Category: Statistics

JAMA Netw Open. 2025 Jan 2;8(1):e2454253. doi: 10.1001/jamanetworkopen.2024.54253.

ABSTRACT

IMPORTANCE: The open-label randomized phase 2 LACOG0415 trial evaluated 3 treatment strategies for patients with advanced castration-sensitive prostate cancer (CSPC): androgen deprivation therapy (ADT) plus abiraterone acetate and prednisone (AAP), apalutamide (APA) alone, or APA plus AAP.

OBJECTIVE: To investigate the association of ADT plus AAP, APA alone, or APA plus AAP with health-related quality of life (HRQOL) in patients with advanced CSPC in the LACOG0415 trial.

DESIGN, SETTING, AND PARTICIPANTS: The LACOG0415 randomized clinical trial comprised 128 patients with advanced CSPC who were randomized (1:1:1) to 1 of 3 treatment arms from October 16, 2017, to April 23, 2019. Statistical analysis was conducted from March to September 2022.

INTERVENTIONS: Patients were randomized (1:1:1) to 1 of 3 treatment arms: ADT plus AAP, APA alone, or APA plus AAP.

MAIN OUTCOMES AND MEASURES: Health-related quality of life was evaluated using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, including its subscales, completed at baseline and every 4 weeks until week 25. FACT-P scores range from 0 to 156, and higher scores indicate better HRQOL. Mean changes in score from baseline to week 25 were adjusted by baseline score and were calculated to evaluate whether there was a difference according to the treatment arm using a mixed-effect model for repeated measures. Time to deterioration was estimated by Kaplan-Meier curves and compared by stratified log-rank test. Analysis was performed on an intention-to-treat basis.

RESULTS: A total of 128 patients with advanced CSPC were randomized to receive ADT plus AAP (n = 42; median age, 69.8 years [IQR, 58.9-71.6 years]), APA alone (n = 42; median age, 69.5 years [IQR, 59.8-72.6 years]), or APA plus AAP (n = 44; median age, 71.0 years [IQR, 63.0-72.3 years]). Metastatic disease was present in 95 patients (74.2%), high-risk biochemical recurrence disease in 22 (17.2%), and locally advanced disease in 11 (8.6%). There was no significant difference in baseline mean (SD) FACT-P total scores and subscales among the 3 treatment arms (FACT-P total score: ADT plus AAP arm, 118.5 [24.3]; APA alone arm, 116.1 [23.9]; AAP plus APA arm, 114.9 [18.1]; P = .69). Health-related quality of life was maintained during treatment period, and there were no statistically significant differences at 25 weeks in mean (SD) FACT-P total scores or subscales between treatment arms (FACT-P total score: ADT plus AAP arm, 122.3 [20.4]; APA alone arm, 119.5 [16.4]; AAP plus APA arm, 119.9 [20.3]). The APA alone and AAP plus APA arms were not associated with meaningful improvements in HRQOL compared with the ADT plus AAP arm, except in time to deterioration of the emotional well-being score, which was more favorable in the APA alone arm (reference arm: ADT plus AAP arm; APA alone arm: hazard ratio, 0.37 [0.15-0.85]; P = .02; ADT plus AAP arm: hazard ratio, 0.56 [0.26-1.19]; P = .13). Limitations include short follow-up period and the absence of other questionnaires to capture differences between therapies.

CONCLUSIONS AND RELEVANCE: In this prespecified secondary analysis of a randomized clinical trial of ADT plus AAP, APA alone, or APA plus AAP for patients with advanced CSPC, HRQOL was not statistically different between treatments with APA alone or APA plus AAP as compared with ADT plus AAP. Larger studies with longer follow-up and more specific questionnaires are needed to further evaluate HRQOL with these treatment strategies.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02867020.

PMID:39804646 | DOI:10.1001/jamanetworkopen.2024.54253

JAMA Netw Open. 2025 Jan 2;8(1):e2454447. doi: 10.1001/jamanetworkopen.2024.54447.

