Impact of the COVID-19 pandemic on symptoms of anxiety and depression and health-related quality of life in older patients with chronic kidney disease.

BACKGROUND: Older patients with advanced chronic kidney disease are at increased risk for a severe course of the coronavirus disease-2019 (COVID-19) and vulnerable to mental health problems. We aimed to investigate prevalence and associated patient (demographic and clinical) characteristics of mental wellbeing (health-related quality of life [HRQoL] and symptoms of depression and anxiety) before and during the COVID-19 pandemic in older patients with advanced chronic kidney disease. METHODS: An ongoing Dutch multicentre prospective cohort study enrols patients of ≥70 years with an eGFR < 20 mL/min/1.73m2 from October 2018 onward. With additional questionnaires during the pandemic (May-June 2020), disease-related concerns about COVID-19 and general anxiety symptoms were assessed cross-sectionally, and depressive symptoms, HRQoL, and emotional symptoms longitudinally. RESULTS: The 82 included patients had a median age of 77.5 years (interquartile range 73.9-82.1), 77% were male and none had tested positive for COVID-19. Cross-sectionally, 67% of the patients reported to be more anxious about COVID-19 because of their kidney disease, and 43% of the patients stated that their quality of life was reduced due to the COVID-19 pandemic. Compared to pre-COVID-19, the presence of depressive symptoms had increased (11 to 22%; p = .022) and physical HRQoL declined (M = 40.4, SD = 10.1 to M = 36.1, SD = 10.4; p < .001), particularly in males. Mental HRQoL (M = 50.3, SD = 9.6 to M = 50.4, SD = 9.9; p = .913) and emotional symptoms remained similar. CONCLUSIONS: Older patients with advanced chronic kidney disease suffered from disease-related anxiety about COVID-19, increased depressive symptoms and reduced physical HRQoL during the COVID-19 pandemic. The impact of the pandemic on this vulnerable patient group extends beyond increased mortality risk, and awareness of mental wellbeing is important. TRIAL REGISTRATION: The study is registered at the Netherlands Trial Register (NTR), trial number NL7104. Date of registration: 06-06-2018.

Rewetting does not return drained fen peatlands to their old selves.

Peatlands have been drained for land use for a long time and on a large scale, turning them from carbon and nutrient sinks into respective sources, diminishing water regulation capacity, causing surface height loss and destroying biodiversity. Over the last decades, drained peatlands have been rewetted for biodiversity restoration and, as it strongly decreases greenhouse gas emissions, also for climate protection. We quantify restoration success by comparing 320 rewetted fen peatland sites to 243 near-natural peatland sites of similar origin across temperate Europe, all set into perspective by 10k additional European fen vegetation plots. Results imply that rewetting of drained fen peatlands induces the establishment of tall, graminoid wetland plants (helophytisation) and long-lasting differences to pre-drainage biodiversity (vegetation), ecosystem functioning (geochemistry, hydrology), and land cover characteristics (spectral temporal metrics). The Paris Agreement entails the rewetting of 500,000 km2 of drained peatlands worldwide until 2050-2070. A better understanding of the resulting locally novel ecosystems is required to improve planning and implementation of peatland rewetting and subsequent management.

Sphagnum growth under N saturation: interactive effects of water level and P or K fertilization.

