Impact of multidisciplinary team meetings on the management of patients with breast cancer in a large private healthcare facility.

AIMS: Multidisciplinary meetings (MDMs) play a crucial role in decision-making in breast cancer patient care. This study aimed to firstly assess the impact of breast cancer MDMs in decision-making for breast cancer patients and secondly to determine the concordance between MDM recommendations and implementation of clinical practice. METHODS: Patient cases to be presented at the weekly breast cancer MDMs were identified and prospectively enrolled. Management plans were predicted by the treating surgeon with the pre-MDM management plans then compared to MDM recommendations. Changes in decision-making were assessed in the following domains: further surgery, systemic therapy (endocrine, chemotherapy or targeted), radiotherapy, enrolment in a clinical trial, further investigations, and referral to other specialists or services. Patient records were subsequently reviewed at 3 months post-MDM to assess the rate of implementation of MDM recommendations and any reasons for discordance. RESULTS: Out of 50 cases, 66% (CI 53-79%; p < .005) experienced a change in management plan as a result of MDM discussion, with a total of 66 episodes of recorded change per decision-making domain affecting the following: further surgery (7.6%), endocrine therapy (4.5%), chemotherapy (19.7%), targeted therapy (4.5%), radiotherapy (18.2%), enrolment for a clinical trial (12.1%), additional investigations (22.7%), and further referrals (10.6%). MDM recommendations were implemented in 83.7% of cases. CONCLUSION: The breast cancer MDMs were found to substantially impact on the management plans for breast cancer patients, with 83.7% of MDM recommendations being implemented into clinical practice. This study reinforces the importance of MDMs in the management of these patients, as well as highlighting the need for further investigating and addressing the potential barriers to the implementation of MDM recommendations.

Datasets for the development of hemp (Cannabis sativa L.) as a crop for the future in tropical environments (Malaysia).

An evidence base was developed to facilitate adoption of hemp (Cannabis sativa L.) in tropical environments (Wimalasiri et al. (2021)). Agro-ecological requirements data of hemp were acquired from international databases and was contrasted against local climate and soil conditions using an augmented species ecological niche modeling. The outputs were then used to map the suitability for all locations for 12 possible calendar-year seasons within peninsular Malaysia. The most probable seasonal map was then used to generate a land suitability map for agricultural areas across 5 standard land suitability categories. Having developed the general suitability maps of hemp in Malaysia, detailed crop growth data were collected from literature and was then used to simulate an ideotype crop model (for both seed and fiber) for selected locations across Malaysia, where detailed daily climate data and soil information were available. Following the development of a downscaled future climate dataset, a simulated dataset of yield for the future conditions were also developed. Next, the simulated seed and fiber yield data were used to create yield maps for hemp across peninsular Malaysia. An economic value and cost-benefit analyses were also carried out using data that were collected from literature and local sources to simulate the true cost and benefit of growing hemp both for now and future conditions. This data provides the first ever evidence base for an underutilized crop in Southeast Asia. All data that was generated using the proposed published framework for the adoption of hemp in the future are stored in their original format in an online repository and is described in this article. The data can be used to map the suitability at finer scales, analyze and re-calibrate a yield model using any climate scenario and evaluate the economics of production using the standard methodology described in the above-mentioned publication.

The role of depression and other psychological factors in work ability among breast cancer survivors in Australia.

OBJECTIVE: Identifying modifiable factors affecting work ability among cancer survivors is important. The primary aim of the present study was to examine the effects of depression and related psychological factors on work ability among breast cancer survivors in Australia. METHODS: In this cross-sectional electronic and postal survey, Australian breast cancer survivors were investigated. Work status and conditions before and after cancer treatment were analysed. Work ability was measured using the Work Limitation Questionnaire©-Short Form (WLQ-SF) with its four domains (time management, physical tasks, mental-interpersonal tasks, and output tasks). Three psychological factors were investigated: depression, fear of cancer recurrence, and demoralisation. Sociodemographic and clinical data were also collected. Multivariate regression analysis was used to identify the associations of psychological factors with WLQ-SF. RESULTS: Among eligible survivors, 310 (50%) responded to the survey and were analysed. Nearly one third reported their work conditions had changed after cancer treatment. The depressed group reported limited work ability in 35%-44% of the four domains of WLQ-SF, while the non-depressed group reported limited work ability in only 8%-13%. At-work productivity loss was approximately fourfold higher in the depressed group than in the non-depressed group. In multivariate analysis, at-work productivity loss was associated with depression, demoralisation, and past history of anxiety. CONCLUSIONS: After breast cancer treatment, work conditions changed toward lower wages and working hours. Depression, demoralisation, and past history of anxiety were associated with lower work ability. Further evaluations of work rehabilitation in breast cancer survivors are warranted.

