Undetectable JC virus CSF PCR in patients with JC virus-induced progressive multifocal leukoencephalopathy.

The diagnosis of progressive multifocal leukoencephalopathy (PML) is based on a combination of clinical, radiographic, and laboratory findings. However, negative JC polyomavirus (JCPyV) PCR in CSF does not always rule out JCPyV-related PML. In this narrative review, we sought to examine the characteristic of biopsy-proven PML in patients with undetectable JCPyV CSF PCR and provide alternative approaches in this scenario.

Ibrutinib-associated cutaneous mucormycosis due to an Apophysomyces species: report of a case and review of the literature.

The use of ibrutinib, a Bruton tyrosine kinase inhibitor, has been associated with invasive fungal infections (IFIs). We describe a case of Apophysomyces infection associated with long-term use of ibrutinib for the treatment of chronic lymphocytic leukemia as well as perform a literature review of Mucormycosis infections in patients on ibrutinib. Our review found that the onset of IFI can occur within months to years of starting tyrosine kinase inhibitors. These reports provide a more complete picture of the risk of IFI while patients are on ibrutinib. Our case also demonstrates the utility of molecular techniques in the diagnosis of IFI, as the diagnosis was made using 28S rDNA/internal transcribed spacer PCR.

Real-world experience with cefiderocol therapy for Pseudomonas aeruginosa and other multidrug resistant gram-negative infections within the Veterans Health Administration, 2019-2022.

Objective: Single-center and regional studies have reported outcomes after treatment with cefiderocol, a novel siderophore cephalosporin. We report on real-world use, clinical outcomes, and microbiological outcomes with cefiderocol therapy within the Veterans' Health Administration (VHA). Design: Prospective, observational descriptive study. Setting: Veterans' Health Administration, 132 sites across the United States, during 2019-2022. Patients: This study included patients admitted to any VHA medical center who received cefiderocol for ≥2 days. Methods: Data were obtained from the VHA Corporate Data Warehouse and through manual chart review. We extracted clinical and microbiologic characteristics and outcomes. Results: In total, 8,763,652 patients received 1,142,940,842 prescriptions during the study period. Of these, 48 unique individuals received cefiderocol. The median age of this cohort was 70.5 years (IQR, 60.5-74), and the median Charlson comorbidity score was 6 (IQR, 3-9). The most common infectious syndromes were lower respiratory tract infection in 23 patients (47.9%) and urinary tract infection in 14 patients (29.2%). The most common pathogen cultured was P. aeruginosa in 30 patients (62.5%). The clinical failure rate was 35.4% (17 of 48), and 15 (88.2%) of these 17 patients died within 3 days of clinical failure. The 30-day and 90-day all-cause mortality rates were 27.1% (13 of 48) and 45.8% (22 of 48), respectively. The 30-day and 90-day microbiologic failure rates were 29.2% (14 of 48) and 41.7% (20 of 48), respectively. Conclusions: In this nationwide VHA cohort clinical and microbiologic failure occurred in >30% of patients treated with cefiderocol, and >40% of these died within 90 days. Cefiderocol is not widely used, and many of the patients who received it had substantial comorbidities.

Bacteriuria in older adults triggers confusion in healthcare providers: A mindful pause to treat the worry.

The evidence base for refraining from screening for or treating asymptomatic bacteriuria (ASB) in older adults is strong, but both practices remain prevalent. Clinical confusion over how to respond to a change from baseline, when to order a urinalysis and urine culture, and what to do with a positive urine culture fuels unnecessary antibiotic use for ASB. If the provider can take a mindful pause to apply evidenced-based assessment tools, the resulting increased clarity in how to manage the situation can reduce overtreatment of ASB.

Quantifying the Implementation and Cost of a Multisite Antibiotic Stewardship Intervention for Asymptomatic Bacteriuria.

Objective: The intensity of an antibiotic stewardship intervention to achieve clinical impact is not known. We conducted a multisite dissemination project of an intervention to reduce treatment of asymptomatic bacteriuria (ASB) and studied: (1) the association between implementation metrics and clinical outcomes and (2) the cost of implementation. Design/Setting/Participants: A central site facilitated a multimodality intervention to decrease unnecessary urine cultures and antibiotic treatment in patients with ASB at 4 Veterans Affairs medical centers. Methods: The intervention consisted of a decision support aid algorithm and interactive teaching cases that provided in the moment audit and feedback on how to manage ASB. Implementation outcomes included minutes spent in intervention delivery, number of healthcare professionals reached, and number of sessions delivered. Clinical outcomes included days of antibiotic therapy (DOT), length of antibiotic therapy (LOT), and number of urine cultures ordered per 1000 bed days. Personnel reported weekly time logs. Results: Minutes spent in intervention delivery were inversely correlated with two clinical outcomes, DOT (R -0.3, P = .04) and LOT (R -0.3, P = .02). Number of healthcare professionals reached and number of sessions delivered were not correlated with clinical outcomes of DOT (R -0.003, P = .98, R = -0.059, P = .69) or LOT (R +0.073, P = .62, R -0.102, P = .49). Physician champions spent an average of 3.8% of effort on the intervention. The implementation cost was USD 22,299/year per site on average. Conclusions: The amount of time local teams spent in delivery of an antibiotic stewardship intervention was correlated with the desired decrease in antibiotic use. Implementing this successful antibiotic stewardship intervention required minimal time.

A survey on self-medication for the prevention or treatment of COVID-19 and distrust in healthcare of veterans in a primary care setting in the United States.

