Impact of mucositis on oral bioavailability and systemic exposure of ciprofloxacin Gram-negative infection prophylaxis in patients with haematological malignancies.

BACKGROUND: Patients with haematological malignancies frequently endure neutropenia and gastrointestinal (GI)-mucositis after high-dose chemotherapy. In these patients, ciprofloxacin is used for Gram-negative infection prophylaxis. OBJECTIVES: We investigate ciprofloxacin pharmacokinetics after oral administration in patients with haematological malignancies and explore the impact of GI-mucositis on oral bioavailability and clearance in order to assure adequate systemic exposure. METHODS: Adult haematological patients from two Dutch University Medical Centres received 500 mg twice daily oral ciprofloxacin for Gram-negative prophylaxis. The ciprofloxacin plasma concentrations were collected at various timepoints after oral ciprofloxacin administration and at various days after completion of chemotherapy. Data obtained after oral and intravenous ciprofloxacin administration in 28 healthy volunteers without mucositis served as a control group (391 samples). For haematological patients the degree of GI-mucositis was assessed using the Daily Gut Score (DGS), plasma citrulline and albumin. Data were analysed by non-linear mixed-effects modelling. RESULTS: In total, 250 blood samples were collected in 47 patients with a wide variety of haematological malignancies between 0-30 days after start of chemotherapy. Mucositis was generally mild [DGS median (IQR) 1 (1-1) and citrulline 16 µmol/L (12-23)]. The time to Cmax was slower in haematological patients compared with healthy volunteers although no association with the degree of mucositis (defined as DGS or citrulline) could be identified. Ciprofloxacin bioavailability and clearance were 60% and 33.2 L/h, respectively. CONCLUSIONS: This study supports oral dosing of ciprofloxacin as Gram-negative infection prophylaxis in haematological patients with mild-to-moderate mucositis capable of oral intake.

A multicentre cluster-randomized clinical trial to improve antibiotic use and reduce length of stay in hospitals: comparison of three measurement and feedback methods.

BACKGROUND: Various metrics of hospital antibiotic use might assist in guiding antimicrobial stewardship (AMS). OBJECTIVES: To compare patient outcomes in association with three methods to measure and feedback information on hospital antibiotic use when used in developing an AMS intervention. METHODS: Three methods were randomly allocated to 42 clusters from 21 Dutch hospitals: (1) feedback on quantity of antibiotic use [DDD, days-of-therapy (DOT) from hospital pharmacy data], versus feedback on (2) validated, or (3) non-validated quality indicators from point prevalence studies. Using this feedback together with an implementation tool, stewardship teams systematically developed and performed improvement strategies. The hospital length of stay (LOS) was the primary outcome and secondary outcomes included DOT, ICU stay and hospital mortality. Data were collected before (February-May 2015) and after (February-May 2017) the intervention period. RESULTS: The geometric mean hospital LOS decreased from 9.5 days (95% CI 8.9-10.1, 4245 patients) at baseline to 9.0 days (95% CI 8.5-9.6, 4195 patients) after intervention (P < 0.001). No differences in effect on LOS or secondary outcomes were found between methods. Feedback on quality of antibiotic use was used more often to identify improvement targets and was preferred over feedback on quantity of use. Consistent use of the implementation tool seemed to increase effectiveness of the AMS intervention. CONCLUSIONS: The decrease in LOS versus baseline likely reflects improvement in the quality of antibiotic use with the stewardship intervention. While the outcomes with the three methods were otherwise similar, stewardship teams preferred data on the quality over the quantity of antibiotic use.

The relationship between time to diagnose and diagnostic accuracy among internal medicine residents: a randomized experiment.

