Cefazolin versus fluoroquinolones for the treatment of community-acquired urinary tract infections in hospitalized patients.

Literature for the treatment of hospitalized patients with community-acquired urinary tract infections (UTI) is limited. Previous outpatient studies do not support the use of oral beta-lactams compared with oral fluoroquinolones (FQ) due to poor clinical cure rates. However, recent studies evaluating intravenous (IV) beta-lactams in more complicated cases demonstrate promising cure rates. In addition, the use of more narrow-spectrum beta-lactams may be preferable when possible, due to a lower incidence of "collateral damage" compared with FQ. This was a retrospective, non-inferiority, single-center, cohort study evaluating the effectiveness of IV cefazolin compared with FQ for the treatment of community-acquired UTI in an inpatient setting. The primary endpoint was clinical failure, defined as the presence of one or more signs or symptoms of UTI that required a change in antibiotics, re-initiation of antibiotics for UTI treatment during the hospital stay, and re-hospitalization with a UTI diagnosis within 30 days after discharge. The secondary endpoints were a microbiological cure, hospital length of stay, inpatient antibiotic duration of treatment, emergence of resistance, and Clostridium difficile infection within 30 days of the end of antibiotic therapy. Overall, 73 patients were treated with either cefazolin (n = 43) or FQ (n = 30) between April 2015 to January 2016. The clinical failure rates were 2% and 7% in the cefazolin and FQ groups, respectively (p = 0.56). Additionally, there were no significant differences between the secondary endpoints. Treatment with cefazolin, a more narrow-spectrum agent with a potential for less "collateral damage," was non-inferior to FQ for community-acquired UTI in an inpatient setting.

Successful use of fondaparinux in the setting of heparin-induced thrombocytopenia with thrombosis confirmed by serotonin-release assay and Factor V Leiden.

WHAT IS KNOWN AND OBJECTIVE: The off-label use of fondaparinux in patients with heparin-induced thrombocytopenia with thrombosis (HITT) has historically been controversial. We present a case of successful fondaparinux use to treat HITT confirmed by the serotonin-release assay in the setting of other significant clotting and bleeding risk factors. CASE SUMMARY: We report a 19-year-old male with a history of Factor V Leiden and recent neurosurgery treated with fondaparinux after developing HITT confirmed by the serotonin-release assay (SRA). The patient achieved full platelet recovery on fondaparinux and was successfully transitioned to warfarin therapy without further thrombotic nor bleeding complications. WHAT IS NEW AND CONCLUSION: This case demonstrates a clear example of success of fondaparinux use to treat SRA-confirmed HITT in the setting of complicating factors and adds to the existing literature supporting the use of fondaparinux for HIT.

Glycated albumin (GA) and inflammation: role of GA as a potential marker of inflammation.

AIMS: Abnormal levels of glycated albumin (GA) are associated with the onset of both diabetes and inflammation. Although inflammation has long been associated with diabetes, this article aims to explore the underlying mechanisms of this relationship as it pertains to the role of GA. METHODS: We have reviewed 52 research articles since the year 2000. Common search terms used were "(inflammatory mediator) and GA" or "inflammation and GA". The findings have been organized according to diabetic complications with respect to the interactions of GA and inflammatory mediators. Glycated albumin and specific inflammatory mediators have been reported to play various roles in the pathogenesis of insulin resistance, atherosclerosis, coronary artery disease, retinopathy, and nephropathy. In the case of nephropathy and recently retinopathy, there is considerable evidence for GA in concert with inflammation playing a direct role in organ pathology. There is copious literature detailing GA's involvement in stimulating inflammatory markers and certain pro-inflammatory cytokines. A recent clinical study has shown GA to be a marker for inflammation in non-diabetic rheumatoid arthritis patients with the significance of standard inflammatory markers. CONCLUSIONS: The clinical utility of GA measurement may likely reside in its versatility as both a mediator of inflammation as well as a marker to track hyperglycemia and other diabetes complications. Further understanding of the role GA plays in glycemic and inflammatory diseases could lead to its acceptance as an independent bio-inflammatory marker.

