Magnetostratigraphic, biostratigraphic, and stable isotope stratigraphy of an Upper Miocene drill core from the Salé Briqueterie (northwestern Morocco):...

We report a high-resolution stable isotope, carbonate, magnetostratigraphic, and biostratigraphic record from a 175-m drill core from the Salé Briqueterie, which is part of the Bou Regreg section in northwestern Morocco. The Salé drill core spans the interval from paleomagnetic Chron C4n partim to C3r (earliest Gilbert), which represents the time leading up to and including the isolation and desiccation of the Mediterranean (i.e., the Messinian salinity crisis). During Chrons C3An and C3Ar (6.935 to 5.894 Ma) the isotope and carbonate signals display quasi-periodic variations with estimated periods of 40 and 100 kyr, respectively. We interpret the 40-kyr δ^18O variations as reflecting changes in global ice volume caused by obliquity-induced changes (41 kyr) in solar insolation in polar regions. The 100-kyr carbonate variations probably represent long-term modulation of the amplitude of the precessional cycle (~21 kyr), which is not resolved by our sampling frequency. The cyclic nature of the oxygen isotope signal permits us to extend the isotope nomenclature of Shackleton et al. (1994a) from stage TG24 in Chron C3r (earliest Gilbert) to stage C3Ar.δ^18O.18 at the base of Chron C3Ar (6.935 Ma). A major change in paleoceanographic conditions is recorded across the Tortonian/Messinian boundary, which we correlate to Chron C3Bn at 7.04 Ma. Benthic foraminiferal δ^18O values increased by an average of 0.4‰ in two steps at 7.17 Ma and 6.8 Ma and δ^13C values decreased by 0.7-0.8‰ between 7.1 and 6.8 Ma, representing the late Miocene carbon shift. The first step in δ^18O values coincides with an inferred reversal in deep water circulation through the Rifian Corridor, and the second correlates with the base of the Tripoli Formation and onset of "crisis conditions" in the Mediterranean. We suggest that the increase in δ^18O values represents, at least in part, an increase in global ice volume that lowered sea level and contributed to the establishment of a negative water budget in the Mediterranean. Average δ^18O values remained high throughout most of Chrons C3Ar and C3An, reaching maximum δ^18O values during isotope stages TG20 and 22 in Chron C3r (earliest Gilbert). The glacio-eustatic falls associated with these events may have resulted in the complete isolation of the Mediterranean from the world ocean (Shackleton et al., 1994a). Following stage TG12 in the Salé record, there exists a trend toward progressively lower δ^18O values that may represent a series of marine transgressions that eventually reflooded the Mediterranean and ended the Salinity Crisis

Inter- and intra-observer variability in the qualitative categorization of coronary angiograms.

The ABC classification of the American College of Cardiology and the American Heart Association is a commonly used categorization to estimate the risk and success of intracoronary intervention, as well as the probability of restenosis. To evaluate the reliability of qualitative angiogram readings, we randomly selected 200 films from single lesion angioplasty procedures. A repeated visual assessment (> or = 2 months interval) by two independent observers resulted in kappa values of inter and intra-observer variability for the ABC lesion classification and for all separate items that compile it. Variability in assessment is expressed in percentage of total agreement, and in kappa value, which is a parameter of the agreement between two or more observations in excess of the chance agreement. Percentage of total agreement and kappa value was 67.8% and 0.33 respectively for the ABC classification, indicating a poor agreement. Probably this is due to the deficiency of strict definitions. Further investigation has to demonstrate whether improvement can be achieved using complete and detailed definitions without ambiguity, and consensus after panel assessment

Temporal patterns of macrophage- and neutrophil-related markers are associated with clinical outcome in heart failure patients