BACKGROUND: Diagnostic errors have been attributed to cognitive biases (reasoning shortcuts), which are thought to result from fast reasoning. Suggested solutions include slowing down the reasoning process. However, slower reasoning is not necessarily more accurate than faster reasoning. In this study, we studied the relationship between time to diagnose and diagnostic accuracy. METHODS: We conducted a multi-center within-subjects experiment where we prospectively induced availability bias (using Mamede et al.'s methodology) in 117 internal medicine residents. Subsequently, residents diagnosed cases that resembled those bias cases but had another correct diagnosis. We determined whether residents were correct, incorrect due to bias (i.e. they provided the diagnosis induced by availability bias) or due to other causes (i.e. they provided another incorrect diagnosis) and compared time to diagnose. RESULTS: We did not successfully induce bias: no significant effect of availability bias was found. Therefore, we compared correct diagnoses to all incorrect diagnoses. Residents reached correct diagnoses faster than incorrect diagnoses (115 s vs. 129 s, p < .001). Exploratory analyses of cases where bias was induced showed a trend of time to diagnose for bias diagnoses to be more similar to correct diagnoses (115 s vs 115 s, p = .971) than to other errors (115 s vs 136 s, p = .082). CONCLUSIONS: We showed that correct diagnoses were made faster than incorrect diagnoses, even within subjects. Errors due to availability bias may be different: exploratory analyses suggest a trend that biased cases were diagnosed faster than incorrect diagnoses. The hypothesis that fast reasoning leads to diagnostic errors should be revisited, but more research into the characteristics of cognitive biases is important because they may be different from other causes of diagnostic errors.

Clinical condition and comorbidity as determinants for blood culture positivity in patients with skin and soft-tissue infections.

The utility of performing blood cultures in patients with a suspected skin infection is debated. We investigated the association between blood culture positivity rates and patients' clinical condition, including acute disease severity and comorbidity. We performed a retrospective study, including patients with cellulitis and wound infection who had been enrolled in three Dutch multicenter studies between 2011 and 2015. Patients' acute clinical condition was assessed using the Modified Early Warning Score (MEWS; severe: MEWS ≥2) and comorbidity with the Charlson Comorbidity Index (CCI; severe: CCI ≥2). A total of 334 patients with a suspected skin infection were included. Blood cultures were performed in 175 patients (52%), 28 of whom (16%) had a positive blood culture. Data on the clinical condition were collected in 275 patients. Blood cultures were performed in 76% of the patients with a severe acute condition, compared with 48% with a non-severe acute condition (OR 3.5; 95% confidence interval: 2.0-6.2; p < 0.001). Blood cultures were positive in 18% and 12% respectively (OR 1.7 (0.7-4.1); p = 0.3). Blood cultures were performed in 53% of patients with severe comorbidity, compared with 61% without severe comorbidity (OR 0.7; 0.4-1.2; p = 0.2). Blood cultures were positive in 25% and 10% respectively (OR = 3.1; 1.2-7.5; p = 0.02). The blood culture positivity rate among hospitalized patients diagnosed with skin infections was higher than the rates reported by the Infectious Diseases Society of America guidelines, particularly in patients with severe comorbidity. Therefore, the recommendations concerning blood culture performance in patients with a skin infection should be reconsidered.

Vaginal high-risk human papillomavirus infection in a cross-sectional study among women of six different ethnicities in Amsterdam, the Netherlands: the HELIUS study.

OBJECTIVE: In the Netherlands the incidence of cervical cancer is higher among ethnic minority populations compared with the general Dutch population. We investigated the prevalence of, and risk factors associated with, vaginal high-risk human papillomavirus (hrHPV) infection in women of six different ethnicities living in Amsterdam. METHODS: For this cross-sectional study we selected women aged 18-34 years old of six ethnicities from the large-scale multiethnic HEalthy LIfe in an Urban Setting study. Self-collected vaginal swabs were tested for HPV DNA and genotyped using a highly sensitive PCR and reverse line blot assay (short PCR fragment (SPF)10-PCR DNA enzyme immunoassay/LiPA25-system version-1, delft diagnostic laboratory (DDL)). Participants completed a questionnaire regarding demographics and sexual behaviour. Logistic regression using generalised estimating equations was used to assess risk factors of hrHPV, and to investigate whether prevalence of hrHPV differed among ethnicities. RESULTS: The study population consisted of 592 women with a median age of 27 (IQR: 23-31) years. Dutch and African Surinamese women reported the highest sexual risk behaviour. HrHPV prevalence was highest in the Dutch (40%) followed by the African Surinamese (32%), Turkish (29%), Ghanaian (26%), Moroccan (26%) and South-Asian Surinamese (18%). When correcting for sexual risk behaviour, the odds to be hrHPV-positive were similar for all non-Dutch groups when compared with that of the Dutch group. CONCLUSIONS: We found an overall higher hrHPV prevalence and higher sexual risk behaviour in the native Dutch population. Further research is needed to unravel the complex problem concerning cervical cancer disparities, such as differences in participation in the cervical cancer screening programme, or differences in clearance and persistence of hrHPV.

