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.

Randomized clinical trial of extended versus single-dose perioperative antibiotic prophylaxis for acute calculous cholecystitis.

BACKGROUND: Many patients who have surgery for acute cholecystitis receive postoperative antibiotic prophylaxis, with the intent to reduce infectious complications. There is, however, no evidence that extending antibiotics beyond a single perioperative dose is advantageous. This study aimed to determine the effect of extended antibiotic prophylaxis on infectious complications in patients with mild acute cholecystitis undergoing cholecystectomy. METHODS: For this randomized controlled non-inferiority trial, adult patients with mild acute calculous cholecystitis undergoing cholecystectomy at six major teaching hospitals in the Netherlands, between April 2012 and September 2014, were assessed for eligibility. Patients were randomized to either a single preoperative dose of cefazolin (2000 mg), or antibiotic prophylaxis for 3 days after surgery (intravenous cefuroxime 750 mg plus metronidazole 500 mg, three times daily), in addition to the single dose. The primary endpoint was rate of infectious complications within 30 days after operation. RESULTS: In the intention-to-treat analysis, three of 77 patients (4 per cent) in the extended antibiotic group and three of 73 (4 per cent) in the standard prophylaxis group developed postoperative infectious complications (absolute difference 0·2 (95 per cent c.i. -8·2 to 8·9) per cent). Based on a margin of 5 per cent, non-inferiority of standard prophylaxis compared with extended prophylaxis was not proven. Median length of hospital stay was 3 days in the extended antibiotic group and 1 day in the standard prophylaxis group. CONCLUSION: Standard single-dose antibiotic prophylaxis did not lead to an increase in postoperative infectious complications in patients with mild acute cholecystitis undergoing cholecystectomy. Registration number: NTR3089 (www.trialregister.nl).

Treatment with anti-inflammatory drugs in community-acquired pneumonia.

Pneumonia exhibits a broad range of severity, from mildly symptomatic at one end to fulminant septic shock and death at the other. Although an adequate inflammatory response is necessary for the clearance of microorganisms, excessive inflammation can lead to ongoing local and systemic damage. Because of this extended inflammatory response despite appropriate antibiotic therapy, as well as increasing antibiotic resistance, adjuvant therapy for pneumonia that can favourably modify the immune response has become an increasingly relevant approach to improve prognosis. Different adjuvant treatment options for pneumonia have recently been proposed. Promising treatment options include corticosteroids, statins, macrolides and Toll-like receptor antagonists. The aim of this review is to summarize the inflammatory response during pneumonia and discuss the current knowledge and future perspectives regarding the anti-inflammatory treatment options for patients with pneumonia.

Optimizing the use of patients' individual outcome information - Development and usability tests of a Chronic Kidney Disease dashboard.

BACKGROUND: Reporting individual clinical and patient-reported outcomes to patients during consultations may add to patients' disease knowledge and activation and stimulate Shared Decision Making (SDM). These outcomes can be presented over time in a clear way by the means of dashboarding. We aimed to systematically develop a Chronic Kidney Disease (CKD) dashboard designed to support consultations, test its usability and explore conditions for optimal use in practice. METHODS: For development a participatory approach with patients and healthcare professionals (HCPs) from three hospitals was used. Working groups and patient focus groups were conducted to identify needs and inform the dashboard's design. Usability was tested in patient interviews. A focus group with HCPs was held to identify conditions for optimal use of the dashboard in daily practice. RESULTS: A dashboard was developed for CKD patients stage 3b-4 visualizing both clinical and patient-reported outcomes over time for use during consultations and accessible for patients at home. Both HCPs and patients indicated that the dashboard can: motivate patients in their treatment by providing feedback on outcomes over time; improve consultation conversations by enhanced preparation of both HCPs and patients; better inform patients, thereby facilitating shared decision making. HCPs and patients both stated that setting a topic agenda for the consultation together is important in effectively discussing the dashboard during consultations. Moreover, the dashboard should not dominate the conversation. Lastly, findings of the usability tests provided design requirements for optimal user-friendliness and clarity. CONCLUSIONS: Dashboarding can be a valuable way of reporting individual outcome information to patients and their clinicians as findings suggest it may stimulate patient activation and facilitate decision making. Co-creation with patients and HCPs was essential for successful development of the dashboard. Gained knowledge from the co-creation process can inform others wishing to develop similar digital tools for use in clinical practice.

Pneumococcal conjugate vaccination response in patients after community-acquired pneumonia, differences in patients with S. pneumoniae versus other pathogens.

