How does the antimicrobial stewardship provider role affect prospective audit and feedback acceptance for restricted antibiotics in a Canadian tertiary-care center?

Of 731 restricted antimicrobial prescriptions subject to antimicrobial stewardship program (ASP) prospective audit and feedback (PAF) over a 3-year period, 598 PAF recommendations (82%) were fully accepted. Physician auditors had an increased odds of PAF recommendation acceptance, reinforcing the complementary role of the ASP physician in the multidisciplinary ASP team.

Efficacy and safety of antimicrobial stewardship prospective audit and feedback in patients hospitalised with COVID-19 (COVASP): a pragmatic, cluster-randomised, non-inferiority trial.

BACKGROUND: The COVID-19 pandemic has been associated with increased antimicrobial use despite low rates of bacterial co-infection. Prospective audit and feedback is recommended to optimise antibiotic prescribing, but high-quality evidence supporting its use for COVID-19 is absent. We aimed to study the efficacy and safety of prospective audit and feedback in patients admitted to hospital for the treatment of COVID-19. METHODS: COVASP was a prospective, pragmatic, non-inferiority, small-unit, cluster-randomised trial comparing prospective audit and feedback plus standard of care with standard of care alone in adults admitted to three hospitals in Edmonton, AB, Canada, with COVID-19 pneumonia. All patients aged at least 18 years who were admitted from the community to a designated study bed with microbiologically confirmed SARS-CoV-2 infection in the preceding 14 days were included if they had an oxygen saturation of 94% or lower on room air, required supplemental oxygen, or had chest-imaging findings compatible with COVID-19 pneumonia. Patients were excluded if they were transferred in from another acute care centre, enrolled in another clinical trial that involved antibiotic therapy, expected to progress to palliative care or death within 48 h of hospital admission, or managed by any member of the research team within 30 days of enrolment. COVID-19 unit and critical care unit beds were stratified and randomly assigned (1:1) to the prospective audit and feedback plus standard of care group or the standard of care group. Patients were masked to their bed assignment but the attending physician and study team were not. The primary outcome was clinical status on postadmission day 15, measured using a seven-point ordinal scale. We used a non-inferiority margin of 0·5. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, NCT04896866, and is now closed. FINDINGS: Between March 1 and Oct 29, 2021, 1411 patients were screened and 886 were enrolled: 457 into the prospective audit and feedback plus standard of care group, of whom 429 completed the study, and 429 into the standard of care group, of whom 404 completed the study. Baseline characteristics were similar for both groups, with an overall mean age of 56·7 years (SD 17·3) and a median baseline ordinal scale of 4·0 (IQR 4·0-5·0). 301 audit and feedback events were recorded in the intervention group and 215 recommendations were made, of which 181 (84%) were accepted. Despite lower antibiotic use in the intervention group than in the control group (length of therapy 364·9 vs 384·2 days per 1000 patient days), clinical status at postadmission day 15 was non-inferior (median ordinal score 2·0 [IQR 2·0-3·0] vs 2·0 [IQR 2·0-4·0]; p=0·37, Mann-Whitney U test). Neutropenia was uncommon in both the intervention group (13 [3%] of 420 patients) and the control group (20 [5%] of 396 patients), and acute kidney injury occurred at a similar rate in both groups (74 [18%] of 421 patients in the intervention group and 76 [19%] of 399 patients in the control group). No intervention-related deaths were recorded. INTERPRETATION: This cluster-randomised clinical trial shows that prospective audit and feedback is safe and effective in optimising and reducing antibiotic use in adults admitted to hospital with COVID-19. Despite many competing priorities during the COVID-19 pandemic, antimicrobial stewardship should remain a priority to mitigate the overuse of antibiotics in this population. FUNDING: None.

Efficacy and safety of antimicrobial stewardship prospective audit and feedback in patients hospitalized with COVID-19: A protocol for a pragmatic clinical trial.