A survey to identify barriers of implementing an antibiotic checklist.

A checklist is an effective implementation tool, but addressing barriers that might impact on the effectiveness of its use is crucial. In this paper, we explore barriers to the uptake of an antibiotic checklist that aims to improve antibiotic use in daily hospital care. We performed an online questionnaire survey among medical specialists and residents with various professional backgrounds from nine Dutch hospitals. The questionnaire consisted of 23 statements on anticipated barriers hindering the uptake of the checklist. Furthermore, it gave the possibility to add comments. We included 219 completed questionnaires (122 medical specialists and 97 residents) in our descriptive analysis. The top six anticipated barriers included: (1) lack of expectation of improvement of antibiotic use, (2) lack of expected patients' satisfaction by checklist use, (3) lack of feasibility of the checklist, (4) negative previous experiences with other checklists, (5) the complexity of the antibiotic checklist and (6) lack of nurses' expectation of checklist use. Remarkably, 553 comments were made, mostly (436) about the content of the checklist. These insights can be used to improve the specific content of the checklist and to develop an implementation strategy that addresses the identified barriers.

Incidence, risk factors, and the impact of allograft pyelonephritis on renal allograft function.

BACKGROUND: The impact of allograft pyelonephritis (AGPN) on renal allograft function is controversial. In this study, we evaluated the incidence, risk factors, and the impact of AGPN on renal allograft function. METHODS: Retrospective cohort study in adult renal allograft recipients with 1-year follow-up after transplantation (Tx). Renal allograft function was evaluated by estimated glomerular filtration rate (eGFR) (by Modification of Diet in Renal Disease formula) and 24-h urine protein excretion. RESULTS: A total of 431 renal allograft recipients were analyzed; 57 (13.2%) developed AGPN within 1 year after Tx. Median time between Tx and AGPN was 50 days. Risk factors for AGPN were the presence of a urological catheter (odds ratio [OR] = 18.93, 95% confidence interval [CI] = 8.00-44.81, P < 0.001) and preceding asymptomatic bacteriuria (ASB) (OR = 2.16, 95% CI = 1.20-3.90, P = 0.009). In 72.7%, the causative microorganism of ASB was identical to that of the succeeding AGPN episode. Multivariable linear regression analysis showed that experiencing AGPN did not decrease the eGFR (P = 0.61) nor did increased proteinuria (P = 0.29) 1 year after Tx. For the eGFR, an interaction was found between AGPN/bacteriuria (BU) and acute rejection (AR): the group experiencing BU preceding AR had significantly (P < 0.001) lower eGFR compared with the group that experienced only AR (21 mL/min/1.73 m2 vs. 48 mL/min/1.73 m2 ), as a result of increased prevalence of combined rejections within the BU group. CONCLUSION: Indwelling urological catheters and preceding ASB are associated with developing AGPN. An incident of AGPN itself does not impair renal allograft function 1 year after Tx. However, a relevant interaction occurs between BU and AR, in which the sequence of occurrence of these 2 events synergistically impairs the eGFR.

Using an index-based approach to assess the population-level appropriateness of empirical antibiotic therapy.

OBJECTIVES: The population-level appropriateness of empirical antibiotic therapy can be conventionally measured by ascertainment of treatment coverage. This method involves a complex resource-intensive case-by-case assessment of the prescribed antibiotic treatment and the resistance of the causative microorganism. We aimed to develop an alternative approach based, instead, on the use of routinely available surveillance data. METHODS: We calculated a drug effectiveness index by combining three simple aggregated metrics: relative frequency of aetiological agents, level of resistance and relative frequency of antibiotic use. To evaluate the applicability of our approach, we used this metric to estimate the population-level appropriateness of guideline-compliant and non-guideline-compliant empirical treatment regimens in the context of the Dutch national guidelines for complicated urinary tract infections. RESULTS: The drug effectiveness index agrees within 5% with results obtained with the conventional approach based on a case-by-case ascertainment of treatment coverage. Additionally, we estimated that the appropriateness of 2008 antibiotic prescribing regimens would have declined by up to 4% by year 2011 in the Netherlands due to the emergence and expansion of antibiotic resistance. CONCLUSIONS: The index-based framework can be an alternative approach to the estimation of point values and counterfactual trends in population-level empirical treatment appropriateness. In resource-constrained settings, where empirical prescribing is most prevalent and comprehensive studies to directly measure appropriateness may not be a practical proposition, an index-based approach could provide useful information to aid in the development and monitoring of antibiotic prescription guidelines.

