Importance:Metformin and glyburide monotherapy are used as alternatives to insulin in managing gestational diabetes. Whether a sequential strategy of these oral agents results in noninferior perinatal outcomes compared with insulin alone is unknown. Objective:To test whether a treatment strategy of oral glucose-lowering agents is noninferior to insulin for prevention of large-for-gestational-age infants. Design, Setting, and Participants:Randomized, open-label noninferiority trial conducted at 25 Dutch centers from June 2016 to November 2022 with follow-up completed in May 2023. The study enrolled 820 individuals with gestational diabetes and singleton pregnancies between 16 and 34 weeks of gestation who had insufficient glycemic control after 2 weeks of dietary changes (defined as fasting glucose >95 mg/dL [>5.3 mmol/L], 1-hour postprandial glucose >140 mg/dL [>7.8 mmol/L], or 2-hour postprandial glucose >120 mg/dL [>6.7 mmol/L], measured by capillary glucose self-testing). Interventions:Participants were randomly assigned to receive metformin (initiated at a dose of 500 mg once daily and increased every 3 days to 1000 mg twice daily or highest level tolerated; n = 409) or insulin (prescribed according to local practice; n = 411). Glyburide was added to metformin, and then insulin substituted for glyburide, if needed, to achieve glucose targets. Main Outcomes and Measures:The primary outcome was the between-group difference in the percentage of infants born large for gestational age (birth weight >90th percentile based on gestational age and sex). Secondary outcomes included maternal hypoglycemia, cesarean delivery, pregnancy-induced hypertension, preeclampsia, maternal weight gain, preterm delivery, birth injury, neonatal hypoglycemia, neonatal hyperbilirubinemia, and neonatal intensive care unit admission. Results:Among 820 participants, the mean age was 33.2 (SD, 4.7) years). In participants randomized to oral agents, 79% (n = 320) maintained glycemic control without insulin. With oral agents, 23.9% of infants (n = 97) were large for gestational age vs 19.9% (n = 79) with insulin (absolute risk difference, 4.0%; 95% CI, -1.7% to 9.8%; P = .09 for noninferiority), with the confidence interval of the risk difference exceeding the absolute noninferiority margin of 8%. Maternal hypoglycemia was reported in 20.9% with oral glucose-lowering agents and 10.9% with insulin (absolute risk difference, 10.0%; 95% CI, 3.7%-21.2%). All other secondary outcomes did not differ between groups. Conclusions and Relevance:Treatment of gestational diabetes with metformin and additional glyburide, if needed, did not meet criteria for noninferiority compared with insulin with respect to the proportion of infants born large for gestational age. Trial Registration:Netherlands Trial Registry Identifier: NTR6134.

IMPORTANCE Metformin and glyburide monotherapy are used as alternatives to insulin in managing gestational diabetes. Whether a sequential strategy of these oral agents results in noninferior perinatal outcomes compared with insulin alone is unknown. OBJECTIVE To test whether a treatment strategy of oral glucose-lowering agents is noninferior to insulin for prevention of large-for-gestational-age infants. DESIGN, SETTING, AND PARTICIPANTS Randomized, open-label noninferiority trial conducted at 25 Dutch centers from June 2016 to November 2022 with follow-up completed in May 2023. The study enrolled 820 individuals with gestational diabetes and singleton pregnancies between 16 and 34 weeks of gestation who had insufficient glycemic control after 2 weeks of dietary changes (defined as fasting glucose >95 mg/dL [>5.3 mmol/L], 1-hour postprandial glucose >140 mg/dL [>7.8 mmol/L], or 2-hour postprandial glucose >120 mg/dL [>6.7 mmol/L], measured by capillary glucose self-testing). INTERVENTIONS Participants were randomly assigned to receive metformin (initiated at a dose of 500 mg once daily and increased every 3 days to 1000 mg twice daily or highest level tolerated; n = 409) or insulin (prescribed according to local practice; n = 411). Glyburide was added to metformin, and then insulin substituted for glyburide, if needed, to achieve glucose targets. MAIN OUTCOMES AND MEASURES The primary outcome was the between-group difference in the percentage of infants born large for gestational age (birth weight >90th percentile based on gestational age and sex). Secondary outcomes included maternal hypoglycemia, cesarean delivery, pregnancy-induced hypertension, preeclampsia, maternal weight gain, preterm delivery, birth injury, neonatal hypoglycemia, neonatal hyperbilirubinemia, and neonatal intensive care unit admission. RESULTS Among 820 participants, the mean age was 33.2 (SD, 4.7) years). In participants randomized to oral agents, 79% (n = 320) maintained glycemic control without insulin. With oral agents, 23.9% of infants (n = 97) were large for gestational age vs 19.9% (n = 79) with insulin (absolute risk difference, 4.0%; 95% CI, -1.7% to 9.8%; P = .09 for noninferiority), with the confidence interval of the risk difference exceeding the absolute noninferiority margin of 8%. Maternal hypoglycemia was reported in 20.9% with oral glucose-lowering agents and 10.9% with insulin (absolute risk difference, 10.0%; 95% CI, 3.7%-21.2%). All other secondary outcomes did not differ between groups. CONCLUSIONS AND RELEVANCE Treatment of gestational diabetes with metformin and additional glyburide, if needed, did not meet criteria for noninferiority compared with insulin with respect to the proportion of infants born large for gestational age.

