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Childhood sexual abuse history amplifies the link between disease burden and inflammation among older adults with HIV

Derry, Heather M; Johnston, Carrie D; Brennan-Ing, Mark; Karpiak, Stephen; Burchett, Chelsie O; Zhu, Yuan-Shan; Siegler, Eugenia L; Glesby, Marshall J
As they age, people living with HIV (PLWH) experience greater rates of inflammation-related health conditions compared to their HIV-negative peers. Because early life adversity can exaggerate proinflammatory effects of later physiological challenges, inflammation may be higher among PLWH with these combined risks, which could inform intervention approaches to mitigate multimorbidity. In this cross-sectional analysis, we investigated individual and combined effects of childhood sexual abuse (CSA) history and physiological burden (Veterans Aging Cohort Study Index scores) on serum cytokine and C-reactive protein (CRP) levels among PLWH. Participants (n ​= ​131; age 54 and older) were patients at an outpatient HIV clinic who completed a psychosocial survey and biomedical research visit as part of a larger study. 93% were virally suppressed, and 40% reported experiencing sexual abuse in childhood. Composite cytokine levels (summarizing IL-6, TNF-α, IFN-γ), CRP, and disease burden did not differ significantly between those who had a history of CSA and those who did not. Participants with greater disease burden had higher composite cytokine levels (r ​= ​0.29, p ​= ​0.001). The disease burden by CSA interaction effect was a significant predictor of composite cytokine levels (but not CRP), and remained significant after controlling for age, sex, race, BMI, anti-inflammatory medication use, selective serotonin reuptake inhibitor use, depressive symptoms, and smoking status (F(1, 114) ​= ​5.68, p ​= ​0.02). In follow-up simple slopes analysis, greater disease burden was associated with higher cytokine levels among those with CSA history (b ​= ​0.03, SE ​= ​0.008, p<0.001), but not among those without CSA history. Further, in the context of greater disease burden, individuals with a CSA history tended to have higher cytokine levels than those without a CSA history (b ​= ​0.38, SE ​= ​0.21, p ​= ​0.07). These data suggest that the physiological sequelae of childhood trauma may persist into older age among those with HIV. Specifically, links between physiological burden and inflammation were stronger among survivors of CSA in this study. The combined presence of CSA history and higher disease burden may signal a greater need for and potential benefit from interventions to reduce inflammation, an area for future work.
PMCID:8474623
PMID: 34589822
ISSN: 2666-3546
CID: 5139382

"One-two Punch": Synergistic β-lactam Combinations for Mycobacterium abscessus and Target Redundancy in the Inhibition of Peptidoglycan Synthesis Enzymes

Nguyen, David C; Dousa, Khalid M; Kurz, Sebastian G; Brown, Sheldon T; Drusano, George; Holland, Steven M; Kreiswirth, Barry N; Boom, W Henry; Daley, Charles L; Bonomo, Robert A
Mycobacterium abscessus subsp. abscessus is one of the most difficult pathogens to treat and its incidence in disease is increasing. Dual β-lactam combinations act synergistically in vitro, but are not widely employed in practice. A recent study shows that a combination of imipenem and ceftaroline significantly lowers the minimum inhibitory concentration (MIC) of clinical isolates despite both drugs targeting the same peptidoglycan synthesis enzymes. The underlying mechanism of this effect provides a basis for further investigations of dual β-lactam combinations in the treatment of M. abscessus subsp. abscessus eventually leading to a clinical trial. Furthermore, dual β-lactam strategies may be explored for other difficult mycobacterial infections.
PMID: 34113990
ISSN: 1537-6591
CID: 4900312

Prognostic significance of aortic valve calcium in relation to coronary artery calcification for long-term, cause-specific mortality: results from the CAC Consortium

