The 18-Year Risk of Cancer, Angioedema, Insomnia, Depression, and Erectile Dysfunction in Association With Antihypertensive Drugs: Post-Trial Analyses From ALLHAT-Medicare Linked Data

PURPOSE: This study aimed to determine the 18-year risk of cancer, angioedema, insomnia, depression, and erectile dysfunction in association with antihypertensive drug use. METHODS: This is a post-trial passive follow-up study of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants between 1994 and 1998 that was conducted by linking their follow-up data with Medicare claims data until 2017 of subjects who were free of outcomes at baseline on 1 January 1999. The main outcomes were the occurrence of cancer (among RESULTS: The 18-year cumulative incidence rate of cancer other than non-melanoma skin cancer from Medicare inpatient claims was 23.9% for chlorthalidone, 23.4% for amlodipine, and 25.3% for lisinopril. There were no statistically significant differences in the 18-year risk of cancer, depression, and erectile dysfunction among the three drugs based on the adjusted hazard ratios. The adjusted 18-year risk of angioedema was elevated in those receiving lisinopril than in those receiving amlodipine (hazard ratio: 1.63, 95% CI: 1.14-2.33) or in those receiving chlorthalidone (1.33, 1.00-1.79), whereas the adjusted 18-year risk of insomnia was statistically significantly decreased in those receiving lisinopril than in those receiving amlodipine (0.90, 0.81-1.00). CONCLUSIONS: The 18-year risk of angioedema was significantly higher in patients receiving lisinopril than in those receiving amlodipine or chlorthalidone; the risk of insomnia was significantly lower in patients receiving lisinopril than in those receiving amlodipine; and the risk of cancer, depression, and erectile dysfunction (in men) was not statistically significantly different among the three drug groups

Risk of Developing alzheimer\u27s Disease and Related Dementias in allhat Trial Participants Receiving Diuretic, ace-inhibitor, or Calcium-Channel Blocker With 18 Years of Follow-Up

BACKGROUND: There is no any large randomized clinical trial of antihypertensive drug treatment with 18-year passive follow-up to examine the risk of Alzheimer\u27s Disease (AD) or Related Dementias (ADRD). METHODS: Post-trial passive follow-up study of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants in 1994-1998 by linking with their Medicare claims data through 2017 among 17,158 subjects in 567 U.S. centers who were free of ADRD at baseline on January 1, 1999. Main outcome was the occurrence of ADRD over 18 years of follow-up. RESULTS: The 18-year cumulative incidence rates were 30.9% for AD, 59.2% for non-AD dementias, and 60.9% for any ADRD. The 18-year cumulative incidence of AD was almost identical for the 3 drug groups (30.5% for chlorthalidone, 31.1% for amlodipine, and 31.4% for lisinopril). The hazard ratios of AD, non-AD dementias and total ADRD were not statistically significantly different among the 3 drug groups. The adjusted hazard ratio of AD was 1.04 (95% CI: 0.94-1.14) for chlorthalidone CONCLUSION: The risk of ADRD did not vary significantly by 3 antihypertensive drugs in ALLHAT trial participants with 18-years of follow-up. The risk of ADRD was significantly associated with age, gender, race/ethnicity, education, and history of vascular diseases

Mortality and Morbidity among individuals With Hypertension Receiving a Diuretic, ace inhibitor, or Calcium Channel Blocker: a Secondary analysis of a Randomized Clinical Trial

