Clinical characteristics, causes, adherence to heart failure treatment guidelines and mortality of patients with acute heart failure: the Groote Schuur Hospital experience

Background: There is limited information on acute heart failure (AHF) and the treatment thereof in sub-Saharan Africa. Therefore, the aim of this study was to describe the clinical characteristics, causes, adherence to heart failure (HF) treatment guidelines and mortality of patients presenting to Groote Schuur Hospital with acute heart failure (AHF). Methods: This is a sub-study of The Sub-Saharan Africa Survey of Heart Failure (THESUSHF). This sub-study is a prospective and observational survey that focused on the enrolment and follow-up of additional patients with AHF presenting to Groote Schuur Hospital entered into the existing registry, following the publication of the primary paper of THESUS-HF in 2012. The patients were classified into prevalent (or existing) or incident (or new) cases of heart failure. Results: Of the 119 patients included, 69 (58%) were female and the mean (SD) age was 49.9 (16.3) years. Prevalent cases were mostly of mixed ancestry (63.3%) with more hypertension (70%), diabetes mellitus (36.7%), hyperlipidaemia (33.3%) and ischaemic heart disease (36.7%) than incident cases. The main causes of heart failure were cardiomyopathy (20.2%), ischaemic heart disease (IHD) (19.3%) and rheumatic valvular heart disease (RHD) (18.5%). Most patients received renin-angiotensin system blockers and loop diuretics on discharge. There was a low rate of β-blocker, aldosterone antagonist and digoxin use. Rehospitalisation at 180 days occurred in 25.2%. In-hospital mortality was 8.4 % and the case fatality rate at six months was 26.1%. Conclusion: In Cape Town the main causes of AHF are cardiomyopathy, IHD and RHD. AHF affects a young population and is associated with a high rate of rehospitalisation and mortality. There is a serious under-use of β-blockers, aldosterone antagonists and digoxin. An emphasis on the rigorous application of treatment guidelines is needed in order to reduce re-admission and mortality

Microlensing optical depth and event rate in the OGLE-IV Galactic plane fields

Searches for gravitational microlensing events are traditionally concentrated on the central regions of the Galactic bulge but many microlensing events are expected to occur in the Galactic plane, far from the Galactic Center. Owing to the difficulty in conducting high-cadence observations of the Galactic plane over its vast area, which are necessary for the detection of microlensing events, their global properties were hitherto unknown. Here, we present results of the first comprehensive search for microlensing events in the Galactic plane. We searched an area of almost 3000 square degrees along the Galactic plane (|b|<7, 0<l<50, 190<l<360 deg) observed by the Optical Gravitational Lensing Experiment (OGLE) during 2013-2019 and detected 630 events. We demonstrate that the mean Einstein timescales of Galactic plane microlensing events are on average three times longer than those of Galactic bulge events, with little dependence on the Galactic longitude. We also measure the microlensing optical depth and event rate as a function of Galactic longitude and demonstrate that they exponentially decrease with the angular distance from the Galactic Center (with the characteristic angular scale length of 32 deg). The average optical depth decreases from $0.5\times 10^{-6}$ at l=10 deg to $1.5\times 10^{-8}$ in the Galactic anticenter. We also find that the optical depth in the longitude range 240<l<330 deg is asymmetric about the Galactic equator, which we interpret as a signature of the Galactic warp.Comment: ApJS, in pres

Microlensing optical depth and event rate in the OGLE-IV Galactic plane fields

Searches for gravitational microlensing events are traditionally concentrated on the central regions of the Galactic bulge but many microlensing events are expected to occur in the Galactic plane, far from the Galactic Center. Owing to the difficulty in conducting high-cadence observations of the Galactic plane over its vast area, which are necessary for the detection of microlensing events, their global properties were hitherto unknown. Here, we present results of the first comprehensive search for microlensing events in the Galactic plane. We searched an area of almost 3000 square degrees along the Galactic plane (|b| < 7°, 0° < l < 50°, 190° < l < 360°) observed by the Optical Gravitational Lensing Experiment (OGLE) during 2013–2019 and detected 630 events. We demonstrate that the mean Einstein timescales of Galactic plane microlensing events are on average three times longer than those of Galactic bulge events, with little dependence on the Galactic longitude. We also measure the microlensing optical depth and event rate as a function of Galactic longitude and demonstrate that they exponentially decrease with the angular distance from the Galactic Center (with the characteristic angular scale length of 32°). The average optical depth decreases from 0.5 × 10⁻⁶ at l = 10° to 1.5 × 10⁻⁸ in the Galactic anticenter. We also find that the optical depth in the longitude range 240° < l < 330° is asymmetric about the Galactic equator, which we interpret as a signature of the Galactic warp