ABSTRACT

IMPORTANCE: Enhanced breast cancer screening with magnetic resonance imaging (MRI) is recommended to women with elevated risk of breast cancer, yet uptake of screening remains unclear after genetic testing.

OBJECTIVE: To evaluate uptake of MRI after genetic results disclosure and counseling.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study was conducted at the University of Southern California Norris Cancer Hospital, the Los Angeles General Medical Center, and the Stanford University Cancer Institute. Patients were recruited from July 1, 2014, through November 30, 2016. Following multiplex gene panel testing and genetic counseling, patients responded to surveys about breast MRI screening at 3, 6, 12, and 24 months and to a final survey between 3 and 4 years after counseling. Participants met standard clinical criteria for genetic testing or had a 2.5% or greater probability of inherited cancer susceptibility. Patients were categorized based on breast cancer risk from genetic testing results and Tyrer-Cuzick model-calculated risk as having (1) a BRCA or other high-risk pathogenic variant (PV), (2) a moderate-risk PV, (3) a higher lifetime breast cancer risk (≥20%), or (4) a lower lifetime breast cancer risk (<20%). Analysis was conducted from September 28 to November 9, 2023.

INTERVENTIONS: Genetic testing with a 25- or 28-gene panel, and pretest and posttest genetic counseling by a genetic counselor or an advanced practice genetics nurse practitioner, which included cancer-specific screening recommendations.

MAIN OUTCOMES AND MEASURES: MRI screening adherence over time across risk groups was estimated using Cox proportional hazards regression modeling. Likelihood of screening adherence (odds ratios [ORs] with 95% CIs), controlling for potential confounders, was estimated using logistic regression.

RESULTS: This study included 638 patients, with a mean (SD) age of 50.7 (13.3) years at testing. There were 43 patients (6.7%) with a BRCA or other high-risk PV, 16 (2.5%) with a moderate-risk PV, 146 (22.9%) with higher lifetime breast cancer risk, and 433 (67.9%) with lower lifetime breast cancer risk. A total of 52 patients (8.2%) identified as Asian, 21 (3.3%) as Black, 271 (42.5%) as Hispanic, and 255 (40.0) as White. Compared with patients with lower lifetime breast cancer risk, patients with a BRCA or other high-risk PV and those with a moderate-risk PV were approximately 10 times (OR, 9.81 [95% CI, 4.05-23.86]; P < .001) and 4 times (OR, 4.12 [95% CI, 1.10-14.35]; P = .03) as likely to undergo MRI, respectively. Patients with a BRCA or other high-risk PV were nearly 16 times (OR, 15.81 [95% CI, 5.17-48.31]) as likely to report consistent yearly MRI screening compared with patients with lower lifetime risk.

CONCLUSIONS AND RELEVANCE: In this study, women with inherited PVs conferring increased breast cancer risk had higher and more consistent MRI uptake than women with lower estimated risk. These findings emphasize the importance of genetic cancer risk assessment for effective enhanced breast cancer screening.

PMID:39804645 | DOI:10.1001/jamanetworkopen.2024.54447

JAMA Netw Open. 2025 Jan 2;8(1):e2454455. doi: 10.1001/jamanetworkopen.2024.54455.

ABSTRACT

IMPORTANCE: Women who use heroin in sub-Saharan Africa face elevated HIV risk linked to structural vulnerability including frequent incarceration. However, little is known about the association between incarceration and drug use and HIV outcomes among women who use heroin in Africa.

OBJECTIVE: To estimate associations between incarceration and adverse HIV-related and drug use-related outcomes among women who used heroin.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included participants from Dar es Salaam, Tanzania, who were recruited using respondent-driven sampling. Eligible participants were women who used heroin who were aged 18 years or older and reported past-month heroin use. Data were collected from November 2018 to February 2019 and analyzed from September 2023 to May 2024.