Han, Donghee; Cordoso, Rhanderson; Whelton, Seamus; Rozanski, Alan; Budoff, Matthew J; Miedema, Michael D; Nasir, Khurram; Shaw, Leslee J; Rumberger, John A; Gransar, Heidi; Dardari, Zeina; Blumenthal, Roger S; Blaha, Michael J; Berman, Daniel S
AIMS/OBJECTIVE:Aortic valve calcification (AVC) has been shown to be associated with increased cardiovascular disease (CVD) risk; however, whether this is independent of traditional risk factors and coronary artery calcification (CAC) remains unclear. METHODS AND RESULTS/RESULTS:From the multicentre CAC Consortium database, 10 007 patients (mean 55.8±11.7 years, 64% male) with concomitant CAC and AVC scoring were included in the current analysis. AVC score was quantified using the Agatston score method and categorized as 0, 1-99, and ≥100. The endpoints were all-cause, CVD, and coronary heart disease (CHD) deaths. AVC (AVC>0) was observed in 1397 (14%) patients. During a median 7.8 (interquartile range: 4.7-10.6) years of study follow-up, 511 (5.1%) deaths occurred; 179 (35%) were CVD deaths, and 101 (19.8%) were CHD deaths. A significant interaction between CAC and AVC for mortality was observed (P<0.001). The incidence of mortality events increased with higher AVC; however, AVC ≥100 was not independently associated with all-cause, CVD, and CHD deaths after adjusting for CVD risk factors and CAC (P=0.192, 0.063, and 0.206, respectively). When further stratified by CAC<100 or ≥100, AVC ≥100 was an independent predictor of all-cause and CVD deaths only in patients with CAC <100, after adjusting for CVD risk factors and CAC [hazard ratio (HR): 1.93, 95% confidence interval (CI): 1.14-3.27; P=0.013 and HR: 2.71, 95% CI: 1.15-6.34; P=0.022, respectively]. CONCLUSION/CONCLUSIONS:Although the overall prognostic significance of AVC was attenuated after accounting for CAC, high AVC was independently associated with all-cause and CVD deaths in patients with low coronary atherosclerosis burden.
PMID: 33331631
ISSN: 2047-2412
CID: 4961762

Protocol: A multi-modal, physician-centered intervention to improve guideline-concordant prostate cancer imaging

Makarov, Danil V; Ciprut, Shannon; Kelly, Matthew; Walter, Dawn; Shedlin, Michele G; Braithwaite, Ronald Scott; Tenner, Craig T; Gold, Heather T; Zeliadt, Steven; Sherman, Scott E
BACKGROUND:Almost half of Veterans with localized prostate cancer receive inappropriate, wasteful staging imaging. Our team has explored the barriers and facilitators of guideline-concordant prostate cancer imaging and found that (1) patients with newly diagnosed prostate cancer have little concern for radiographic staging but rather focus on treatment and (2) physicians trust imaging guidelines but are apt to follow their own intuition, fear medico-legal consequences, and succumb to influence from imaging-avid colleagues. We used a theory-based approach to design a multi-level intervention strategy to promote guideline-concordant imaging to stage incident prostate cancer. METHODS:We designed the Prostate Cancer Imaging Stewardship (PCIS) intervention: a multi-site, stepped wedge, cluster-randomized trial to determine the effect of a physician-focused behavioral intervention on Veterans Health Administration (VHA) prostate cancer imaging use. The multi-level intervention, developed according to the Theoretical Domains Framework (TDF) and Behavior Change Wheel, combines traditional physician behavior change methods with novel methods of communication and data collection. The intervention consists of three components: (1) a system of audit and feedback to clinicians informing individual clinicians and their sites about how their behavior compares to their peers' and to published guidelines, (2) a program of academic detailing with the goal to educate providers about prostate cancer imaging, and (3) a CPRS Clinical Order Check for potentially guideline-discordant imaging orders. The intervention will be introduced to 10 participating geographically distributed study sites. DISCUSSION/CONCLUSIONS:This study is a significant contribution to implementation science, providing VHA an opportunity to ensure delivery of high-quality care at the lowest cost using a theory-based approach. The study is ongoing. Preliminary data collection and recruitment have started; analysis has yet to be performed. TRIAL REGISTRATION/BACKGROUND:CliniclTrials.gov NCT03445559. Prospectively registered on February 26, 2018.
PMCID:8522153
PMID: 34663435
ISSN: 1745-6215
CID: 5037252