Background: Few studies evaluated the performance of noninvasive diagnostic strategies for suspected acute pulmonary embolism (PE) in pregnant women.Objectives: The aim of this study was to establish the safety and efficiency of the Wells rule with fixed and adapted D-dimer threshold, and the YEARS algorithm, combined with compression ultrasonography (CUS), in pregnant women with suspected PE in an individual patient data meta-analysis.Methods: We performed a systematic review to identify prospective diagnostic management studies in pregnant women with suspected PE. Primary outcomes were safety, defined as the failure rate, ie, the 3-month venous thromboembolism (VTE) incidence after excluding PE without chest imaging, and efficiency, defined as the proportion of patients in whom chest imaging could be avoided.Results: We identified 2 relevant studies, of which individual patient-level data were analyzed in a fixed-effect meta-analysis, totaling 893 pregnant women. The Wells rule with fixed and adapted D-dimer threshold as well as the YEARS algorithm could safely rule out acute PE (failure rate, 0.37%-1.4%), but efficiency improved considerably when applying pretest probability-adapted D-dimer thresholds. The efficiency of bilateral CUS was limited (2.3% overall; number needed to test 43), especially in patients without symptoms of deep-vein thrombosis (efficiency 0.79%; number needed to test 127).Conclusion: This study supports the latest guideline recommendations (European Society of Cardiology 2019) to apply pretest probability assessment and D-dimer tests to rule out PE in pregnant women. From an efficiency perspective, the use of a strategy with pretest probability-adapted D-dimer threshold is preferred. The yield of CUS was very limited in patients without concomitant symptoms of deep-vein thrombosis.

Lyme neuroborreliosis (LNB) is a tick-borne infection caused by Borrelia burgdorferi which can affect the nervous system in adults and children. The clinical course of LNB in adults is often different than in children. Studies comparing these differences are scarce. The aim of this study was to compare the clinical characteristics and outcome of LNB between children and adults. We performed an observational retrospective study among patients with LNB who presented at Gelre Hospital from 2007 to 2020 and had cerebrospinal fluid pleocytosis. Data were collected from electronic medical records. A total of 127 patients with LNB were identified. Included were 58 children (median age 8 years) and 69 adults (median age 56 years). The incidence of LNB was 3.2 per 100,000 inhabitants per year. The most common neurological manifestation in adults and in children was facial nerve palsy (67%). Unilateral facial nerve palsy was more prevalent in children (85%) than in adults (42%) (P < 0.001). Headache was also more prevalent in children (59%) than in adults (32%) (P = 0.003). (Poly)radiculitis was more prevalent in adults (51%) than in children (3%) (P < 0.001), encephalitis was not reported in children. In children, the time between symptom onset and diagnosis was 10 days versus 28 days in adults (P < 0.001). Complete recovery was reported significantly more often in children (83%) compared to adults (40%) (P < 0.001).    Conclusion: In a Lyme-endemic area in the Netherlands, LNB commonly presents with facial nerve palsy. Facial nerve palsy and headache are more prevalent in children, while radiculitis and encephalitis are mostly reported in adults.

