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1.
Infect Control Hosp Epidemiol ; : 1-6, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39297374

RESUMEN

OBJECTIVE: Many preoperative urine cultures are of low value and may even lead to patient harms. This study sought to understand practices around ordering preoperative urine cultures and prescribing antibiotic treatment. DESIGN: Open-ended, semi-structured qualitative interviews. SETTING: 5 Veterans Affairs hospitals. PARTICIPANTS: Interviews with 14 surgeons (9 surgeons, 5 surgical leaders), 7 infectious disease physicians, 8 surgical advanced practice providers (APPs), 1 surgical nurse manager, 3 infectious disease pharmacists, 1 hospitalist, and 1 lab manager. METHODS: We interviewed participants using a qualitative semi-structured interview guide. Collected data was coded inductively and with the Dual Process Model (DPM) using MAXQDA software. Data in the "Testing Decision-Making" code was further reviewed using the concept of perceived risk as a sensitizing concept. RESULTS: We identified themes relating to surgeons' concerns about de-implementing preoperative urine cultures to detect asymptomatic bacteriuria (ASB) in patients undergoing non-urological procedures: (1) anxiety and uncertainty surrounding missing infection signs spanned surgical specialties, (2) there were perceived risks of negative consequences associated with omitting urine cultures and treatment prior to specific procedure sites and types, and additionally, (3) participants suggested potential routes for adjusting these perceived risks to facilitate de-implementation acceptance. Notably, participants suggested that leadership support and peer engagement could help improve surgeon buy-in. CONCLUSIONS: Concerns about perceived risks sometimes outweigh the evidence against routine preoperative urine cultures to detect ASB. Evidence from trusted peers may improve openness to de-implementing preoperative urine cultures.

3.
Infect Dis Clin North Am ; 38(2): 325-341, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38599896

RESUMEN

Urinary tract infections (UTIs) are common in women; more than 50% of women will be diagnosed with a UTI in her lifetime. Many of these women will go on to develop recurrent UTI. Nevertheless, evidence-based prevention of recurrent UTI is under-utilized. Here, the authors provide detailed practical advice on UTI prevention with a thorough review of the evidence. Non-antibiotic prevention measures discussed include increased fluid intake, vaginal estrogen therapy, methenamine, and cranberry. Antibiotic prophyalxis for carefully selected patients is also discussed.


Asunto(s)
Infecciones Urinarias , Humanos , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/prevención & control , Femenino , Factores de Riesgo , Recurrencia , Antibacterianos/uso terapéutico , Prevención Secundaria/métodos
4.
Am J Infect Control ; 52(7): 849-851, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38583778

RESUMEN

Experimental evidence suggests that Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) remains viable within aerosols with a half-life of approximately 3 hours; however, it remains unclear how long airborne SARS-CoV-2 can transmit infection. Whole genome sequencing during an outbreak suggested in-room transmission of SARS-CoV-2 to two patients admitted nearly 2 and 5 hours, respectively, after discharge of an asymptomatic infected patient. These findings suggest that airborne SARS-CoV-2 may transmit infection for over 4 hours, even in a hospital setting.


Asunto(s)
COVID-19 , SARS-CoV-2 , Secuenciación Completa del Genoma , Humanos , COVID-19/transmisión , COVID-19/epidemiología , COVID-19/virología , SARS-CoV-2/genética , Aerosoles , Genoma Viral , Factores de Tiempo , Masculino , Infección Hospitalaria/transmisión , Infección Hospitalaria/virología , Microbiología del Aire , Persona de Mediana Edad
6.
JAMA Netw Open ; 7(3): e240900, 2024 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-38436958