Circulatory collapse, right ventricular dilatation, and alveolar dead space: A triad for the rapid diagnosis of massive pulmonary embolism.

A triad of circulatory collapse, right ventricular dilatation, and large alveolar dead space is proposed for the rapid diagnosis and treatment of massive pulmonary embolism. A 17year-old female on oral contraceptives collapsed at home becoming incoherent with shallow breathing. Paramedics initiated mechanical chest compression and transported the patient to our emergency department, arriving minimally responsive with undetectable blood pressure but having positive corneal reflexes and bradycardia with wide QRS. The trachea was intubated and goal-directed echocardiography revealed marked right ventricular dilatation with septal flattening. The arterial PCO2 was 40mmHg with an end-tidal PCO2 of 8mmHg, revealing a large alveolar dead space. Persistent hypotension, bradycardia, and fading alertness despite epinephrine and norepinephrine infusions prompted resumption of chest compression. Intravenous alteplase (10mg bolus over 10min followed by 90mg over 110min) begun 125min after collapse improved hemodynamic function within 10min allowing discontinuation of chest compression. Five and a half hours after starting alteplase, the patient was hemodynamically stable and had normal end-tidal PCO2. A CT-angiogram showed the pulmonary arteries free of emboli but a thrombus in the right common iliac vein. The patient recovered fully and was discharged home on warfarin 8days later. Based on this and other reports, we propose a triad of circulatory collapse, right ventricular dilatation, and large alveolar dead space for the rapid diagnosis and treatment of massive pulmonary embolism, with systemic fibrinolysis as the first-line intervention.

Predicting Medical Student Performance With a Situational Judgment Test in Admissions.

PURPOSE: To explore correlations between AAMC situational judgment test (SJT) scores, other admissions data, and learners' medical school performance. METHOD: First- and second-year medical students from 8 U.S. MD-granting medical schools completed a prototype version of the AAMC SJT in 2017. Outcomes included research-only faculty ratings of student performance, final course grades, and faculty evaluations of student performance, 2017-2018 and 2018-2019 academic years. Bivariate correlations were used to investigate the relationship between SJT scores and student performance outcomes and hierarchical regressions to investigate whether SJT scores provided incremental validity over MCAT total scores and cumulative undergraduate grade point averages (UGPAs) for predicting student performance outcomes. RESULTS: In general, there were small positive correlations with research-only faculty ratings from the first year of medical school, with the highest for social skills/service orientation ( rcorrected = .33, P < .05). Correlations were higher, with the highest for social skills/service orientation and cultural competence ( rcorrected = .33 and .36, respectively, P < .05) in the second year in medical school. SJT scores improved prediction of research-only faculty ratings over MCAT total scores and UGPAs for reliability and dependability/capacity for improvement, cultural competence, social skills/service orientation, and the overall composite score in the first year and for resilience and adaptability, social skills/service orientation, cultural competence, and the overall composite score in the second year. SJT scores demonstrated small correlations with course grades ( rsample-weighted = .10, P = ns) and faculty evaluations related to professionalism skills ( rsample-weighted = .14, P < .05); however, MCAT total scores explained most of the variance associated with course outcomes. CONCLUSIONS: These studies provide initial evidence that SJT scores may add value to the medical school admissions process because scores were related to faculty ratings of professional behaviors and provided unique information relative to MCAT scores and UGPAs.

Evaluating a Situational Judgment Test for Use in Medical School Admissions: Two Years of AAMC PREview Exam Administration Data.

