CT pulmonary angiography: optimising acute thoracic imaging by fixed-timing contrast medium delivery with a modified breathing instruction.

AIM: To compare the thoracic vascular opacification achieved using the standard bolus-tracking protocol (BTP) with a fixed-timing protocol (FTP) with a modified breathing instruction during computed tomography pulmonary angiography (CTPA) examinations. MATERIALS AND METHODS: A single-centre review of CTPA examinations performed between July 2018 and January 2019 using the BTP or FTP and weight-based contrast dosing of 20 mg iodine/kg body weight/s for 20 seconds at 100 kV tube potential. Radiodensity (in Hounsfield units) was analysed in the right ventricle, main pulmonary artery (MPA), left atrium, left ventricle, and ascending and descending thoracic aorta (DTA). A p-value of <0.05 was considered significant. RESULTS: Of 782 examinations, 88 BTP and 90 FTP examinations were included. Mean attenuation of the MPA was similar in the FTP (396 ± 106 HU) and BTP (362 ± 119 HU; p=0.06); however, good-quality (≥250 HU) MPA opacification was achieved in more FTP examinations (87/90, 96.7%) compared to the BTP (73/88, 82.9%; p=0.002). Mean attenuation of the DTA was better in the FTP (325 ± 72 HU) than the BTP (228 ± 75 HU; p <0.0001), with good-quality opacification (≥250 HU) in 76/90 (84.4%) FTP examinations compared with 36/88 (40.9%) BTP examinations (p <0.001). CONCLUSION: The FTP achieves better opacification of the MPA and DTA compared to the BTP.

Providers' perspectives on the reproductive decision-making of BRCA-positive women.

BACKGROUND: Reproductive decision-making is difficult for BRCA-positive women. Our objective was to assess the complexities of decision-making and identify decisional supports for patients and providers when discussing reproductive options prior to risk-reducing salpingo-oophorectomy (RRSO). METHODS: This study was of qualitive design, using data collection via semi-structured interviews conducted from November 2018 to October 2020. Individuals were included if they were identified to provide care to BRCA-positive women. In total, 19 providers were approached and 15 consented to participate. Providers were recruited from three clinics in Toronto, Ontario located at academic centers: [1] A familial ovarian cancer clinic, [2] A familial breast cancer clinic and [3] A fertility clinic, all of which treat carriers of the BRCA1/BRCA2 genetic mutation. The interview guide was developed according to the Ottawa Decision Support Framework and included questions regarding reproductive options available to patients, factors that impact the decision-making process and the role of decisional support. Interviews were transcribed and transcripts were analyzed thematically using NVIVO 12. RESULTS: Providers identified three major decisions that reproductive-aged women face when a BRCA mutation is discovered: [1] "Do I want children?"; [2] "Do I want to take the chance of passing on this the mutation?"; and [3] "Do I want to carry a child?" Inherent decision challenges that are faced by both providers and patients included difficult decision type, competing options, scientifically uncertain outcomes, and challenging decision timing. Modifiable decisional needs included: inadequate knowledge, unrealistic expectations, unclear values and inadequate support or resources. Identified clinical gaps included counselling time constraints, lack of reliable sources of background information for patients or providers and need for time-sensitive, geographically accessible, and centralized care. CONCLUSION: Our study identified a need for a patient information resource that can be immediately provided to patients who carry a BRCA genetic mutation. Other suggestions for clinical practice include more time during consultation appointments, adequate follow-up, value-centric counseling, access to psychosocial support, and a specialized decisional coach.

Choosing Wisely Canada: Canadian fertility and andrology society's list of top items physicians and patients should question in fertility medicine.

