The global burden of antimicrobial resistance - urinary tract infections.

Antimicrobial resistance (AMR) has emerged as a significant global healthcare problem. Antibiotic use has accelerated the physiologic process of AMR, particularly in Gram-negative pathogens. Urinary tract infections (UTIs) are predominantly of a Gram-negative nature. Uropathogens are evolutionarily highly adapted and selected strains with specific virulence factors, suggesting common mechanisms in how bacterial cells acquire virulence and AMR factors. The simultaneous increase in resistance and virulence is a complex and context-dependent phenomenon. Among known AMR mechanisms, the plenitude of different ß-lactamases is especially prominent. The risk for AMR in UTIs varies in different patient populations. A history of antibiotic consumption and the physiology of urinary flow are major factors that shape AMR prevalence. The urinary tract is in close crosstalk with the microbiome of other compartments, including the gut and genital tracts. In addition, pharmacokinetic properties and the physiochemical composition of urinary compartments can contribute to the emergence of AMR. Alternatives to antibiotic treatment and a broader approach to address bacterial infections are needed. Among the various alternatives studied, antimicrobial peptides and bacteriophage treatment appear to be highly promising approaches. We herein summarize the present knowledge of clinical and microbiological AMR in UTIs and discuss innovative approaches, namely new risk prediction tools and the use of non-antibiotic approaches to defend against uropathogenic microbes.

Adherence to antiseizure medications in an underserved population with epilepsy.

BACKGROUND AND PURPOSE: Antiseizure medications (ASM) effectively prevent seizures in about 70% of adult epilepsy patients, but nonadherence to medication is the primary cause of breakthrough seizures, accounting for 26% to 79% of cases. Factors such as age, education, dosing frequency, forgetfulness, fear of side effects, and socioeconomic status contribute to poor adherence, especially among underserved populations. This study aimed to assess medication adherence during routine follow-up visits and identify the role of education in reducing non adherence in an underserved patient population. METHODS: The study involved a retrospective chart review of adult epilepsy patients seen at the University of Illinois Hospital between December 2016 and April 2020. Data on patient demographics, epilepsy and seizure classification, medication details, emergency visits, and adherence were collected from electronic medical records using the RedCap system. Descriptive statistics and statistical tests were conducted using STATA 17.0 for data analysis, including chi-squared analysis for categorical data and t-tests for continuous data. RESULTS: The study enrolled a total of 286 adult epilepsy patients who met the eligibility criteria. Among them, 111 patients (38.81 %) were classified as nonadherent based on ASM levels. Caucasian/white race and income > $50,000 per year, were significantly associated with adherence (p = 0.009 and p = 0.006 respectively). Moreover, patients with weekly seizures were more likely to be adherent (p = 0.042). No significant differences were found regarding medication adherence and sex, education, employment, epilepsy type, age at diagnosis, seizure type or number of current ASM medications. Even though not significant, a trend towards college educated patients being more adherent was observed (70.37 %). Of self-reported adherent patients, 33.33 % were found to be nonadherent based on ASM levels. Nurse phone calls reminding 70 non adherent patients about adherence increased the chances of becoming adherent by 80.39 %. Finally, although not statistically significant, the majority of adherent patients had no history of hospitalizations for breakthrough seizures (73.89 %). CONCLUSION: More than a third of our patients were found to be non-adherent during routine follow-up visits. Lower socio-economic status and lower education were associated with increased chances of being non adherent. Rates of adherence were improved by nurse's phone calls discussing the importance of adherence and risks of SUDEP. The findings emphasize the importance of education in improving medication adherence among these populations, suggesting the need for social interventions, community outreach programs, and targeted educational initiatives.

COVID-19-associated pulmonary aspergillosis in immunocompetent patients: a virtual patient cohort study.