OGLE-2018-BLG-0532Lb: Cold Neptune With Possible Jovian Sibling

We report the discovery of the planet OGLE-2018-BLG-0532Lb, with very obvious signatures in the light curve that lead to an estimate of the planet-host mass ratio $q=M_{\rm planet}/M_{\rm host}\simeq 1\times10^{-4}$. Although there are no obvious systematic residuals to this double-lens/single-source (2L1S) fit, we find that $\chi^2$ can be significantly improved by adding either a third lens (3L1S, $\Delta\chi^2=81$) or second source (2L2S, $\Delta\chi^2=65$) to the lens-source geometry. After thorough investigation, we conclude that we cannot decisively distinguish between these two scenarios and therefore focus on the robustly-detected planet. However, given the possible presence of a second planet, we investigate to what degree and with what probability such additional planets may affect seemingly single-planet light curves. Our best estimates for the properties of the lens star and the secure planet are: a host mass $M\sim 0.25\,M_\odot$, system distance $D_L\sim 1\,$kpc and planet mass $m_{p,1}= 8\,M_\oplus$ with projected separation $a_{1,\perp}=1.4\,$au. However, there is a relatively bright $I=18.6$ (and also relatively blue) star projected within $<50\,$mas of the lens, and if future high-resolution images show that this is coincident with the lens, then it is possible that it is the lens, in which case, the lens would be both more massive and more distant than the best-estimated values above.Comment: 48 pages, 9 figures, 7 table

OGLE-2019-BLG-0960 Lb: The Smallest Microlensing Planet

We report the analysis of OGLE-2019-BLG-0960, which contains the smallest mass-ratio microlensing planet found to date (q = 1.2-1.6 × 10-5 at 1s). Although there is substantial uncertainty in the satellite parallax measured by Spitzer, the measurement of the annual parallax effect combined with the finite source effect allows us to determine the mass of the host star (M L = 0.3-0.6 M o?), the mass of its planet (m p = 1.4-3.1 M ?), the projected separation between the host and planet (a ? = 1.2-2.3 au), and the distance to the lens system (D L = 0.6-1.2 kpc). The lens is plausibly the blend, which could be checked with adaptive optics observations. As the smallest planet clearly below the break in the mass-ratio function, it demonstrates that current experiments are powerful enough to robustly measure the slope of the mass-ratio function below that break. We find that the cross-section for detecting small planets is maximized for planets with separations just outside of the boundary for resonant caustics and that sensitivity to such planets can be maximized by intensively monitoring events whenever they are magnified by a factor A \u3e 5. Finally, an empirical investigation demonstrates that most planets showing a degeneracy between (s \u3e 1) and (s \u3c 1) solutions are not in the regime (log s| » 0) for which the close / wide degeneracy was derived. This investigation suggests that there is a link between the close / wide and inner/outer degeneracies and also that the symmetry in the lens equation goes much deeper than symmetries uncovered for the limiting cases

Study protocol for a phase 2A trial of the safety and tolerability of increased dose rifampicin and adjunctive linezolid, with or without aspirin, for HIV-associated tuberculous meningitis [LASER-TBM] [version 1; peer review: 2 approved]

Background: Tuberculous meningitis (TBM) is the most lethal form of tuberculosis with a mortality of ~50% in those co-infected with HIV-1. Current antibiotic regimens are based on those known to be effective in pulmonary TB and do not account for the differing ability of the drugs to penetrate the central nervous system (CNS). The host immune response drives pathology in TBM, yet effective host-directed therapies are scarce. There is sufficient data to suggest that higher doses of rifampicin (RIF), additional linezolid (LZD) and adjunctive aspirin (ASA) will be beneficial in TBM yet rigorous investigation of the safety of these interventions in the context of HIV associated TBM is required. We hypothesise that increased dose RIF, LZD and ASA used in combination and in addition to standard of care for the first 56 days of treatment with be safe and tolerated in HIV-1 infected people with TBM. Methods: In an open-label randomised parallel study, up to 100 participants will receive either; i) standard of care (n=40, control arm), ii) standard of care plus increased dose RIF (35mg/kg) and LZD (1200mg OD for 28 days, 600mg OD for 28 days) (n=30, experimental arm 1), or iii) as per experimental arm 1 plus additional ASA 1000mg OD (n=30, experimental arm 2). After 56 days participants will continue standard treatment as per national guidelines. The primary endpoint is death and the occurrence of solicited treatment-related adverse events at 56 days. In a planned pharmacokinetic (PK) sub-study we aim to assess PK/pharmacodynamic (PD) of oral vs IV rifampicin, describe LZD and RIF PK and cerebrospinal fluid concentrations, explore PK/PD relationships, and investigate drug-drug interactions between LZD and RIF. Safety and pharmacokinetic data from this study will inform a planned phase III study of intensified therapy in TBM. Clinicaltrials.gov registration: NCT03927313 (25/04/2019