PURPOSE: To examine the relationship between the Association of American Medical Colleges (AAMC) Professional Readiness Exam (PREview) scores and other admissions data, group differences in mean PREview scores, and whether adding a new assessment tool affected the volume and composition of applicant pools. METHOD: Data from the 2020 and 2021 PREview exam administrations were analyzed. Two U.S. schools participated in the PREview pilot in 2020 and 6 U.S. schools participated in 2021. PREview scores were paired with data from the American Medical College Application Service (undergraduate grade point averages [GPAs], Medical College Admission Test [MCAT] scores, race, and ethnicity) and participating schools (interview ratings). RESULTS: Data included 19,525 PREview scores from 18,549 unique PREview examinees. Correlations between PREview scores and undergraduate GPAs ( r = .16) and MCAT scores ( r = .29) were small and positive. Correlations between PREview scores and interview ratings were also small and positive, ranging between .09 and .14 after correcting for range restriction. Small group differences in mean PREview scores were observed between White and Black or African American and White and Hispanic, Latino, or of Spanish origin examinees. The addition of the PREview exam did not substantially change the volume or composition of participating schools' applicant pools. CONCLUSIONS: Results suggest the PREview exam measures knowledge of competencies that are distinct from those measured by other measures used in medical school admissions. Observed group differences were smaller than group differences observed with traditional academic assessments and evaluations. The addition of the PREview exam did not substantially change the overall volume of applications or the proportions of out-of-state, underrepresented in medicine, or lower socioeconomic status applicants. While more research is needed, these results suggest the PREview exam may provide unique information to the admissions process without adversely affecting applicant pools.

Rhino-Cerebral Aspergillosis in an Immunocompetent Patient.

Rhino-cerebral aspergillosis is a rare phenomenon describing a contiguous spread of Aspergillus species from the paranasal sinuses to the intracranial space. In this case report, we describe a case of invasive rhino-cerebral aspergillosis arising in the setting of prolonged intranasal steroid use in an 81-year-old patient with chronic sinusitis. This case report emphasizes the importance of recognizing steroid use as a risk factor for invasive aspergillosis in otherwise immunocompetent individuals.

Intermittent fasting in health and disease.

CONTEXT: Intermittent fasting, a new-age dietary concept derived from an age-old tradition, involves repetitive cycles of fasting/calorie restriction and eating. OBJECTIVE: We aim to take a deep dive into the biological responses to intermittent fasting, delineate the disease-modifying and cognitive effects of intermittent fasting, and also shed light on the possible side effects. METHODS: Numerous in vitro and in vivo studies were reviewed, followed by an in-depth analysis, and compilation of their implications in health and disease. RESULTS: Intermittent fasting improves the body's stress tolerance, which is further amplified with exercise. It impacts various pathological conditions like cancer, obesity, diabetes, cardiovascular disease, and neurodegenerative diseases. CONCLUSION: During dietary restriction, the human body experiences a metabolic switch due to the depletion of liver glycogen, which promotes a shift towards utilising fatty acids and ketones in the system, thereby significantly impacting adiposity, ageing and the immune response to various diseases.

Intermittent fasting (IF) comprises repetitive fasting and feeding cycles.There are many variations of IF schedules.Individuals practicing an appropriate IF pattern reap numerous health benefits.The possible side effects should be considered before commencing a new IF regimen.

The role of tumor-educated platelets in ovarian cancer: A comprehensive review and update.

Platelets have recently surfaced as critical players in cancer metastasis and the local and systemic responses to tumor growth. The emerging concept of "Tumor-educated platelets (TEPs)" comprises the exchange of biomolecules between tumor cells and platelets, thereby leading to the "education" of platelets. Increased platelet numbers have long been associated with cancer patients' tumor metastasis and poor clinical prognosis. However, it is very recently that researchers have delved deeper into the tumor-microenvironment and probed the mechanism of interactions between tumor cells and platelets. Designing strategies to target the TEPs and the communications between platelets and tumor cells can prove to be a promising breakthrough in cancer therapy. Through this review, we aim to analyze the recent developments in this field and discuss the characteristics of TEPs, focusing on ovarian cancer-associated TEPs and their characteristics, the interplay between ovarian cancer-associated TEPs and cancer cells, and the purview of TEP-targeted cancer diagnosis and therapy, including platelet biomarkers and inhibitors.

Metabolomic Analysis in Neurocritical Care Patients.