EXPOSURE: The exposure was recent incarceration, defined as self-report of being held in prison or jail in the past 6 months.

MAIN OUTCOMES AND MEASURES: Main outcomes were self-reported HIV testing in the past 6 months, self-reported HIV status, and lifetime nonfatal overdose. Associations between recent incarceration and outcomes were examined using modified Poisson regression with robust variance estimation.

RESULTS: This study included 195 women who used heroin (median [IQR] age, 33 [27-39] years); 119 women (61%) reported incarceration in the past 6 months. In bivariate analyses, incarceration was associated with transactional sex (111 of 119 [93.3%]), symptoms of anxiety (104 of 119 [87.4%]), physical violence victimization (83 of 118 [70.3%]), and stigma from family (eg, 99 of 119 women [83.2%] reported being treated differently) and health care clinicians (eg, 46 of 119 women [38.7%] reported receiving poor health care). In adjusted analyses, incarceration was associated with higher prevalence of sexual concurrency (101 of 119 [84.9%] vs 41 of 76 [54.0%]; aPR, 1.43; 95% CI, 1.16-1.78), stimulant use (26 of 119 [21.9%] vs 3 of 76 [4.0%]; aPR, 5.60; 95% CI, 1.63-19.28), and lifetime nonfatal overdose (51 of 119 [42.9%] vs 17 of 76 [22.4%]; aPR, 1.62; 95% CI, 1.01-2.61). Among women who used heroin living with HIV, incarceration was associated with stopping HIV care (9 of 27 [33.3%] vs 1 of 24 [4.2%]; aPR, 9.74; 95% CI, 1.22-77.22).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of HIV-related outcomes among recently incarcerated women who used heroin in sub-Saharan Africa, behavioral and structural vulnerabilities associated with incarceration were identified, which may exacerbate HIV disparities. Elevated stimulant use among recently incarcerated women who used heroin is of particular concern, given associations with adverse HIV outcomes. In the context of highly criminalized drug use, interventions targeting policing practices may be effective at reducing incarceration-associated risks. Findings could inform development and evaluation of multilevel interventions to reduce service interruptions and ensure linkage to HIV and substance use services during incarceration and reentry.

PMID:39804644 | DOI:10.1001/jamanetworkopen.2024.54455

JAMA Netw Open. 2025 Jan 2;8(1):e2454516. doi: 10.1001/jamanetworkopen.2024.54516.

ABSTRACT

IMPORTANCE: Literature suggests that well-being and health status differ by generational status among Asian American individuals.

OBJECTIVE: To compare young children’s well-being and health behaviors and their parents’ parenting practices among families of second-generation Asian American, third- or later-generation Asian American, and third- or later-generation non-Hispanic White children in the US.

DESIGN, SETTING, AND PARTICIPANTS: For this survey study, secondary data analysis was conducted from September 2, 2023, to June 19, 2024, using data from the 2018 to 2022 National Survey of Children’s Health participants aged 6 months to 5 years. Parents completed a survey about their positive parenting practices and their child’s psychological well-being and health behaviors via mail or online. Multivariable logistic and linear regression analyses were conducted to compare psychological well-being and health behaviors by study groups and positive parenting practices, adjusting for sociodemographic variables.

MAIN OUTCOMES AND MEASURES: Positive parenting practices (ie, reading, storytelling or singing, and family meals), psychological well-being (ie, flourishing, social-emotional development, and self-regulation), and health behaviors.

