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Gut Microbiome-Dependent Metabolic Pathways and Risk of Lethal Prostate Cancer: Prospective Analysis of a PLCO Cancer Screening Trial Cohort.
Reichard, CA, Naelitz, BD, Wang, Z, Jia, X, Li, J, Stampfer, MJ, Klein, EA, Hazen, SL, Sharifi, N
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2022;(1):192-199
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BACKGROUND Diet and the gut microbiome have a complex interaction that generates metabolites with an unclear effect on lethal prostate cancer risk. Identification of modifiable risk factors for lethal prostate cancer is challenging given the long natural history of this disease and difficulty of prospectively identifying lethal cancers. METHODS Mass spectrometry was performed on baseline serum samples collected from 173 lethal prostate cancer cases and 519 controls enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening trial. Baseline serum levels of choline, carnitine, betaine, γ-butyrobetaine, crotonobetaine, phenylacetylglutamine, hippuric acid, and p-cresol sulfate were quantified and analyzed by quartile. Conditional multivariable logistic regression analysis associated analyte levels with lethal prostate cancer incidence after adjusting for body mass index and PSA. The Cochran-Armitage test evaluated analyte level trends across quartiles. RESULTS Relative to those in the first quartile, cases with the highest baseline levels of choline (Q4 OR: 2.19; 95% CI, 1.23-3.90; P-trend: 0.005) and betaine (Q4 OR: 1.86; 95% CI, 1.05-3.30; P-trend: 0.11) exhibited increased odds of developing lethal prostate cancer. Higher baseline serum levels of phenylacetylglutamine (Q4 OR: 2.55; 95% CI, 1.40-4.64; P-trend: 0.003), a gut microbiome metabolite of phenylalanine with adrenergic activity, were also associated with lethal prostate cancer. CONCLUSIONS Baseline serum levels of one-carbon methyl donors and adrenergic compounds resulting from human and gut microbiota-mediated metabolism are associated with increased lethal prostate cancer risk. IMPACT Dietary composition, circulating metabolite levels, and downstream signaling pathways may represent modifiable risk factors associated with incident lethal prostate cancer. Beta-adrenergic blockade represents an additional target for oncologic risk reduction.
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Association of Cognitive Function Screening Results with Adherence and Performance in a Pedometer-Based Intervention.
Sheshadri, A, Kittiskulnam, P, Delgado, C, Sudore, RL, Lai, JC, Johansen, KL
American journal of nephrology. 2021;(5):420-428
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INTRODUCTION A randomized, controlled trial of a pedometer-based walking intervention with weekly activity goals led to increased walking among dialysis patients. We examined whether impairment per cognitive function screening is associated with adherence and performance in the intervention. METHODS Thirty dialysis patients were randomly assigned to a 3-month pedometer-based intervention with weekly goals. Participants were administered the Telephone Interview of Cognitive Status (TICS), a test of global mental status. We examined the association of levels of impairment on the TICS (≥33: unimpaired, 26-32: ambiguous impairment, 21-25: mild cognitive impairment [MCI]) with adherence, achieving weekly goals, and increasing steps, physical performance (Short Physical Performance Battery, SPPB), and self-reported physical function (PF) through multivariable linear mixed-model and logistic regression analyses adjusted for age, sex, BMI, dialysis modality, baseline steps, baseline SPPB, and stroke status. RESULTS One-third of participants were unimpaired, and 13% had MCI. Participants with worse results on cognitive function screening missed more calls and completed fewer weekly goals than participants with better results. During the intervention, a worse result on cognitive function screening was associated with smaller increases in steps compared to those without impairment: (ambiguous: -620 [95% CI -174, -1,415], MCI: -1,653 [95% CI -120, -3,187]); less improvement in SPPB (ambiguous: -0.22 points [95% CI -0.08, -0.44], MCI: -0.45 [95% CI -0.13, -0.77]); and less improvement in PF (ambiguous: -4.0 points [95% CI -12.2, 4.1], MCI: -14.0 [95% CI -24.9, -3.1]). During the postintervention period, a worse result on cognitive function screening was associated with smaller increases in SPPB (ambiguous: -0.54 [95% CI -1.27, 0.19], MCI: -0.97 [95% CI -0.37, -1.58]) and PF (ambiguous: -3.3 [95% CI -6.5, -0.04], MCI: -10.5 [95% CI -18.7, -2.3]). DISCUSSION/CONCLUSION Participants with worse results on cognitive function screening had worse adherence and derived less benefit from this pedometer-based intervention. Future exercise interventions should be developed incorporating methods to address cognitive impairment, for example, by including caregivers when planning such interventions.