BACKGROUND: The use of broad-spectrum antibiotics is widespread in patients with COVID-19 despite a low prevalence of bacterial co-infection, raising concerns for the accelerated development of antimicrobial resistance. Antimicrobial stewardship (AMS) is vital but there are limited randomized clinical trial data supporting AMS interventions such as prospective audit and feedback (PAF). High quality data to demonstrate safety and efficacy of AMS PAF in hospitalized COVID-19 patients are needed. METHODS AND DESIGN: This is a prospective, multi-center, non-inferiority, pragmatic randomized clinical trial evaluating AMS PAF intervention plus standard of care (SOC) versus SOC alone. We include patients with microbiologically confirmed SARS-CoV-2 infection requiring hospital admission for severe COVID-19 pneumonia. Eligible ward beds and critical care unit beds will be randomized prior to study commencement at each participating site by computer-generated allocation sequence stratified by intensive care unit versus conventional ward in a 1:1 fashion. PAF intervention consists of real time review of antibacterial prescriptions and immediate written and verbal feedback to attending teams, performed by site-based AMS teams comprised of an AMS pharmacist and physician. The primary outcome is clinical status at post-admission day 15 measured using a 7-point ordinal scale. Patients will be followed for secondary outcomes out to 30 days. A total of 530 patients are needed to show a statistically significant non-inferiority, with 80% power and 2.5% one-sided alpha assuming standard deviation of 2 and the non-inferiority margin of 0.5. DISCUSSION: This study protocol presents a pragmatic clinical trial design with small unit cluster randomization for AMS intervention in hospitalized COVID-19 that will provide high-level evidence and may be adopted in other clinical situations. TRIAL REGISTRATION: This study is being performed at the University of Alberta and is registered at ClinicalTrials.gov (NCT04896866) on May 17, 2021.

Salvage regional therapy using hepatic artery infusion pump in unresectable chemotherapy resistant colorectal liver metastases.

BACKGROUND: Little is known about the influence of hepatic artery infusion pump (HAIP) therapy in the setting of chemotherapy resistant hepatic disease in the era of modern systemic therapies. METHODS: Patients who underwent HAIP therapy for chemotherapy resistant and unresectable colorectal liver metastases (CRLM) were reviewed retrospectively. RESULTS: A total of 25 patients met inclusion criteria. 52% had isolated CRLM and 92% had five or more metastatic lesions. Partial response was noted in 40% of patients. Median hepatic progression-free survival (PFS) was 7 months in those with extrahepatic disease versus 6 months in those with isolated CRLM at the time of HAIP placement (p = 0.75). Median overall survival was 8 months in patients with extrahepatic disease and 14 months in patients with isolated CRLM (p = 0.06). CONCLUSIONS: Our findings are comparable to published data and augment the literature which supports HAIP use in chemotherapy-resistant, liver-predominant metastatic colorectal cancer patients.

Pneumocystis jirovecii: a review with a focus on prevention and treatment.

Introduction: Pneumocystis jirovecii (PJ) is an opportunistic fungal pathogen that can cause severe pneumonia in immunocompromised hosts. Risk factors for Pneumocystis jirovecii pneumonia (PJP) include HIV, organ transplant, malignancy, certain inflammatory or rheumatologic conditions, and associated therapies and conditions that result in cell-mediated immune deficiency. Clinical signs of PJP are nonspecific and definitive diagnosis requires direct detection of the organism in lower respiratory secretions or tissue. First-line therapy for prophylaxis and treatment remains trimethoprim-sulfamethoxazole (TMP-SMX), though intolerance or allergy, and rarely treatment failure, may necessitate alternate therapeutics, such as dapsone, pentamidine, atovaquone, clindamycin, primaquine and most recently, echinocandins as adjunctive therapy. In people living with HIV (PLWH), adjunctive corticosteroid use in treatment has shown a mortality benefit.Areas covered: This review article covers the epidemiology, pathophysiology, diagnosis, microbiology, prophylaxis indications, prophylactic therapies, and treatments.Expert opinion: TMP-SMX has been first-line therapy for treating and preventing pneumocystis for decades. However, its adverse effects are not uncommon, particularly during treatment. Second-line therapies may be better tolerated, but often sacrifice efficacy. Echinocandins show some promise for new combination therapies; however, further studies are needed to define optimal antimicrobial therapy for PJP as well as the role of corticosteroids in those without HIV.

Regorafenib and Nivolumab or Pembrolizumab Combination and Circulating Tumor DNA Response Assessment in Refractory Microsatellite Stable Colorectal Cancer.

