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Item does not contain fulltext, BACKGROUND: Rezafungin is a next-generation, once-a-week echinocandin in development for the treatment of candidaemia and invasive candidiasis and for the prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis spp after blood and marrow transplantation. We aimed to compare the efficacy and safety of intravenous rezafungin versus intravenous caspofungin in patients with candidaemia and invasive candidiasis. METHODS: ReSTORE was a multicentre, double-blind, double-dummy, randomised phase 3 trial done at 66 tertiary care centres in 15 countries. Adults (≥18 years) with systemic signs and mycological confirmation of candidaemia or invasive candidiasis were eligible for inclusion and randomly assigned (1:1) to receive intravenous rezafungin once a week (400 mg in week 1, followed by 200 mg weekly, for a total of two to four doses) or intravenous caspofungin (70 mg loading dose on day 1, followed by 50 mg daily) for no more than 4 weeks. The primary endpoints were global cure (consisting of clinical cure, radiological cure, and mycological eradication) at day 14 for the European Medical Agency (EMA) and 30-day all-cause mortality for the US Food and Drug Administration (FDA), both with a target non-inferiority margin of 20%, assessed in the modified intention-to-treat population (all patients who received one or more doses of study drug and had documented Candida infection based on a culture from blood or another normally sterile site obtained within 96 h before randomisation). Safety was evaluated by the incidence and type of adverse events and deaths in the safety population, defined as all patients who received any amount of study drug. The trial is registered with ClinicalTrials.gov, NCT03667690, and is complete. FINDINGS: Between Oct 12, 2018, and Aug 29, 2021, 222 patients were screened for inclusion, and 199 patients (118 [59%] men; 81 [41%] women; mean age 61 years [SD 15·2]) were randomly assigned (100 [50%] patients to the rezafun

Radboud University, 03 februari 2023, Promotores : Kullberg, B.J., Joosten, L.A.B., Hovius, J.W. Co-promotor : Wijngaard, C.C. van den, Contains fulltext : 288651.pdf (Publisher’s version ) (Closed access)

Contains fulltext : 293169.pdf (Publisher’s version ) (Open Access), OBJECTIVE: The diagnosis of Lyme borreliosis is based on two-tier testing using an ELISA and Western blot. About 5-10% of patients report persistent symptoms of unknown etiology after treatment, resulting in substantial difficulties in further diagnostic workup. This paper presents a study aimed at determining whether serology can differentiate between patients with persistent symptoms attributed to Lyme and other patients with Lyme borreliosis. METHODS: A retrospective cohort study included 162 samples from four subgroups: patients with persistent symptoms of Lyme (PSL), early Lyme borreliosis with erythema migrans (EM), patients tested in a general practitioner setting (GP), and healthy controls (HC). ELISA, Western blots, and multiplex assays from different manufacturers were used to determine inter-test variations in PSL and to compare reactivity against Borrelia-specific antigens among the groups. RESULTS: In comparing the IgG and IgM reactivity by Western blot, IgG was more often positive in the PSL group than in the GP group. The individual antigen reactivity was similar between the PSL and EM or GP groups. Inter-test agreement among the manufacturers was variable, and agreement was higher for IgG testing compared to IgM. CONCLUSIONS: Serological testing is unable to define the subgroup of patients with persistent symptoms attributed to Lyme borreliosis. Additionally, the current two-tier testing protocol shows a large variance among different manufacturers in these patients.