The opportunistic fungus Aspergillus fumigatus infects the lungs of immunocompromised hosts, including patients undergoing chemotherapy or organ transplantation. More recently however, immunocompetent patients with severe SARS-CoV2 have been reported to be affected by COVID-19 Associated Pulmonary Aspergillosis (CAPA), in the absence of the conventional risk factors for invasive aspergillosis. This paper explores the hypothesis that contributing causes are the destruction of the lung epithelium permitting colonization by opportunistic pathogens. At the same time, the exhaustion of the immune system, characterized by cytokine storms, apoptosis, and depletion of leukocytes may hinder the response to A. fumigatus infection. The combination of these factors may explain the onset of invasive aspergillosis in immunocompetent patients. We used a previously published computational model of the innate immune response to infection with Aspergillus fumigatus. Variation of model parameters was used to create a virtual patient population. A simulation study of this virtual patient population to test potential causes for co-infection in immunocompetent patients. The two most important factors determining the likelihood of CAPA were the inherent virulence of the fungus and the effectiveness of the neutrophil population, as measured by granule half-life and ability to kill fungal cells. Varying these parameters across the virtual patient population generated a realistic distribution of CAPA phenotypes observed in the literature. Computational models are an effective tool for hypothesis generation. Varying model parameters can be used to create a virtual patient population for identifying candidate mechanisms for phenomena observed in actual patient populations.

Sex Differences in Pain and Its Treatment.

Pain is a highly personal experience. Pain is often considered to be a purely neurologic phenomenon, but in actuality, it is a combination of both sensory and emotional experiences. This has sometimes been translated clinically toward a more mechanistic approach to the assessment and treatment of pain instead of one that does not discount pain mechanisms, but also is more inclusive of the need for humanism - considering the individual. In today's medical environment, more than ever before there is a significant amount of attention being paid to educating clinicians to better understand that several physiological, neurophysiological, and psychosocial factors can significantly impact responses to pain. The composition of these factors will be unique to that individual's life narrative, context, sex, and prior life experiences. Thus, the concept that a templated approach to pain assessment and pharmacotherapeutic treatment planning should not be expected to provide optimal patient satisfaction and treatment outcomes in the majority. The hypotheses that there may be sex-based differences in the pain experience in a variety of ways including pain sensitivity, tolerance to pain, threshold at which something becomes painful, and the effectiveness of endogenous pain modulation systems are not new and have been well represented in the literature. This chapter reviews important key findings in the scientific literature with respect to sex-based differences in pain and pain responses to experimentally induced painful stimuli, pain experienced in commonly occurring painful medical conditions, and variations in responses to pain treatments. Possible explanations to account for observed differences or similarities will also be discussed.

A comprehensive medical Spanish curriculum model: the Vida Medical Spanish Curriculum.

INTRODUCTION: Racial and language disparities in the United States healthcare system have long undermined the quality of care provided to minority patients. With the projected growth of the Hispanic population, there is an urgent need for medical schools to integrate high-quality medical Spanish and cultural competency content. We propose a comprehensive medical Spanish curriculum aligned with the preclinical curriculum as a solution to these issues. The primary goal of this study is to demonstrate the effectiveness of a clinically focused, culturally competent medical Spanish program and advocate for its widespread adoption in medical institutions nationwide. METHODS: The study utilized the Kirkpatrick Model to evaluate the success of the medical Spanish curriculum. A total of 111 medical students voluntarily enrolled in the medical Spanish course. Out of these students, 47 completed the final evaluation, which included a Spanish Objective Structured Clinical Examination and a 40-question Multiple-Choice Exam assessing the integration of Spanish language skills and cultural competency. Both assessment methods took place in clinical skills facilities. Descriptive statistics summarized exam results, and two-tailed t-tests compared mean exam scores between students of different proficiency levels. RESULTS AND DISCUSSION: Students achieved a mean score of over 80% on all components of the Spanish Objective Structured Clinical Examination and the Multiple-Choice Exam. Survey data suggest that students felt able to communicate in Spanish with patients after completing the course series. The study also provides a model for a medical Spanish curriculum that applies expert-recommended best practices to meet the needs of Hispanic patient populations. LIMITATIONS AND CONCLUSIONS: Students who sat for the OSCE and MCE were self-selected. Baseline data on student perceptions and Spanish competency are not sufficient for making comparisons.