RESUMEN

Importance: Although recent guidelines recommend against performance of preoperative urine culture before nongenitourinary surgery, many clinicians still order preoperative urine cultures and prescribe antibiotics for treatment of asymptomatic bacteriuria in an effort to reduce infection risk. Objective: To assess the association between preoperative urine culture testing and postoperative urinary tract infection (UTI) or surgical site infection (SSI), independent of baseline patient characteristics or type of surgery. Design, Setting, and Participants: This cohort study analyzed surgical procedures performed from January 1, 2017, to December 31, 2019, at any of 112 US Department of Veterans Affairs (VA) medical centers. The cohort comprised VA enrollees who underwent major elective noncardiac, nonurological operations. Machine learning and inverse probability of treatment weighting (IPTW) were used to balance the characteristics between those who did and did not undergo a urine culture. Data analyses were performed between January 2023 and January 2024. Exposures: Performance of urine culture within 30 days prior to surgery. Main Outcomes and Measures: The 2 main outcomes were UTI and SSI occurring within 30 days after surgery. Weighted logistic regression was used to estimate odds ratios (ORs) for postoperative infection based on treatment status. Results: A total of 250 389 VA enrollees who underwent 288 858 surgical procedures were included, with 88.9% (256 753) of surgical procedures received by males and 48.9% (141 340) received by patients 65 years or older. Baseline characteristics were well balanced among treatment groups after applying IPTW weights. Preoperative urine culture was performed for 10.5% of surgical procedures (30 384 of 288 858). The IPTW analysis found that preoperative urine culture was not associated with SSI (adjusted OR [AOR], 0.99; 95% CI, 0.90-1.10) or postoperative UTI (AOR, 1.18; 95% CI, 0.98-1.40). In analyses limited to orthopedic surgery and neurosurgery as a proxy for prosthetic implants, the adjusted risks for UTI and SSI were also not associated with preoperative urine culture performance. Conclusions and Relevance: This cohort study found no association between performance of a preoperative urine culture and lower risk of postoperative UTI or SSI. The results support the deimplementation of urine cultures and associated antibiotic treatment prior to surgery, even when using prosthetic implants.


Asunto(s)
Procedimientos Ortopédicos , Infección de la Herida Quirúrgica , Estados Unidos/epidemiología , Masculino , Humanos , Puntaje de Propensión , Estudios de Cohortes , Infección de la Herida Quirúrgica/diagnóstico , Infección de la Herida Quirúrgica/epidemiología , Urinálisis , Antibacterianos/uso terapéutico
7.
Am J Occup Ther ; 78(2)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38345946

RESUMEN

IMPORTANCE: Occupational therapy practitioners use yoga in practice to achieve holistic care, and the American Occupational Therapy Association has provided guidance on the use of yoga in occupational therapy. For people with acquired brain injury (ABI), however, it is unknown whether yoga affects occupational performance. OBJECTIVE: To explore the perceived impact of an adapted yoga intervention on occupational performance using the Occupational Therapy Practice Framework: Domain and Process (4th ed.; OTPF-4) for participants with ABI. DESIGN: Qualitative descriptive study using virtual, semistructured interviews. An inductive, holistic, open-coding process, followed by a deductive process to map open codes to the OTPF-4. PARTICIPANTS: Nine individuals with ABI were recruited from a yoga intervention study. RESULTS: The theme generated from the data-"Yoga participants with ABI realized that they could still do quite a bit"-was supported by two major categories from the OTPF-4: Occupations and Performance Skills. Participants described improvements in their functional performance (i.e., motor skills, process skills) and how these factors were synergistically connected to their occupational performance (i.e., self-care, leisure). CONCLUSIONS AND RELEVANCE: This study provides novel insight into how functional performance improved so participants could "still do things," such as engaging in occupations. When participants described improved performance skills, they simultaneously described re-engagement with their meaningful occupations. Participants also perceived an improvement in their mind-body connection, which should be further explored in future studies. This study generated original findings about participants' perceptions of an adapted yoga intervention as they relate to the OTPF-4. Plain-Language Summary: This study reports individuals' perceptions of their re-engagement with occupations and changes in occupational performance skills after participating in an adaptive yoga intervention. We highlight the distinct contribution that adaptive yoga-an intervention modality that can be used by occupational therapy practitioners-may have, using the OTPF-4 to connect the participants' perceptions about their improvements in occupational performance.


Asunto(s)
Lesiones Encefálicas , Meditación , Terapia Ocupacional , Yoga , Humanos , Actividades Recreativas
8.
J Parkinsons Dis ; 14(1): 81-94, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38189765

