Course and predictors of excellent response to therapy in patients with differentiated thyroid cancer at long-term follow-up.

OBJECTIVES: To investigate the long-term outcomes of differentiated thyroid cancer (DTC) and the predictive factors for excellent and incomplete responses to therapy on long-term follow-up of patients. METHODS: A retrospective chart review and analysis was carried out at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Demographic, histological, and therapeutic data were collected from patients older than 13 years at the time of diagnosis, with a minimum follow-up of 18 months. Outcomes were divided into excellent, indeterminate, biochemically incomplete, and structurally incomplete responses. Odds ratios (ORs) for predictors of incomplete response at the last visit were determined. We first tested associations univariately with incomplete responses, and then variables with significant associations were included in a multivariable logistic model. RESULTS: Among 230 patients with DTC, 61.7% had excellent responses to therapy on long-term follow-up, and 24.3% had incomplete biochemical and structural responses. The median follow-up was 4.6 years. Factors significantly associated with incomplete response to therapy in the multivariate analysis (p<0.05) were age >55 years (OR=5) and lymph node (OR=3.4) and distant metastases (OR=29). Older age did not affect the outcome in low-risk patients with DTC but was significantly associated with incomplete responses in those with intermediate risk (p=0.04) and high risk (p=0.003). CONCLUSION: We strongly advocate incorporating age into recurrence risk assessment for patients with DTC.

Gaps in Referral to Bariatric Surgery for Patients With Type 2 Diabetes Seen in Endocrinology Clinics.

OBJECTIVES: One-third of adults in Canada are overweight and 26.8% experience obesity. Bariatric surgery confers effective weight loss and reduces obesity-related complications, including type 2 diabetes, but remains an underutilized treatment. Our objective in this study was to determine whether a gap exists in bariatric program referrals for patients with type 2 diabetes seen in endocrinology clinics at an ambulatory tertiary care hospital in Toronto, Canada. METHODS: A retrospective chart review was conducted of 843 consecutive patients with type 2 diabetes in endocrinology clinics between January 1, 2015 and December 31, 2020. Inclusion criteria were age ≥18 years, type 2 diabetes and body mass index (BMI)>35 kg/m2. Exclusion criteria were recent active cancer, uncontrolled psychiatric disease or active substance use disorder within 6 months of the initial visit. Referrals to bariatric surgery were assessed within a 5-year follow-up period and compared with baseline referral rates from the Ontario Bariatric Network (OBN). An online survey of 48 endocrinologists in Toronto, Ontario, was also conducted to assess physician-level barriers to referral. RESULTS: The proportion of patients with class II obesity (BMI>35 kg/m2) and type 2 diabetes meeting the eligibility criteria for bariatric referral was 4.6% (n=38). A documented discussion about bariatric surgery occurred with 7 (18.0%) of these eligible patients, and 1 patient (2.6%) was referred for surgery. Aside from surgical referrals, only 2.6% of eligible patients were referred to cognitive-behavioural therapy, 36.8% were initiated on obesity pharmacotherapy and 42.1% were referred to a dietitian. Baseline OBN data demonstrated that most surgical referrals (n=6,360) were from family physicians (65.0%) and only 8.8% were from a medical specialist. Eight percent of surveyed endocrinologists reported that they discussed bariatric surgery with at least half of their eligible patients. The most frequent barrier to discussing bariatric surgery during visits was time constraints. Physicians identified that simplifying the referral process and providing bariatric surgery handouts would be helpful interventions to improve referral rates. CONCLUSIONS: Our gap analysis demonstrated a low bariatric surgery referral rate by tertiary care endocrinologists. Our study also identified a large gap in the appropriate treatment of obesity with poor utilization of behavioural, lifestyle and pharmacotherapy practices. As obesity and diabetes rates increase, better education, training and knowledge translation will be necessary to overcome weight bias and prioritize obesity management.

Accuracy and efficiency of germline variant calling pipelines for human genome data.

Advances in next-generation sequencing technology have enabled whole genome sequencing (WGS) to be widely used for identification of causal variants in a spectrum of genetic-related disorders, and provided new insight into how genetic polymorphisms affect disease phenotypes. The development of different bioinformatics pipelines has continuously improved the variant analysis of WGS data. However, there is a necessity for a systematic performance comparison of these pipelines to provide guidance on the application of WGS-based scientific and clinical genomics. In this study, we evaluated the performance of three variant calling pipelines (GATK, DRAGEN and DeepVariant) using the Genome in a Bottle Consortium, "synthetic-diploid" and simulated WGS datasets. DRAGEN and DeepVariant show better accuracy in SNP and indel calling, with no significant differences in their F1-score. DRAGEN platform offers accuracy, flexibility and a highly-efficient execution speed, and therefore superior performance in the analysis of WGS data on a large scale. The combination of DRAGEN and DeepVariant also suggests a good balance of accuracy and efficiency as an alternative solution for germline variant detection in further applications. Our results facilitate the standardization of benchmarking analysis of bioinformatics pipelines for reliable variant detection, which is critical in genetics-based medical research and clinical applications.

Norwegian e-Infrastructure for Life Sciences (NeLS).