Mottling in Septic Shock: Ethnicity and Skin Color Matter.

Background: Skin mottling as a clinical perfusion marker in septic shock is significantly associated with severity and outcome in white-skinned population and its validity as a clinical sign in dark-skinned population is not known. The objectives of this study were to evaluate mottling in septic shock in the Indian ethnic population who has different skin color as compared to the white-skinned population and to assess mottling as an outcome predictor with capillary refill time (CRT) and other biochemical parameters which are the established clinical markers of perfusion in septic shock. Materials and methods: We conducted a prospective observational study of patients with skin color categories 21-34 on the von Luschan scale or Fitzprick type IV-VI who had septic shock needing a high dose of norepinephrine ≥0.2 µg/kg/min after fluid optimization. The study was conducted in a mixed medical-surgical ICU over 12 months. Two blinded experts (a Dermatologist and a plastic surgeon) independently classified the skin type, validated the occurrence of mottling, and scored mottling in our patients. We recorded the demographics, hemodynamic variables, and mottling score and observed the incidence of mottling and its correlation with predictors of the severity of septic shock. We also compared CRT, arterial lactate, central venous oxygen saturation, and venoarterial PCO2 gap with occurrence of mottling in septic shock patients. Results: We included 108 patients with age 61 ± 16 years. Mean Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores at enrolment were 10.3-21.9, respectively. Incidence of mottling was 20.3% (22/108). CRT >3 seconds was observed in 50.9% (55/108). Development of mottling was significantly associated with 90-day mortality; 20/22 (90.9%) patients died in the mottling group versus 58/86 (65.1%) in the non-mottling group (p = 0.028). Capillary refill time >3 seconds did not corelate with mortality; 40/55 (72.7%) Patients with CRT >3 seconds died versus 32/53 (60.4%) patients died in CRT ≤3 seconds group. Occurrence of mottling could predict mortality; positive predictive value of 90.9% which was comparable to positive predictive value of lactate levels >4 mmol/L, i.e., 94.1%. Conclusion: The incidence of mottling in septic shock is much less in patients of Indian ethnicity with brown skin color than in white-skinned population. Occurrence of mottling and not delayed CRT, is a better predictor of outcome in this setting. How to cite this article: Jog SA, Narasimhan VL, Rajhans PA, Akole PV, Pawar B, Bhurke B, et al. Mottling in Septic Shock: Ethnicity and Skin Color Matter. Indian J Crit Care Med 2023;27(12):902-909.

Lessons Learned: Recruiting Research Participants from an Underrepresented Patient Population at a Safety Net Hospital.

BACKGROUND: Recruiting participants to clinical research studies is challenging, especially when conducted in safety net settings. We sought to compare the efficacy of different recruitment strategies in an NIH-funded study assessing treatment burden in patients with multiple chronic conditions (MCCs). METHODS: Targeted mailing, in-person table-based recruitment ("tabling") in the waiting room, and telephone calling were used to enroll subjects into one of two studies of treatment burden: a survey study to validate a brief measure of treatment burden for quality assessment (study 1) or a qualitative study to develop a treatment burden clinical communication tool (study 2). RESULTS: Over 50% of subjects in each study were African American or African immigrants. In study 1, the enrollment goal of 200 was reached within 4 months. Tabling enrolled 78.5% of patients, while the remainder (21.5%) were enrolled from phone calls to eligible patients identified through the electronic medical record (EMR). In study 2, 340 eligible patients were identified through the EMR, and 7 (2.1%) were successfully enrolled via mailed invitations and responses. Retention rates (66% in study 1 and 71% in study 2) were reasonable in all groups. CONCLUSIONS: Study recruiting goals in our safety net population were rapidly reached using the tabling method, which had substantively higher enrollment rates than mailings or telephone calls based on EMR reports. Future trials could compare recruitment strategies across settings and clinical populations.