RESUMEN

BACKGROUND: Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are characterized by diffuse spread of alpha-synuclein (α-syn) throughout the brain. Patients with PDD and DLB have a neuropsychological pattern of deficits that include executive dysfunction, such as abnormalities in planning, timing, working memory, and behavioral flexibility. The prefrontal cortex (PFC) plays a major role in normal executive function and often develops α-syn aggregates in DLB and PDD. OBJECTIVE: To investigate the long-term behavioral and cognitive consequences of α-syn pathology in the cortex and characterize pathological spread of α-syn. METHODS: We injected human α-syn pre-formed fibrils into the PFC of wild-type male mice. We then assessed the behavioral and cognitive effects between 12- and 21-months post-injection and characterized the spread of pathological α-syn in cortical, subcortical, and brainstem regions. RESULTS: We report that PFC PFFs: 1) induced α-syn aggregation in multiple cortical and subcortical regions with sparse aggregation in midbrain and brainstem nuclei; 2) did not affect interval timing or spatial learning acquisition but did mildly alter behavioral flexibility as measured by intraday reversal learning; and 3) increased open field exploration. CONCLUSIONS: This model of cortical-dominant pathology aids in our understanding of how local α-syn aggregation might impact some symptoms in PDD and DLB.


Asunto(s)
Enfermedad de Alzheimer , Demencia , Enfermedad de Parkinson , Humanos , Masculino , Ratones , Animales , alfa-Sinucleína/metabolismo , Enfermedad de Parkinson/patología , Corteza Prefrontal/patología
9.
J Urol ; 211(1): 144-152, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37820311

RESUMEN

PURPOSE: Recurrent cystitis guidelines recommend relying on a local antibiogram or prior urine culture to guide empirical prescribing, yet little data exist to quantify the predictive value of a prior culture. We constructed a urinary antibiogram and evaluated test metrics (sensitivity, specificity, and Bayes' positive and negative predictive values) of a prior gram-negative organism on predicting subsequent resistance or susceptibility among patients with uncomplicated, recurrent cystitis. MATERIALS AND METHODS: We performed a retrospective database study of adults with recurrent, uncomplicated cystitis (cystitis occurring 2 times in 6 months or 3 times in 12 months) from urology or primary care clinics between November 1, 2016, and December 31, 2018. We excluded pregnant females, patients with complicated cystitis, or pyelonephritis. Test metrics were calculated between sequential, paired cultures using standard formulas. RESULTS: We included 597 visits from 232 unique patients wherein 310 (51.2%) visits had a urine culture and 165 had gram-negative uropathogens isolated. Patients with gram-negative uropathogens were mostly females (97%), with a median age of 58.5 years. Our antibiogram found 38.0%, 27.9%, and 5.5% of Escherichia coli isolates had resistance to trimethoprim-sulfamethoxazole, ciprofloxacin, and nitrofurantoin, respectively. Prior cultures (within 2 years) had good predictive value for detecting future susceptibility to first-line agents nitrofurantoin (0.85) and trimethoprim-sulfamethoxazole (0.78) and excellent predictive values (≥0.90) for cefepime, ceftriaxone, cefuroxime, ciprofloxacin, levofloxacin, gentamicin, tobramycin, piperacillin-tazobactam, and imipenem. CONCLUSIONS: Considerable antibiotic resistance was detected among E coli isolates in patients with recurrent, uncomplicated cystitis. Using a prior culture as a guide can enhance the probability of selecting an effective empirical agent.


Asunto(s)
Cistitis , Infecciones Urinarias , Adulto , Femenino , Humanos , Persona de Mediana Edad , Masculino , Combinación Trimetoprim y Sulfametoxazol , Nitrofurantoína , Escherichia coli , Estudios Retrospectivos , Teorema de Bayes , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/diagnóstico , Ciprofloxacina , Cistitis/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Farmacorresistencia Bacteriana
11.
JAMA Netw Open ; 6(7): e2324516, 2023 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-37471087