RESULTS: The analysis included 42 846 participants (5456 in 2018, 5140 in 2019, 7494 in 2020, 12 817 in 2021, and 11 939 in 2022; 46.6% female and 53.4% male). Participants were categorized into 3 groups: 2881 (6.7%) were second-generation Asian American children aged 0 to 5 years, 570 (1.3%) third- or later-generation Asian American children aged 0 to 5 years, and 39 395 (92.0%) third- or later-generation non-Hispanic White children aged 0 to 5 years. Compared with White children, Asian American children were less likely to flourish (odds ratio [OR], 0.57 [95% CI, 0.52-0.63] for second-generation Asian American; OR, 0.82 [95% CI, 0.65-1.03] for third- or later-generation Asian American), have regular bedtimes (OR, 0.80 [95% CI, 0.69-0.92] for second-generation Asian American; OR, 0.66 [95% CI, 0.49-0.88] for third- or later-generation Asian American), and have moderate screen time (OR, 0.92 [95% CI, 0.84-1.00] for second-generation Asian American; OR, 0.82 [95% CI, 0.69-0.97] for third- or later-generation Asian American). Results for regular reading and storytelling or singing were the lowest among second-generation Asian American children (1430 [49.6%] for reading and 1629 [56.5%] for storytelling or singing), followed by the third- or later-generation Asian American children (376 [66.0%] for reading and 412 [72.3%] for storytelling or singing) and than White children (28 628 [72.7%] for reading and 30 375 [77.1%] for storytelling or singing) (P < .001). Results for family meals were similar between second-generation (2356 [81.8%]) and third- or later-generation (467 [81.9%]) Asian American children; however, both were significantly lower than for White children (33 928 [86.1%]) (P < .001). All 3 positive parenting practices were positively associated with children’s psychological well-being and health behaviors.

CONCLUSIONS AND RELEVANCE: This survey study of young children found lower likelihoods of flourishing, regular bedtimes, and moderate screen time among Asian American children compared with non-Hispanic White children in the US. Reading and storytelling or singing parenting practices, which were associated with children’s well-being and health behaviors, were particularly less frequent among parents of second-generation Asian American children than those of third- or later-generation Asian American children. Promotion of these practices among Asian immigrant parents may help improve the psychological well-being and health behaviors of their young Asian American children.

PMID:39804643 | DOI:10.1001/jamanetworkopen.2024.54516

JAMA Netw Open. 2025 Jan 2;8(1):e2454565. doi: 10.1001/jamanetworkopen.2024.54565.

ABSTRACT

IMPORTANCE: Improving access to high-quality maternity care and reducing maternal morbidity and mortality are major policy priorities in the US. Previous research has primarily focused on access to general obstetric care rather than access to high-risk pregnancy care provided by maternal-fetal medicine subspecialists (MFMs).

OBJECTIVE: To measure access to MFM services and determine patient factors associated with MFM service use, including MFM telemedicine.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study identified pregnancies in commercial health insurance claims from the Health Care Cost Institute from 2016 to 2021. More than 2.1 million pregnancies were included, where age at delivery was 18 years or greater and people were continuously enrolled for the duration of their pregnancy. The association of patient and pregnancy covariates with MFM involvement in care was analyzed using logistic regression; and rates of telemedicine for pregnancies in urban and rural areas were reported over time. Data were analyzed from June 2022 to March 2024.

MAIN OUTCOMES AND MEASURES: Primary study outcomes included whether a pregnancy ever had a service from an MFM, the type of MFM services provided, and whether MFM care occurred via telemedicine.

RESULTS: There were 2 169 026 pregnancies among 1 968 091 unique people (1 325 212 [61.2%] aged 25 to 34 years). Among 1 625 237 pregnancies at risk for conditions that might require MFM involvement, 838 493 (51.6%) had an MFM service. Rates of MFM involvement in care varied considerably by geography, with pregnancies in rural areas having lower use than urban areas. Use of telemedicine-enabled MFM care increased in 2020 and 2021 but remained low: in 2021, 2.7% of urban pregnancies (7535 of 276 599) and 1.7% of rural pregnancies (550 of 32 949) received telemedicine-enabled MFM care.

