Nationally Subsidized Continuous Glucose Monitoring: A Cost-effectiveness Analysis.

OBJECTIVE: The Continuous Glucose Monitoring (CGM) Initiative recently introduced universal subsidized CGM funding for people with type 1 diabetes under 21 years of age in Australia. We thus aimed to evaluate the cost-effectiveness of this CGM Initiative based on national implementation data and project the economic impact of extending the subsidy to all age-groups. RESEARCH DESIGN AND METHODS: We used a patient-level Markov model to simulate disease progression for young people with type 1 diabetes and compared government-subsidized access to CGM with the previous user-funded system. Three years of real-world clinical input data were sourced from analysis of the Australasian Diabetes Data Network and National Diabetes Services Scheme registries. Costs were considered from the Australian health care system's perspective. An annual discount rate of 5% was applied to future costs and outcomes. Uncertainty was evaluated with probabilistic and deterministic sensitivity analyses. RESULTS: Government-subsidized CGM funding for young people with type 1 diabetes compared with a completely user-funded model resulted in an incremental cost-effectiveness ratio (ICER) of AUD 39,518 per quality-adjusted life-year (QALY) gained. Most simulations (85%) were below the commonly accepted willingness-to-pay threshold of AUD 50,000 per QALY gained in Australia. Sensitivity analyses indicated that base-case results were robust, though strongly impacted by the cost of CGM devices. Extending the CGM Initiative throughout adulthood resulted in an ICER of AUD 34,890 per QALY gained. CONCLUSIONS: Providing subsidized access to CGM for people with type 1 diabetes was found to be cost-effective compared with a completely user-funded model in Australia.

The Cost of Control: Cost-effectiveness Analysis of Hybrid Closed-Loop Therapy in Youth.

OBJECTIVE: Hybrid closed-loop (HCL) therapy is an efficacious management strategy for young people with type 1 diabetes. However, high costs prevent equitable access. We thus sought to evaluate the cost-effectiveness of HCL therapy compared with current care among young people with type 1 diabetes in Australia. RESEARCH DESIGN AND METHODS: A patient-level Markov model was constructed to simulate disease progression for young people with type 1 diabetes using HCL therapy versus current care, with follow-up from 12 until 25 years of age. Downstream health and economic consequences were compared via decision analysis. Treatment effects and proportions using different technologies to define "current care" were based primarily on data from an Australian pediatric randomized controlled trial. Transition probabilities and utilities for health states were sourced from published studies. Costs were considered from the Australian health care system's perspective. An annual discount rate of 5% was applied to future costs and outcomes. Uncertainty was evaluated with probabilistic and deterministic sensitivity analyses. RESULTS: Use of HCL therapy resulted in an incremental cost-effectiveness ratio of Australian dollars (AUD) $32,789 per quality-adjusted life year (QALY) gained. The majority of simulations (93.3%) were below the commonly accepted willingness-to-pay threshold of AUD $50,000 per QALY gained in Australia. Sensitivity analyses indicated that the base-case results were robust. CONCLUSIONS: In this first cost-effectiveness analysis of HCL technologies for the management of young people with type 1 diabetes, HCL therapy was found to be cost-effective compared with current care in Australia.

Trends in glycaemic control and drug use in males and females with type 2 diabetes: Results of the Australian National Diabetes Audit from 2013 to 2019.