RESUMEN

Importance: While current evidence has demonstrated a surgical site infection (SSI) prevention bundle consisting of preoperative Staphylococcus aureus screening, nasal and skin decolonization, and use of appropriate perioperative antibiotic based on screening results can decrease rates of SSI caused by S aureus, it is well known that interventions may need to be modified to address facility-level factors. Objective: To assess the association between implementation of an SSI prevention bundle allowing for facility discretion regarding specific component interventions and S aureus deep incisional or organ space SSI rates. Design, Setting, and Participants: This quality improvement study was conducted among all patients who underwent coronary artery bypass grafting, cardiac valve replacement, or total joint arthroplasty (TJA) at 11 Veterans Administration hospitals. Implementation of the bundle was on a rolling basis with the earliest implementation occurring in April 2012 and the latest implementation occurring in July 2017. Data were collected from January 2007 to March 2018 and analyzed from October 2020 to June 2023. Interventions: Nasal screening for S aureus; nasal decolonization of S aureus carriers; chlorhexidine bathing; and appropriate perioperative antibiotic prophylaxis according to S aureus carrier status. Facility discretion regarding how to implement the bundle components was allowed. Main Outcomes and Measures: The primary outcome was deep incisional or organ space SSI caused by S aureus. Multivariable logistic regression with generalized estimating equation (GEE) and interrupted time-series (ITS) models were used to compare SSI rates between preintervention and postintervention periods. Results: Among 6696 cardiac surgical procedures and 16 309 TJAs, 95 S aureus deep incisional or organ space SSIs were detected (25 after cardiac operations and 70 after TJAs). While the GEE model suggested a significant association between the intervention and decreased SSI rates after TJAs (adjusted odds ratio, 0.55; 95% CI, 0.31-0.98), there was not a significant association when an ITS model was used (adjusted incidence rate ratio, 0.88; 95% CI, 0.32-2.39). No significant associations after cardiac operations were found. Conclusions and Relevance: Although this quality improvement study suggests an association between implementation of an SSI prevention bundle and decreased S aureus deep incisional or organ space SSI rates after TJAs, it was underpowered to see a significant difference when accounting for changes over time.


Asunto(s)
Infecciones Estafilocócicas , Veteranos , Humanos , Staphylococcus aureus , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/prevención & control , Infección de la Herida Quirúrgica/etiología , Antibacterianos/uso terapéutico , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/prevención & control
12.
J Allergy Clin Immunol Pract ; 11(9): 2848-2854.e3, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37352930

RESUMEN

BACKGROUND: Unconfirmed penicillin allergies are common and may contribute to adverse outcomes, especially in frail older patients. Evidence-based clinical pathways for evaluating penicillin allergies have been effectively and safely applied in selected settings, but not in nursing home populations. OBJECTIVE: To identify potential facilitators and barriers to implementing a strategy to verify penicillin allergies in Veterans Health Administration nursing homes, known as Community Living Centers (CLCs). METHODS: We conducted semistructured interviews with staff, patients, and family members at 1 CLC to assess their understanding of penicillin allergies and receptiveness to verifying the allergy. We also asked staff about the proposed allergy assessment strategy, including willingness to delabel by history and feasibility of performing oral challenges or skin testing on their unit. RESULTS: From 24 interviews (11 front-line staff, 4 leadership, 3 patients, 6 family members), we identified several facilitators or barriers. Staff recognized the importance of allergy verification and were willing to support and assist in implementing verification strategies. The CLC residents were willing to have their allergy status verified. However, some family members expressed reluctance to verifying their relative's allergy status owing to safety concerns. Front-line staff also expressed concern over having the necessary resources, including time and expertise, to implement the strategy. Staff suggested involving clinical pharmacists and educating staff, patients, and family members as ways to overcome these barriers. CONCLUSIONS: Concerns about safety and staff resources are important potential barriers to implementing verification strategies. Involvement of pharmacists and education of both staff and patients and family members will be important components of any successful intervention.


Asunto(s)
Hipersensibilidad , Veteranos , Humanos , Casas de Salud , Farmacéuticos , Penicilinas/efectos adversos
13.
Infect Control Hosp Epidemiol ; 44(10): 1693-1696, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37039605

RESUMEN

Sickness presenteeism among healthcare workers (HCW) risks nosocomial infection, but its prevalence among HCW with COVID-19 is unknown. Contemporaneous interviews revealed a sickness presenteeism prevalence of 49.8% among 255 HCW with symptomatic COVID-19. Presenteeism prevalence did not differ among HCW with and without specific COVID-19 symptoms or direct patient care.


Asunto(s)
COVID-19 , Humanos , Presentismo , Pandemias , Estudios Transversales , Estudios de Cohortes , Personal de Salud
14.
JAMA Netw Open ; 6(3): e234876, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36976565

RESUMEN

This cohort study emulates a trial within a large national veteran population to assess the risk of adverse postoperative outcomes among patients with recent COVID-19 infection.


Asunto(s)
COVID-19 , Humanos , Personal de Salud , SARS-CoV-2 , Resultado del Tratamiento , Estudios de Cohortes
15.
Artículo en Inglés | MEDLINE | ID: mdl-36483431

RESUMEN

Prophylaxis against spontaneous bacterial peritonitis (SBP) is recommended for select patients with cirrhosis, but long-term antibiotic therapy has risks. We evaluated concordance with guideline recommendations in 179 veterans with cirrhosis; 55% received guideline-concordant management of SBP prophylaxis. Despite stable guideline recommendations since 2012, guideline adherence remains low.