Sphagnum biomass is a promising material that could be used as a substitute for peat in growing media and can be sustainably produced by converting existing drainage-based peatland agriculture into wet, climate-friendly agriculture (paludiculture). Our study focuses on yield maximization of Sphagnum as a crop. We tested the effects of three water level regimes and of phosphorus or potassium fertilization on the growth of four Sphagnum species (S. papillosum, S. palustre, S. fimbriatum, S. fallax). To simulate field conditions in Central and Western Europe we carried out a glasshouse experiment under nitrogen-saturated conditions. A constant high water table (remaining at 2 cm below capitulum during growth) led to highest productivity for all tested species. Water table fluctuations between 2 and 9 cm below capitulum during growth and a water level 2 cm below capitulum at the start but falling relatively during plant growth led to significantly lower productivity. Fertilization had no effect on Sphagnum growth under conditions with high atmospheric deposition such as in NW Germany (38 kg N, 0.3 kg P, 7.6 kg K·ha-1 ·year-1 ). Large-scale maximization of Sphagnum yields requires precise water management, with water tables just below the capitula and rising with Sphagnum growth. The nutrient load in large areas of Central and Western Europe from atmospheric deposition and irrigation water is high but, with an optimal water supply, does not hamper Sphagnum growth, at least not of regional provenances of Sphagnum.

Treatable Vascular Risk and Cognitive Performance in Persons Aged 35 Years or Older: Longitudinal Study of Six Years.

BACKGROUND: Poor cognitive performance is associated with high vascular risk. However, this association is only investigated in elderly. As neuropathological changes precede clinical symptoms of cognitive impairment by several decades, it is likely that cognitive performance is already associated with vascular risk at middle-age. OBJECTIVES: To investigate the association of cognitive performance with treatable vascular risk in middle-aged and old persons. DESIGN: Longitudinal study with three measurements during follow-up period of 5.5 years. SETTING: City of Groningen, the Netherlands. PARTICIPANTS: Cohort of 3,572 participants (age range, 35-82 years; mean age, 54 years; men, 52%). EXPOSURE: Treatable vascular risk as defined by treatable components of the Framingham Risk Score for Cardiovascular Disease at the first measurement (diabetes mellitus, smoking, hypercholesterolemia and hypertension). MEASUREMENTS: Change in cognitive performance during follow-up. Cognitive performance was measured with Ruff Figural Fluency Test (RFFT) and Visual Association Test (VAT), and calculated as the average of the standardized RFFT and VAT score per participant. RESULTS: The mean (SD) cognitive performance changed from 0.00 (0.79) at the first measurement to 0.15 (0.83) at second measurement and to 0.39 (0.82) at the third measurement (Ptrend<0.001). This change was negatively associated with treatable vascular risk: the change in cognitive performance between two measurements decreased with 0.004 per one-point increment of treatable vascular risk (95%CI, -0.008 to 0.000; P=0.05) and with 0.006 per one-year increment of age (95%CI, -0.008 to -0.004; P<0.001). CONCLUSIONS: Change in cognitive performance was associated with treatable vascular risk in persons aged 35 years or older.

[Zosteriform cutaneous metastasis in melanoma]. / Mélanome avec métastases cutanées zostériformes.

INTRODUCTION: Cutaneous metastases are common in patients with malignant melanoma. In rare cases, they are distributed on a dermatome, in which case they are known as zosteriform metastases. OBSERVATION: We report the case of a patient with zosteriform metastasis of a malignant melanoma, progressing unfavourably despite surgical excision and immunotherapy. DISCUSSION: The physiopathology of this condition continues to be poorly understood.

Determination of single cell lag times of Cronobacter spp. strains exposed to different stress conditions: Impact on detection.

The variability of stress resistance and lag time of single cells can have a big impact on their growth and therefore on the probability of their detection in food. In this study, six strains of Cronobacter spp. were subjected to heat, acid and desiccation stress and single cell lag times were determined using optical density measurements. The duration of lag time was highest after acid stress and did not correlate to stress resistance. The effect that the inactivation caused by stress and an extended lag time had on the projected cfu level reached after enrichment was simulated in different scenarios. For most strains, an enrichment time of 18h was sufficient for stressed cells to reach the suggested minimum level of cell inoculum for the Cronobacter screening broth detection. Particular strains may require longer recovery periods. Further, probability calculations showed that the number of samples taken from a batch may have an important effect on detection probability, especially at low contamination rates. Therefore, in addition to increasing the recovery period, increasing the number of samples is a suitable strategy to improve detection.