The Norwegian e-Infrastructure for Life Sciences (NeLS) has been developed by ELIXIR Norway to provide its users with a system enabling data storage, sharing, and analysis in a project-oriented fashion. The system is available through easy-to-use web interfaces, including the Galaxy workbench for data analysis and workflow execution. Users confident with a command-line interface and programming may also access it through Secure Shell (SSH) and application programming interfaces (APIs).  NeLS has been in production since 2015, with training and support provided by the help desk of ELIXIR Norway. Through collaboration with NorSeq, the national consortium for high-throughput sequencing, an integrated service is offered so that sequencing data generated in a research project is provided to the involved researchers through NeLS. Sensitive data, such as individual genomic sequencing data, are handled using the TSD (Services for Sensitive Data) platform provided by Sigma2 and the University of Oslo. NeLS integrates national e-infrastructure storage and computing resources, and is also integrated with the SEEK platform in order to store large data files produced by experiments described in SEEK.   In this article, we outline the architecture of NeLS and discuss possible directions for further development.

GSuite HyperBrowser: integrative analysis of dataset collections across the genome and epigenome.

Background: Recent large-scale undertakings such as ENCODE and Roadmap Epigenomics have generated experimental data mapped to the human reference genome (as genomic tracks) representing a variety of functional elements across a large number of cell types. Despite the high potential value of these publicly available data for a broad variety of investigations, little attention has been given to the analytical methodology necessary for their widespread utilisation. Findings: We here present a first principled treatment of the analysis of collections of genomic tracks. We have developed novel computational and statistical methodology to permit comparative and confirmatory analyses across multiple and disparate data sources. We delineate a set of generic questions that are useful across a broad range of investigations and discuss the implications of choosing different statistical measures and null models. Examples include contrasting analyses across different tissues or diseases. The methodology has been implemented in a comprehensive open-source software system, the GSuite HyperBrowser. To make the functionality accessible to biologists, and to facilitate reproducible analysis, we have also developed a web-based interface providing an expertly guided and customizable way of utilizing the methodology. With this system, many novel biological questions can flexibly be posed and rapidly answered. Conclusions: Through a combination of streamlined data acquisition, interoperable representation of dataset collections, and customizable statistical analysis with guided setup and interpretation, the GSuite HyperBrowser represents a first comprehensive solution for integrative analysis of track collections across the genome and epigenome. The software is available at: https://hyperbrowser.uio.no.

Quality of life among adults with beta-thalassemia major in western Saudi Arabia.

OBJECTIVES: To assess the quality of life in the thalassemia adult patients and clarify how effective the management is of these patients and whether a change in care is warranted. METHODS: In this cross-sectional study, adult thalassemia patients (>18 years) of both genders, attending the day care unit in King Abdulaziz University Hospital, Jeedah, Saudi Arabia were surveyed using SF-36 questionnaire. Data were collected between October 2012 and December 2012. The questions highlighted 3 health status scales; physical functioning (PF), emotional functioning (EF), and social functioning (SF). Scores were analyzed using SPSS. RESULTS: Forty-eight adults were surveyed (mean+/-SD: 26.02+/-5.56). These were made up of 60.4% males and 41.7% were Saudis. The frequency of blood transfusion was every 3 weeks in 81.3% of patients, but 18.8% were having transfusions less frequently. Half of our sampled patients were splenectomized (54.2%). The PF score for the total sample was 61.4 (SD=22.7), the SF score was 75 (SD=26.4) and the EF score was 69.7 (SD= 21.6); the SF and EF scores were lower in females and non-Saudis compared to male Saudis. CONCLUSION: The PF score in our sample was low compared to other regional studies; the SF and EF scores were low in females and non-Saudis. 

Quality of life among children with beta-thalassemia major treated in Western Saudi Arabia.

OBJECTIVE: To assess the quality of life among children and adolescents with thalassemia major. METHODS: This cross-sectional study used the Pediatric Quality of Life Inventory (PedsQL). Children and adolescents with beta-thalassemia major who attended the Day Care Unit at King Abdulaziz University Hospital, Jeddah, Saudi Arabia from October 2012 to February 2013 were surveyed. The questions highlighted 4 health status scales, namely physical functioning (PF), emotional functioning (EF), school performance (SC), and social functioning (SF). Scores were calculated for each patient and data were analyzed using the Statistical Package for Social Sciences. RESULTS: We recruited 46 children (60.9% males). The median age of the sample was 12 years (range, 2-18 years). Most patients (84.8%) had 3 weekly blood transfusions. The mean+/-SD physical functioning (PF) score was 57.2+/-25.9; the EF score was 74.1+/-20.3, SF score was 78.5+/-24, and SC score was 54.3+/-24.2. The PF score was significantly lower in patients with a family history of thalassemia (p=0.003), and in those whose families had low incomes (p=0.049). Conversely, the SF score was significantly higher in school-educated patients (p=0.01). CONCLUSION: The quality of life of thalassemic children is affected by multiple factors, such as family income and a family history of thalassemia. Education appeared to increase patient functionality. Supportive measures could improve the quality of life in thalassemic patients.