Long-Term Complications in Youth-Onset Type 2 Diabetes.

BACKGROUND: The prevalence of type 2 diabetes in youth is increasing, but little is known regarding the occurrence of related complications as these youths transition to adulthood. METHODS: We previously conducted a multicenter clinical trial (from 2004 to 2011) to evaluate the effects of one of three treatments (metformin, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention) on the time to loss of glycemic control in participants who had onset of type 2 diabetes in youth. After completion of the trial, participants were transitioned to metformin with or without insulin and were enrolled in an observational follow-up study (performed from 2011 to 2020), which was conducted in two phases; the results of this follow-up study are reported here. Assessments for diabetic kidney disease, hypertension, dyslipidemia, and nerve disease were performed annually, and assessments for retinal disease were performed twice. Complications related to diabetes identified outside the study were confirmed and adjudicated. RESULTS: At the end of the second phase of the follow-up study (January 2020), the mean (±SD) age of the 500 participants who were included in the analyses was 26.4±2.8 years, and the mean time since the diagnosis of diabetes was 13.3±1.8 years. The cumulative incidence of hypertension was 67.5%, the incidence of dyslipidemia was 51.6%, the incidence of diabetic kidney disease was 54.8%, and the incidence of nerve disease was 32.4%. The prevalence of retinal disease, including more advanced stages, was 13.7% in the period from 2010 to 2011 and 51.0% in the period from 2017 to 2018. At least one complication occurred in 60.1% of the participants, and at least two complications occurred in 28.4%. Risk factors for the development of complications included minority race or ethnic group, hyperglycemia, hypertension, and dyslipidemia. No adverse events were recorded during follow-up. CONCLUSIONS: Among participants who had onset of type 2 diabetes in youth, the risk of complications, including microvascular complications, increased steadily over time and affected most participants by the time of young adulthood. Complications were more common among participants of minority race and ethnic group and among those with hyperglycemia, hypertension, and dyslipidemia. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov numbers, NCT01364350 and NCT02310724.).

Na+ riboswitches regulate genes for diverse physiological processes in bacteria.

Organisms presumably have mechanisms to monitor and physiologically adapt to changes in cellular Na+ concentrations. Only a single bacterial protein has previously been demonstrated to selectively sense Na+ and regulate gene expression. Here we report a riboswitch class, previously called the 'DUF1646 motif', whose members selectively sense Na+ and regulate the expression of genes relevant to sodium biology. Many proteins encoded by Na+-riboswitch-regulated genes are annotated as metal ion transporters, whereas others are involved in mitigating osmotic stress or harnessing Na+ gradients for ATP production. Na+ riboswitches exhibit dissociation constants in the low mM range, and strongly reject all other alkali and alkaline earth ions. Likewise, only Na+ triggers riboswitch-mediated transcription and gene expression changes. These findings reveal that some bacteria use Na+ riboswitches to monitor, adjust and exploit Na+ concentrations and gradients, and in some instances collaborate with c-di-AMP riboswitches to coordinate gene expression during osmotic stress.

Initial Insights into the Genetic Variation Associated with Metformin Treatment Failure in Youth with Type 2 Diabetes.

Metformin is the first-line treatment for type 2 diabetes (T2D) in youth but with limited sustained glycemic response. To identify common variants associated with metformin response, we used a genome-wide approach in 506 youth from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study and examined the relationship between T2D partitioned polygenic scores (pPS), glycemic traits, and metformin response in these youth. Several variants met a suggestive threshold (P < 1 × 10-6), though none including published adult variants reached genome-wide significance. We pursued replication of top nine variants in three cohorts, and rs76195229 in ATRNL1 was associated with worse metformin response in the Metformin Genetics Consortium (n = 7,812), though statistically not being significant after Bonferroni correction (P = 0.06). A higher ß-cell pPS was associated with a lower insulinogenic index (P = 0.02) and C-peptide (P = 0.047) at baseline and higher pPS related to two insulin resistance processes were associated with increased C-peptide at baseline (P = 0.04,0.02). Although pPS were not associated with changes in glycemic traits or metformin response, our results indicate a trend in the association of the ß-cell pPS with reduced ß-cell function over time. Our data show initial evidence for genetic variation associated with metformin response in youth with T2D.