AIM: To investigate temporal changes in glycaemic control and the use of antihyperglycaemic therapies in females and males with type 2 diabetes from 2013 to 2019. METHODS: Data from adult patients with type 2 diabetes (n = 11 930; 44.9% females, mean [SD] age of 62.9 [12.9] years) were analysed from the 2013 to 2019 biennial cross-sectional Australian National Diabetes Audit. RESULTS: Mean HbA1c remained similar throughout the years examined and between the sexes (7.8%-8.3%, 62-67 mmol/mol; P > .05). The number of antihyperglycaemic agents used by both sexes increased from 2013 to 2019 (P < .001), with more agents used by males (P = .014). From 2013 to 2019, there were increasing proportions of both sexes using dipeptidyl peptidase-4 inhibitors (females: 11.7%-25.7%, P = .045; males: 11.6%-29.5%, P = .036) and glucagon-like peptide-1 receptor agonists (females: 5.9%-15.3%; males: 4.9%-11.1%; P = .043 for both). Sodium-glucose co-transporter-2 inhibitors were not available in 2013; however, their use increased substantially from 2015 to 2019 in both females (4.9%-26.3%, P = .013) and males (4.7%-32.2%, P = .019). CONCLUSIONS: From 2013 to 2019, mean HbA1c levels remained unchanged despite a concurrent increase in the number of antihyperglycaemic medications used. Overall, there was a trend towards preferencing newer agents with some differences in treatment regimens relating to sex and renal function.

Utilisation, access and recommendations regarding technologies for people living with type 1 diabetes: consensus statement of the ADS/ADEA/APEG/ADIPS Working Group.

INTRODUCTION: Type 1 diabetes presents significant challenges for optimal management. Despite intensive glycaemic control being the standard of care for several decades, glycaemic targets are infrequently achieved and the burden of complications remains high. Therefore, the advancement of diabetes management technologies has a major role in reducing the clinical and economic impact of the disease on people living with type 1 diabetes and on health care systems. However, a national framework is needed to ensure equitable and sustainable implementation of these technologies as part of holistic care. MAIN RECOMMENDATIONS: This consensus statement considers technologies for insulin delivery, glucose sensing and insulin dose advice that are commercially available in Australia. While international position statements have provided recommendations for technology implementation, the ADS/ADEA/APEG/ADIPS Working Group believes that focus needs to shift from strict trial-based glycaemic criteria towards engagement and individualised management goals that consider the broad spectrum of benefits offered by technologies. CHANGES IN MANAGEMENT AS RESULT OF THIS STATEMENT: This Australian consensus statement from peak national bodies for the management of diabetes across the lifespan outlines a national framework for the optimal implementation of technologies for people with type 1 diabetes. The Working Group highlights issues regarding equity of access to technologies and services, scope of clinical practice, credentialling and accreditation requirements, regulatory issues with "do-it-yourself" technology, national benchmarking, safety reporting, and ongoing patient advocacy.

Glycaemia and utilisation of technology across the lifespan of adults with type 1 diabetes: Results of the Australian National Diabetes Audit (ANDA).

AIMS: To evaluate the utilisation of technologies and associated glycaemia among adults with type 1 diabetes. METHODS: De-identified data from adults with type 1 diabetes (≥18 years old) in the Australian National Diabetes Audit (ANDA)-2019 were analysed. Proportions using insulin pumps or injections with continuous glucose monitoring (CGM) or capillary-glucose testing were compared. Technology use among adults was compared to young people (<21 years old) with subsidised CGM. Glycaemia and complication-burden were assessed across management strategies. RESULTS: 1,693 adults were analysed. Mean(±SD) age, diabetes duration, and HbA1c were 43.3 ± 17.0 years, 20.3 ± 14.3 years and 8.4% ± 1.7 [68 ± 19 mmol/mol], respectively. Among adults, 40% used at least one device, 27% used insulin pumps, and 23% used CGM. CGM was used by 62% of young people with subsidised access. Mean HbA1c was consistently lower among adults using CGM, insulin pumps, or combined insulin pump and CGM compared to standard care (8.3% ± 1.6 [67 ± 18 mmol/mol], 8.2% ± 1.4 [66 ± 15 mmol/mol], and 7.8% ± 1.4 [62 ± 15 mmol/mol] respectively compared to 8.6% ± 1.8 [70 ± 20 mmol/mol], p < 0.001). Technology use was not associated with diabetic ketoacidosis but CGM was associated with more hypoglycaemia. CONCLUSIONS: Government subsidy is an important consideration for utilisation of technologies among adults with type 1 diabetes. Technology use across the adult lifespan was associated with lower HbA1c than insulin injections and capillary-glucose testing.

