intraprocedural decisions regarding overlapping ablations were recorded. Two readers retrospectively interpreted intraprocedural perfusion PET and postprocedural contrast-enhanced MRI. Assessability of the ablation margin and minimum margin measurements were recorded. Imaging follow-up for local progression ranged from 30 to 574 days (mean 310). Regression modeling of minimum margin measurements was performed. Hazard ratios were calculated to correlate an ablation margin threshold of 5 mm with outcomes. RESULTS: Intraprocedural perfusion PET prompted additional overlapping ablations of two tumors, neither of which progressed. Incomplete ablation or local progression occurred in 8/31 (26%) tumors. With repeat ablation, secondary efficacy was 26 (84%) of 31. Both study readers deemed ablation margins fully assessable more often using perfusion PET than MRI (OR 69.7; CI 6.0, 806.6; p = 0.001). Minimum ablation margins ≥ 5 mm on perfusion PET correlated with a low risk of incomplete ablation/local progression by both study readers (HR 0.08 and 0.02, p < 0.001). CONCLUSION: Intraprocedural FDG perfusion PET consistently enabled complete liver tumor microwave ablation margin assessments, and the perfusion PET minimum ablation margin measurements correlated well with local outcomes. Clinical trial registration clinicaltrials.gov (NCT02018107).

Healthy beginnings: a system of care for children in Atlanta.

For more than a decade the Annie E. Casey Foundation's Atlanta Civic Site has invested in a comprehensive community change strategy in five neighborhoods near downtown Atlanta. The foundation pursues a three-prong strategy focused on improving educational outcomes for children, encouraging family economic success for adults, and positively transforming the community's physical environment. The foundation recently integrated a focus on health into its community and family strengthening strategies. In this article we review the foundation's Healthy Beginnings System of Care. Healthy Beginnings seeks to prevent or reduce health disparities through a community-based, coordinated care approach based in a high-quality early learning center. An initial evaluation found that in 2013 the program exceeded all of its performance requirements for the 279 enrolled children. Ninety-seven percent of the children had health insurance, 92 percent were up to date with immunizations, and 98 percent were current with developmental screenings. By building upon the partnerships formed through the foundation's community change effort, Healthy Beginnings has dramatically increased neighborhood children's access to health care and forms the basis for a cost-effective approach that can be replicated in other communities.

VAX1 mutation associated with microphthalmia, corpus callosum agenesis, and orofacial clefting: the first description of a VAX1 phenotype in humans.

Vax1 and Vax2 have been implicated in eye development and the closure of the choroid fissure in mice and zebrafish. We sequenced the coding exons of VAX1 and VAX2 in 70 patients with anophthalmia/microphthalmia (A/M). In VAX1, we observed homozygosity for two successive nucleotide substitutions c.453G>A and c.454C>A, predicting p.Arg152Ser, in a proband of Egyptian origin with microphthalmia, small optic nerves, cleft lip/palate, and corpus callosum agenesis. This mutation affects an invariant residue in the homeodomain of VAX1 and was absent from 96 Egyptian controls. It is likely that the mutation results in a loss of function, as the mutation results in a phenotype similar to the Vax1 homozygous null mouse. We did not identify any mutations in VAX2. This is the first description of a phenotype associated with a VAX1 mutation in humans and establishes VAX1 as a new causative gene for A/M.

Manitoba-oculo-tricho-anal (MOTA) syndrome is caused by mutations in FREM1.

