Time to improve informed consent for dialysis: an international perspective

The literature reveals that current nephrology practice in obtaining informed consent for dialysis falls short of ethical and legal requirements. Meeting these requirements represents a significant challenge, especially because the benefits and risks of dialysis have shifted significantly with the growing number of older, comorbid patients. The importance of informed consent for dialysis is heightened by several concerns, including: (1) the proportion of predialysis patients and patients on dialysis who lack capacity in decision making and (2) whether older, comorbid, and frail patients understand their poor prognosis and the full implications to their independence and functional status of being on dialysis. This article outlines the ethical and legal requirements for a valid informed consent to dialysis: (1) the patient was competent, (2) the consent was made voluntarily, and (3) the patient was given sufficient information in an understandable manner to make the decision. It then considers the application of these requirements to practice across different countries. In the process of informed consent, the law requires a discussion by the physician of the material risks associated with dialysis and alternative options. We argue that, legally and ethically, this discussion should include both the anticipated trajectory of the illness and the effect on the life of the patient with particular regard to the outcomes most important to the individual. In addition, a discussion should occur about the option of a conservative, nondialysis pathway. These requirements ensure that the ethical principle of respect for patient autonomy is honored in the context of dialysis. Nephrologists need to be open to, comfortable with, and skillful in communicating this information. From these clear, open, ethically, and legally valid consent discussions, a significant dividend will hopefully flow for patients, families, and nephrologists alike

Validation and verification of the GeneFinder (TM) COVID-19 Plus RealAmp kit on the ELITe InGenius (R) instrument

Background: Throughout the SARS-CoV-2 pandemic, a rapid identification of the virus was essential to quickly recognize positive cases and limit further spread by applying appropriate infection prevention. Many diagnostic laboratories use a multiplex Real-Time PCR assay, as they are not only highly sensitive but also specific. Currently, there are several assays and platforms in the market available which target different SARS-CoV-2 genes. The aim of this study was to validate and verify the GeneFinder (TM) COVID-19 PLUS RealAmp kit on the ELITe InGenius (R) instrument and compare to the national reference method. Methods: GeneFinder (TM) COVID-19 PLUS RealAmp kit was evaluated against the routine WHO in- house RealTime PCR assay, which is also the national reference method in the Netherlands and used in our laboratory. The sensitivity was tested using the analytical panel from Qnostics (Glasgow, United Kingdom) and the specificity was tested with patient material comprising of other seasonal respiratory viruses. In addition, 96 clinical samples initially analyzed by routine Real-Time PCR were tested using the GeneFinder (TM) COVID-19 PLUS RealAmp kit on the ELITe InGenius (R) instrument. Results: The GeneFinder (TM) COVID-19 PLUS RealAmp kit had a similar performance compared to routine in-house testing, with a limit of detection of 500 dC/mL for the RdRp-gene and E gene. Meanwhile, the N gene showed a limit of detection of 50 dC/mL. The SARS-CoV-2 test was highly specific and detected no other respiratory viruses. The results of the clinical samples were comparable between both assays with similar Ct values observed for the in-house Real-Time-PCR and the GeneFinder (TM) COVID-19 PLUS RealAmp kit for the N gene. Conclusion: The GeneFinder (TM) COVID-19 PLUS RealAmp kit on the ELITe InGenius (R) instrument had an appropriate sensitivity and specificity that could be used in small scale laboratories or during night shifts where accurate diagnostics are crucial

Over a third of palliative medicine physicians meet burnout criteria: Results from a survey study during the COVID-19 pandemic