PURPOSE: To create a Choosing Wisely Canada list of the top 5 diagnostic and therapeutic interventions that should be questioned in Reproductive Endocrinology and Infertility in Canada. METHODS: The Canadian Fertility and Andrology Society (CFAS) National Working Group developed an initial list of recommendations of diagnostic and therapeutic interventions that are commonly used, but are not supported by evidence, and could expose patients to unnecessary harm. These were chosen based on their prevalence, cost, potential for harm, and quality of supporting evidence. A modified Delphi consensus was used over 5 rounds to generate ideas, review supporting evidence, assess clinical relevance, estimate recommendation impact and narrow the recommendations list to 5 items. RESULTS: Fifty unique ideas were first proposed by the working group, and after 5 rounds including a survey of Canadian Fertility and Andrology Society (CFAS) members, the final list of recommendations was created, including topics related to unnecessary investigations and interventions for patients with infertility and recurrent pregnancy loss, and those undergoing IVF. In this article, we describe not only the Delphi process used to determine the list, but also provide a summary of the evidence behind each of the final recommendations. CONCLUSIONS: The list of five recommendations highlights opportunities to initiate conversations between clinicians and patients about the risks, benefits, harms and costs of unnecessary fertility treatments and procedures in a Canadian context.

Safety and efficacy of subcutaneous alpha-tocopherol in healthy adult horses.

Vitamin E is essential for neuromuscular function. The primary treatment, oral supplementation with natural ('RRR') α-tocopherol, is not effective in all horses. The objectives of this pilot study were to evaluate the safety and efficacy of a subcutaneously administered RRR-α-tocopherol preparation. Horses were randomly assigned in a cross-over design to initially receive RRR-α-tocopherol (5000 IU/450 kg of 600 IU/mL) subcutaneously (n = 3) or orally (n = 3) or were untreated sentinels (n = 2). Tissue reactions following injection in Phase I of the study necessitated adjustment of the preparation with reduction of the RRR-α-tocopherol concentration to 500 IU/mL in Phase 2. Following an 8-week washout period, horses received the reciprocal treatment route with the new preparation (5000 IU/450 kg of 500 IU/mL). Serum, CSF and muscle α-tocopherol concentrations were determined by high-performance liquid chromatography over a 14-day period during each phase. Serum and CSF α-tocopherol concentrations increased significantly postinjection only when the 500 IU/mL product was administered (P<0.0001). There was no significant difference in the muscle concentration of α-tocopherol following either treatment. All eight horses had marked tissue reaction to subcutaneous injection, regardless of product concentration. Whilst we have demonstrated that this route may be a useful alternative to oral supplementation, the marked tissue reaction makes use of such products limited at this time to only the most refractory of cases.

Are medical comorbidities contributing to the use of opioid analgesics in patients with knee osteoarthritis?

BACKGROUND: Although opioid analgesics are not generally recommended for treatment of knee osteoarthritis (OA), they are frequently used. We sought to determine the association between medical comorbidities and self-reported opioid analgesic use in these patients. METHODS: This cross-sectional study recruited patients referred to two provincial hip and knee clinics in Alberta, Canada for consideration of total knee arthroplasty. Standardized questionnaires assessed demographic (age, gender, income, education, social support, smoking status) and clinical (pain, function, total number of troublesome joints) characteristics, comorbid medical conditions, and non-surgical OA management participants had ever used or were currently using. Multivariable Poisson regression with robust estimate of the standard errors assessed the association between comorbid medical conditions and current opioid use, controlling for potential confounders. RESULTS: 2,127 patients were included: mean age 65.4 (SD 9.1) years and 59.2% female. Currently used treatments for knee OA were: 57.6% exercise and/or physiotherapy, 61.1% NSAIDs, and 29.8% opioid analgesics. In multivariable regression, controlling for potential confounders, comorbid hypertension (RR 1.18, 95% CI 1.02-1.37), gastrointestinal disease (RR 1.31, 95% CI 1.07-1.60), depressed mood (RR 1.25, 95% CI 1.05-1.48) and a higher number of troublesome joints (RR 1.04 per joint, 95% CI 1.00-1.09) were associated with opioid use, with no association found with having ever used recommended non-opioid pharmacological or non-pharmacological treatments. CONCLUSIONS: In a large cohort of patients with knee OA, of 12 comorbidities assessed, comorbid hypertension, gastrointestinal disease, and depressed mood were associated with current use of opioid analgesics, in addition to total burden of troublesome joints. Improved guidance on the management of painful OA in the setting of common comorbidities is warranted.