Effects of different media on the enrichment of low numbers of Shiga toxin-producing Escherichia coli in mung bean sprouts and on the development of the sprout microbiome.

Sprouted seeds have been implicated in a number of serious outbreaks caused by Salmonella and Shiga toxin-producing Escherichia coli. Sprouts pose a very complex challenge to bacterial pathogen enrichment and detection since they naturally contain high levels of background microflora including members of the Enterobacteriaceae. As such, the currently used method cannot ensure reliable detection of STEC in sprouts. In this study, we compared different media for the enrichment of Enterobacteriaceae in their ability to promote the growth of stressed STEC at 37°C and 42°C. Mung bean sprouts were spiked with low levels of STEC and their growth was recorded over time. In addition, the microbiome of mung bean sprouts was analysed before and after enrichment. Our results indicate that the growth of dry-stressed STEC is comparable in all of the tested enrichment media except for mTSB+Novobiocin and not influenced by the incubation temperature. Low levels of STEC spiked into the sprouts resuspended in media only grew to levels of around 4logcfu/ml during enrichment, which could reduce the probability of detection. Proteobacteria was the dominant phylum detected within the microbiome of non-enriched mung bean sprouts. During enrichment in EE-broth, Proteobacteria remained the most abundant phylum. In contrast, during enrichment in BPW the relative abundance of Proteobacteria decreased whereas Firmicutes increased when compared to the non-enriched mung bean sprout microbiome. The microbiome composition was not significantly influenced by the incubation temperature during enrichment in both BPW and EE-broth. This is the first study to examine the microbiome on sprouted mung bean seeds during BPW and EE enrichment and relates the bacterial community composition changes to the enrichment of pathogens.

Evaluation of different buffered peptone water (BPW) based enrichment broths for detection of Gram-negative foodborne pathogens from various food matrices.

This study evaluated the effects of changing the composition of the pre-enrichment medium buffered peptone water (BPW) on the growth of stressed and unstressed Gram-negative foodborne pathogens in a one-broth enrichment strategy. BPW supplemented with an available iron source and sodium pyruvate, along with low levels of 8-hydroxyquinoline and sodium deoxycholate (BPW-S) improved the recovery of desiccated Cronobacter spp. from powdered infant formula. Growth of Salmonella and STEC was comparable in all BPW variants tested for different food matrices. In products with high levels of Gram-negative background flora (e.g. sprouts), the target organisms could not be reliably detected by PCR in any of the BPW variants tested unless the initial level exceeded 10(3) cfu/10 g of sprouts. Based on these results we suggest BPW-S for a one-broth enrichment strategy of stressed Gram-negative foodborne pathogens from dry products. However, a one-broth enrichment strategy based on BPW variants tested in this evaluation is not recommended for produce with a high level of Gram-negative background flora due to very high detection limits.

An aid to the diagnosis of genetic disorders underlying adult-onset renal failure: a literature review.

Several genetic disorders can present in adult patients with renal insufficiency. Genetic renal disease other than ADPKD accounts for ESRD in 3% of the adult Dutch population. Because of this low prevalence and their clinical heterogeneity most adult nephrologists are less familiar with these disorders. As a guideline to differential diagnosis, we provide an overview of the clinical manifestations and the pathogenesis of the main genetic disorders with chronic renal insufficiency surfacing in adulthood and add an algorithm plus 4 tables. We also indicate where molecular genetics nowadays can be of aid in the diagnostic process. The following disorders are discussed by mode of inheritance: 1) Autosomal dominant: autosomal dominant polycystic kidney disease, nephropathies associated with uromodulin (medullary cystic disease and familial juvenile hyperuricemic nephropathy), renal cysts and diabetes syndrome, nail-patella syndrome, glomerulopathy with fibronectin deposits. 2) Not autosomal dominant: Nephronophthisis, Fabry disease, primary oxalosis, Adenine Phosphoribosyl Transferase deficiency, Alport syndrome, Lecithin-cholesterol acyltransferase deficiency, adult-onset cystinosis.

eGFR and creatinine clearance in relation to metabolic changes in an unselected patient population.

