Patient-Reported Outcomes Through 1 Year of an HIV-1 Clinical Trial Evaluating Long-Acting Cabotegravir and Rilpivirine Administered Every 4 or 8 Weeks (ATLAS-2M)

BACKGROUND: Advances in HIV-1 therapeutics have led to the development of a range of daily oral treatment regimens, which share similar high efficacy rates. Consequently, more emphasis is being placed upon the individual\u27s experience of treatment and impact on quality of life. The first long-acting injectable antiretroviral therapy for HIV-1 (long-acting cabotegravir + rilpivirine [CAB + RPV LA]) may address challenges associated with oral treatment for HIV-1, such as stigma, pill burden/fatigue, drug-food interactions, and adherence. Patient-reported outcomes (PROs) collected in an HIV-1 clinical trial (ATLAS-2M; NCT03299049) comparing participants\u27 experience with two dosing regimens (every 4 weeks [Q4W] vs. every 8 weeks [Q8W]) of CAB + RPV LA are presented herein. METHODS: PRO endpoints evaluated through 48 weeks of therapy included treatment satisfaction (HIV Treatment Satisfaction Questionnaire [HIVTSQ]), treatment acceptance ( General Acceptance domain of the Chronic Treatment Acceptance [ACCEPT RESULTS: Overall, 1045 participants were randomized to the Q8W (n = 522) and Q4W (n = 523) regimens; 37% (n = 391/1045) had previously received CAB + RPV in ATLAS. For participants without prior CAB + RPV exposure, large increases from baseline were reported in treatment satisfaction in both long-acting arms (HIVTSQ status version), with Q8W dosing statistically significantly favored at Weeks 24 (p = 0.036) and 48 (p = 0.004). Additionally, improvements from baseline were also observed in the General Acceptance domain of the ACCEPT questionnaire in both long-acting arms for participants without prior CAB + RPV exposure; however, no statistically significant difference was observed between arms at either timepoint (Week 24, p = 0.379; Week 48, p = 0.525). Significant improvements (p \u3c 0.001) in the Acceptance of Injection Site Reactions domain of the PIN questionnaire were observed from Week 8 to Weeks 24 and 48 in both arms for participants without prior CAB + RPV exposure. Participants with prior CAB + RPV exposure reported high treatment satisfaction (mean [HIVTSQ status version]: Q8W 62.2/66.0; Q4W 62.0/66.0), treatment acceptance (mean: Q8W 89.3/100; Q4W 91.2/100), and acceptance of injection site reactions (mean [5 = not at all acceptable; 1 = totally acceptable]: Q8W 1.72; Q4W 1.59) at baseline/Week 8 that were maintained over time. Participants without prior CAB + RPV exposure who received Q8W dosing preferred this regimen over oral CAB + RPV (98%, n = 300/306). Among those with prior Q4W exposure, 94% (n = 179/191) preferred Q8W dosing versus Q4W dosing (3%, n = 6/191) or oral CAB + RPV (2%, n = 4/191). CONCLUSIONS: Both long-acting regimens provided high treatment satisfaction and acceptance, irrespective of prior CAB + RPV exposure, with most participants preferring Q8W dosing over both the Q4W regimen and their previous daily oral regimen. The PRO data collected at Week 48 support the therapeutic potential of CAB + RPV LA. FUNDING: ViiV Healthcare and Janssen. TRIAL REGISTRATION: ATLAS-2M: ClinicalTrials.gov NCT03299049, registered October 2, 2017

Outcome and Predictors for Mortality in Patients with Cardiogenic Shock:A Dutch Nationwide Registry-Based Study of 75,407 Patients with Acute Coronary Syndrome Treated by PCI