CONCLUSIONS AND RELEVANCE: In this cohort study, access to MFM services varied across geography, even among pregnancies at risk for conditions that might require MFM involvement. These results suggested a need to improve access to MFM care for at-risk pregnancies and to further explore expanded access via telemedicine.

PMID:39804642 | DOI:10.1001/jamanetworkopen.2024.54565

JAMA Netw Open. 2025 Jan 2;8(1):e2454694. doi: 10.1001/jamanetworkopen.2024.54694.

ABSTRACT

IMPORTANCE: Compared with cisgender (CG) individuals, transgender and gender-diverse (TGD) individuals experience substantial social and economic disparities that can result in adverse mental health consequences. It is critical to understand potential barriers to care and to address the causes of the disparities in the future.

OBJECTIVE: To characterize mental health care utilization among TGD veterans with depression.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used electronic health record data from the US Department of Veterans Affairs (VA) to create a 1:3 age group-matched and VA facility-matched nationwide cohort of TGD and CG veterans with documentation of depression during 2018 to 2020. Data analysis was performed from January to November 2023.

EXPOSURE: TGD identity was ascertained by diagnosis of a gender identity disorder.

MAIN OUTCOMES AND MEASURES: The primary outcome was mental health care utilization, including counts of outpatient (in specialty care and primary care settings), telehealth, emergency department, and inpatient visits in this cohort. Descriptive statistics were used to characterize counts of mental health utilization, and statistically significant differences between TGD and CG veterans were tested using χ2 and Fisher exact tests. Wilcoxon rank-sum tests were used to test for differences in utilization between the 2 groups. Adjusted logistic regression, controlling for age group, administrative sex, race, Charlson Comorbidity Index, and number of mental health medications (eg, antidepressant, antipsychotic, and anxiolytic medications), was also used to compare utilization between TGD and CG veterans.

RESULTS: Among 10 564 veterans with depression (mean [SD] age, 46.4 [15.2] years; 8050 male [76.2%]), 2643 TGD veterans were matched with 7921 CG veterans. TGD veterans had 6 more specialty mental health visits per year than CG veterans (mean [SD], 13.93 [20.08] vs 8.46 [14.96] visits a year; median [range], 7.14 [0.00-246.30] vs 3.76 [0.00-202.38] visits per year). In adjusted models, compared with CG veterans, TGD veterans were 2.6 times more likely to have an outpatient mental-health visit (odds ratio, 2.60; 95% CI, 2.16-3.15).

CONCLUSIONS AND RELEVANCE: In this cohort study of veterans with depression, TGD veterans had significantly higher utilization of mental health services compared with CG veterans, even after adjusting for several relevant health factors. Different health system resources may be required to meet the needs of this population. Further studies are needed to understand the determinants of these disparities and subsequently how to address them.

PMID:39804641 | DOI:10.1001/jamanetworkopen.2024.54694

JAMA Neurol. 2025 Jan 13. doi: 10.1001/jamaneurol.2024.4631. Online ahead of print.

ABSTRACT

IMPORTANCE: There is a lack of long-term efficacy and safety data on hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN) and on RNA interference (RNAi) therapeutics in general. This study presents the longest-term data to date on patisiran for hATTR-PN.

OBJECTIVE: To present the long-term efficacy and safety of patisiran in adults with hATTR-PN.

DESIGN, SETTING, AND PARTICIPANTS: This global open-label extension (OLE) of the APOLLO randomized clinical trial and phase 2 OLE study enrolled patients from 43 hospitals or clinical centers across 19 countries between July 2015 and August 2017, with follow-up until November 2022. Of 212 eligible patients with hATTR who completed the phase 3 APOLLO or phase 2 OLE parent studies, 211 enrolled in and 138 completed the global OLE.

INTERVENTION: Patisiran, 0.3 mg/kg, intravenously once every 3 weeks for up to 5 years.