Risk Factors for Complications in Ulnar Shortening Osteotomies: A Multicenter Retrospective Review.

PURPOSE: Ulnar shortening osteotomy (USO) is commonly performed to alleviate pathologies causing ulnar-sided wrist pain. Surgical complications include nonunion and hardware removal, with rates up to 18% and 45%, respectively. The primary objective of the study was to report the overall complication rate of USO. The secondary objective was to identify risk factors for complications. METHODS: A retrospective multicenter cohort review was undertaken, including six Canadian cities over a 6-year period (January 2013-December 2018). Chart review was used to collect demographic data, surgical technique, implant used, and postoperative complications. Descriptive statistics of demographics and operative characteristics, including plate positioning, type of osteotomy, plate type, and ulnar variance (mm), were analyzed. Univariate analyses were used to select predictor variables for nonunion and hardware removal. These predictor variables were then entered into an adjusted multivariable logistic regression model. RESULTS: A total of 361 USOs were performed. Mean age was 46 ± 16 years (60.7% men). The overall complication rate was 37.1%, hardware removal rate was 29.6%, and nonunion rate was 9.4%. There was a workers' compensation claim associated with 21.6% of all complications, and it was a risk factor for both hardware removal (odds ratio [OR] = 3.81) and nonunion (OR = 2.88). Neither smoking nor diabetes was associated with complication rates. Seventy percent of plates were placed volarly, 25.5% dorsally, and 3.9% directly ulnar. Osteotomies were oblique in 83.7% of cases and transverse in 15.5%. Adjusted multivariate regression analysis revealed that younger age (OR = 0.98) was a risk factor for hardware removal and male sex (OR = 2.49) was a risk factor for nonunion. A surgical factor associated with hardware removal was direct ulnar plate placement (OR = 9.93). No surgical factors were associated with nonunions. CONCLUSIONS: There are substantial rates of complications with USOs. Direct ulnar plate placement should be avoided. Patients should be thoroughly counseled on the risks of complications prior to proceeding with USO. LEVEL OF EVIDENCE: Therapeutic IV.

Infections in the first year of life and development of beta cell autoimmunity and clinical type 1 diabetes in high-risk individuals: the TRIGR cohort.

AIMS/HYPOTHESIS: Accumulated data suggest that infections in early life contribute to the development of type 1 diabetes. Using data from the Trial to Reduce IDDM in the Genetically at Risk (TRIGR), we set out to assess whether children who later developed diabetes-related autoantibodies and/or clinical type 1 diabetes had different exposure to infections early in life compared with those who did not. METHODS: A cohort of 2159 children with an affected first-degree relative and HLA-conferred susceptibility to type 1 diabetes were recruited between 2002 and 2007 and followed until 2017. Infections were registered prospectively. The relationship between infections in the first year of life and the development of autoantibodies or clinical type 1 diabetes was analysed using univariable and multivariable Cox regression models. As this study was exploratory, no adjustment was made for multiple comparisons. RESULTS: Adjusting for HLA, sex, breastfeeding duration and birth order, those who had seven or more infections during their first year of life were more likely to develop at least one positive type 1 diabetes-related autoantibody (p=0.028, HR 9.166 [95% CI 1.277, 65.81]) compared with those who had no infections. Those who had their first viral infection aged between 6 and 12 months were less likely to develop at least one positive type 1 diabetes-related antibody (p=0.043, HR 0.828 [95% CI 0.690, 0.994]) or multiple antibodies (p=0.0351, HR 0.664 [95% CI 0.453, 0.972]). Those who had ever had an unspecified bacterial infection were more likely to develop at least one positive type 1 diabetes-related autoantibody (p=0.013, HR 1.412 [95% CI 1.075, 1.854]), to develop multiple antibodies (p=0.037, HR 1.652 [95% CI 1.030, 2.649]) and to develop clinical type 1 diabetes (p=0.011, HR 2.066 [95% CI 1.182, 3.613]). CONCLUSIONS/INTERPRETATION: We found weak support for the assumption that viral infections early in life may initiate the autoimmune process or later development of type 1 diabetes. In contrast, certain bacterial infections appeared to increase the risk of both multiple autoantibodies and clinical type 1 diabetes.

