Living kidney donation represents the optimal renal replacement therapy, but recent data suggest an increased long-term renal risk for the donor. Here, we evaluated the risk for reduced estimated ...glomerular filtration rate (eGFR), death, and major cardiovascular events such as nonfatal myocardial infarction or cerebrovascular event including TIA (transient ischemic attack) and stroke in 225 donors, who underwent pre-donation examinations and live donor nephrectomy between 1985 and 2014 at our center. The median follow-up time was 8.7 years (1.0-29.1). In multivariate analysis, age and arterial hypertension at baseline were significantly associated with a higher risk of adverse renal outcomes, such as (1) eGFR <60 mL/min/1.73 m
(age per year: HR (hazard ratio) 1.05, 95% confidence interval (CI) 1.03-1.08, hypertension: HR 2.25, 95% CI 1.22-3.98), (2) eGFR <60 mL/min/1.73 m
and a decrease of ≥40% from baseline (age: HR 1.08, 95% CI 1.03-1.13, hypertension: HR 4.22, 95% CI 1.72-10.36), and (3) eGFR <45 mL/min/1.73 m
(age: HR 1.12, 95% CI 1.05-1.20, hypertension: HR 5.06, 95% CI 1.49-17.22). In addition, eGFR at time of donation (per mL/min/1.73 m
) was associated with a lower risk of (1) eGFR <60 mL/min/1.73 m
(HR 0.98, 95% CI 0.97-1.00) and (2) eGFR <45 mL/min/1.73 m
(HR 0.95, 95% CI 0.90-1.00). Age was the only significant predictor for death or major cardiovascular event (HR 1.08, 95% CI 1.01-1.16). In conclusion, arterial hypertension, lower eGFR, and age at the time of donation are strong predictors for adverse renal outcomes in living kidney donors.
Background Separating ill or possibly infectious people from their healthy community is one of the core principles of non-pharmaceutical interventions. However, there is scarce evidence on how to ...successfully implement quarantine orders. We investigated a community quarantine for an entire village in Germany (Neustadt am Rennsteig, March 2020) with the aim of better understanding the successful implementation of quarantine measures. Methods This cross-sectional survey was conducted in Neustadt am Rennsteig six weeks after the end of a 14-day mandatory community quarantine. The sample size consisted of 562 adults (64% of the community), and the response rate was 295 adults, or 52% (33% of the community). Findings National television was reported as the most important channel of information. Contact with local authorities was very limited, and partners or spouses played a more important role in sharing information. Generally, the self-reported information level was judged to be good (211/289 73.0%). The majority of participants (212/289 73.4%) approved of the quarantine, and the reported compliance was 217/289 (75.1%). A self-reported higher level of concern as well as a higher level of information correlated positively with both a greater acceptance of quarantine and self-reported compliant behaviour. Interpretation The community quarantine presented a rare opportunity to investigate a public health intervention for an entire community. In order to improve the implementation of public health interventions, public health risk communication activities should be intensified to increase both the information level (potentially leading to better compliance with community quarantine) and the communication level (to facilitate rapport and trust between public health authorities and their communities).
Malaria patients are frequently coinfected with HIV and mycobacteria causing tuberculosis, which increases the use of coadministered drugs and thereby enhances the risk of pharmacokinetic drug-drug ...interactions. Activation of the pregnane X receptor (PXR) by xenobiotics, which include many drugs, induces drug metabolism and transport, thereby resulting in possible attenuation or loss of the therapeutic responses to the drugs being coadministered. While several artemisinin-type antimalarial drugs have been shown to activate PXR, data on nonartemisinin-type antimalarials are still missing. Therefore, this study aimed to elucidate the potential of nonartemisinin antimalarial drugs and drug metabolites to activate PXR. We screened 16 clinically used antimalarial drugs and six major drug metabolites for binding to PXR using the two-hybrid PXR ligand binding domain assembly assay; this identified carboxymefloquine, the major and pharmacologically inactive metabolite of the antimalarial drug mefloquine, as a potential PXR ligand. Two-hybrid PXR-coactivator and -corepressor interaction assays and PXR-dependent promoter reporter gene assays confirmed carboxymefloquine to be a novel PXR agonist which specifically activated the human receptor. In the PXR-expressing intestinal LS174T cells and in primary human hepatocytes, carboxymefloquine induced the expression of drug-metabolizing enzymes and transporters on the mRNA and protein levels. The crucial role of PXR for the carboxymefloquine-dependent induction of gene expression was confirmed by small interfering RNA (siRNA)-mediated knockdown of the receptor. Thus, the clinical use of mefloquine may result in pharmacokinetic drug-drug interactions by means of its metabolite carboxymefloquine. Whether these in vitro findings are of in vivo relevance has to be addressed in future clinical drug-drug interaction studies.