Background: The SARS-CoV-2 (COVID-19) pandemic brought the public overwhelming and conflicting information. Rates of trust in healthcare professionals have been declining among laypersons over the past five decades. In this setting, we sought to evaluate the use of medications, both with or without a prescription, to prevent and treat SARS-CoV-2 as well as trust in healthcare among patients in a primary care clinic. Design: We surveyed 150 veterans in primary care clinic waiting rooms at a large southwestern tertiary care Veterans Affairs hospital. This survey was performed in March-November 2021. Methods: The survey asked about respondents' demographics, use of medications, nutritional supplements, and other remedies for the prevention and treatment of COVID-19, perceived access to care using Agency for Healthcare Research and Quality (AHRQ) Consumer Assessment of Healthcare Providers and System (CAHPS), overall health status, and barriers to medical appointments in the last 12 months. Distrust was measured using the Revised Health Care Distrust scale. We used univariate and multivariate linear regression analyses to study predictors of distrust to healthcare. Results: Forty-two (28%) of 150 respondents reported taking an agent for the prevention of COVID-19, while 4% reported storing antibiotics for the treatment of COVID-19, if diagnosed. Medications were obtained from medical providers, US stores or markets, the Internet, home stockpiles, and other countries. Medications with potentially harmful effects taken for the prevention and treatment of COVID-19 included hydroxychloroquine, pseudoephedrine, and antibiotics. Among those surveyed, the mean (SD) on the health system distrust score was 2.2 (0.6) on a scale of 1-5, with 5 indicating higher distrust. Younger age, self-reported poor health, lack of a regular physician, and self-reported poor access to care were independently associated with distrust in healthcare. Conclusion: Self-medication to prevent COVID-19 infection with unproven therapies was common among respondents, as was some level of distrust in the healthcare system. Access to care was one of the modifiable factors associated with distrust. Future studies may explore whether improving trust may moderate self-treatment behavior and storage of potentially harmful medications. Plain Language Summary: Self-Medication Habits and Trust in Healthcare Among Patients in a Primary Care Setting in the United States The public has received information from many different sources on COVID-19. Trust in healthcare leadership has also been impacted. We studied self-medication habits to prevent or treat COVID-19 among a group of primary care patients in a large hospital system in the Southwest United States. We also explored these patients' trust in their healthcare system.We asked people waiting in primary care clinic waiting rooms whether they had taken any medications, nutritional supplements, or other remedies to prevent or treat COVID-19. We also asked people whether they stored medications in the event that they were diagnosed with COVID. The survey explored patients' trust in the healthcare system through a validated trust survey tool. The survey also assessed basic demographic information, health literacy, access to care, and self-reported health status. These survey answers were analyzed to see whether there was an association between trust in healthcare and other factors including self-medication habits, access to care, demographics, or perceived health.This study found that over 25% of the 150 people surveyed had taken a medication, nutritional supplement, or remedy in an attempt to prevent COVID. We found that some people were taking potentially harmful medications, including hydroxychloroquine, pseudoephedrine, and antibiotics. We found that patients' distrust score was 2.2 on a scale of 1-5 (5 is associated with higher distrust). Self-medication for the prevention or treatment of COVID was not associated with distrust; however, younger age, self-perceived lack of access to healthcare, self-perceived poor overall health, and not having a regular doctor were predictors for lower trust. This information provides a basis to further study self-medication habits as well as ways to improve trust in the healthcare system.

Postacute COVID-19: An Overview and Approach to Classification.

As the coronavirus disease 2019 (COVID-19) pandemic has progressed, a large volume of literature has developed delineating the clinical manifestations of acute infection. Recent reports have also started to describe persistent symptoms extending beyond the period of initial illness or hospitalization. Anecdotes of different signs and symptoms occurring after acute infection have also arisen in the lay press. Here we describe the current existing medical literature on the emerging concept of postacute COVID-19 and suggest an approach to classifying different manifestations of the syndrome. We also review long-term clinical manifestations observed in patients who recovered from infection due to other epidemic coronaviruses and briefly discuss potential mechanisms driving the phenomenon of postacute COVID-19.

Vibrational spectroscopic analysis of hydroxyapatite in HYP mice and individuals with X-linked hypophosphatemia.

BACKGROUND: X-linked hypophosphatemia (XLH) is the most common form of familial phosphate-wasting disorders, due to an inactivating mutation in the phosphate-regulating neutral endopeptidase, X-linked gene. Persistent osteomalacia, enthesophytes, osteophytes, degenerative arthritis and dental abscesses/periodontal disease dominate the adult disorder. However, the impact of insufficient phosphate on hydroxyapatite composition, the major inorganic component of bone and teeth, is unknown in individuals with XLH. METHODS: Using Raman spectroscopy, the carbonate (CO3 2-) to phosphate (PO4 3-) ion ratio was measured in HYP and wild-type mice and in primary and permanent teeth from XLH individuals and unaffected controls. RESULTS: There was a significant difference in carbonate ion substitution between the HYP and wild-type femoral cortical bone (0.36 ± 0.08 versus 0.24 ± 0.04; p < 0.001). Carbonate ion substitution levels were also higher in permanent XLH teeth compared with unaffected individuals (0.39 ± 0.12 versus 0.23 ± 0.04; p < 0.001), but not in primary teeth (0.29 ± 0.11 versus 0.26 ± 0.02; p = 0.29). Complementary Fourier transform infrared analyses demonstrated higher relative intensities of the four major vibrational bands originating from the carbonate anion in XLH teeth compared with unaffected controls. CONCLUSION: Ionic substitution within the crystal lattice is a common feature of hydroxyapatite and one that confers the physiological properties of bone that impact mechanical strength and the process of bone remodeling. Our data demonstrating anionic substitution in human dentin from individuals with XLH validate the use of dentin as a proxy for bone and to better understand the molecular adaptations that occur in the biochemical milieu of XLH.