Tracking Risk Factors Related to an Outbreak of COVID-19 Among Healthcare Workers in a General Medicine Ward.

Background An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection occurred in a medical ward involving patients and hospital staff from May to June 2020. Aim The aim of this study is to determine risk factors related to the outbreak of SARS-CoV-2 in six healthcare workers (HCWs) in a medical ward with initially unrecognized coronavirus disease 2019 (COVID-19) positive patients. Methods A retrospective cross-sectional study was conducted using a comprehensive questionnaire and personal interviews to determine the risk factors for COVID-19 infection in HCWs. Findings A total of 6/34 HCWs were diagnosed with COVID-19 in a medical ward. There were no differences between COVID-19 negative HCWs and COVID-19 positive HCWs in terms of mean duration of hours worked in the unit during the cluster event (180.2 vs 177.5 hours) (p>0.05), mean total time spent in contact with COVID-19 positive patients (12.8 vs 10.5 hours) (p>0.05), mean total time spent on aerosol-generating procedures (1.9 vs 0.9 hours) (p>0.05), and mean total time spent on non-aerosol generating procedures (10.9 vs 9.6 hours ) (p>0.05). There was no difference in exposure to COVID-19 positive family members among the HCWs (33% vs 3.7%, p=0.08). In contrast, exposure to COVID-19 positive contacts in the community was significantly greater in infected vs non-infected HCWs (16.7% vs 0%, p=0.03). Conclusion There was no significant difference in risk factors for contracting SARs-CoV2 among HCWs due to hospital exposures. COVID-19 positive HCWs were more likely to be exposed to positive individuals in their households and community, indicating that the source of SARS-CoV-2 infection came from outside the hospital.

Bioprinting of exosomes: Prospects and challenges for clinical applications.

453Three-dimensional bioprinting (3DBP) is an additive manufacturing technique that has emerged as a promising strategy for the fabrication of scaffolds, which can successfully recapitulate the architectural, biochemical, and physical cues of target tissues. More importantly, 3DBP offers fine spatiotemporal control and high submicron scale resolution, which can be leveraged for the incorporation and directional gradient release of single or multiple biomimetic cues, including cell-derived exosomes (EXOs). EXOs are extracellular vesicles that originate from the endosomal compartment of various cell types, with sizes ranging from 30 to120 nm. They act as cell mediators and contain discrete cell constituents, including growth factors, cytokines, lipid moieties, nucleic acids, metabolites, and cell surface markers, depending on the cell type. Essentially, owing to their therapeutic potential, EXOs derived from mesenchymal stem cells (MSCs) have been recently investigated in several clinical trials for the treatment of various conditions, including cancer, diabetes, dry eyes, periodontitis, and acute ischemic stroke. The 3DBP strategy of EXOs is especially useful in tissue engineering and regenerative medicine applications, as tissues can be biofabricated to closely mimic the complex microarchitecture and developmental profiles of native heterogeneous tissues for restoring biological functions. Moreover, EXOs can be manipulated to carry exogenous cargo such as genes or proteins of therapeutic interest, confer multifunctional attributes, and further enhance their tissue regenerative potential. However, significant challenges, including the selection of appropriate bioink, pattern resolution, engineering-defined exosomal gradient, spatial presentation and modulation of EXO release kinetics, as well as EXO stability and storage conditions, must be addressed for the successful translation of therapeutic grade EXOs to clinical settings. In this review, we highlight the recent advances and offer future perspectives on the bioprinting of EXOs as regenerative biotherapeutics for the fabrication of complex heterogeneous tissues that are suitable for clinical transplantation.

Shared reproductive disruption, not neural crest or tameness, explains the domestication syndrome.

