Diffusion in Fissured Media

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A Nonlinear Pseudoparabolic Diffusion Equation

Diffusion in a fissured medium with absorption or partial saturation effects leads to a pseudoparabolic equation nonlinear in both the enthalpy and the permeability. The corresponding initial-boundary value problem is shown to have a solution in various Sobolev-Besov spaces, and sufficient conditions are given for the problem to be well-posed

Systolic blood pressure, cardiovascular outcomes and efficacy and safety of sacubitril/valsartan (LCZ696) in patients with chronic heart failure and reduced ejection fraction: results from PARADIGM-HF

Background: Compared to heart failure patients with higher systolic blood pressure (SBP), those with lower SBP have a worse prognosis. To make matters worse, the latter patients often do not receive treatment with life-saving therapies that might lower blood pressure further. We examined the association between SBP and outcomes in the Prospective Comparison of angiotensin receptor-neprilysin inhibitor (ARNI) with an angiotensin-converting enzyme (ACE) inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF), as well as the effect of sacubitril/valsartan, compared with enalapril, according to baseline SBP. Methods: We analysed the effect of treatment on SBP and on the primary composite outcome (cardiovascular death or heart failure hospitalization), its components and all-cause death. We examined baseline SBP as a categorical (<110, 110 to < 120, 120 to < 130, 130 to < 140 and ≥140 mmHg) and continuous variable, as well as average in-trial SBP and time-updated SBP. Findings: All-cause and cardiovascular mortality rates were highest in patients with the lowest SBP whereas there was a U-shaped relationship between SBP and the rate of heart failure hospitalization. The benefit of sacubitril/valsartan over enalapril was consistent across all baseline SBP categories for all outcomes. For example, the sacubitril/valsartan versus enalapril hazard ratio for the primary endpoint was 0.88 (95%CI 0.74–1.06) in patients with a baseline SBP <110 mmHg and 0.81 (0.65–1.02) for those with a SBP ≥140 mmHg (P for interaction = 0.55). Symptomatic hypotension, study drug dose-reduction and discontinuation were more frequent in patients with a lower SBP. Interpretation: In PARADIGM-HF, patients with lower SBP at randomization, notably after tolerating full doses of both study drugs during a run-in period, were at higher risk but generally tolerated sacubitril/valsartan and had the same relative benefit over enalapril as patients with higher baseline SBP

The Paediatric Glaucoma Diagnostic Ability of Optical Coherence Tomography: A Comparison of Macular Segmentation and Peripapillary Retinal Nerve Fibre Layer Thickness

Paediatric glaucoma leads to a decreased thickness of the peripapillary retinal nerve fibre layer (pRNFL) and of the macula. These changes can be precisely quantified using spectral domain-optical coherence tomography (SD-OCT). Despite abundant reports in adults, studies on the diagnostic capacity of macular SD-OCT in paediatric glaucoma are rare. The aim of this study was to compare the glaucoma discriminative ability of pRNFL and macular segment thickness in paediatric glaucoma patients and healthy children. Data of 72 children aged 5–17 years (glaucoma: 19 (26.4%), healthy: 53 (73.6%)) examined with SD-OCT (SPECTRALIS®, Heidelberg Engineering) were analysed retrospectively. The thickness of pRNFL sectors and of macular segment subfields were compared between diseased and healthy participants. Areas under the receiver-operating characteristic curves (AUC), sensitivity, and specificity from logistic regression were used to evaluate the glaucoma discriminative capacity of single and combined pRNFL and macular segments’ thickness. The results revealed a reduced thickness of the pRNFL and of the three inner macular layers in glaucoma patients, which correlates highly with the presence of glaucoma. The highest glaucoma discriminative ability was observed for the combination of pRNFL sectors or inner macular segments (AUC: 0.83 and 0.85, respectively), although sensitivity remained moderate (both 63% at 95% specificity). In conclusion, while confirmation from investigations in larger cohorts is required, SD-OCT-derived pRNFL and macular thickness measurements seem highly valuable for the diagnosis of paediatric glaucoma

Microvascular and Morphologic Changes of the Macula over Lifetime.