Cost-effectiveness of health technologies in adults with type 1 diabetes: a systematic review and narrative synthesis.

BACKGROUND: With the rapid development of technologies for type 1 diabetes, economic evaluations are integral in guiding cost-effective clinical and policy decisions. We therefore aimed to review and synthesise the current economic literature for available diabetes management technologies and outline key determinants of cost-effectiveness. METHODS: A systematic search was conducted in April 2019 that focused on modelling or trial based economic evaluations. Searched databases included Medline, Medline in-process and other non-indexed citations, EMBASE, PubMed, All Evidenced Based Medicine Reviews, EconLit, Cost-effectiveness analysis Registry, Research Papers in Economics, Web of Science, PsycInfo, CINAHL, and PROSPERO from inception. We assessed quality of included studies with the Questionnaire to Assess Relevance and Credibility of Modeling Studies for Informing Health Care Decision Making an ISPOR-AMCP-NPC good practice task force report. Screening of abstracts and full-texts, appraisal, and extraction were performed by two independent researches. RESULTS: We identified 16,772 publications, of which 35 were analysed and included 11 health technologies. Despite a lack of consensus, most studies reported that insulin pumps (56%) or interstitial glucose sensors (62%) were cost-effective, although incremental cost-effectiveness ratios ranged widely ($14,266-$2,997,832 USD). Cost-effectiveness for combined insulin pumps and glucose sensors was less clear. Determinants of cost-effectiveness included treatment effects on glycosylated haemoglobin and hypoglycaemia, costing of technologies and complications, and measures of utility. CONCLUSIONS: Insulin pumps or glucose sensors appeared cost-effective, particularly in populations with higher HbA1c levels and rates of hypoglycaemia. However, cost-effectiveness for combined insulin pumps and glucose sensors was less clear. REGISTRATION: The study was registered with PROSPERO, number CRD42017077221.

Time in Range for Multiple Technologies in Type 1 Diabetes: A Systematic Review and Network Meta-analysis.

BACKGROUND: Time in range is a key glycemic metric, and comparisons of management technologies for this outcome are critical to guide device selection. PURPOSE: We conducted a systematic review and network meta-analysis to compare and rank technologies for time in glycemic ranges. DATA SOURCES: We searched Evidenced-Based Medicine Reviews, CINAHL, Embase, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, PROSPERO, PsycInfo, PubMed, and Web of Science until 24 April 2019. STUDY SELECTION: We included randomized controlled trials ≥2 weeks' duration comparing technologies for management of type 1 diabetes in adults (≥18 years of age), excluding pregnant women. DATA EXTRACTION: Data were extracted using a predefined template. Outcomes were percent time with sensor glucose levels 3.9-10.0 mmol/L (70-180 mg/dL), >10.0 mmol/L (180 mg/dL), and <3.9 mmol/L (70 mg/dL). DATA SYNTHESIS: We identified 16,772 publications, of which 14 eligible studies compared eight technologies comprising 1,043 participants. Closed-loop systems led to greater percent time in range than any other management strategy, and mean percent time in range was 17.85 (95% predictive interval 7.56-28.14) longer than with usual care of multiple daily injections with capillary glucose testing. Closed-loop systems ranked best for percent time in range or above range with use of Surface Under the Cumulative RAnking curve (SUCRA) (98.5% and 93.5%, respectively). Closed-loop systems also ranked highly for time below range (SUCRA 62.2%). LIMITATIONS: Overall risk of bias ratings were moderate for all outcomes. Certainty of evidence was very low. CONCLUSIONS: In the first integrated comparison of multiple management strategies considering time in range, we found that the efficacy of closed-loop systems appeared better than all other approaches.

Cost-Effectiveness Analysis of a Hybrid Closed-Loop System Versus Multiple Daily Injections and Capillary Glucose Testing for Adults with Type 1 Diabetes.

