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Background: Outbreaks of yellow fever and a frequently depleted vaccine stock increase demand for a dose-sparing strategy. A fractional dose of 17D yellow fever virus (17D-YFV) vaccine has been shown to be noninferior to the standard dose in inducing seroprotection.Objective: To evaluate whether fractional-dose vaccination can confer long-term immunity.Design: 10-year follow-up of a subgroup of a randomized, controlled, noninferiority trial. (Dutch Trial Register: NTR7094 [current study] and ISRCTN46326316 [original study]).Setting: The Netherlands.Participants: Seventy-five of 155 participants in the original trial provided a blood sample for this study. These 75 participants had received primary vaccination with 17D-YFV vaccine 10 years before. Forty received a 0.1-mL fractional dose intradermally, and 35 received the standard 0.5-mL dose subcutaneously.Measurements: Virus-neutralizing antibody responses were measured by a plaque reduction neutralization test.Results: Thirty-nine of 40 (98% [95% CI, 89% to 100%]) participants had protective levels of yellow fever-neutralizing antibodies more than 10 years after receiving a fractional dose of 17D-YFV vaccine compared with 34 of 35 (97% [CI, 87% to 100%]) in the standard-dose group.Limitation: Only 48% of participants from the original trial participated in this study.Conclusion: Intradermal administration of a one-fifth dose of yellow fever vaccine induced a protective immune response that lasted for 10 years after vaccination. Persons receiving a fractional dose of yellow fever vaccine do not require a booster vaccination for long-term protection against yellow fever.Primary Funding Source: Leiden University Medical Center and the International Society of Travel Medicine. [ABSTRACT FROM AUTHOR]

Objectives: : Residents living in a long-term care facility (LTCF) are more susceptible to infections. Treatment with antimicrobials is sometimes necessary; however, antibiotic use is considered one of the most important drivers of the development of antibiotic resistance. Surveillance data on antibiotic use in these LTCFs are necessary to get more insight into these patterns. The objective of this study was to describe antibiotic use in LTCFs in the Netherlands.Methods: : One hundred and seventy-seven LTCFs in the Netherlands were contacted and asked to participate in a study concerning antibiotic resistance and antibiotic use. Associated pharmacies were asked to provide data about systemic antibiotic use for each participating LTCF location over 1 year. Results on antibiotic use are reported here.Results: : Antibiotic use data from 96 LTCFs were collected from the pharmacies, and 68 of these LTCFs completed additional questionnaires on general characteristics of their location. Mean total use of systemic antimicrobials was 73 DDDs/1000 residents per day (range 2-197 DDDs/1000 residents per day). Co-amoxiclav (23 DDDs/1000 residents/day, range 0-70) was used the most, followed by nitrofurantoin derivatives (12 DDDs/1000 residents/day, range 0-38) and fluoroquinolones (12 DDDs/1000 residents/day, range 0-52). Statistical analysis revealed no significant correlations between the LTCF characteristics and the level of antibiotic use.Conclusions: There was a high use of broad-spectrum antimicrobials, with a large variation in total antibiotic use between individual locations. Further analysis of more in-depth data and possible influencing factors is needed. [ABSTRACT FROM AUTHOR]