Contains fulltext : 249005.pdf (Publisher’s version ) (Open Access), INTRODUCTION: Intra-abdominal infections represent the second most frequently acquired infection in the intensive care unit (ICU), with mortality rates ranging from 20% to 50%. Candida spp. may be responsible for up to 10-30% of cases. This study assesses risk factors for development of intra-abdominal candidiasis (IAC) among patients admitted to ICU. METHODS: We performed a case-control study in 26 European ICUs during the period January 2015-December 2016. Patients at least 18 years old who developed an episode of microbiologically documented IAC during their stay in the ICU (at least 48 h after admission) served as the case cohort. The control group consisted of adult patients who did not develop episodes of IAC during ICU admission. Matching was performed at a ratio of 1:1 according to time at risk (i.e. controls had to have at least the same length of ICU stay as their matched cases prior to IAC onset), ICU ward and period of study. RESULTS: During the study period, 101 case patients with a diagnosis of IAC were included in the study. On univariate analysis, severe hepatic failure, prior receipt of antibiotics, prior receipt of parenteral nutrition, abdominal drain, prior bacterial infection, anastomotic leakage, recurrent gastrointestinal perforation, prior receipt of antifungal drugs and higher median number of abdominal surgical interventions were associated with IAC development. On multivariate analysis, recurrent gastrointestinal perforation (OR 13.90; 95% CI 2.65-72.82, p = 0.002), anastomotic leakage (OR 6.61; 95% CI 1.98-21.99, p = 0.002), abdominal drain (OR 6.58; 95% CI 1.73-25.06, p = 0.006), prior receipt of antifungal drugs (OR 4.26; 95% CI 1.04-17.46, p = 0.04) or antibiotics (OR 3.78; 95% CI 1.32-10.52, p = 0.01) were independently associated with IAC. CONCLUSIONS: Gastrointestinal perforation, anastomotic leakage, abdominal drain and prior receipt of antifungals or antibiotics may help to identify critically ill patients with higher probability

Item does not contain fulltext, Previous studies have shown that monocytes can be 'trained' or tolerized by certain stimuli to respond stronger or weaker to a secondary stimulation. Rewiring of glucose metabolism was found to be important in inducing this phenotype. As we previously found that Borrelia burgdorferi (B. burgdorferi), the causative agent of Lyme borreliosis (LB), alters glucose metabolism in monocytes, we hypothesized that this may also induce long-term changes in innate immune responses. We found that exposure to B. burgdorferi decreased cytokine production in response to the TLR4-ligand lipopolysaccharide (LPS). In addition, B. burgdorferi exposure decreased baseline levels of glycolysis, as assessed by lactate production. Using GWAS analysis, we identified a gene, microfibril-associated protein 3-like (MFAP3L) as a factor influencing lactate production after B. burgdorferi exposure. Validation experiments proved that MFAP3L affects lactate- and cytokine production following B. burgdorferi stimulation. This is mediated by functions of MFAP3L, which includes activating ERK2 and through activation of platelet degranulation. Moreover, we showed that platelets and platelet-derived factors play important roles in B. burgdorferi-induced cytokine production. Certain platelet-derived factors, such chemokine C-X-C motif ligand 7 (CXCL7) and (C-C motif) ligand 5 (CCL5), were elevated in the circulation of LB patients in comparison to healthy individuals.

Item does not contain fulltext, BACKGROUND: Cellular tests for Lyme borreliosis might be able to overcome major shortcomings of serological testing, such as its low sensitivity in early stages of infection. Therefore, we aimed to assess the sensitivity and specificity of three cellular tests. METHODS: This was a nationwide, prospective, multiple-gate case-control study done in the Netherlands. Patients with physician-confirmed Lyme borreliosis, either early localised or disseminated, were consecutively included as cases at the start of antibiotic treatment. Controls were those without Lyme borreliosis from the general population (healthy controls) and those with potentially cross-reactive conditions (eg, autoimmune disease). We used three cellular tests for Lyme borreliosis (Spirofind Revised, iSpot Lyme, and LTT-MELISA) as index tests, and standard two-tier serological testing (STTT) as a comparator. Clinical data from Lyme borreliosis patients were collected at baseline and at 12 weeks after inclusion, and blood samples were obtained at baseline, 6 weeks, and 12 weeks. Control participants underwent clinical and laboratory assessments at baseline only. FINDINGS: Cases comprised 271 patients with Lyme borreliosis (of whom 245 had early-localised Lyme borreliosis and 26 had disseminated disease) and controls comprised 228 participants without Lyme borreliosis from the general population and 41 participants with potentially cross-reactive conditions. Recruitment occurred between May 14, 2018, and March 16, 2020. The specificity of STTT in healthy controls (216 of 228 samples [94·7%, 95% CI 91·5-97·7]) was higher than that of the cellular tests: Spirofind (140 of 171 [81·9%, 76·1-87·2]), iSpot Lyme (32 of 103 [31·1%, 21·5-40·3]) and LTT-MELISA (100 of 190 [52·6%, 44·9-60·3]). Cellular tests had varying sensitivities: Spirofind (88 of 204 [43·1%, 36·4-50·4]), iSpot Lyme (51 of 94 [54·3%, 44·5-63·7]), and LTT-MELISA (66 of 218 [30·3%, 23·8-36·7]). The Spirofind and iSpot Lyme outperformed STTT for sen

Item does not contain fulltext, Independence is crucial for the quality and credibility of scientific recommendations and guidelines. The composition of advisory committees requires a full understanding of the relationships and interests of prospective committee members. In addition to financial relationships, intellectual interests, professional interests, and reputation may also play a role. In addition to preventing conflicts of interest among committee members, precautions are also required during the review and authorisation stages of draft recommendations. We describe which potential or perceived conflicts of interests may occur, and how quality and independence of the advisory process can be safeguarded.