IMPORTANCE: The long-term relative risk of antihypertensive treatments with regard to mortality and morbidity is not well understood. OBJECTIVE: to determine the long-term posttrial risk of primary and secondary outcomes among trial participants who were randomized to either a thiazide-type diuretic, calcium channel blocker (CCB), or angiotensin-converting enzyme (ACE) inhibitor with up to 23 years of follow-up. DESIGN, SETTING, AND PARTICIPANTS: This prespecified secondary analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a multicenter randomized, double-blind, active-controlled clinical trial, followed up with participants aged 55 years or older with a diagnosis of hypertension and at least 1 other coronary heart disease risk factor for up to 23 years, from February 23, 1994, to December 31, 2017. Trial participants were linked with administrative databases for posttrial mortality (N = 32 804) and morbidity outcomes (n = 22 754). Statistical analysis was performed from January 2022 to October 2023. INTERVENTIONS: Participants were randomly assigned to receive a thiazide-type diuretic (n = 15 002), a CCB (n = 8898), or an ACE inhibitor (n = 8904) for planned in-trial follow-up of approximately 4 to 8 years and posttrial passive follow-up for up to 23 years. MAIN OUTCOMES AND MEASURES: The primary end point was mortality due to cardiovascular disease (CVD). Secondary outcomes included all-cause mortality, combined fatal and nonfatal (morbidity) CVD, and both mortality and morbidity for coronary heart disease, stroke, heart failure, end-stage renal disease, and cancer. RESULTS: A total of 32 804 participants (mean [SD] age, 66.9 [7.7] years; 17 411 men [53.1%]; and 11 772 Black participants [35.9%]) were followed up for all-cause mortality and a subgroup of 22 754 participants (mean [SD] age, 68.7 [7.2] years; 12 772 women [56.1%]; and 8199 Black participants [36.0%]) were followed up for fatal or nonfatal CVD through 2017 (mean [SD] follow-up, 13.7 [6.7] years; maximum follow-up, 23.9 years). Cardiovascular disease mortality rates per 100 persons were 23.7, 21.6, and 23.8 in the diuretic, CCB, and ACE inhibitor groups, respectively, at 23 years after randomization (adjusted hazard ratio [AHR], 0.97 [95% CI, 0.89-1.05] for CCB vs diuretic; AHR, 1.06 [95% CI, 0.97-1.15] for ACE inhibitor vs diuretic). The long-term risks of most secondary outcomes were similar among the 3 groups. Compared with the diuretic group, the ACE inhibitor group had a 19% increased risk of stroke mortality (AHR, 1.19 [95% CI, 1.03-1.37]) and an 11% increased risk of combined fatal and nonfatal hospitalized stroke (AHR, 1.11 [95% CI, 1.03-1.20]). CONCLUSIONS AND RELEVANCE: In this secondary analysis of a randomized clinical trial in an adult population with hypertension and coronary heart disease risk factors, CVD mortality was similar between all 3 groups. ACE inhibitors increased the risk of stroke outcomes by 11% compared with diuretics, and this effect persisted well beyond the trial period. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00000542

Lack of a significant legacy effect of baseline blood pressure 'treatment naivety' on all-cause and cardiovascular mortality in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial

Objectives: To investigate legacy effects at 14-year follow-up of all-cause and cardiovascular disease (CVD) mortality in 'treatment-naive' or 'previous treatment' groups based on blood pressure (BP)-lowering treatment status at baseline. Methods: A post-hoc observational study of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. We excluded participants with a previous history of CVD events. Cox proportional hazard model and 95% confidence interval were used to estimate the effects of treatment naive on mortality outcomes. Moreover, a subgroup analysis by estimated 10-year Framingham risk score was performed. Results: In multivariable models adjusting for baseline and in-trial characteristics (BP values and number of BP medications as time-dependent variables), there was no statistically significant difference in 5 and 14-year all-cause mortality with a hazard ratio of 0.93 (95% confidence interval 0.80-1.09) and hazard ratio 0.95 (0.88-1.03) and in 5 and 14-year CVD mortality hazard ratio 0.94 (0.72-1.23) and hazard ratio 0.93 (0.80-1.08). In subgroup by absolute CVD risk, no heterogeneity of the association between treatment naive and short-term or long-term all-cause or CVD mortality were found. All comparisons are between the treatment-naive and previous treatment groups. Conclusion: Physicians are concerned about 'legacy effects' of not treating individuals with a BP of 140 mmHg or over and low absolute risk. When treatment intensification was taken into consideration in the primary prevention population in this study, no adverse legacy effect as a result of baseline BP 'treatment naivety' was evident in 14 years of follow-up. The nonsignificant associations were consistent across the CVD risk subgroups. However, the results may be biased due to unobserved residual confounding and therefore should be interpreted with caution

AGN-Host Galaxy Connection: Morphology and Colours of X-ray Selected AGN at z < 2

The connection between AGN and their host galaxies has been widely studied over recent years, showing it to be of great importance for providing answers to some fundamental questions related with AGN fueling mechanisms, their formation and evolution. Using X-ray and one of the deepest broad-band optical data sets, we studied morphology and colours in relationship with X-ray properties for sources at redshifts z < 2.0, using a sample of 262 AGN in the Subaru/XMM-Newton Deep Survey (SXDS). Morphological classification was obtained using the galSVM code, one of the new methods useful especially when dealing with high-redshift sources and low-resolution data. Colour-magnitude diagrams were studied in relationship with redshift, morphology, X-ray obscuration, and X-ray-to-optical flux ratio. Finally, the significance of different regions was analysed on colour-magnitude diagrams, relating the observed properties of AGN populations with some models of their formation and evolution.Comment: 24 pages, 19 figures, accepted for publication in Astronomy&Astrophysic

