LDL cholesterol level as a risk factor for retinopathy and nephropathy in children and adults with type 1 diabetes mellitus: A nationwide cohort study.

BACKGROUND: Microvascular complications are common in people with diabetes, where poor glycaemic control is the major contributor. The aim of this study was to explore the association between elevated LDL cholesterol levels and the risk of retinopathy or nephropathy in young individuals with type 1 diabetes. METHODS: This was a nationwide observational population-based cohort study, including all children and adults with a duration of type 1 diabetes of ≤ 10 years, identified in the Swedish National Diabetes Register between 1998 and 2017. We calculated the crude incidence rates with 95% confidence intervals (CIs) and used multivariable Cox regression to estimate crude and adjusted hazard ratios (HRs) of retinopathy or nephropathy in four LDL cholesterol categories: <2.6 (Reference), 2.6-3.4, 3.4-4.1 and > 4.1 mmol L-1 . RESULTS: In total, 11 024/12 350 (retinopathy/nephropathy, both cohorts, respectively) children and adults (median age 21 years, female 42%) were followed up to 28 years from diagnosis until end of study. Median duration of diabetes when entering the study was 6 and 7 years in the retinopathy and nephropathy cohort, respectively. Median LDL cholesterol was 2.4 mmol L-1 , and median HbA1c level was 61 mmol mol-1 (7.7 %). After multivariable adjustment, the HRs (95% CI) for retinopathy in individuals with LDL cholesterol levels of 2.6-3.4, 3.4-4.1 or > 4.1 mmol L-1 were as follows: 1.13 (1.03-1.23), 1.16 (1.02-1.32) and 1.18 (0.99-1.41), compared with the reference. The corresponding numbers for nephropathy were as follows: 1.15 (0.96-1.32), 1.30 (1.03-1.65) and 1.41 (1.06-1.89). CONCLUSIONS: Young individuals with type 1 diabetes exposed to high LDL cholesterol levels have an increased risk of retinopathy and nephropathy independent of glycaemia and other identified risk factors for vascular complications.

One-carbon metabolism markers are associated with cardiometabolic risk factors.

BACKGROUND AND AIMS: Alterations to one-carbon metabolism, especially elevated plasma homocysteine (Hcy), have been suggested to be both a cause and a consequence of the metabolic syndrome (MS). A deeper understanding of the role of other one-carbon metabolites in MS, including s-adenosylmethionine (SAM), s-adenosylhomocysteine (SAH), and the methylation capacity index (SAM:SAH ratio) is required. METHODS AND RESULTS: 118 men and women with MS-risk factors were included in this cross-sectional study and cardiometabolic outcomes along with markers of one-carbon metabolism, including fasting plasma SAM, SAH, Hcy and vitamin B12 concentrations, were analysed. Multiple linear regression models were also used to examine the association between plasma one-carbon metabolites and cardiometabolic health features. We found that fasting plasma concentrations of Hcy, SAM and SAH were all positively correlated with markers of adiposity, including BMI (increase in BMI per 1-SD increase in one-carbon metabolite: 0.92 kg/m2 95% CI (0.28; 1.56), p = 0.005; 0.81 (0.15; 1.47), p = 0.02; 0.67 (-0.01; 1.36), p = 0.05, respectively). Hcy, but not SAM, SAH or SAM:SAH ratio was associated with BMI and body fat percentage after mutual adjustments. SAM concentrations were associated with higher fasting insulin (9.5% 95% CI (0.3; 19.5) per SD increase in SAM, p = 0.04), HOMA-IR (10.8% (0.8; 21.9), p = 0.03) and TNF-α (11.8% (5.0; 19.0), p < 0.001). CONCLUSION: We found little evidence for associations between SAM:SAH ratio and cardiometabolic variables, but higher plasma concentrations of SAM, SAH and Hcy are related to an overall higher risk of metabolic dysfunctions. The studies were registered at www.clinicaltrials.gov (NCT01719913 &NCT01731366).