Chondrocalcinosis: Advances in Diagnostic Imaging

Sullivan, Jeremy; Pillinger, Michael H; Toprover, Michael
PURPOSE OF REVIEW/OBJECTIVE:Calcium pyrophosphate deposition disease (CPPD) arises from calcium pyrophosphate deposition throughout the body, leading to different clinical syndromes that may be diagnosed using various imaging modalities. The purpose of this review is to highlight recent updates in the imaging of CPPD. RECENT FINDINGS/RESULTS:Conventional radiography remains the initial test when imaging CPPD; but musculoskeletal ultrasound and conventional computed tomography (CT) may also assist in diagnosing and characterizing CPP deposits, with increased sensitivity. Dual-energy CT is also being used to differentiate CPP crystals from other crystal deposition diseases. CPP discitis has been diagnosed with MRI, but MRI has lower sensitivity and specificity than the aforementioned imaging studies in CPPD diagnosis. Assorted imaging modalities are increasingly used to diagnose CPPD involving atypical joints, avoiding invasive procedures. Each modality has its advantages and disadvantages. Future imaging may be able to provide more utility than what is currently available.
PMID: 34623546
ISSN: 1534-6307
CID: 5027062

Colonization with Fluoroquinolone-Resistant Enterobacterales Decreases the Effectiveness of Fluoroquinolone Prophylaxis in Hematopoietic Cell Transplant Recipients

Satlin, Michael J; Chen, Liang; Douglass, Claire; Hovan, Michael; Davidson, Emily; Soave, Rosemary; La Spina, Marisa; Gomez-Arteaga, Alexandra; van Besien, Koen; Mayer, Sebastian; Phillips, Adrienne; Hsu, Jing-Mei; Malherbe, Rianna; Small, Catherine B; Jenkins, Stephen G; Westblade, Lars F; Kreiswirth, Barry N; Walsh, Thomas J
BACKGROUND:Levofloxacin prophylaxis is recommended to prevent Gram-negative bloodstream infections (BSIs) in patients with prolonged chemotherapy-induced neutropenia. However, increasing fluoroquinolone resistance may decrease the effectiveness of this approach. METHODS:We assessed the prevalence of colonization with fluoroquinolone-resistant Enterobacterales (FQRE) among patients admitted for hematopoietic cell transplantation (HCT) from November 2016-August 2019 and compared the risk of Gram-negative BSI between FQRE-colonized and non-colonized patients. All patients received levofloxacin prophylaxis during neutropenia. Stool samples were collected upon admission for HCT and weekly thereafter until recovery from neutropenia, and underwent selective culture for FQRE. All isolates were identified and underwent antimicrobial susceptibility testing by broth microdilution. FQRE isolates also underwent whole-genome sequencing. RESULTS:Fifty-four (23%) of 234 patients were colonized with FQRE prior to HCT, including 30 (25%) of 119 allogeneic and 24 (21%) of 115 autologous HCT recipients. Recent antibacterial use was associated with FQRE colonization (P=0.048). Ninety-one percent of colonizing FQRE isolates were Escherichia coli and 29% produced extended-spectrum ß-lactamases. Seventeen (31%) FQRE-colonized patients developed Gram-negative BSI despite levofloxacin prophylaxis, compared to only two (1.1%) of 180 patients who were not colonized with FQRE on admission (P<0.001). Of the 17 Gram-negative BSIs in FQRE-colonized patients, 15 (88%) were caused by FQRE isolates that were genetically identical to the colonizing strain. CONCLUSIONS:Nearly one-third of HCT recipients with pre-transplant FQRE colonization developed Gram-negative BSI while receiving levofloxacin prophylaxis and infections were typically caused by their colonizing strains. In contrast, levofloxacin prophylaxis was highly effective in patients not initially colonized with FQRE.
PMID: 33956965
ISSN: 1537-6591
CID: 4866662