Graft choice or drilling technique does not influence outcomes of ACL reconstruction in patients over forty-five.

PURPOSE: To evaluate whether graft-type and tunnel location in ACL reconstruction impact patient-reported outcomes in individuals over the age of 45. METHODS: From 2015 to 2018, patients over 45 years old undergoing primary ACL reconstruction without multi-ligamentous injuries were enrolled in an institutional registry. Baseline International Knee Documentation Committee (IKDC) subjective scores, Knee Injury and Osteoarthritis Outcome Scores (KOOS), Marx Activity Scale, and patient characteristics were collected. Follow-up occurred at a minimum of two years to obtain patient-reported outcomes. RESULTS: Of the 51 patients who qualified for the study, 44 (86.3%) patients were available at a minimum of two years after surgery date (range 24-60 months). Average age at time of surgery of the available patients was 51.6 ± 4.87 (range 45-66). Between femoral tunnel drilling methods, there were no differences in the proportion of patients achieving clinically significant improvement or post-operative outcome scores. While patients who received patellar tendon autografts were more likely to achieve clinically significant improvement in the KOOS sports subscale, there were no other differences in outcomes measures between graft types. Two patients had a retear of their graft, and an additional five patients complained of subjective instability. CONCLUSIONS: In patients over the age of 45, neither the method used to create the femoral tunnel nor the graft type used in ACL reconstruction caused a significant difference in post-operative PROMs with a minimum of two years of follow-up. LEVEL OF EVIDENCE: Therapeutic IV, Case Series.

Weekly chemotherapy as first line treatment in frail head and neck cancer patients in the immunotherapy era.

OBJECTIVE: First-line therapy for metastatic squamous cell carcinoma of the head and neck (R/M HNSCC) has been revolutionized by the introduction of anti-checkpoint monoclonal antibodies, which have shown a significant improvement in overall survival (OS) gaining approval in a first line setting. Efficacy and safety of first-line weekly chemotherapy, compared to 3-weeks treatment, was retrospectively evaluated in a frail patient population with R/M HNSCC with the aim to evaluate its role as part of a personalized first-line approach. METHODS: A total of 124 patients with locally incurable R/M HNSCC receiving weekly (21) or three-weekly (103) chemotherapy plus cetuximab in a first line setting from December 2010 to September 2020 were retrospectively reviewed. Treatment outcomes in terms of objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicities were analysed. RESULTS: Patients in the three-week subgroup were ECOG PS 0 (39) and 1 (64) while patients in weekly group (21) were all PS 2. No significant differences were reported in terms of age, sex, smoking and previous alcohol abuse considering the two distinct subgroups. Moreover, no statistically significant difference was found in PFS and OS between the two treatment subgroups. The response rate was 35% (36 patients) and 34% (7 patients) in three-week and weekly treatment group, respectively. Seventy patients (68%) in the three-week group experienced chemotherapy-related toxicities, predominantly G3. In the weekly group a predominantly low-grade toxicity was found in a lower number of patients (52%). CONCLUSION: The weekly schedule appears to be an active and safe strategy in frail patients with R/M HNSCC. Based on these data, a weekly schedule could be considered as a first line treatment in all frail patients excluded from pembrolizumab treatment and a study on the combination of weekly chemotherapy and immunotherapy should be performed.

Reducing falls through the implementation of a multicomponent intervention on a rural mixed rehabilitation ward.