16.
Artículo en Inglés | MEDLINE | ID: mdl-36310787

RESUMEN

Objectives: We characterized antibiotic prescribing patterns and management practices among recurrent urinary tract infection (rUTI) patients, and we identified factors associated with lack of guideline adherence to antibiotic choice, duration of treatment, and urine cultures obtained. We hypothesized that prior resistance to nitrofurantoin or trimethoprim-sulfamethoxazole (TMP-SMX), shorter intervals between rUTIs, and more frequent rUTIs would be associated with fluoroquinolone or ß-lactam prescribing, or longer duration of therapy. Methods: This study was a retrospective database study of adult women with International Classification of Diseases, Tenth Revision (ICD-10) cystitis codes meeting American Urological Association rUTI criteria at outpatient clinics within our academic medical center between 2016 and 2018. We excluded patients with ICD-10 codes indicative of complicated UTI or pyelonephritis. Generalized estimating equations were used for risk-factor analysis. Results: Among 214 patients with 566 visits, 61.5% of prescriptions comprised first-line agents of nitrofurantoin (39.7%) and TMP-SMX (21.5%), followed by second-line choices of fluoroquinolones (27.2%) and ß-lactams (11%). Most fluoroquinolone prescriptions (86.7%), TMP-SMX prescriptions (72.2%), and nitrofurantoin prescriptions (60.2%) exceeded the guideline-recommended duration. Approximately half of visits lacked a urine culture. Receiving care through urology via telephone was associated with receiving a ß-lactam (adjusted odds ratio [aOR], 6.34; 95% confidence interval [CI], 2.58-15.56) or fluoroquinolone (OR, 2.28; 95% CI, 1.07-4.86). Having >2 rUTIs during the study period and seeking care from a urology practice (RR, 1.28, 95% CI, 1.15-1.44) were associated with longer antibiotic duration. Conclusions: We found low guideline concordance for antibiotic choice, duration of therapy and cultures obtained among rUTI patients. These factors represent new targets for outpatient antibiotic stewardship interventions.

18.
JAMA Netw Open ; 5(6): e2216176, 2022 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-35675074

RESUMEN

Importance: Aerosol-borne SARS-CoV-2 has not been linked specifically to nosocomial outbreaks. Objective: To explore the genomic concordance of SARS-CoV-2 from aerosol particles of various sizes and infected nurses and patients during a nosocomial outbreak of COVID-19. Design, Setting, and Participants: This cohort study included patients and nursing staff in a US Department of Veterans Affairs inpatient hospital unit and long-term-care facility during a COVID-19 outbreak between December 27, 2020, and January 8, 2021. Outbreak contact tracing was conducted using exposure histories and screening with reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV-2. Size-selective particle samplers were deployed in diverse clinical areas of a multicampus health care system from November 2020 to March 2021. Viral genomic sequences from infected nurses and patients were sequenced and compared with ward nurses station aerosol samples. Exposure: SARS-CoV-2. Main Outcomes and Measures: The primary outcome was positive RT-PCR results and genomic similarity between SARS-CoV-2 RNA in aerosols and human samples. Air samplers were used to detect SARS-CoV-2 RNA in aerosols on hospital units where health care personnel were or were not under routine surveillance for SARS-CoV-2 infection. Results: A total of 510 size-fractionated air particle samples were collected. Samples representing 3 size fractions (>10 µm, 2.5-10 µm, and <2.5 µm) obtained at the nurses station were positive for SARS-CoV-2 during the outbreak (3 of 30 samples [10%]) and negative during 9 other collection periods. SARS-CoV-2 partial genome sequences for the smallest particle fraction were 100% identical with all 3 human samples; the remaining size fractions shared >99.9% sequence identity with the human samples. Fragments of SARS-CoV-2 RNA were detected by RT-PCR in 24 of 300 samples (8.0%) in units where health care personnel were not under surveillance and 7 of 210 samples (3.3%; P = .03) where they were under surveillance. Conclusions and Relevance: In this cohort study, the finding of genetically identical SARS-CoV-2 RNA fragments in aerosols obtained from a nurses station and in human samples during a nosocomial outbreak suggests that aerosols may have contributed to hospital transmission. Surveillance, along with ventilation, masking, and distancing, may reduce the introduction of community-acquired SARS-CoV-2 into aerosols on hospital wards, thereby reducing the risk of hospital transmission.