Little is known on coping strategies in patients with chronic symptoms suspected of Lyme borreliosis (LB). Different coping strategies might influence quality of life (QoL). We assessed coping strategies and QoL in patients with chronic symptoms suspected of LB. Adult patients referred to the Lyme Center Apeldoorn were included (November 2019–April 2021). Participants completed the RAND-36 to assess QoL and the Utrecht Coping List to assess coping strategies. Patient data were extracted from medical records. Patients were categorized based on clinical LB and serology. Linear regression analyses were conducted to examine an association between coping strategies and QoL subscales. Included were 201 patients. Patients suspected of LB had a different coping profile and lower QoL compared to the reference population. Patients with negative serology and no clinical LB scored lowest on all QoL subscales. In multivariate analyses, correcting for age, gender, comorbidity, and patient category, a negative association was found between passive coping and the QoL subscales physical functioning (β(SE) = − 1.1(0.5)), social functioning (β(SE) = − 3.3(0.5)), role limitations (emotional) (β(SE) = − 5.5(0.8)), mental health (β(SE) = − 3.7(0.3)), vitality (β(SE) = − 2.3(0.3)), pain (β(SE) = − 2.3(0.5)), and general health (β(SE) = − 2.7(0.3)). A negative association was also found between palliative coping and the QoL subscale role limitations (physical) (β(SE) = − 1.8(0.6)) and between expressing emotions and mental health (β(SE) = − 1.3(0.6)). A positive association was found between active coping and the QoL subscales mental health (β(SE) = 1.0(0.3)) and role limitations (emotional) (β(SE) = 1.9(0.8)). In patients suspected of LB, dysfunctional coping strategies were associated with worse quality of life. There is a need for interventions that can guide patients with chronic symptoms suspected of LB towards more active coping and increase QoL.

BACKGROUND AND PURPOSE:To diagnose Lyme neuroborreliosis (LNB), cerebrospinal fluid (CSF) is tested for pleocytosis and intrathecal antibody production. The Dutch guideline for Lyme borreliosis indicates a lumbar puncture in the case of positive Borrelia serology or a strong clinical suspicion of LNB. This suggests that LNB might be underdiagnosed in patients with negative Borrelia serology and/or a minor clinical suspicion. The objective was to assess how often negative Borrelia serology occurs in the case of LNB.METHOD:A retrospective study was performed among patients with LNB visiting Gelre Hospitals between January 2007 and December 2020. Electronic medical records of patients with pleocytosis were reviewed to identify patients with LNB. Data were collected from medical records.RESULTS:Included were 127 patients with LNB, 58 of whom were children. In 67 patients Borrelia antibodies were present in both serum and CSF. In 53 of 67 patients there was intrathecal antibody production. In 28 patients there was intrathecal antibody production but serum antibodies were absent. Of patients with positive serology 77% had antibodies in CSF versus 83% of patients with negative serology (p = 0.435). Of patients with positive serology 61% had intrathecal antibody production versus 78% of patients with negative serology (p = 0.073).CONCLUSIONS:Twenty-eight LNB patients had intrathecal antibody production but no antibodies in serum. In this specific patient population, positive serum serology was not associated with antibodies in CSF nor with intrathecal antibody production. In Lyme endemic areas, in patients with symptoms suggestive for LNB, there is a need to lower the threshold for a lumbar puncture.

