187 research outputs found
Incidence of angioedema after initiation of angiotensin-converting enzyme inhibitors in adults with heart failure
Background: Angioedema, a potentially life-threatening adverse event associated with angiotensin-converting enzyme inhibitor (ACEI) use, occurs more often among Black patients than non-Black patients. Specific angioedema incidence rates (IRs) among heart failure (HF) patients initiating an ACEI are limited.
Objectives: To provide estimates of angioedema incidence among HF patients initiating an ACEI, particularly among Black patients.
Methods: We conducted a retrospective cohort study among adult (≥18 years) patients with HF who initiated ACEI use at 5 health care delivery systems within the Cardiovascular Research Network between July 2015 and May 2019. We required patients to have ≥12 months of continuous medical and prescription drug coverage and no ACEI dispensings in the 1 year before treatment initiation. Our primary outcome was serious angioedema, defined as a primary or secondary diagnosis of ICD-9 code 995.1 (‘Angioneurotic edema not elsewhere classified’) or ICD-10 codes in the T78.3 series (‘Angioneurotic edema’) during hospitalization. Our secondary out-come was ‘any angioedema’, which included serious angioedema and non-serious angioedema that was diagnosed in the outpatient setting. We followed patients from ACEI initiation until first angioedema diagnosis or a censoring event (treatment discontinuation, initiation of another renin-angiotensin-aldosterone system blocking agent, disenrollment, death, or end of 365-day follow-up or study). We calculated crude IRs and exact 95% confidence intervals (CI) for angioedema among HF patients initiating an ACEI. Results: We identified 14 ,241 ACEI users, of which 6,156 (43 .2%)were women and 2,105 (15%) were self-reported Black. Mean age was 70 ± 14 years. We observed 6 serious angioedema events overall (IR: 0.8/1,000 person-years (PYs), 95% CI: 0.3-1.7), with 2 events occurring among Black patients (IR: 1.8/1,000 PYs, 95%CI: 0.2-6.5) and 4 events among non-Black patients (IR: 0.6/1,000PYs, 95% CI: 0.2-1.5). We observed 43 angioedema events overall (IR: 5.4/1,000 PYs, 95% CI: 3.9-7.3), with 21 events occurring among Black patients (IR: 19/1,000 PYs, 95% CI: 11.8-29.1) and 22 events among non-Black patients (IR: 3.2/1,000 PYs, 95%CI: 2.0-4.9).
Conclusions: Our estimate of angioedema incidence among HF patients who initiated an ACEI (5.4 events/1,000 PYs) is slightly higher than a previously published estimate (3.3/1,000 PYs) among a similarly-defined population identified through administrative claims data. Similar to prior reports, we found a higher incidence of angioedema, both serious and non-serious, among Black ACEI users than among non-black ACEI users
Ovarian cancer
Ovarian cancer is not a single disease and can be subdivided into at least five different histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents and poly(ADP-ribose) polymerase inhibitors are used, and immunological therapies are currently being tested. High-grade serous carcinoma (HGSC) is the most commonly diagnosed form of ovarian cancer and at diagnosis is typically very responsive to platinum-based chemotherapy. However, in addition to the other histologies, HGSCs frequently relapse and become increasingly resistant to chemotherapy. Consequently, understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study in ovarian cancer. Substantial progress has been made in identifying genes that are associated with a high risk of ovarian cancer (such as BRCA1 and BRCA2), as well as a precursor lesion of HGSC called serous tubal intraepithelial carcinoma, which holds promise for identifying individuals at high risk of developing the disease and for developing prevention strategies
metabolic bone disease and osteoporosis in children
To understand the basics of pediatric bone metabolism and mechanisms underlying osteoporosi
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference
Renin-angiotensin system inhibitors and risk of fractures: a prospective cohort study and meta-analysis of published observational cohort studies
The renin-angiotensin system (RAS) represents an important target of antihypertensive medications. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), which are widely-used RAS inhibiting drugs, have been suggested to have beneficial effects on bone tissue. We aimed to assess the associations of use of ACEIs and/or ARBs with the risk of fractures using a population-based prospective cohort and a meta-analysis of published prospective cohort studies. Information on antihypertensive medication use (including both ACEIs and ARBs) were assessed in 1743 men and women of the Kuopio Ischemic Heart Disease prospective cohort study. Hazard ratios (HRs) [95% confidence intervals (CI)] of ACEIs or ARBs use with incident fractures were calculated. A total of 203 composite (hip, humeral, and wrist) fractures occurred during a median follow-up of 14.8 years. In multivariate adjusted analysis, the HR for composite fractures comparing users of ACEIs or ARBs with non-users was 1.00 (0.59–1.69). The corresponding adjusted HR for hip fractures comparing users versus non-users of ACEIs or ARBs was 0.89 (0.32–2.47). Including the current study, a total of 11 observational cohort studies involving 3526,319 participants and >323,355 fractures were included in a meta-analysis. Comparing ACEI users with non-users and ARB users with non-users, the HRs for composite fractures were 1.09 (0.89–1.33) and 0.87 (0.76–1.01) respectively. The corresponding HRs for hip fractures were 0.91 (0.86–0.95) and 0.80 (0.75–0.85) respectively. Use of RAS inhibitors was not associated with long-term risk of composite fractures in both primary and pooled analyses. Pooled evidence however suggests a beneficial effect of RAS blockers on hip fracture risk.</p
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