Background: Hybrid closed-loop systems may offer improved HbA1c levels, more time-in-range, and less hypoglycemia than alternative treatment strategies. However, it is unclear if glycemic improvements offset this technology's higher acquisition costs. Among adults with type 1 diabetes in Australia, we sought to evaluate the cost-effectiveness of a hybrid closed-loop system in comparison with the current standard of care, comprising insulin injections and capillary glucose testing. Methods: Cost-effectiveness analysis was performed using decision analysis in combination with a Markov model to simulate disease progression in a cohort of adults with type 1 diabetes and compare the downstream health and economic consequences of hybrid closed-loop therapy versus current standard of care. Transition probabilities and utilities were sourced from published studies. Costs were considered from the perspective of the Australian health care system. A lifetime horizon was considered, with annual discount rates of 5% applied to future costs and outcomes. Uncertainty was assessed with probabilistic and deterministic sensitivity analyses. Results: Use of a hybrid closed-loop system resulted in an incremental cost-effectiveness ratio of Australian dollars (AUD) 37,767 per quality-adjusted life year (QALY) gained. This is below the traditionally cited willingness to pay a threshold of $50,000 per QALY gained in the Australian setting. Sensitivity analyses that varied baseline glycemic control, treatment effects, technology costs, age, discount rates, and time horizon indicated the results to be robust. Conclusions: For adults with type 1 diabetes, hybrid closed-loop therapy is likely to be cost-effective compared with multiple daily injections and capillary glucose testing in Australia.

The Efficacy of Technology in Type 1 Diabetes: A Systematic Review, Network Meta-analysis, and Narrative Synthesis.

Background: Existing technologies for type 1 diabetes have not been compared against the full range of alternative devices. Multiple metrics of glycemia and patient-reported outcomes for evaluating technologies also require consideration. We thus conducted a systematic review, network meta-analysis, and narrative synthesis to compare the relative efficacy of available technologies for the management of type 1 diabetes. Methods: We searched MEDLINE, MEDLINE In-Process and other nonindexed citations, EMBASE, PubMed, All Evidence-Based Medicine Reviews, Web of Science, PsycINFO, CINAHL, and PROSPERO (inception-April 24, 2019). We included RCT ≥6 weeks duration comparing technologies for type 1 diabetes management among nonpregnant adults (>18 years of age). Data were extracted using a predefined tool. Primary outcomes were A1c (%), hypoglycemia rates, and quality of life (QoL). We estimated mean difference for A1c and nonsevere hypoglycemia, rate ratio for severe hypoglycemia, and standardized mean difference for QoL in network meta-analysis with random effects. Results: We identified 16,772 publications, of which 52 eligible studies compared 12 diabetes management technologies comprising 3,975 participants in network meta-analysis. Integrated insulin pump and continuous glucose monitoring (CGM) systems with low-glucose suspend or hybrid closed-loop algorithms resulted in A1c levels 0.96% (predictive interval [95% PrI] 0.04-1.89) and 0.87% (95% PrI 0.12-1.63) lower than multiple daily injections with either flash glucose monitoring or capillary glucose testing, respectively. In addition, integrated systems had the best ranking for A1c reduction utilizing the surface under the cumulative ranking curve (SUCRA-96.4). While treatment effects were nonsignificant for many technology comparisons regarding severe hypoglycemia and QoL, simultaneous evaluation of outcomes in cluster analyses as well as narrative synthesis appeared to favor integrated insulin pump and continuous glucose monitors. Overall risk of bias was moderate-high. Certainty of evidence was very low. Conclusions: Integrated insulin pump and CGM systems with low-glucose suspend or hybrid closed-loop capability appeared best for A1c reduction, composite ranking for A1c and severe hypoglycemia, and possibly QoL. Registration: PROSPERO, number CRD42017077221.

Evaluation of ultrasonographically determined ratios of kidney length to aorta diameter for assessment of kidney size in healthy young dogs.

