Race-associated disparities often occur in patients who undergo lower extremity total joint arthroplasty (TJA). Although it is imperative to elucidate and describe the disparities in race and ethnicity that may influence patient perception, satisfaction, and surgical outcomes, there is a paucity of reports detailing the nature of potential racial disparities in TJA. Therefore, the purpose of this review was to examine racial and ethnic disparities in the (1) physician-patient relationship; (2) use of TJA; (3) intraoperative and 30-day postoperative complications; and (4) patient-reported outcomes. Although there are limited studies that evaluated this topic, it has been shown that there are race-specific differences in physician-patient relationships. Specifically, African American patients report lower satisfaction rates in communication with their physician than their Caucasian counterparts and physicians were more apt to describe African Americans as less "medically cooperative." The majority of the studies the authors found regarding TJA use indicated that African Americans and Hispanics were less likely to undergo lower extremity TJA than Caucasians. Furthermore, racial minorities may have higher 30-day readmission and intra- and postoperative complication rates compared with Caucasians. Despite these compelling findings, concrete conclusions are difficult to make due to the presence of multiple confounding patient factors, and more studies examining the racial and ethnic disparities in patients with TJA are needed.
Purpose To investigate the effect of early evening exercise training at different intensities on nocturnal sleep and cardiac autonomic activity in endurance-trained runners. Methods Eight runners completed three experimental trials in a randomised, counterbalanced order. In the early evening (end of exercise 3.5 h before bedtime), participants performed either: (i) a 1 h high-intensity interval running session (HIGH, 6 × 5 min at 90% VO 2peak interspersed with 5 min recovery); (ii) a 1 h low-intensity running session (LOW, 60 min at 45% VO 2peak) or (iii) no exercise (CON). Subsequent nocturnal sleep was assessed using polysomnography, wristwatch actigraphy, and subjective sleep quality. A two-lead electrocardiogram recorded nocturnal cardiac autonomic activity. Results Total sleep time increased after HIGH (477.4 ± 17.7 min, p = 0.022) and LOW (479.6 ± 15.6 min, p = 0.006) compared with CON (462.9 ± 19.0 min). Time awake was lower after HIGH (31.8 ± 18.5 min, p = 0.047) and LOW (30.4 ± 15.7 min, p = 0.008) compared with CON (46.6 ± 20.0 min). There were no differences between conditions for actigraphy and subjective sleep quality (p > 0.05). Nocturnal heart rate variability was not different between conditions, but average nocturnal heart rate increased after HIGH (50 ± 5 beats min −1) compared with LOW (47 ± 5 beats min −1 , p = 0.02) and CON (47 ± 5 beats min −1 , p = 0.028). Conclusion When performed in the early evening, high-intensity exercise does not disrupt and may even improve subsequent nocturnal sleep in endurance-trained runners, despite increased cardiac autonomic activity. Additionally, low-intensity exercise induced positive changes in sleep behaviour that are comparable to those obtained following high-intensity exercise.
A series of nonnucleoside 3-aminopyridin-2(1H)-one derivatives was synthesized and evaluated for HIV-1 RT inhibitory properties. Several analogs proved to be potent and highly selective antagonists with in vitro IC50 values as low as 19 nM in the enzyme assay using rC.dG as template-primer. Two compounds from this series, 3-[[(4,7-dimethylbenzoxazol-2-yl)methyl]-amino]-5-ethyl-6-methy lpyridin-2(1H)-one (34, L-697,639) and the corresponding 4,7-dichloro analogue (37, L-697,661) inhibited the spread of HIV-1 IIIb infection by 95% in MT4 cell culture at concentrations of 25-50 nM and were selected for clinical trials as antiviral agents.
A potent (IC50 = 30 nM), specific nonnucleoside HIV-1 reverse transcriptase (RT) inhibitor 3-[N-(phthalimidomethyl)amino]-5-ethyl-6-methylpyridin-2(1H) -one (1), was discovered through an in vitro screening program. This compound did not inhibit (IC50 > 300 microns) other DNA and RNA polymerases, including HIV-2 RT and SIV-RT. Unfortunately, hydrolytic instability of this (aminomethyl)phthalimide precluded use as an antiviral agent. In the first paper of this series, preliminary development efforts are described which produced ethylphthalimide 20, a hydrolytically stable compound with reduced (100-fold) HIV-1 RT inhibitory activity and weak (CIC95 = 40 microM) antiviral activity in H9 cells. Structure-activity studies demonstrated the importance of the 5-ethyl, 6-methyl substituent pattern on the pyridinone ring and the need for a flexible two-atom linker between the pyridinone and phthalimide heterocycles. These leads, 1 and 20, provided a basis for the further development of this structural class of inhibitors from which several compounds, the subject of accompanying reports, were selected for clinical evaluation.
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