The SMS, Phone, and medical Examination sports injury surveillance system is a feasible and valid approach to measuring handball exposure, injury occurrence, and consequences in elite youth sport.

Current methods of sports injury surveillance are limited by lack of medical validation of self-reported injuries and/or incomplete information about injury consequences beyond time loss from sport. The aims of this study were to (a) evaluate the feasibility of the SMS, Phone, and medical Examination injury surveillance (SPEx) system (b) to evaluate the proportion of injuries and injury consequences reported by SPEx when compared to outcomes from a modified version of the Oslo Sports Trauma Research Centre (OSTRC) Overuse Injury Questionnaire. We followed 679 elite adolescent handball players over 31 weeks using the SPEx system. During the last 7 weeks, we also implemented a modified OSTRC questionnaire in a subgroup of 271 players via telephone interviews. The weekly response proportions to the primary SPEx questions ranged from 85% to 96% (mean 92%). SMS responses were received from 79% of the participants within 1 day. 95% of reported injuries were classified through the telephone interview within a week, and 67% were diagnosed by medical personnel. Comparisons between reported injuries from SPEx and OSTRC demonstrated fair (κ = 39.5% [25.1%-54.0%]) to substantial prevalence-adjusted bias-adjusted kappa (PABAK = 66.8% [95% CI 58.0%-75.6%]) agreement. The average injury severity score difference between SPEx and the OSTRC approach was -0.2 (95% CI -3.69-3.29) of possible 100 with 95% limits of agreement from(-14.81-14.41). These results support the feasibility and validity of the SPEx injury surveillance system in elite youth sport. Future studies should evaluate the external validity of SPEx system in different cohorts of athletes.

Validity of the SMS, Phone, and medical staff Examination sports injury surveillance system for time-loss and medical attention injuries in sports.

The accurate measurement of sport exposure time and injury occurrence is key to effective injury prevention and management. Current measures are limited by their inability to identify all types of sport-related injury, narrow scope of injury information, or lack the perspective of the injured athlete. The aims of the study were to evaluate the proportion of injuries and the agreement between sport exposures reported by the SMS messaging and follow-up telephone part of the SMS, Phone, and medical staff Examination (SPEx) sports injury surveillance system when compared to measures obtained by trained on-field observers and medical staff (comparison method). We followed 24 elite adolescent handball players over 12 consecutive weeks. Eighty-six injury registrations were obtained by the SPEx and comparison methods. Of them, 35 injury registrations (41%) were captured by SPEx only, 10 injury registrations (12%) by the comparison method only, and 41 injury registrations (48%) by both methods. Weekly exposure time differences (95% limits of agreement) between SPEx and the comparison method ranged from -4.2 to 6.3 hours (training) and -1.5 to 1.0 hours (match) with systematic differences being 1.1 hours (95% CI 0.7 to 1.4) and -0.2 (95% CI -0.3 to -0.2), respectively. These results support the ability of the SPEx system to measure training and match exposures and injury occurrence among young athletes. High weekly response proportions (mean 83%) indicate that SMS messaging can be used for player measures of injury consequences beyond time-loss from sport. However, this needs to be further evaluated in large-scale studies.

Glycaemic control and excess risk of ischaemic and haemorrhagic stroke in patients with type 1 diabetes: a cohort study of 33 453 patients.