Quality Problem: Inappropriate antibiotic use drives development of antimicrobial resistance. Worldwide, guideline adherence for antibiotic treatment of infectious disease is far from optimal. Insight in prescribing quality is pivotal for healthcare professionals and policy makers to intervene appropriately.Initial Assessments: European countries uniformly monitor antibiotic use, which is reported yearly by the European Centre for Disease Prevention and Control. Unfortunately, this has not had enough impact to decrease prescribing and resistance levels.Choice Of Solution: Quality indicators (QIs) could provide better insight in prescribing quality and enable benchmarking to other countries; this could trigger action to improve antimicrobial prescribing. European Surveillance of Antimicrobial Consumption (ESAC) proposed 12 antibiotic QIs.Implementation: Trends in use of antibiotic subgroups and the 12 ESAC QI values were determined for Dutch primary care (2004-2013); outcomes were compared to other European countries. Dutch antibiotic use is low within the European context. Nitrofurantoin use is higher than the European average, use of small-spectrum antibiotics lowers. Use of macrolides, quinolones and amoxicillin/clavulanate declined, which was not supported by the broad/narrow QI results.Evaluation: QIs expressing antibiotic subgroup use in Defined Daily Doses/1000 inhabitants/day, particularly small-spectrum and non-first choices, provide proper insight in prescribing quality and are useful for benchmarking purposes. QIs measuring percentages were not considered useful. The broad/narrow ratio could be more informative when adjusted to national guidelines, or when more antibiotic subgroups are included based on better European consensus.Lessons Learnt: Benchmarking the above mentioned Dutch QI values to other countries provides direction for three specific strategies to further improve Dutch antibiotic prescribing practice. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to assess carriage of antimicrobial-resistant commensal microorganisms, i.e. Escherichia coli and Staphylococcus aureus, and its predictors in long-term-care facilities (LTCFs).Methods: Nasal swabs and/or urine or incontinence samples were collected from participating residents in 111 LTCFs and tested for the presence of S. aureus and/or E. coli, respectively. Antimicrobial resistance to eight antimicrobials was linked to antimicrobial usage in the year preceding sampling and to LTCF characteristics. Using multilevel logistic regression, predictors of carriage of ESBL-producing E. coli in LTCFs were identified.Results: S. aureus was identified in 1269/4763 (26.6%) nasal swabs, including 13/4763 (0.3%) MRSA carriers in 9/107 (8%) LTCFs. Of the 5359 urine/incontinence samples, 2934 (55%) yielded E. coli, including 123 (4.2%) producing ESBL, which were found in 53/107 locations (range 1%-33%). For all but one antimicrobial (i.e. nitrofurantoin) >20% of isolated E. coli were resistant. Multilevel multivariable logistic regression identified two predictors of carriage of ESBL-producing E. coli: (i) antimicrobial usage (OR 1.8, 95% CI 1.1-3.0 for each extra 50 DDD/1000 residents/day); and (ii) presence of MRSA carriers in the LTCFs (OR 2.4, 95% CI 1.0-5.6).Conclusions: The low proportion of 4.2% ESBL-producing E. coli and the low prevalence of 0.3% MRSA carriage found in LTCF residents suggest that Dutch LTCFs are not yet an important reservoir of MDR potential pathogens. Nevertheless, the large variation between LTCFs warrants close monitoring of antimicrobial resistance in LTCFs. Integrated surveillance, i.e. linking data sources on antimicrobial usage, microbiological testing, clinical background data and epidemiological data, is needed. [ABSTRACT FROM AUTHOR]

Study design: A prospective treatment study with a new brace was conducted Objective. To evaluate radiological and subjective clinical results after one year conservative brace treatment with pressure onto lordosis at the thoracolumbar joint in children with scoliosis and kyphosis. Summary of background data: Conservative brace treatment of adolescent scoliosis is not proven to be effective in terms of lasting correction. Conservative treatment in kyphotic deformities may lead to satisfactory correction. None of the brace or casting techniques is based on sagittal forces only applied at the thoracolumbar spine (TLI= thoracolumbar lordotic intervention). Previously we showed in patients with scoliosis after forced lordosis at the thoracolumbar spine a radiological instantaneous reduction in both coronal curves of double major scoliosis. Methods: A consecutive series of 91 children with adolescent scoliosis and kyphosis were treated with a modified symmetric 30 degrees Boston brace to ensure only forced lordosis at the thoracolumbar spine. Scoliosis was defined with a Cobb angle of at least one of the curves [greater than or equal to] 25 degrees and kyphosis with or without a curve <25 degrees in the coronal plane. Standing radiographs were made i) at start, ii) in brace at beginning and iii) after one year treatment without brace. Results: Before treatment start 'in brace' radiographs showed a strong reduction of the Cobb angles in different curves in kyphosis and scoliosis groups (sagittal n = 5 all p < 0.001, pelvic obliquity p < 0.001). After one year of brace treatment in scoliosis and kyphosis group the measurements on radiographs made without brace revealed an improvement in 3 Cobb angles each. Conclusion: Conservative treatment using thoracolumbar lordotic intervention in scoliotic and kyphotic deformities in adolescence demonstrates a marked improvement after one year also in clinical and postural criteria. An effect not obtained with current brace techniques. [ABSTRACT FROM AUTHOR]