Metabolomics is the analytical study of metabolites in biological matrices using high-throughput profiling. Traditionally, the metabolome has been studied to identify various biomarkers for the diagnosis and pathophysiology of disease. Over the last decade, metabolomic research has grown to include the identification of prognostic markers, the development of novel treatment strategies, and the prediction of disease severity. In this review, we summarized the available evidence on the use of metabolome profiling in neurocritical care populations. Specifically, we focused on aneurysmal subarachnoid hemorrhage, traumatic brain injury, and intracranial hemorrhage to identify the gaps in the current literature and to provide direction for future studies. A primary literature search of the Medline and EMBASE databases was conducted. Upon removing duplicate studies, abstract screening and full-text screening were performed. We screened 648 studies and extracted data from 17 studies. Based on the current evidence, the utility of metabolomic profiling has been limited due to inconsistencies amongst studies and a lack of reproducible data. Studies identified various biomarkers for diagnosis, prognosis, and treatment modification. However, studies evaluated and identified different metabolites, resulting in an inability to compare the study results. Future research towards addressing the gaps in the current literature, including reproducing data on the use of specific metabolite panels, is needed.

Oncologic safety of breast conservation following NACT in women with locally advanced breast cancer.

Introduction: Breast conservation surgery (BCS) is the accepted standard of treatment for early breast cancer, with evidence from randomized controlled and population-based studies. The oncological outcome of BCS in locally advanced breast cancer (LABC) is mainly available from retrospective series with a small sample size and a shorter follow-up duration. Methods: A retrospective observational study of 411 non-metastatic LABC patients who received neoadjuvant chemotherapy (NACT) followed by surgery from 2011 to 2016. We retrieved the data from a prospectively maintained database and electronic medical records. Survival data were analyzed by Kaplan-Meier curves and Cox regression using Statistical Package for the Social Sciences 25 and STATA 14. Results: 146/411 (35.5%) women had BCS with a margin positivity rate of 3.42%. With a median follow-up of 64 months (IQR 61, 66), the local relapse rate was 8.9% in BCS and 8.3% after mastectomy. The estimated 5-year locoregional recurrence-free survival (LRFS), recurrence-free survival (RFS), distant disease-free survival (DDFS) and overall survival (OS) rates of BCS were 86.9%, 63.9%, 71% and 79.3%, and 90.1%, 57.9%, 58.3% and 71.5% in the mastectomy group. On univariate analysis, BCS showed superior survival outcomes compared to mastectomy (unadjusted HR (95% CI) for RFS: 0.70 (0.50-1), DDFS: 0.57 (0.39-0.84), OS: 0.58 (0.36-0.93)). After adjusting for age, cT stage, cN stage, poorer chemotherapy response (ypT0/is, N0) and radiotherapy, BCS and mastectomy groups were found comparable in terms of LRFS (HR: 1.1, 0.53-2.3), DDFS (HR: 0.67, 0.45-1.01), RFS (HR: 0.80, 0.55-1.17) and OS (HR: 0.69, 0.41-1.14). Conclusion: BCS is technically feasible in LABC patients. LABC patients who respond well to NACT can be offered BCS without compromising survival outcomes.

Deciphering the role of MitomiRs in cancer: A comprehensive review.

MicroRNAs (miRNAs) are short non-coding RNAs that regulate many metabolic and signal transduction pathways. The role of miRNAs, usually found in the cytoplasm, in regulating gene expression and cancer progression has been extensively studied in the last few decades. However, very recently, miRNAs were found to localize in the mitochondria. MiRNAs that specifically localize in the mitochondria and the cytoplasmic miRNAs associated with mitochondria that directly or indirectly modulate specific mitochondrial functions are termed as "mitomiRs". Although it is not clear about the origin of mitomiRs that are situated within mitochondria (nuclear or mitochondrial origin), it is evident that they have specific functions in modulating gene expression and regulating important mitochondrial metabolic pathways. Through this review, we aim to delineate the mechanisms by which mitomiRs alter mitochondrial metabolic pathways and influence the initiation and progression of cancer. We further discuss the functions of particular mitomiRs, which have been widely studied in the context of mitochondrial metabolism and oncogenic signaling pathways. Based on the current knowledge, we can conclude that mitomiRs contribute significantly to mitochondrial function and metabolic regulation, and that dysregulation of mitomiRs can aid the proliferation of cancer cells. Therefore, the less explored area of mitomiRs' biology can be an important topic of research investigation in the future for targeting cancer cells.