MAIN OUTCOMES AND MEASURES: Outcomes evaluated at year 5 of the global OLE included disability (polyneuropathy disability [PND] score); polyneuropathy severity (Neuropathy Impairment Score [NIS]), nutritional status (modified body mass index [mBMI]), quality of life (Norfolk Quality of Life-Diabetic Neuropathy [Norfolk QOL-DN]), and Rasch-Built Overall Disability Scale (R-ODS), with no statistical hierarchy. Safety, survival probability, and mortality were also assessed.

RESULTS: At the global OLE baseline, the mean (SD) age was 61.3 (12.3) years, and 156 patients (73.9%) were male. In 138 patients completing the study, PND scores remained stable or improved in 89 patients (65.0%), NISs showed a mean (SD) change of 10.9 (14.7), and mean (SD) mBMI (calculated as weight in kilograms divided by height in meters squared times serum albumin in grams per liter) increased by 46.4 (120.7) over 5 years from baseline. Norfolk QOL-DN and R-ODS scores showed mean (SD) changes of 4.1 (16.7) and -3.7 (6.2), respectively. Adverse events (AEs) leading to study withdrawal occurred in 47 patients (22.3%). Infusion-related reactions were the most common treatment-related AE (n = 34 [16.1%]). Overall, 41 patients (19.4%) died during the study. Patisiran treatment in the parent study and low familial amyloid polyneuropathy score at parent study baseline were associated with significantly improved survival.

CONCLUSIONS AND RELEVANCE: In the longest study of an RNAi therapeutic for any disease, patisiran treatment resulted in modest changes for patients with hATTR-PN with an acceptable safety profile. These results highlight the importance of initiating early treatment for hATTR and the potential of RNAi therapeutics in medicine.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02510261.

PMID:39804640 | DOI:10.1001/jamaneurol.2024.4631

Invest Ophthalmol Vis Sci. 2025 Jan 2;66(1):31. doi: 10.1167/iovs.66.1.31.

ABSTRACT

PURPOSE: This study aimed to comprehensively assess visual performance in eyes with idiopathic epiretinal membrane (iERM). Additionally, it sought to explore the associations between optical coherence tomography (OCT) imaging biomarkers and visual performance in patients with iERM.

METHODS: In this prospective, non-interventional study, 57 participants with treatment-naïve iERM from the University of Turin, between September 2023 and March 2024 were enrolled. Visual performance was measured using distance best-corrected visual acuity (BCVA), near BCVA, and maximum reading speed (MaxRS). Structural retinal imaging biomarkers were obtained from OCT, focusing on retinal layer thicknesses and epiretinal membrane characteristics. Statistical analyses, including linear regression and multivariate analysis, were used to determine relationships between visual function and imaging metrics.

RESULTS: Monocular distance BCVA (0.37 ± 0.23 LogMAR), near BCVA (0.59 ± 0.18 LogMAR), and MaxRS (108.88 [68.38] words per minute [wpm]) in patients with iERM were significantly reduced compared with reference values. Both near BCVA and reading speed exhibited a greater percentage reduction than distance visual acuity. Patients with phakic showed worse visual acuity than patients with pseudophakia, although their reading performance was similar. Higher outer plexiform layers thickness and inner retinal thickness were associated with decreased distance and near visual acuity and reduced reading speed (beta, P value).

CONCLUSIONS: The iERM predominantly impacts near visual performance, with near visual acuity and reading speed being more affected than distance visual acuity. Structural OCT biomarkers, particularly retinal thickness in specific regions, correlate with worse functional impairments. This highlights the importance of near vision assessments and imaging biomarkers for a comprehensive evaluation of visual impairment in iERM.

PMID:39804627 | DOI:10.1167/iovs.66.1.31

Sleep Breath. 2025 Jan 13;29(1):73. doi: 10.1007/s11325-024-03231-w.