Background: Yellow fever vaccination (YF-17D) can cause serious adverse events (SAEs). The mechanism of these SAEs is poorly understood. Older age has been identified as a risk factor. We tested the hypothesis that the humoral immune response to yellow fever vaccine develops more slowly in elderly than in younger subjects. Method: We vaccinated young volunteers (18-28 yrs, N = 30) and elderly travelers (60-81 yrs, N = 28) with YF-17D and measured their neutralizing antibody titers and plasma YF-17D RNA copy numbers before vaccination and 3, 5, 10, 14 and 28 days after vaccination. Results: Ten days after vaccination seroprotection was attained by 77% (23/30) of the young participants and by 50% (14/ 28) of the elderly participants (p = 0.03). Accordingly, the Geometric Mean Titer of younger participants was higher than the GMT of the elderly participants. At day 10 the difference was +2.9 IU/ml (95% CI 1.8-4.7, p = 0.00004) and at day 14 +1.8 IU/ ml (95% CI 1.1-2.9, p = 0.02, using a mixed linear model. Viraemia was more common in the elderly (86%, 24/28) than in the younger participants (60%, 14/30) (p = 0.03) with higher YF-17D RNA copy numbers in the elderly participants. Conclusions: We found that elderly subjects had a delayed antibody response and higher viraemia levels after yellow fever primovaccination. We postulate that with older age, a weaker immune response to yellow fever vaccine allows the attenuated virus to cause higher viraemia levels which may increase the risk of developing SAEs. This may be one piece in the puzzle of the pathophysiology of YEL-AVD. [ABSTRACT FROM AUTHOR]

We show that the transcriptional repressor Tel plays an evolutionarily conserved role in angiogenesis: it is indispensable for the sprouting of human endothelial cells and for normal development of the Danio rerio blood circulatory system. Tel orchestrates endothelial sprouting by binding to the generic co-repressor, CtBP. The Tel-CtBP complex temporally restricts a VEGF (vascular endothelial growth factor)-mediated pulse of dll4 expression and thereby directly links VEGF receptor intracellular signalling and intercellular Notch-Dll4 signalling. It further controls branching by regulating expression of other factors that constrain angiogenesis such as sprouty family members and ve-cadherin. Thus, the Tel-CtBP complex conditions endothelial cells for angiogenesis by controlling the balance between stimulatory and antagonistic sprouting cues. Tel control of branching seems to be a refinement of invertebrate tracheae morphogenesis that requires Yan, the invertebrate orthologue of Tel. This work highlights Tel and its associated networks as potential targets for the development of therapeutic strategies to inhibit pathological angiogenesis. [ABSTRACT FROM AUTHOR]