Prescribing habits and caregiver satisfaction with resources for dosing children: rationale for more informative dosing guidance.

BACKGROUND: Physicians, nurses and hospital pharmacists were surveyed to assess attitudes of hospital-based pediatric caregivers regarding the dosing of medicine to children. Our objectives were to gauge how current resources are utilized to guide the management of pediatric pharmacotherapy, assess drugs and drug classes where guidance is most critical and examine the prevalence and practice of dose adjustment in pediatric patients. METHODS: Questionnaire categories included demographics, pharmacotherapy resources, dosing adjustment and modification, and valuation of additional tools to provide improved pharmacotherapy guidance. The questionnaire was developed in collaboration with representative nurse, pharmacist and physician team members using the SurveyMonkey.com site and survey tool. The survey link was distributed to caregivers via email. The questionnaire results of 303 respondents were collected into MS Excel and imported into SAS for data summarization. RESULTS: A total of 313 responses were obtained. Physician and nurse practitioner groups comprised the majority of the responses. Approximately 80% of the responders considered dosing adjustment important in pediatric pharmacotherapy. While there was general satisfaction with available resources, nearly 75% responded in support of access to predictive tools that facilitate individualized patient pharmacotherapy. The majority of respondents (> 65%) indicated that dosing outside standard practice occurs in 1-20% of their patients, while still a substantial number of respondents (a range of 8 to 20% reflecting the resident and fellow categories) estimated between 20 and 50% of their patients required adjustments outside the standard practice. CONCLUSIONS: Differences in prescribing habits based on caregiver role, specialty and location were small and likely require further exploration. Existing resources are generally viewed as helpful but inadequate to guide recommendations for individual patients. Decision support systems connected to hospital-based electronic medical records offer the promise of informative and individualized pharmacotherapy guidance.

A Study of the Validity of the New MCAT Exam.

PURPOSE: To conduct a study of the validity of the new Medical College Admission Test (MCAT). METHOD: Deidentified data for first- and second-year medical students (185 women, 54.3%; 156 men, 45.7%) who matriculated in 2016 and 2017 to the University of Minnesota Medical School-Twin Cities were included. Of those students, 220 (64.5%) had taken the new MCAT exam and 182 (53.4%) had taken the old MCAT exam (61 [17.9%] had taken both). The authors calculated descriptive statistics and Pearson product moment correlations (r) between new and old MCAT section scores. They conducteda regression analysis of MCAT section scores with Step 1 scores and with preclerkship course performance. They also conducted an exploratory factor analysis (principal component analysis with varimax rotation) of MCAT scores, undergraduate grade point average, Step 1 scores, and course performance. RESULTS: The new MCAT exam section mean score percentiles ranged from 72 to 78 (mean composite score percentile of 80). The old MCAT exam section mean score percentiles ranged from 84 to 88 (mean composite score percentile of 83). The pattern of correlations among and between new and old MCAT exam section scores (range of r: 0.03-0.67; P < .01) provided evidence of both divergent and convergent validities. Backward multiple regression of new MCAT exam section scores and Step 1 scores resulted in a multiple R of .440; the same analysis with Human Behavior course performance as the dependent variable provided a similar solution with the expected sections of the new MCAT exam (multiple R = .502). The factor analysis resulted in 4 cohesive, theoretically meaningful factors: biomedical knowledge, basic science concepts, cognitive reasoning, and general achievement. CONCLUSIONS: This study provided empirical evidence of multiple types of validity for the new MCAT exam.

Population pharmacokinetics of the selective serotonin 5-HT1A receptor partial agonist piclozotan.