A Markov Multi-State model of lupus nephritis urine biomarker panel dynamics in children: Predicting changes in disease activity.

BACKGROUND: A urine 'biomarker panel' comprising alpha-1-acid-glycoprotein, ceruloplasmin, transferrin and lipocalin-like-prostaglandin-D synthase performs to an 'excellent' level for lupus nephritis identification in children cross-sectionally. The aim of this study was to assess if this biomarker panel predicts lupus nephritis flare/remission longitudinally. METHODS: The novel urinary biomarker panel was quantified by enzyme linked immunoabsorbant assay in participants of the United Kingdom Juvenile Systemic Lupus Erythematosus (UK JSLE) Cohort Study, the Einstein Lupus Cohort, and the South African Paediatric Lupus Cohort. Monocyte chemoattractant protein-1 and vascular cell adhesion molecule-1 were also quantified in view of evidence from other longitudinal studies. Serial urine samples were collected during routine care with detailed clinical and demographic data. A Markov Multi-State model of state transitions was fitted, with predictive clinical/biomarker factors assessed by a corrected Akaike Information Criterion (AICc) score (the better the model, the lower the AICc score). RESULTS: The study included 184 longitudinal observations from 80 patients. The homogeneous multi-state Markov model of lupus nephritis activity AICc score was 147.85. Alpha-1-acid-glycoprotein and ceruloplasmin were identified to be the best predictive factors, reducing the AICc score to 139.81 and 141.40 respectively. Ceruloplasmin was associated with the active-to-inactive transition (hazard ratio 0.60 (95% confidence interval [0.39, 0.93])), and alpha-1-acid-glycoprotein with the inactive-to-active transition (hazard ratio 1.49 (95% confidence interval [1.10, 2.02])). Inputting individual alpha-1-acid-glycoprotein/ceruloplasmin values provides 3, 6 and 12 months probabilities of state transition. CONCLUSIONS: Alpha-1-acid-glycoprotein was predictive of active lupus nephritis flare, whereas ceruloplasmin was predictive of remission. The Markov state-space model warrants testing in a prospective clinical trial of lupus nephritis biomarker led monitoring.

Development of quality indicators for hip and knee arthroplasty rehabilitation.

OBJECTIVE: To develop quality indicators (QIs) reflecting the minimum acceptable standard of rehabilitation care before and after elective total hip arthroplasty (THA) and total knee arthroplasty (TKA) for osteoarthritis (OA). METHODS: Informed by high quality evidence and using a modified RAND-UCLA Delphi approach, an 18-member Canadian panel of clinicians, researchers and patients considered 81 proposed QIs (40 for THA, 42 for TKA) addressing rehabilitation before and after elective THA and TKA. Panelists rated QIs for their importance and validity on a 9-point Likert scale through two rounds of online rating interspersed with a moderated and anonymous online discussion forum. Those QIs with median ratings of ≥7 for importance and validity with no disagreement based on the inter-percentile range adjusted for symmetry were included in the final sets. RESULTS: Fifteen panelists from seven provinces and varied practice settings completed the Delphi process. Of the 81 plus one additional QIs (total of 82), 67 (82%) were rated as both important and valid (31 for THA, 36 for TKA). For THA, 14 pre-op, six acute and eight post-acute QIs were accepted. For TKA, 16 pre-op, 10 acute and eight post-acute indicators were accepted. Two of three 'across-continuum' QIs were rated appropriate for both procedures. CONCLUSION: This work represents the first QIs with which to measure, report and benchmark quality of care in patients receiving rehabilitation before and after THA/TKA surgery. The QIs will be further tested for reliability and feasibility before being widely disseminated in clinical settings and used to assess care gaps.

Increased concentration of plasma TNFR1 and TNFR2 in paediatric lupus nephritis.