Background. Travelers with diabetes mellitus to developing countries are thought to have symptomatic infectious diseases more often and longer than travelers without diabetes. Evidence for this is needed. This study evaluates whether travelers with diabetes are at increased risk of symptomatic infectious diseases. Methods. A prospective study was performed between October 2003 and February 2008 among adult medication-dependent travelers with diabetes, with their healthy travel companions without diabetes serving as matched controls. Thus, travelers with diabetes and controls were assumed to have comparable exposure to infection. Data on symptoms of infectious diseases were recorded by using a structured diary. Results. Among 70 travelers with insulin-dependent diabetes, the incidence of travel-related diarrhea was 0.99 per person-month, and the median number of symptomatic days 1.54 per month. For their 70 controls, figures were 0.74 and 1.57, respectively ( p > 0.05). Among 82 travelers with non-insulin-dependent diabetes, incidence was 0.75, and the median number of symptomatic days was 1.68. For their 82 controls, figures were 0.70 and 1.68, respectively ( p > 0.05). As for other symptoms, no significant travel-related differences were found. Only 17% of travelers with diabetes suffering from diarrhea used their stand-by antibiotics. Conclusions. Medication-dependent travelers with diabetes traveling to developing countries do not have symptomatic infectious diseases more often or longer than travelers without diabetes. Routine prescription of stand-by antibiotics for travelers with diabetes to areas with good health facilities is probably not more useful than for healthy travelers. [ABSTRACT FROM AUTHOR]

Abstract: Trial registration: NTR1043 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1043). Background: Five to ten percent of immunocompetent persons fail to develop a protective immune response to hepatitis B vaccination, and are defined non-responders (NR). We investigated the immune response to intradermal hepatitis B vaccination after pre-treatment of the skin with the TLR7 agonist imiquimod. Methods: Twenty-one non-responders (anti-HBs <10IU/l after at least 6 intramuscular hepatitis B vaccinations) were randomly assigned to the control group (N =11) or the experimental group (N =10). Participants in both groups received 3 intradermal (ID) vaccinations with 5μg HBsAg (0.125mL) at 0, 1 and 6 months. In the experimental group, the dermal site of injection was pre-treated with 250mg imiquimod ointment. Anti-HBs antibodies were determined at 0, 1, 2, 6 and 7 months. Results: In both study groups, 70% of the participants developed a protective immune response (anti-HBs ≥10IU/l), after the 3rd intradermal vaccination. Conclusion: The application of imiquimod on the skin prior to intradermal vaccination did not enhance the humoral response to hepatitis B vaccine. However, irrespective of imiquimod application, 70% of the NR who had not responded to 6 previous intramuscular vaccinations, developed a protective immune response with high affinity antibodies after 3 ID hepatitis B vaccinations with 5μg HBsAg. [Copyright &y& Elsevier]

Abstract: Pre-exposure vaccination of persons at risk with intradermally administered reduced dose cell culture rabies vaccines remains controversial in low-enzootic countries. In a prospective clinical trial of adult volunteers (N =25), we studied the immune response to purified chick embryo cell vaccine (PCECV) administered intradermally at a reduced dose (0.1mL) in a three-dose schedule (0, 7 and 21 days). In 10 subjects, immunogenicity of intradermally administered one-dose booster vaccination with 0.1mL PCECV was investigated. All participants were seroconverted 3 weeks after primary and 1 week after booster vaccination (antibody titre ≥0.5EU/mL, measured by enzyme linked immunosorbent assay). Local adverse events such as erythema and swelling were moderate and transitory. The intradermal vaccination route offers an efficacious and cost-reducing strategy to increase the accessibility of cell culture rabies vaccines. [Copyright &y& Elsevier]