Appropriate antibiotic use for patients with complicated urinary tract infections in 38 Dutch Hospital Departments: a retrospective study of variation and determinants.

BACKGROUND: Appropriate antibiotic use in patients with complicated urinary tract infections can be measured by a valid set of nine quality indicators (QIs). We evaluated the performance of these QIs in a national setting and investigated which determinants influenced appropriate antibiotic use. For the latter, we distinguished patient, department and hospital characteristics, including organizational interventions aimed at improving the quality of antibiotic use (antibiotic stewardship elements). METHODS: A retrospective, observational multicentre study included 1964 patients (58% male sex) with a complicated urinary tract infection treated at Internal Medicine and Urology departments of 19 Dutch university and non-university hospitals. Data of 50 patients per department were extracted from medical charts. QI performance scores were calculated using previously constructed algorithms. Department and hospital characteristics were collected using questionnaires filled in by an internal medicine physician and an urologist. Regression analysis was performed to identify determinants of QI performance. Clustering at department and hospital level was taken into account through inclusion of random effects in a multi-level model. RESULTS: Median QI performance of departments varied between 31% ('Treat urinary tract infection in men according to local guideline') and 77% ('Perform urine culture'). The patient characteristics non-febrile urinary tract infection, female sex and presence of a urinary catheter were negatively associated with performance on many QIs. The presence of an infectious diseases physician and an antibiotic formulary were positively associated with 'Prescribe empirical therapy according to guideline'. No other department or hospital characteristics, including stewardship elements, were consistently associated with better QI performance. CONCLUSIONS: A large inter-department variation was demonstrated in the appropriateness of antibiotic use. In particular certain patient characteristics (more than department or hospital characteristics) influenced the quality of antibiotic use. Some, but not all antibiotic stewardship elements did translate into better QI performance.

Nonantibiotic prophylaxis for recurrent urinary tract infections: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Increasing antimicrobial resistance has stimulated interest in nonantibiotic prophylaxis of recurrent urinary tract infections. We assessed the effectiveness, tolerability and safety of nonantibiotic prophylaxis in adults with recurrent urinary tract infections. MATERIALS AND METHODS: MEDLINE®, EMBASE™, the Cochrane Library and reference lists of relevant reviews were searched to April 2013 for relevant English language citations. Two reviewers selected randomized controlled trials that met the predefined criteria for population, interventions and outcomes. The difference in the proportions of patients with at least 1 urinary tract infection was calculated for individual studies, and pooled risk ratios were calculated using random and fixed effects models. Adverse event rates were also extracted. The Jadad score was used to assess risk of bias (0 to 2-high risk and 3 to 5-low risk). RESULTS: We identified 5,413 records and included 17 studies with data for 2,165 patients. The oral immunostimulant OM-89 decreased the rate of urinary tract infection recurrence (4 trials, sample size 891, median Jadad score 3, RR 0.61, 95% CI 0.48-0.78) and had a good safety profile. The vaginal vaccine Urovac® slightly reduced urinary tract infection recurrence (3 trials, sample size 220, Jadad score 3, RR 0.81, 95% CI 0.68-0.96) and primary immunization followed by booster immunization increased the time to reinfection. Vaginal estrogens showed a trend toward preventing urinary tract infection recurrence (2 trials, sample size 201, Jadad score 2.5, RR 0.42, 95% CI 0.16-1.10) but vaginal irritation occurred in 6% to 20% of women. Cranberries decreased urinary tract infection recurrence (2 trials, sample size 250, Jadad score 4, RR 0.53, 95% CI 0.33-0.83) as did acupuncture (2 open label trials, sample size 165, Jadad score 2, RR 0.48, 95% CI 0.29-0.79). Oral estrogens and lactobacilli prophylaxis did not decrease the rate of urinary tract infection recurrence. CONCLUSIONS: The evidence of the effectiveness of the oral immunostimulant OM-89 is promising. Although sometimes statistically significant, pooled findings for the other interventions should be considered tentative until corroborated by more research. Large head-to-head trials should be performed to optimally inform clinical decision making.