BACKGROUND:Venous thromboembolism constitutes substantial health care costs amounting to approximately 60 million euros per year in the Netherlands. Compared with initial hospitalization, home treatment of pulmonary embolism (PE) is associated with a cost reduction. An accurate estimation of cost savings per patient treated at home is currently lacking. AIM:The aim of this study was to compare health care utilization and costs during the first 3 months after a PE diagnosis in patients who are treated at home versus those who are initially hospitalized. METHODS:Patient-level data of the YEARS cohort study, including 383 normotensive patients diagnosed with PE, were used to estimate the proportion of patients treated at home, mean hospitalization duration in those who were hospitalized, and rates of PE-related readmissions and complications. To correct for baseline differences within the two groups, regression analyses was performed. The primary outcome was the average total health care costs during a 3-month follow-up period for patients initially treated at home or in hospital. RESULTS:Mean hospitalization duration for the initial treatment was 0.69 days for those treated initially at home (n = 181) and 4.3 days for those initially treated in hospital (n = 202). Total average costs per hospitalized patient were €3,209 and €1,512 per patient treated at home. The adjusted mean difference was €1,483 (95% confidence interval: €1,181-1,784). CONCLUSION:Home treatment of hemodynamically stable patients with acute PE was associated with an estimated net cost reduction of €1,483 per patient. This difference underlines the advantage of triage-based home treatment of these patients.

Background Diagnostic strategies for suspected pulmonary embolism (PE) have not been prospectively evaluated in COVID-19 patients. Methods Prospective, multicenter, outcome study in 707 patients with both (suspected) COVID-19 and suspected PE in 14 hospitals. Patients on chronic anticoagulant therapy were excluded. Informed consent was obtained by opt-out approach. Patients were managed by validated diagnostic strategies for suspected PE. We evaluated the safety (3-month failure rate) and efficiency (number of computed tomography pulmonary angiographies [CTPAs] avoided) of the applied strategies. Results Overall PE prevalence was 28%. YEARS was applied in 36%, Wells rule in 4.2%, and “CTPA only” in 52%; 7.4% was not tested because of hemodynamic or respiratory instability. Within YEARS, PE was considered excluded without CTPA in 29%, of which one patient developed nonfatal PE during follow-up (failure rate 1.4%, 95% CI 0.04–7.8). One-hundred seventeen patients (46%) managed according to YEARS had a negative CTPA, of whom 10 were diagnosed with nonfatal venous thromboembolism (VTE) during follow-up (failure rate 8.8%, 95% CI 4.3–16). In patients managed by CTPA only, 66% had an initial negative CTPA, of whom eight patients were diagnosed with a nonfatal VTE during follow-up (failure rate 3.6%, 95% CI 1.6–7.0). Conclusion Our results underline the applicability of YEARS in (suspected) COVID-19 patients with suspected PE. CTPA could be avoided in 29% of patients managed by YEARS, with a low failure rate. The failure rate after a negative CTPA, used as a sole test or within YEARS, was non-negligible and reflects the high thrombotic risk in these patients, warranting ongoing vigilance.

BACKGROUND:Studies have shown the safety of home treatment of patients with pulmonary embolism (PE) at low risk of adverse events. Management studies focusing on home treatment have suggested that 30% to 55% of acute PE patients could be treated at home, based on the HESTIA criteria, but data from day-to-day clinical practice are largely unavailable.AIM:To determine current practice patterns of home treatment of acute PE in the Netherlands.METHOD:We performed a post-hoc analysis of the YEARS study. The main outcomes were the proportion of patients who were discharged <24 h and reasons for admission if treated in hospital. Further, we compared the 3-month incidence of PE-related unscheduled readmissions between patients treated at home and in hospital.RESULTS:Of the 404 outpatients with PE included in this post-hoc analysis of the YEARS study, 184 (46%) were treated at home. The median duration of admission of the hospitalized patients was 3.0 days. The rate of PE-related readmissions of patients treated at home was 9.7% versus 8.6% for hospitalized patients (crude hazard ratio 1.1 (95% CI 0.57-2.1)). The 3-month incidence of any adverse event was 3.8% in those treated at home (2 recurrent VTE, 3 major bleedings and two deaths) compared to 10% in the hospitalized patients (3 recurrent VTE, 6 major bleedings and fourteen deaths).CONCLUSIONS:In the YEARS study, 46% of patients with PE were treated at home with low incidence of adverse events. PE-related readmission rates were not different between patients treated at home or in hospital.