BACKGROUND: Juvenile-onset systemic lupus erythematous (JSLE) is a debilitating condition that frequently involves the kidneys (lupus nephritis; LN). Tumour necrosis factor alpha (TNF-α), an important pro-inflammatory cytokine, is expressed locally in the kidney and correlates with LN disease activity. The aim of this study was to ascertain whether soluble receptors for TNF-α (sTNFR1/sTNFR2) are significantly increased in children with LN. METHODS: Plasma samples were collected from JSLE patients at routine review. Concentrations of sTNFR1 and sTNFR2 were measured (median; interquartile range, IQR) using enzyme-linked immunosorbent assay (ELISA) in 25 JSLE patients (seven LN) and 20 healthy controls (HCs). RESULTS: sTNFR2 concentration was significantly increased in JSLE (5149 pg/dl, 3413-8561) compared to HCs (3858 pg/dl, 2254-5165; p = 0.049). sTNFR1 concentration was significantly increased in active LN (n = 7, 1765 pg/dl, IQR 1133-4167) compared to inactive LN (n = 18, 1104 pg/dl, 886-1272; p = 0.018). There was a non-significant increase in sTNFR2 concentration in active LN (9829 pg/dl, 3298-21271) compared to inactive LN (4595 pg/dl, 3345-6993; p = 0.146). sTNFR1 concentration correlated moderately with sTNFR2 (r = 0.66, p < 0.001). sTNFR2 demonstrated strong positive correlations with ESR (r = 0.941, p < 0.01) and anti-dsDNA antibodies (r = 0.998, p = 0.041). Both receptors also positively correlated with creatinine (TNFR1 r = 0.81, p < 0.001; TNFR2 r = 0.50, p = 0.015) and urinary albumin creatinine ratio (TNFR1 r = 0.64, p < 0.01; TNFR2 r = 0.63, p < 0.01). CONCLUSIONS: These data indicate that sTNFR1 and sTNFR2 concentrations are elevated in LN and may reflect renal activity. These results provide basis for further investigation into the pathological pathways underlying LN.

Pilot surveillance for childhood encephalitis in Australia using the Paediatric Active Enhanced Disease Surveillance (PAEDS) network.

We aimed to assess the performance of active surveillance for hospitalized childhood encephalitis in New South Wales (NSW) using the Paediatric Active Enhanced Disease Surveillance (PAEDS) network to inform methodology for the nationwide Australian childhood encephalitis (ACE) study. We piloted active surveillance for suspected encephalitis from May to December 2013 at the Children's Hospital at Westmead, Sydney, NSW. Cases were ascertained using four screening methods: weekday nurse screening of admission records (PAEDS), cerebrospinal fluid (CSF) microscopy records, magnetic resonance imaging (MRI) reports, and pharmacy dispensing records. Comprehensive clinical data were prospectively collected on consented participants and subsequently reviewed by an expert panel. Cases were categorized as confirmed encephalitis or 'not encephalitis'; encephalitis cases were sub-categorized as infectious, immune-mediated or unknown. We performed an ICD-10 diagnostic code audit of hospitalizations for the pilot period. We compared case ascertainment in the four screening methods and with the ICD code audit. Forty-eight cases of suspected encephalitis were identified by one or more methods. PAEDS was the most efficient mechanism (yield 34%), followed by MRI, CSF, and pharmacy audits (yield 14%, 12%, and 7% respectively). Twenty-five cases met the criteria for confirmed encephalitis. PAEDS was the most sensitive of the mechanisms for confirmed encephalitis (92%) with a positive predictive value (PPV) of 72%. The ICD audit was moderately sensitive (64%) but poorly specific (Sp 9%, PPV 14%). Of the 25 confirmed encephalitis cases, 19 (76%) were sub-categorized as infectious, three (12%) were immune-mediated, and three (12%) were 'unknown'. We identified encephalitis cases associated with two infectious disease outbreaks (enterovirus 71, parechovirus 3). PAEDS is an efficient, sensitive and accurate surveillance mechanism for detecting cases of childhood encephalitis including those associated with emerging infectious diseases. Active surveillance significantly increases the ascertainment of encephalitis cases compared with passive approaches.