Longitudinal progression of diabetes mellitus in Wolfram syndrome: The Washington University Wolfram Research Clinic experience.

OBJECTIVE: (1) Describe the progression of diabetes mellitus over time in an observational study of Wolfram syndrome, a rare, genetic, neurodegenerative disorder, which often includes diabetes mellitus and is typically diagnosed during childhood or adolescence. (2) Determine whether C-peptide could be used as a marker of diabetes progression in interventional trials for Wolfram syndrome. METHODS: N = 44 (25F/19M) participants with genetically confirmed Wolfram syndrome attended the Washington University Wolfram Research Clinic annually from 2010 to 2019. Medical history, physical examinations, blood sampling, and questionnaires were used to collect data about diabetes mellitus and other components of Wolfram syndrome. Beta-cell function was assessed by determination of C-peptide during a mixed meal tolerance test. Random coefficients models evaluated the rate of progression of C-peptide over time, and power analyses were used to estimate the number of subjects needed to detect a change in C-peptide decline during an intervention trial. RESULTS: 93.2% of patients had diabetes mellitus. Mean HbA1c across all study visits was 7.9%. C-peptide significantly decreased with increasing duration of diabetes mellitus (p < 0.0001); an optimal break point in C-peptide decline was identified to occur between 0.1 and 2.3 years after diabetes mellitus diagnosis. Twenty patients per group (active vs. control) were estimated to be needed to detect a 60% slowing of C-peptide decline during the first 2.3 years following diabetes diagnosis. CONCLUSION: C-peptide declines over time in Wolfram syndrome and could potentially be used as a marker of diabetes progression in interventional studies for Wolfram syndrome, especially within the first 2 years after diabetes diagnosis.

Architectures and complex functions of tandem riboswitches.

Riboswitch architectures that involve the binding of a single ligand to a single RNA aptamer domain result in ordinary dose-response curves that require approximately a 100-fold change in ligand concentration to cover nearly the full dynamic range for gene regulation. However, by using multiple riboswitches or aptamer domains in tandem, these ligand-sensing structures can produce additional, complex gene control outcomes. In the current study, we have computationally searched for tandem riboswitch architectures in bacteria to provide a more complete understanding of the diverse biological and biochemical functions of gene control elements that are made exclusively of RNA. Numerous different arrangements of tandem homologous riboswitch architectures are exploited by bacteria to create more 'digital' gene control devices, which operate over a narrower ligand concentration range. Also, two heterologous riboswitch aptamers are sometimes employed to create two-input Boolean logic gates with various types of genetic outputs. These findings illustrate the sophisticated genetic decisions that can be made by using molecular sensors and switches based only on RNA.

Electrical Discharges in Oil-Lubricated Rolling Contacts and Their Detection Using Electrostatic Sensing Technique.

The reliability of rolling element bearings has been substantially undermined by the presence of parasitic and stray currents. Electrical discharges can occur between the raceway and the rolling elements and it has been previously shown that these discharges at relatively high current density levels can result in fluting and corrugation damages. Recent publications have shown that for a bearing operating at specific mechanical conditions (load, temperature, speed, and slip), electrical discharges at low current densities (<1 mA/mm2) may substantially reduce bearing life due to the formation of white etching cracks (WECs) in bearing components, often in junction with lubricants. To date, limited studies have been conducted to understand the electrical discharges at relatively low current densities (<1 mA/mm2), partially due to the lack of robust techniques for in-situ quantification of discharges. This study, using voltage measurement and electrostatic sensors, investigates discharges in an oil-lubricated steel-steel rolling contact on a TE74 twin-roller machine under a wide range of electrical and mechanical conditions. The results show that the discharges events between the rollers are influenced by temperature, load, and speed due to changes in the lubricant film thickness and contact area, and the sensors are effective in detecting, characterizing and quantifying the discharges. Hence, these sensors can be effectively used to study the influence of discharges on WEC formation.

