Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The HYSTER study: the effect of intracervically administered terlipressin versus placebo on the number of gaseous emboli and fluid intravasation during hysteroscopic surgery: study protocol for a randomized controlled clinical trial

Abstract Background Transcervical resection of myoma or endometrium is a safe, hysteroscopic, minimally invasive procedure. However, intravasation of distension fluid is a common phenomenon during these procedures. In a previous study we observed venous gas emboli in almost every patient. The severity of hysteroscopic-derived embolization has been shown to be correlated to the amount of intravasation. In addition, paradoxical gas embolism, which is potentially dangerous, was observed in several patients. Studies have shown a reduction of intravasation by using intracervically administered vasopressin during hysteroscopy. We think that its analog, terlipressin, should have the same effect. In our previous research we observed more gaseous emboli as intravasation increased. Whether or not the insertion of intracervically administered terlipressin leads to a lower incidence and severity of gas embolism is unknown. We hypothesize that intracervically administered terlipressin leads to a reduction of intravasation with a lower incidence and severity of gas embolism. Terlipressin may be of benefit during hysteroscopic surgery. Methods/design Forty-eight patients (ASA 1 or 2) scheduled for transcervical resection of large, types 1–2 myoma or extensive endometrium resection will be included. In a double-blind fashion patients will be randomized 1:1 according to surgical treatment using either intracervically administered terlipressin or placebo. Transesophageal echocardiography will be used to observe and record embolic events. A pre- and post-procedure venous blood sample will be taken to calculate intravasation based on hemodilution. Our primary endpoint will be how terlipressin influences the severity of embolic events. Secondary endpoints include the effect of terlipressin on the amount of intravasation and on hemodynamic parameters. Discussion If terlipressin does indeed reduce the number of gaseous emboli and intravasation occurring during hysteroscopic surgery, it would be a simple method to minimize potential adverse events. It also allows for prolonged operating time before the threshold of intravasation is reached, thereby reducing the need for a second operation. Trial registration Nederlands Trial Register (Dutch Trial Register), ID: NTR5577. Registered retrospectively on 18 December 2015

A multidisciplinary evidence-based guideline for minimally invasive surgery.: Part 1: entry techniques and the pneumoperitoneum

The Dutch Society for Endoscopic Surgery together with the Dutch Society of Obstetrics and Gynecology initiated a multidisciplinary working group to develop a guideline on minimally invasive surgery to formulate multidisciplinary agreements for minimally invasive surgery aiming towards better patient care and safety. The guideline development group consisted of general surgeons, gynecologists, an anesthesiologist, and urologist authorized by their scientific professional association. Two advisors in evidence-based guideline development supported the group. The guideline was developed using the "Appraisal of Guidelines for Research and Evaluation" instrument. Clinically important aspects were identified and discussed. The best available evidence on these aspects was gathered by systematic review. Recommendations for clinical practice were formulated based on the evidence and a consensus of expert opinion. The guideline was externally reviewed by members of the participating scientific associations and their feedback was integrated. Identified important topics were: laparoscopic entry techniques, intra-abdominal pressure, trocar use, electrosurgical techniques, prevention of trocar site herniation, patient positioning, anesthesiology, perioperative care, patient information, multidisciplinary user consultation, and complication registration. The text of each topic contains an introduction with an explanation of the problem and a summary of the current literature. Each topic was discussed, considerations were evaluated and recommendations were formulated. The development of a guideline on a multidisciplinary level facilitated a broad and rich discussion, which resulted in a very complete and implementable guidelin

Explaining the ineffectiveness of a Tai Chi fall prevention training for community-living older people: A process evaluation alongside a randomized clinical trial (RCT)

