Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine.

BACKGROUND: The safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known. METHODS: In this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru. RESULTS: A total of 32,451 participants underwent randomization, in a 2:1 ratio, to receive AZD1222 (21,635 participants) or placebo (10,816 participants). AZD1222 was safe, with low incidences of serious and medically attended adverse events and adverse events of special interest; the incidences were similar to those observed in the placebo group. Solicited local and systemic reactions were generally mild or moderate in both groups. Overall estimated vaccine efficacy was 74.0% (95% confidence interval [CI], 65.3 to 80.5; P<0.001) and estimated vaccine efficacy was 83.5% (95% CI, 54.2 to 94.1) in participants 65 years of age or older. High vaccine efficacy was consistent across a range of demographic subgroups. In the fully vaccinated analysis subgroup, no severe or critical symptomatic Covid-19 cases were observed among the 17,662 participants in the AZD1222 group; 8 cases were noted among the 8550 participants in the placebo group (<0.1%). The estimated vaccine efficacy for preventing SARS-CoV-2 infection (nucleocapsid antibody seroconversion) was 64.3% (95% CI, 56.1 to 71.0; P<0.001). SARS-CoV-2 spike protein binding and neutralizing antibodies increased after the first dose and increased further when measured 28 days after the second dose. CONCLUSIONS: AZD1222 was safe and efficacious in preventing symptomatic and severe Covid-19 across diverse populations that included older adults. (Funded by AstraZeneca and others; ClinicalTrials.gov number, NCT04516746.).

When Antimicrobial Treatment and Surgical Prophylaxis Collide: A Stewardship Opportunity.

Background: In 2002, the Centers for Medicare and Medicaid Services (CMS) in collaboration with the Centers for Disease Control and Prevention (CDC) established the Surgical Infection Prevention (SIP) project for the purposes of developing and standardizing quality improvement measures known to reduce the rates of post-operative surgical site infections (SSIs). Four years later the Surgical Care Improvement Project (SCIP), an expansion of SIP, was published in governmental Specifications Manual for National Inpatient Quality Measures and provided several additional initiatives applicable to the perioperative period. Central to both projects are the assurance of the timeliness, selection, and duration of peri-operative surgical prophylactic antibiotics. In support of this objective, various medical associations, such as the American Society of Health-System Pharmacists (ASHP) and the Infectious Diseases Society of America (IDSA), have developed the Clinical Practice Guidelines for Antimicrobial Prophylaxis in Surgery. To ensure compliance with quality measures, hospitals are required to report data to the Physicians Quality Reporting System, which is then reviewed by CMS for reimbursement purposes and to measure hospital performance. To maintain optimal standards of care and satisfy all core measures, it is expected that patients undergoing most categories of surgical procedures receive prophylactic antibiotics. We recognized that patients already being administered antimicrobial therapy as treatment for the condition requiring the surgery not uncommonly also were prescribed unwarranted and redundant pre-operative antibiotics. Our study was meant to quantify such antibiotic redundancy, which only risks the development of antimicrobial resistance and adverse events, to bolster our and other hospitals antimicrobial stewardship programs. Methods: A retrospective analysis of computerized hospital records over a one-month period of time (November 2022) was conducted focusing on hospital admissions that involved surgical operative procedures. Only those patients who had received a pre-operative surgical prophylactic antibiotic were included in the analysis. Results: Of the 92 surgeries that fulfilled the inclusion criteria, 38 (41.3%) were performed on patients who were already receiving therapeutic antibiotics for more than 24 hours targeted to treat the infection for which they were undergoing surgery. These included laparoscopic cholecystectomy (24), appendectomy (12), wound debridement (12), and soft tissue incision and drainage procedures (9), comprising nearly 50% of each type of these operations performed during the study time period. Conclusion: These findings demonstrate a clear opportunity to strengthen both our, and presumably other, hospitals antimicrobial stewardship programs. Together with physician education, granting the pharmacy the ability to cancel unnecessary and redundant surgical prophylactic antibiotics would conceivably be of great benefit.

Preparing Our Future Physicians: "We Will Reap What We Sow".

As Designated Institutional Officer (LMB) and Program Director (EM) in a community teaching hospital, we are intimately involved with all aspects of Graduate Medical Education (GME) and find the rewarding part to consist of contributing towards the teaching of our future physicians, as well as the challenges imposed by the continuously evolving training requirements as set forth by the Accreditation Council for Graduate Medical Education (ACGME). While we are very aware of the standard training requisites that are put in place without exception for all accredited GME residency programs, whether they are part of a major (University) or minor (Community) teaching medical center, in this manuscript we are hoping to perhaps initiate a dialogue among clinical educators as to the future of graduate medical training, and how we as a medical community can commit to providing the best education experience for our residents, while preparing them to be the physicians our patients expect and deserve.

The anthrax attacks 10 years later.