Dose escalated simultaneous integrated boost of gross nodal disease in gynecologic cancers: a multi-institutional retrospective analysis and review of the literature.

PURPOSE: Typical doses of 45-50.4 Gy used to treat regional nodes have demonstrated inadequate control of gross nodal disease (GND) in gynecologic cancer, and accelerated repopulation may limit the efficacy of a sequential boost. We reviewed outcomes of patients treated with a simultaneous integrated boost (SIB) at 2.25 Gy per fraction to positron emission tomography (PET) avid GND to evaluate toxicity and tumor control using this dose-escalated regimen. MATERIALS AND METHODS: A total of 83 patients with gynecologic cancer and PET avid inguinal, pelvic, or para-aortic lymphadenopathy were treated using intensity-modulated radiation therapy (IMRT) with SIB. Primary cancers were mostly cervical (51%) and endometrial (34%), and included patients who received concurrent chemotherapy (59%) and/or brachytherapy boost (78%). RESULTS: Median follow-up from radiation completion was 12.6 months (range, 2.7 to 92.9 months). Median dose to elective lymphatics was 50.4 Gy (range, 45 to 50.4 Gy) at 1.8 Gy/fraction. Median SIB dose and volume were 63 Gy (range, 56.3 to 63 Gy) and 72.8 mL (range, 6.8 to 1,134 mL) at 2-2.25 Gy/fraction. Nodal control was 97.6% in the SIB area while 90.4% in the low dose area (p = 0.013). SIB radiotherapy (RT) field failure-free, non-SIB RT field failure-free, and out of RT field failure-free survival at 4 years were 98%, 86%, and 51%, respectively. Acute and late grade ≥3 genitourinary toxicity rates were 0%. Acute and late grade ≥3 gastrointestinal toxicity rates were 7.2% and 12.0%, respectively. CONCLUSION: Dose escalated SIB to PET avid adenopathy results in excellent local control with acceptable toxicity.

Crop model ideotyping for agricultural diversification.

Evidence based crop diversification requires modelling for crops that are currently neglected or underutilised. Crop model calibration is a lengthy and resource consuming effort that is typically done for a particular variety or a set of varieties of a crop. Whilst calibration data are widely available for major crops, such data are rarely available for underutilised crops due to limited funding for detailed field data collection and model calibration. Subsequently, the lack of evidence on their performance will lead to the lack of interest from the policy and regulatory communities to include these crops in the agricultural development plans. In order to motivate further research into the use of state of the art techniques in modelling for less known crops, we have developed and validated an ideotyping technique that approximates the crop modelling parameters based on already calibrated crops of different lineage. The method has been successfully tested for hemp (Cannabis sativa L.) based on a well-known crop model. In this paper we present the method and provide an impetus on the way forward to further develop such methods for modelling the performance of minor crops and their varieties.•The approach works based on modelling the performance of hemp using the knowledge from an existing model that was developed for sugar cane.•The customisation uses one of the most prominent models (AquaCrop) to approximate growth coefficients for hemp (Cannabis sativa L.).•A sequential procedure was used to approximate the phenological stages in the growth model that performs well in the calibration and validation steps.

Evaluation of FGFR targeting in breast cancer through interrogation of patient-derived models.

