This paper examines the role of credit and the macroeconomy in small and medium enterprise (SME) distress during a prolonged economic downturn. Specifically, we estimate the determinants of SME ...distress in Ireland during the severe financial and economic crisis which began in 2007/2008. We use a measure of distress, insolvencies, which captures both bank and non-bank forms of credit. We conduct a survival analysis of insolvent liquidations and find that, controlling for firm location and economic activity, both variables capturing a build-up of stress in the macroeconomy and those capturing bank credit standards and availability throughout the cycle are determinants of firm survival.
Isolated systolic hypertension occurs in about 15% of people aged 60 years or older. In 1989, the European Working Party on High Blood Pressure in the Elderly investigated whether active treatment ...could reduce cardiovascular complications of isolated systolic hypertension. Fatal and non-fatal stroke combined was the primary endpoint.
All patients (≥60 years) were initially started on masked placebo. At three run-in visits 1 month apart, their average sitting systolic blood pressure was 160–219 mm Hg with a diastolic blood pressure lower than 95 mm Hg. After stratification for centre, sex, and previous cardiovascular complications, 4695 patients were randomly assigned to nitrendipine 10–40 mg daily, with the possible addition of enalapril 5–20 mg daily and hydrochlorothiazide 12·5–25·0 mg daily, or matching placebos. Patients withdrawing from double-blind treatment were still followed up. We compared occurrence of major endpoints by intention to treat.
At a median of 2 years' follow-up, sitting systolic and diastolic blood pressures had fallen by 13 mm Hg and 2 mm Hg in the placebo group (n=2297) and by 23 mm Hg and 7 mm Hg in the active treatment group (n=2398). The between-group differences were systolic 10·1 mm Hg (95% CI 8·8–11·4) and diastolic, 4·5 mm Hg (3·9–5·1). Active treatment reduced the total rate of stroke from 13·7 to 7·9 endpoints per 1000 patient-years (42% reduction; p=0·003). Non-fatal stroke decreased by 44% (p=0·007). In the active treatment group, all fatal and non-fatal cardiac endpoints, including sudden death, declined by 26% (p=0·03). Non-fatal cardiac endpoints decreased by 33% (p=0·03) and all fatal and non-fatal cardiovascular endpoints by 31% (p<0·001). Cardiovascular mortality was slightly lower on active treatment (27%, p=0·07), but all-cause mortality was not influenced (−14%; p=0·22).
Among elderly patients with isolated systolic hypertension, antihypertensive drug treatment starting with nitrendipine reduces the rate of cardiovascular complications. Treatment of 1000 patients for 5 years with this type of regimen may prevent 29 strokes or 53 major cardiovascular endpoints.
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DOBA, GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SIK, UILJ, UKNU, UL, UM, UPCLJ, UPUK, VSZLJ
Excessive inflammation-associated coagulation is a feature of infectious diseases, occurring in such conditions as bacterial sepsis and COVID-19. It can lead to disseminated intravascular ...coagulation, one of the leading causes of mortality worldwide. Recently, type I interferon (IFN) signaling has been shown to be required for tissue factor (TF; gene name F3) release from macrophages, a critical initiator of coagulation, providing an important mechanistic link between innate immunity and coagulation. The mechanism of release involves type I IFN-induced caspase-11 which promotes macrophage pyroptosis. Here we find that F3 is a type I IFN-stimulated gene. Furthermore, F3 induction by lipopolysaccharide (LPS) is inhibited by the anti-inflammatory agents dimethyl fumarate (DMF) and 4-octyl itaconate (4-OI). Mechanistically, inhibition of F3 by DMF and 4-OI involves suppression of Ifnb1 expression. Additionally, they block type I IFN- and caspase-11-mediated macrophage pyroptosis, and subsequent TF release. Thereby, DMF and 4-OI inhibit TF-dependent thrombin generation. In vivo, DMF and 4-OI suppress TF-dependent thrombin generation, pulmonary thromboinflammation, and lethality induced by LPS, E. coli, and S. aureus, with 4-OI additionally attenuating inflammation-associated coagulation in a model of SARS-CoV-2 infection. Our results identify the clinically approved drug DMF and the pre-clinical tool compound 4-OI as anticoagulants that inhibit TF-mediated coagulopathy via inhibition of the macrophage type I IFN-TF axis.
