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We also extracted data on treatment-related adverse events and immune-related adverse events (irAEs).
Overall, 10 randomised controlled clinical trials (n=5765) were included. As first-line treatment for advanced NSCLC, IC tended to yield better PFS, OS and ORR than did IO. Furthermore, IC yielded significantly better PFS than IO when tumour PD-L1 expression was at least 50% (HR 1.81, 95% CI 1.18 to 2.78) and yielded a better OS and PFS when tumour PD-L1 expression was at least 1%; IO resulted in fewer adverse events than did IC. However, the incidence of irAEs was higher for IO than for IC.
The findings of the indirect comparison indicate that IC as first-line treatment for advanced NSCLC is significantly more effective than IO in patients with PD-L1 expression in at least 50% of tumour cells.
CRD 42018116589.
CRD 42018116589.
Diurnal temperature range (DTR) is an important meteorological indicator of global climate change; high values of DTR may induce stroke morbidity, while the related high-risk periods and sensitive populations are not clear. This study aims to evaluate the effects of DTR on first-ever strokes in different seasons and in relation to sensitive populations.
We collected data on 142 569 first-ever strokes during 2005-2016 in Shenzhen. We fitted a time-series Poisson model in our study, estimating the associations between DTR and first-ever strokes, with a distributed lag non-linear model. Then, we calculated strokes attributable to high DTR in different genders, age groups, education levels and stroke subtypes.
High DTR had a significant association with first-ever strokes, and the risk of stroke increased with the rise of DTR in the summer and winter. In total, 3.65% (95% empirical CI (eCI) 1.81% to 5.53%) of first-ever strokes were attributable to high DTR (5.5°C and higher) in the summer, while 2.42% (95%aged and low-education populations are sensitive in the winter. It is recommended that the DTR values be reported and emphasised in weather forecast services, together with the forecasts of heat and cold.
Long-term glycemic control reduces retinopathy risk, but transient worsening can occur with glucose control intensification. Glucagon-like peptide 1 receptor agonists (GLP-1RA) lower glucose, but the long-term impact on retinopathy is unknown. GLP-1RA cardiovascular outcome trials (CVOTs) provide long-term follow-up, allowing examination of retinopathy outcomes.
To examine the associations between retinopathy, HbA
, systolic blood pressure (SBP), and weight in GLP-1RA CVOTs.
Systematic review identified six placebo-controlled GLP-1RA CVOTs reporting prespecified retinopathy outcomes.
Published trial reports were used as the primary data sources.
HbA
, SBP, and weight data throughout follow-up by treatment group were extracted.
Random-effects model meta-analysis showed no association between GLP-1RA treatment and retinopathy (odds ratio [OR] 1.10; 95% CI 0.93, 1.30), with high heterogeneity between studies (
= 52.2%;
statistic
= 0.063). Univariate meta-regression showed an association hen intensifying glucose-lowering therapy.
HbA1c reduction was significantly associated with increased retinopathy risk in meta-regression for GLP-1RA CVOTs. The magnitude of HbA1c reduction was correlated with retinopathy risk in people with diabetes and additional cardiovascular risk factors, but the long-term impact of improved glycemic control on retinopathy was unmeasured in these studies. Retinopathy status should be assessed when intensifying glucose-lowering therapy.Current dietary advice for women with gestational diabetes mellitus is to avoid diets that result in elevated ketone levels. This guidance stems from a concern that maternal ketones are associated with poor fetal and childhood outcomes, including reduced childhood intelligence quota. buy MPTP The evidence behind these guidelines is conflicting and inconsistent. Given that dietary counseling is the initial treatment strategy for women with diabetes in pregnancy, it is important that clinicians understand the concern regarding maternal ketones. This review examines the physiology of ketogenesis in pregnancy, the prevalence of elevated maternal ketone levels, and the relationship between maternal ketones and fetal and childhood outcomes.
To prove equivalence of individual, clinically titrated basal insulin doses of glargine 300 units ⋅ mL
(Gla-300) and degludec 100 units ⋅ mL
(Deg-100) under steady state conditions in a single-blind, randomized, crossover study, on the glucose pharmacodynamics (PD) in people with type 1 diabetes (T1D).
Subjects with T1D (
= 22, 11 men, age 44.3 ± 12.4 years, disease duration 25.5 ± 11.7 years, A1C 7.07 ± 0.63% [53.7 ± 6.9 mmol ⋅ mL
], BMI 22.5 ± 2.7 kg · m
), naïve to Gla-300 and Deg-100, underwent 24-h euglycemic clamps with individual clinical doses of Gla-300 (0.34 ± 0.08 units ⋅ kg
) and Deg-100 (0.26 ± 0.06 units ⋅ kg
), dosing at 2000 h, after 3 months of optimal titration of basal (and bolus) insulin.
At the end of 3 months, Gla-300 and Deg-100 reduced slightly and, similarly, A1C versus baseline. Clamp average plasma glucose (0-24 h) was euglycemic with both insulins. The area under curve of glucose infused (AUC-GIR
) was equivalent for the two insulins (ratio 1.04, 90% CI 0.91-1.18). Suppression of endogenous glucose production, free fatty acids, glycerol, and β-hydroxybutyrate was 9%, 14%, 14%, and 18% greater, respectively, with Gla-300 compared with Deg-100 during the first 12 h, while glucagon suppression was no different. Relative within-day PD variability was 23% lower with Gla-300 versus Deg-100 (ratio 0.77, 90% CI 0.63-0.92).
In T1D, individualized, clinically titrated doses of Gla-300 and Deg-100 at steady state result in similar glycemic control and PD equivalence during euglycemic clamps. Clinical doses of Gla-300 compared with Deg-100 are higher and associated with quite similar even 24-h distribution of PD and antilipolytic effects.
In T1D, individualized, clinically titrated doses of Gla-300 and Deg-100 at steady state result in similar glycemic control and PD equivalence during euglycemic clamps. Clinical doses of Gla-300 compared with Deg-100 are higher and associated with quite similar even 24-h distribution of PD and antilipolytic effects.
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