Notes

Confounding: Connecting Evidence to Practice.
To assess lipid-lowering drug (LLD) use patterns during 1996-2017 and examine lipid levels in relation to the use of LLDs and prevalent atherosclerotic cardiovascular disease (ASCVD).

Using a nationwide diabetes register, 404 389 individuals with type 2 diabetes living in Denmark during 1996-2017 were identified. Individuals were followed from 1 January 1996 or date of type 2 diabetes diagnosis until date of emigration, death or 1 January 2017. Redemptions of prescribed LLDs were ascertained from the nationwide Register of Medicinal Products Statistics. Data on lipid levels were sourced from the National Laboratory Database since 2010. LLD coverage was calculated at any given time based on the redeemed amount and dose. Trends in lipid levels were estimated using an additive mixed-effect model. Low-density lipoprotein cholesterol (LDL-C) goal attainment was assessed based on recommended targets by the 2011, 2016 and 2019 guidelines for management of dyslipidaemias.

LLD use has decreased since 2012 and only 55% of those with type 2 diabetes were LLD users in 2017. A decline in levels of total cholesterol and LDL-C, and an increase in triglycerides, was observed during 2010-2017. Annual mean levels of LDL-C were lower among LLD users compared with non-users (in 2017 1.84 vs. 2.57 mmol/L). A greater fraction of LLD users achieved the LDL-C goal of less than 1.8 mmol/L compared with non-users (in 2017 51.7% and 19%, respectively). Among LLD users with prevalent ASCVD, 26.9% and 55% had, as recommended by current 2019 European guidelines, an LDL-C level of less than 1.4 mmol/L and less than1.8 mmol/L, respectively, in 2017.

LLD use and LDL-C levels are far from optimal in the Danish type 2 diabetes population and improvement in LLD use could reduce ASCVD events.
LLD use and LDL-C levels are far from optimal in the Danish type 2 diabetes population and improvement in LLD use could reduce ASCVD events.
The elevated lifetime risk of cardiovascular disease in women who develop gestational diabetes mellitus (GDM) has been attributed to adverse life-course trajectories of cardiovascular risk factors that arise before pregnancy and continue thereafter. We hypothesized that pregnancy may differentially affect these trajectories in women who develop GDM and those who do not.

With population-based administrative databases, we identified all nulliparous women in Ontario, Canada, who had singleton pregnancies between January 2011 and December 2016 and ≥2 measurements of the following analytes both before and after pregnancy glycated haemoglobin (HbA1c), glucose, lipids and transaminases. In total, 39 581 women (4373 with GDM) had 3.9 ± 3.4 tests before and 4.6 ± 5.4 tests after pregnancy.

Both before and after pregnancy, women who developed GDM had higher HbA1c, fasting glucose, low-density lipoprotein (LDL)-cholesterol and triglycerides than their peers, with lower high-density lipoprotein (HDL)-cholesterol (arsist but do not differentially worsen after pregnancy.Numerous studies have reported that individuals' loneliness, anxiety, and depression levels increased during the COVID-19 pandemic period. However, reciprocal associations among loneliness, anxiety, and depression, as well as gender differences in these associations, have not been investigated. Therefore, temporal associations among loneliness, anxiety, and depression and gender differences in these associations were examined in a longitudinal study during the COVID-19 pandemic period. The loneliness, anxiety, and depression levels of 458 university students were evaluated at three timepoints (T1, T2, and T3) during the COVID-19 pandemic period in China. The timepoints were separated by 1 month. Cross-lagged panel designs were used to examine reciprocal associations among loneliness, anxiety, and depression as well as the stability and gender differences of these associations. Cross-lagged panel analysis revealed that T1 depression positively predicted T2 anxiety and loneliness, T1 loneliness positively predicted T2 depression, T2 anxiety positively predicted T3 depression, T2 depression positively predicted T3 anxiety and loneliness, T2 loneliness positively predicted T3 depression, and T1 loneliness positively predicted T3 anxiety through the mediating role of T2 depression. No gender differences were observed in the cross-lagged associations. During the COVID-19 pandemic period, loneliness and depression predicted each other across time, and loneliness predicted anxiety across time, mediated by depression. Apoptosis inhibitor No gender differences were observed in the cross-lagged associations among loneliness, anxiety, and depression.
To investigate factors associated with delays in receiving glucose-lowering therapy in patients newly diagnosed with type 2 diabetes mellitus (T2DM), and explore the preferential order and time of intensifications.

Retrospective cohort study including 120 409 adults with T2DM initiating first- to fourth-line glucose-lowering therapy in primary care between 2000 and 2018, using the UK Clinical Practice Research Datalink linked to Hospital Episode Statistics, Office of National Statistics death registration, and 2007 Index of Multiple Deprivation data. Associations were investigated using time-to-event analysis.

The longest delays to prescription of first-line therapy were observed in older patients, of black or other ethnicities, and with multimorbidity. People from the most deprived areas received earlier first-line treatment than those from the least deprived areas. The majority were treated with metformin (82.4%) as the first-line prescription, sulphonylurea (50.4%) as second-line, dipeptidyl peptidasrtia particularly at an earlier stage for older patients, from ethnic minorities and with multimorbidities.Traumatic heterotopic ossification (HO) is the abnormal formation of bone in soft tissues as a consequence of injury. However, the pathological mechanisms leading to traumatic HO remain unknown. Here, we report that aberrant expression of IL-17 promotes traumatic HO formation by activating β-catenin signalling in mouse model. We found that elevated IL-17 and β-catenin levels are correlated with a high degree of HO formation in specimens from patients and HO animals. We also show that IL-17 initiates and promotes HO progression in mice. Local injection of an IL-17 neutralizing antibody attenuates ectopic bone formation in a traumatic mouse model. IL-17 enhances the osteoblastic differentiation of mesenchymal stem cells (MSCs) by activating β-catenin signalling. Moreover, inhibition of IL-17R or β-catenin signalling by neutralizing antibodies or drugs prevents the osteogenic differentiation of isolated MSCs and decreases HO formation in mouse models. Together, our study identifies a novel role for active IL-17 as the inducer and promoter of ectopic bone formation and suggests that IL-17 inhibition might be a potential therapeutic target in traumatic HO.
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