OBJECTIVES: The goal of this study is to investigate the immune response to the 13-valent pneumococcal conjugate vaccine (PCV13) in former pneumococcal CAP patients. We hypothesize that an impaired or suboptimal humoral immune response against (specific) pneumococcal serotypes might explain the vulnerability for pneumococcal disease. METHODS: Hospitalised adult CAP patients who participated in two trials (2004-2006 (n=201) and, 2007-2009 (n=304)) were screened. Patients eligible for inclusion had CAP caused by either S. pneumoniae (pneuCAP) or due to another well-defined pathogen (otherCAP). Serotype-specific pneumococcal antibody concentrations (total IgG and IgG2/IgG1) before and 3-4weeks after PCV13 administration were measured (Luminex) and compared between pneuCAP and otherCAP patients. RESULTS: We vaccinated 60 patients:i.e. 34 pneuCAP and 26 otherCAP patients. In the pneuCAP group, 74% of patients were categorized as good responders (≥9/13 serotypes with concentration≥1300ng/ml), versus 77% in the otherCAP group. Significantly fewer full responders (i.e. 13/13 serotypes with a concentration≥1300ng/mL) were identified in the pneuCAP group (15% vs 42% respectively, p=0.02). For serotype 1, total IgG and IgG2/IgG1 subset post-vaccination concentrations were significantly lower among pneuCAP patients. Our additional case-series showed that of 16 pneuCAP patients who were infected by a serotype included in PCV13 three patients did not respond against the serotype originally responsible for their CAP episode, including one former bacteraemic pneumococcal CAP patient who also failed to show a response against the serotype responsible for CAP during infection. Thirteen patients did respond to the previously infecting serotype following PCV13 including three patients who had bacteraemic pneumococcal pneumonia and did not show a response during infection against the serotype responsible for CAP. CONCLUSIONS: Our results confirm the immunogenic properties of PCV13 in former pneumococcal CAP patients including patients previously regarded as potential hyporesponders. A slightly diminished overall humoral response to polysaccharides characterizes the former pneumococcal CAP patients. ClinicalTrials.gov Identifier: NCT02141009.

[Is a salt-restricted diet now up for discussion?] / Staat zoutbeperking nu ter discussie?

A recent meta-analysis published in The Lancet related sodium excretion to mortality in both hypertensive and normotensive subjects. High salt excretion, measured in a spot urine test, was related to increased mortality in hypertensive subjects only, whereas low sodium excretion was related to increased mortality in both hypertensive and normotensive subjects. Here we discuss practical consequences of this analysis. The data underline the importance of salt restriction in hypertension; the analysis also shows that there is a lower limit to salt restriction. Since salt intake cannot be assessed adequately from the sodium content of a single urine sample, 24-hour urine collection is advised in subjects on a salt-restricted diet. A 24-hour urine collection allows checking for unnecessarily strict salt restriction or, as will more often be the case, shows the patient that adequate salt restriction has not yet been attained.

Chlamydia psittaci: a relevant cause of community-acquired pneumonia in two Dutch hospitals.

BACKGROUND: Of all hospitalised community-acquired pneumonias (CAPs) only a few are known to be caused by Chlamydia psittaci. Most likely the reported incidence, ranging from of 0% to 2.1%, is an underestimation of the real incidence, since detection of psittacosis is frequently not incorporated in the routine microbiological diagnostics in CAP or serological methods are used. METHODS: C. psittaci real-time polymerase chain reaction (PCR) was routinely performed on the sputum of 147 patients hospitalised with CAP, who participated in a clinical trial conducted in two Dutch hospitals. In 119/147 patients the paired complement fixation test (CFT) was also performed for the presence of Chlamydia antibodies. Positive CFTs were investigated by micro- Immunofluorescence for psittacosis specificity. Case criteria for psittacosis were a positive PCR or a fourfold rise of antibody titre in CFT confirmed by micro- Immunofluorescence. Furthermore, we searched for parameters that could discriminate psittacosis from CAPs with other aetiology. RESULTS: 7/147 (4.8%) patients were diagnosed with psittacosis: six with PCR and one patient with a negative PCR, but with CFT confirmed by micro- Immunofluorescence. Psittacosis patients had had a higher temperature (median 39.6 vs. 38.2 °C;) but lower white blood cell count (median 7.4 vs. 13.7 x 109/l) on admission compared with other CAP patients. CONCLUSION: In this study, C. psittaci as CAP-causing pathogen was much higher than previously reported. To detect psittacosis, PCR was performed on all CAP patients for whom a sputum sample was available. For clinical use, PCR is a fast method and sputum availability allows genotyping; additional serology can optimise epidemiological investigations.

A Randomised Controlled Trial of Consent Procedures for the Use of Residual Tissues for Medical Research: Preferences of and Implications for Patients, Research and Clinical Practice.