OBJECTIVE: To estimate the excess risk of stroke in relation to glycaemic control in patients with type 1 diabetes. METHODS: In this prospective, matched cohort study, we identified patients with type 1 diabetes, aged ≥18 years, who were registered in the Swedish National Diabetes Register from 1998-2011 and five control subjects for each case from the general population, matched for age, sex and county of residence. The risks of all strokes, ischaemic stroke and haemorrhagic stroke were estimated using Cox hazard regression. RESULTS: Of 33 453 type 1 diabetes patients [mean age, 35.5 (SD 14.4) years; mean follow-up, 7.9 (SD 4.3) years; and mean diabetes duration, 20.2 years (SD 14.6)], 762 (2.3%) were diagnosed with stroke compared with 1122 (0.7%) of 159 924 control subjects [mean follow-up, 8.2 (SD 4.3) years]. The overall multiple-adjusted hazard ratios (HRs) for type 1 diabetes patients versus control subjects were 3.29 (95% CI: 2.96-3.66) and 2.49 (95% CI: 1.96-3.16) for ischaemic and haemorrhagic stroke, respectively. The risk of ischaemic and haemorrhagic stroke incrementally increased with increasing HbA1c; the risk of ischaemic stroke was significantly increased with HbA1c within target [≤6.9% (≤52 mmol mol-1 )] [multiple-adjusted HR 1.89 (95% CI: 1.44-2.47)]. For HbA1c ≥9.7% (≥83 mmol mol-1 ), there was a markedly increased risk of both ischaemic and haemorrhagic stroke, with multiple-adjusted HRs of 7.94 (95% CI: 6.29-10.03) and 8.17 (95% CI 5.00-13.35), respectively. CONCLUSIONS: Individuals with type 1 diabetes have an increased risk of ischaemic and haemorrhagic stroke, increasing markedly with poor glycaemic control.

Long-term excess risk of stroke in people with Type 2 diabetes in Sweden according to blood pressure level: a population-based case-control study.

AIMS: To estimate the risk of stroke in people with Type 2 diabetes with different blood pressure levels compared with the risk in the general population in Sweden. METHODS: This prospective case-control study included 408 076 people with Type 2 diabetes, aged ≥ 18 years, and free of prior stroke, registered in the Swedish National Diabetes Register 1998-2011. Age- and sex-matched control subjects (n = 1 913 507) without stroke from the general population were included. Stroke diagnoses were retrieved using International Classification of Disease codes from the Swedish patient and death registers. Cox hazard ratios and 95% confidence intervals (CIs) were estimated at six different blood pressure levels. RESULTS: During a median follow-up of 4 years, 19 548 (4.8%) people with Type 2 diabetes and 61 690 (3.2%) without diabetes were diagnosed with stroke, corresponding to an adjusted hazard ratio of 1.43 (95% CI 1.41-1.46) for people with Type 2 diabetes as a group. Compared with people without diabetes, the risk of stroke for people with Type 2 diabetes with different blood pressure levels was significantly higher, starting at blood pressure levels > 130/80 mmHg. Hazard ratios for stroke were 1.20 (95% CI 1.16-1.24), 1.47 (95% CI 1.43-1.50), and 1.97 (95% CI 1.90-2.03) for blood pressure categories of 130-139/80-89 mmHg, 140-159/90-99 mmHg and ≥ 160/≥ 100 mmHg, respectively, after adjustment for age, sex, diabetes duration, being born in Sweden, maximum education level and baseline comorbidities. CONCLUSIONS: People with Type 2 diabetes and blood pressure < 130/80 mmHg had a risk of stroke similar to that of the general population.

Handball load and shoulder injury rate: a 31-week cohort study of 679 elite youth handball players.

BACKGROUND: Knowledge of injury patterns, an essential step towards injury prevention, is lacking in youth handball. AIM: To investigate if an increase in handball load is associated with increased shoulder injury rates compared with a minor increase or decrease, and if an association is influenced by scapular control, isometric shoulder strength or glenohumeral range of motion (ROM). METHODS: 679 players (14-18 years) provided weekly reports on shoulder injury and handball load (training and competition hours) over 31 weeks using the SMS, phone and medical examination system. Handball load in a given week was categorised into (1) <20% increase or decrease (reference), (2) increase between 20% and 60% and (3) increase >60% relative to the weekly average amount of handball load the preceding 4 weeks. Assessment of shoulder isometric rotational and abduction strength, ROM and scapular control was performed at baseline and midseason. RESULTS: An increase in handball load by >60% was associated with greater shoulder injury rate (HR 1.91; 95% CI 1.00 to 3.70, p=0.05) compared with the reference group. The effect of an increase in handball load between 20% and 60% was exacerbated among players with reduced external rotational strength (HR 4.0; 95% CI 1.1 to 15.2, p=0.04) or scapular dyskinesis (HR 4.8; 95% CI 1.3 to 18.3, p=0.02). Reduced external rotational strength exacerbated the effect of an increase above 60% (HR 4.2; 95% CI 1.4 to 12.8, p=0.01). CONCLUSIONS: A large increase in weekly handball load increases the shoulder injury rate in elite youth handball players; particularly, in the presence of reduced external rotational strength or scapular dyskinesis.