Aims: Evidence on the association of macrophage- and neutrophil-related blood biomarkers with clinical outcome in heart failure patients is limited, and, with the exception of C-reactive protein, no data exist on their temporal evolution. We aimed to investigate whether temporal patterns of these biomarkers are related to clinical outcome in patients with stable chronic heart failure (CHF). Methods and Results: In 263 patients with CHF, we performed serial plasma measurements of scavenger receptor cysteine-rich type 1 protein M130 (CD163), tartrate-resistant acid phosphatase type 5 (TRAP), granulins (GRN), spondin-1 (SPON1), peptidoglycan recognition protein 1 (PGLYRP1), and tissue factor pathway inhibitor (TFPI). The Cardiovascular Panel III (Olink Proteomics AB, Uppsala, Sweden) was used. During 2.2 years of follow-up, we collected 1984 samples before the occurrence of the composite primary endpoint (PE) or censoring. For efficiency, we selected 567 samples for the measurements (all baseline samples, the last two samples preceding the PE, and the last sample before censoring in event-free patients). The relationship between repeatedly measured biomarker levels and the PE was evaluated by joint models. Mean (±standard deviation) age was 67 ± 13 years; 189 (72%) were men; left ventricular ejection fraction (%) was 32 ± 11. During follow-up, 70 (27%) patients experienced the PE. Serially measured biomarkers predicted the PE in a multivariable model adjusted for baseline clinical characteristics [hazard ratio (95% confidence interval) per 1-standard deviation change in biomarker]: CD163 [2.07(1.47–2.98), P < 0.001], TRAP [0.62 (0.43–0.90), P = 0.009], GRN [2.46 (1.64–3.84), P < 0.001], SPON1 [3.94 (2.50–6.50), P < 0.001], and PGLYRP1 [1.62 (1.14–2.31), P = 0.006]. Conclusions: Changes in plasma levels of CD163, TRAP, GRN, SPON1, and PGLYRP1 precede adverse cardiovascular events in patients with CHF

SYNTAX score II predicts long-term mortality in patients with one- or two-vessel disease

Objective SYNTAX score II (SSII) is a long-term mortality prediction model to guide the decision making of the heart-team between coronary artery bypass grafting or percutaneous coronary intervention (PCI) in patients with left main or three-vessel coronary artery disease. This study aims to investigate the long-term predictive value of SSII for all-cause mortality in patients with one- or two-vessel disease undergoing PCI. Methods A total of 628 patients (76% men, mean age: 61±10 years) undergoing PCI due to stable angina pectoris (43%) or acute coronary syndrome (57%), included between January 2008 and June 2013, were eligible for the current study. SSII was calculated using the original SYNTAX score website (www.syntaxscore.com). Cox regression analysis was used to assess the association between continuous SSII and long-term all-cause mortality. The area under the receiver-operating characteristic curve was used to assess the performance of SSII. Results SSII ranged from 6.6 to 58.2 (median: 20.4, interquartile range: 16.1–26.8). In multivariable analysis, SSII proved to be an independent significant predictor for 4.5-year mortality (hazard ratio per point increase: 1.10; 95% confidence interval: 1.07–1.13; p<0.001). In terms of discrimination, SSII had a concordance index of 0.77. Conclusion In addition to its established value in patients with left main and three-vessel disease, SSII may also predict long-term mortality in PCI-treated patients with one- or two-vessel disease

Barriers and Facilitators of Conducting Medication Reviews in Nursing Home Residents:A Qualitative Study