PROBLEM: There is an absence of literature to guide staff in how falls can be reduced in a diverse patient population on a mixed acute/subacute rehabilitation unit, especially one with daily fluctuations in acuity that occurs due to frequent changes in its acute/rehabilitation patient ratio. DESIGN: Pre-intervention and post-intervention audits. SETTING: The Rehabilitation Unit at Tamworth Rural Referral Hospital in Tamworth, NSW. KEY MEASURES FOR IMPROVEMENT: Improvement in the number of falls and repeat fallers. STRATEGIES FOR CHANGE: A multicomponent intervention involving: (a) in-service education sessions for nursing staff about falls risk-increasing drugs, (b) patient and family education regarding falls risks and prevention strategies, (c) improving documentation of incident reports by using a set template, (d) ensuring that the correct patient mobility status information is handed over between nursing shifts and physiotherapists providing timely and regular updates, (e) the introduction of the 'traffic light mobility system' and (f) enhancing the use of existing falls prevention strategies. EFFECTS OF CHANGE: The total falls reduced in number from 36 falls to 19 with a decrease in the number of repeat fallers from 8 to 4. There was also increased compliance with existing falls risk tools and improved documentation of each falls incident which provided insight into activities and times with higher falls risk. LESSONS LEARNT: A multicomponent approach remained effective even when applied to a mixed acute/subacute rehabilitation ward setting.

Considerations for Dose Selection and Clinical Pharmacokinetics/Pharmacodynamics for the Development of Antibacterial Agents.

In June 2017, The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, organized a workshop entitled "Pharmacokinetics-Pharmacodynamics (PK/PD) for Development of Therapeutics against Bacterial Pathogens" to discuss details and critical parameters of various PK/PD methods and identify approaches for linking human pharmacokinetic (PK) data and drug efficacy analyses. The workshop participants included individuals from academia, industry, and government. This and the accompanying minireview on nonclinical PK/PD summarize the workshop discussions and recommendations. It is important to consider how information like PK/PD can support the clinical effectiveness of new antibacterial drugs, as PK/PD data have become central to antibacterial drug development programs. Key clinical considerations for antibacterial dose selection and clinical PK/PD characterization discussed in this minireview include a robust assessment of PK in the patient population of interest, critical considerations for assessing drug penetration in the lung for the treatment of pneumonia, and an emphasis on special populations, including patients with renal impairment and augmented renal function, as well as on dosing in obese and pediatric patients. Successful application of such approaches is now used to provide a more informative drug development package to support the approval of new antibiotics.

Expanding the Concept of Diagnostic Reference Levels to Noise and Dose Reference Levels in CT.

OBJECTIVE. Diagnostic reference levels were developed as guidance for radiation dose in medical imaging and, by inference, diagnostic quality. The objective of this work was to expand the concept of diagnostic reference levels to explicitly include noise of CT examinations to simultaneously target both dose and quality through corresponding reference values. MATERIALS AND METHODS. The study consisted of 2851 adult CT examinations performed with scanners from two manufacturers and two clinical protocols: abdominopelvic CT with IV contrast administration and chest CT without IV contrast administration. An institutional informatics system was used to automatically extract protocol type, patient diameter, volume CT dose index, and noise magnitude from images. The data were divided into five reference patient size ranges. Noise reference level, noise reference range, dose reference level, and dose reference range were defined for each size range. RESULTS. The data exhibited strong dependence between dose and patient size, weak dependence between noise and patient size, and different trends for different manufacturers with differing strategies for tube current modulation. The results suggest size-based reference intervals and levels for noise and dose (e.g., noise reference level and noise reference range of 11.5-12.9 HU and 11.0-14.0 HU for chest CT and 10.1-12.1 HU and 9.4-13.7 HU for abdominopelvic CT examinations) that can be targeted to improve clinical performance consistency. CONCLUSION. New reference levels and ranges, which simultaneously consider image noise and radiation dose information across wide patient populations, were defined and determined for two clinical protocols. The methods of new quantitative constraints may provide unique and useful information about the goal of managing the variability of image quality and dose in clinical CT examinations.

Occult Spinal Cord Injury after Blunt Force Trauma in a Patient with Achondroplasia: A Case Report and Review of Trauma Management Strategy.