It is important to gain more insight into the cardiogenic shock (CS) population, as currently, little is known on how to improve outcomes. Therefore, we assessed clinical outcome in acute coronary syndrome (ACS) patients treated by percutaneous coronary intervention (PCI) with and without CS at admission. Furthermore, the incidence of CS and predictors for mortality in CS patients were evaluated. The Netherlands Heart Registration (NHR) is a nationwide registry on all cardiac interventions. We used NHR data of ACS patients treated with PCI between 2015 and 2019. Among 75,407 ACS patients treated with PCI, 3028 patients (4.1%) were identified with CS, respectively 4.3%, 3.9%, 3.5%, and 4.3% per year. Factors associated with mortality in CS were age (HR 1.02, 95%CI 1.02-1.03), eGFR (HR 0.98, 95%CI 0.98-0.99), diabetes mellitus (DM) (HR 1.25, 95%CI 1.08-1.45), multivessel disease (HR 1.22, 95%CI 1.06-1.39), prior myocardial infarction (MI) (HR 1.24, 95%CI 1.06-1.45), and out-of-hospital cardiac arrest (OHCA) (HR 1.71, 95%CI 1.50-1.94). In conclusion, in this Dutch nationwide registry-based study of ACS patients treated by PCI, the incidence of CS was 4.1% over the 4-year study period. Predictors for mortality in CS were higher age, renal insufficiency, presence of DM, multivessel disease, prior MI, and OHCA

Characteristics, Treatment Strategies and Outcome in Cardiogenic Shock Complicating Acute Myocardial Infarction:A Contemporary Dutch Cohort

Cardiogenic shock (CS) complicating acute myocardial infarction (AMI) is associated with high morbidity and mortality. Our study aimed to gain insights into patient characteristics, outcomes and treatment strategies in CS patients. Patients with CS who underwent percutaneous coronary intervention (PCI) between 2017 and 2021 were identified in a nationwide registry. Data on medical history, laboratory values, angiographic features and outcomes were retrospectively assessed. A total of 2328 patients with a mean age of 66 years and of whom 73% were male, were included. Mortality at 30 days was 39% for the entire cohort. Non-survivors presented with a lower mean blood pressure and increased heart rate, blood lactate and blood glucose levels (p-value for all &lt;0.001). Also, an increased prevalence of diabetes, multivessel coronary artery disease and a prior coronary event were found. Of all patients, 24% received mechanical circulatory support, of which the majority was via intra-aortic balloon pumps (IABPs). Furthermore, 79% of patients were treated with at least one vasoactive agent, and multivessel PCI was performed in 28%. In conclusion, a large set of hemodynamic, biochemical and patient-related characteristics was identified to be associated with mortality. Interestingly, multivessel PCI and IABPs were frequently applied despite a lack of evidence.</p

Long-acting injectable Cabotegravir + Rilpivirine for HIV maintenance therapy: Week 48 pooled analysis of phase 3 ATLAS and FLAIR trials

BACKGROUND: Long-acting (LA) injectable regimens are a potential therapeutic option in people living with HIV-1. SETTING: ATLAS (NCT02951052) and FLAIR (NCT02938520) were 2 randomized, open-label, multicenter, multinational phase 3 studies. METHODS: Adult participants with virologic suppression (plasma HIV-1 RNA &lt;50 copies/mL) were randomized (1:1) to continue with their current antiretroviral regimen (CAR) or switch to the long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). In the LA arm, participants initially received oral CAB + RPV once-daily for 4 weeks to assess individual safety and tolerability, before starting monthly injectable therapy. The primary endpoint of this combined analysis was antiviral efficacy at week 48 (FDA Snapshot algorithm: noninferiority margin of 4% for HIV-1 RNA ≥50 copies/mL). Safety, tolerability, and confirmed virologic failure (2 consecutive plasma HIV-1 RNA ≥200 copies/mL) were secondary endpoints. RESULTS: The pooled intention-to-treat exposed population included 591 participants in each arm [28% women (sex at birth), 19% aged ≥50 years]. Noninferiority criteria at week 48 were met for the primary (HIV-1 RNA ≥50 copies/mL) and key secondary (HIV-1 RNA &lt;50 copies/mL) efficacy endpoints. Seven individuals in each arm (1.2%) developed confirmed virologic failure; 6/7 (LA) and 3/7 (CAR) had resistance-associated mutations. Most LA recipients (83%) experienced injection site reactions, which decreased in incidence over time. Injection site reactions led to the withdrawal of 6 (1%) participants. The serious adverse event rate was 4% in each arm. CONCLUSION: This combined analysis demonstrates monthly injections of CAB + RPV LA were noninferior to daily oral CAR for maintaining HIV-1 suppression