Ten years ago, just weeks after the September 11 attacks, the United States experienced a deliberate act of bioterrorism. Through use of the postal service, anthrax spores were widely disseminated, including to homes, the Senate, and major newsrooms, resulting in morbidity and mortality and effectively disrupting our way of life and revealing our vulnerability. Even though such attacks had been the subject of much writing and had been planned for, detection of and the appropriate response to an attack with an agent from the so-called "Category 'A' List" had only been considered in theoretical terms. What transpired during the following difficult weeks, including how public health and federal government agencies performed, has been both praised and criticized. An intertwined epidemiologic and criminal investigation of such magnitude was unprecedented in U.S. history. To address the question of whether we as a nation are now better prepared for future threats involving biologic agents, it is important to learn from the lessons of the 2001 anthrax attacks, including the critical role of clinicians in surveillance. As physicians involved in diagnosing anthrax in the index case and alerting authorities, we offer our perspective on these events a decade after their occurrence.

Invasive Fungal Rhinosinusitis Caused by Curvularia in a Patient With Type 1 Diabetes Mellitus: A Case Report.

Invasive fungal rhinosinusitis (IFRS) is a serious illness requiring early diagnosis, surgical debridement, and administration of antifungals. We report a case of an acute IFRS caused by Curvularia in a patient with diabetes mellitus. An 18-year-old female presented to the emergency department with an acute onset of fever, headache, facial discomfort, and a blood glucose reading of 500 mg/dL. The patient was admitted for the management of hyperosmolar hyperglycemia. Her past medical history includes uncontrolled type 1 diabetes mellitus and a recent toothache. A computed tomography scan of the facial maxillary region revealed sinus disease with bony erosion. Empiric therapy with liposomal amphotericin B 400 mg i.v. every 24 hours, piperacillin/tazobactam 4.5 g i.v. every 6 hours and vancomycin 1 g i.v. every 12 hours was started. A functional endoscopic sinus surgery revealed invasive rhinosinusitis and cultures were positive for fungal elements. The patient was discharged on liposomal amphotericin B 400 mg i.v. daily and cefuroxime 500 mg orally twice daily. However, she was readmitted for the management of acute kidney injury and was discharged on itraconazole capsules 200 mg orally twice daily. Sinus cultures grew Curvularia and itraconazole was prescribed for 6 weeks, but the patient discontinued treatment after 3 weeks and had no signs or symptoms of rhinosinusitis when she was last seen in the clinic. The possibility of IFRS should be explored in patients with diabetes and signs and symptoms of rhinosinusitis.

Synthesis and pharmacological evaluation of 4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalenyl amines as triple reuptake inhibitors.

The present work describes a series of novel chiral amines that potently inhibit the in vitro reuptake of serotonin, norepinephrine and dopamine (triple reuptake inhibitors) and were active in vivo in a mouse model predictive of antidepressant like activity. The detailed synthesis and in vitro activity and ADME profile of compounds is described, which represent a previously undisclosed triple reuptake inhibitor chemotype.

Mycobacterial prosthetic valve endocarditis.

Prosthetic valve endocarditis (PVE) due to mycobacteria is a rare but frequently fatal complication that may occur early after the surgical procedure, or even years later. Infection has been described with both mechanical and biologic valvular prosthesis. The most commonly implicated mycobacterial species belong to the rapid-grower group (M. chelonei, M. fortuitum, and M. abscessus) of nontuberculous mycobacteria (NTM). The source of infection in this context is thought to be nosocomial, likely related to preoperative or intraoperative contamination of the prosthesis by contact with aqueous solutions containing the organisms. These infections are difficult to diagnose because blood cultures are often negative. Clinically, it is important to recognize the possibility of NTM-PVE in the differential diagnosis of culture-negative patients who develop signs and symptoms of endocarditis, whether they present early or late in onset after the surgical procedure. These patients should be treated with surgical removal of the infected valve, followed by adequate antimicrobial therapy based on the susceptibility of the species isolated from the valve or perivalvular tissue culture. In a significant number of patients, however, an unstable hemodynamic condition ensues, precluding surgical intervention, and therefore leading to a high mortality rate.

Soft tissue anaplastic large T-cell lymphoma associated with a metallic orthopedic implant: case report and review of the current literature.

On occasion, the placement of orthopedic prosthetic components or stabilization hardware leads to surgical site infections, in some cases presenting at a point in time distant from the surgical procedure. Although infectious complications are the most common etiology for surgical site pain and inflammation, malignancies can also develop around prosthetic devices and metallic implants. When encountered, such malignancies are most often sarcoma, but rarely B-cell non-Hodgkin's lymphoma has also been described. In this article, we describe what we believe to be the first published case of anaplastic large T-cell lymphoma associated with a stainless steel fixation plate that was implanted several years earlier for repair of a tibial fracture. Appropriate to this case, we review the medical literature on the association of orthopedic implants with the development of neoplasm, along with the theorized pathogenic mechanisms leading to such an association.