The results of a randomized clinical trial (RCT) on the effects of a Tai Chi fall prevention in community-living older people with a high risk of falling in the Netherlands showed no beneficial effects on falls and secondary outcomes (e.g., balance, fear of falling). The aim of this study is to provide insight in process-related factors that may have influenced the effectiveness of the intervention. The intervention consisted of Tai Chi Chuan (TCC) training for 1. h twice a week for 13 weeks. We used self-administered questionnaires and registration forms to collect data from participants and instructors. We analyzed quantitative data by means of descriptive statistics and categorized qualitative data based on the content of the answers given. Of the participants, that started the program 89 (79%) completed the intervention, but a minority of 47% attended 80% of more of the lessons. All participants and instructors were positive about the program and most participants reported benefits from the intervention. Suggestions for improvements mainly relate to adjustments of training aspects. The main process-related factors that may be have influenced the lack of beneficial effects on falls and secondary outcomes are the relatively high withdrawal and the low adherence rates

Development and Characterization of Clinical-Grade Zr-89-Trastuzumab for HER2/neu ImmunoPET Imaging

The anti-human epidermal growth factor receptor 2 (HER2/neu) antibody trastuzumab is administered to patients with HER2/neu-overexpressing breast cancer. Whole-body noninvasive HER2/neu scintigraphy could help to assess and quantify the HER2/neu expression of all lesions, including nonaccessible metastases. The aims of this study were to develop clinical-grade radiolabeled trastuzumab for clinical HER2/neu immunoPET scintigraphy, to improve diagnostic imaging, to guide antibody-based therapy, and to support early antibody development. The PET radiopharmaceutical Zr-89-trastuzumab was compared with the SPECT tracer In-111-trastuzumab, which we have tested in the clinic already. Methods: Trastuzumab was labeled with Zr-89 and (for comparison) with In-111. The minimal dose of trastuzumab required for optimal small-animal PET imaging and biodistribution was determined with human HER2/neu-positive or -negative tumor xenograft-bearing mice. Results: Trastuzumab was efficiently radiolabeled with Zr-89 at a high radiochemical purity and specific activity. The antigen-binding capacity was preserved, and the radiopharmaceutical proved to be stable for up to 7 d in solvent and human serum. Of the tested protein doses, the minimal dose of trastuzumab (100 mu g) proved to be optimal for imaging. The comparative biodistribution study showed a higher level of Zr-89-trastuzumab in HER2/neu-positive tumors than in HER2/neu-negative tumors, especially at day 6 (33.4 +/- 7.6 [mean +/- SEM] vs. 7.1 +/- 0.7 percentage injected dose per gram of tissue). There were good correlations between the small-animal PET images and the biodistribution data and between Zr-89-trastuzumab and In-111-trastuzumab uptake in tumors (R-2 = 0.972). Conclusion: Clinical-grade Zr-89-trastuzumab showed high and HER2/neu-specific tumor uptake at a good resolution

A nursing service change strategy for health clinics

M.Cur.It is evident that the current political changes presently taking place in South Africa need to be accompanied by a dramatic transformation to accommodate the economic, social, technological and health changes amongst others. The nursing discipline is no exception. For a change to be felt by nursing staff and by health consumers, effective management strategies need to be developed to accommodate transformation guidelines as outlined by the Reconstruction and Development Programme, the National Health Plan and the Constitution which all emphasize the right to health, hence this study. This study focuses on a primary health care clinics. This is a qualitative, contextual, exploratory and descriptive study with the overall aim of exploring and describing a nursing service strategy for change in Soweto Primary Health clinics where the researcher is employed. To accomplish this aim, the following objectives were formulated: to explore and describe the expectations of the managers and the functional nurses concerning the required nursing service strategy for change within Soweto Primary Health Clinics; to explore and describe the expectations of health consumers concerning the required nursing service strategy for change in Soweto Primary Health Clinics; to describe the required nursing service strategy for Soweto Primary Health Clinics. Through purposive sampling, three focus groups were selected from the role players within Soweto who represent the nursing managers, the functional nurses' and the health consumers in order to infer the required change strategy for the nursing service. i. Data was collected through these focus groups interviews using semi-structured questions. Data management and data analysis was done using the methods of content analysis according to Kerlinger (1986: 480). An research expert, was utilised as a reliability measure to identify and categorise themes separately from the researcher. The categories that emerged were subsequently refined through consensus discussions between the researcher and the independent researcher. Woods and Catanzaro' s measures (1988: 136) to ensure validity and reliability were applied in this study