Estimation of individual beneficial and adverse effects of intensive glucose control for patients with type 2 diabetes

AIMS/HYPOTHESIS: Intensive glucose control reduces the risk of vascular complications while increasing the risk of severe hypoglycaemia at a group level. We sought to estimate individual beneficial and adverse effects of intensive glucose control in patients with type 2 diabetes. METHODS: We performed a post hoc analysis of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial, a randomised controlled trial evaluating standard vs intensive glucose control (HbA1c target ≤6.5% [48 mmol/mol]). In 11,140 participants, we estimated the individual 5 year absolute risk reduction (ARR) for the composite outcome of major micro- and macrovascular events and absolute risk increase (ARI) for severe hypoglycaemia for intensive vs standard glucose control. Predictions were based on competing risks models including clinical characteristics and randomised treatment. RESULTS: Based on these models, 76% of patients had a substantial estimated 5 year ARR for major vascular events (>1%, 5 year number-needed-to-benefit [NNTB5] 200). Similarly, 36% of patients had a substantial estimated ARI for severe hypoglycaemia (5 year number-needed-to-harm [NNTH5] 200). When assigning similar or half the weight to severe hypoglycaemia compared with a major vascular event, net benefit was positive in 85% or 99% of patients, respectively. Limiting intensive treatment to the 85% patient subgroup had no significant effect on the overall incidence of major vascular events and severe hypoglycaemia compared with treating all patients. CONCLUSIONS/INTERPRETATION: Taking account of the effects of intensive glucose control on major micro- and macrovascular events and severe hypoglycaemia for individual patients, the estimated net benefit was positive in the majority of the participants in the ADVANCE trial. The estimated individual effects can inform treatment decisions once individual weights assigned to positive and adverse effects have been specified. TRIAL REGISTRATION: ClinicalTrials.gov NCT00145925

Pitfalls in the Measurement of the Nocturnal Blood Pressure Dip in Adolescents with Type 1 Diabetes

OBJECTIVE—The purpose of this study was to screen adolescents with type 1 diabetes using ambulatory blood pressure monitoring (ABPM) to 1) test the hypothesis that using a preset sleep time results in an overdiagnosis of abnormal nocturnal dipping in systolic blood pressure and 2) assess the reproducibility of an abnormal nocturnal systolic blood pressure dip

Nanoscale mosaicity revealed in peptide microcrystals by scanning electron nanodiffraction.

Changes in lattice structure across sub-regions of protein crystals are challenging to assess when relying on whole crystal measurements. Because of this difficulty, macromolecular structure determination from protein micro and nanocrystals requires assumptions of bulk crystallinity and domain block substructure. Here we map lattice structure across micron size areas of cryogenically preserved three-dimensional peptide crystals using a nano-focused electron beam. This approach produces diffraction from as few as 1500 molecules in a crystal, is sensitive to crystal thickness and three-dimensional lattice orientation. Real-space maps reconstructed from unsupervised classification of diffraction patterns across a crystal reveal regions of crystal order/disorder and three-dimensional lattice tilts on the sub-100nm scale. The nanoscale lattice reorientation observed in the micron-sized peptide crystal lattices studied here provides a direct view of their plasticity. Knowledge of these features facilitates an improved understanding of peptide assemblies that could aid in the determination of structures from nano- and microcrystals by single or serial crystal electron diffraction

Blood Pressure Control in Italian Essential Hypertensives Treated by General Practitioners

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Effects of Isolated Systolic Hypertension and Essential Hypertension on Large and Middle-sized Artery Compliance

Systolic hypertension of the elderly is characterized by a reduction in arterial compliance. Whether and to what extent this involves arteries of various structure and size is not well known.To study carotid and radial artery compliance in systolic hypertension of the elderly, compared to essential hypertension and normotension.We investigated 28 elderly patients with systolic hypertension (age 68.6 +/- 1.4 years, mean +/- SE; systolic blood pressure160 mmHg and diastolic blood pressure90 mmHg) plus 17 age-matched patients with essential hypertension and 15 age-matched healthy normotensive subjects. Radial and carotid artery compliance were evaluated using echotracking techniques. In both arteries compliance was assessed statistically and dynamically, i.e. as compliance values throughout the diasto-systolic pressure range. Measurements included intima-media wall thickness of the radial artery.Compared to normotensive subjects, carotid artery compliance was reduced in essential hypertension and more so in systolic hypertension. However, although in both groups radial artery wall thickness was markedly greater than in the normotensive group, radial artery compliance was markedly reduced in systolic hypertension, but unchanged in essential hypertension.In systolic hypertension of the elderly the reduction of arterial compliance is marked in both muscular and large elastic arteries, while in elderly essential hypertensives changes in arterial compliance are more heterogeneous, i.e. only carotid artery compliance is reduced. The different effects of these two types of hypertension on arterial mechanics are visible throughout the physiological range of blood pressure and probably accounted for by different alterations in vessel wall structure