BACKGROUND: Particular breast cancer subtypes pose a clinical challenge due to limited targeted therapeutic options and/or poor responses to the existing targeted therapies. While cell lines provide useful pre-clinical models, patient-derived xenografts (PDX) and organoids (PDO) provide significant advantages, including maintenance of genetic and phenotypic heterogeneity, 3D architecture and for PDX, tumor-stroma interactions. In this study, we applied an integrated multi-omic approach across panels of breast cancer PDXs and PDOs in order to identify candidate therapeutic targets, with a major focus on specific FGFRs. METHODS: MS-based phosphoproteomics, RNAseq, WES and Western blotting were used to characterize aberrantly activated protein kinases and effects of specific FGFR inhibitors. PDX and PDO were treated with the selective tyrosine kinase inhibitors AZD4547 (FGFR1-3) and BLU9931 (FGFR4). FGFR4 expression in cancer tissue samples and PDOs was assessed by immunohistochemistry. METABRIC and TCGA datasets were interrogated to identify specific FGFR alterations and their association with breast cancer subtype and patient survival. RESULTS: Phosphoproteomic profiling across 18 triple-negative breast cancers (TNBC) and 1 luminal B PDX revealed considerable heterogeneity in kinase activation, but 1/3 of PDX exhibited enhanced phosphorylation of FGFR1, FGFR2 or FGFR4. One TNBC PDX with high FGFR2 activation was exquisitely sensitive to AZD4547. Integrated 'omic analysis revealed a novel FGFR2-SKI fusion that comprised the majority of FGFR2 joined to the C-terminal region of SKI containing the coiled-coil domains. High FGFR4 phosphorylation characterized a luminal B PDX model and treatment with BLU9931 significantly decreased tumor growth. Phosphoproteomic and transcriptomic analyses confirmed on-target action of the two anti-FGFR drugs and also revealed novel effects on the spliceosome, metabolism and extracellular matrix (AZD4547) and RIG-I-like and NOD-like receptor signaling (BLU9931). Interrogation of public datasets revealed FGFR2 amplification, fusion or mutation in TNBC and other breast cancer subtypes, while FGFR4 overexpression and amplification occurred in all breast cancer subtypes and were associated with poor prognosis. Characterization of a PDO panel identified a luminal A PDO with high FGFR4 expression that was sensitive to BLU9931 treatment, further highlighting FGFR4 as a potential therapeutic target. CONCLUSIONS: This work highlights how patient-derived models of human breast cancer provide powerful platforms for therapeutic target identification and analysis of drug action, and also the potential of specific FGFRs, including FGFR4, as targets for precision treatment.

Open Data to Support Agricultural Diversification (version October 2020).

Following the development of a database that was specifically designed to store value chain information, particularly for underutilised crops, this article describes the data that are currently stored in the database and accessible through its web portal. The data includes various datasets on utilisation status, agro-ecological requirements and season lengths, potential yield and nutritional composition of crops. The data are stored in the form of tables with fixed data elements (column attributes). This article outlines the standard procedures (SOPs) that were developed in-house for data collection, metadata creation and data curation. These processes were used to ensure the quality and reusability of the data that is made available publicly through the database interface. Various statistics and example visualisations are provided to demonstrate the significance of such data for developing solutions for sustainable agricultural diversification.

Factitious Disorder (Munchausen Syndrome) in Plastic Surgery: A Systematic Review of 42 Cases.