Danish VISA-A questionnaire with validation and reliability testing for Danish-speaking Achilles tendinopathy patients.

The VISA-A questionnaire has proven to be a valid and reliable tool for assessing severity of Achilles tendinopathy (AT). The aim was to translate and cross-culturally adapt the VISA-A questionnaire for a Danish-speaking AT population, and subsequently perform validity and reliability tests. Translation and following cross-cultural adaptation was performed as translation, synthesis, reverse translation, expert review, and pretesting. The final Danish version (VISA-A-DK) was tested for reliability on healthy controls (n = 75) and patients (n = 36). Tests for internal consistency, validity, and structure were performed on 71 patients. VISA-A-DK showed good reliability for patients (r = 0.80 ICC = 0.79) and healthy individuals (r = 0.98 ICC = 0.97). Internal consistency was 0.73 (Cronbach's alpha). The mean VISA-A-DK score in AT patients was 51 [47-55]. This was significantly lower than healthy controls with a score of 93 (90-95). Criterion validity was considered good when comparing the scores of the Danish version with the original version in both healthy individuals and patients. VISA-A-DK is a valid and reliable instrument and has shown compatible to the original version in assessment of AT patients. VISA-A-DK is a useful tool in the assessment of AT, both in research and in a clinical setting.

Trends in arthroscopy-documented cartilage injuries of the knee and repair procedures among 15-60-year-old patients.

We validated a registry-based method of identifying patients with knee cartilage injury and estimated temporal changes in the incidence of arthroscopy-documented cartilage injuries of the knee and the proportion leading to repair procedures in Denmark. After excluding patients with diagnosed osteoarthritis, we identified 21,392 patients aged 15-60 years with a first recorded procedure code indicating knee cartilage injury in the Danish National Registry of Patients (DNRP) from 1996 to 2011. Using the surgical descriptions of arthroscopy findings in medical records as gold standard, the positive and negative predictive value of procedure codes for knee cartilage injury was 88% and 99%, respectively. The arthroscopy-documented overall incidence of cartilage injury of the knee was 40/100,000 person-years (py) [95% confidence interval (CI): 39.5-40.6] during the period 1996-2011. The arthroscopy-documented age-standardized annual incidence of knee cartilage injury increased from 22 (95% CI: 20.5-23.7) in 1996 to 61 (95% CI: 58.7-64.0) in 2011, per 100,000 py. An increase occurred in all age groups and both sexes. Only 1/6 (17%) patients with knee cartilage injury had a repair procedure. The validity of procedure codes for knee cartilage injury in the DNRP is high. The arthroscopy-documented incidence of knee cartilage injuries increased substantially during the 15-year period.

Gene expression associated with intersterility in Heterobasidion.

Intersterility (IS) is thought to prevent mating compatibility between homokaryons that belong to different species. Although IS in Heterobasidion is regulated by the genes located at the IS loci, it is not yet known how the IS genes influence sexual compatibility and heterokaryon formation. To increase our understanding of the molecular events underlying IS, we studied mRNA abundance changes during IS compatible and incompatible interactions over time. The clustering of the transcripts into expression profiles, followed by the application of Gene Ontology (GO) enrichment pathway analysis of each of the clusters, allowed inference of biological processes participating in IS. These analyses identified events involved in mating and sexual development (i.e., linked with IS compatibility), which included processes associated with cell-cell adhesion and recognition, cell cycle control and signal transduction. We also identified events potentially involved in overriding mating between individuals belonging to different species (i.e., linked with IS incompatibility), which included reactive oxygen species (ROS) production, responses to stress (especially to oxidative stress), signal transduction and metabolic biosynthesis. Our findings thus enabled detection and characterization of gene expression changes associated with IS in Heterobasidion, as well as identification of important processes and pathways associated with this phenomenon. Overall, the results of this study increase current knowledge regarding the molecular mechanisms underpinning IS in Heterobasidion and allowed for the establishment of a vital baseline for further studies.