A capaciflector provides continuous and accurate respiratory rate monitoring for patients at rest and during exercise.

Respiratory rate (RR) is a marker of critical illness, but during hospital care, RR is often inaccurately measured. The capaciflector is a novel sensor that is small, inexpensive, and flexible, thus it has the potential to provide a single-use, real-time RR monitoring device. We evaluated the accuracy of continuous RR measurements by capaciflector hardware both at rest and during exercise. Continuous RR measurements were made with capaciflectors at four chest locations. In healthy subjects (n = 20), RR was compared with strain gauge chest belt recordings during timed breathing and two different body positions at rest. In patients undertaking routine cardiopulmonary exercise testing (CPET, n = 50), RR was compared with pneumotachometer recordings. Comparative RR measurement bias and limits of agreement were calculated and presented in Bland-Altman plots. The capaciflector was shown to provide continuous RR measurements with a bias less than 1 breath per minute (BPM) across four chest locations. Accuracy and continuity of monitoring were upheld even during vigorous CPET exercise, often with narrower limits of agreement than those reported for comparable technologies. We provide a unique clinical demonstration of the capaciflector as an accurate breathing monitor, which may have the potential to become a simple and affordable medical device.Clinical trial number: NCT03832205 https://clinicaltrials.gov/ct2/show/NCT03832205 registered February 6th, 2019.

Cannabis use patterns among patients with upper extremity conditions at the time of legalization in Canada.

BACKGROUND: Recreational cannabis use was legalized in Canada in 2018. Cannabis use patterns and patient attitudes toward cannabis use, particularly in the context of these legal changes, are not well understood. Our aim was to evaluate baseline cannabis use patterns and attitudes at the time of legalization among patients with upper extremity conditions in Canada. METHODS: In 2018, we conducted a multicentre cross-sectional survey study of 1561 patients with upper extremity conditions at 7 surgical centres. Participants were asked whether they currently use cannabis. If yes, they were asked questions regarding usage patterns and perceptions of cannabis use, including likelihood of use, safety and comfort discussing it with their physician. RESULTS: In the 6 months after legalization, 790 (51%) participants felt that cannabis was safer than prescription narcotics, with 450 (29%) currently using cannabis. Reasons for cannabis use included pain (56%), stress (51%) and recreation (42%). Of the 1105 patients not using cannabis, 267 (24%) were more likely to consider it after legalization. Of the 450 cannabis users, 73 (16%) had been using it for less than 6 months, 206 (46%) stated they were more comfortable discussing cannabis with their physician after legalization and 195 (43%) were using cannabis more than 4 times per week. CONCLUSION: Many patients with upper extremity conditions were regularly using cannabis. Patients were more comfortable discussing cannabis with their physician than before legalization. Treating surgeons should be aware of these trends and expect to receive questions regarding cannabis use.

Implementation of School Diabetes Care in the United States: A Scoping Review.

Diabetes management at school demands close collaboration of multiple stakeholders, including students with diabetes and parents, school nurses, teachers/staff, and local health care providers. This scoping review identified and synthesized evidence concerning factors that contributed to the quality and effectiveness of diabetes care implementation in U.S. K-12 schools. Forty-six studies met the eligibility criteria and were included. Five common factors emerged surrounding training and experiences, communications, parent engagement, resource allocations, and school environment. Complex interactions between multiple stakeholders jointly determined the quality of school diabetes care. A conceptual model was established to elucidate the complex interactions between multiple stakeholders and the relevant facilitators and barriers. Future research should improve sample representativeness, contrast school diabetes care practices to the national guidelines, and assess the impact of the social, economic, and political environment at federal, state, local/district levels on school diabetes care implementation.