Altered neural crest cell (NCC) behaviour is an increasingly cited explanation for the domestication syndrome in animals. However, recent authors have questioned this explanation, while others cast doubt on whether domestication syndrome even exists. Here, we review published literature concerning this syndrome and the NCC hypothesis, together with recent critiques of both. We synthesize these contributions and propose a novel interpretation, arguing shared trait changes under ancient domestication resulted primarily from shared disruption of wild reproductive regimes. We detail four primary selective pathways for 'reproductive disruption' under domestication and contrast these succinct and demonstrable mechanisms with cryptic genetic associations posited by the NCC hypothesis. In support of our perspective, we illustrate numerous important ways in which NCCs contribute to vertebrate reproductive phenotypes, and argue it is not surprising that features derived from these cells would be coincidentally altered under major selective regime changes, as occur in domestication. We then illustrate several pertinent examples of Darwin's 'unconscious selection' in action, and compare applied selection and phenotypic responses in each case. Lastly, we explore the ramifications of reproductive disruption for wider evolutionary discourse, including links to wild 'self-domestication' and 'island effect', and discuss outstanding questions.

Prehospital management of exertional heat stroke at sports competitions for Paralympic athletes.

OBJECTIVES: To adapt key components of exertional heat stroke (EHS) prehospital management proposed by the Intenational Olympic Committee Adverse Weather Impact Expert Working Group for the Olympic Games Tokyo 2020 so that it is applicable for the Paralympic athletes. METHODS: An expert working group representing members with research, clinical and lived sports experience from a Para sports perspective reviewed and revised the IOC consensus document of current best practice regarding the prehospital management of EHS. RESULTS: Similar to Olympic competitions, Paralympic competitions are also scheduled under high environmental heat stress; thus, policies and procedures for EHS prehospital management should also be established and followed. For Olympic athletes, the basic principles of EHS prehospital care are: early recognition, early diagnosis, rapid, on-site cooling and advanced clinical care. Although these principles also apply for Paralympic athletes, slight differences related to athlete physiology (eg, autonomic dysfunction) and mechanisms for hands-on management (eg, transferring the collapsed athlete or techniques for whole-body cooling) may require adaptation for care of the Paralympic athlete. CONCLUSIONS: Prehospital management of EHS in the Paralympic setting employs the same procedures as for Olympic athletes with some important alterations.

Prognostic accuracy of triage tools for adults with suspected COVID-19 in a pre-hospital setting: an observational cohort study

Study ObjectiveTools proposed to triage patient acuity in COVID-19 infection have only been validated in hospital populations. We estimated the accuracy of five risk-stratification tools recommended to predict severe illness and compare accuracy to existing clinical decision-making in a pre-hospital setting. MethodsAn observational cohort study using linked ambulance service data for patients attended by EMS crews in the Yorkshire and Humber region of England between 18th March 2020 and 29th June 2020 was conducted to assess performance of the PRIEST tool, NEWS2, the WHO algorithm, CRB-65 and PMEWS in patients with suspected COVID-19 infection. The primary outcome was death or need for organ support. ResultsOf 7549 patients in our cohort, 17.6% (95% CI:16.8% to 18.5%) experienced the primary outcome. The NEWS2, PMEWS, PRIEST tool and WHO algorithm identified patients at risk of adverse outcomes with a high sensitivity (>0.95) and specificity ranging from 0.3 (NEWS2) to 0.41 (PRIEST tool). The high sensitivity of NEWS2 and PMEWS was achieved by using lower thresholds than previously recommended. On index assessment, 65% of patients were transported to hospital and EMS decision to transfer patients achieved a sensitivity of 0.84 (95% CI 0.83 to 0.85) and specificity of 0.39 (95% CI 0.39 to 0.40). ConclusionUse of NEWS2, PMEWS, PRIEST tool and WHO algorithm could improve sensitivity of EMS triage of patients with suspected COVID-19 infection. Use of the PRIEST tool would improve sensitivity of triage without increasing the number of patients conveyed to hospital.

