Publications by authors named "J Kelly"

6,544 Publications

Total Synthesis and Antimalarial Activity of 2-(-Hydroxybenzyl)-prodigiosins, Isoheptylprodigiosin, and Geometric Isomers of Tambjamine MYP1 Isolated from Marine Bacteria.

J Med Chem 2021 Jun 10. Epub 2021 Jun 10.

Department of Chemistry, Portland State University, Portland, Oregon 97201, United States.

Highly efficient and straightforward synthetic routes toward the first total synthesis of 2-(-hydroxybenzyl)-prodigiosins (-), isoheptylprodigiosin (), and geometric isomers of tambjamine MYP1 ((/)-) have been developed. The crucial steps involved in these synthetic routes are the construction of methoxy-bipyrrole-carboxaldehydes (MBCs) and a 20-membered macrocyclic core and a regioselective demethylation of MBC analogues. These new synthetic routes enabled us to generate several natural prodiginines - in larger quantity. All of the synthesized natural products exhibited potent asexual blood-stage antiplasmodial activity at low nanomolar concentrations against a panel of parasites, with a great therapeutic index. Notably, prodiginines and - provided curative in vivo efficacy against erythrocytic at 25 mg/kg × 4 days via oral route in a murine model. No overt clinical toxicity or behavioral change was observed in any mice treated with prodiginines and tambjamines.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00748DOI Listing
June 2021

New recommendations to reduce unnecessary blood tests following robot assisted radical prostatectomy.

BJU Int 2021 Jun 10. Epub 2021 Jun 10.

Department of Uro-oncology, University College London Hospitals NHS Foundation Trust, London, UK.

Radical prostatectomy (RP) is a standard treatment for men with localised prostate cancer. Robot Assisted Radical Prostatectomy (RARP) is associated with fewer intraoperative adverse events, reduced blood loss and lower complication rates compared to open and laparoscopic surgery but delivers comparable oncological and functional outcomes (1). Furthermore, the use of Enhanced Recovery after Surgery (ERAS) pathways for RARP, have improved patient recovery and experience, reducing costs and maintaining patient safety (2).
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http://dx.doi.org/10.1111/bju.15511DOI Listing
June 2021

Association of Social and Behavioral Risk Factors With Mortality Among US Veterans With COVID-19.

JAMA Netw Open 2021 06 1;4(6):e2113031. Epub 2021 Jun 1.

San Francisco VA Medical Center, San Francisco, California.

Importance: The US Department of Veterans Affairs (VA) offers programs that reduce barriers to care for veterans and those with housing instability, poverty, and substance use disorder. In this setting, however, the role that social and behavioral risk factors play in COVID-19 outcomes is unclear.

Objective: To examine whether social and behavioral risk factors were associated with mortality among US veterans with COVID-19 and whether this association might be modified by race/ethnicity.

Design, Setting, And Participants: This cohort study obtained data from the VA Corporate Data Warehouse to form a cohort of veterans who received a positive COVID-19 test result between March 2 and September 30, 2020, in a VA health care facility. All veterans who met the inclusion criteria were eligible to participate in the study, and participants were followed up for 30 days after the first SARS-CoV-2 or COVID-19 diagnosis. The final follow-up date was October 31, 2020.

Exposures: Social risk factors included housing problems and financial hardship. Behavioral risk factors included current tobacco use, alcohol use, and substance use.

Main Outcomes And Measures: The primary outcome was all-cause mortality in the 30-day period after the SARS-CoV-2 or COVID-19 diagnosis date. Multivariable logistic regression was used to estimate odds ratios, clustering for health care facilities and adjusting for age, sex, race, ethnicity, marital status, clinical factors, and month of COVID-19 diagnosis.

Results: Among 27 640 veterans with COVID-19 who were included in the analysis, 24 496 were men (88.6%) and the mean (SD) age was 57.2 (16.6) years. A total of 3090 veterans (11.2%) had housing problems, 4450 (16.1%) had financial hardship, 5358 (19.4%) used alcohol, and 3569 (12.9%) reported substance use. Hospitalization occurred in 7663 veterans (27.7%), and 1230 veterans (4.5%) died. Housing problems (adjusted odds ratio [AOR], 0.96; 95% CI, 0.77-1.19; P = .70), financial hardship (AOR, 1.13; 95% CI, 0.97-1.31; P = .11), alcohol use (AOR, 0.82; 95% CI, 0.68-1.01; P = .06), current tobacco use (AOR, 0.85; 95% CI, 0.68-1.06; P = .14), and substance use (AOR, 0.90; 95% CI, 0.71-1.15; P = .41) were not associated with higher mortality. Interaction analyses by race/ethnicity did not find associations between mortality and social and behavioral risk factors.

Conclusions And Relevance: Results of this study showed that, in an integrated health system such as the VA, social and behavioral risk factors were not associated with mortality from COVID-19. Further research is needed to substantiate the potential of an integrated health system to be a model of support services for households with COVID-19 and populations who are at risk for the disease.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.13031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190626PMC
June 2021

Attitudes toward opioid use disorder pharmacotherapy among recovery community center attendees.

J Subst Abuse Treat 2021 May 8;131:108464. Epub 2021 May 8.

Recovery Research Institute, Massachusetts General Hospital and Harvard Medical School, 151 Merrimac Street, Boston, MA 02114, United States of America.

