BackgroundIdiopathic pulmonary fibrosis (IPF) is an adult-onset Idiopathic Interstitial Pneumonia (IIP) usually diagnosed between age 50 to 70 years. Individuals with Familial Pulmonary Fibrosis (FPF) have at least one affected first or second-degree relative and account for 0.5-20% of cases.MethodsWe ascertained and collected DNA samples from a large population-based cohort of IPF patients from Newfoundland, Canada. For each proband, a family history was documented and medical records were reviewed. Each proband was classified as familial (28 patients) or sporadic (50 patients) and all 78 probands were screened for variants in four highly penetrant, adult-onset PF genes (SFTPC, SFTPA2, TERT,TERC).ResultsSeventy-eight IPF probands were enrolled of whom 28 (35.9%) had a positive family history. These 28 familial patients led to the recruitment of an additional 49 affected relatives (total of 77 FPF patients). By age 60 years, 42% of the familial cohort had been diagnosed with PF compared with only 16% of the sporadic patient collection (χ2 = 8.77, p = 0.003). Mean age of diagnosis in the familial group was significantly younger than the sporadic group (61.4 years vs. 66.6 yrs, p = 0.012) with a wider age range of diagnosis (19–92 years compared with 47–82 years). Thirty-three of 77 (42.8%) FPF patients had a tissue diagnosis and all but five had usual interstitial pneumonia histology. Compared with other published case series, the familial IIP histologies were more homogeneous. Three of 28 familial probands (10.7%) and none of the 50 sporadic probands had pathogenic variants in the four genes tested. All three familial probands had mutations in TERT. Other phenotypes associated with telomerase deficiency were present in these families including cirrhosis, bone marrow hypoplasia and premature graying. Telomere length assays were performed on mutation carriers from two families and confirmed telomere-related deficiency.ConclusionThe proportion of familial cases in our cohort is higher than any previously reported estimate and we suggest that this is due to the fact that Newfoundland cohort is ethnically homogeneous and drawn from a founder population. In our patient collection, diagnosis with IPF prior to age 45 years predicted familial disease. In two of the three TERT mutation families, the pedigree appearance is consistent with genetic anticipation. In the other 25 FPF families negative for mutations in known PF genes, we did not identify other telomerase associated medical problems (bone marrow dysfunction, cirrhosis) and we hypothesize that there are novel PF genes segregating in our population.

A recent report detailed the occurrence of both somatic and constitutional variants in the GALNT12 gene, located at 9q22.33, in some colorectal cancer (CRC) patients. In this study, we investigate the occurrence of inherited deleterious variants in GALNT12 in 118 families referred to a cancer genetics clinic. We discovered two deleterious variants (c.907G>A (p.Asp303Asn); c.1187A>G (p.Tyr396Cys)) in 4/118 probands. The variants, which were not found in 149 control individuals (P = 0.0376), cosegregate with CRC and/or adenomatous polyps in other family members. The probability by chance that cosegregation of c.907G>A with CRC and/or adenomatous polyps occurred, in the two pedigrees combined, was 1.56%. Although this study does not provide irrefutable evidence that GALNT12 variants are highly penetrant alleles that predispose to CRC in the majority of unexplained hereditary CRC families, it does provide additional evidence to support an important role of these variants in a proportion of this considerable high-risk group.

A novel missense mutation in the pore-forming region of the sodium channel gene SCN1A causes GEFS+ with a variable phenotype that includes mood and anxiety disorders, as well as ataxia, expanding the GEFS+ spectrum to include neuropsychiatric disease.

BackgroundSevere congenital neutropenia type 4 (SCN4) is an autosomal recessive disorder caused by mutations in the third subunit of the enzyme glucose-6-phosphatase (G6PC3). Its core features are congenital neutropenia and a prominent venous skin pattern, and affected individuals have variable birth defects. Oculocutaneous albinism type 4 (OCA4) is caused by autosomal recessive mutations in SLC45A2.MethodsWe report a sister and brother from Newfoundland, Canada with complex phenotypes. The sister was previously reported by Cullinane et al., 2011. We performed homozygosity mapping, next generation sequencing and conventional Sanger sequencing to identify mutations that cause the phenotype in this family. We have also summarized clinical data from 49 previously reported SCN4 cases with overlapping phenotypes and interpret the medical histories of these siblings in the context of the literature.ResultsThe siblings’ phenotype is due in part to a homozygous mutation in G6PC3, [c.829C > T, p.Gln277X]. Their ages are 38 and 37 years respectively and they are the oldest SCN4 patients published to date. Both presented with congenital neutropenia and later developed Crohn disease. We suggest that the latter is a previously unrecognized SCN4 manifestation and that not all affected individuals have an intellectual disability. The sister also has a homozygous mutation in SLC45A2, which explains her severe oculocutaneous hypopigmentation. Her brother carried one SLC45A2 mutation and was diagnosed with “partial OCA” in childhood.ConclusionsThis family highlights that apparently novel syndromes can in fact be caused by two known autosomal recessive disorders.