Prognostic accuracy of emergency department triage tools for adults with suspected COVID-19: The PRIEST observational cohort study

ObjectivesThe World Health Organisation (WHO) and National Institute for Health and Care Excellence (NICE) recommend various triage tools to assist decision-making for patients with suspected COVID-19. We aimed to estimate the accuracy of triage tools for predicting severe illness in adults presenting to the emergency department (ED) with suspected COVID-19 infection. MethodsWe undertook a mixed prospective and retrospective observational cohort study in 70 EDs across the United Kingdom (UK). We collected data from people attending with suspected COVID-19 between 26 March 2020 and 28 May 2020, and used presenting data to determine the results of assessment with the following triage tools: the WHO algorithm, NEWS2, CURB-65, CRB-65, PMEWS and the swine flu adult hospital pathway (SFAHP). We used 30-day outcome data (death or receipt of respiratory, cardiovascular or renal support) to determine prognostic accuracy for adverse outcome. ResultsWe analysed data from 20892 adults, of whom 4672 (22.4%) died or received organ support (primary outcome), with 2058 (9.9%) receiving organ support and 2614 (12.5%) dying without organ support (secondary outcomes). C-statistics for the primary outcome were: CURB-65 0.75; CRB-65 0.70; PMEWS 0.77; NEWS2 (score) 0.77; NEWS2 (rule) 0.69; SFAHP (6-point) 0.70; SFAHP (7-point) 0.68; WHO algorithm 0.61. All triage tools showed worse prediction for receipt of organ support and better prediction for death without organ support. At the recommended threshold, PMEWS and the WHO criteria showed good sensitivity (0.96 and 0.95 respectively), at the expense of specificity (0.31 and 0.27 respectively). NEWS2 showed similar sensitivity (0.96) and specificity (0.28) when a lower threshold than recommended was used. ConclusionCURB-65, PMEWS and NEWS2 provide good but not excellent prediction for adverse outcome in suspected COVID-19, and predicted death without organ support better than receipt of organ support. PMEWS, the WHO criteria and NEWS2 (using a lower threshold than usually recommended) provide good sensitivity at the expense of specificity. RegistrationISRCTN registry, ISRCTN28342533, http://www.isrctn.com/ISRCTN28342533

Prognostic accuracy of emergency department triage tools for children with suspected COVID-19: The PRIEST observational cohort study

ObjectivesEmergency department clinicians can use triage tools to predict adverse outcome and support management decisions for children presenting with suspected COVID-19. We aimed to estimate the accuracy of triage tools for predicting severe illness in children presenting to the emergency department (ED) with suspected COVID-19 infection. MethodsWe undertook a mixed prospective and retrospective observational cohort study in 44 EDs across the United Kingdom (UK). We collected data from children attending with suspected COVID-19 between 26 March 2020 and 28 May 2020, and used presenting data to determine the results of assessment using the WHO algorithm, swine flu hospital pathway for children (SFHPC), Paediatric Observation Priority Score (POPS) and Childrens Observation and Severity Tool (COAST). We recorded 30-day outcome data (death or receipt of respiratory, cardiovascular or renal support) to determine prognostic accuracy for adverse outcome. ResultsWe collected data from 1530 children, including 26 (1.7%) with an adverse outcome. C-statistics were 0.80 (95% confidence interval 0.73-0.87) for the WHO algorithm, 0.80 (0.71-0.90) for POPS, 0.76 (0.67-0.85) for COAST, and 0.71 (0.59-0.82) for SFHPC. Using pre-specified thresholds, the WHO algorithm had the highest sensitivity (0.85) and lowest specificity (0.75), but POPS and COAST could optimise sensitivity (0.96 and 0.92 respectively) at the expense of specificity (0.25 and 0.38 respectively) by using a threshold of any score above zero instead of the pre-specified threshold. ConclusionExisting triage tools have good but not excellent prediction for adverse outcome in children with suspected COVID-19. POPS and COAST could achieve an appropriate balance of sensitivity and specificity for supporting decisions to discharge home by considering any score above zero to be positive. RegistrationISRCTN registry, ISRCTN28342533, http://www.isrctn.com/ISRCTN28342533

Characterisation of 22446 patients attending UK emergency departments with suspected COVID-19 infection: Observational cohort study