Placebo effects can be induced by learning and conditioning processes, which in turn are influenced and modulated by glucocorticoids. Accordingly, previous research has shown that ...intervention-related associative learning can be modulated through exogenous as well as endogenous glucocorticoids. Thus, the aim of this study was to elucidate whether placebo effects induced by conditioning is modulated by daily fluctuations of endogenous cortisol levels in healthy male and female subjects.
Overall 77 participants underwent a two-phased placebo conditioning paradigm for pain analgesia. Subjects were randomized in two groups, which underwent placebo preconditioning either in the morning (08:00–10:00, i.e. with high endogenous cortisol levels) or in the afternoon (16:00–18:00, i.e. with low endogenous cortisol levels). Placebo effects were assessed two days later at noontime (12:00–13:00), with possible differences between groups as an indicator of glucocorticoid modulation on the placebo learning.
Results indicated a significant conditioned placebo-induced analgesia, resulting in a placebo effect of small to medium size. Cortisol levels on conditioning day significantly differed between groups and cortisol levels were similar during assessment of placebo effects. Groups did not differ in their mean reduction in pain sensation, thus the placebo effect was not affected by differences in cortisol levels during the conditioning of placebo effects.
The present study does not indicate a moderation of placebo conditioning by endogenous glucocorticoid levels.
•Placebo effects rely conditioning, which in turn are influenced and modulated by glucocorticoids.•Is placebo conditioning modulated by daily fluctuations of endogenous cortisol levels in healthy male and female subject?•Placebo effects are not affected by differences in endogenous cortisol levels during the conditioning of placebo effects.•Thus, present study does not indicate a moderation of placebo conditioning by endogenous cortisol levels.
Purpose
The prevalence of long-term olfactory and gustatory dysfunction in participants suffering from sudden chemosensory loss due to coronavirus disease 2019 (COVID-19) is unknown. Furthermore, ...evaluations of the reliability of participants’ self-reporting of olfactory function (SOF) and gustatory function (SGF) using extended objective psychophysical testing are missing.
Methods
In this population-based cohort study in a PCR-tested community in Thuringia, Germany, olfactory function was extensively examined 4 months after a COVID-19 outbreak using the “Sniffin Sticks” test battery to determine the TDI
a
score, i.e., the sum of results obtained for threshold, discrimination, and identification scores averaged for both nasal sides. Gustatory function was assessed using the three-drop test resulting in the gustatory composite score (CS
g
). The data were compared with SOF and SGF.
Results
Of 43 adult convalescents (median age: 68 years; 58% female) after SARS-CoV‑2 infection, 18 participants (42%) had olfactory complaints due to SOF, one participant (2%) complained of taste disturbance due to SGF. The TDI
a
was 22.0 ± 5.9. Normosmia, hyposmia, and anosmia were seen in 17, 18, and eight participants, respectively. TDI
a
correlated with SOF (
r
s
= −0.434,
p
= 0.004); CS
g
was 23.5 ± 2.7. Normogeusia and hypogeusia were objectified in 39 and four participants, respectively. The prevalence of long-term olfactory dysfunction and gustatory dysfunction in the study group was 60.5 and 9.3%, respectively.
Conclusion
The SOF was reliable, especially for participants who felt a sudden chemosensory dysfunction during the outbreak. At 4 months after SARS-CoV‑2 infection, a high proportion of participants were dysosmic, whereas nearly all of them had normal taste function.
PDF