INTRODUCTION: Patients with factitious disorder (FD) or "Munchausen syndrome" intentionally fabricate or induce medical problems for psychological gratification. They may deceive plastic surgeons into performing multiple unnecessary procedures. We undertook the first systematic review of FD case reports in plastic surgery. Our aims were 2-fold: (1) describe the adverse outcomes associated with these cases and (2) identify strategies for their prevention by surgeons. METHODS: MEDLINE, EMBASE, and SCOPUS databases were searched. We included cases in which an adult with FD presented to a plastic surgeon. Our search returned a total of 42 eligible cases reported from North America (43%), Europe (37%), and Asia (20%). RESULTS: Seventy-six percent of patients were women, and 62% worked in health care. Sixty percent had a comorbid psychiatric disorder, the most common (50%) being depression. Ninety-three percent of our sample presented with self-induced lesions. The average delay in diagnosis of FD was 54 months, with 46% of patients receiving multiple surgical procedures in this time, including debridement (36%) and skin grafts (39%). Surgical wounds were frequently exploited by patients to remain in, or return to, hospital: 50% contaminated or manipulated their wounds to prevent healing. Thirty-six percent of cases resulted in significant long-term disability (24%) or disfigurement (12%). Ten percent of patients received an amputation. Outcomes were improved when patients were confronted by surgeons, however, and 62% were willing to see a psychiatrist. Surgeons were able to support recovery in 33% of cases-for example, by using occlusive wound dressings. CONCLUSIONS: Patients with FD who present to plastic surgeons are high risk: the majority require surgical intervention for severe self-injury, and many engage in harmful behaviors, such as "doctor-shopping." Early recognition of FD in plastic surgery is, therefore, crucial and may be achieved via careful examination of lesions for unusual morphology. Medical records may reveal extensive health care service use and negative investigations. Finally, plastic surgeons may play an important role in managing such patients. Management strategies include direct observation by nursing staff in the postoperative period and use of strict occlusive dressings to prevent access to surgical wounds.

Dose escalated simultaneous integrated boost of gross nodal disease in gynecologic cancers: a multi-institutional retrospective analysis and review of the literature

Purpose@#Typical doses of 45–50.4 Gy used to treat regional nodes have demonstrated inadequate control of gross nodal disease (GND) in gynecologic cancer, and accelerated repopulation may limit the efficacy of a sequential boost. We reviewed outcomes of patients treated with a simultaneous integrated boost (SIB) at 2.25 Gy per fraction to positron emission tomography (PET) avid GND to evaluate toxicity and tumor control using this dose-escalated regimen. @*Materials and Methods@#A total of 83 patients with gynecologic cancer and PET avid inguinal, pelvic, or para-aortic lymphadenopathy were treated using intensity-modulated radiation therapy (IMRT) with SIB. Primary cancers were mostly cervical (51%) and endometrial (34%), and included patients who received concurrent chemotherapy (59%) and/or brachytherapy boost (78%). @*Results@#Median follow-up from radiation completion was 12.6 months (range, 2.7 to 92.9 months). Median dose to elective lymphatics was 50.4 Gy (range, 45 to 50.4 Gy) at 1.8 Gy/fraction. Median SIB dose and volume were 63 Gy (range, 56.3 to 63 Gy) and 72.8 mL (range, 6.8 to 1,134 mL) at 2–2.25 Gy/fraction. Nodal control was 97.6% in the SIB area while 90.4% in the low dose area (p = 0.013). SIB radiotherapy (RT) field failure-free, non-SIB RT field failure-free, and out of RT field failure-free survival at 4 years were 98%, 86%, and 51%, respectively. Acute and late grade ≥3 genitourinary toxicity rates were 0%. Acute and late grade ≥3 gastrointestinal toxicity rates were 7.2% and 12.0%, respectively. @*Conclusion@#Dose escalated SIB to PET avid adenopathy results in excellent local control with acceptable toxicity.

Dose escalated simultaneous integrated boost of gross nodal disease in gynecologic cancers: a multi-institutional retrospective analysis and review of the literature

Purpose@#Typical doses of 45–50.4 Gy used to treat regional nodes have demonstrated inadequate control of gross nodal disease (GND) in gynecologic cancer, and accelerated repopulation may limit the efficacy of a sequential boost. We reviewed outcomes of patients treated with a simultaneous integrated boost (SIB) at 2.25 Gy per fraction to positron emission tomography (PET) avid GND to evaluate toxicity and tumor control using this dose-escalated regimen. @*Materials and Methods@#A total of 83 patients with gynecologic cancer and PET avid inguinal, pelvic, or para-aortic lymphadenopathy were treated using intensity-modulated radiation therapy (IMRT) with SIB. Primary cancers were mostly cervical (51%) and endometrial (34%), and included patients who received concurrent chemotherapy (59%) and/or brachytherapy boost (78%). @*Results@#Median follow-up from radiation completion was 12.6 months (range, 2.7 to 92.9 months). Median dose to elective lymphatics was 50.4 Gy (range, 45 to 50.4 Gy) at 1.8 Gy/fraction. Median SIB dose and volume were 63 Gy (range, 56.3 to 63 Gy) and 72.8 mL (range, 6.8 to 1,134 mL) at 2–2.25 Gy/fraction. Nodal control was 97.6% in the SIB area while 90.4% in the low dose area (p = 0.013). SIB radiotherapy (RT) field failure-free, non-SIB RT field failure-free, and out of RT field failure-free survival at 4 years were 98%, 86%, and 51%, respectively. Acute and late grade ≥3 genitourinary toxicity rates were 0%. Acute and late grade ≥3 gastrointestinal toxicity rates were 7.2% and 12.0%, respectively. @*Conclusion@#Dose escalated SIB to PET avid adenopathy results in excellent local control with acceptable toxicity.