Background: Nonspecific symptoms in children suspected of Lyme borreliosis (LB) are challenging for clinicians. We assessed whether nonspecific symptoms are more prevalent among children with positive immunoglobulin G (IgG) serology or a history of clinical LB. Methods: We included children (<18 years) suspected of LB who visited the Lyme Center Apeldoorn of Gelre Hospital between 2008 and 2017. Serum samples were taken, and questionnaires on nonspecific symptoms completed. Clinical data were collected from patients’ medical records. The prevalence of nonspecific symptoms was compared between patients with positive versus negative IgG serology and between patients with versus without previous LB with the χ 2 and Fisher exact tests with Bonferroni correction. A history of LB was anamnestically determined. Patients with active Lyme manifestations were excluded. Results: Included were 149 children (66% female; median age 13 years); 29 (19%) had positive IgG serology; 36 (24%) had previous LB; 12 (8%) had both. Common nonspecific symptoms were sleep disturbances (58%), severe fatigue (57%) and headache (42%). The prevalence of nonspecific symptoms was similar in children with positive versus negative IgG serology. None of the nonspecific symptoms occurred more frequently in children with previous LB compared with children without. More prevalent in children without previous LB were sleep disturbances (40 vs. 66%; P = 0.002) and tingling (6 vs. 34%; P < 0.001). Conclusions: Nonspecific symptoms were not more prevalent in children with positive IgG serology nor in children with previous LB, where some were significantly less prevalent. Hence, questionnaires on nonspecific symptoms cannot be used to identify children for serologic testing in Lyme centers.

Making a distinction between facial palsy due to Lyme neuroborreliosis (LNB) and idiopathic facial palsy (IFP) is of importance to ensure timely and adequate treatment. The study objective was to assess incidence and patient characteristics of facial palsy due to LNB. Hospital records were reviewed of adult patients with facial palsy visiting the departments of neurology and/or otorhinolaryngology of Gelre hospitals between June 2007 and December 2017. Gelre hospitals are located in an area endemic for Lyme borreliosis. Patients with LNB had pleocytosis and intrathecal antibody production or pleocytosis with positive IgG serology. Patients with IFP had negative serology. Clinical characteristics were compared between patients with LNB and patients with IFP. Five hundred and fifty-nine patients presented with facial palsy, 4.7% (26) had LNB and 39.4% (220) IFP. The incidence of facial palsy due to LNB was 0.9/100 000 inhabitants/year. Over 70% of patients with facial palsy due to LNB did not report a recent tick bite and/or erythema migrans (EM). Patients with facial palsy due to LNB presented more often in July to September (69.2% vs. 21.9%, P < 0.001), and had more often headache (42.3% vs. 15.5%, P < 0.01). To reduce the risk of underdiagnosing LNB in an endemic area, we recommend testing for LNB in patients with facial palsy in summer months especially when presenting with headache, irrespective of a recent tick bite and/or EM.

•SCORE with age adjustment overestimates cardiovascular risk in RA patients. •SAF measurement yields similar results compared to the SCORE without age adjustment. •SCORE with no age adjustment combined with SAF might be the best strategy for RA.

IntroductionIn women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM.MethodsThe SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle.Ethics and disseminationThe study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals.Trial registration numberNTR6134; Pre-results.

(Abstracted from N Engl J Med 2019;380:1139–1149) Acute pulmonary embolism is one of the leading causes of maternal death, with the overall incidence reported to be 1.72 cases per 1000 deliveries, accounting for approximately 1 death in every 100,000 deliveries. Since the d-dimer test has low specificity and sensitivity, it is common for pregnant women with suspected pulmonary embolism to undergo computed tomography (CT) pulmonary angiography or ventilation-perfusion (V/Q) scanning, both of which involve radiation exposure to the mother and fetus.