BACKGROUND: Achondroplastic dwarfism is associated with anatomic abnormalities that can predispose to occult injury and challenges in trauma management. Airway anatomy is problematic due to macrocephaly, midface hypoplasia, and a narrow nasopharynx. Manipulation of the neck is very dangerous due to the high likelihood of preexisting cervicomedullary stenosis. Restrictive lung disease and obstructive sleep apnea may complicate respiratory status. Peripheral and central venous access can be difficult to obtain. Orthopedic and metabolic comorbidities can lead to a prolonged hospital course. CASE REPORT: A 17-year-old male patient with achondroplasia presented to the Emergency Department after a high-speed motor vehicle collision. Despite a negative computed tomography scan of the cervical spine and absence of neck pain, a magnetic resonance imaging evaluation was obtained due to severe neurologic deficits; it revealed disruption of the anterior longitudinal ligament at C2/3 and spinal cord contusion from C3-C6. The patient had a difficult intubation and prolonged weaning from the ventilator after his operation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians must maintain preparedness for all patients and situations, no matter how rare. Prior knowledge of key differences in management of the ABCDs (airway, breathing, circulation, neurological deficit) in patients with achondroplasia will reduce morbidity and mortality.

Anterior transarticular atlantoaxial screw fixation in combination with dens screw fixation for type II odontoid fractures with associated atlanto-odontoid osteoarthritis.

PURPOSE: The purpose of this study was to evaluate the 1-year outcome after anterior transarticular atlantoaxial fixation and odontoid fusion (TAFOF) for type II odontoid fractures and atlanto-odontoid osteoarthritis (AO) in elderly patients. METHODS: All geriatric patients, age 70 or older, with acute traumatic type II odontoid fractures and moderate or severe AO treated by TAFOF were included. The study was performed at a single institution between June 2008 and August 2013. Patients were evaluated clinically and radiologically after 1 year. Main parameter of interest were in-hospital and 1-year mortality rates, complication rates (re-operations, prolonged hospital stay, blood transfusion; non-union), and the patients' pain (0: no pain; 10: maximal pain) and satisfaction level (0: lowest satisfaction; 10: highest satisfaction) after 1 year. RESULTS: A total of 83 patients were included with an average age of 84.7 years (range 70-101 years). 39 patients were subdivided as "old" with an age 70-84 years and 44 patients were defined as "very old" with an age of 85 or higher. The average operation time was 64.7 min. Three patients died during the inpatient stay (3.6 %). Twenty patients (24.1 %) were lost contact follow-up. The 1-year mortality was 25.4 % with a significantly higher mortality rate in very old patient group (p = 0.01). At the 1-year follow-up, the mean pain level was 3.3 and the mean patient satisfaction level was 6.5. Osseous consolidation of the dens was visible in 90.2 % of patients. Revision surgery was performed in three patients (3.6 %). Generally, a significantly higher complication rate was seen after single-screw fixation of the dens compared to a double-screw fixation in combination with TAF (p = 0.042). CONCLUSIONS: Anterior TAFOF leads to promising 1-year results with low in-hospital mortality and a high fusion rate in geriatric patients with type II odontoid fractures and relevant AO. Double-screw dens fixation seems to reduce the complication rate.

Precise definitions of some terminology for longitudinal clinical trials: subjects, patient populations, analysis sets, intention to treat, and related terms.

Biostatisticians recognize the importance of precise definitions of technical terms in randomized controlled clinical trial (RCCT) protocols, statistical analysis plans, and so on, in part because definitions are a foundation for subsequent actions. Imprecise definitions can be a source of controversies about appropriate statistical methods, interpretation of results, and extrapolations to larger populations. This paper presents precise definitions of some familiar terms and definitions of some new terms, some perhaps controversial. The glossary contains definitions that can be copied into a protocol, statistical analysis plan, or similar document and customized. The definitions were motivated and illustrated in the context of a longitudinal RCCT in which some randomized enrollees are non-adherent, receive a corrupted treatment, or withdraw prematurely. The definitions can be adapted for use in a much wider set of RCCTs. New terms can be used in place of controversial terms, for example, subject. We define terms specifying a person's progress through RCCT phases and that precisely define the RCCT's phases and milestones. We define terms that distinguish between subsets of an RCCT's enrollees and a much larger patient population. 'The intention-to-treat (ITT) principle' has multiple interpretations that can be distilled to the definitions of the 'ITT analysis set of randomized enrollees'. Most differences among interpretations of 'the' ITT principle stem from an RCCT's primary objective (mainly efficacy versus effectiveness). Four different 'authoritative' definitions of ITT analysis set of randomized enrollees illustrate the variety of interpretations. We propose a separate specification of the analysis set of data that will be used in a specific analysis. Copyright © 2016 John Wiley & Sons, Ltd.