Background: Despite their proven efficacy, medications for opioid use disorder (MOUD) are underutilized. Negative beliefs and attitudes toward MOUD are quite common, yet rapidly expanding recovery community centers (RCCs) may offer a promising venue for fostering MOUD support as they operate under the maxim, "many pathways [to recovery], all should be celebrated" and are utilized mainly by those with opioid use disorder. The current study provides a first look at MOUD attitudes and their correlates in RCC attendees.

Methods: The study conducted a cross-sectional survey (N = 320) of recovering adults attending 31 RCCs across New England, assessing demographic, treatment, and recovery-relevant factors, as well attitudes (positive vs. negative) toward the use of agonist and antagonist MOUD. The study used frequencies and confidence intervals to obtain prevalence estimates for positive and negative attitudes toward agonist and antagonist MOUD, and to examine differences between them. Spearman correlations identified correlates of MOUD attitudes (at p < 0.10), and significant correlates were assessed for unique contributions via multivariable logistic regression.

Results: Positive attitudes were common and more prevalent than negative attitudes for both agonist (positive: 71.4 [66.1, 76.3]%; negative: 28.6 [23.7, 33.9]%) and antagonist (positive: 76.5 [71.4, 81.1]%; negative: 23.5 [18.9, 28.6]%) MOUD, which did not differ. The study identified several correlates of MOUD attitudes at the p < 0.10 level, but only four variables emerged as unique predictors controlling for other correlates. Lifetime history of agonist MOUD treatment was uniquely associated with positive agonist attitudes (p = 0.008), whereas greater social support for recovery was associated with positive antagonist attitudes (p = 0.007). Lower educational attainment was uniquely associated with negative antagonist attitudes (p = 0.005), and a greater degree of spirituality was related to negative attitudes toward both agonists (p = 0.005) and antagonists (p = 0.01).

Conclusions: Findings reveal very high rates of positive MOUD attitudes among RCC participants, highlighting the potential for this growing tier of recovery support to foster acceptance and peer support for medication-facilitated recovery pathways. Correlates of attitudes further reveal opportunities for facilitating MOUD acceptance within and beyond the RCC network.
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http://dx.doi.org/10.1016/j.jsat.2021.108464DOI Listing
May 2021

Recovery of health-related quality of life in patients undergoing robotic radical cystectomy with intracorporeal diversion.

BJU Int 2021 Jun 5. Epub 2021 Jun 5.

Department of Urology, University College London Hospitals NHS Foundation Trust, London, UK.

Background: To report the health-related quality of life (HRQoL) after robotic assisted radical cystectomy and intracorporeal urinary diversion (iRARC) and to identify factors impacting on return to baseline.

Patients And Methods: Consecutive patients undergoing iRARC between January 2016 - December 2017 completed the EORTC-QLQ-C30 and EORTC-QLQ-BLM30 questionnaires before surgery and had a minimum of 12 months follow-up postoperatively.

Results: A total of 76 patients met the inclusion criteria at 12 months. Neobladder (NB) cases (n = 24) were younger (57.0 years vs 71.0 years, p <0.001) and fitter than ileal conduit (IC) cases (n = 52) and had higher physical (100.0 vs 93.3, p = 0.039), and sexual functioning (66.7 vs 50.0, p = 0.013) scores at baseline. Longitudinal analysis of the EORTC-QLQ-C30 showed that physical (NB: 93.3 vs 100.0, p=0.020; IC: 80.0 vs 93.3, p<0.001) and role functioning scores (NB: 83.3 vs 100.0, p=0.010; IC: 83.3 vs 100.0, p=0.017) decreased and fatigue score (NB: 22.2 vs 11.1, p=0.026; IC: 33.3 vs 22.2, p = 0.008) increased at 3 months in both diversion groups. Scores returned to baseline at 6 months except physical functioning score in ileal conduit patients that remained below baseline till 12 months (86.7 vs 93.3, p=0.012). Global HRQoL score did not show significant change postoperatively in both groups. A major 90-day Clavien-Dindo complication was a significant predictor (OR: 0.11, CI: 0.02-0.62, p=0.012) of deteriorated global HRQoL score at 3 months, while occurrence of a late complication (OR: 0.14, CI: 0.03-0.65, p=0.013) was predictor of deteriorated global HRQoL score at 12 months. Longitudinal analysis of the EORTC-QLQ-BLM30 showed that urinary problems (NB: 14.3 vs 38.3, p<0.001; IC: 5.6 vs 19.1, p<0.001) and future perspective (NB: 33.3 vs 44.4, p=0.004; IC: 22.2 vs 44.4, p<0.001) scores were better than baseline at 3 months. Sexual function deteriorated significantly at 3 months (NB: 8.3 vs 66.7, p<0.001; IC: 4.2 vs 50.0, p<0.001) , then showed improvement at 12 months but was still below baseline (NB: 33.3 vs 66.7, p=0.001; IC: 25.0 vs 50.0, p<0.001). Involvement in penile rehabilitation was shown to be a significant predictor (β: 18.62, CI: 6.06-30.45, p=0.005) of higher sexual function score at 12 months.

Conclusion: While most functional domains and symptoms scales recover to or exceed baseline within 6 months after iRARC, physical function remains below baseline in ileal conduit patients up to 12 months. Global HRQoL is preserved for both types of urinary diversion, however, postoperative complications seem to be the main driving factor for global HRQoL. Sexual function is adversely affected after iRARC suggesting that structured rehabilitation of sexual function should be an integral part of cystectomy pathway.
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http://dx.doi.org/10.1111/bju.15505DOI Listing
June 2021