Distribution and evolution of het gene homologs in the basidiomycota.

In filamentous fungi a system known as somatic incompatibility (SI) governs self/non-self recognition. SI is controlled by a regulatory signaling network involving proteins encoded at the het (heterokaryon incompatible) loci. Despite the wide occurrence of SI, the molecular identity and structure of only a small number of het genes and their products have been characterized in the model fungi Neurospora crassa and Podospora anserina. Our aim was to identify and study the distribution and evolution of putative het gene homologs in the Basidiomycota. For this purpose we used the information available for the model fungi to identify homologs of het genes in other fungi, especially the Basidiomycota. Putative het-c, het-c2 and un-24 homologs, as well as sequences containing the NACHT, HET or WD40 domains present in the het-e, het-r, het-6 and het-d genes were identified in certain members of the Ascomycota and Basidiomycota. The widespread phylogenetic distribution of certain het genes may reflect the fact that the encoded proteins are involved in fundamental cellular processes other than SI. Although homologs of het-S were previously known only from the Sordariomycetes (Ascomycota), we also identified a putative homolog of this gene in Gymnopus luxurians (Basidiomycota, class Agaricomycetes). Furthermore, with the exception of un-24, all of the putative het genes identified occurred mostly in a multi-copy fashion, some with lineage and species-specific expansions. Overall our results indicated that gene duplication followed by gene loss and/or gene family expansion, as well as multiple events of domain fusion and shuffling played an important role in the evolution of het gene homologs of Basidiomycota and other filamentous fungi.

The association between BMI and hospitalization for heart failure in 83,021 persons with Type 2 diabetes: a population-based study from the Swedish National Diabetes Registry.

AIM'S: The aim was to To study the relationship between BMI and hospitalization for heart failure in people with Type 2 diabetes. METHODS: We identified 83 021 individuals with Type 2 diabetes from the Swedish National Diabetes Registry during 1998-2003, who were followed until hospitalization for heart failure, death or end of follow-up on 31 December 2009. Cox regression analyses were performed, adjusting for age, sex, HbA(1c), blood pressure, diabetes duration, smoking, microalbuminuria, cardiac co-morbidities, glucose-lowering and anti-hypertensive medications. RESULTS: During a median follow-up of 7.2 years, 10 969 patients (13.2%) were hospitalized with heart failure. By categories of BMI, with BMI 20 to < 25 kg/m(2) as the reference, hazard ratios for patients during follow-up were 1.07 (95% CI 0.91-1.26) for a mean BMI of < 20 kg/m(2), 1.04 (95% CI 0.98-1.11) for BMI 25 to < 27.5 kg/m(2), 1.22 (95% CI 1.15-1.30) for BMI 27.5 to < 30 kg/m(2), 1.54 (95% CI 1.45-1.63) for BMI 30 to < 35 kg/m(2), 2.16 (95% CI 2.00-2.33) for BMI 35 to < 40 kg/m(2) and 3.22 (95% CI 2.88-3.60) for BMI 40 kg/m(2) or higher. There was a significant interaction between BMI and sex (P = 0.0006), with numerically higher hazard ratios for hospitalization for heart failure within each BMI category for men than for women. CONCLUSIONS: Obesity is strongly related to hospitalization for heart failure in people with Type 2 diabetes, and the relationship is somewhat stronger for men than for women. Preventing weight gain and promoting weight loss may be crucial in reducing the incidence of future hospitalizations for heart failure in this population.

Mortality trends in patients with and without diabetes in Ontario, Canada and the UK from 1996 to 2009: a population-based study.