Background: Palliative medicine physicians may be at higher risk of burnout due to increased stressors and compromised resilience during the COVID-19 pandemic. Burnout prevalence and factors influencing this among UK and Irish palliative medicine physicians is unknown. Aim: To determine the prevalence of burnout and the degree of resilience among UK and Irish palliative medicine physicians during the COVID-19 pandemic, and associated factors. Design: Online survey using validated assessment scales assessed burnout and resilience: The Maslach Burnout Inventory Human Services Survey for Medical Personnel [MBI-HSS (MP)] and the Connor-Davidson Resilience Scale (CD-RISC). Additional tools assessed depressive symptoms, alcohol use, and quality of life. Setting/participants: Association of Palliative Medicine of UK and Ireland members actively practising in hospital, hospice or community settings. Results: There were 544 respondents from the 815 eligible participants (66.8%), 462 provided complete MBI-HSS (MP) data and were analysed. Of those 181/462 (39.2%) met burnout criteria, based on high emotional exhaustion or depersonalisation subscales of the MBI-HSS (MP). A reduced odds of burnout was observed among physicians who worked ⩽20 h/week (vs 31–40 h/week, adjusted odds ratio (aOR) 0.03, 95% confidence interval (CI) 0.002–0.56) and who had a greater perceived level of clinical support (aOR 0.70, 95% CI 0.62–0.80). Physicians with higher levels of depressive symptoms had higher odds of burnout (aOR 18.32, 95% CI 6.75–49.73). Resilience, mean (SD) CD-RISC score, was lower in physicians who met burnout criteria compared to those who did not (62.6 (11.1) vs 70.0 (11.3); p < 0.001). Conclusions: Over one-third of palliative medicine physicians meet burnout criteria. The provision of enhanced organisational and colleague support is paramount in both the current and future pandemics

Whole-genome sequencing analysis reveals the spread of a vanB-carrying transposon among different vancomycin-resistant Enterococcus faecium clinical isolates in a non-endemic setting

Background: Vancomycin-resistant enterococci (VRE), particularly Enterococcus faecium (VREfm), can cause serious nosocomial infections, and have been responsible for healthcare-associated outbreaks. Spreading of VREfm can occur both clonally and by the dissemination of mobile genetic elements. Aim: To report prospective analysis of whole-genome sequencing (WGS) data, including both core-genome multi-locus sequence typing (cgMLST) and transposon analysis, during a vanB VREfm outbreak. Methods: Screening for vanB-positive VREfm isolates was performed by real-time polymerase chain reaction (PCR) on an overnight enriched broth and, if positive, subculture was performed. vanB-positive VREfm isolates underwent WGS. Generated data were used for molecular typing that was performed by cgMLST using SeqSphere. For transposon characterization, sequence data were mapped against the reference sequence of transposon Tn1549 using CLC Genomics Workbench, or de-novo assemblies were used for BLASTN comparisons. Results: In total, 1358 real-time PCRs were performed. Two hundred and fifty-one specimens from 207 patients tested positive on PCR for vanB, of which 13 specimens obtained from six patients were identified as vanB VREfm positive on culture. These six patients harboured seven unique isolates belonging to four cluster types: CT118 (N=2), CT2483 (N=3), CT2500 (N=1) and CT2501 (N=1). Transposon analysis revealed the presence of an identical vanB-carrying transposon in the isolates cultured from all six patientsBackground: Vancomycin-resistant enterococci (VRE), particularly Enterococcus faecium (VREfm), can cause serious nosocomial infections, and have been responsible for healthcare-associated outbreaks. Spreading of VREfm can occur both clonally and by the dissemination of mobile genetic elements.Aim: To report prospective analysis of whole-genome sequencing (WGS) data, including both core-genome multi-locus sequence typing (cgMLST) and transposon analysis, during a vanB VREfm outbreak.Methods: Screening for vanB-positive VREfm isolates was performed by real-time polymerase chain reaction (PCR) on an overnight enriched broth and, if positive, subculture was performed. vanB-positive VREfm isolates underwent WGS. Generated data were used for molecular typing that was performed by cgMLST using SeqSphere. For transposon characterization, sequence data were mapped against the reference sequence of transposon Tn1549 using CLC Genomics Workbench, or de-novo assemblies were used for BLASTN comparisons.Results: In total, 1358 real-time PCRs were performed. Two hundred and fifty-one specimens from 207 patients tested positive on PCR for vanB, of which 13 specimens obtained from six patients were identified as vanB VREfm positive on culture. These six patients harboured seven unique isolates belonging to four cluster types: CT118 (N=2), CT2483 (N=3), CT2500 (N=1) and CT2501 (N=1). Transposon analysis revealed the presence of an identical vanB-carrying transposon in the isolates cultured from all six patients that could be linked based on epidemiological data.Conclusion: A vanB VREfm outbreak occurred in the study hospital, including six patients with isolates belonging to four cluster types. In-depth transposon analysis revealed that &amp; nbsp;dissemination of transposon Tn1549 rather than clonal spread was the cause of the outbreak.(C)&amp; nbsp;2021 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.</p