Risk of Toxicity After Initiating Immune Checkpoint Inhibitor Treatment in Patients With Rheumatoid Arthritis

Efuni, Elizaveta; Cytryn, Samuel; Boland, Patrick; Niewold, Timothy B; Pavlick, Anna; Weber, Jeffrey; Sandigursky, Sabina
INTRODUCTION/BACKGROUND:Immune checkpoint inhibitors (ICIs) are increasingly used to treat advanced cancer. Rheumatoid arthritis (RA) is associated with an increased risk of malignancies; however, patients with RA have been excluded from ICI trials. In this study, we evaluated risk of toxicity after initiation of ICI treatment in RA patients. METHODS:We conducted a single-institution, medical records review analysis to assess the incidence of immune-related adverse events (irAEs) and autoimmune disease (AID) flares among patients with AIDs treated with ICIs from 2011 to 2018. A subgroup analysis for RA patients was performed with frequencies of irAEs and AID flares reported. RESULTS:Twenty-two patients with RA who were treated with ICI for malignancy were identified. At the time of ICI initiation, 86% had inactive RA disease activity. Immune-related adverse events occurred in 7 (32%) of patients, with 2 (9%) developing grade 3 (i.e., severe) irAEs. Immune checkpoint inhibitors were temporarily discontinued because of irAEs in 5 patients (23%), and permanently in 1 patient. Rheumatoid arthritis flares occurred in 12 patients (55%). Of those, 10 (83%) received oral corticosteroids with an adequate treatment response. CONCLUSIONS:Our analysis suggests that irAEs following ICI treatment are not increased among RA patients compared with other cancer patients. Heightened RA disease activity during ICI treatment is common, but most adverse events are manageable with oral corticosteroids, and few require permanent ICI discontinuation. A close collaboration between the oncologist and rheumatologist is advisable when considering ICIs in patients with RA.
PMID: 31977647
ISSN: 1536-7355
CID: 4273562

Continuity of Nursing Care in Home Health: Impact on Rehospitalization Among Older Adults With Dementia

Ma, Chenjuan; McDonald, Margaret V; Feldman, Penny H; Miner, Sarah; Jones, Simon; Squires, Allison
BACKGROUND:Home health care (HHC) is a leading form of home and community-based services for persons with dementia (PWD). Nurses are the primary providers of HHC; however, little is known of nursing care delivery and quality. OBJECTIVE:The objective of this study was to examine the association between continuity of nursing care in HHC and rehospitalization among PWD. RESEARCH DESIGN/METHODS:This is a retrospective cohort study using multiple years (2010-2015) of HHC assessment, administrative, and human resources data from a large urban not-for-profit home health agency. SUBJECTS/METHODS:This study included 23,886 PWD receiving HHC following a hospitalization. MEASURES/METHODS:Continuity of nursing care was calculated using the Bice and Boxerman method, which considered the number of total visits, nurses, and visits from each nurse during an HHC episode. The outcome was all-cause rehospitalization during HHC. Risk-adjusted logistic regression was used for analysis. RESULTS:Approximately 24% of PWD were rehospitalized. The mean continuity of nursing care score was 0.56 (SD=0.33). Eight percent of PWD received each nursing visit from a different nurse (no continuity), and 26% received all visits from one nurse during an HHC episode (full continuity). Compared with those receiving high continuity of nursing care (third tertile), PWD receiving low (first tertile) or moderate (second tertile) continuity of nursing care had an adjusted odds ratio of 1.33 (95% confidence interval: 1.25-1.46) and 1.30 (95% confidence interval: 1.22-1.43), respectively, for being rehospitalized. CONCLUSIONS:Wide variations exist in continuity of nursing care to PWD. Consistency in nurse staff when providing HHC visits to PWD is critical for preventing rehospitalizations.
PMID: 34166269
ISSN: 1537-1948
CID: 4935792