Appropriate patient population for future visual system axon regeneration therapies.

A number of blinding diseases caused by damage to the optic nerve result in progressive vision loss or loss of visual acuity. Secondary glaucoma results from traumatic injuries, pseudoexfoliation or pigmentary dispersion syndrome. Progressive peripheral vision loss is common to all secondary glaucoma irrespective of the initial event. Axon regeneration is a potential therapeutic avenue to restore lost vision in these patients. In contrast to the usual approach of having the worst possible patient population for initial therapies, axon regeneration may require consideration of appropriate patient population even for initial treatment trials. The current state of axon regeneration therapies, their potential future and suitable patient population when ready is discussed in this perspective. The selection of patients are important for adoption of axon regeneration specifically in the areas of central nervous system regenerative medicine. This article is categorized under: Neurological Diseases > Molecular and Cellular Physiology Neurological Diseases > Biomedical Engineering Metabolic Diseases > Molecular and Cellular Physiology.

Analysis of Inclisiran in the US FDA Adverse Event Reporting System (FAERS): a focus on overall patient population and sex-specific subgroups.

BACKGROUND: Our study aimed to identify inclisiran-related adverse events(AEs) for primary hypercholesterolemia and arteriosclerotic cardiovascular disease(ASCVD) from the US FDA Adverse Event Reporting System (FAERS) database, analyzing its links to AEs in the overall patient population and sex-specific subgroups to improve medication safety. METHODS: We analyzed inclisiran-related AEs signals by using statistical methods like Reporting Odds Ratio (ROR), Proportional Reporting Ratios (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma-Poisson Shrinker (MGPS). RESULTS: Analyzing 2,400 AE reports with inclisiran as the primary suspected drug in the FAERS database, we identified 70 AE signals over 13 organ systems using the above four methods. Notable findings were strong signals for systemic diseases and various reactions at the site of administration (ROR 1.49, 95% CI 1.41-1.57), and various musculoskeletal and connective tissue diseases (ROR 4.07, 95% CI 3.83-4.03) in overall and gender-specific populations. Myalgia, a new ADE signal not in the drug insert, was a top signal by intensity and frequency (ROR 14.76, 95% CI 12.84-16.98). CONCLUSION: Our study revealed the strongest AE signals associated with inclisiran in both the overall population and gender subgroups, highlighting potential risks in clinical medication use and guiding balanced clinical decision-making.

Antibiotic Treatment Practices and Microbial Profile in Diabetic Foot Ulcers: A Retrospective Cohort Study.