Abstract Background Acute pulmonary embolism (PE) is the leading cause of maternal mortality in Western countries, accounting for 20 to 30% of all maternal deaths. Therefore, the threshold to test for PE during pregnancy is low. Because evidence regarding the safety of ruling out PE with clinical decision rules and D-dimer tests in pregnant women is unavailable, all women with a suspected PE need to undergo an imaging test, with potential harm to patient and fetus by exposure to ionizing radiation. In the present international, multicenter, prospective management study, we evaluated the safety and efficiency of the YEARS diagnostic algorithm for ruling out PE in pregnant patients with clinically suspected PE (Netherlands Trial Registry number 5913). YEARS is a simple diagnostic algorithm designed to reduce the number of required computed tomography (CT) scans in the diagnostic work-up of PE in non-pregnant patients, and was recently shown to be as safe as conventional algorithms but associated with a significant absolute 14% reduction in the number of CT scans (van der Hulle et al., Lancet 2017). Methods The Artemis study was performed in 11 Dutch hospitals, 8 French hospitals and 1 Irish hospital. Consecutive pregnant patients with suspected acute PE were included. Exclusion criteria were treatment with therapeutically dosed anticoagulants >24 hours or contraindications for CT. The YEARS algorithm was slightly adjusted for application during pregnancy (figure 1): in patients with signs of deep vein thrombosis (DVT), compression ultrasonography was obligatory before CT scanning was considered. In patients with proven DVT, anticoagulant treatment was initiated and no further diagnostic tests were undertaken. In patients with no YEARS items (Figure 1), a D-dimer threshold of <1.0 µg/ml was sufficient to rule out PE. In the remaining patients D-dimer threshold was <0.5 µg/mL. CT scanning was only performed in patients with a D-dimer level above the threshold. Anticoagulant therapy was withheld if PE was excluded. The primary safety endpoint was the occurrence of symptomatic venous thromboembolism during 3 months of follow-up, the primary efficiency endpoint was the proportion of patients in whom CTPA could be avoided. All safety endpoints were adjudicated by an independent committee. Assuming a 1.0% diagnostic failure rate and defining a maximum acceptable failure rate of 2.7%, a total study population of 472 patients was required (one-sided alpha 0.05, beta 80%). Results and conclusion: The last patient was included in May 2018. At baseline, 48% of pregnant women with suspected acute PE had no YEARS item and a D-dimer threshold of 1.0 µg/mL was applied. A total of 42% had a D-dimer level below the relevant threshold and were managed without CT scanning. Follow-up and endpoint adjudication was not completed at the abstract submission deadline; full study results will be presented at the ASH meeting. Disclosures Couturaud: Pfizer: Research Funding; Bayer: Honoraria, Other: Travel Support; AstraZeneca: Honoraria; Actelion: Other: Travel Support; Intermune: Other: Travel Support; Leo Pharma: Other: Travel Support; Daiichi Sankyo: Other: Travel Support.

Objectives: There is controversy whether non-specific symptoms can be related to previous Lyme borreliosis (LB). Positive serology can be considered a proxy for previous or persistent LB. We assessed nonspecific symptoms and serology in patients suspected of LB referred to a Lyme centre. Methods: Included were adult patients who visited a Lyme centre between 2008 and 2014. Before medical consultation, serum samples were taken and questionnaires on non-specific symptoms completed. The prevalence of non-specific symptoms was calculated for patients with positive and negative IgG serology. Logistic regression was used to obtain odds ratios (ORs) with 95% confidence interval (CI) for an association between positive serology and non-specific symptoms. Results: Of 1439 included patients, 31.6% (455/1439) had positive serology. The most common nonspecific symptoms were severe fatigue (61.4%, 883/1439), sleep disturbances (54.8%, 789/1439) and stiffness of neck/back (52.6%, 757/1439). The prevalence of severe fatigue was 53.0% (241/455) in patients with positive serology vs. 65.2% (642/984) in patients with negative serology (OR = 0.74; 95% CI, 0.58-0.94). The prevalence of sleep disturbances was respectively 46.2% (210/455) vs. 58.8% (579/984) (OR = 0.73; 95% CI, 0.58-0.93). The prevalence of stiffness of neck/back was respectively 47.7% (217/455) vs. 54.9% (540/984) (OR = 0.85; 95% CI, 0.67-1.06). Conclusions: In patients referred to a Lyme centre, non-specific symptoms did not occur more frequently in patients with positive serology compared to patients with negative serology. Hence, a questionnaire on non-specific symptoms cannot be used for identifying patients with possible post-LB symptoms in clinical practice. (C) 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

OBJECTIVE:Here we describe a rare case of systemic sarcoidosis in a healthy young man with neuroborreliosis as a putative trigger.CASE:A 21-year-old forestry worker was diagnosed with systemic sarcoidosis involving his lungs, kidneys and skin. Additional diagnostics revealed signs indicative of a recent infection with Borrelia burgdorferi. The patient was treated successfully with prednisolone and antibiotics.CONCLUSION:Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology. This case suggests that an infection with B. burgdorferi, the causal agent of Lyme disease, could act as a trigger for sarcoidosis.LEARNING POINT:We should maintain a high index of suspicion for underlying infectious processes like neuroborreliosis in patients with new-onset sarcoidosis before starting immunosuppressive regimens.