BackgroundHospital emergency departments play a crucial role in the Initial management of suspected COVID-19 infection. We aimed to characterise patients attending emergency departments with suspected COVID-19, including subgroups based on sex, ethnicity and COVID-19 test results. MethodsWe undertook a mixed prospective and retrospective observational cohort study in 70 emergency departments across the United Kingdom (UK). We collected presenting data from 22446 people attending with suspected COVID-19 between 26 March 2020 and 28 May 2020. Outcomes were admission to hospital, COVID-19 result, organ support (respiratory, cardiovascular or renal), and death, by record review at 30 days. ResultsAdults were acutely unwell (median NEWS2 score 4) and had high rates of admission (67.1%), COVID-19 positivity (31.2%), organ support (9.8%) and death (15.9%). Children had much lower rates of admission (27.4%), COVID-19 positivity (1.2%), organ support (1.4%) and death (0.3%). Adult men and women presented in similar numbers (10210 versus 10506), but men were more likely to be admitted (72.9% v 61.4%), require organ support (12.2% v 7.7%) and die (18.7% v 13.3%). Black or Asian adults tended to be younger than White adults (median age 54, 50 and 67 years), were less likely to be admitted (60.8%, 57.3%, 69.6%) or die (11.9%, 11.2%, 16.8%), but were more likely to require organ support (15.9%, 14.3%, 8.9%) or have a positive COVID-19 test (40.8%, 42.1%, 30.0%). Adults admitted with confirmed COVID-19 had similar age and comorbidities (except chronic lung disease) to those who did not have COVID-19 confirmed, but were much more likely to need organ support (22.2% v 8.9%) or die (32.7% v 15.9%). ConclusionsImportant differences exist between patient groups presenting to the emergency department with suspected COVID-19. People with confirmed COVID-19 have a poor prognosis, compared with similar emergency admissions without confirmed COVID-19. RegistrationISRCTN registry, ISRCTN56149622, http://www.isrctn.com/ISRCTN28342533

Post-exertion oxygen saturation as a prognostic factor for adverse outcome in patients attending the emergency department with suspected COVID-19: Observational cohort study

BackgroundMeasurement of post-exertion oxygen saturation has been proposed to assess illness severity in suspected COVID-19 infection. We aimed to determine the accuracy of post-exertional oxygen saturation for predicting adverse outcome in suspected COVID-19. MethodsWe undertook an observational cohort study across 70 emergency departments during first wave of the COVID-19 pandemic in the United Kingdom. We collected data prospectively, using a standardised assessment form, and retrospectively, using hospital records, from patients with suspected COVID-19, and reviewed hospital records at 30 days for adverse outcome (death or receiving organ support). Patients with post-exertion oxygen saturation recorded were selected for this analysis. ResultsWe analysed data from 817 patients with post-exertion oxygen saturation recorded after excluding 54 in whom measurement appeared unfeasible. The c-statistic for post-exertion change in oxygen saturation was 0.589 (95% confidence interval 0.465 to 0.713), and the positive and negative likelihood ratios of a 3% or more desaturation were respectively 1.78 (1.25 to 2.53) and 0.67 (0.46 to 0.98). Multivariable analysis showed that post-exertion oxygen saturation was not a significant predictor of adverse outcome when baseline clinical assessment was taken into account (p=0.368). Secondary analysis excluding patients in whom post-exertion measurement appeared inappropriate resulted in a c-statistic of 0.699 (0.581 to 0.817), likelihood ratios of 1.98 (1.26 to 3.10) and 0.61 (0.35 to 1.07), and some evidence of additional prognostic value on multivariable analysis (p=0.019). ConclusionsPost-exertion oxygen saturation provides modest prognostic information in the assessment of patients attending the emergency department with suspected COVID-19. RegistrationISRCTN registry, ISRCTN56149622, http://www.isrctn.com/ISRCTN28342533 Key messagesWhat is already known on this subject? O_LIPost exertional decrease in oxygen saturation can be used to predict prognosis in chronic lung diseases C_LIO_LIPost exertional desaturation has been proposed as a way of predicting adverse outcome in people with suspected COVID-19 C_LI What this study adds: O_LIPost-exertion oxygen saturation provides modest prognostic information in the assessment of patients attending the emergency department with suspected COVID-19 C_LI

Physiological Correlates to In-race Paratriathlon Cycling Performance.