Asunto(s)
COVID-19 , Infección Hospitalaria , Estaciones de Enfermería , Aerosoles , COVID-19/epidemiología , Estudios de Cohortes , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Brotes de Enfermedades , Hospitales , Humanos , ARN Viral , SARS-CoV-2/genética , Estados Unidos
19.
Cancer Discov ; 12(8): 1886-1903, 2022 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-35554512

RESUMEN

Chimeric antigen receptor T-cell (CAR-T cell) therapy directed at CD19 produces durable remissions in the treatment of relapsed/refractory non-Hodgkin lymphoma (NHL). Nonetheless, many patients receiving CD19 CAR-T cells fail to respond for unknown reasons. To reveal changes in 4-1BB-based CD19 CAR-T cells and identify biomarkers of response, we used single-cell RNA sequencing and protein surface marker profiling of patient CAR-T cells pre- and postinfusion into patients with NHL. At the transcriptional and protein levels, we note the evolution of CAR-T cells toward a nonproliferative, highly differentiated, and exhausted state, with an enriched exhaustion profile in CAR-T cells of patients with poor response marked by TIGIT expression. Utilizing in vitro and in vivo studies, we demonstrate that TIGIT blockade alone improves the antitumor function of CAR-T cells. Altogether, we provide evidence of CAR-T cell dysfunction marked by TIGIT expression driving a poor response in patients with NHL. SIGNIFICANCE: This is the first study investigating the mechanisms linked to CAR-T patient responses based on the sequential analysis of manufactured and infused CAR-T cells using single-cell RNA and protein expression data. Furthermore, our findings are the first to demonstrate an improvement of CAR-T cell efficacy with TIGIT inhibition alone. This article is highlighted in the In This Issue feature, p. 1825.


Asunto(s)
Linfoma no Hodgkin , Receptores Quiméricos de Antígenos , Receptores Inmunológicos , Linfocitos T , Antígenos CD19 , Humanos , Inmunoterapia Adoptiva , Linfoma no Hodgkin/genética , Receptores de Antígenos de Linfocitos T , Receptores Quiméricos de Antígenos/genética , Receptores Inmunológicos/genética , Linfocitos T/patología
20.
Contemp Clin Trials ; 116: 106756, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35398532

RESUMEN

BACKGROUND: Although many large, randomized controlled trials (RCT) have been conducted on antibiotic therapy for patients with primary C. difficile infections (CDI), few RCTs have been performed for patients with recurrent CDI (rCDI). In addition, fecal microbial transplant (FMT) is neither FDA-approved or guideline-recommended for patients with pauci-rCDI (first or second recurrences). Therefore, a rigorous RCT of sufficient size was designed to determine the optimal treatment among three antibiotic regimens in current practice for treatment of pauci-rCDI. METHODS: VA Cooperative Studies Program (CSP) #596 is a prospective, double-blind, multi-center clinical trial of veteran patients with pauci-rCDI comparing fidaxomicin (FDX) 200 mg twice daily for 10 days and vancomycin (VAN) 125 mg four times daily for 10 days followed by a 3-week vancomycin taper and pulse (VAN-T/P) regimen to a standard course of VAN 125 mg four times daily for 10 days. The primary endpoint is sustained clinical response at day 59, with sustained response measured as a diarrhea composite outcome (D-COM) that includes symptom resolution during treatment (before day 10) without recurrence of diarrhea or other clinically important outcomes through day 59. DISCUSSION: CSP study 596 is designed to compare three current antibiotic treatments for recurrent CDI that are in clinical practice, but which lack high-quality evidence to support strong guideline recommendations. The design of the study which included a pilot phase initiated at six sites with expansion to 24 sites is described along with protocol modifications based on early trial experience and clinical realities including the COVID-19 pandemic. TRIAL REGISTRATION: This study is registered with clinicaltrials.gov (Identifier: NCT02667418).


Asunto(s)
COVID-19 , Clostridioides difficile , Infecciones por Clostridium , Antibacterianos , Infecciones por Clostridium/diagnóstico , Infecciones por Clostridium/tratamiento farmacológico , Diarrea/inducido químicamente , Diarrea/tratamiento farmacológico , Fidaxomicina/uso terapéutico , Humanos , Recurrencia , Resultado del Tratamiento , Vancomicina/uso terapéutico
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