Risk factors for revision of total knee arthroplasty: a scoping review.

BACKGROUND: In spite of the increasing incidence of total knee arthroplasties (TKA), evidence is limited regarding risk factors for revision. The objective of this scoping review was to identify and assess demographic, surgical and health services factors that may increase the risk for revision surgery following TKA. METHODS: A scoping review was undertaken following an electronic search in MEDLINE (1990 to December 2013), CINAHL (to December 2013), EMBASE (1990 to December 2013) and Web of Science (1990 to December 2013). RESULTS: Of the 4460 articles screened, 42 were included of which 26 articles were based on registry data. Increased risk of revision was associated with demographic factors (younger age, African American), surgical factors related to the primary TKA (uncemented components, implant malalignment, increased surgery duration), and health services (low volume hospitals). CONCLUSIONS: Identifying emerging trends in characteristics of those requiring revision following TKA can help identify those at risk and allocate appropriate resources. Further primary clinical articles on risk factors for revision of TKA are necessary to ensure maximal function and lifespan following TKAs.

Development of postgraduate research supervisors within a teaching hospital setting.

The recent trend to embed medical research at point of care has created a need for postgraduate research supervisors in hospitals who are practising clinicians and lab-based researchers. We explored the training needs of supervisors to inform the design and evaluation of a hospital-based development programme. We found that if hospital-based supervisors are to improve their practice, the programme needs to be on-site to ensure access and relevance to local issues.

Consensus guidelines for the investigation and management of encephalitis in adults and children in Australia and New Zealand.

Encephalitis is a complex neurological syndrome caused by inflammation of the brain parenchyma. The management of encephalitis is challenging because: the differential diagnosis of encephalopathy is broad; there is often rapid disease progression; it often requires intensive supportive management; and there are many aetiologic agents for which there is no definitive treatment. Patients with possible meningoencephalitis are often encountered in the emergency care environment where clinicians must consider differential diagnoses, perform appropriate investigations and initiate empiric antimicrobials. For patients who require admission to hospital and in whom encephalitis is likely, a staged approach to investigation and management is preferred with the potential involvement of multiple medical specialties. Key considerations in the investigation and management of patients with encephalitis addressed in this guideline include: Which first-line investigations should be performed?; Which aetiologies should be considered possible based on clinical features, risk factors and radiological features?; What tests should be arranged in order to diagnose the common causes of encephalitis?; When to consider empiric antimicrobials and immune modulatory therapies?; and What is the role of brain biopsy?

Impact of perioperative dexamethasone on postoperative analgesia and side-effects: systematic review and meta-analysis.

BACKGROUND: The analgesic efficacy and adverse effects of a single perioperative dose of dexamethasone are unclear. We performed a systematic review to evaluate the impact of a single i.v. dose of dexamethasone on postoperative pain and explore adverse events associated with this treatment. METHODS: MEDLINE, EMBASE, CINAHL, and the Cochrane Register were searched for randomized, controlled studies that compared dexamethasone vs placebo or an antiemetic in adult patients undergoing general anaesthesia and reported pain outcomes. RESULTS: Forty-five studies involving 5796 patients receiving dexamethasone 1.25-20 mg were included. Patients receiving dexamethasone had lower pain scores at 2 h {mean difference (MD) -0.49 [95% confidence interval (CI): -0.83, -0.15]} and 24 h [MD -0.48 (95% CI: -0.62, -0.35)] after surgery. Dexamethasone-treated patients used less opioids at 2 h [MD -0.87 mg morphine equivalents (95% CI: -1.40 to -0.33)] and 24 h [MD -2.33 mg morphine equivalents (95% CI: -4.39, -0.26)], required less rescue analgesia for intolerable pain [relative risk 0.80 (95% CI: 0.69, 0.93)], had longer time to first dose of analgesic [MD 12.06 min (95% CI: 0.80, 23.32)], and shorter stays in the post-anaesthesia care unit [MD -5.32 min (95% CI: -10.49 to -0.15)]. There was no dose-response with regard to the opioid-sparing effect. There was no increase in infection or delayed wound healing with dexamethasone, but blood glucose levels were higher at 24 h [MD 0.39 mmol litre(-1) (95% CI: 0.04, 0.74)]. CONCLUSIONS: A single i.v. perioperative dose of dexamethasone had small but statistically significant analgesic benefits.