BACKGROUND:People with severe mental illness (SMI) show significantly shorter life expectancy, mostly due to more prevalent cardiovascular disease. Although age is a prominent contributor to contemporary risk assessment and SMI usually affects younger people, these assessments still do not reveal the actual risk. By assessing advanced glycation end products (AGEs), cardiovascular risk can be assessed independent of age.AIMS:To establish whether detection of AGEs with the AGE-reader will give a more accurate cardiovascular risk assessment in people with SMI.METHOD:We compared assessment with the AGE-reader with that of the Systematic Coronary Risk Evaluation (SCORE) table in a group of 120 patients with SMI.RESULTS:The AGE-reader showed an increased cardiovascular risk more often than the SCORE table, especially in the youngest group.CONCLUSIONS:Because of its ease of use and substantiation by studies done on other chronic diseases, we advocate use of the AGE-reader in daily care for patients with SMI to detect cardiovascular risk as early as possible. However, the findings of the current study should be evaluated with caution and should be seen as preliminary findings that require confirmation by a prospective longitudinal cohort study with a substantial follow-up observation period.DECLARATION OF INTEREST:None.

Little is known on Lyme borreliosis (LB) in patients aged ≥65 years. To optimize management of older patients referred to a tertiary Lyme centre, characteristics of older patients need to be assessed. We published a study on depressive symptoms in patients referred to a tertiary Lyme centre [ [1] Zomer T.P. Vermeeren Y.M. Landman G.W. Zwerink M. van Hees B.C. van Bemmel T. et al. Depressive symptoms in patients referred to a tertiary Lyme center: high prevalence in those without evidence of Lyme borreliosis. Clin Infect Dis. 2017; 65: 1689-1694https://doi.org/10.1093/cid/cix605 Crossref PubMed Scopus (11) Google Scholar ]. Following that study, we now assessed prevalence of LB and prevalence of depressive symptoms in patients suspected of LB aged ≥65 years compared to 18–64 years old.

A two-step testing strategy is recommended in serological testing for Lyme borreliosis; positive and indeterminate enzyme-linked immunosorbent assay (ELISA) results are confirmed with immunoblots. Several ELISAs quantify the concentration of antibodies tested, however, no recommendation exists for an upper cut-off value at which an IgG ELISA is sufficient and the immunoblot can be omitted. The study objective was to determine at which IgG antibody level an immunoblot does not have any additional predictive value compared to ELISA results. Data of adult patients who visited a tertiary Lyme centre between 2008 and 2014 were analysed. Both an ELISA (Enzygnost Lyme link VlsE IgG) and immunoblot (recomLine blot Borrelia) were performed. Clinical data were extracted from the patient's digital medical record. Positive predictive values (PPVs) for either previous or active infection with Borrelia burgdorferi s.l. were calculated for different cut-off ELISA IgG antibody levels where the immunoblot was regarded as reference test. In total, 1454 patients were included. According to the two-step test strategy, 486 (33%), 69 (5%) and 899 (62%) patients had positive, indeterminate and negative Borrelia IgG serology, respectively. At IgG levels of 500 IU/ml and higher, all immunoblots were positive, resulting in a 100% PPV (95% CI: 97.0-100). At IgG levels of 200 IU/ml and higher, the PPV was 99.3% (95% CI: 97.4-99.8). In conclusion, at IgG levels of 200 IU/ml and higher, an ELISA was sufficient to detect antibodies to Borrelia burgdorferi s.l. At those IgG levels, a confirmatory immunoblot may be omitted in patients referred to a tertiary Lyme centre. Before these results can be implemented in routine diagnosis of Lyme borreliosis, confirmation of the results is necessary in other patient populations and using other quantitative ELISAs and immunoblots.