Risk factors for high anti-HHV-8 antibody titers (≥1:51,200) in black, HIV-1 negative South African cancer patients: a case control study

Background: Infection with human herpesvirus 8 (HHV-8) is the necessary causal agent in the development of Kaposi's sarcoma (KS). Infection with HIV-1, male gender and older age all increase risk for KS. However, the geographic distribution of HHV-8 and KS both prior to the HIV/AIDS epidemic and with HIV/AIDS suggest the presence of an additional co-factor in the development of KS. Methods: Between January 1994 and October 1997, we interviewed 2576 black in-patients with cancer in Johannesburg and Soweto, South Africa. Blood was tested for antibodies against HIV-1 and HHV-8 and the study was restricted to 2191 HIV-1 negative patients. Antibodies against the latent nuclear antigen of HHV-8 encoded by orf73 were detected with an indirect immunofluorescence assay. We examined the relationship between high anti-HHV-8 antibody titers (≥1:51,200) and sociodemographic and behavioral factors using unconditional logistic regression models. Variables that were significant at p = 0.10 were included in multivariate analysis. Results: Of the 2191 HIV-1 negative patients who did not have Kaposi's sarcoma, 854 (39.0%) were positive for antibodies against HHV-8 according to the immunofluorescent assay. Among those seropositive for HHV-8, 530 (62.1%) had low titers (1:200), 227 (26.6%) had medium titers (1:51,200) and 97 (11.4%) had highest titers (1:204,800). Among the 2191 HIV-1 negative patients, the prevalence of high anti-HHV-8 antibody titers (≥1:51,200) was independently associated with increasing age (ptrend = 0.04), having a marital status of separated or divorced (p = 0.003), using wood, coal or charcoal as fuel for cooking 20 years ago instead of electricity (p = 0.02) and consuming traditional maize beer more than one time a week (p = 0.02; p-trend for increasing consumption = 0.05) although this may be due to chance given the large number of predictors considered in this analysis. Conclusions: Among HIV-negative subjects, patients with high anti-HHV-8 antibody titers are characterized by older age. Other associations that may be factors in the development of high anti- HHV-8 titers include exposure to poverty or a low socioeconomic status environment and consumption of traditional maize beer. The relationship between these variables and high anti- HHV-8 titers requires further, prospective study

RXTE all-sky slew survey. Catalog of X-ray sources at |b|>10deg

We report results of a serendipitous hard X-ray (3--20 keV), nearly all-sky (|b|>10deg) survey based on RXTE/PCA observations performed during satellite reorientations in 1996--2002. The survey is 80% (90%) complete to a 4$\sigma$ limiting flux of ~1.8 (2.5) e-11 erg/s/cm2 in the 3--20 keV band. The achieved sensitivity in the 3--8 keV and 8--20 keV subbands is similar to and an order of magnitude higher than that of the previously record HEAO-1 A1 and HEAO-1 A4 all-sky surveys, respectively. A combined 7000 sq. deg area of the sky is sampled to flux levels below 1e-11 erg/s/cm2 (3--20 keV). In total 294 sources are detected and localized to better than 1 deg. 236 (80%) of these can be confidently associated with a known astrophysical object; another 22 likely result from the superposition of 2 or 3 closely located known sources. 35 detected sources remain unidentified, although for 12 of these we report a likely soft X-ray counterpart from the ROSAT all-sky survey bright source catalog. Of the reliably identified sources, 63 have local origin (Milky Way, LMC or SMC), 64 are clusters of galaxies and 100 are active galactic nuclei (AGN). The fact that the unidentified X-ray sources have hard spectra suggests that the majority of them are AGN, including highly obscured ones (nH>1e23 cm^{-2}). For the first time we present a logN-logS diagram for extragalactic sources above 4e-12 erg/s/cm2 at 8-20 keV.Comment: 19 pages, 9 figures. Accepted for publication in A&

Translating the Knowledge Gap Between Researchers and Communication Designers for Improved mHealth Research