AIMS/HYPOTHESIS: The aim of this study was to determine the contemporary rate ratio of mortality and changes over time in individuals with vs without diabetes. METHODS: Annual age- and sex-adjusted mortality rates were compared for adults (>20 years) with and without diabetes in Ontario, Canada, and the UK from January 1996 to December 2009 using The Health Improvement Network (THIN) and Ontario databases. The total number of individuals evaluated increased from 8,757,772 in 1996 to 12,696,305 in 2009. RESULTS: The excess risk of mortality for individuals with diabetes in both cohorts was significantly lower during later vs earlier years of the follow-up period (1996-2009). In Ontario the diabetes mortality rate ratio decreased from 1.90 (95% CI 1.86, 1.94) in 1996 to 1.51 (1.48, 1.54) in 2009, and in THIN from 2.14 (1.97, 2.32) to 1.65 (1.57, 1.72), respectively. In Ontario and THIN, the mortality rate ratios among diabetic patients in 2009 were 1.67 (1.61, 1.72) and 1.81 (1.68, 1.94) for those aged 65-74 years and 1.11 (1.10, 1.13) and 1.19 (1.14, 1.24) for those aged over 74 years, respectively. Corresponding rate ratios in Ontario and THIN were 2.45 (2.36, 2.54) and 2.64 (2.39, 2.89) for individuals aged 45-64 years, and 4.89 (4.35, 5.45) and 5.18 (3.73, 6.69) for those aged 20-44 years. CONCLUSIONS/INTERPRETATION: The excess risk of mortality in individuals with vs without diabetes has decreased over time in both Canada and the UK. This may be in part due to earlier detection and higher prevalence of early diabetes, as well as to improvements in diabetes care.

Mechanical stability of the femoral fixation for single- and double-bundle ACL reconstruction in an in vitro experimental model.

Anterior cruciate ligament ACL reconstruction using the double-bundle (DB) technique is gaining popularity. A possible weak link in the DB technique could be that two tendon grafts of smaller diameters are used. The purpose of this study was to test different femoral fixation methods and graft diameters representing single-bundle (SB) and DB ACL reconstructions and compare their biomechanical properties. We hypothesized that SB 6-mm graft constructs had inferior biomechanical properties than SB 9-mm grafts or DB 2 × 6-mm grafts. Furthermore, we hypothesized that interference (IF) screw fixation would demonstrate less elongation and a higher stiffness than Endobutton (Smith & Nephew®, Inc., Andover, Massachusetts, USA) fixation (EBF). We performed an in vitro study using porcine knees and extensor tendons. The mechanical test consisted of a cyclic test followed by a load-to-failure test. We found that 6-mm graft constructs had an ultimate failure load that was up to 40% less than both the 9-mm and 2 × 6-mm graft constructs, despite the fixation method (P-values ≥ 0.004). Comparing fixation methods, EBF was superior to IF concerning maximum load to failure (P < 0.001); IF resulted in a higher stiffness of the femur/graft complex than the EBF (P < 0.001) but no significant difference in elongation between fixation methods. Since the two graft strands are subjected to different loads in different knee flexion angles, the reduced strength of the individual graft strands in DB ACL reconstruction could be a concern.

Infrequent attention to dietary and physical activity behaviours in conversations in Swedish child health services.

AIM: To investigate conversations between nurses and parents in Swedish child health services and to assess to what extent attention is directed towards dietary and physical activity behaviours in children. METHODS: Twenty-three nurses audio-recorded one session each. Recordings were assessed and topics were classified according to predetermined categories. RESULTS: The three most frequent topics of conversation concerned physical examinations of the child (30% of session time), talking to the child to establish or maintain contact and interest (15%), and development of language skills (12%). Dietary habits came on fourth place (10%), and physical activity ranked 14 (4%). CONCLUSION: Attention to dietary and physical activity behaviours in children is infrequent in Swedish child health services. Concern is raised about the efficacy of prevention efforts against childhood obesity.