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Four-Year Screening Interval and Vision-Threatening Retinopathy in Type 2 Diabetes Patients With Good Glycemic Control.
Tsujimoto, T, Kajio, H
Mayo Clinic proceedings. 2021;(2):322-331
Abstract
OBJECTIVE To assess whether vision-threatening retinopathy developed after 4 years in patients with type 2 diabetes with good glycemic control during follow-up. PATIENTS AND METHODS Using data from the Action to Control Cardiovascular Risk in Diabetes and Action to Control Cardiovascular Risk in Diabetes Follow-on studies (conducted from January 1, 2001, to October 14, 2014), we investigated the incidence of vision-threatening retinopathy after 4 years in patients with type 2 diabetes with good or poor glycemic control. Patients with proliferative diabetic retinopathy at baseline were excluded. Vision-threatening retinopathy was defined as severe nonproliferative diabetic retinopathy, proliferative diabetic retinopathy, laser photocoagulation, or vitrectomy. Good and poor glycemic control was defined as mean glycated hemoglobin level less than 7% and 7% or greater during follow-up, respectively. RESULTS This study included 2285 patients. Among patients with no retinopathy at baseline, the 4-year incidence of vision-threatening retinopathy was 0% (0 of 386) and 0.8% (6 of 721) in those with good and poor glycemic control, respectively (P=.54). Similarly, severe retinopathy was not observed at 8 years in patients who did not have retinopathy at 4 years. Among patients with mild to moderate nonproliferative diabetic retinopathy at baseline, the 4-year incidence of vision-threatening retinopathy was significantly higher in those with poor glycemic control than in those with good glycemic control (9.7% [77 of 790] vs 4.4% [13 of 297]; P=.004). Additionally, the remission rate of diabetic retinopathy was low in patients with a long duration of diabetes. Four-year incidences of vision-threatening retinopathy were higher in patients with retinopathy at baseline who had poorer glycemic control and longer durations of diabetes. CONCLUSION It may be safe to extend screening intervals for diabetic retinopathy to 4 years or longer in patients with type 2 diabetes with no retinopathy.
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Comparative Effectiveness of Two Interventions to Increase Colorectal Cancer Screening for Those at Increased Risk Based on Family History: Results of a Randomized Trial.
Paskett, ED, Bernardo, BM, Young, GS, Katz, ML, Reiter, PL, Tatum, CM, Oliveri, JM, DeGraffinreid, CR, Gray, DM, Pearlman, R, et al
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2020;(1):3-9
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BACKGROUND First-degree relatives (FDR) of patients with colorectal cancer are at risk for colorectal cancer, but may not be up to date with colorectal cancer screening. We sought to determine whether a one-time recommendation about needing colorectal cancer screening using patient navigation (PN) was better than just receiving the recommendation only. METHODS Participants were FDRs of patients with Lynch syndrome-negative colorectal cancer from participating Ohio hospitals. FDRs from 259 families were randomized to a website intervention (528 individuals), which included a survey and personal colorectal cancer screening recommendation, while those from 254 families were randomized to the website plus telephonic PN intervention (515 individuals). Primary outcome was adherence to the personal screening recommendation (to get screened or not to get screened) received from the website. Secondary outcomes examined who benefited from adding PN. RESULTS At the end of the 14-month follow-up, 78.6% of participants were adherent to their recommendation for colorectal cancer screening with adherence similar between arms (P = 0.14). Among those who received a recommendation to have a colonoscopy immediately, the website plus PN intervention significantly increased the odds of receiving screening, compared with the website intervention (OR: 2.98; 95% confidence interval, 1.68-5.28). CONCLUSIONS Addition of PN to a website intervention did not improve adherence to a colorectal cancer screening recommendation overall; however, the addition of PN was more effective in increasing adherence among FDRs who needed screening immediately. IMPACT These findings provide important information as to when the additional costs of PN are needed to assure colorectal cancer screening among those at high risk for colorectal cancer.