BACKGROUND: Metastatic colorectal cancers (MCRCs) with microsatellite stability (MSS) are resistant to immunotherapy with programmed cell death protein 1 (PD-1) and programmed death-ligand 1 inhibitors. However, the addition of regorafenib to nivolumab was recently associated with a high response rate and a protracted progression-free survival in a small cohort of MSS Japanese patients with metastatic colorectal cancer. MATERIALS AND METHODS: We evaluated the outcome of patients with MSS metastatic colorectal cancer who were treated on a compassionate basis with PD-1 inhibitors in combination with regorafenib in a single U.S. center. RESULTS: A total of 18 patients were treated with a combination of regorafenib and PD-1 inhibitors. No treatment-related grade 3 or above toxicities were noted. Thirteen patients (69%) had progressive disease, and five patients (31%) experienced stable disease as best response. Four out of five stable diseases occurred in patients without liver metastases, whereas only 1 of 14 patients with history of liver metastases had a short disease stabilization. A rise in circulating tumor DNA (ctDNA) at the 4-week time pointuniversally predicted tumor progression at 2 months, whereas a decline was associated with radiographic disease stabilization. CONCLUSIONS: Regorafenib and nivolumab combination was associated with modest clinical activity in patients with MSS chemotherapy-resistant metastatic colorectal cancer. Selection for patients without history of liver metastases may identify a cohort of patients with MSS colorectal cancer with a higher likelihood of benefit from this combination. ctDNA may represent a powerful tool for predicting early therapeutic efficacy of immunotherapy in the MSS colorectal cancer population. IMPLICATIONS FOR PRACTICE: This study showed that the combination of regorafenib and nivolumab was associated with a modest clinical activity in patients with advanced microsatellite stability (MSS) metastatic colorectal cancer. This combination should be avoided in clinical practice, especially in patients with MSS colorectal cancer with liver metastases. Further investigation of regorafenib plus PD-1 inhibitors should be considered in MSS colorectal cancer without liver metastases.

Symptom-based patient stratification in mental illness using clinical notes.

Mental illnesses are highly heterogeneous with diagnoses based on symptoms that are generally qualitative, subjective, and documented in free text clinical notes rather than as structured data. Moreover, there exists significant variation in symptoms within diagnostic categories as well as substantial overlap in symptoms between diagnostic categories. These factors pose extra challenges for phenotyping patients with mental illness, a task that has proven challenging even for seemingly well characterized diseases. The ability to identify more homogeneous patient groups could both increase our ability to apply a precision medicine approach to psychiatric disorders and enable elucidation of underlying biological mechanism of pathology. We describe a novel approach to deep phenotyping in mental illness in which contextual term extraction is used to identify constellations of symptoms in a cohort of patients diagnosed with schizophrenia and related disorders. We applied topic modeling and dimensionality reduction to identify similar groups of patients and evaluate the resulting clusters through visualization and interrogation of clinically interpretable weighted features. Our findings show that patients diagnosed with schizophrenia may be meaningfully stratified using symptom-based clustering.

Curcumin: An age-old anti-inflammatory and anti-neoplastic agent.

Curcumin is a natural anti-inflammatory agent that has been used for treating medical conditions for many years. Several experimental and pharmacologic trials have demonstrated its efficacy in the role as an anti-inflammatory agent. Curcumin has been shown to be effective in treating chronic conditions like rheumatoid arthritis, inflammatory bowel disease, Alzheimer's and common malignancies like colon, stomach, lung, breast, and skin cancers. As treatments in medicine become more and more complex, the answer may be something simpler. This is a review article written with the objective to systematically analyze the wealth of information regarding the medical use of curcumin, the "curry spice", and to understand the existent gaps which have prevented its widespread application in the medical community.

App Use in Psychiatric Education: A Medical Student Survey.

OBJECTIVE: The objective of the study is to understand and appraise app use by medical students during their clerkships. METHODS: Following Creighton University IRB approval, a voluntary and anonymous paper-based, 15-question survey was distributed to third-year medical students. Data were analyzed using Microsoft Excel. RESULTS: Of 112 medical students available, 76.7% (86) participated in the survey. All participants owned a smartphone or tablet with 84.9% using Apple iOS, followed by 12.8% using Android platform. Students reported using the fewest number of apps during surgery, psychiatry, and obstetrics and gynecology clerkships. The largest number of apps were used during the internal medicine rotation (70.3%). The three most popular apps were Epocrates, UpToDate, and UWorld. The most common uses for these apps were as references during the clerkship, followed by improving knowledge, and test taking. Perceived major benefits included accessibility (96% of student respondents) and interactivity (39.5%). Common apps used during the psychiatry clerkship included UpToDate (71%), Epocrates (51%), and Medscape (43%). Despite less frequent app use during their psychiatry clerkship, 90% felt there was a utility for educational apps in psychiatric education. CONCLUSIONS: Consistent with the previous literature on medical students preferring educational apps, students suggest developers focus on question bank-type apps, followed by clinical support-focused and self-directed case-based learning apps for psychiatry clerkship learning. Educators should factor these modes of educational delivery into future educational app development. This survey shows a high degree of smartphone and tablet use among medical students, and they attest to mobile phone app utility in psychiatric education.