Direct Oral Anticoagulant Use and Risk of Diverticular Hemorrhage: A Systematic Review of the Literature.

Background: Anticoagulants carry a significant risk of gastrointestinal bleeding. With the increase in use and availability of direct oral anticoagulants ("DOACs") more data are available regarding the risks of these medications. With diverticular bleeds being common, and hospitalization associated with gastrointestinal bleed increasing 30-day mortality, it is paramount to better understand the potential risks of using DOACs in this population. Methods: A systematic review of the literature was undertaken, using the databases PubMed, EMBASE, Cochrane Library, and CINAHL. Two reviewers independently searched the literature, and initial screening was performed through title and abstract reading. Search terms included "direct" AND "anticoagulant" AND "diverticular bleed" OR "diverticular hemorrhage". The references of the selected studies were manually reviewed for any further relevant articles. Results: Literature search across the databases garnered 182 articles-157 unique abstracts after duplicate removal. Based on inclusion and exclusion criteria, 6 studies were deemed relevant. The selected studies' reference lists yielded no further relevant articles. Discussion: Across the 6 studies, the incidence of diverticular bleeding in patients using DOACs was extremely low. Of 23,990 patients taking DOACs identified from two separate institutions, only 60 were found to have diverticular hemorrhage. Similarly, among 15,056 patients with diverticular hemorrhage, only 246 (1.6%) among them were taking DOACs. Generally, the studies found no increased diverticular bleeding rate between patients taking DOACs and those who were taking other anticoagulants, such as warfarin, or the general population. The studies also did not find an increased risk of rebleeding with DOAC continuation. Conclusion: The evidence suggests the risk of diverticular bleed among DOAC users is equivocal to those not taking DOACs, and the overall incidence of diverticular bleed in the DOAC population is low. As it stands, the risk of thrombotic events from not starting DOACs apparently outweighs the risk of diverticular bleed.

Crops For the Future (CFF): an overview of research efforts in the adoption of underutilised species.

MAIN CONCLUSION: Crops For the Future (CFF), as an entity, has established a broad range of research activities to promote the improvement and adoption of currently underutilised crops. This paper summarises selected research activities at Crops For the Future (CFF) in pursuit of its mission 'to develop solutions for diversifying future agriculture using underutilised crops'. CFF is a research company focussed on the improvement of underutilised crops, so that they might be grown and consumed more widely with benefits to human food and nutritional security; its founding guarantors were the Government of Malaysia and the University of Nottingham. From its base in Malaysia, it engages in research around the world with a focus on species and system diversification. CFF has adopted a food system approach that adds value by delivering prototype food, feed and knowledge products. Bambara groundnut (Vigna subterranea) was adopted as an exemplar crop around which to develop CFF's food system approach with emphasis on the short-day photoperiod requirement for pod-filling and the hard-to-cook trait. Selective breeding has allowed the development of lines that are less susceptible to photoperiod but also provided a range of tools and approaches that are now being exploited in other crops such as winged bean (Psophocarpus tetragonolobus), amaranth (Amaranthus spp.), moringa (Moringa oleifera) and proso (Panicum miliaceum) and foxtail (Setaria italica) millets. CFF has developed and tested new food products and demonstrated that several crops can be used as feed for black soldier fly which can, in turn, be used to feed fish thereby reducing the need for fishmeal. Information about underutilised crops is widely dispersed; so, a major effort has been made to develop a knowledge base that can be interrogated and used to answer practical questions about potential exploitation of plant and nutritional characteristics. Future research will build on the success with Bambara groundnut and include topics such as urban agriculture, rural development and diversification, and the development of novel foods.