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Contains fulltext : 232415.pdf (Publisher’s version ) (Closed access), The EORTC/MSGERC recently revised and updated the consensus definitions of invasive fungal disease (IFD). These definitions primarily focus on patients with cancer and stem cell or solid-organ transplant patients. They may therefore not be suitable for intensive care unit (ICU) patients. More in detail, while the definition of proven IFD applies to a broad range of hosts, the categories of probable and possible IFD were primarily designed for classical immunocompromised hosts and may therefore not be ideal for other populations. Moreover, the scope of the possible category of IFD has been diminished in the recently revised definitions for classically immunocompromised hosts. Diagnosis of IFD in the ICU presents many challenges, which are different for invasive candidiasis and for invasive aspergillosis. The aim of this article is to review progresses made in recent years and difficulties remaining in the development of definitions applicable in the ICU setting.

Contains fulltext : 236930.pdf (Publisher’s version ) (Open Access)

Radboud University, 15 februari 2021, Promotores : Gyssens, I.C.J., Hulscher, M.E.J.L., Kullberg, B.J. Co-promotor : Schouten, J.A., Contains fulltext : 230165.pdf (publisher's version ) (Open Access)

Item does not contain fulltext, INTRODUCTION/OBJECTIVE: Expectancies about symptom improvement or deterioration are reliable predictors of symptom progression and treatment outcomes (symptom resolution or symptomatic improvement) in many (non-)pharmacological studies and treatments. This study examined predictors of symptom improvement after antimicrobial therapy for persistent symptoms attributed to Lyme disease, hypothesizing particularly pre-treatment expectancies regarding symptom improvement to be predictive. METHODS: A predictive study was performed on pre-treatment and post-treatment individual characteristics, including expectancies, and physical and mental health-related quality of life (HRQoL) from the PLEASE-trial comparing randomized 12-weeks of doxycycline, clarithromycin-hydroxychloroquine, or placebo following 2 weeks of intravenous ceftriaxone. At end-of-treatment (14 weeks after trial start) and follow-up (52 weeks), complete data of 231 and 170 (of initial 280) patients with persistent symptoms temporally related to a history of erythema migrans or otherwise confirmed symptomatic Lyme disease, or accompanied by B. burgdorferi IgG or IgM antibodies, were examined through hierarchical regression analyses. RESULTS: In addition to pre-treatment HRQoL, pre-treatment expectancies regarding symptom improvement were consistently associated with stronger physical and mental HRQoL improvements at both end-of-treatment and follow-up (95% CI range: .09;.54, p < .01 to .27;.92, p < .001). Post-treatment expectancies regarding having received antibiotics vs. placebo was associated with more HRQoL improvement at end-of-treatment, but not at follow-up (95% CI-range 1.00;4.75, p = .003 to -7.34; -2.22, p < .001). CONCLUSIONS: The present study shows that, next to pre-treatment functioning, patients' pre-treatment and post-treatment expectancies regarding improvement of persistent symptoms attributed to Lyme disease relate to a more beneficial symptom course. Expectancies of patients may be releva

Radboud University, 13 april 2021, Promotores : Kullberg, B.J., Hulscher, M.E.J.L. Co-promotores : Schouten, J.A., Oever, J. ten, Contains fulltext : 231216.pdf (publisher's version ) (Open Access)