BACKGROUND: It is widely assumed that moderate to severe renal failure (creatinine clearance <60 ml/min; or an MDRD-4 (Modification of Diet in Renal Disease equation) <60 ml/min/1.73 m(2)) is associated with metabolic changes, often needing further assessment and treatment. We investigated whether such abnormalities are already present at earlier stages of kidney disease, as assessed by 24-hour urine sampling and MDRD-4 calculation. METHODS: A select, retrospective cohort study was conducted. Creatinine clearance was measured by collecting 24-hour urines. The individual eGFRs were calculated with the MDRD-4 formula and patients were then divided by renal function category (<15, 15-30, 30-45, 45-60, 60-90, >90 ml/min(/1.73 m(2))). Per clearance category the number of people with anaemia, hypokalaemia, uraemia and hyperphosphataemia was evaluated. RESULTS: The median creatinine clearance rate was 67.3 ml/min (quartiles: 42.9-95.8) versus a median MDRD-4-eGFR of 51.6 ml/min/1.73 m(2) (35.8-67.7). Anaemia, hyperkalaemia, hypocalcaemia, and uraemia were found to be present at higher levels of creatinine clearance rate and eGFR than previously reported (p<0.0005). This increased prevalence was more pronounced in elderly subjects, particularly with respect to anaemia (OR 2.71 and 2.02 for MDRD-4 and creatinine clearance respectively, p<0.0005). The same holds for the proportion with uraemia (OR 1.85, p<0.0005) and hypocalcaemia (OR 1.97, p=0.011) for MDRD-4. CONCLUSION: Metabolic changes in an in- and outpatient hospital population are present at earlier stages than was stated in recent guidelines, especially when creatinine clearance levels are used as indicators. This might have implications for testing and treatment of patients with suspected kidney disease and/or loss of renal function.

Modification of diet in renal disease and Cockcroft-Gault formulas do not predict mortality (ZODIAC-6).

AIMS: An inverse relationship between estimates of renal function, with formulas such as the Modification of diet in renal disease (MDRD) study equation or the Cockcroft-Gault formula, and mortality has been suggested. These formulas both contain the variables sex, serum creatinine and age and the latter also contains body weight. We investigated whether these formulas predict mortality better than the variables they contain together in patients with Type 2 diabetes. METHODS: In 1998, 1143 primary care patients with Type 2 diabetes participated in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) Study, in the Netherlands. Clinical and laboratory data were collected at baseline. Life status was assessed after 6 years. We used Cox proportional hazard modelling to investigate the association between estimates of renal function (continuous data) and the variables they contain and mortality, adjusting for confounders. Both formulas were compared with models consisting of the variables present in the formulas. Predictability was assessed using Bayesian information criterion (BIC) and Harrell's C statistics. RESULTS: At follow-up, 335 patients had died. All variables, except sex, influenced mortality. Predictive capability, indicated by lower BIC values and higher Harrell's C values, was up to 10% better for models containing the separate variables as compared with Cockcroft-Gault or MDRD. CONCLUSIONS: Using estimates of renal function to assess mortality risk decreases predictability as compared with the combination of the risk factors they contain. These formulas, therefore, could be used to estimate renal function; however, they should not be used as a tool to predict mortality risk.

Attachment of enteric viruses to bottles.