Comprehensive discovery of novel structured noncoding RNAs in 26 bacterial genomes.

Comparative sequence analysis methods are highly effective for uncovering novel classes of structured noncoding RNAs (ncRNAs) from bacterial genomic DNA sequence datasets. Previously, we developed a computational pipeline to more comprehensively identify structured ncRNA representatives from individual bacterial genomes. This search process exploits the fact that genomic regions serving as templates for the transcription of structured RNAs tend to be present in longer than average noncoding 'intergenic regions' (IGRs) that are enriched in G and C nucleotides compared to the remainder of the genome. In the present study, we apply this computational pipeline to identify structured ncRNA candidates from 26 diverse bacterial species. Numerous novel structured ncRNA motifs were discovered, including several riboswitch candidates, one whose ligand has been identified and others that have yet to be experimentally validated. Our findings support recent predictions that hundreds of novel ribo-switch classes and other ncRNAs remain undiscovered among the limited number of bacterial species whose genomes have been completely sequenced.

The Staircase Drive-A Novel Actuator Design Optimised for Daisy-Chaining and Minimum Stress Load Coupling.

This work presents a novel type of actuator that improves over the standard cantilever by permitting daisy-chaining while minimising stress to the joint connecting to the load. A detailed structural and functional comparison of the proposed device against the cantilever actuator as a baseline is given, led by a brief revision of the cantilever actuator as the state-of-the-art that highlights its limitations with respect to daisy-chaining and the stress it inherently creates within the joint connecting to the load when attempting out-of-plane displacement without rotation. Simulations of both devices' performance confirm that the newly proposed device yields the targeted displacement profile that both enables the daisy-chaining of such a device into a higher-order actuator for increased displacement and reduce stress in the joint with the load. This comes at the cost of reduced maximum displacement compared to the cantilever, which can be overcome by daisy-chaining. The proposed device's performance is further evaluated on the basis of manufactured prototypes measured by means of a laser scanning vibrometer. The prototype was manufactured on a 150 µm alumina substrate, and both electrodes and piezoelectric layer were deposited in a thick-film printing process.

Management of patients with hip fracture receiving anticoagulation: What are we doing in Canada?

BACKGROUND: Direct oral anticoagulants (DOACs) are rapidly replacing warfarin for therapeutic anticoagulation; however, many DOACs are irreversible and may complicate bleeding in emergent situations such as hip fracture. In this setting, there is a lack of clear guidelines for the timing of surgery. The purpose of this study was to evaluate the current practices of Canadian orthopedic surgeons who manage patients with hip fracture receiving anticoagulation. METHODS: In January-March 2018, we administered a purpose-specific cross-sectional survey to all currently practising orthopedic surgeons in Canada who had performed hip fracture surgery in 2017. The survey evaluated approaches to decision-making and timing of surgery in patients with hip fracture receiving anticoagulation. RESULTS: A total of 280 surgeons representing a mix of academic and community practice, seniority and fellowship training responded. Nearly one-quarter of respondents (66 [23.4%]) were members of the Canadian Orthopaedic Trauma Society (COTS). Almost three-quarters (206 [73.6%]) felt that adequate clinical guidelines for patients with hip fracture receiving anticoagulation did not exist, and 177 (61.9%) indicated that anesthesiology or internal medicine had a greater influence on the timing of surgery than the attending surgeon. A total of 117/273 respondents (42.9%) indicated that patients taking warfarin should have immediate surgery (with or without reversal), compared to 63/270 (23.3%) for patients taking a DOAC (p < 0.001). Members of COTS were more likely than nonmembers to advocate for immediate surgery in all patients (p < 0.05). CONCLUSION: There is wide variability in Canada in the management of patients with hip fracture receiving anticoagulation. Improved multidisciplinary communication, prospectively evaluated treatment guidelines and focus on knowledge translation may add clarity to this issue. LEVEL OF EVIDENCE: IV.