Our industry insight focuses on the challenges for health researchers collaborating with communication designers during the development of an App for improving maternal mental health and parenting stress. We discuss the challenges around explicating and communicating tacit and domain knowledge across disciplinary boundaries. We believe this report can widen communication design’s traditional focus on users in mHealth research to consider partnerships with academic researchers. The lessons learned from our experience developing a mHealth program can be used to reduce challenges in future mHealth research, especially for collaborations between health researchers and communications designers. Considering the growth of interest in mHealth, this is extremely relevant for future team satisfaction, the optimal use of research funds and industry time, and faster development of effective mHealth tools.This is the accepted manuscript version of the following publication: Rioux, C., Weedon, S., MacKinnon, A. L., Watts, D., Salisbury, M. R., Penner-Goeke, L., Simpson, K. M., Harrington, J., Tomfohr-Madsen, L. M. & Roos, L. E. (2022). Translating the Knowledge Gap Between Researchers and Communication Designers for Improved mHealth Research. SIGDOC '22: The 40th ACM International Conference on Design of Communication, USA, 157–160. doi: 10.1145/3513130.3558997BEAM was funded by a Research Manitoba COVID-19 Rapid Response Operating Grant. CR was supported by a Postdoctoral fellowship from Research Manitoba and the Children’s Hospital Foundation of Manitoba. ALM was supported by a Social Sciences & Humanities Research Council (SSHRC) Banting Postdoctoral Fellowship (#01353-000).Ye

Identification of the initial molecular changes in response to circulating angiogenic cells-mediated therapy in critical limb ischemia

BackgroundCritical limb ischemia (CLI) constitutes the most aggressive form of peripheral arterial occlusive disease, characterized by the blockade of arteries supplying blood to the lower extremities, significantly diminishing oxygen and nutrient supply. CLI patients usually undergo amputation of fingers, feet, or extremities, with a high risk of mortality due to associated comorbidities.Circulating angiogenic cells (CACs), also known as early endothelial progenitor cells, constitute promising candidates for cell therapy in CLI due to their assigned vascular regenerative properties. Preclinical and clinical assays with CACs have shown promising results. A better understanding of how these cells participate in vascular regeneration would significantly help to potentiate their role in revascularization.Herein, we analyzed the initial molecular mechanisms triggered by human CACs after being administered to a murine model of CLI, in order to understand how these cells promote angiogenesis within the ischemic tissues.MethodsBalb-c nude mice (n:24) were distributed in four different groups: healthy controls (C, n:4), shams (SH, n:4), and ischemic mice (after femoral ligation) that received either 50 mu l physiological serum (SC, n:8) or 5x10(5) human CACs (SE, n:8). Ischemic mice were sacrificed on days 2 and 4 (n:4/group/day), and immunohistochemistry assays and qPCR amplification of Alu-human-specific sequences were carried out for cell detection and vascular density measurements. Additionally, a label-free MS-based quantitative approach was performed to identify protein changes related.ResultsAdministration of CACs induced in the ischemic tissues an increase in the number of blood vessels as well as the diameter size compared to ischemic, non-treated mice, although the number of CACs decreased within time. The initial protein changes taking place in response to ischemia and more importantly, right after administration of CACs to CLI mice, are shown.ConclusionsOur results indicate that CACs migrate to the injured area; moreover, they trigger protein changes correlated with cell migration, cell death, angiogenesis, and arteriogenesis in the host. These changes indicate that CACs promote from the beginning an increase in the number of vessels as well as the development of an appropriate vascular network.Institute of Health Carlos III, ISCIII; Junta de Andaluci

Distribution and Phylogeny of EFL and EF-1α in Euglenozoa Suggest Ancestral Co-Occurrence Followed by Differential Loss

BACKGROUND: The eukaryotic elongation factor EF-1alpha (also known as EF1A) catalyzes aminoacyl-tRNA binding by the ribosome during translation. Homologs of this essential protein occur in all domains of life, and it was previously thought to be ubiquitous in eukaryotes. Recently, however, a number of eukaryotes were found to lack EF-1alpha and instead encode a related protein called EFL (for EF-Like). EFL-encoding organisms are scattered widely across the tree of eukaryotes, and all have close relatives that encode EF-1alpha. This intriguingly complex distribution has been attributed to multiple lateral transfers because EFL's near mutual exclusivity with EF-1alpha makes an extended period of co-occurrence seem unlikely. However, differential loss may play a role in EFL evolution, and this possibility has been less widely discussed. METHODOLOGY/PRINCIPAL FINDINGS: We have undertaken an EST- and PCR-based survey to determine the distribution of these two proteins in a previously under-sampled group, the Euglenozoa. EF-1alpha was found to be widespread and monophyletic, suggesting it is ancestral in this group. EFL was found in some species belonging to each of the three euglenozoan lineages, diplonemids, kinetoplastids, and euglenids. CONCLUSIONS/SIGNIFICANCE: Interestingly, the kinetoplastid EFL sequences are specifically related despite the fact that the lineages in which they are found are not sisters to one another, suggesting that EFL and EF-1alpha co-occurred in an early ancestor of kinetoplastids. This represents the strongest phylogenetic evidence to date that differential loss has contributed to the complex distribution of EFL and EF-1alpha