Aim and objective Diabetic foot ulcers (DFUs) are a frequent complication of diabetes mellitus, impacting more than one in 10 diabetic patients, with roughly half of these ulcers progressing to infection. Existing literature indicates that these infections are predominantly polymicrobial, with gram-positive isolates being the most common. This microbial profile informs the empiric antibiotic strategies employed in first-world countries, often including highly potent nephrotoxic antibiotics. This retrospective cohort study aims to assess the microbial profile and antibiotic treatment practices in patients with infected DFUs at Ochsner LSU Health Shreveport Academic Medical Center in Shreveport, Louisiana, United States. Materials and methods A total of 115 patients diagnosed with infected DFUs were included in the study. Patient records were reviewed to identify bacterial pathogens cultured from foot wounds, antibiotic treatment regimens administered, and the prevalence of acute kidney injury (AKI). Results The study found a predominance of gram-negative isolates (199; 59.4%), facultative anaerobes (246; 73.4%), and polymicrobial infections (67; 78.8%) in infected DFUs. Vancomycin was administered to 95 patients (82.6%), with only a small number subsequently testing positive for methicillin-resistant Staphylococcus aureus (MRSA). Combination therapy with vancomycin and Zosyn was given to 71 patients (61.7%), which increased the potential risk of antibiotic-induced nephrotoxicity. AKI was prevalent, affecting 58 patients (50.4%). Conclusions This study highlights a discrepancy between the microbial profile of infected DFUs and empiric antibiotic treatment practices at Ochsner LSU Health Shreveport Academic Medical Center. The predominance of gram-negative bacteria underscores the need for a polymicrobial, gram-negative-focused empiric treatment approach. Alternative antibiotics with broad-spectrum coverage and minimal nephrotoxicity, such as ceftriaxone, clindamycin, metronidazole, amoxicillin-clavulanate, and linezolid, should be considered. Tailored antibiotic strategies, guided by local microbial profiles and patient-specific factors, are essential to optimize treatment outcomes in this high-risk population.

An FDA Guide on Indications for Use and Device Reporting of Artificial Intelligence-Enabled Devices: Significance for Pediatric Use.

Radiology has been a pioneer in adopting artificial intelligence (AI)-enabled devices into the clinic. However, initial clinical experience has identified concerns of inconsistent device performance across different patient populations. Medical devices, including those using AI, are cleared by the FDA for their specific indications for use (IFUs). IFU describes the disease or condition the device will diagnose or treat, including a description of the intended patient population. Performance data evaluated during the premarket submission support the IFU and include the intended patient population. Understanding the IFUs of a given device is thus critical to ensuring that the device is used properly and performs as expected. When devices do not perform as expected or malfunction, medical device reporting is an important way to provide feedback about the device to the manufacturer, the FDA, and other users. This article describes the ways to retrieve the IFU and performance data information as well as the FDA medical device reporting systems for unexpected performance discrepancy. It is crucial that imaging professionals, including radiologists, know how to access and use these tools to improve the informed use of medical devices for patients of all ages.

Tislelizumab in Patients with Previously Treated Advanced Hepatocellular Carcinoma (RATIONALE-208): A Multicenter, Non-Randomized, Open-Label, Phase 2 Trial.

Introduction: Tislelizumab (anti-programmed cell death protein 1 antibody) showed preliminary antitumor activity and tolerability in patients with advanced solid tumors, including hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of tislelizumab in patients with previously treated advanced HCC. Methods: The multiregional phase 2 study RATIONALE-208 examined single-agent tislelizumab (200 mg intravenously every 3 weeks) in patients with advanced HCC with Child-Pugh A, Barcelona Clinic Liver Cancer stage B or C, and who had received one or more prior lines of systemic therapy. The primary endpoint was objective response rate (ORR), radiologically confirmed per Response Evaluation Criteria in Solid Tumors version 1.1 by the Independent Review Committee. Safety was assessed in patients who received ≥1 dose of tislelizumab. Results: Between April 9, 2018, and February 27, 2019, 249 eligible patients were enrolled and treated. After a median study follow-up of 12.7 months, ORR was 13% (n = 32/249; 95% confidence interval [CI], 9-18), including five complete and 27 partial responses. The number of prior lines of therapy did not impact ORR (one prior line, 13% [95% CI, 8-20]; two or more prior lines, 13% [95% CI, 7-20]). Median duration of response was not reached. The disease control rate was 53%, and median overall survival was 13.2 months. Of the 249 total patients, grade ≥3 treatment-related adverse events were reported in 38 (15%) patients; the most common was liver transaminase elevations in 10 (4%) patients. Treatment-related adverse events led to treatment discontinuation in 13 (5%) patients or dose delay in 46 (19%) patients. No deaths were attributed to the treatment per investigator assessment. Conclusion: Tislelizumab demonstrated durable objective responses, regardless of the number of prior lines of therapy, and acceptable tolerability in patients with previously treated advanced HCC.