Background: In March 2016, an Enhanced Recovery After Surgery (ERAS) initiative was implemented for all elective colorectal resections at an urban hospital in St. John's, Newfoundland and Labrador, Canada. An ERAS coordinator supervised and enforced guideline compliance for 6 months. The aim of this study was to evaluate the sustainability of the ERAS program after supervision of guideline compliance was eliminated. Methods: Patient outcomes and guideline compliance were compared between surgeries performed under standard practice (April 2014 to March 2015) and those performed during and after the implementation of the ERAS initiative (March 2016 to August 2016 was the implementation phase and September 2016 to February 2017 was the sustainability phase). Results: Hospital length of stay decreased from 7.26 days at baseline to 5.44 days during the implementation phase of the ERAS program (p < 0.001). There was no significant difference between length of stay at baseline and during the 6-month sustainability phase of the ERAS program (7.10 d). There were no significant differences in rates of readmission or mortality during and after implementation. Rate of ileus decreased significantly from 13.8% during the implementation phase to 4.6% during the sustainability phase (p = 0.036). Total guideline compliance increased from 52.2% at baseline to 80.7% during the implementation phase (p < 0.001), and decreased to 74.7% during the sustainability phase (p < 0.001). Adherence to postoperative guidelines regressed: 79.2% in the implementation phase and 68.6% in the sustainability phase (p < 0.001). Conclusion: Hospital length of stay decreased when the ERAS program was implemented and the ERAS coordinator was present on the surgical ward. Methods for sustaining guideline implementation are vital to the success of similar programs in the future. Contexte : En mars 2016, une initiative de récupération améliorée après la chirurgie (RAAC) a été mise en place pour toutes les résections colorectales électives effectuées dans un hôpital

Introduction While numerous guidelines do not recommend preoperative tests for low risk patients undergoing low risk surgeries, they are often routinely performed. Canadian data suggests preoperative tests (e.g. ECGs and chest x-rays) preceded 17.9%-35.5% of low-risk procedures. Translating guidelines into clinical practice can be challenging and it is important to understand what is driving behaviour when developing interventions to change it. Aim Thus, we completed a theory-based investigation of the perceived barriers and enablers to reducing unnecessary preoperative tests for low-risk surgical procedures in Newfoundland, Canada. Method We used snowball sampling to recruit surgeons, anaesthesiologists, or preoperative clinic nurses. Interviews were conducted by two researchers using an interview guide with 31 questions based on the theoretical domains framework. Data was transcribed and coded into the 14 theoretical domains and then themes were identified for each domain. Results We interviewed 17 surgeons, anaesthesiologists, or preoperative clinic nurses with 1 to 34 years’ experience. Overall, while respondents agreed with the guidelines they described several factors, across seven relevant theoretical domains, that influence whether tests are ordered. The most common included uncertainty about who is responsible for test ordering, inability to access patient records or to consult/communicate with colleagues about ordering decisions and worry about surgery delays/cancellation if tests are not ordered. Other factors included workplace norms that conflicted with guidelines and concerns about missing something serious or litigation. In terms of enablers, respondents believed that clear institutional guidelines including who is responsible for test ordering and information about the risk of missing something serious, supported by improved communication between those involved in the ordering process and periodic evaluation will reduce any unnecessary preoperative testing. Conclusion These findings suggest that both health system and health provider factors need to be addressed in an intervention to reduce pre-operative testing.

Background Low back pain (LBP) is a leading cause of disability and is among the top five reasons that patients visit their family doctors. Over-imaging for non-specific low back pain remains a problem in primary care. To inform a larger study to develop and evaluate a theory-based intervention to reduce inappropriate imaging, we completed an assessment of the barriers and facilitators to reducing unnecessary imaging for NSLBP among family doctors in Newfoundland and Labrador (NL). Methods This was an exploratory, qualitative study describing family doctors’ experiences and practices related to diagnostic imaging for non-specific LBP in NL, guided by the Theoretical Domains Framework (TDF). Data were collected using in-depth, semi-structured interviews. Transcripts were analyzed deductively (assigning text to one or more domains) and inductively (generating themes at each of the domains) before the results were examined to determine which domains should be targeted to reduce imaging. Results Nine family doctors (four males; five females) working in community (n = 4) and academic (n = 5) clinics in both rural (n = 6) and urban (n = 3) settings participated in this study. We found five barriers to reducing imaging for patients with NSLBP: 1) negative consequences, 2) patient demand 3) health system organization, 4) time, and 5) access to resources. These were related to the following domains: 1) beliefs about consequences, 2) beliefs about capabilities, 3) emotion, 4) reinforcement, 5) environmental context and resources, 6) social influences, and 7) behavioural regulation. Conclusions Family physicians a) fear that if they do not image they may miss something serious, b) face significant patient demand for imaging, c) are working in a system that encourages unnecessary imaging, d) don’t have enough time to counsel patients about why they don’t need imaging, and e) lack access to appropriate practitioners, community programs, and treatment modalities to prescribe to their patients. These barriers were related to seven TDF domains. Successfully reducing inappropriate imaging requires a comprehensive intervention that addresses these barriers using established behaviour change techniques. These techniques should be matched directly to relevant TDF domains. The results of our study represent the important first step of this process – identifying the contextual barriers and the domains to which they are related.

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