OBJECTIVE: To determine whether previously described cutoffs for ultrasonographically determined kidney length-to-aorta diameter ratio (KL:Ao) for evaluation of kidney size in adult dogs are applicable to healthy dogs 1 to 18 months of age and to assess interobserver and intraobserver variability for ultrasonographic kidney and aorta measurements in these dogs grouped according to age. ANIMALS: 82 dogs. PROCEDURES: 41 university-owned dogs and 41 client- or staff-owned dogs of 3 age groups (approx 1, 6, and 12 to 18 months of age) underwent ultrasonographic examination by 3 observers. Kidney length, kidney width, and diameter of the aorta were measured by each observer 3 times, and KL:Ao and kidney length-to-body weight ratio were calculated for each dog. Measurements and calculated ratios for the 3 age groups were compared by statistical methods; interobserver and intraobserver variability were calculated. RESULTS: Mean kidney length, kidney width, and aorta diameter were smaller, and calculated KL:Ao and kidney length-to-body weight ratio were larger, for dogs of the 1-month age group than for dogs of the 6-month and 12 to 18-month age groups. There were significant interobserver differences for ultrasonographic measurements in all age groups; these were most frequent in the youngest group of dogs and affected KL:Ao for that group only. CONCLUSIONS AND CLINICAL RELEVANCE: Results revealed that 1-month-old dogs have larger kidneys relative to body weight and aorta diameter than do older dogs. Interobserver variability for the youngest group of dogs indicated limited usefulness of these measurements and related ratios for neonatal dogs in clinical practice. The KL:Ao values for dogs ≥ 6 months of age in this study were similar to values previously described for dogs > 12 months of age.

Stifle joint osteoarthritis at the time of diagnosis of cranial cruciate ligament injury is higher in Boxers and in dogs weighing more than 35 kilograms.

Osteoarthritis is a ubiquitous disease in dogs. The purpose of this retrospective study was to characterize the severity and distribution of osteoarthritis (OA) within the joint and to identify differences among dog breeds in the severity of OA in the cranial cruciate ligament (CCL)-deficient stifle joint. Radiographs of 240 stifles from 51 Boxers, 66 German Shepherds, 100 Labrador Retrievers, and 23 Siberian Huskies with confirmed CCL rupture were included. Radiographs of the stifle joint were evaluated and OA severity was graded at 33 sites within and around the joint, and patella alta was graded as present or absent for a potential total stifle OA score of 100. Osteophyte size was correlated to OA severity score. Total OA scores were calculated and compared within and between breeds globally as well as at each joint site. Dogs weighing >35 kg had a higher total OA score than those weighing <35 kg. Osteoarthritis scores were highest at the apical patella, proximolateral tibia, and sesamoid bones, corresponding to the proximal, lateral, and caudal aspects of the joint, respectively. No statistically significant differences were found among the mean OA scores of various stifle joint regions. Boxer dogs had a higher total OA score than other breeds. We concluded that dogs have a consistent distribution pattern of OA within the stifle joint after CCL injury. Radiographic OA is more severe in the proximal, lateral, and caudal aspects of the joint. Boxers had more severe OA than the other breeds evaluated in the study.

Risk-adjustment of diabetes health outcomes improves the accuracy of performance benchmarking.

Benchmarking clinical performance by comparing diabetes health outcomes across healthcare providers drives quality improvement. Non-care related patient risk factors are likely to confound clinical performance, but few studies have tested this. This cross-sectional study is the first Australian investigation to analyse the effect of risk-adjustment for non-care related patient factors on benchmarking. Data from 4,670 patients with type 2 (n = 3,496) or type 1 (n = 1,174) were analysed across 49 diabetes centres. Diabetes health outcomes (HbA1c levels, LDL-cholesterol levels, systolic blood pressure and rates of severe hypoglycaemia) were risk-adjusted for non-care related patient factors using multivariate stepwise linear and logistic regression models. Unadjusted and risk-adjusted funnel plots were constructed for each outcome to identify low-performing and high-performing outliers. Unadjusted funnel plots identified 27 low-performing outliers and 15 high-performing outliers across all diabetes health outcomes. After risk-adjustment, 22 (81%) low-performing outliers and 13 (87%) high-performing outliers became inliers. Additionally, one inlier became a low-performing outlier. Risk-adjustment of diabetes health outcomes significantly reduced false positives and false negatives for outlier performance, hence providing more accurate information to guide quality improvement activity.