Objectives: Inappropriate medication prescribing is a recognized clinical problem in nursing home residents of whom many have polypharmacy. However, results about the effectiveness of medication reviews targeted at improving prescribing and deprescribing have been equivocal. We therefore examined barriers and facilitators of conducting medication reviews. Method: We purposively sampled medication reviews to capture salient barriers and facilitators of conducting medication reviews both in nursing home care units for dementia and disabling conditions. We held semi-structured interviews about consecutive steps of medication reviews. Interviews were transcribed verbatim and analyzed with the "method of constant comparison." Results: Six nursing home residents/relatives of nursing home residents, 8 elder care physicians, 5 pharmacists, and 10 nurses took part in the semi-structured interviews. We observed four overarching themes of barriers and facilitators: "realizing fidelity of the patient perspective (theme 1)," "level of comprehensiveness of medication reviews (theme 2)," "inclinations of healthcare providers (theme 3)," and "inter-professional collaboration and alliances (theme 4)." Theme 1 "realizing fidelity of the patient perspective" referred to the observation that assessing the patient perspective was a delicate balance between the value and the impediments of a proper assessment of the patient perspective. Theme 2 "level of comprehensiveness of medication reviews" reflected the struggle of practitioners to find an optimum between medication reviews being both comprehensive and feasible. Theme 3 "inclinations of healthcare providers" concerned setting intervention targets that were complementary to the practices of physicians and keeping the pharmacist blind to the patient perspective as a countermeasure to physicians' inclinations. Finally, theme 4 "inter-professional collaboration and alliances" highlighted mutual support and inter-professional collaboration to strengthen healthcare practitioners' contributions. Discussion: These themes of barriers and facilitators emphasize the need to improve meta-communication during the medication review process. This pertains to the need for healthcare providers to appraise the fidelity of the patient perspective in a dialogue with residents/relatives. Furthermore, discourse between healthcare practitioners is needed beforehand about the level of comprehensiveness intervention targets, and inter-professional collaboration

Identifying plasma proteomic signatures from health to heart failure, across the ejection fraction spectrum

Circulating proteins may provide insights into the varying biological mechanisms involved in heart failure (HF) with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). We aimed to identify specific proteomic patterns for HF, by comparing proteomic profiles across the ejection fraction spectrum. We investigated 4210 circulating proteins in 739 patients with normal (Stage A/Healthy) or elevated (Stage B) filling pressures, HFpEF, or ischemic HFrEF (iHFrEF). We found 2122 differentially expressed proteins between iHFrEF-Stage A/Healthy, 1462 between iHFrEF-HFpEF and 52 between HFpEF-Stage A/Healthy. Of these 52 proteins, 50 were also found in iHFrEF vs. Stage A/Healthy, leaving SLITRK6 and NELL2 expressed in lower levels only in HFpEF. Moreover, 108 proteins, linked to regulation of cell fate commitment, differed only between iHFrEF-HFpEF. Proteomics across the HF spectrum reveals overlap in differentially expressed proteins compared to stage A/Healthy. Multiple proteins are unique for distinguishing iHFrEF from HFpEF, supporting the capacity of proteomics to discern between these conditions.</p

Randomized comparison of primary stenting and provisional balloon angioplasty guided by flow velocity measurement.

BACKGROUND: Coronary stenting improves outcomes compared with balloon angioplasty, but it is costly and may have other disadvantages. Limiting stent use to patients with a suboptimal result after angioplasty (provisional angioplasty) may be as effective and less expensive. METHODS AND RESULTS: To analyze the cost-effectiveness of provisional angioplasty, patients scheduled for single-vessel angioplasty were first randomized to receive primary stenting (97 patients) or balloon angioplasty guided by Doppler flow velocity and angiography (523 patients). Patients in the latter group were further randomized after optimization to either additional stenting or termination of the procedure to further investigate what is "optimal." An optimal result was defined as a flow reserve >2.5 and a diameter stenosis <36%. Bailout stenting was needed in 129 patients (25%) who were randomized to balloon angioplasty, and an optimal result was obtained in 184 of the 523 patients (35%). There was no significant difference in event-free survival at 1 year between primary stenting (86.6%) and provisional angioplasty (85.6%). Costs after 1 year were significantly higher for provisional angioplasty (EUR 6573 versus EUR 5885; P:=0.014). Results after the second randomization showed that stenting was also more effective after optimal balloon angioplasty (1-year event free survival, 93.5% versus 84.1%; P:=0. 066). CONCLUSIONS: After 1 year of follow-up, provisional angioplasty was more expensive and without clinical benefit. The beneficial value of stenting is not limited to patients with a suboptimal result after balloon angioplasty