The purpose was to determine the physiological correlates to cycling performance within a competitive paratriathlon. Five wheelchair user and ten ambulant paratriathletes undertook laboratory-based testing to determine their: peak rate of oxygen uptake; blood lactate- and ventilatory-derived physiological thresholds; and, their maximal aerobic power. These variables were subsequently expressed in absolute (l∙min -1 or W), relative (ml∙kg-1∙min -1 or W∙kg -1) and scaled relative (or ml∙kg - 0.82 ∙min -1, ml∙kg - 0.32 ∙min -1 or W∙kg -0.32) terms. All athletes undertook a paratriathlon race with 20 km cycle. Pearson's correlation test and linear regression analyses were produced between laboratory-derived variables and cycle performance to generate correlation coefficients (r), standard error of estimates and 95% confidence intervals. For wheelchair users, performance was most strongly correlated to relative aerobic lactate threshold (W∙kg -1) (r=-0.99; confidence intervals: -0.99 to -0.99; standard error of estimate=22 s). For ambulant paratriathletes, the greatest correlation was with maximal aerobic power (W∙kg -0.32) (r=-0.91; -0.99 to -0.69; standard error of estimate=88 s). Race-category-specificity exits regarding physiological correlates to cycling performance in a paratriathlon race with further differences between optimal scaling factors between paratriathletes. This suggests aerobic lactate threshold and maximal aerobic power are the pertinent variables to infer cycling performance for wheelchair users and ambulant paratriathletes, respectively.

Female status, food security, and stature sexual dimorphism: Testing mate choice as a mechanism in human self-domestication.

OBJECTIVES: Humans exhibit multiple anatomical and behavioral signatures of domestication syndrome, leading evolutionary-minded scholars to suggest Homo sapiens is a "self-domesticated" species. We examined one of three mechanisms proposed to explain human self-domestication-that is, intersexual selection against reactive aggression. We hypothesized that this process has been, at least in part, caused by context-dependent female preferences for less-aggressive males. We predicted that societies where women have higher social status will show relatively elevated signs of self-domestication-as indicated by lower stature sexual dimorphism (SSD)-and that this relationship should be mediated by food security. MATERIALS AND METHODS: To test our prediction, we used male and female stature data for 28 societies from the Standard Cross-Cultural Sample. We applied multivariate regression to examine our hypothesis while controlling for theoretically important confounders. RESULTS: We found convincing support for the prediction that the relationship between SSD and female status is mediated by food security. As predicted, higher female status was associated with less sexual dimorphism and the effect is stronger when food resources are secure. DISCUSSION: Context-dependent female mate choices significantly contribute to lower SSD, suggesting female mate choice is likely to have played an influential role in human self-domestication. Future research on this theme will benefit by including more of the expected symptoms of human self-domestication and examining other potential drivers of this process.

Interaction of silver nanoparticles with serum proteins affects their antimicrobial activity in vivo.

The emergence of multidrug-resistant bacteria is a global threat for human society. There exist recorded data that silver was used as an antimicrobial agent by the ancient Greeks and Romans during the 8th century. Silver nanoparticles (AgNPs) are of potential interest because of their effective antibacterial and antiviral activities, with minimal cytotoxic effects on the cells. However, very few reports have shown the usage of AgNPs for antibacterial therapy in vivo. In this study, we deciphered the importance of the chosen methods for synthesis and capping of AgNPs for their improved activity in vivo. The interaction of AgNPs with serum albumin has a significant effect on their antibacterial activity. It was observed that uncapped AgNPs exhibited no antibacterial activity in the presence of serum proteins, due to the interaction with bovine serum albumin (BSA), which was confirmed by UV-Vis spectroscopy. However, capped AgNPs [with citrate or poly(vinylpyrrolidone)] exhibited antibacterial properties due to minimized interactions with serum proteins. The damage in the bacterial membrane was assessed by flow cytometry, which also showed that only capped AgNPs exhibited antibacterial properties, even in the presence of BSA. In order to understand the in vivo relevance of the antibacterial activities of different AgNPs, a murine salmonellosis model was used. It was conclusively proved that AgNPs capped with citrate or PVP exhibited significant antibacterial activities in vivo against Salmonella infection compared to uncapped AgNPs. These results clearly demonstrate the importance of capping agents and the synthesis method for AgNPs in their use as antimicrobial agents for therapeutic purposes.