Adequacy of an evidence-based treatment guideline for complicated urinary tract infections in the Netherlands and the effectiveness of guideline adherence.

Guideline recommendations on empirical antibiotic treatment are based on the literature, expert opinion, expected pathogens and resistance data, but their adequacy in the real-life setting is often unknown. We investigated the adequacy of the Dutch evidence-based guideline-recommended treatment options for patients with complicated urinary tract infections (UTIs) 2 years after guideline publication and, additionally, the adequacy of actually prescribed empirical therapy for patients treated with guideline-adherent versus non-guideline-adherent therapy. A retrospective, observational multicentre study in the Netherlands included 810 patients with a complicated UTI without special conditions and 174 with a urinary catheter. The susceptibility patterns of cultured uropathogens were compared with guideline-recommended treatment options, which included specific recommendations for patients with a catheter, and with actually prescribed empirical therapy. We considered inadequate coverage rates below 10% as acceptable. Of the recommended regimens for patients with a UTI without other conditions, only the guideline-recommended combination of amoxicillin-gentamicin was acceptable (inadequate coverage rate 6%). For patients with a catheter, inadequate coverage rates of recommended regimens ranged from 3 to 24%. In patients with a UTI without other conditions, actually prescribed guideline-adherent therapy resulted in less broad-spectrum but not in less adequate therapy; in patients with a catheter, actually prescribed guideline-adherent therapy resulted in a higher coverage rate than those prescribed non-guideline-adherent therapy. Due to the continuously changing resistance rates and differences between the epidemiologies of uropathogens assumed in the guideline and those in real life, regular real-life assessments of recommended treatment options are necessary. Guideline adherence seems to be effective for increasing coverage rates without prescribing unnecessarily broad regimens.

The effect of an intervention bundle to prevent central venous catheter-related bloodstream infection in a national programme in the Netherlands.

INTRODUCTION: Central venous catheters (CVCs) can lead to central line-related bloodstream infections (CRBSIs). A six-item bundle was introduced in 2009 to prevent CRBSI in Dutch hospitals. AIM: This study aimed to determine the impact of an intervention bundle on CRBSI risk. METHODS: Data were obtained from hospitals participating in the national CRBSI surveillance between 2009 and 2019. Bundle compliance was evaluated as a total ('overall') bundle (all six items) and as an insertion bundle (four items) and a maintenance bundle (two daily checks). We estimated the impact of the overall and partial bundles, using multi-level Cox regression. FINDINGS: Of the 66 hospitals in the CRBSI surveillance 56 (84.8%) recorded annual bundle (non)compliance for >80% of the CVCs, for one to nine years. In these 56 hospitals CRBSI incidence decreased from 4.0 to 1.6/1000 CVC days. In the intensive care units (ICUs), compliance was not associated with CRBSI risk (hazard ratio (HR) for the overall, insertion and maintenance bundle were 1.14 (95% confidence interval 0.80-1.64), 1.05 (0.56-1.95) and 1.13 (0.79-1.62)), respectively. Outside the ICU the non-significant association of compliance with the overall bundle (HR 1.36 (0.96-1.93)) resulted from opposite effects of the insertion bundle, associated with decreased risk (HR 0.50 (0.30-0.85)) and the maintenance bundle, associated with increased risk (HR 1.68 (1.19-2.36)). CONCLUSION: Following a national programme to introduce an intervention bundle, CRBSI incidence decreased significantly. In the ICU, bundle compliance was not associated with CRBSI risk, but outside the ICU improved compliance with the insertion bundle resulted in a decreased CRBSI risk.

Patient engagement to counter catheter-associated urinary tract infections with an app (PECCA): a multicentre, prospective, interrupted time-series and before-and-after study.