Fatal postpartum air embolism due to uterine inversion and atonic hemorrhage

We report a case of a 19-year-old woman who developed a persistent uterine hemorrhage after spontaneous delivery of a healthy child. Emergency laparotomy was indicated and then begun under stable circulatory conditions. Cardiac arrest occurred during the course of massive manual compression and packing of the uterus. After successful resuscitation, a supracervical hysterectomy was performed. During the suturing of the remaining cervix, a second cardiac arrest followed. The procedure was completed under constant external heart massage. Resuscitation was terminated due to the persistence of widened pupils. An autopsy was ordered by the public prosecutor as the manner of death was declared to be unascertained. An X-ray and a CT scan prior to the autopsy showed extensive gas embolism in both arterial and venous vessels extending from the pelvic region to the head. During the autopsy, gas was collected by aspirometer from the right ventricle of the heart. The autopsy showed no additional relevant findings, and gas analysis confirmed the suspicion of air embolism. The histological examination of the excised uterus especially in the corpus/fundus revealed an edema of the local smooth muscle cells and dilated vessels showing no sign of thrombogenesis. Upon evaluation of the clinical records, it became evident that, in addition to uterine atony, there had been a complete uterine inversion. This inversion was manually repositioned. After this maneuver, manual compression was performed. The air embolism, thus, was a complication of the manual repositioning of the uterine inversion. There is no evidence for other possible entries of the detected gas. In order to perform an effective exploration, the availability of all clinical records should be mandatory for medico-legal investigations of unexpected postpartum deaths

Assessment of Cardiac Device Position on Supine Chest Radiograph in the ICU: Introduction and Applicability of the Aortic Valve Location Ratio

The use of intracardiac assist devices is expanding, and correct position of these devices is required for optimal functioning. The aortic valve is an important landmark for positioning of those devices. It would be of great value if the device position could be easily monitored on plain supine chest radiograph in the ICU. We introduce a ratio-based tool for determination of the aortic valve location on plain supine chest radiograph images, which can be used to evaluate intracardiac device position. Retrospective observational study. Large academic medical center. Patients admitted to the ICU and supported by an intracardiac assist device. We developed a ratio to determine the aortic valve location on supine chest radiograph images. This ratio is used to assess the position of a cardiac assist device and is compared with echocardiographic findings. Supine anterior-posterior chest radiographs of patients with an aortic valve prosthesis (n = 473) were analyzed to determine the location of the aortic valve. We calculated several ratios with the potential to determine the position of the aortic valve. The aortic valve location ratio, defined as the distance between the carina and the aortic valve, divided by the thoracic width, was found to be the best performing ratio. The aortic valve location ratio determines the location of the aortic valve caudal to the carina, at a distance of 0.25 ± 0.05 times the thoracic width for male patients and 0.28 ± 0.05 times the thoracic width for female patients. The aortic valve location ratio was validated using CT images of patients with angina pectoris without known valvular disease (n = 95). There was a good correlation between cardiac device position (Impella) assessed with the aortic valve location ratio and with echocardiography (n = 53). The aortic valve location ratio enables accurate and reproducible localization of the aortic valve on supine chest radiograph. This tool is easily applicable and can be used for assessment of cardiac device position in patients on the IC

A combined surgical and percutaneous approach through the axillary artery to introduce the Impella LP5.0 for short-term circulatory support

We describe a novel axillary approach for insertion and usage of the Impella LP5.0, a low cost micro-axial flow pump, in five patients requiring circulatory support after acute ST-segment elevation myocardial infarction (STEMI). This alternative approach for implantation of the Impella LP5.0 has been proven simple, safe and feasible, and less invasive in severely compromised patients. Our hybrid, percutaneous and surgical, approach offered acute short-term circulatory support in STEMI patients with acute heart failure, allowing myocardial recovery or selection for long-term mechanical suppor