Coupling between conformational dynamics and catalytic function at the active site of the lead-dependent ribozyme.

In common with other self-cleaving RNAs, the lead-dependent ribozyme (leadzyme) undergoes dynamic fluctuations to a chemically activated conformation. We explored the connection between conformational dynamics and self-cleavage function in the leadzyme using a combination of NMR spin-relaxation analysis of ribose groups and conformational restriction via chemical modification. The functional studies were performed with a North-methanocarbacytidine modification that prevents fluctuations to C2'-endo conformations while maintaining an intact 2'-hydroxyl nucleophile. Spin-relaxation data demonstrate that the active-site Cyt-6 undergoes conformational exchange attributed to sampling of a minor C2'-endo state with an exchange lifetime on the order of microseconds to tens of microseconds. A conformationally restricted species in which the fluctuations to the minor species are interrupted shows a drastic decrease in self-cleavage activity. Taken together, these data indicate that dynamic sampling of a minor species at the active site of this ribozyme, and likely of related naturally occurring motifs, is strongly coupled to catalytic function. The combination of NMR dynamics analysis with functional probing via conformational restriction is a general methodology for dissecting dynamics-function relationships in RNA.

Parameter estimation for functional-structural plant models when data are scarce: using multiple patterns for rejecting unsuitable parameter sets.

BACKGROUND AND AIMS: Functional-structural plant (FSP) models provide insights into the complex interactions between plant architecture and underlying developmental mechanisms. However, parameter estimation of FSP models remains challenging. We therefore used pattern-oriented modelling (POM) to test whether parameterization of FSP models can be made more efficient, systematic and powerful. With POM, a set of weak patterns is used to determine uncertain parameter values, instead of measuring them in experiments or observations, which often is infeasible. METHODS: We used an existing FSP model of avocado (Persea americana 'Hass') and tested whether POM parameterization would converge to an existing manual parameterization. The model was run for 10 000 parameter sets and model outputs were compared with verification patterns. Each verification pattern served as a filter for rejecting unrealistic parameter sets. The model was then validated by running it with the surviving parameter sets that passed all filters and then comparing their pooled model outputs with additional validation patterns that were not used for parameterization. KEY RESULTS: POM calibration led to 22 surviving parameter sets. Within these sets, most individual parameters varied over a large range. One of the resulting sets was similar to the manually parameterized set. Using the entire suite of surviving parameter sets, the model successfully predicted all validation patterns. However, two of the surviving parameter sets could not make the model predict all validation patterns. CONCLUSIONS: Our findings suggest strong interactions among model parameters and their corresponding processes, respectively. Using all surviving parameter sets takes these interactions into account fully, thereby improving model performance regarding validation and model output uncertainty. We conclude that POM calibration allows FSP models to be developed in a timely manner without having to rely on field or laboratory experiments, or on cumbersome manual parameterization. POM also increases the predictive power of FSP models.

PrEvention of posttraumatic contractuRes with Ketotifen 2 (PERK 2) - protocol for a multicenter randomized clinical trial.