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Infant TB Infection Prevention Study (iTIPS): a randomised trial protocol evaluating isoniazid to prevent M. tuberculosis infection in HIV-exposed uninfected children.
LaCourse, SM, Richardson, BA, Kinuthia, J, Warr, AJ, Maleche-Obimbo, E, Matemo, D, Cranmer, LM, Escudero, JN, Hawn, TR, John-Stewart, GC
BMJ open. 2020;(1):e034308
Abstract
INTRODUCTION HIV-exposed uninfected (HEU) infants in tuberculosis (TB) endemic settings are at high risk of Mycobacterium tuberculosis (Mtb) infection and TB disease, even in the absence of known Mtb exposure. Because infancy is a time of rapid progression from primary infection to active TB disease, it is important to define when and how TB preventive interventions exert their effect in order to develop effective prevention strategies in this high-risk population. METHODS AND ANALYSIS We designed a non-blinded randomised controlled trial to determine efficacy of isoniazid (INH) to prevent primary Mtb infection among HEU children. Target sample size is 300 (150 infants in each arm). Children are enrolled at 6 weeks of age from maternal and child health clinics in Kenya and are randomised to receive 12 months of daily INH ~10 mg/kg plus pyridoxine or no INH. The primary endpoint is Mtb infection, assessed by interferon-gamma release assay QuantiFERON-TB Gold Plus (QFT-Plus) or tuberculin skin test after 12 months post-enrolment. Secondary outcomes include severe adverse events, expanded Mtb infection definition using additional QFT-Plus supernatant markers and determining correlates of Mtb infection. Exploratory analyses include a combined outcome of TB infection, disease and mortality, and sensitivity analyses excluding infants with baseline TB-specific responses on flow cytometry. ETHICS AND DISSEMINATION An external and independent Data and Safety Monitoring Board monitors adverse events. Results will be disseminated through peer-reviewed journals, presentations at local and international conferences to national and global policy-makers, the local community and participants. TRIAL REGISTRATION NUMBER NCT02613169; Pre-results.
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A prospective RCT comparing combined chromoendoscopy with water exchange (CWE) vs water exchange (WE) vs air insufflation (AI) in adenoma detection in screening colonoscopy.
Leung, JW, Yen, AW, Jia, H, Opada, C, Melnik, A, Atkins, J, Feller, C, Wilson, MD, Leung, FW
United European gastroenterology journal. 2019;(4):477-487
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BACKGROUND A low adenoma detection rate (ADR) increases risks of interval cancers (ICs). Proximal colon flat polyps, e.g. serrated lesions (SLs), are difficult to find. Missed proximal colon flat lesions likely contribute to IC. AIMS We compared chromoendoscopy with water exchange (CWE), water exchange (WE) and air insufflation (AI) in detecting adenomas in screening colonoscopy. METHODS After split-dose preparation, 480 veterans were randomized to AI, WE and CWE. RESULTS Primary outcome of proximal ADR (55.6% vs 53.4% vs 52.2%, respectively) were similar in all groups. Adenoma per colonoscopy (APC) and adenoma per positive colonoscopy (APPC) were comparable. Detection rate of proximal colon SLs was significantly higher for CWE and WE than AI (26.3%, 23.6% and 11.3%, respectively, p = 0.002). Limitations: single operator; SLs only surrogate markers of but not IC. CONCLUSIONS When an endoscopist achieves high-quality AI examinations with overall ADR twice (61.6%) the recommended standard (30%), use of WE and CWE does not produce further improvement in proximal or overall ADR. Comparable APC and APPC confirm equivalent withdrawal inspection techniques. WE alone is sufficient to significantly improve detection of proximal SLs. The impact of increased detection of proximal SLs by WE on prevention of IC deserves to be studied. This study is registered at ClinicalTrial.gov (NCT#01607255).