Background: Implementation of yellow fever vaccination is currently hampered by limited supply of vaccine. An alternative route of administration with reduced amounts of vaccine but without loss of vaccine efficacy would boost vaccination programmes. Methods and Findings: A randomized, controlled, non-inferiority trial was conducted in a Dutch university center between August 2005 and February 2007. A total of 155 primary vaccinated and 20 previously vaccinated volunteers participated. Participants were randomly assigned in a 1:1 ratio to receive intradermal (i.d.) vaccination with live attenuated yellow fever 17D vaccine at a reduced dose (1/5th; 0·1 mL) or the conventional subcutaneous (s.c.) vaccination (0·5 mL). Antibody neutralization titers were determined at 2, 4 and 8 weeks and 1 year after vaccination by counting the reduction in virusinduced plaques in the presence of serial serum dilutions. Adverse events were documented in a 3-week dairy. Viraemia was measured 5 days after vaccination. From 2 weeks up to one year after vaccination, the maximum serum-dilution at which 80% of the virus plaques were neutralized, which indicates protection against yellow fever, did not differ between those given a reduced i.d. dose or standard s.c. dose of vaccine. In all cases the WHO standard of seroprotection (i.e. 80% virus neutralization) was reached (in 77/77 and 78/78, respectively). Similar results were found in the previously vaccinated individuals. Viraemia was detected in half of the primary vaccinated participants, which was not predictive of serological response. In revaccinees no viraemia was detected. Conclusions: Intradermal administration of one fifth of the amount of yellow fever vaccine administered subcutaneously results in protective seroimmunity in all volunteers. Albeit this vaccination route should enable vaccination of five-times as many individuals at risk for disease, these results should now be confirmed in field studies in areas with potential yellow fever virus transmission to change vaccination policy. [ABSTRACT FROM AUTHOR]

Background: Falciparum malaria remains a major occupational illness that accounts for several deaths per year and numerous lost working days among the expatriate population, working or living in high-risk malarious areas. Compliance to preventive strategies is poor in travellers, especially business travellers, expatriates and long-term travellers. Methods: In this cross-sectional, web-based study the adherence to and outcome of a preventive malaria programme on knowledge, attitudes and practices, including the practice of self-diagnosis and standby treatment (curative malaria kit, CMK) was evaluated in 2,350 non-immune expatriates, who had been working in highly malaria endemic areas. Results: One-third (N = 648) of these expatriates visited a doctor for malaria symptoms and almost half (29 of 68) of all hospitalizations were due to malaria. The mandatory malaria training for non-immunes was completed by 92% of those who visited or worked in a high risk malaria country; 70% of the respondents at risk also received the CMK. The malaria awareness training and CMK significantly increased malaria knowledge [relative risk (RR) of 1.5, 95%CI 1.2-2.1], attitudes and practices, including compliance to chemoprophylaxis [RR = 2.2, 95%CI 1.6-3.2]. Hospitalization for malaria tended to be reduced by the programme [RR = 0.4, 95%CI 0.1-1.1], albeit not significantly. Respondents who did not receive instructions on the rapid diagnostic test were two times [RR = 2.3, 95%CI 1.6-3.3] more likely to have difficulties. Those who did receive instructions adhered poorly to the timing of repeating the test. Moreover, 6% (31 of 513) of those with a negative test result were diagnosed with malaria by a local doctor. 77% (N = 393) of the respondents with a negative test result did not take curative medication. 57% (252 of 441) of the respondents who took the curative medication that was included in the kit did not have a positive self-test or clinical malaria diagnosis made by a doctor. Conclusion: This survey demonstrated that a comprehensive programme targeting malaria prevention in expatriates can be effectively implemented and that it significantly increased malaria awareness. [ABSTRACT FROM AUTHOR]

A cross-sectional, descriptive study was conducted among Dutch kidney transplant recipients to investigate travel health knowledge, attitudes and practices while staying abroad. A total of 290 individuals visiting the nephrology outpatient clinic completed the questionnaires. Thirty four percent of the responders had traveled outside Western Europe (WE) and Northern America (NA); 22% of these travelers did not seek pre-travel health advice. Transplant physicians were most frequently consulted for pre-travel advice (53%). Of the responders traveling outside WE and NA 29% were ill during their most recent journey. Diabetic transplant recipients were at the highest risk. Four of seventeen ill recipients (24%) were hospitalized, reflecting the high morbidity of travel-related disease in this patient group. Our data show that there is need for improvement of pre-travel healthcare, and suggest an important role for transplant physicians in providing adequate counseling. [ABSTRACT FROM AUTHOR]