Tick borne illness-Lyme disease.

Lyme disease is the most commonly reported tick-borneillness in the United States. Thecausative spirochete, Borrelia burgdorferi is transmitted by 4 species of Ixodes tick species. Over 90% of US cases occur in northeasternstates from Maine to Virginia, and in Wisconsin, Minnesota, and Michigan. Infection also takes place in northern California and Oregon. Lyme borreliosis is also diagnosed in parts of Europe, China, and Japan. The white-footed mouse is the primary animal reservoir for B. burgdorferi in the U.S. and the preferred host for nymphal and larval forms of the deer tick. Deer are hosts for the adult ticks but do not carry the spirochete. Signs and symptomsof infection occur in 3 stages; early localized, typified by erythema migrans; early disseminated with a flu-like syndrome, neurologic, and cardiac manifestations; and late, characteristically with arthritis. Although, the term 'Chronic Lyme Disease' has been assigned to many patients with a variety of unexplained symptoms, experts in the field question the validity of this diagnosis and warn against prolonged unproven antimicrobial therapies. Diagnosis relies upon clinical evaluation and is supported by serologic testing using a 2-step process which requires careful interpretation. Treatmentvaries with stage of disease, but normally includes doxycycline, amoxicillin,and ceftriaxone. Currently, no preventative vaccine is available. In some geographic areas, patients may be confected with Babesia, Ehrlichia, and Anaplasma since the same Ixodes ticks transmit these pathogens.

AIDS-Associated Cardiac Lymphoma-A Review: Apropos a Case Report.

Despite treatment with potent and effective combination antiretroviral medications, the incidence of non-Hodgkin lymphoma (NHL) in the population living with HIV/AIDS remains significantly higher than that in noninfected individuals. The majority of the HIV-infected patients with NHL present with advanced stage extranodal disease of the B-cell phenotype. Lymphomas are the second most common tumors involving the heart in HIV-infected patients. Although the heart may serve as the primary focus of the lymphoma, in most HIV-related cases, cardiac lymphomatous involvement is part of a metastatic process that originated elsewhere.

Iatrogenic Cushing syndrome and secondary adrenal insufficiency related to concomitant triamcinolone and ritonavir administration: a case report and review.

Triamcinolone is a long-acting glucocorticoid medication that can be responsible for transient suppression of the hypothalamic­pituitary­adrenal (HPA) axis. This physiologic alteration may persist for weeks after repeated or even single localized injection of this agent. However, when this glucocorticoid agent is given to patients receiving the HIV protease inhibitor (PI) ritonavir (RTV),inhibition of their shared cytochrome P450 3A4 degradation pathway leads to an increased bioavailability of triamcinolone, with subsequent heightening and prolongation of the glucocorticoid serum levels. In those instances, iatrogenic Cushing syndrome may ensue. The authors encountered such an event in an HIV-infected patient on chronic treatment with an antiretroviral regimen containing RTV. The patient's clinical presentation and laboratory investigations confirmed a diagnosis of Cushing syndrome and secondary adrenal insufficiency. This was believed to have occurred in close association following cervical vertebral column facet joint injections with triamcinolone acetonide for cephalagia deemed related to cervical spine disease. The discontinuation of the RTV-boosted PI therapy alone, promoting the clearance of the elevated triamcinolone serum levels and restoration of HPAhomeostasis, proved successful in this patient. For this case, the authors review the published English medical literature relating to this uncommon phenomenon.

Iatrogenic Cushing syndrome and secondary adrenal insufficiency related to concomitant triamcinolone and ritonavir administration: a case report and review.

Triamcinolone is a long-acting glucocorticoid medication that can be responsible for transient suppression of the hypothalamic­pituitary­adrenal (HPA) axis. This physiologic alteration may persist for weeks after repeated or even single localized injection of this agent. However, when this glucocorticoid agent is given to patients receiving the HIV protease inhibitor (PI) ritonavir (RTV),inhibition of their shared cytochrome P450 3A4 degradation pathway leads to an increased bioavailability of triamcinolone, with subsequent heightening and prolongation of the glucocorticoid serum levels. In those instances, iatrogenic Cushing syndrome may ensue. The authors encountered such an event in an HIV-infected patient on chronic treatment with an antiretroviral regimen containing RTV. The patient's clinical presentation and laboratory investigations confirmed a diagnosis of Cushing syndrome and secondary adrenal insufficiency. This was believed to have occurred in close association following cervical vertebral column facet joint injections with triamcinolone acetonide for cephalagia deemed related to cervical spine disease. The discontinuation of the RTV-boosted PI therapy alone, promoting the clearance of the elevated triamcinolone serum levels and restoration of HPAhomeostasis, proved successful in this patient. For this case, the authors review the published English medical literature relating to this uncommon phenomenon.