BACKGROUND: Injuries and resulting stiffness around joints, especially the elbow, have huge psychological effects by reducing quality of life through interference with normal daily activities such as feeding, dressing, grooming, and reaching for objects. Over the last several years and through numerous research results, the myofibroblast-mast cell-neuropeptide axis of fibrosis had been implicated in post-traumatic joint contractures. Pre-clinical models and a pilot randomized clinical trial (RCT) demonstrated the feasibility and safety of using Ketotifen Fumarate (KF), a mast cell stabilizer to prevent elbow joint contractures. This study aims to evaluate the efficacy of KF in reducing joint contracture severity in adult participants with operately treated elbow fractures and/or dislocations. METHODS/DESIGN: A Phase III randomized, controlled, double-blinded multicentre trial with 3 parallel groups (KF 2 mg or 5 mg or lactose placebo twice daily orally for 6 weeks). The study population consist of adults who are at least 18 years old and within 7 days of injury. The types of injuries are distal humerus (AO/OTA type 13) and/or proximal ulna and/or proximal radius fractures (AO/OTA type 2 U1 and/or 2R1) and/or elbow dislocations (open fractures with or without nerve injury may be included). A stratified randomization scheme by hospital site will be used to assign eligible participants to the groups in a 1:1:1 ratio. The primary outcome is change in elbow flexion-extension range of motion (ROM) arc from baseline to 12 weeks post-randomization. The secondary outcomes are changes in ROM from baseline to 6, 24 & 52 weeks, PROMs at 2, 6, 12, 24 & 52 weeks and impact of KF on safety including serious adverse events and fracture healing. Descriptive analysis for all outcomes will be reported and ANCOVA be used to evaluate the efficacy KF over lactose placebo with respect to the improvement in ROM. DISCUSSION: The results of this study will provide evidence for the use of KF in reducing post-traumatic joint contractures and improving quality of life after joint injuries. TRIAL REGISTRATION: This study was prospectively registered (July 10, 2018) with ClinicalTrials.gov reference: NCT03582176.

Does diabetes prevention translate into reduced long-term vascular complications of diabetes?

The global epidemic of type 2 diabetes has prompted numerous studies and public health efforts to reduce its development. A variety of interventions, including lifestyle modifications and pharmacological agents directed at ameliorating the major risk factors for type 2 diabetes, are of proven efficacy in reducing the development of type 2 diabetes in people with impaired glucose tolerance. While prevention of the hyperglycaemia characteristic of diabetes is arguably an important, clinically relevant outcome, a more compelling outcome with greater clinical significance is the prevention or reduction of the relatively diabetes-specific microvascular and less-specific cardiovascular disease (CVD) complications associated with diabetes. These complications cause the majority of morbidity and excess mortality associated with diabetes. Any reduction in diabetes should, logically, also reduce the occurrence of its long-term complications; however, most diabetes prevention trials have not been of sufficient duration to allow such an evaluation. The limited long-term data, largely from the Da Qing Diabetes Prevention Study (DQDPS) and the Diabetes Prevention Program (DPP) and their respective follow-up studies (DQDPOS and DPPOS), suggest a reduction in microvascular complications and amelioration of CVD risk factors. Only the DQDPOS and Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) studies have shown a reduction in CVD events and only DQDPOS has demonstrated a decrease in CVD and overall mortality. While these limited data are promising, whether diabetes prevention directly reduces complication-related morbidity and mortality remains unclear. Longer follow-up of prevention studies is needed to supplement the limited current clinical trial data, to help differentiate the effects of diabetes prevention itself from the means used to reduce diabetes development and to understand the balance among benefits, risks and costs of prevention.

Screening eye exams in youth with type 1 diabetes under 18 years of age: Once may be enough?

Case series and registry data suggest that diabetic retinopathy requiring treatment is rare in youth with type 1 diabetes (T1D) prior to 18 years of age. We evaluated this question in the standardized clinical trial setting by retrospectively reviewing diabetic retinopathy examinations from participants in the Diabetes Control and Complications Trial (DCCT) who were 13 to <18 years of age at randomization. Standardized stereoscopic 7-field fundus photographs were obtained every 6 months during DCCT (1983-1993). Photographs were graded centrally using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Transitions in diabetic retinopathy status over time were described. A total of 195 participants with median baseline glycated hemoglobin (HbA1c) of 9.3% (103 in the conventional and 92 in the intensive treatment groups) had an average of 5.3 diabetic retinopathy assessments during 2.3 years of follow-up (range 1-11) while under 18 years of age during the DCCT. No participant developed severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy and only one participant (in the intensive group) reached clinically significant macular edema (CSME) while less than 18 years of age. In this incident case, baseline characteristics included diabetes duration 9.3 years, HbA1c 10.3%, LDL 131 mg/dL, and mild non-proliferative diabetic retinopathy (35/35 ETDRS scale); CSME resolved without treatment. Similar analyses using age cut-offs of <19, 20, or 21 years showed a slight rise in diabetic retinopathy requiring treatment over late adolescence. Clinical trial evidence suggests that frequent eye exams may not be universally necessary in youth <18 years of age with T1D.