ABSTRACT

BACKGROUND: Fatigue, sleep disorders, and daytime sleepiness are interconnected, posing significant risks to occupational health and workplace safety. However, the literature on their relationships remains fragmented, with notable gaps, particularly concerning working populations. This descriptive cross-sectional study aimed to evaluate sleep quality (SQ), daily sleep time in hours (DST), daytime sleepiness, fatigue levels among employees in an automotive workplace, and their interrelationships.

METHODS: This study assessed fatigue, DST, SQ, and daytime sleepiness (DTS) among employees aged 21-51 years working under the same conditions. Data were collected using questionnaires and two validated scales: the Check Individual Strength Scale (CIS) for fatigue and the Epworth Sleepiness Scale (ESS) for excessive daytime sleepiness.

RESULTS: None of the Check Individual Strength Scale (CIS), or SQ points, mean values or DST hours values significantly differ due to any sociodemographic independent variables. Epworth Sleepiness Scale (ESS) points mean values differ significantly due to BMI values. However, statistically significant relationships were identified among CIS, ESS, SQ points, and DST hours. Additionally, a positive correlation was observed between ESS and CIS scores. These findings suggest reciprocal effects among fatigue, SQ, DST, and daytime sleepiness.

CONCLUSION: While sleep problems cause fatigue also chronic fatigue syndrome may be the reason of worse SQ. Further research is necessary to emphasize the importance of addressing the interplay between fatigue, excessive daytime sleepiness, SQ, and DST in hours to improve workplace safety and employee well-being.

PMID:39804542 | DOI:10.1007/s11325-024-03231-w

Dig Dis Sci. 2025 Jan 13. doi: 10.1007/s10620-024-08828-5. Online ahead of print.

ABSTRACT

BACKGROUND: Pouchitis is common among patients with ulcerative colitis (UC) who have had colectomy with ileal pouch-anal anastomosis. Antibiotics are first-line therapy for pouch inflammation, increasing the potential for gut colonization with multi-drug resistant organisms (MDRO). Fecal microbial transplant (FMT) is being studied in the treatment of pouchitis and in the eradication of MDRO. Prior work using aerobic antibiotic culture disks suggests that some patients with chronic pouchitis may regain fluoroquinolone sensitivity after FMT. However, gut MDRO include anaerobic, fastidious organisms that are difficult to culture using traditional methods.

AIM: We aimed to assess whether FMT reduced the abundance of antibiotic resistance genes (ARG) or affected resistome diversity, evenness, or richness in patients with chronic pouchitis.

METHODS: We collected clinical characteristics regarding infections and antibiotic exposures for 18 patients who had previously been enrolled in an observational study investigating FMT as a treatment for pouchitis. Twenty-six pre- and post-FMT stool samples were analyzed using FLASH (Finding Low Abundance Sequences by Hybridization), a CRISPR/Cas9-based shotgun metagenomic sequence enrichment technique that detects acquired and chromosomal bacterial ARGs. Wilcoxon rank sum tests were used to assess differences in clinical characteristics, ARG counts, resistome diversity and ARG richness, pre- and post-FMT.

RESULTS: All 13 of the patients with sufficient stool samples for analysis had recently received antibiotics for pouchitis prior to a single endoscopic FMT. Fecal microbiomes of all patients had evidence of multi-drug resistance genes and ESBL resistance genes at baseline; 62% encoded fluoroquinolone resistance genes. A numerical decrease in overall ARG counts was noted post-FMT, but no statistically significant differences were noted (P = 0.19). Richness and diversity were not significantly altered. Three patients developed infections during the 5-year follow-up period, none of which were associated with MDRO.

CONCLUSION: Antibiotic resistance genes are prevalent among antibiotic-exposed patients with chronic pouchitis. FMT led to a numerical decrease, but no statistically significant change in ARG, nor were there significant changes in the diversity, richness, or evenness of ARGs. Further investigations to improve FMT engraftment and to optimize FMT delivery in patients with inflammatory pouch disorders are warranted.

PMID:39804518 | DOI:10.1007/s10620-024-08828-5