Domestic cats are susceptible to infection with low pathogenic avian influenza viruses from shorebirds.

Domestic cats are susceptible to infection with highly pathogenic avian influenza virus H5N1, resulting in pneumonia and in some cases, systemic spread with lesions in multiple organ systems. Recent transmission of the 2009 pandemic H1N1 influenza virus from humans to cats also resulted in severe pneumonia in cats. Data regarding the susceptibility of cats to other influenza viruses is minimal, especially regarding susceptibility to low pathogenic avian influenza viruses from wild birds, the reservoir host. In this study, the authors infected 5-month-old cats using 2 different North American shorebird avian influenza viruses (H1N9 and H6N4 subtypes), 3 cats per virus, with the goal of expanding the understanding of avian influenza virus infections in this species. These viruses replicated in inoculated cats based on virus isolation from the pharynx in 2 cats, virus isolation from the lung of 1 cat, and antigen presence in the lung via immunohistochemistry in 2 cats. There was also seroconversion and lesions of patchy bronchointerstitial pneumonia in all of the cats. Infection in the cats did not result in clinical disease and led to variable pharyngeal viral shedding with only 1 of the viruses; virus was localized in the alveolar epithelium via immunohistochemistry. These findings demonstrate the capacity of wild bird influenza viruses to infect cats, and further investigation is warranted into the pathogenesis of these viruses in cats from both a veterinary medical and public health perspective.

Delineating the impact of obesity and its relationship on recovery after total joint arthroplasties.

OBJECTIVE: The primary aim of this study was to determine the impact of obesity in predicting short and long-term pain relief and functional recovery in total joint arthroplasty (TJA) either as an independent risk factor or a factor mediated by two chronic conditions associated with obesity-cardiac disease and diabetes mellitus. METHOD: A prospective observational study of 520 patients with primary joint arthroplasties. Pain and functional outcomes were evaluated with the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index within a month of surgery and then 6 months and 3 years post-operatively. Obesity, cardiac disease and diabetes mellitus were examined as potential risk factors for poor recovery. Patients were classified into four groups based on body mass index (BMI): (normal<25.0 kg/m(2); overweight 25.0-29.9 kg/m(2); obese Class 1 30.0-34.9 kg/m(2); severe obese Class 2&3 35.0 ≥ kg/m(2)). Linear mixed models for each joint type (hip and knee arthroplasty) were developed to examine the pattern of recovery and the effect of obesity. RESULTS: Ninety-nine (19%) patients were severely obese, 127 (24%) had cardiac disease and 58 (11%) had diabetes mellitus. Baseline pain and functional scores were similar regardless of BMI classification. Severe obesity was a significant risk factor for worse pain and functional recovery at 6 months but no longer at 3 years following total hip and knee arthroplasty. Cardiac disease predicted a slower recovery after hip arthroplasty. No significant interactions existed between obesity and cardiac disease or diabetes mellitus. DISCUSSION: Severe obesity is an independent risk factor for slow recovery over 3 years for both hip and knee arthroplasties.

Adiposity changes after a 1-year aerobic exercise intervention among postmenopausal women: a randomized controlled trial.