Chitosan-dextran sulphate nanocapsule drug delivery system as an effective therapeutic against intraphagosomal pathogen Salmonella.

OBJECTIVES: The ability to target conventional drugs efficiently inside cells to kill intraphagosomal bacteria has been a major hurdle in treatment of infective diseases. We aimed to develop an efficient drug delivery system for combating infection caused by Salmonella, a well-known intracellular and intraphagosomal pathogen. Chitosan-dextran sulphate (CD) nanocapsules were assessed for their efficiency in delivering drugs against Salmonella. METHODS: The CD nanocapsules were prepared using the layer-by-layer method and loaded with ciprofloxacin or ceftriaxone. Antibiotic-loaded nanocapsules were analysed in vitro for their ability to enter epithelial and macrophage cells to kill Salmonella. In vivo pharmacokinetics and organ distribution studies were performed to check the efficiency of the delivery system. The in vivo antibacterial activity of free antibiotic and antibiotic loaded into nanocapsules was tested in a murine salmonellosis model. RESULTS: In vitro and in vivo experiments showed that this delivery system can be used effectively to clear Salmonella infection. CD nanocapsules were successfully employed for efficient targeting and killing of the intracellular pathogen at a dosage significantly lower than that of the free antibiotic. The increased retention time of ciprofloxacin in the blood and organs when it was delivered by CD nanocapsules compared with the conventional routes of administration may be the reason underlying the requirement for a reduced dosage and frequency of antibiotic administration. CONCLUSIONS: CD nanocapsules can be used as an efficient drug delivery system to treat intraphagosomal pathogens, especially Salmonella infection. This delivery system might be used effectively for other vacuolar pathogens including Mycobacteria, Brucella and Legionella.

Pulmonary arterial hypertension in mixed connective tissue disease: successful treatment with Iloprost.

This paper describes a 61-year-old woman who presented with mixed connective tissue disease, which was complicated by the development of pulmonary arterial hypertension (PAH). Her condition worsened rapidly, with development of haemopthysis, tachypnoe and cardiac arrest. Doppler echocardiography showed a high systolic pulmonary arterial pressure (98 mmHg), confirmed by the right heart catheterization. Vasculopathy of the pulmonary artery vessels was detected following open lung biopsy. No pulmonary embolism was found. Because of suspicion of flare of her underlying disease, which leads to PAH, immunosuppressive treatment was started with high doses of corticosteroid and cyclophosphamide, in combination with the prostacyclin analogue, Iloprost, and low molecular weight heparin. The therapy resulted in slow recovery over 6 weeks, with control echocardiography showing normalization of the high pulmonary pressure, and the patient being capable of returning to everyday activities.

Dietary self-efficacy: determinant of compliance behaviours and biochemical outcomes in haemodialysis patients.

BACKGROUND: Despite the diversity of proposed theories, researchers are still unable to fully explain dietary compliance behaviours of dialysis patients. Dietary self-efficacy, a concept less studied in dialysis, has been linked to positive compliance outcomes in the chronic illness literature. Therefore, the aim of the present research was to determine how dietary self-efficacy is related to selected biochemical markers and self-reported behavioural outcomes in haemodialysis patients. METHODS: 107 subjects participated in a cross-sectional study. Four questionnaires assessed dietary self-efficacy, compliance attitudes and behaviours, and staff-patient relationships. Laboratory outcomes were retrospectively obtained from patients' medical records and averaged for the previous 6 months. RESULTS: Of the behavioural measures, only dietary self-efficacy was associated with laboratory outcomes. Dietary self-efficacy was also positively related to staff-patient relationships and to patients' self-reported assessment of compliance behaviours. Women had greater dietary self-efficacy than men. The number of family members living with the respondent was inversely related to dietary self-efficacy. CONCLUSIONS: Results indicated that dietary self-efficacy determined both behaviours and laboratory outcomes. Patients with greater dietary self-efficacy had lower serum potassium and weight gain, showed favourable compliance attitudes and behaviours toward prescribed regimens and fostered better relationships with staff. Based on these findings we recommend an experimental approach to clarify whether maximizing dietary self-efficacy efforts is without psychological burden to patients and whether the positive effect of increased dietary self-efficacy is maintained in long-term dialysis patients.