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Feasibility and Outcomes of an HIV Testing Intervention in African American Churches.
Berkley-Patton, JY, Thompson, CB, Moore, E, Hawes, S, Berman, M, Allsworth, J, Williams, E, Wainright, C, Bradley-Ewing, A, Bauer, AG, et al
AIDS and behavior. 2019;(1):76-90
Abstract
The updated National HIV/AIDS Strategy recommends widespread HIV education and testing and calls the faith community to assist in these efforts. Yet, limited information exist on church-based HIV testing interventions. This study examined feasibility and assessed HIV testing outcomes of Taking It to the Pews (TIPS), a multilevel HIV education and testing intervention. Four African American churches were matched and randomized to TIPS or a standard-information control arm. Intervention churches delivered the religiously-tailored TIPS Tool Kit, which included educational materials to individuals and ministry groups; pastoral activities (e.g., sermons preached, receipt of HIV testing role-modeled), responsive readings, and church bulletin inserts in church services; and HIV testing during church services and church outreach events. All churches delivered 2-3 tools/month and coordinated 3 HIV testing events. At 12 months, significant increases in receipt of HIV testing (59% vs. 42%, p = 0.008), and particularly church-based testing (54% vs. 15%, p < 0.001), relative to controls were found. TIPS has great potential to increase reach, feasibility, and impact of HIV testing in African American churches.
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Bundled HIV and Hepatitis C Testing in the Emergency Department: A Randomized Controlled Trial.
Cowan, E, Herman, HS, Rahman, S, Zahn, J, Leider, J, Calderon, Y
The western journal of emergency medicine. 2018;(6):1049-1056
Abstract
INTRODUCTION An estimated 25% of the 1.2 million individuals living with human immunodeficiency virus (HIV) in the U.S. are co-infected with hepatitis C (HCV). The Centers for Disease Control and Prevention recommends HCV testing for high-risk groups. Our goal was to measure the impact of bundled HIV and HCV testing vs. HIV testing alone on test acceptance and identification of HCV and HIV. METHODS We conducted a two-armed, randomized controlled trial on a convenience sample of 478 adult patients in the Jacobi Medical Center emergency department from December 2012 to May 2013. Participants were randomized to receive either an offer of bundled HIV/HCV testing or HIV testing alone. We compared the primary outcome, HIV test acceptance, between the two groups. Secondary outcomes included HIV and HCV prevalence, and HCV test acceptance, refusal, risk, and knowledge. RESULTS We found no significant difference in HIV test acceptance between the bundled HCV/HIV (91.8%) and HIV-only (90.6%) groups (p=0.642). There were also no significant differences in test acceptance based on gender, race, or ethnicity. A majority of participants (76.6%) reported at least one HCV risk factor. No participants tested positive for HIV, and one (0.5%) tested positive for HCV. CONCLUSION Integrating bundled, rapid HCV/HIV testing into an established HIV testing program did not significantly impact HIV test acceptance. Future screening efforts for HCV could be integrated into current HIV testing models to target high-risk cohorts.
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Diabetes primary prevention program: New insights from data analysis of recruitment period.