Burden of cardiovascular risk factors and disease among patients with type 1 diabetes: results of the Australian National Diabetes Audit (ANDA).

BACKGROUND: Cardiovascular risk stratification is complex in type 1 diabetes. We hypothesised that traditional and diabetes-specific cardiovascular risk factors were prevalent and strongly associated with cardiovascular disease (CVD) among adults with type 1 diabetes attending Australian diabetes centres. METHODS: De-identified, prospectively collected data from patients with type 1 diabetes aged ≥ 18 years in the 2015 Australian National Diabetes Audit were analysed. The burden of cardiovascular risk factors [age, sex, diabetes duration, glycated haemoglobin (HbA1c), blood pressure, lipid profile, body mass index, smoking status, retinopathy, renal function and albuminuria] and associations with CVD inclusive of stroke, myocardial infarction, coronary artery bypass graft surgery/angioplasty and peripheral vascular disease were assessed. Restricted cubic splines assessed for non-linearity of diabetes duration and likelihood ratio test assessed for interactions between age, diabetes duration, centre type and cardiovascular outcomes of interest. Discriminatory ability of multivariable models were assessed with area under the receiver operating characteristic (ROC) curves. RESULTS: Data from 1169 patients were analysed. Mean (± SD) age and median diabetes duration was 40.0 (± 16.7) and 16.0 (8.0-27.0) years respectively. Cardiovascular risk factors were prevalent including hypertension (21.9%), dyslipidaemia (89.4%), overweight/obesity (56.4%), ever smoking (38.5%), albuminuria (31.1%), estimated glomerular filtration rate < 60 mL/min/1.73 m2 (10.3%) and HbA1c > 7.0% (53 mmol/mol) (81.0%). Older age, longer diabetes duration, smoking and antihypertensive therapy use were positively associated with CVD, while high density lipoprotein-cholesterol and diastolic blood pressure were negatively associated (p < 0.05). Association with CVD and diabetes duration remained constant until 20 years when a linear increase was noted. Longer diabetes duration also had the highest population attributable risk of 6.5% (95% CI 1.4, 11.6). Further, the models for CVD demonstrated good discriminatory ability (area under the ROC curve 0.88; 95% CI 0.84, 0.92). CONCLUSIONS: Cardiovascular risk factors were prevalent and strongly associated with CVD among adults with type 1 diabetes attending Australian diabetes centres. Given the approximate J-shaped association between type 1 diabetes duration and CVD, the impact of cardiovascular risk stratification and management before and after 20 years duration needs to be further assessed longitudinally. Diabetes specific cardiovascular risk stratification tools incorporating diabetes duration should be an important consideration in future guideline development.

Depression and diabetes distress in adults with type 2 diabetes: results from the Australian National Diabetes Audit (ANDA) 2016.

This study explores the prevalence of, and factors associated with, likely depression and diabetes distress in adults with type 2 diabetes in a large, national sample. Australian National Diabetes Audit data were analysed from adults with type 2 diabetes attending 50 diabetes centres. The Brief Case find for Depression and Diabetes Distress Score 17 were administered to screen for likely depression and diabetes-related distress, respectively. A total of 2,552 adults with type 2 diabetes participated: (mean ± SD) age was 63 ± 13 years, diabetes duration was 12 ± 10 years, and HbA1c was 8 ± 2%. Twenty-nine percent of patients had likely depression, 7% had high diabetes distress, and 5% had both. Difficulty following dietary recommendations, smoking, forgetting medications, and diabetes distress were all associated with greater odds of depression whereas higher own health rating was associated with lower odds (all p < 0.02). Female gender, increasing HbA1c, insulin use, difficulty following dietary recommendations and depression were all associated with greater odds of diabetes distress & older age, higher own health rating and monitoring blood glucose levels as recommended were associated with lower odds (all p < 0.04). Depression was associated with sub-optimal self-care, while diabetes distress was associated with higher HbA1c and sub-optimal self-care.