BACKGROUND/AIMS: Serotonin (5-HT) and its receptors are known to play important roles in various physiological and pathophysiological processes. The 5-HT1A receptor subtype is thought to be involved in psychiatric disorders, immunomodulation, and in cerebral ischemic conditions. Piclozotan, a selective and potent partial agonist of 5-HT1A, has been shown to be neuroprotective against ischemic neuronal damage in animal models. Its pharmacokinetics (PK), tolerability, and safety have been evaluated in patients with acute ischemic stroke. The aim of the study was to describe piclozotan PK, using population PK modeling. METHODS: A total of 1308 plasma piclozotan concentration measurements from 84 healthy subjects and 412 plasma piclozotan measurements from 74 stroke patients were included in the analysis. Covariates considered during the model building process included disease status, age, weight, sex, smoking status, and alcohol consumption. Data were analyzed using nonlinear mixed-effects modeling with the NONMEM software system. The final model was qualified via predictive check and nonparametric bootstrap procedures. RESULTS: Piclozotan PK was well described using a 3-compartment model with first-order elimination. Parameter estimates (intersubject variability) were V1, central volume: 64.0 L (66.5%) and CL, systemic clearance: 18.0 L/h (31.4%). Peripheral volumes (V2, V3) were related to total body weight, whereas CL was related to ideal body weight. Clearance decreased with advancing age, yielding a decrease of 35%-65% in patients aged 70-90. There was no discernable difference in PK between healthy subjects and stroke patients. CONCLUSIONS: Piclozotan disposition was well described by the population model, and the intersubject variability around the estimated parameters was moderate in magnitude (<60%). The population PK analysis of piclozotan allows for characterization of piclozotan exposure in individual subjects based on their age and body weight. The availability of a population PK model will facilitate dose optimization and further clinical development of piclozotan.

A SAS-based solution to evaluate study design efficiency of phase I pediatric oncology trials via discrete event simulation.

Previous exploration of oncology study design efficiency has focused on Markov processes alone (probability-based events) without consideration for time dependencies. Barriers to study completion include time delays associated with patient accrual, inevaluability (IE), time to dose limiting toxicities (DLT) and administrative and review time. Discrete event simulation (DES) can incorporate probability-based assignment of DLT and IE frequency, correlated with cohort in the case of DLT, with time-based events defined by stochastic relationships. A SAS-based solution to examine study efficiency metrics and evaluate design modifications that would improve study efficiency is presented. Virtual patients are simulated with attributes defined from prior distributions of relevant patient characteristics. Study population datasets are read into SAS macros which select patients and enroll them into a study based on the specific design criteria if the study is open to enrollment. Waiting times, arrival times and time to study events are also sampled from prior distributions; post-processing of study simulations is provided within the decision macros and compared across designs in a separate post-processing algorithm. This solution is examined via comparison of the standard 3+3 decision rule relative to the "rolling 6" design, a newly proposed enrollment strategy for the phase I pediatric oncology setting.

An informatics approach to assess pediatric pharmacotherapy: design and implementation of a hospital drug utilization system.

Drug utilization in the inpatient setting can provide a mechanism to assess drug prescribing trends, efficiency, and cost-effectiveness of hospital formularies and examine subpopulations for which prescribing habits may be different. Such data can be used to correlate trends with time-dependent or seasonal changes in clinical event rates or the introduction of new pharmaceuticals. It is now possible to provide a robust, dynamic analysis of drug utilization in a large pediatric inpatient setting through the creation of a Web-based hospital drug utilization system that retrieves source data from our accounting database. The production implementation provides a dynamic and historical account of drug utilization at the authors' institution. The existing application can easily be extended to accommodate a multi-institution environment. The creation of a national or even global drug utilization network would facilitate the examination of geographical and/or socioeconomic influences in drug utilization and prescribing practices in general.

Comparison of health behaviors among single- and multiple-member households.

OBJECTIVE: To assess the differences in health behavior between multiple-member and single-member households by gender. METHODS: Face-to-face household survey interviews were conducted. The relationship between health behaviors and living arrangement was assessed by adjusting for SES. RESULTS: Women living alone exercised more and ate less food high in fat. More highly educated men were less likely to exercise 5 or more times a week than high school or less educated men. CONCLUSIONS: By analyzing local data, a profile can be established to develop and implement appropriate public health programs aimed at these various target communities for effective intervention and healthy change in the community.