In ocular, neurologic, and cardiovascular diseases, macular segmentation data from spectral-domain optical coherence tomography (SD-OCT) provide morphologic, and OCT-angiography (OCTA) results give microvascular information about the macula. Age was shown to influence both methods' measurements. To further characterize this association, macular SD-OCT and OCTA changes were investigated in a population of juvenile, adult, and older individuals. Macular segment thickness and superficial (SCP) and deep plexus (DCP) vascular density (VD) of 157 healthy individuals aged 10-79 years were analyzed retrospectively. One-way analysis of variance (ANOVA) was used to compare age groups. The association between macular segmentation and OCTA parameters and between these and age was evaluated using linear regression. ANOVA and linear regression analysis showed a thickness decrease in the whole macular and in the ganglion cell and inner plexiform layers with age. While the foveal avascular zone area remained constant between age groups, VD of the SCP and DCP also decreased with age. In multiple linear regression, SCP and DCP VD were associated with inner macular segment thickness in an age-independent way. To conclude, the age-related microvascular and morphological changes in the macula described in this study can contribute to improving the understanding of macular aging processes and better interpreting OCT(A) results in healthy individuals and patients suffering from various retinal diseases

Budget impact of adding ivabradine to standard of care in patients with chronic systolic heart failure in the United States

BACKGROUND: Heart failure (HF) costs $21 billion annually in direct health care costs, 80 OBJECTIVE: To estimate the budget impact of ivabradine from a U.S. commercial payer perspective. METHODS: A budget impact model estimated the per-member-per month (PMPM) impact of introducing ivabradine to existing formularies by comparing a reference scenario (SoC) and a new drug scenario (ivabradine + SoC) in hypothetical 1 million-member commercial and Medicare Advantage plans. In both scenarios, U.S. claims data were used for the reference cumulative annual rates of hospitalizations (HF, non-HF cardiovascular [CV], and non-CV), and hospitalization rates were adjusted using SHIFT data. The model controlled for mortality risk using SHIFT and U.S. life table data, and hospitalization costs were obtained from U.S. claims data: HF-related =$37,507; non-HF CV = $28,951; and non-CV =$17,904. The annualized wholesale acquisition cost of ivabradine was $4,500, with baseline use for this new drug at 2 RESULTS: Based on the approved U.S. indication, approximately 2,000 commercially insured patients from a 1 million-member commercial plan were eligible to receive ivabradine. Ivabradine resulted in a PMPM cost savings of$0.01 and $0.04 in years 1 and 3 of the core model, respectively. After including the acquisition price for ivabradine, the model showed a decrease in total costs in the commercial ($991,256 and $474,499, respectively) and Medicare populations ($13,849,262 and $4,280,291, respectively) in year 1. This decrease was driven by ivabradine’s reduction in hospitalization rates. For the core model, the estimated pharmacy-only PMPM in year 1 was$0.01 for the commercial population and $0.24 for the Medicare Advantage population. CONCLUSIONS: Adding ivabradine to SoC led to lower average annual treatment costs. The negative PMPM budget impact indicates that ivabradine is an affordable option for U.S. payers

Adherence to Antihypertensive Drugs Assessed by Hyphenated High-Resolution Mass Spectrometry Analysis of Oral Fluids

Background It is currently unknown if antihypertensive drugs can be monitored in oral fluid (OF) using liquid chromatography coupled to high-resolution mass spectrometry. Methods and Results We assessed adherence using liquid chromatography coupled to high-resolution mass spectrometry in OF, plasma, and urine of 56 consecutive patients with hypertension referred to a tertiary hypertension unit. Of these patients, 59% were completely adherent (all drugs detectable in urine), whereas 29% and 13% were partially adherent (1 drug not detectable in urine) or nonadherent (>1 drug not detectable in urine), respectively. Adherent patients were on fewer antihypertensive drugs (P=0.001), had fewer daily drug doses (P=0.012), and had lower 24-hour ambulatory systolic (P=0.012) and diastolic (P=0.009) blood pressures than nonadherent or partially adherent patients. Most drugs were detected in urine compared with plasma and OF (181 versus 119 versus 88; P=0.001). Compared with urine and plasma, detection rates of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and diuretics were lower in OF. There was no difference in the frequency of detecting β blockers (P=1.0) and calcium channel blockers (P=0.063) when comparing OF with urine. There was no difference in the number of calcium channel blockers (P=0.727), β blockers (P=1.000), thiazide diuretics (P=0.125), and α-2 agonists (P=0.125) identified between OF and plasma. Conclusions This study shows the feasibility of drug adherence testing for several antihypertensive drugs, especially those without acidic components, in OF, with a similar recovery compared with plasma. Therefore, drug adherence testing in OF should be further explored as a noninvasive approach, which can easily be performed in an "out-of-office" setting