BACKGROUND: The risk of urinary tract infections (UTIs) is increased by unnecessary placement and prolonged use of urinary catheters. AIM: To assess whether inappropriate use of catheters and catheter-associated UTI were reduced through patient participation. METHODS: In this multicentre, interrupted time-series and before-and-after study, we implemented a patient-centred app which provides catheter advice for patients, together with clinical lessons, feedback via e-mails and support rounds for staff members. Data on catheter use and infections were collected during a six-month baseline and a six-month intervention period on 13 wards in four hospitals in the Netherlands. Dutch Trial Register: NL7178. FINDINGS: Between June 25th, 2018 and August 1st, 2019, 6556 patients were included in 24 point-prevalence surveys, 3285 (50%) at baseline and 3271 (50%) during the intervention. During the intervention 249 app users and a median of seven new app users per week were registered (interquartile range: 5.5-13.0). At baseline, inappropriate catheter use was registered for 175 (21.9%) out of 798 catheters, compared to 55 (7.0%) out of 786 during the intervention. Time-series analysis showed a non-significant decrease of inappropriate use of 5.8% (95% confidence interval: -3.76 to 15.45; P = 0.219), with an odds ratio of 0.27 (0.19-0.37; P < 0.001). Catheter-associated UTI decreased by 3.0% (1.3-4.6; P = 0.001), with odds ratio 0.541 (0.408-0.716; P < 0.001). CONCLUSION: Although UTI significantly decreased after the implementation, patient participation did not significantly reduce the prevalence of inappropriate urinary catheter use. However, the inappropriate catheter reduction of 5.8% and an odds ratio of 0.27 suggest a positive trend. Patient participation appears to reduce CAUTI and could reduce other healthcare-associated infections.

Current evidence on the adoption of indicator condition guided testing for HIV in western countries: A systematic review and meta-analysis.

BACKGROUND: Indicator condition (IC) guided testing for HIV is an effective way to identify undiagnosed people living with HIV, but studies suggest its implementation is lacking. This systematic review provides an overview of the adoption of IC-guided testing in Western countries. METHODS: Seven ICs were selected: tuberculosis (TB), malignant lymphoma, hepatitis B, hepatitis C, cervical/vulvar carcinoma/intraepithelial neoplasia grade 2+ (CC/CIN2+, VC/VIN2+), and peripheral neuropathy (PN). Embase and Ovid MEDLINE were searched up to November 20th, 2020. Publications of all types, using data from ≥2009, reporting on HIV test ratios in patients ≥18 years in all settings in Western countries were eligible. HIV test ratios and positivity were reported per IC. A random effects-model for proportions was used to calculate estimated proportions (ES) with 95% CIs. This study was registered at PROSPERO, registration number CRD42020160243. FINDINGS: Fifty-seven references, including 23 full-text articles and 34 other publications were included. Most (28/57) reported on HIV testing in TB. No reports on HIV testing in VC/VIN2+ or PN patients were eligible for inclusion. Large variation in HIV test ratios was observed between and within ICs, resulting from different testing approaches. Highest HIV test ratios (pooled ratio: 0·72, 95%CI 0·63-0·80) and positivity (0·05, 95% CI 0·03-0·06) were observed among TB patients, and lowest among CC/CIN2+ patients (pooled ES test ratio: 0·12, 95%CI 0·01-0·31, positivity: 0·00, 95%CI 0·00-0·00). INTERPRETATION: IC-guided HIV testing is insufficiently implemented in Western countries. The large variation in test ratios provides insight into priority areas for implementing routine IC-guided HIV testing in the future. FUNDING: HIV Transmission Elimination in Amsterdam (H-TEAM) consortium and Aidsfonds (grant number P-42,702).

A randomised controlled trial testing the efficacy of Fit after COVID, a cognitive behavioural therapy targeting severe post-infectious fatigue following COVID-19 (ReCOVer): study protocol.

BACKGROUND: Coronavirus disease 2019 (COVID-19) results in debilitating long-term symptoms, often referred to as Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), in a substantial subgroup of patients. One of the most prevalent symptoms following COVID-19 is severe fatigue. Prompt delivery of cognitive behavioural therapy (CBT), an evidence-based treatment that has shown benefit in reducing severe fatigue in other conditions, may reduce post-COVID-19 fatigue. Based on an existing CBT protocol, a blended intervention of 17 weeks, Fit after COVID, was developed to treat severe fatigue after the acute phase of infection with SARS-CoV-2. METHOD: The ReCOVer study is a multicentre 2-arm randomised controlled trial (RCT) to test the efficacy of Fit after COVID on severe post-infectious fatigue. Participants are eligible if they report severe fatigue 3 up to and including 12 months following COVID-19. One hundred and fourteen participants will be randomised to either Fit after COVID or care as usual (ratio 1:1). The primary outcome, the fatigue severity subscale of the Checklist Individual Strength (CIS-fatigue), is assessed in both groups before randomisation (T0), directly post CBT or following care as usual (T1), and at follow-up 6 months after the second assessment (T2). In addition, a long-term follow-up (T3), 12 months after the second assessment, is performed in the CBT group only. The primary objective is to investigate whether CBT will lead to a significantly lower mean fatigue severity score measured with the CIS-fatigue across the first two follow-up assessments (T1 and T2) as compared to care as usual. Secondary objectives are to determine the proportion of participants no longer being severely fatigued (operationalised in different ways) at T1 and T2 and to investigate changes in physical and social functioning, in the number and severity of somatic symptoms and in problems concentrating across T1 and T2. DISCUSSION: This is the first trial testing a cognitive behavioural intervention targeting severe fatigue after COVID-19. If Fit after COVID is effective in reducing fatigue severity following COVID-19, this intervention could contribute to alleviating the long-term health consequences of COVID-19 by relieving one of its most prevalent and distressing long-term symptoms. TRIAL REGISTRATION: Netherlands Trial Register NL8947 . Registered on 14 October 2020.

