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

High-risk sexual behaviour in men attending a sexually transmitted infection clinic in Durban, South Africa.

OBJECTIVES: A study of men with genital ulcer disease (GUD) in Durban, South Africa, at the start of the local HIV epidemic in 1988/1989 found that 36% of men with GUD continued with sexual intercourse despite symptoms. The aim of this study was to determine whether this high-risk behaviour was still prevalent and to enquire about similar risk behaviours with other sexually transmitted infection (STI)-related problems. METHODS: 650 Men attending the main Durban STI clinic with a new complaint were enrolled. A standard questionnaire was administered. Polymerase chain reaction (PCR) tests were performed to diagnose genital herpes from ulcer specimens and gonorrhoea and chlamydia from those with urethral discharge and/or dysuria. Serology tests were performed for HIV, herpes simplex virus type 2 (HSV-2) and syphilis. RESULTS: Sex since the start of symptoms was reported by between 33.3% and 43.9% of men with GUD, herpetic ulcers, gonorrhoea and/or chlamydia or dysuria. The incidence of condom use was very low in all groups having sex despite symptoms. In 87 men with genital ulcers confirmed positive for genital herpes by PCR testing, 30 (34.4%) had had sex since the start of symptoms, 28 (93.3%) of whom had had unprotected sex. CONCLUSIONS: There is a high level of risk behaviour in this group of men in whom genital herpes is the most common cause of GUD. This risky sexual behaviour could reflect disinhibition, possibly because so many have already been infected with HSV-2, lack of education or other unknown factors. Syndromic STI management should be strengthened with intensive health education to promote community awareness of both genital ulceration and genital herpes and their role in facilitating HIV transmission. The low level of condom use indicates that condom promotion programmes still have much to achieve

High-risk sexual behaviour in men attending a sexually transmitted infection clinic in Durban, South Africa

OBJECTIVES: A study of men with genital ulcer disease (GUD) in Durban, South Africa, at the start of the local HIV epidemic in 1988/1989 found that 36% of men with GUD continued with sexual intercourse despite symptoms. The aim of this study was to determine whether this high-risk behaviour was still prevalent and to enquire about similar risk behaviours with other sexually transmitted infection (STI)-related problems. METHODS: 650 Men attending the main Durban STI clinic with a new complaint were enrolled. A standard questionnaire was administered. Polymerase chain reaction (PCR) tests were performed to diagnose genital herpes from ulcer specimens and gonorrhoea and chlamydia from those with urethral discharge and/or dysuria. Serology tests were performed for HIV, herpes simplex virus type 2 (HSV-2) and syphilis. RESULTS: Sex since the start of symptoms was reported by between 33.3% and 43.9% of men with GUD, herpetic ulcers, gonorrhoea and/or chlamydia or dysuria. The incidence of condom use was very low in all groups having sex despite symptoms. In 87 men with genital ulcers confirmed positive for genital herpes by PCR testing, 30 (34.4%) had had sex since the start of symptoms, 28 (93.3%) of whom had had unprotected sex. CONCLUSIONS: There is a high level of risk behaviour in this group of men in whom genital herpes is the most common cause of GUD. This risky sexual behaviour could reflect disinhibition, possibly because so many have already been infected with HSV-2, lack of education or other unknown factors. Syndromic STI management should be strengthened with intensive health education to promote community awareness of both genital ulceration and genital herpes and their role in facilitating HIV transmission. The low level of condom use indicates that condom promotion programmes still have much to achieve

Pharmacists implementing transitions of care in inpatient, ambulatory and community practice settings

Objective: To introduce pharmacists to the process, challenges, and opportunities of creating transitions of care (TOC) models in the inpatient, ambulatory, and community practice settings. Methods: TOC literature and resources were obtained through searching PubMed, Ovid, and GoogleScholar. The pharmacist clinicians, who are the authors in this manuscript are reporting their experiences in the development, implementation of, and practice within the TOC models. Results: Pharmacists are an essential part of the multidisciplinary team and play a key role in providing care to patients as they move between health care settings or from a health care setting to home. Pharmacists can participate in many aspects of the inpatient, ambulatory care, and community pharmacy practice settings to implement and ensure optimal TOC processes. This article describes establishing the pharmacist’s TOC role and practicing within multiple health care settings. In these models, pharmacists focus on medication reconciliation, discharge counseling, and optimization of medications. Additionally, a checklist has been created to assist other pharmacists in developing the pharmacist’s TOC roles in a practice environment or incorporating more TOC elements in their practice setting. Conclusion: Optimizing the TOC process, reducing medication errors, and preventing adverse events are important focus areas in the current health care system, as emphasized by The Joint Commission and other health care organizations. Pharmacists have the unique opportunity and skillset to develop and participate in TOC processes that will enhance medication safety and improve patient care

Single Injection Depot Progesterone Prior to Surgery and Survival in Women with Operable Breast Cancer: A Randomized Controlled Trial.

Abstract Background:The relationship between timing of surgery during menstrual cycle and survival in women with operable breast cancer (OBC) has been a subject of much debate. A meta-analysis of 37 retrospective studies revealed a modest survival benefit of 15%±8(2P=0.003) for those operated during progestogenic phase, whereas three prospective studies did not show any difference. Another meta-analysis of effect of circulating progesterone at the time of surgery showed a 53%±4(2P&amp;lt;0.001) improvement in survival when progesterone levels were high. The effect was confined to women with tumours that harboured lymph node metastasis(LN mets). We tested the effect of pharmacological induction of a progestogenic environment at the time of surgery on survival in women with OBC in a randomized controlled trial.Methods: One thousand women with OBC stratified by menopausal status and tumour size were randomly assigned to standard treatment (control) or an additional injection of depot preparation of hydroxy-progesterone(500 mg) 4-14 days prior to definitive surgery (treatment). Standard international guidelines were followed for adjuvant treatment. The primary endpoints were local, regional or distant recurrence(DFS) and secondary endpoint was death. Univariate comparison between treatment and control groups was performed using Kaplan Meier analysis and log rank test. A planned stratified analysis by lymph node status was also carried out. Cox proportional hazard model was used to assess the impact of tumour size, LN mets, menopausal status, treatment and an interaction between treatment and LN mets on DFS.Results: At median follow up of 65 months, 273 recurrences and 188 deaths have been recorded. In 982 eligible women DFS was 74% in treatment group and 70% in control group (RR=0.82, CI=0.67-1.08, P=0.195) while in women with LN mets DFS was 64.7% in treatment group and 54.6% in control group (RR=0.73,CI=0.54-0.97 p = 0.03). OAS was 81.5% in treatment arm and 80.2% in control arm (OR=0.94,CI=0.70-1.25, p=0.65) and, in women with LN mets, 76.3% in treatment arm and 69.9 % in control group (RR=0.74,CI=0.52-1.06, p=0.104). A Cox proportional hazard model for DFS revealed a significant impact of lymph node metastases (RR=2.22, CI=1.58-3.11, p=0.0005], hormone receptor positivity (RR=1.47,CI=1.15-1.87, p=0.002), and the interaction term between treatment and lymph node metastases (RR=1.15, CI=1.01-1.32, p=0.039) .Conclusions:A progestogenic milieu at the time of surgery significantly improves DFS in women with OBC and lymph node metastases. This could be a simple and inexpensive intervention for women with OBC, more so in developing world where lymph node positivity is high. A short term pre-operative intervention could be a novel window to explore impact of new drugs in a cost-effective manner. [NCT00123669]. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 72.</jats:p