BACKGROUND: Manitoba-oculo-tricho-anal (MOTA) syndrome is a rare condition defined by eyelid colobomas, cryptophthalmos and anophthalmia/microphthalmia, an aberrant hairline, a bifid or broad nasal tip, and gastrointestinal anomalies such as omphalocele and anal stenosis. Autosomal recessive inheritance had been assumed because of consanguinity in the Oji-Cre population of Manitoba and reports of affected siblings, but no locus or cytogenetic aberration had previously been described. METHODS AND RESULTS: This study shows that MOTA syndrome is caused by mutations in FREM1, a gene previously mutated in bifid nose, renal agenesis, and anorectal malformations (BNAR) syndrome. MOTA syndrome and BNAR syndrome can therefore be considered as part of a phenotypic spectrum that is similar to, but distinct from and less severe than, Fraser syndrome. Re-examination of Frem1(bat/bat) mutant mice found new evidence that Frem1 is involved in anal and craniofacial development, with anal prolapse, eyelid colobomas, telecanthus, a shortened snout and reduced philtral height present in the mutant mice, similar to the human phenotype in MOTA syndrome. CONCLUSIONS: The milder phenotypes associated with FREM1 deficiency in humans (MOTA syndrome and BNAR syndrome) compared to that resulting from FRAS1 and FREM2 loss of function (Fraser syndrome) are also consistent with the less severe phenotypes resulting from Frem1 loss of function in mice. Together, Fraser, BNAR and MOTA syndromes constitute a clinically overlapping group of FRAS-FREM complex diseases.

A male with unilateral microphthalmia reveals a role for TMX3 in eye development.

Anophthalmia and microphthalmia are important birth defects, but their pathogenesis remains incompletely understood. We studied a patient with severe unilateral microphthalmia who had a 2.7 Mb deletion at chromosome 18q22.1 that was inherited from his mother. In-situ hybridization showed that one of the deleted genes, TMX3, was expressed in the retinal neuroepithelium and lens epithelium in the developing murine eye. We re-sequenced TMX3 in 162 patients with anophthalmia or microphthalmia, and found two missense substitutions in unrelated patients: c.116G>A, predicting p.Arg39Gln, in a male with unilateral microphthalmia and retinal coloboma, and c.322G>A, predicting p.Asp108Asn, in a female with unilateral microphthalmia and severe micrognathia. We used two antisense morpholinos targeted against the zebrafish TMX3 orthologue, zgc:110025, to examine the effects of reduced gene expression in eye development. We noted that the morphant larvae resulting from both morpholinos had significantly smaller eye sizes and reduced labeling with islet-1 antibody directed against retinal ganglion cells at 2 days post fertilization. Co-injection of human wild type TMX3 mRNA rescued the small eye phenotype obtained with both morpholinos, whereas co-injection of human TMX3(p.Arg39Gln) mutant mRNA, analogous to the mutation in the patient with microphthalmia and coloboma, did not rescue the small eye phenotype. Our results show that haploinsufficiency for TMX3 results in a small eye phenotype and represents a novel genetic cause of microphthalmia and coloboma. Future experiments to determine if other thioredoxins are important in eye morphogenesis and to clarify the mechanism of function of TMX3 in eye development are warranted.

A maternally inherited chromosome 18q22.1 deletion in a male with late-presenting diaphragmatic hernia and microphthalmia-evaluation of DSEL as a candidate gene for the diaphragmatic defect.

Using an Affymetrix GeneChip(R) Human Mapping 100K Set to study a patient with a late-presenting, right-sided diaphragmatic hernia and microphthalmia, we found a maternally inherited deletion that was 2.7 Mb in size at chromosome 18q22.1. Mapping of this deletion using fluorescence in situ hybridization revealed three deleted genes-CDH19, DSEL, and TXNDC10, and one gene that contained the deletion breakpoint, CCDC102B. We selected DSEL for further study in 125 patients with diaphragmatic hernias, as it is involved in the synthesis of decorin, a protein that is required for normal collagen formation and that is upregulated during myogenesis. We found p.Met14Ile in an unrelated patient with a late-presenting, anterior diaphragmatic hernia. In the murine diaphragm, Dsel was only weakly expressed at the time of diaphragm closure and its expression in C2C12 myoblast cells did not change significantly during myoblast differentiation, thus reducing the likelihood that the gene is involved in myogenesis of the diaphragm. Although it is possible that the 18q22.1 deletion and haploinsufficiency for DSEL contributed to the diaphragmatic defect in the patient, a definite role for DSEL and decorin in the formation of the collagen-containing, central tendon of the diaphragm has not yet been established.