Contains fulltext : 245707.pdf (Publisher’s version ) (Open Access), The Fungal Infections Definitions in Intensive Care Unit (ICU) patients (FUNDICU) project aims to provide standard sets of definitions for invasive fungal diseases (IFDs) in critically ill, adult patients, including invasive aspergillosis (IA), invasive candidiasis (IC), Pneumocystis jirovecii pneumonia (PJP), and other non-IA, non-IC IFDs. The first step of the project was the conduction of separated systematic reviews of the characteristics and applicability to critically ill, adult patients outside classical populations at risk (hematology patients, solid organ transplant recipients) of available definitions and diagnostic tests for IFDs. We report here the results of two systematic reviews exploring the performance of available definitions and tests, for PJP and for other non-IA, non-IC IFDs. Starting from 2585 and 4584 records for PJP and other IFDs, respectively, 89 and 61 studies were deemed as eligible for full-text evaluation. However, only two studies for PJP and no studies for other IFDs met the FUNDICU protocol criteria for inclusion in qualitative synthesis. Currently, there is no sufficient solid data for directly evaluating the performance of existing definitions and laboratory tests for the diagnosis of PJP and other non-IA, non-IC IFDs in critically ill adult patients outside classical populations at risk.

Contains fulltext : 238089.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 228673.pdf (publisher's version ) (Open Access)

Item does not contain fulltext, OBJECTIVES: To summarize the available evidence on the diagnostic performance for invasive aspergillosis (IA) in non-hematological, non-solid organ transplantation critically ill patients of the following: (i) existing definitions of IA (developed either for classical immunocompromised populations or for non-immunocompromised critically ill patients); (ii) laboratory tests; (iii) radiology tests. METHODS: A systematic review was performed by evaluating studies assessing the diagnostic performance for IA of a definition/s and/or laboratory/radiology test/s vs. a reference standard (histology) or a reference definition. RESULTS: Sufficient data for evaluating the performance of existing definitions and laboratory tests for the diagnosis of IA in critically ill patients is available only for invasive pulmonary aspergillosis. Against histology/autopsy as reference, the AspICU definition showed a promising diagnostic performance but based on small samples and applicable only to patients with positive respiratory cultures. Studies on laboratory tests consistently indicated a better diagnostic performance of bronchoalveolar lavage fluid (BALF) galactomannan (GM) than serum GM, and a suboptimal specificity of BALF and serum (1,3)-β-D-glucan. CONCLUSIONS: Evidence stemming from this systematic review will guide the discussion for defining invasive aspergillosis within the FUNDICU project. The project aims to develop a standard set of definitions for invasive fungal diseases in critically ill, adult patients.

Contains fulltext : 225781.pdf (Publisher’s version ) (Open Access), BACKGROUND: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. METHODS: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. RESULTS: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. CONCLUSIONS: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.

Contains fulltext : 220683.pdf (publisher's version ) (Closed access), Lyme borreliosis is the most common vectorborne disease in the northern hemisphere. It usually begins with erythema migrans; early disseminated infection particularly causes multiple erythema migrans or neurologic disease, and late manifestations predominantly include arthritis in North America, and acrodermatitis chronica atrophicans (ACA) in Europe. Diagnosis of Lyme borreliosis is based on characteristic clinical signs and symptoms, complemented by serological confirmation of infection once an antibody response has been mounted. Manifestations usually respond to appropriate antibiotic regimens, but the disease can be followed by sequelae, such as immune arthritis or residual damage to affected tissues. A subset of individuals reports persistent symptoms, including fatigue, pain, arthralgia, and neurocognitive symptoms, which in some people are severe enough to fulfil the criteria for post-treatment Lyme disease syndrome. The reported prevalence of such persistent symptoms following antimicrobial treatment varies considerably, and its pathophysiology is unclear. Persistent active infection in humans has not been identified as a cause of this syndrome, and randomized treatment trials have invariably failed to show any benefit of prolonged antibiotic treatment. For prevention of Lyme borreliosis, post-exposure prophylaxis may be indicated in specific cases, and novel vaccine strategies are under development.

Contains fulltext : 228680.pdf (publisher's version ) (Open Access)