The relationship between glycaemic control and heart failure in 83,021 patients with type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to examine the relationship between glycaemic control and hospitalisation for heart failure in patients with type 2 diabetes. METHODS: Patients included in the Swedish National Diabetes Register (NDR) during 1998-2003 were followed until hospitalisation for heart failure, death or 31 December 2009. Unadjusted and adjusted incidence rates for heart failure were estimated by Poisson regression and relative risk was estimated by Cox regression. RESULTS: In 83,021 patients with type 2 diabetes, 10,969 (13.2%) were hospitalised with a primary or secondary diagnosis of heart failure during a mean follow-up of 7.2 years. The incidence increased by male sex (p < 0.001), older age (p < 0.001) and longer diabetes duration (p < 0.001). In Cox regression adjusting for risk factors of heart failure the HR per each percentage unit higher HbA(1c) (10 mmol/mol) for heart-failure hospitalisation was 1.12 (95% CI 1.10, 1.14). By category of HbA(1c) the HR for heart failure hospitalisation was: HbA(1c) 6.0 to <7.0% (42 to <53 mmol/mol), 0.91 (95% CI 0.84, 0.98); HbA(1c) 7.0 to <8.0% (53 to <64 mmol/mol), 0.99 (95% CI 0.91, 1.07); HbA(1c) 8.0 to <9.0% (64 to < 75 mmol/mol), 1.10 (95% CI 1.01, 1.20); HbA(1c) 9.0 to <10.0% (75 to <86 mmol/mol), 1.27 (95% CI 1.15, 1.41); HbA(1c) ≥ 10.0 % (≥ 86 mmol/mol), 1.71 (1.51, 1.93) (reference HbA(1c) <6% [42 mmol/mol]). The HR for patients with HbA(1c) 7.0 to <8.0% (53 to < 64 mmol/mol) compared with patients with HbA(1c) 6.0 to <7.0% (42 to <53 mmol/mol) was 1.09 (95% CI 1.03, 1.14). CONCLUSIONS/INTERPRETATION: Poor glycaemic control (HbA(1c) >7% [53 mmol/mol]) is associated with an increased risk of hospitalisation for heart failure in patients with type 2 diabetes.

Von Willebrand factor predicts major bleeding and mortality during oral anticoagulant treatment.

AIMS: Oral anticoagulation (OAC), predominantly with warfarin, is an effective treatment to prevent thromboembolic events. Serious bleeding is a frequent and feared treatment complication. In this longitudinal cohort study of OAC-treated patients, we aimed to evaluate the relationship between von Willebrand factor (VWF) levels and risk of bleeding complications, cardiovascular mortality and all-cause mortality. METHODS AND RESULTS: A total of 719 patients receiving warfarin treatment were observed for a mean duration of 4.2 years. All bleeding complications causing hospitalization were registered and classified into clinically relevant bleeding (CRB) and major bleeding. Ischaemic stroke, peripheral arterial embolism, myocardial infarction, and death were also recorded. We identified 113 cases of CRB and 73 of major bleeding. In total, 161 deaths occurred during follow-up with cardiovascular disease identified as the cause of death in 110 patients. Patients in the highest tertile of VWF had a significantly increased risk of bleeding complications: hazard ratio (HR) 2.53 (95% CI 1.41-4.56) for major bleeding and HR 2.19 (95% CI 1.38-3.48) for CRB. VWF, expressed either in tertiles or as a continuous variable, showed a significant association with cardiovascular mortality (HR 1.68, 95% CI 1.40-2.01) and all-cause mortality (HR 1.77, 95% CI 1.52-2.05). In multivariate Cox regression analysis, the findings remained significant after adjusting for age, high-sensitivity C-reactive protein and creatinine. CONCLUSIONS: Patients with high levels of VWF had an increased risk of bleeding complications, cardiovascular mortality and all-cause mortality during OAC treatment. Our findings imply that the use of VWF as a risk marker for thromboembolic events is complicated by the association of VWF with bleeding complications.