Evaluating optimal utilisation of technology in type 1 diabetes mellitus from a clinical and health economic perspective: protocol for a systematic review.

BACKGROUND: Technology has been implemented since the 1970s with the hope of improving glycaemic control and reducing the burden of complications for those living with type 1 diabetes. A clinical and cost-effectiveness comparison of all available technologies including continuous subcutaneous insulin infusion (CSII), continuous glucose monitors (CGMs), sensor-augmented pump therapy (including either low-glucose suspend or predictive low-glucose suspend), hybrid closed-loop systems, closed-loop (single-hormone or dual-hormone) systems, flash glucose monitoring (FGM), insulin bolus calculators, and 'smart-device' applications is currently lacking. This systematic review, network meta-analysis, and narrative synthesis aims to summarise available evidence regarding the clinical and cost-effectiveness of available technologies in the management of patients with type 1 diabetes. METHODS: Relevant studies will be searched using a comprehensive strategy through MEDLINE, MEDLINE in-process and other non-indexed citations, EMBASE, PubMed, all evidenced-based medicine reviews, EconLit, Cost-effectiveness Analysis Registry, Research Papers in Economics, Web of Science, PsycInfo, CINAHL, and PROSPERO for randomised controlled trials and economic evaluations. The search strategy will assess if there are combinations of currently available technologies that are superior to each other or to insulin injections and capillary blood glucose testing with regard to glycaemic control, morbidity/mortality, quality of life, and cost-effectiveness. Two reviewers will screen all articles for eligibility and then independently evaluate risk of bias, complete quality assessment, and extract data for included studies. Network meta-analyses will be performed where there is sufficient homogenous clinical data. Narrative synthesis will be performed for heterogeneous clinical data that cannot be pooled for network meta-analysis with critical appraisal of economic evaluations. DISCUSSION: This systematic review protocol utilises rigorous methodology and pre-determined eligibility criteria to provide a uniquely comprehensive search for a broad spectrum of clinical and economic outcomes in comparing multiple currently available technologies for managing type 1 diabetes. Evidence on which technologies may be most appropriate for particular patient groups will be examined as well as the economic justification for funding of different technologies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ( CRD42017077221 ).

Microphthalmia, corneal dermoids, and congenital anomalies resembling Goldenhar syndrome in a cat.

CASE DESCRIPTION An 18-month-old spayed female domestic shorthair cat was evaluated because of conjunctivitis and skin-fold dermatitis secondary to bilateral microphthalmia, corneal dermoids, and ankyloblepharon. CLINICAL FINDINGS Physical examination revealed bilateral microphthalmia, bilaterally symmetrical corneal dermoids, ankyloblepharon, superior and inferior entropion, prognathism, and facial asymmetry with deviation of the nasal septum. Computed tomography revealed malformed, thickened bony orbits with mineralization of the orbital ligament bilaterally. Moderate rightward deviation of the nasal septum and ventral nasal meatus was also evident, with no identifiable maxillary sinuses. Results of MRI of the brain were unremarkable. Abdominal ultrasonography showed an irregularly marginated left kidney and a right kidney defect suggestive of chronic renal infarction. An abnormal, well-demarcated, focally thickened region of the muscularis externa of the jejunum was also evident. TREATMENT AND OUTCOME Transpalpebral enucleation was performed bilaterally. Histologic examination of ocular tissues confirmed the corneal dermoids and microphthalmia with anterior and posterior segment dysgenesis and cataracts in both eyes. Ocular discomfort resolved after postoperative recovery, and follow-up revealed that the patient's activity level and quality of life were excellent. No clinical signs of upper respiratory, urinary, or gastrointestinal tract disease were observed during the approximately 3.5-year follow-up period. CLINICAL RELEVANCE The congenital abnormalities observed resembled those described for human patients with Goldenhar syndrome, and the outcome of treatment was favorable. This report may prompt clinicians to consider this diagnosis when evaluating young cats with similar clinical signs.