Glucose homeostasis dependency on acini-islet-acinar (AIA) axis communication: a new possible pathophysiological hypothesis regarding diabetes mellitus.

Studies have highlighted the existence of two intra-pancreatic axes of communication: one involved in the regulation of enzyme production by insulin-the insular-acinar axis; and another involved in the regulation of insulin release by pancreatic enzymes-the acini-insular axis. Previous studies by our laboratory show that pancreatic enzymes can affect blood glucose homeostasis and insulin secretion independently of their digestive functions, both from the gut lumen and probably from the blood. As a result we would like to introduce here the concept of acini-islet-acinar (AIA) axis communication (feedback), which could play an important role in the development of obesity and diabetes type 2. The AIA feedback links the endocrine and exocrine parts of the pancreas and emphasizes the essential role that the pancreas plays, as a single organ, in the regulation of glucose homeostasis by amylase most probably in gut epithelium and by insulin and glucagon in peripheral blood.

Relationship Between Glycated Hemoglobin and Stroke Risk: A Systematic Review and Meta-Analysis.

BACKGROUND: Diabetes mellitus is a major risk factor for ischemic stroke. Rising hemoglobin A1c (HbA1c) levels are associated with microvascular diabetes mellitus complication development; however, this relationship has not been established for stroke risk, a macrovascular complication. METHODS AND RESULTS: We conducted a systematic review and meta-analysis of observational cohort and nested case-control cohort studies assessing the association between rising HbA1c levels and stroke risk in adults (≥18 years old) with and without type 1 or type 2 diabetes mellitus. Random-effects model meta-analyses were used to calculate pooled adjusted hazard ratios (HRs) and their precision. The systematic review yielded 36 articles, of which 29 articles (comprising n=532 779 participants) were included in our meta-analysis. Compared to non-diabetes mellitus range HbA1c (<5.7%), diabetes mellitus range HbA1c (≥6.5%) was associated with an increased risk of first-ever stroke with average HR (95% confidence interval) of 2.15 (1.76, 2.63), whereas pre-diabetes mellitus range HbA1c (5.7-6.5%) was not (average HR [95% confidence interval], 1.19 [0.87, 1.62]). For every 1% HbA1c increment (or equivalent), the average HR (95% confidence interval) for first-ever stroke was 1.12 (0.91, 1.39) in non-diabetes mellitus cohorts and 1.17 (1.09, 1.25) in diabetes mellitus cohorts. For every 1% HbA1c increment, both non-diabetes mellitus and diabetes mellitus cohorts had a higher associated risk of first-ever ischemic stroke with average HR (95% confidence interval) of 1.49 (1.32, 1.69) and 1.24 (1.11, 1.39), respectively. CONCLUSIONS: A rising HbA1c level is associated with increased first-ever stroke risk in cohorts with a diabetes mellitus diagnosis and increased risk of first-ever ischemic stroke in non-diabetes mellitus cohorts. These findings suggest that more intensive HbA1c glycemic control targets may be required for optimal ischemic stroke prevention.

Hospitalizations due to self-poisoning at a Canadian paediatric hospital.

BACKGROUND: Adolescent self-harm by drug ingestion (i.e., self-poisoning) is a serious mental health issue. In Newfoundland and Labrador (NL), paediatricians suspected an increase in the number of adolescents hospitalized due to self-poisoning in the province. Our primary aim was to evaluate the number of hospital admissions of adolescents for self-poisoning between 2008 and 2013 to determine whether there was indeed an increase in hospitalizations. We also wanted to examine the characteristics of these admissions to better understand this patient population. METHOD: A retrospective chart review was conducted to identify cases of self-poisoning admitted to the only paediatric hospital in NL over a 6-year period. A data abstraction form was developed to collect patient demographic information and details about these incidences of self-poisoning. RESULTS: A total of 156 patient admissions were identified; 97 (62.2%) first time admissions and 59 (37.8%) recurrent admissions. The number of admissions for self-poisoning increased over the study period from 2.1% of total hospital admissions in 2008 to 6.5% in 2013. Mean (SD) age at the time of admission was 15.4 years, 122 patients (78.2%) were female and 86.5% had at least 1 previous mental health diagnosis. The most common drugs ingested were analgesics (38.0%) and antidepressants (32.2%), with 73 patients (48.7%) ingesting multiple drugs. CONCLUSIONS: The study contributes to the growing recognition of adolescent self-poisoning as a serious paediatric mental health issue. It also confirmed that an increase in adolescent hospitalizations due to self-poisoning has occurred in NL. Further research is warranted to identify effective prevention strategies for this serious problem.