BACKGROUND: Despite much debate, there is little evidence on consequences of consent procedures for residual tissue use. Here, we investigated these consequences for the availability of residual tissue for medical research, clinical practice, and patient informedness. METHODS: We conducted a randomised clinical trial with three arms in six hospitals. Participants, patients from whom tissue had been removed for diagnosis or treatment, were randomised to one of three arms: informed consent, an opt-out procedure with active information provision (opt-out plus), and an opt-out procedure without active information provision. Participants received a questionnaire six weeks post-intervention; a subsample of respondents was interviewed. Health care providers completed a pre- and post-intervention questionnaire. We assessed percentage of residual tissue samples available for medical research, and patient and health care provider satisfaction and preference. Health care providers and outcome assessors could not be blinded. RESULTS: We randomised 1,319 patients, 440 in the informed consent, 434 in the opt-out plus, and 445 in the opt-out arm; respectively 60.7%, 100%, and 99.8% of patients' tissue samples could be used for medical research. Of the questionnaire respondents (N = 224, 207, and 214 in the informed consent, opt-out plus, and opt-out arms), 71%, 69%, and 31%, respectively, indicated being (very) well informed. By questionnaire, the majority (53%) indicated a preference for informed consent, whereas by interview, most indicated a preference for opt-out plus (37%). Health care providers (N = 35) were more likely to be (very) satisfied with opt-out plus than with informed consent (p = 0.002) or opt-out (p = 0.039); the majority (66%) preferred opt-out plus. CONCLUSION: We conclude that opt-out with information (opt-out plus) is the best choice to balance the consequences for medical research, patients, and clinical practice, and is therefore the most optimal consent procedure for residual tissue use in Dutch hospitals. TRIAL REGISTRATION: Dutch Trial Register NTR2982.

Alcohol and arterial wave reflections in middle aged and elderly men.

BACKGROUND: Augmentation index (AIx) is a measure of arterial wave reflection, providing information on the workload of the heart. and is a possible marker for cardiovascular disease risk. The relation of alcohol consumption with cardiovascular disease (CVD) risk is U-shaped with a protective effect of moderate alcohol consumption. The relation of alcohol consumption level with AIx has not been widely investigated, which prompted this study of the relation of alcohol consumption with AIx in a population-based cohort of men aged 40-80 years. METHODS: Three hundred and seventy-four men (mean age 60.5 years) participated in this cross-sectional study. Alcohol consumption and smoking habits were determined through a validated questionnaire. Fasting blood samples were drawn and analyzed for glucose and lipid levels and AIx was estimated by radial applanation tonometry using the SphygmoCor Device. The resultant data were analyzed using linear regression models. RESULTS: Age, height, heart rate, blood pressure, packyears, current smoking, presence of CVD and hypertension were independently related to AIx. The relation of alcohol consumption with AIx was U-shaped, with a significantly lower AIx in the group drinking 4-8 glasses/week (difference = -2.91%, 95% CI [-5.65; -0.18]) relative to those drinking 0-3 glasses/week. Additional adjustment for current smoking did not change this relationship, but adjustment for pulse wave velocity attenuated the relation. CONCLUSIONS: In a population-based cohort of men aged 40-80 years the relation of alcohol consumption level with AIx was U-shaped, further expanding the evidence for vascular protective effects of moderate alcohol intake.

Determinants of augmentation index in young men: the ARYA study.

BACKGROUND: There is an increasing interest in the augmentation index (AIx), the proportion of the central pulse pressure resulting from peripheral arterial wave reflection, which has been related to cardiovascular disease risk and mortality. Most of the data on the AIx have been collected in patients with established cardiovascular disease. In contrast, data in the young are scarce. However, as AIx might be used to evaluate cardiovascular disease risk already at an early age, we aimed to study determinants of AIx in a population of healthy young men. MATERIALS AND METHODS: Three hundred and thirty males (mean age of 28 years) of the Atherosclerosis Risk in Young Adults study (ARYA-study) were studied in this cross sectional, population-based study. Anthropometrics and risk factors for cardiovascular disease were determined and AIx was estimated by radial applanation tonometry. The data were analysed using linear regression models. RESULTS: Augmentation index was associated with age, height (inverse), heart rate (inverse) and mean arterial pressure (positive). After adjustment for these determinants, smoking (beta = 0.31%/pack years, 95% CI [0.06; 0.55]) and LDL-cholesterol (beta = 1.28%/(mmol L(-1)), 95% CI [0.04; 2.51]) were statistically significant related to AIx. CONCLUSIONS: This study among young adult males shows that smoking and LDL-cholesterol are positively related to AIx. These findings support the view that AIx may be used as a marker for early vascular damage and cardiovascular disease risk.