Storage of water that was deliberately contaminated with enteric viruses in polyethylene terephthalate (PET) bottles led to a rapid decrease of the apparent viral load, thereby hampering the development of samples for a collaborative evaluation of viral detection methods for bottled water. To determine if this decrease was due to spontaneous inactivation or to adhesion, an elution protocol was developed and combined with a rapid and sensitive real-time reverse transcription-PCR-based method to quantify adsorbed norovirus (NV), hepatitis A virus (HAV), and rotavirus (RV) on bottle walls. The NV retention on PET bottle walls after 20 and 62 days reached an average level of 85% and 95% of the recovered inoculum, respectively. HAV and RV also showed adsorption onto PET bottles, reaching 90% and 80%, respectively, after 20 days of storage. NV and RV attachment was demonstrated to be dependent on the presence of autochthonous flora, whereas HAV adsorption was independent of it. Application of the elution and viral detection protocol to 294 commercially available water bottles obtained from 25 different countries did not give any positive result, thereby providing further evidence that the sources used for this product are free from enteric viruses and support for the theory that bottled water is not a vehicle for viral diseases.

Understanding reasons for asthma outpatient (non)-attendance and exploring the role of telephone and e-consulting in facilitating access to care: exploratory qualitative study.

OBJECTIVE: To understand factors influencing patients' decisions to attend for outpatient follow up consultations for asthma and to explore patients' attitudes to telephone and email consultations in facilitating access to asthma care. DESIGN: Exploratory qualitative study using in depth interviews. SETTING: Hospital outpatient clinic in West London. PARTICIPANTS: Nineteen patients with moderate to severe asthma (12 "attenders" and 7 "non-attenders"). RESULTS: Patients' main reasons for attending were the wish to improve control over asthma symptoms and a concern not to jeopardise the valued relationship with their doctor. Memory lapses, poor health, and disillusionment with the structure of outpatient care were important factors implicated in non-attendance. The patients were generally sceptical about the suggestion that greater opportunity for telephone consulting might improve access to care. They expressed concerns about the difficulties in effectively communicating through non-face to face media and were worried that clinicians would not be in a position to perform an adequate physical examination over the telephone. Email and text messaging were viewed as potentially useful for sending appointment reminders and sharing clinical information but were not considered to be acceptable alternatives to the face to face clinic encounter. CONCLUSIONS: Memory lapses, impaired mobility due to poor health, and frustration with outpatient clinic organisation resulting in long waiting times and discontinuity of care are factors that deter patients from attending for hospital asthma assessments. The idea of telephone review assessments was viewed with scepticism by most study subjects. Particular attention should be given to explaining to patients the benefits of telephone consultations, and to seeking their views as to whether they would like to try them out before replacing face to face consultations with them. Email and text messaging may have a role in issuing reminders about imminent appointments.

Detection and differentiation of human hepatitis A strains by commercial quantitative real-time RT-PCR tests.

Performance characteristics of two commercial quantitative Hepatitis A virus (HAV) RT-PCR assays, the LightCycler Hepatitis A virus quantification kit (Roche Diagnostics) and the RealArt HAV LC RT PCR kit (artus GmbH) for detection and quantification of HAV were evaluated. Both assays rely on reverse transcription and amplification of extracted RNA. Dilutions of two HAV strains, belonging to different subtypes, were prepared to determine the precision, accuracy, linearity and the detection limit. Both assays were found to be suitable for quantification measurement of HAV RNA, but only the Roche kit was able to distinguish the different HAV strains tested. The linear range for the artus assay was 10(4)-10(6)IU/ml and 2 x 10(4) to 2 x 10(8) RNA copies/ml for the Roche assay. The detection limit of Roche kit was 2 TCID(50)/ml or 500 RNA copies/ml and 5 TCID(50)/ml or 50 IU/ml for the artus kit. Despite these small differences it is concluded that both assays are very suitable for detection and quantification of most prevalent HAV subtypes.

A simple and rapid cultural method for detection of Enterobacter sakazakii in environmental samples.