Gagliardino, JJ, Elgart, JF, Bourgeois, M, Etchegoyen, G, Fantuzzi, G, Ré, M, Ricart, JP, García, S, Giampieri, C, González, L, et al
Diabetes/metabolism research and reviews. 2018;(1)
Abstract
BACKGROUND Primary Prevention of Diabetes Program in Buenos Aires Province evaluates the effectiveness of adopting healthy lifestyle to prevent type 2 diabetes (T2D) in people at high risk of developing it. We aimed to present preliminary data analysis of FINDRISC and laboratory measurements taken during recruitment of people for the Primary Prevention of Diabetes Program in Buenos Aires Province in the cities of La Plata, Berisso, and Ensenada, Argentina. METHODS People were recruited through population approach (house-to-house survey by FINDRISC in randomized areas) and opportunistic approach (FINDRISC completed by participants during consultations for nonrelated prediabetes/diabetes symptoms in public and private primary care centres of cities involved). In people with FINDRISC score ≥ 13 points, we evaluated blood concentrations of HbA1c , creatinine, lipids, and an oral glucose tolerance test (OGTT). RESULTS Approximately 3415 individuals completed the FINDRISC populational survey and 344 the opportunistic survey; 43% of the 2 groups scored over 13 points; 2.8 and 75.4% of them, respectively, took the prescribed OGTT. Approximately 53.7% of the OGTT showed normal values and 5.2% unknown T2D. The remaining cases showed 69.5% impaired fasting glucose, 13.6% impaired glucose tolerance, and 16.9% both impairments. HbA1c values showed significant differences compared with normal glucose tolerance (4.96 ± 0.43%), prediabetes (5.28 ± 0.51%), and T2D (5.60 ± 0.51%). Participants with prediabetes and T2D showed a predominant increase in low-density lipoprotein-cholesterol values. In prediabetes, >50% showed insulin resistance. CONCLUSIONS People with prediabetes/T2D had dyslipidemia associated with insulin resistance, which promotes the development of T2D and cardiovascular disease. Thus, it merits its appropriate treatment.
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Improving Cancer Preventive Behaviors: A Randomized Trial of Tailored Lifestyle Feedback in Colorectal Cancer Screening.
Knudsen, MD, Hjartåker, A, Robb, KA, de Lange, T, Hoff, G, Berstad, P
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2018;(12):1442-1449
Abstract
BACKGROUND Cancer screening provides an opportunity to increase awareness of cancer-preventive lifestyle behaviors such as nonsmoking, physical activity, low alcohol consumption, and a healthy diet. We tested the effect of standardized, individually tailored written feedback (TF), and a standard leaflet (SL) on 1-year lifestyle behaviors in a colorectal cancer screening setting. METHODS A total of 3,642 men and women aged 50-74 years invited to sigmoidoscopy screening were randomly assigned to: (i) TF; (ii) SL for cancer-preventive lifestyle behaviors; or (iii) control. Participants were mailed two self-reported lifestyle questionnaires (LSQ) 1 year apart. The TF intervention was based on the prescreening LSQ answers. We analyzed differences [with 95% confidence intervals (CI)] by comparing prescreening to 1-year follow-up of single cancer-preventive factors and the number of cancer-preventive lifestyle behaviors (range 0-4) between the groups by multivariable logistic regression and analysis of covariance (ANCOVA). RESULTS A total of 1,054 screening participants without neoplastic findings (29% of those invited to screening) were included in this study. Participants in the TF group increased their number of cancer-preventive lifestyle behaviors significantly compared with those in the control group by 0.11 (95% CI, 0.02 to 0.19). Overweight/obese individuals in the TF group had a -0.84 kg (95% CI, -1.47 to -0.22) larger reduction in body weight compared with the control group. CONCLUSIONS TF at sigmoidoscopy screening led to small improvements in cancer-preventive behaviors. IMPACT Colorectal cancer screening is a suitable setting for increasing awareness of cancer-preventive behavior.