Harmonization of the American College of Cardiology/American Heart Association and European Society of Cardiology/European Society of Hypertension Blood Pressure/Hypertension Guidelines: Comparisons, Reflections, and Recommendations

The 2017 American College of Cardiology/American Heart Association and 2018 European Society of Cardiology/European Society of Hypertension clinical practice guidelines for management of high blood pressure/hypertension are influential documents. Both guidelines are comprehensive, were developed using rigorous processes, and underwent extensive peer review. The most notable difference between the 2 guidelines is the blood pressure cut points recommended for the diagnosis of hypertension. There are also differences in the timing and intensity of treatment, with the American College of Cardiology/American Heart Association guideline recommending a somewhat more intensive approach. Overall, there is substantial concordance in the recommendations provided by the 2 guideline-writing committees, with greater congruity between them than their predecessors. Additional harmonization of future guidelines would help to underscore the commonality of their core recommendations and could serve to catalyze changes in practice that would lead to improved prevention, awareness, treatment, and control of hypertension, worldwide

Clinical Utility of Short-Term Blood Pressure Measures to Inform Long-Term Blood Pressure Management

Background: Decisions about hypertension management are substantially influenced by blood pressure (BP) levels measured before and soon after starting BP lowering drugs. We aimed to assess the utility of short-term BP changes in individuals in terms of long-term treatment response. Methods: Post hoc analyses of 2 randomized trials with 4-to-6 weeks active run-in for all participants, followed by randomization to active BP lowering treatment (combination perindopril±indapamide) or placebo. We categorized individuals by degree of systolic BP (SBP) change during active run-in treatment and assessed associations with subsequent postrandomization placebo-corrected BP reduction, cardiovascular events, and tolerability. We included individuals with baseline BP ≥140/90 mm Hg from the PROGRESS trial (Perindopril Protection Against Recurrent Stroke Study; 4275 individuals with cerebrovascular disease) and ADVANCE trial (The Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation; 6610 individuals with diabetes). Results: During the active run-in period, the proportion of participants with initial SBP changes in 4 categories (SBP increase, 0-9.9 mm Hg decrease, 10-19.9 mm Hg decrease, and ≥20 mm Hg decrease) were 17%, 27%, 28%, and 28% in PROGRESS and 21%, 22%, 24%, and 33% in ADVANCE. Randomization to active therapy achieved similar placebo-corrected long-term BP reductions across the 4 initial SBP change groups in both trials (P-values for heterogeneity >0.1). There was no significant difference in achieving BP 0.1). Conclusions: An individual's apparent BP change immediately after commencing therapy has limited clinical utility. Therefore, more emphasis should be given to use of evidence-based regimens and measures over the long-term to ensure sustained BP control. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00145925

Searches for neutrino counterparts of gravitational waves from the LIGO/Virgo third observing run with KM3NeT

The KM3NeT neutrino telescope is currently being deployed at two different sites in the Mediterranean Sea. First searches for astrophysical neutrinos have been performed using data taken with the partial detector configuration already in operation. The paper presents the results of two independent searches for neutrinos from compact binary mergers detected during the third observing run of the LIGO and Virgo gravitational wave interferometers. The first search looks for a global increase in the detector counting rates that could be associated with inverse beta decay events generated by MeV-scale electron anti-neutrinos. The second one focuses on upgoing track-like events mainly induced by muon (anti-)neutrinos in the GeV–TeV energy range. Both searches yield no significant excess for the sources in the gravitational wave catalogs. For each source, upper limits on the neutrino flux and on the total energy emitted in neutrinos in the respective energy ranges have been set. Stacking analyses of binary black hole mergers and neutron star-black hole mergers have also been performed to constrain the characteristic neutrino emission from these categories.Grants PID2021-124591NB-C41, -C42, -C43 funded by MCIN/AEI/10.13039/501100011033 and, as appropriate, by “ERDF A way of making Europe”, by the “European Union” or by the “European Union NextGenerationEU/PRTR”Programa de Planes Complementarios I+D+I (refs. ASFAE/2022/023, ASFAE/2022/014)Programa Prometeo (PROMETEO/2020/019) and GenT (refs. CIDEGENT/2018/034, /2019/043, /2020/049. /2021/23) of the Generalitat ValencianaJunta de Andalucía (ref. SOMM17/6104/UGR, P18-FR-5057)MSC program (ref. 101025085)Programa María Zambrano (Spanish Ministry of Universities, funded by the European Union, NextGenerationEU)The European Union’s Horizon 2020 Research and Innovation Programme (ChETEC-INFRA — Project no. 101008324)Francqui foundatio