Implementation of 'Choosing Wisely Netherlands' for internal medicine.

BACKGROUND: The Choosing Wisely campaign aims to reduce low-value care to improve quality and lower healthcare costs. Our objective was to determine the current implementation of the Choosing Wisely Netherlands campaign and the 10 recommendations (released in 2014) for internal medicine. METHODS: We actively surveyed physicians and residents in the departments of internal medicine in 13 hospitals in the Netherlands. The survey was performed during a presentation about Choosing Wisely and we asked whether they thought that the recommendations were implemented. RESULTS: Between May and November 2018, we surveyed 281 physicians and residents, of which we received 2625 answers (response rate 85%). We found that 178 (68.5%) of 260 physicians were unaware of the Choosing Wisely campaign. For the implementation of recommendations, 1506 (75.2%) of 2003 answers stated that physicians applied the recommendations in clinical practice. We found no differences in implementation of physicians who were aware or unaware of the campaign, respectively 529 (76.1%) of 695 versus 854 (74.2%) of 1151 of the recommendations were implemented; p = 0.357. The recommendation that was implemented least was 'Do not routinely order coagulation tests before invasive procedures', in which 28% stated that they applied this in clinical practice. CONCLUSION: Four years after the introduction, only one-third of physicians and residents of internal medicine were aware of the Choosing Wisely Netherlands campaign. Nevertheless, most Choosing Wisely recommendations were implemented sufficiently in clinical practice. There is room for improvement, mainly in recommendations that need a multidisciplinary approach.

A healthcare failure mode and effect analysis to optimise the process of blood culture performance.

BACKGROUND: Blood cultures are essential diagnostic tools to identify pathogens in systemic infections. However, logistics of blood culture performance is often suboptimal. This study analyses the pre-analytic phase of blood culture processing through different types of risk assessments. METHODS: We performed direct observations to gain in-depth knowledge of the root causes of suboptimal blood culture performance. These findings were summarised in a Bow-Tie chart. We then utilised a healthcare failure mode and effect analysis to prioritise failures per step in the process and to organise improvement activities. Finally, improvement actions were planned. RESULTS: Not obtaining a second set of blood cultures in the logistics of blood culture performance had the highest priority for action. Several failure modes, including human and system factors, were identified. Improvement actions included training and clinical lessons for nurses in the emergency department, updating hospital search engines to ease identification of relevant protocols, and an evaluation of the workload at the emergency department. Failure modes caused by human factors appear easy to address, however changing human behaviour is challenging. CONCLUSIONS: The analysis provided useful insight into the different steps in the logistics of blood culture performance and facilitated the organisation of actions focused on addressing the most urgent root causes.

Prevalence and risk factors of inappropriate use of intravenous and urinary catheters in surgical and medical patients.