OBJECTIVE: We examined the effects of an aerobic exercise intervention on adiposity outcomes that may be involved in the association between physical activity and breast cancer risk. DESIGN: This study was a two-centre, two-armed, randomized controlled trial. The 1-year-long exercise intervention included 45 min of moderate-to-vigorous aerobic exercise five times per week, with at least three of the sessions being facility based. The control group was asked not to change their activity and both groups were asked not to change their diet. SUBJECTS: A total of 320 postmenopausal, sedentary, normal weight-to-obese women aged 50-74 years who were cancer-free, nondiabetic and nonhormone replacement therapy users were included in this study. MEASUREMENTS: Anthropometric measurements of height, weight and waist and hip circumferences; dual energy X-ray absorptiometry measurements of total body fat; and computerized tomography measurements of abdominal adiposity were carried out. RESULTS: Women in the exercise group exercised a mean of 3.6 days (s.d.=1.3) per week and 178.5 min (s.d.=76.1) per week. Changes in all measures of adiposity favored exercisers relative to controls (P<0.001). The mean difference between groups was: -1.8 kg for body weight; -2.0 kg for total body fat; -14.9 cm(2) for intra-abdominal fat area; and -24.1 cm(2) for subcutaneous abdominal fat area. A linear trend of greater body fat loss with increasing volume of exercise was also observed. CONCLUSION: A 1-year aerobic exercise program consistent with current public health guidelines resulted in reduced adiposity levels in previously sedentary postmenopausal women at higher risk of breast cancer.

Meal-induced increases in C-reactive protein, interleukin-6 and tumour necrosis factor α are attenuated by prandial + basal insulin in patients with Type 2 diabetes.

AIM: To determine if a regimen with prandial + basal insulin compared with basal insulin attenuates post-meal inflammatory and glycative biomarkers in patients with Type 2 diabetes. METHODS: This test-meal sub-study in the USA is from a previously reported clinical trial comparing the effect on glycaemic control of 24 weeks of thrice-daily pre-meal insulin lispro mix 50 (50% insulin lispro, 50% insulin lispro protamine suspension) or bedtime insulin glargine, both plus metformin. In the sub-study, glucose, insulin, triglycerides, high-sensitivity C-reactive protein, tumour necrosis factor α, interleukin-6, methylglyoxal and 3-deoxyglucosone were measured during the post-meal period of a mixed-meal breakfast at the final visit. Prandial + basal (n = 25) and basal (n = 21) insulin were administered at the same times as during the previous 24 weeks. RESULTS: Post-meal, the prandial + basal insulin group had significantly higher insulin, lower glucose and triglycerides, as well as lower high-sensitivity C-reactive protein, tumour necrosis factor α and interleukin-6, than the basal insulin group. Glucose incremental area under the concentration curve significantly correlated with high-sensitivity C-reactive protein, tumour necrosis factor α, interleukin-6, methylglyoxal and 3-deoxyglucosone incremental area under the concentration curve. Insulin incremental area under the concentration curve correlated inversely with high-sensitivity C-reactive protein and tumour necrosis factor α incremental area under the concentration curve. However, after adjusting for glucose incremental area under the concentration curve, these inverse correlations were no longer significant. Triglyceride incremental area under the concentration curve was not correlated with any biomarker incremental area under the concentration curve. CONCLUSIONS: Controlling post-meal hyperglycaemia with prandial + basal insulin in patients with Type 2 diabetes attenuates meal-induced increases in high-sensitivity C-reactive protein, interleukin-6 and tumour necrosis factor α compared with basal insulin. The rise in post-meal glucose, but not triglycerides, significantly correlated with the rise in post-meal inflammatory and glycative biomarkers.

CTLA4 promoter polymorphisms are associated with canine diabetes mellitus.