A method was developed to detect and identify Enterobacter sakazakii in environmental samples. The method is based on selective enrichment at 45+/-0.5 degrees C in lauryl sulfate tryptose broth supplemented with 0.5 M NaCl and 10 mg/liter vancomycin (mLST) for 22 to 24 h followed by streaking on tryptone soy agar with bile salts. When exposed to light during incubation at 37 degrees C, E. sakazakii produces yellow colonies within 24 h; identification was confirmed by testing for alpha-glucosidase activity and by using API 20E strips. All of the E. sakazakii strains tested (n = 99) were able to grow in mLST at 45+/-0.5 degrees C, whereas 35 of 39 strains of potential competitors, all belonging to the Enterobacteriaceae, were suppressed. A survey was carried out with 192 environmental samples from four different milk powder factories. Using this new protocol, E. sakazakii was isolated from almost 40% of the samples, whereas the reference procedure (enrichment in buffered peptone water, isolation on violet red bile glucose agar, and biochemical identification of randomly chosen colonies) only yielded 26% positive results. This selective method can be very useful for the rapid and reliable detection of E. sakazakii in environmental samples.

Genotoxicity of hormonal steroids.

Hormonal steroids have a widespread use in medicine and their side effects are continuously debated. The possible genotoxic activity of steroids has been the subject of many investigations. The natural estrogens estradiol, estrone and estriol are generally negative in the ICH core battery of tests, but several positive results have been obtained when using additional endpoints of genotoxicity. The genotoxic activity of the 4-hydroxy metabolites of estradiol and estrone is well established. The synthetic steroidal estrogens have a comparable profile of negative and positive test results. Cyproterone acetate and some of its analogues have a special position within the group of progestins. Their genotoxic potential has been established. Other progestins are generally negative in the routine tests. Anti-glucocorticoids, anti-progestins, corticosteroids, androgens, anabolics and anti-androgens appear to be devoid of genotoxic activities. The genotoxic potential of estradiol, estrone and cyproterone acetate with its analogues may play no role under normal physiological and therapeutic conditions. The metabolic conditions that are needed for the formation of DNA-reactive metabolites and oxygen radicals may not be present in humans. Epidemiological cancer data seem to support this view. The importance of thresholds in the dose-effect-relationship of genotoxicity data and their use in risk assessment is discussed.

Desiccation and heat tolerance of Enterobacter sakazakii.

AIMS: Enterobacter sakazakii is an opportunistic pathogen which has been isolated at low levels from powdered infant formulas. This study was performed to demonstrate that Ent. sakazakii is not particularly thermotolerant, but can adapt to osmotic and dry stress. METHODS AND RESULTS: We determined the heat, osmotic and dry stress resistance of Ent. sakazakii. The D-value at 58 degrees C ranged from 0.39 to 0.60 min, which is comparable with that of other Enterobacteriaceae, but much lower than reported previously (Nazarowec-White and Farber 1997, Letters in Applied Microbiology 24: 9-13). However, stationary phase Ent. sakazakii cells were found to be more resistant to osmotic and dry stress than Escherichia coli, Salmonella and other strains of Enterobacteriaceae tested. Further analysis indicated that the dry resistance is most likely linked to accumulation of trehalose in the cells. CONCLUSIONS: The high tolerance to desiccation provides a competitive advantage for Ent. sakazakii in dry environments, as found in milk powder factories, and thereby increases the risk of postpasteurization contamination of the finished product. SIGNIFICANCE AND IMPACT OF THE STUDY: Understanding of the physiology and survival strategies of Ent. sakazakii is an important step in the efforts to eliminate this bacterium from the critical food production environments.

Production of ochratoxin A by Aspergillus carbonarius on coffee cherries.

Robusta coffee cherries collected before and during sun drying from two coffee farms in Thailand were examined for moulds producing ochratoxin A (OA). Aspergillus ochraceus was only detected in one sample, whereas Aspergillus carbonarius was isolated from 7 out of 14 samples. On gamma-irradiated coffee cherries, each of the six tested A. carbonarius strains produced OA. More than 4800 microg kg(-1) of toxin were detected under optimal conditions (25 degrees C, a(w) 0.99). OA production was strongly reduced (230 microg kg(-1)) at an a(w) of 0.94.