Assessing the influence of patient language preference on 30 day hospital readmission risk from home health care: A retrospective analysis

Squires, Allison; Ma, Chenjuan; Miner, Sarah; Feldman, Penny; Jacobs, Elizabeth A; Jones, Simon A
BACKGROUND:In home health care, language barriers are understudied. Language barriers between patients and providers are known to affect a variety of patient outcomes. How a patient's language preference influences hospital readmission risk from home health care has yet to be determined. OBJECTIVE:To determine if home care patients' language preference is associated with their risk for hospital readmission from home health care within 30 days of hospital discharge. DESIGN/METHODS:Retrospective cross-sectional study of hospital readmissions from an urban home health care agency's administrative records and the national electronic home health care record for the United States, captured between 2010 and 2015. SETTING/METHODS:New York City, New York, USA. PARTICIPANTS/METHODS:The dataset comprised 90,221 post-hospitalization patients and 6.5 million home health care visits. METHODS:First, a Chi-square test was used to determine if there were significant differences in crude readmission rates based on language group. Inverse probability of treatment weighting was used to adjust for significant differences in known hospital readmission risk factors between to examine all-cause hospital readmission during a home health care stay. The final matched sample included 87,561 patients with a language preference of English, Spanish, Russian, Chinese, or Korean. English-speaking patients were considered the comparison group to the non-English speaking patients. A Marginal Structural Model was applied to estimate the impact of non-English language preference against English language preference on rehospitalization. The results of the marginal structural model were expressed as an odds ratio of likelihood of readmission to the hospital from home health care. RESULTS:Home health patients with a non-English language preference had a higher hospital readmission risk than English-speaking patients. Crude readmission rate for the limited English proficiency patients was 20.4% (95% CI, 19.9-21.0%) overall compared to 18.5% (95% CI, 18.7-19.2%) for English speakers (p < 0.001). Being a non-English-speaking patient was associated with an odds ratio of 1.011 (95% CI, 1.004-1.018) in increased hospital readmission rates from home health care (p = 0.001). There were also statistically significant differences in readmission rate by language group (p < 0.001), with Korean speakers having the lowest rate and Spanish speakers having the highest, when compared to English speakers. CONCLUSIONS:People with a non-English language preference have a higher readmission rate from home health care. Hospital and home healthcare agencies may need specialized care coordination services to reduce readmission risk for these patients. Tweetable abstract: A new US-based study finds that home care patients with language barriers are at higher risk for hospital readmission.
PMID: 34710627
ISSN: 1873-491x
CID: 5037332

A Comparison of Alternative Medicine Users and Non-Users in Patients With Hidradenitis Suppurativa

Lane, Jordan; Emmerich, Veronica; Senthilnathan, Aditi; Kolli, Sree S; Cardwell, Leah A; Richardson, Irma M; Feldman, Steven R; Pichardo, Rita O
BACKGROUND:Hidradenitis suppurativa patients often seek non-prescription therapies. OBJECTIVE:To determine the prevalence of alternative medicine use and characterize the differences between patients who report using alternative medications versus those who do not. METHODS:We surveyed 67 patients with hidradenitis suppurativa regarding demographics, alternative medicine use, disease severity, and quality of life. RESULTS:25 (37.2%) of the HS subjects reported alternative medicine use. Alternative medicine users tended to be younger (36.7 vs 40.8 years), have a shorter time since diagnosis (12.6 vs14.6 years), and reported worse quality of life (14.1 vs 11.0) than non-users. These differences were not statistically significant. LIMITATIONS/CONCLUSIONS:Limitations included a small sample size. CONCLUSION/CONCLUSIONS:Alternative medicine use among patients with hidradenitis is common regardless of disease severity; even mild disease may drive patients to seek alternative treatment. J Drugs Dermatol. 2021;20(10):1072-1074. doi:10.36849/JDD.6046.
PMID: 34636524
ISSN: 1545-9616
CID: 5505662