Early referral and planned initiation of dialysis: what impact on quality of life?

BACKGROUND: Early patient referral correlates with improved patient survival on dialysis. We examine whether early referral and a planned first dialysis affect quality of life (QoL). METHODS: All patients commencing dialysis in nine centres in seven European countries between 1 July 1998 and 31 October 1999 were recruited. DEFINITIONS: early referral=followed by a nephrologist >1 month before first dialysis (<1 month=late referral); planned=early referral and previous serum creatinine >300 micro mol/l and non-urgent first dialysis (early referral and no creatinine >300 micro mol/l or urgent first dialysis=unplanned). QoL was measured at 8 weeks using a visual analogue scale (VAS) and Short Form 36 (SF-36). RESULTS: VAS was significantly higher in early referral patients [mean (SD) 58.4 (20) vs 50.4 (19), P=0.005], particularly if the first dialysis was planned [60.7 (20) vs 54.2 (20), P=0.03]. Planned patients also had higher SF-36 mental summary scores [45.4 (12) vs 39.7 (11), P=0.003], role emotional scores [58.0 (43) vs 30.9 (38), P=0.003], and mental health scores [63.7 (24) vs 54.6 (22), P=0.01] than unplanned patients. Adjusting for centre and other confounding variables showed that having a planned first dialysis had an independent effect on QoL (VAS, and the SF-36's mental summary score, physical functioning, role physical, general health, role emotional and mental health). Early referral had no independent effect on QoL. Socio-economic status had an important positive effect on physical QoL. CONCLUSIONS: While the effect of early referral to a nephrologist on QoL appeared centre dependent, a smooth transition onto dialysis was associated with significantly better early QoL, independent of other variables.

[Frequency of hyperhomocysteinemia in hemodialysis patients with folic acid supplementation]. / A hyperhomocysteinaemia gyakorisága, folsavpótlásban részesüló hemodializált betegekben.

BACKGROUND: It is known that hyperhomocystinemia is an independent risk factor for development of atherosclerosis. In end stage renal disease the frequency of hyperhomocystinemia is much greater than in normal populations. AIM: In this study homocystein (Hcy), folic acid and vitamin B12 concentrations were determined in 125 chronic renal failure patients being on folic acid supplementation (3 mg/day). In 107 patients the frequency of C667T polymorphism of methylene tetrahyrofolate reductase (MTHFR) was also determined. The relationships between these parameters were also studied. RESULTS: It was found that in these patients who are under continuous folic acid supplementation the mean level of homocysteine was 16.8 +/- 7.2 mumol/L, a value considerably lower than the homocysteine concentration reported for non-supplemented patients. The elevation of homocysteine concentrations was independent of gender, time spent in renal replacement therapy, and the type of renal replacement therapy (hemodialysis: 17.6 +/- 12.6; hemodiafiltration: 16.6 +/- 12.9 mumol/L). Data showed an inverse relation between plasma homocysteine concentrations and the concentrations of folic acid and vitamin B12. Moderately severe hyperhomocystinemia (Hcy > 20 mumol/L) was found in about 30% of patients. In those the frequency of patients for homozygous T677 allele of MTHFR was about 25-30%. However, in all ESRD patients the frequency of the homozygotes was the same then in the normal population. Homocysteine plasma levels correlated with MTHFR polymorphism: in the wild type group Hcy was 14 +/- 7 mumol/L, in the heterozygous group was 17.2 +/- 6.2 mumol/L, and in the homozygous group was 21 +/- 19 mumol/L. CONCLUSIONS: Long-term folic acid supplementation decreased the homocysteine level in end stage renal disease patients. However, in folic acid resistant group, who were in 30% homozygotes for C667T of MTHFR (suggesting that homocysteine-methionine remethylation cycle is disturbed), instead of the administration of folic acid, methylene tetrahydrofolate supplementation might be considered.