Surgical outcomes of chronic isolated scapholunate interosseous ligament injuries: a systematic review of 805 wrists

Background: Management of chronic isolated scapholunate interosseous ligament (SLIL) injuries has generated a substantial volume of low-quality literature with descriptions of multiple new surgical techniques, and the impact of instability pattern and the optimal surgical technique remain unclear. The primary goal of this review was to compare clinical, radiographic and patient-rated outcomes between current surgical techniques. Methods: We performed a systematic literature search using multiple databases. We analyzed clinical, radiographic and patient-reported outcomes. We used a fixed-effects model weighted by sample size with combined outcomes estimated via least squares means with 95% confidence intervals. We also performed a subgroup analysis of static versus dynamic instability. Results: We assessed 805 procedures from 37 study groups, with 429 procedures used in subgroup analysis. There were no statistically significant differences in outcomes between surgical techniques or in subgroup analysis. Overall, postoperative wrist flexion and pain scores decreased, and grip strength and patient-rated outcomes improved. Conclusion: Compared to overall preoperative values, modest improvements in pain score, grip strength and functional outcome scores were obtained from a range of reconstructive procedures performed for chronic isolated SLIL injuries. No significant differences could be ascertained between surgical techniques, potentially owing to the low quality of evidence and procedure heterogeneity. This study provides accurate preoperative reference values for future studies, highlights the controversial clinical impact of instability classification, and the need for higher-quality multicentre or collaborative trials to improve our understanding and management of this common injury.

Contexte: La prise en charge des blessures chroniques du ligament interosseux scapho-lunaire (LISL) a généré un volume substantiel d'articles de faible qualité où sont décrites plusieurs nouvelles techniques chirurgicales, mais l'impact du modèle d'instabilité et la technique chirurgicale optimale restent à clarifier. Le principal objectif de cette revue était de comparer les résultats cliniques, radiographiques et autodéclarés par les patients entre les diverses techniques chirurgicales actuelles. Méthodes: Nous avons procédé à une interrogation systématique de la littérature dans plusieurs bases de données. Nous avons analysé les résultats cliniques, radiographiques et autodéclarés par les patients. Nous avons utilisé un modèle à effets fixes pondéré par la taille de l'échantillon, avec paramètres mixtes estimés par les moyennes des moindres carrés et des intervalles de confiance à 95 %. Nous avons aussi effectué une analyse de sous-groupes (instabilité radiographique dynamique c. statique). Résultats: Nous avons évalué 805 interventions dans 37 groupes étudiés, et 429 interventions ont été utilisées dans les analyses de sous-groupes. On n'a noté aucune différence statistiquement significative pour ce qui est des résultats entre les techniques chirurgicales ni dans les analyses de sous-groupes. Globalement, la flexion du poignet et la douleur ont diminué, et la force préhensile et autres paramètres autodéclarés par les patients se sont améliorés. Conclusion: Comparativement aux valeurs préopératoires globales, de modestes améliorations du score de douleur, de la force préhensile et des paramètres fonctionnels ont été obtenues au moyen de diverses interventions de reconstruction effectuées pour des blessures chroniques isolées du LISL. Aucune différence significative n'a pu être confirmée entre les techniques chirurgicales, probablement en raison de la faible qualité des données et de l'hétérogénéité des interventions. Cette étude fournit des valeurs de référence préopératoires précises pour de futures études et souligne l'impact clinique controversé de la classification de l'instabilité, ainsi que la nécessité de procéder à des essais multicentriques ou collaboratifs de meilleure qualité pour mieux comprendre et prendre en charge ce type fréquent de blessure.