BACKGROUND: Previously, the RICAT (Reduction of Inappropriate use of intravenous and urinary CATheters) study had been conducted by ourselves to reduce inappropriate use of intravenous and urinary catheters in medical wards to prevent healthcare-associated infections. AIM: To compare surgical and medical wards, and to determine risk factors for inappropriate catheter use. METHODS: A cross-sectional study was performed from October, 2017, to May, 2018, in surgical wards of two university hospitals in the Netherlands. Patients were prospectively observed every other week for seven months. Inappropriate use was compared with non-surgical wards in the RICAT study. FINDINGS: In all, 409 surgical patients were included, and they were compared with 1781 medical patients. Inappropriate use occurred in 36 (8.5%) out of 425 peripheral intravenous catheters in 373 surgical patients, compared to 400 (22.9%) out of 1747 peripheral intravenous catheters in 1665 medical patients, a difference of 14.4% (95% confidence interval (CI): 11.1-17.8; P < 0.001). Inappropriate use of urinary catheters occurred in 14 (10.4%) out of 134 surgical patients, compared to 105 (32.4%) out of 324 medical patients, a difference of 22.0% (95% CI: 14.7-29.2; P < 0.001). Subgroup analysis in the two university hospitals confirmed these differences. The main risk factor for inappropriate use of peripheral intravenous catheters was admission in medical wards (odds ratio (OR): 3.50; 95% CI: 2.15-5.69), which was also one of the main risk factors for urinary catheters (OR: 2.75; 95% CI: 1.36-5.55). CONCLUSION: Inappropriate use of catheters is more common in medical wards compared to surgical wards. Prevention strategies to reduce healthcare-associated infections should primarily focus on sites with high prevalence of inappropriate use.

Trends in prevalence of healthcare-associated infections and antimicrobial use in hospitals in the Netherlands: 10 years of national point-prevalence surveys.

BACKGROUND: Prevalence of healthcare-associated infections (HCAIs) and antimicrobial use in hospitals in the Netherlands has been measured using voluntary biannual national point-prevalence surveys (PPSs). AIM: To describe trends in the prevalence of patients with HCAI, risk factors, and antimicrobial use in 2007-2016. METHODS: In the PPS, patient characteristics, use of medical devices and antimicrobials, and presence of HCAI on the survey day are reported for all hospitalized patients, excluding patients in the day-care unit and psychiatric wards. Analyses were performed using linear and (multivariate) logistic regression, accounting for clustering of patients within hospitals. FINDINGS: PPS data were reported for 171,116 patients. Annual prevalence of patients with HCAI with onset during hospitalization decreased from 6.1% in 2007 to 3.6% in 2016. The adjusted odds ratio (OR) for trend was 0.97 (95% confidence interval: 0.96-0.98). Most prominent trends were seen for surgical site infections (1.6%-0.8%; OR: 0.91 (0.90-0.93)) and urinary tract infections (2.1%-0.6%; OR: 0.85 (0.83-0.87)). From 2014 on, HCAIs at admission were also registered with a stable prevalence of approximately 1.5%. The mean length of stay decreased from 10 to 7 days. The percentage of patients treated with antibiotics increased from 31% to 36% (OR: 1.03 (1.02-1.03)). CONCLUSION: Repeated PPS data from 2007 to 2016 show a decrease in the prevalence of patients with HCAI with onset during hospitalization, and a stable prevalence of patients with HCAI at admission. The adjusted OR of 0.97 for HCAI during hospitalization indicates a true reduction in prevalence of approximately 3% per year.

Comprehensive longitudinal analysis of hepatitis C virus (HCV)-specific T cell responses during acute HCV infection in the presence of existing HIV-1 infection.

The aim of this study was to study the development of HCV-specific T cell immunity during acute HCV infection in the presence of an existing HIV-1 infection in four HIV-1 infected men having sex with men. A comprehensive analysis of HCV-specific T cell responses was performed at two time points during acute HCV infection using a T cell expansion assay with overlapping peptide pools spanning the entire HCV genome Three patients with (near) normal CD4+ T cell counts (range 400-970 x 10(6)/L) either resolved (n=1) or temporary suppressed HCV RNA. In contrast, one patient with low CD4+ T cell counts (330 x 10(6)/L), had sustained high HCV RNA levels. All four patients had low HCV-specific CD8+ T cell responses, and similar magnitudes of CD4+ T cell responses. Interestingly, individuals with resolved infection or temporary suppression of HCV-RNA had HCV-specific CD4+ T cell responses predominantly against nonstructural (NS) proteins. While the individual with high HCV RNA plasma concentrations had CD4+ T cell responses predominantly directed against Core. Our data show that an acute HCV infection in an HIV-1 infected person can be suppressed in the presence of HCV-specific CD4+ T cell response targeting non-structural proteins. However further research is needed in a larger group of patients to evaluate the role of HIV-1 on HCV-specific T cell responses in relation to outcome of acute HCV infection.