Canine diabetes mellitus (DM) shares many similarities with human type 1 diabetes (T1D). It is a complex genetic disorder, which shows marked differences in breed susceptibility, with Samoyed dogs being highly susceptible, whereas the Boxer breed is relatively resistant. A number of immune response genes, which have been associated with human T1D, have also been implicated in determining susceptibility to canine DM, suggesting an immune-mediated component to the disease pathogenesis. Single nucleotide polymorphisms (SNPs) in the CTLA4 gene have consistently and reproducibly been associated with human T1D and other autoimmune diseases but the canine CTLA4 gene has not previously been investigated for involvement in canine DM. SNPs of particular interest in the human association studies are those in the promoter region which affect CTLA4 expression levels, and that of exon 1 which results in a non-synonymous amino acid change. We performed a canine SNP discovery investigation of CTLA4 on a region of DNA containing exon 1 and 1.5 kb upstream sequence in order to identify promoter region SNPs. Confirmed SNPs were used in a genetic association study of a canine diabetic cohort showing that CTLA4 promoter polymorphisms were associated with diabetes in crossbreed dogs and in five Pedigree breeds-Samoyed, Miniature Schnauzer, West Highland White Terrier, Border Terrier and Labrador. Meta-analysis of these breeds showed 9 out of 15 SNPs were associated with DM and genotype and haplotype analyses also confirmed the allelic associations in these breeds.

The use of cannabis and perceptions of its effect on fertility among infertility patients.

STUDY QUESTION: What is the prevalence of cannabis use and the perceptions of its impact on fertility among infertility patients? SUMMARY ANSWER: A total of 13% of infertility patients used cannabis within the last year, and current usage is associated with patient perceptions of negative effects of cannabis on fertility and pregnancy. WHAT IS KNOWN ALREADY: Cannabis use is increasing among the general population and pregnant women, particularly in places where cannabis use is legal despite having known and potential negative effects on fertility and pregnancy. STUDY DESIGN SIZE DURATION: A cross-sectional patient survey study was performed between July 2017 and September 2017. Patients attending a university-affiliated hospital-based fertility clinic (n = 290) were invited to complete a written survey. Inclusion criteria were limited to the ability to read English. There were no exclusion criteria. PARTICIPANTS/MATERIALS SETTING METHODS: Of the 290 patients approached, 270 (93%) agreed to participate. The questions covered demographics, cannabis usage, perceptions of the effect of cannabis on fertility and pregnancy, cessation of use due to infertility and personal history of disclosing cannabis use to healthcare providers (HCP). MAIN RESULTS AND THE ROLE OF CHANCE: The results showed that 13% of respondents disclosed use of cannabis in the past year (past year users) and 38% had not used cannabis in the past year but had previously used cannabis (>1 year users) while 49% had never used cannabis (never users). Baseline demographics were similar for the three groups, but across four measures of fertility and pregnancy health, past-year users perceived less of a negative effect compared to >1 year users, and never users (P values of 0.02, 0.03, 0.01, <0.001 for questions on pregnancy, offspring health, male fertility and female fertility, respectively). Of past year users, 72% said they had or would disclose use to their HCP, but only 9.4% reported that their HCP had actually instructed them to discontinue use. LIMITATIONS REASONS FOR CAUTION: Self-reported patient surveys are subject to reporting bias and may not reflect actual use and perceptions. WIDER IMPLICATIONS OF THE FINDINGS: This study suggests that cannabis use is common among infertility patients. Given the known negative impacts of cannabis on pregnancy, the authors would have expected informed infertility patients to cease cannabis use as part of their efforts to conceive. As the prevalence of cannabis use in the last year among infertility patients is similar to that in the general Canadian population, it is unclear whether the prevalence of cannabis use in the sample population merely reflects the average usage in society or, after taking into account those who reduced their usage to improve their fertility, is a factor contributing to infertility and thus prompting fertility referral. Given concern about the potential negative impact of cannabis use on fertility, and that only 9% of past year users had been instructed by an HCP to cease cannabis use, HCPs should consider the benefits of counselling about cannabis cessation for patients who are attempting to conceive. Future research should focus on analysing the effects of cannabis use on female fertility and determining whether a reduction in use among patients with infertility can improve conception rates. STUDY FUNDING/COMPETING INTERESTS: Michelle Shin, Clinical Research Associate, is supported by the University of Toronto GREI Fellowship Fund, which is sponsored by unrestricted research grants from EMD Serono, Merck Canada and Ferring Pharmaceuticals. The authors have no potential conflicts of interest to disclose.