Hidden sodium in effervescent-tablet dietary supplements and over-the-counter drugs: a comparative cross-sectional study

Objective Dietary sodium intake represents a risk factor for cardiovascular disease and mortality. The study sought to analyse the sodium content of effervescent dietary supplements and drugs in Germany and the USA. Design Comparative cross-sectional study. Setting and methods The sodium content of 39 dietary supplement effervescent tablets available in Germany was measured in May and June 2022 using optical emission spectrometry with inductively coupled argon plasma. The sodium content of 33 common pharmacyonly effervescent tablets (over-the-counter (OTC) drugs) in Germany was obtained from the summary of product characteristics. We compared the sodium content of the measured German dietary supplement effervescent tablets to that of 51 dietary supplement effervescent tablets available in the USA (data: National Institutes of Health’s Dietary Supplement Label Database). Results The measured sodium content in the German dietary supplements was 283.9±122.6 mg sodium/tablet, equivalent to 14±6% of the maximum recommended daily sodium intake (MRDSI). Vitamin products had the highest (378.3±112.8 mg, 19±6% of MRDSI), and calcium products had the lowest mean sodium content (170.4±113.2 mg, 9±6% of MRDSI). Vitamin products contained significantly more sodium than magnesium (378.3 mg vs 232.7 mg; p=0.004), calcium (378.3 mg vs 170.4 mg; p=0.006) and mineral products (378.3 mg vs 191.6 mg; p=0.048). The sodium content measured in products available in Germany was higher when compared with the declared sodium content on the label of the products sold in the USA (283.9 mg vs 190.0 mg; p<0.001). The median summary of product characteristics-declared sodium content of a single dose of the German OTC drugs was 157.0 mg (IQR: 98.9–417.3 mg); pain/common cold drugs contained the most sodium (median: 452.1 mg; IQR: 351.3–474.0 mg). Conclusion Effervescent tablets of nutritional supplements and OTC drugs contain high amounts of sodium, which often is not disclosed

Manipulation of the spontaneous emission dynamics of quantum dots in two-dimensional photonic crystals

We demonstrate the ability to control the spontaneous emission dynamics of self-assembled quantum dots via the local density of optical modes in 2D-photonic crystals. We show that an incomplete 2D photonic bandgap is sufficient to significantly lengthen the spontaneous emission lifetime ($>2\times$) over a wide bandwidth ($\Delta\lambda\geq40$ nm). For dots that are both \textit{spectrally} and \textit{spatially} coupled to strongly localized ($V_{mode}\sim1.5(\lambda/n)^{3}$), high $Q\sim2700$ optical modes, we have directly measured a strong Purcell enhanced shortening of the emission lifetime $\geq5.6\times$, limited only by our temporal resolution. Analysis of the spectral dependence of the recombination dynamics shows a maximum lifetime shortening of $19\pm4$. From the directly measured enhancement and suppression we show that the single mode coupling efficiency for quantum dots in such structures is at least $\beta=92$ and is estimated to be as large as $\sim97$.Comment: 11 pages, 3 figure

Twisted partial actions of Hopf algebras

In this work, the notion of a twisted partial Hopf action is introduced as a unified approach for twisted partial group actions, partial Hopf actions and twisted actions of Hopf algebras. The conditions on partial cocycles are established in order to construct partial crossed products, which are also related to partially cleft extensions of algebras. Examples are elaborated using algebraic groups