High frequency of mitochondrial genome instability in human endometrial carcinomas

To investigate the occurrence of somatic mitochondrial DNA (mtDNA) mutations in human primary endometrial carcinomas, we sequenced the D-loop region, the 12S and 16S rRNA genes of mtDNA of cancer tissues and their matched normal controls. About 56% (28 out of 50) of cases carry one or more somatic changes in mtDNA including deletion, point mutation and mitochondrial microsatellite instability (mtMSI), namely the change in length of short base-repetitive sequences of mtDNA. In particular, mtMSI was frequently detected in 89% (25 out of 28) of all the cases carrying somatic changes followed by point mutations (25%; seven out of 28) and deletion (3.5%; one out of 28). The CCCCCTCCCC sequences located in the Hypervariable Regions I and II of the D-loop and 12S rRNA gene are instability hot spot regions in endometrial carcinomas. It is suggested that errors in replication may account for the high frequency of mtMSI in human endometrial carcinomas. The relatively high prevalence of mtMSI may be a potential new tool for detection of endometrial cancer. © 2003 Cancer Research UK.link_to_subscribed_fulltex

Effect of Curcuma longa and Ocimum sanctum on myocardial apoptosis in experimentally induced myocardial ischemic-reperfusion injury

BACKGROUND: In the present investigation, the effect of Curcuma longa (Cl) and Ocimum sanctum (Os) on myocardial apoptosis and cardiac function was studied in an ischemia and reperfusion (I-R) model of myocardial injury. METHODS: Wistar albino rats were divided into four groups and orally fed saline once daily (sham, control IR) or Cl (100 mg/kg; Cl-IR) or Os (75 mg/kg; Os-IR) respectively for 1 month. On the 31(st )day, in the rats of the control IR, Cl-IR and Os-IR groups LAD occlusion was undertaken for 45 min, and reperfusion was allowed for 1 h. The hemodynamic parameters{mean arterial pressure (MAP), heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular peak positive (+) LVdP/dt (rate of pressure development) and negative (-) LVdP/dt (rate of pressure decline)} were monitored at pre-set points throughout the experimental duration and subsequently, the animals were sacrificed for immunohistopathological (Bax, Bcl-2 protein expression & TUNEL positivity) and histopathological studies. RESULTS: Chronic treatment with Cl significantly reduced TUNEL positivity (p < 0.05), Bax protein (p < 0.001) and upregulated Bcl-2 (p < 0.001) expression in comparison to control IR group. In addition, Cl demonstrated mitigating effects on several myocardial injury induced hemodynamic {(+)LVdP/dt, (-) LVdP/dt & LVEDP} and histopathological perturbations. Chronic Os treatment resulted in modest modulation of the hemodynamic alterations (MAP, LVEDP) but failed to demonstrate any significant antiapoptotic effects and prevent the histopathological alterations as compared to control IR group. CONCLUSION: In the present study, significant cardioprotection and functional recovery demonstrated by Cl may be attributed to its anti-apoptotic property. In contrast to Os, Cl may attenuate cell death due to apoptosis and prevent the impairment of cardiac performance

Characterization of human Sec16B: indications of specialized, non-redundant functions

The endoplasmic reticulum (ER) represents the entry point into the secretory pathway and from here newly synthesized proteins and lipids are delivered to the Golgi. The selective cargo export from the ER is mediated by COPII-assembly at specific sites of the ER, the so-called transitional ER (tER). The peripheral membrane protein Sec16, first identified in yeast, localizes to transitional ER and plays a key role in organization of these sites. Sec16 defines the tER and is thought to act as a scaffold for the COPII coat assembly. In humans two isoforms of Sec16 are present, the larger Sec16A and the smaller Sec16B. Nevertheless, the functional differences between the two isoforms are ill-defined. Here we describe characterization of the localization and dynamics of Sec16B relative to Sec16A, provide evidence that Sec16B is likely a minor or perhaps specialized form of Sec16, and that it is not functionally redundant with Sec16A