Contains fulltext : 218588.pdf (publisher's version ) (Open Access), BACKGROUND: Our aim in this study was to develop quality indicators (QIs) for outpatient parenteral antimicrobial therapy (OPAT) care that can be used as metrics for quality assessment and improvement. METHODS: A RAND-modified Delphi procedure was used to develop a set of QIs. Recommendations on appropriate OPAT care in adults were retrieved from the literature using a systematic review and translated into potential QIs. These QIs were appraised and prioritized by a multidisciplinary panel of international OPAT experts in 2 questionnaire rounds combined with a meeting between rounds. RESULTS: The procedure resulted in 33 OPAT-specific recommendations. The following QIs that describe recommended OPAT care were prioritized by the expert panel: the presence of a structured OPAT program, a formal OPAT care team, a policy on patient selection criteria, and a treatment and monitoring plan; assessment for OPAT should be performed by the OPAT team; patients and family should be informed about OPAT; there should be a mechanism in place for urgent discussion and review of emergent clinical problems, and a system in place for rapid communication; laboratory results should be delivered to physicians within 24 hours; and the OPAT team should document clinical response to antimicrobial management, document adverse events, and monitor QIs for OPAT care and make these data available. CONCLUSIONS: We systematically developed a set of 33 QIs for optimal OPAT care, of which 12 were prioritized by the expert panel. These QIs can be used to assess and improve the quality of care provided by OPAT teams.

Contains fulltext : 229344.pdf (Publisher’s version ) (Closed access), Candida auris is among the most important emerging fungal pathogens, yet mechanistic insights into its immune recognition and control are lacking. Here, we integrate transcriptional and functional immune-cell profiling to uncover innate defence mechanisms against C. auris. C. auris induces a specific transcriptome in human mononuclear cells, a stronger cytokine response compared with Candida albicans, but a lower macrophage lysis capacity. C. auris-induced innate immune activation is mediated through the recognition of C-type lectin receptors, mainly elicited by structurally unique C. auris mannoproteins. In in vivo experimental models of disseminated candidiasis, C. auris was less virulent than C. albicans. Collectively, these results demonstrate that C. auris is a strong inducer of innate host defence, and identify possible targets for adjuvant immunotherapy.

Purpose: Invasive pulmonary aspergillosis is increasingly reported in patients with influenza admitted to the intensive care unit (ICU). Classification of patients with influenza-associated pulmonary aspergillosis (IAPA) using the current definitions for invasive fungal diseases has proven difficult, and our aim was to develop case definitions for IAPA that can facilitate clinical studies. Methods: A group of 29 international experts reviewed current insights into the epidemiology, diagnosis and management of IAPA and proposed a case definition of IAPA through a process of informal consensus. Results: Since IAPA may develop in a wide range of hosts, an entry criterion was proposed and not host factors. The entry criterion was defined as a patient requiring ICU admission for respiratory distress with a positive influenza test temporally related to ICU admission. In addition, proven IAPA required histological evidence of invasive septate hyphae and mycological evidence for Aspergillus. Probable IAPA required the detection of galactomannan or positive Aspergillus culture in bronchoalveolar lavage (BAL) or serum with pulmonary infiltrates or a positive culture in upper respiratory samples with bronchoscopic evidence for tracheobronchitis or cavitating pulmonary infiltrates of recent onset. The IAPA case definitions may be useful to classify patients with COVID-19-associated pulmonary aspergillosis (CAPA), while awaiting further studies that provide more insight into the interaction between Aspergillus and the SARS-CoV-2-infected lung. Conclusion: A consensus case definition of IAPA is proposed, which will facilitate research into the epidemiology, diagnosis and management of this emerging acute and severe Aspergillus disease, and may be of use to study CAPA.

Contains fulltext : 203702.pdf (publisher's version ) (Closed access)

Contains fulltext : 206783.pdf (publisher's version ) (Closed access), BACKGROUND: Isavuconazole was compared to caspofungin followed by oral voriconazole in a Phase 3, randomized, double-blind, multinational clinical trial for the primary treatment of patients with candidemia or invasive candidiasis. METHODS: Adult patients were randomized 1:1 to isavuconazole (200 mg intravenous [IV] three-times-daily [TID] for 2 days, followed by 200 mg IV once-daily [OD]) or caspofungin (70 mg IV OD on day 1, followed by 50 mg IV OD [70 mg in patients > 80 kg]) for a maximum of 56 days. After day 10, patients could switch to oral isavuconazole (isavuconazole arm) or voriconazole (caspofungin arm). Primary efficacy endpoint was successful overall response at the end of IV therapy (EOIVT) in patients with proven infections who received >/=1 dose of study drug (modified-intent-to-treat [mITT] population). The pre-specified noninferiority margin was 15%. Secondary outcomes in the mITT population were successful overall response at 2 weeks after the end of treatment, all-cause mortality at days 14 and 56, and safety. RESULTS: Of 450 patients randomized, 400 comprised the mITT population. Baseline characteristics were balanced between groups. Successful overall response at EOIVT was observed in 60.3% of patients in the isavuconazole arm and 71.1% in the caspofungin arm (adjusted difference -10.8, 95% confidence interval -19.9--1.8). The secondary endpoints, all-cause mortality, and safety were similar between arms. Median time to clearance of the bloodstream was comparable between groups. CONCLUSIONS: This study did not demonstrate non-inferiority of isavuconazole to caspofungin for primary treatment of invasive candidiasis. Secondary endpoints were similar between both groups. CLINICAL TRIALS REGISTRATION: NCT00413218.