Association of type 1 diabetes and concentrations of drinking water components in Newfoundland and Labrador, Canada.

OBJECTIVE: To determine the association between drinking water quality and rates of type 1 diabetes in the Newfoundland and Labrador (NL) population, which has one of the highest incidences of type 1 diabetes reported globally. RESEARCH DESIGN AND METHODS: The study used a community-based, case-control design. We first calculated incidence rates of type 1 diabetes at the provincial, regional and community levels. The connection between incidence rates and components in public water supplies were then analyzed in three ways: to evaluate differences in water quality between communities with and without incident cases of type 1 diabetes, and to analyze the relationship between water quality and incidence rates of type 1 diabetes at both the community and regional levels. RESULTS: The provincial incidence of type 1 diabetes was 51.7/100 000 (0-14 year age group) for the period studied. In the community-based analysis, there were significant associations found between higher concentrations of arsenic (ß=0.268, P=0.013) and fluoride (ß=0.202, P=0.005) in drinking water and higher incidence of type 1 diabetes. In the regional analysis, barium (ß=-0.478, P=0.009) and nickel (ß=-0.354, P=0.050) concentrations were negatively associated with incidence of type 1 diabetes. CONCLUSIONS: We confirmed the high incidence of type 1 diabetes in NL. We also found that concentrations of some components in drinking water were associated with higher incidence of type 1 diabetes, but no component was found to have a significant association across the three different levels of analysis performed.

Metabolic markers of protein maldigestion after a 15N test meal in minipigs with pancreatic exocrine insufficiency.

The effect of pancreatic exocrine insufficiency (PEI) on protein malabsorption is little documented, partly due to methodological barriers. We aimed to validate biomarkers of protein malabsorption using a 15N test meal in a minipig model of PEI. Six pancreatic duct-ligated minipigs were used as a model of PEI and four nonoperated animals as a control. All animals were equipped with an ileocecal reentrant cannula. Minipigs were given a test meal containing [15N]casein. The PEI animals repeated the test three times, in the absence of any pancreatic enzymes, or after pancreatic substitution at two levels [ A or B: 7,500 or 75,000 (lipase) and 388 or 3881 (protease) FIP U]. Ileal chyme, urine, and blood were collected postprandially. Nitrogen and 15N were measured in digestive and metabolic pools. We obtained a gradient of ileal protein digestibility from 29 ± 11% in PEI to 89 ± 6% in the controls and a dose- dependent response of enzymes. Insulin and gastric inhibitory polypeptide secretions were decreased by PEI, an effect that was counteracted with the enzymes at level B. The total recovery of 15N in urinary urea and plasma proteins was 14 ± 5.1% in the control group and decreased to 5.5 ± 2.1% by PEI. It was dose dependently restored by the treatment. Both 15N recovery in plasma and urine were correlated to protein digestibility. We confirm that the 15N transfer in those pools is a sensitive marker of protein malabsorption. Nevertheless, an optimization of the test meal conditions would be necessary in the view of implementing a clinical test. NEW & NOTEWORTHY We designed an intervention study to create a gradient of ileal protein digestibility in minipigs with pancreatic exocrine insufficiency and to validate reliable metabolic markers using a 15N oral meal test. 15N recovery in plasma proteins and to a higher extent in urine was sensitive to protein malabsorption. This test is minimally invasive and could be used to reveal protein malabsorption in patients.