Development of a minimally invasive approach to equine cervical articular facet joints for placement of an ND:YAG LASER.

The purpose of this study was to develop a minimally invasive approach to equine cervical articular facet joints for application of an ND:YAG LASER and to evaluate the effects of the laser fiber on the surrounding tissue. Under general anesthesia, an ND:YAG LASER was used to apply 2000 J of energy to 5 cervical articular facet joints in 3 horses (15 joints total). Horses were euthanized and the cervical facets and spinal cords were examined grossly and histologically. Gross pathology of the articular facets revealed evidence of articular cartilage charring and diffuse roughening of the surface. Histopathology confirmed coagulative necrosis. This novel technique allowed access to the cervical articular facet joints with the ND:YAG LASER and has the potential to allow performance of a minimally invasive facilitated ankylosis procedure. Further validation in sedated, standing horses is required to establish safety and efficacy of this technique.

Développement d'une approche minimalement invasive pour les facettes vertébrales lombaires équines pour le placement d'un LASER ND:YAG. Le but de cette étude était de développer une approche minimalement invasive pour l'application d'un LASER ND:YAG sur les facettes vertébrales lombaires équines et l'évaluation des effets de la fibre laser sur les tissus environnants. Sous anesthésie générale, un LASER ND:YAG a été utilisé pour appliquer 2000 J d'énergie à 5 facettes vertébrales lombaires chez 3 chevaux (total de 15 articulations). Les chevaux ont été euthanasiés et les facettes vertébrales et les colonnes vertébrales ont été examinées macroscopiquement et histologiquement. La pathologie macroscopique des facettes vertébrales lombaires a révélé des preuves de carbonisation du cartilage dens articulaires et un durcissement diffus de la surface. L'histopathologie a confirmé la nécrose decoagulatio. Cette technique nouvelle a permis l'accès aux facettes vertébrales lombaires avec le LASER ND:YAG et a le potentiel de permettre la réalisation d'interventions d'ankylose minimalement invasives. De nouvelles études de validation chez des chevaux debout sous sédation sont requises pour établir l'innocuité et l'efficacité de cette technique.(Traduit par Isabelle Vallières).

Corrigendum: Review of Evidence for Adult Diabetic Ketoacidosis Management Protocols.

[This corrects the article on p. 106 in vol. 8, PMID: 28659865.].

Correlation of dickkopf-1 concentrations in plasma and synovial fluid to the severity of radiographic signs of equine osteoarthritis.

OBJECTIVE: The purpose of this study was to determine whether there was a correlation between circulating and intra-synovial Dkk-1 and radiographic signs of equine osteoarthritis. METHODS: Circulating and intra-synovial Dkk-1 levels were measured in clinical cases using a commercially available human Dkk-1 ELISA. Radiographs were performed of the joints from which fluid was collected and these were assessed and scored by a boarded radiologist for joint narrowing, subchondral bone sclerosis, subchondral bone lysis, and periarticular modelling. Comparisons were made between radiographic scores and the concentrations of Dkk-1 using a Kruskal-Wallis one-way ANOVA. Correlations were calculated using Kendall's statistic. RESULTS: A total of 42 synovial fluid samples from 21 horses were collected and used in the analysis. No significant correlation was identified between Dkk-1 concentrations and radiographic signs of osteoarthritis. Intra-synovial Dkk-1 concentrations were significantly greater (p <0.001) in low motion joints (mean concentration, 232.68 pg/mL; range, 109.07-317.17) when compared to high-motion joints (28.78 pg/mL; 0.05-186.44 pg/mL) (p <0.001). CLINICAL SIGNIFICANCE: Low motion joints have significantly higher concentrations of Dkk-1 compared to high motion joints. Further research is needed to establish the importance of this finding and whether potential diagnostic or therapeutic applications of Dkk-1 exist in the horse.