Objective: Globally, it is estimated that 10.4 million people die each year due to raised blood pressure (BP). Unfortunately, at least 40% of those with high BP globally are unaware of their ...condition. In the most recent UK and Ireland community-based data, 66.5% of people were unaware of their high BP(1). The UK and Ireland have taken part in the global May Measurement Month (MMM) campaign, in a bid to increase awareness of BP and to evidence the proportion of those in the community with undiagnosed high BP. The aim of this study was to investigate the large and combined 2017, 2018 and 2019 MMM dataset, to evidence the proportion of people with raised BP, undiagnosed hypertension and levels of hypertension not treated to target in the UK and Ireland. Design and method: As part of the MMM protocol, community-based opportunistic BP screening sites were set up across the UK and Ireland in places of worship, supermarkets, pharmacies, GP surgeries, workplaces, gyms and other public spaces in 2017, 2018 and 2019. A questionnaire recording medical history, lifestyle and demographics was used to collate participant information. BP was measured three times and the average of 2nd and 3rd readings used for analyses. Multiple imputations were performed to impute the mean BP, where data were missing. The term Hypertension was used for those with systolic BP >/ = 140 or diastolic BP >/ = 90 mmHg, or the participant was on BP medication. Controlled BP was considered as < 140 and < 90 mmHg. Results: Data on 22,910 individuals were analysed as part of the combined MMM dataset. Mean age of participants was 52 ± 18 years, with 60% reporting as female gender. See Table 1 below for the proportion of those considered hypertensive, levels of awareness and the proportion of hypertensives treated to target. Conclusion: In the largest community-based BP dataset to date in the UK and Ireland, our data highlight the concerning levels of people with high BP unaware of their condition and poor levels of controlled BP in hypertensive patients. Better community based and primary care screening initiatives are required to improve awareness and early identification of those at high risk of cardiovascular disease. REFERENCES: (1) McDonnell BJ, Rees E, Cockcroft JR, et al. May Measurement Month 2019: an analysis of blood pressure screening results from the UK and the Republic of Ireland. Eur Heart J Suppl. 2021 May;23 Suppl_B. 147–150.
Objective: Automated oscillometric devices are increasingly replacing auscultation for assessment of systolic (SBP) and diastolic (DBP) blood pressure, but determine mean pressure (MAP) and ...extrapolate SBP and DBP. Major adverse cardiovascular events (MACE) are closest associated with 24 H blood pressure levels. We determined outcome-driven 24 H MAP thresholds and assessed association of MAP, SBP and DBP with MACE. Design and method: In a population-based cohort (n = 11,596), blood pressure and risk factors were measured at baseline. Office MAP, computed from SBP and DBP, was categorized according to the 2017 American guideline. 24 H MAP was recorded oscillometrically. Statistics included multivariable Cox regression and the log-likelihood ratio test. Results: Baseline office and 24 H MAP averaged 97.4 and 90.1 mm Hg. Over 13.6 years (median), 2034 MACE occurred. 24 H MAP levels of < 90, 90–92, 93–96 and = > 96 mm Hg yielded equivalent 10 year MACE risks as the office MAP standard and delineated normotension (n = 6304), elevated 24 H MAP (n = 1074), and hypertension stages 1 (n = 1732) and 2 (n = 2484). MACE rates per 1000 person-years increased (P < 0.001) with higher 24 H MAP category from 11.9 (95% CI, 11.1–13.2) to 12.5 (10.7–14.7), 16.2 (14.6–18.1) and 22.0 (20.4–24.1). Compared with 24 H MAP normotension, the corresponding hazard ratios were 1.06 (0.88–1.25), 1.43 (1.26–1.63) and 1.78 (1.59–2.00). Adding 24 H MAP to covariables, SBP and DBP improved the model fit (P < 0.001). On top of MAP, higher SBP increased, whereas higher DBP attenuated risk (P < 0.001). Conclusions: The oscillometrically determined 24 H MAP used in conjunction with SBP and DBP substantially refined estimates of MACE risk.
In recent years, the renin-angiotensin-aldosterone system has been shown to be crucial not only in blood pressure haemostasis but also in the evolution of atherosclerosis, which ultimately determines ...morbidity and mortality. The angiotensin-converting enzyme inhibitors and, recently, the angiotensin receptor blockers (with their low adverse-effect profile) have added a new dimension to the drug treatment of hypertension. Just a decade after the introduction of angiotensin receptor blockers, physicians treating hypertension are now offered another exciting approach to achieving blockade of the renin-angiotensin-aldosterone system through the inhibition of renin. This review outlines the background evidence for aliskiren, the first orally active renin inhibitor.
In order to determine reference values for ambulatory blood pressure, a sample of 815 healthy bank employees (399 men and 416 women), aged 17-79 years, were investigated. Ambulatory blood pressure ...was recorded over 24 h, taking measurements at 30-min intervals. Blood pressure was also measured by trained observers in the clinic. Ambulatory blood pressure in the 815 subjects averaged 118/72 mmHg over 24 h, 124/78 mmHg during the day (1000-2259 h) and 106/61 mmHg at night (0100-0659 h). Office blood pressure, measured by an observer, was 4/2 mmHg lower (p less than 0.0001) than daytime ambulatory pressure. The 95th centiles for the daytime ambulatory pressure in men were: 114/88 mmHg for the age group 17-29 years (n = 107); 143/91 mmHg from 30-39 years (n = 123); 150/98 mmHg from 40-49 years (n = 109); and 155/103 mmHg in 50-79 year old men (n = 60); for the corresponding age groups in women, the 95th centiles of the daytime pressure were: 131/83 mmHg (n = 174); 132/85 mmHg (n = 149); 150/94 mmHg (n = 55); and 177/97 mmHg (n = 38).
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