Contains fulltext : 203376.pdf (publisher's version ) (Open Access)

Contains fulltext : 202898.pdf (publisher's version ) (Open Access), OBJECTIVE: To investigate whether longer-term antibiotic treatment improves cognitive performance in patients with persistent symptoms attributed to Lyme borreliosis. METHODS: Data were collected during the Persistent Lyme Empiric Antibiotic Study Europe (PLEASE) trial, a randomized, placebo-controlled study. Study participants passed performance-validity testing (measure for detecting suboptimal effort) and had persistent symptoms attributed to Lyme borreliosis. All patients received a 2-week open-label regimen of intravenous ceftriaxone before the 12-week blinded oral regimen (doxycycline, clarithromycin/hydroxychloroquine, or placebo). Cognitive performance was assessed at baseline and after 14, 26, and 40 weeks with neuropsychological tests covering the cognitive domains of episodic memory, attention/working memory, verbal fluency, speed of information processing, and executive function. RESULTS: Baseline characteristics of patients enrolled (n = 239) were comparable in all treatment groups. After 14 weeks, performance on none of the cognitive domains differed significantly between the treatment arms (p = 0.49-0.82). At follow-up, no additional treatment effect (p = 0.35-0.98) or difference between groups (p = 0.37-0.93) was found at any time point. Patients performed significantly better in several cognitive domains at weeks 14, 26, and 40 compared to baseline, but this was not specific to a treatment group. CONCLUSIONS: A 2-week treatment with ceftriaxone followed by a 12-week regimen of doxycycline or clarithromycin/hydroxychloroquine did not lead to better cognitive performance compared to a 2-week regimen of ceftriaxone in patients with Lyme disease-attributed persistent symptoms. CLINICALTRIALSGOV IDENTIFIER: NCT01207739. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that longer-term antibiotics in patients with borreliosis-attributed persistent symptoms does not increase cognitive performance compared to shorter-term antibiotics.

Contains fulltext : 207350.pdf (publisher's version ) (Open Access)

Contains fulltext : 208241.pdf (publisher's version ) (Open Access), Background: Persistent symptoms attributed to Lyme borreliosis often include self-reported cognitive impairment. However, it remains unclear whether these symptoms can be substantiated by objective cognitive testing. Methods: For this observational study, cognitive performance was assessed in 280 adults with persistent symptoms attributed to Lyme borreliosis (as part of baseline data collected for the Dutch PLEASE study). Cognitive testing covered the five major domains: episodic memory, working memory / attention, verbal fluency, information-processing speed and executive function. Patients’ profiles of test scores were compared to a large age-, education- and sex-adjusted normative sample using multivariate normative comparison. Performance validity was assessed to detect suboptimal effort, and questionnaires were administered to measure self-reported cognitive complaints, fatigue, anxiety, depressive symptoms and several other psychological factors. Results: Of 280 patients, one was excluded as the test battery could not be completed. Of the remaining 279 patients, 239 (85.4%) displayed sufficient performance validity. Patients with insufficient performance validity felt significantly more helpless and physically fatigued, and less orientated. Furthermore, they had a lower education level and less often paid work. Of the total study cohort 5.7% (n = 16) performed in the impaired range. Among the 239 patients who displayed sufficient performance validity, 2.9% (n = 7) were classified as cognitively impaired. No association between subjective cognitive symptoms and objective impairment was found. Conclusions: Only a small percentage of patients with borreliosis-attributed persistent symptoms have objective cognitive impairment. Performance validity should be taken into account in neuropsychological examinations of these patients. Self-report questionnaires are insufficiently valid to diagnose cognitive impairment. Trial registration: ClinicalTrials.gov NCT01207739.

Contains fulltext : 204758.pdf (publisher's version ) (Closed access)