Availability of insulin pump therapy in clinical practice.

AIM: To examine the availability of insulin pump therapy in patients with Type 1 diabetes. METHODS: Patients using insulin pumps among a cohort of 7224 patients with Type 1 diabetes were studied. RESULTS: In logistic regression, used to evaluate variables not changing over time among the total cohort, use of insulin pumps varied by outpatient clinic (P<0.001) and sex (P<0.001). Cox regression analysis in 5854 patients with detailed patient data prior to use of an insulin pump showed higher HbA(1c) (P<0.0001), lower creatinine (P=0.002), high and low insulin doses (P<0.0001), younger age (P<0.0001) and female sex (P<0.0001) to be associated with use of an insulin pump. Women were 1.5-fold more likely to start using an insulin pump (hazard ratio 1.52, 95% confidence interval 1.29-1.79) and patients in the 20- to 30-years age range were more than twice as likely to begin use of an insulin pump than patients aged 40-50 years (hazard ratio 8.63, 95% confidence interval 5.91-12.59 and hazard ratio 3.98, 95% confidence interval 2.80-5.64, respectively). A 10-µmol/l higher level of creatinine was associated with a hazard ratio of 0.56 (95% confidence interval 0.39-0.81) of starting use of an insulin pump. CONCLUSIONS: At 10 hospital outpatient clinics in Sweden, use of insulin pumps therapy varied by clinic. A higher proportion of women began using insulin pumps. Younger patients and patients with fewer complications were also more likely to start using an insulin pump. Further research is needed to confirm these findings in other geographical regions and to understand whether the availability of insulin pumps today is optimized.

Trauma exposure, alcohol consumption, and sleep quality: a latent growth curve model.

This study examined the relations among precollege trauma exposure, alcohol use upon entering college, growth in alcohol use, and sleep quality in a sample of undergraduate students. Participants were 932 students from a large, urban, public university. Participants completed a survey upon entering college and then subsequent follow-up surveys each Spring semester. Precollege trauma exposure was associated with both baseline and growth in alcohol use, whereby higher levels of trauma were associated with higher baseline alcohol use, but with less steep increases in growth rate, as compared to those with lower levels of trauma. Baseline alcohol use was associated with sleep quality whereby those with higher levels of consumption demonstrated worsened sleep quality. This study provides longitudinal evidence for the relations among trauma, alcohol use, and sleep quality. Although the relationship between trauma and alcohol is well-established, further work is needed to identify how this relationship impacts additional health outcomes.

A phase II trial evaluating two schedules of sagopilone (ZK-EPO), a novel epothilone, in patients with platinum-resistant ovarian cancer.

BACKGROUND: Sagopilone, the first fully synthetic epothilone, has shown promising preclinical activity in tumour models. This open-label randomised phase II study investigated two infusion schedules of sagopilone in women with ovarian cancer. PATIENTS AND METHODS: Women with ovarian cancer recurring within 6 months of end of last platinum-containing treatment received sagopilone 16 mg/m(2) as a 3- or 0.5-h i.v. infusion every 21 days for up to 6 weeks. RESULTS: Sixty-three patients received sagopilone as a 3-h (n=38) or 0.5-h (n=25) infusion. There were nine confirmed tumour responses [by modified RECIST (n=8) and by Gynecologic Cancer Intergroup CA-125 criteria (n=1)] in 57 patients assessable for efficacy overall [three (13%) with 0.5-h and six (18%) with 3-h infusions]. The 0.5-h arm was closed when it failed to meet its target efficacy. Main drug-related adverse events were peripheral sensory neuropathy (73%; 16% grade 3), nausea (37%; 2% grade 3), fatigue (35%; 3% grade 3) and arthralgia (30%; 5% grade 3). Overall incidence of peripheral sensory neuropathy was similar in both treatment arms, with no grade 4 neuropathy events. No acute allergic infusion reactions were observed. CONCLUSION: Sagopilone is effective, with balanced tolerability, in patients with recurrent platinum-resistant ovarian cancer.