The present study combined molecular and neuroimaging techniques to examine if free radical-mediated damage to barrier function in hypoxia would result in extracellular edema, raise intracranial pressure (ICP) and account for the neurological symptoms typical of high-altitude headache (HAH) also known as acute mountain sickness (AMS). Twenty-two subjects were randomly exposed for 18 h to 12% (hypoxia) and 21% oxygen (O2 (normoxia)) for collection of venous blood (0 h, 8 h, 15 h, 18 h) and CSF (18 h) after lumbar puncture (LP). Electron paramagnetic resonance (EPR) spectroscopy identified a clear increase in the blood and CSF concentration of O2 and carbon-centered free radicals (P<0.05 versus normoxia) subsequently identified as lipid-derived alkoxyl (LO•) and alkyl (LC•) species. Magnetic resonance imaging (MRI) demonstrated a mild increase in brain volume (7.0±4.8 mL or 0.6%±0.4%, P<0.05 versus normoxia) that resolved within 6 h of normoxic recovery. However, there was no detectable evidence for gross barrier dysfunction, elevated lumbar pressures, T2 prolongation or associated neuronal and astroglial damage. Clinical AMS was diagnosed in 50% of subjects during the hypoxic trial and corresponding headache scores were markedly elevated (P<0.05 versus non-AMS). A greater increase in brain volume was observed, though this was slight, independent of oxidative stress, barrier dysfunction, raised lumbar pressure, vascular damage and measurable evidence of cerebral edema and only apparent in the most severe of cases. These findings suggest that free-radical-mediated vasogenic edema is not an important pathophysiological event that contributes to the mild brain swelling observed in HAH.Journal of Cerebral Blood Flow & Metabolism (2006) 26, 99–111. doi:10.1038/sj.jcbfm.9600169; published online 15 June 2005 [ABSTRACT FROM AUTHOR]

Introduction: This guideline was written by a multidisciplinary committee with mandated members of the Dutch Society for Infectious Diseases, Dutch Society for Hematology, Dutch Society for Medical Oncology, Dutch Association of Hospital Pharmacists, Dutch Society for Medical Microbiology, and Dutch Society for Pediatrics. The guideline is written for adults and pediatric patients. Method: The recommendations are based on the answers to nine questions formulated by the guideline committee. To provide evidence-based recommendations we used all relevant clinical guidelines published since 2010 as a source, supplemented with systematic searches and evaluation of the recent literature (2010–2020) and, where necessary, supplemented by expert-based advice. Results: For adults the guideline distinguishes between high- and standard-risk neutropenia based on expected duration of neutropenia (> 7 days versus ≤ 7 days). Where possible a distinction has been made between pediatric and adult patients. Conclusion: This guideline was written to aid diagnosis and management of patients with febrile neutropenia due to chemotherapy in the Netherlands. The guideline provides recommendation for children and adults. Adults patient are subdivided as having a standard- or high-risk neutropenic episode based on estimated duration of neutropenia. The most important recommendations are as follows. In adults with high-risk neutropenia (duration of neutropenia > 7 days) and in children with neutropenia, ceftazidime, cefepime, and piperacillin–tazobactam are all first-choice options for empirical antibiotic therapy in case of fever. In adults with standard-risk neutropenia (duration of neutropenia ≤ 7 days) the MASCC score can be used to assess the individual risk of infectious complications. For patients with a low risk of infectious complications (high MASCC score) oral antibiotic therapy in an outpatient setting is recommended. For patients with a high risk of infectious complications (low MASCC score) antibiotic therapy per protocol sepsis of unknown origin is recommended. [ABSTRACT FROM AUTHOR]

The article discusses methods on preventing yellow fever that is caused as a result of unchecked urbanisation which is a breeding group for the mosquito Aedes aegypti.

Rationale for review: The global yellow fever vaccine supply is insufficient to provide full-dose vaccination to millions threatened by outbreaks. Given the excess of live-attenuated 17D yellow fever virus in the current single dose vials, dose sparing would increase available vaccine doses manifold. Fractional-dose yellow fever vaccination is now accepted as an emergency solution, as short-term protection has been confirmed in an outbreak situation in the Democratic Republic of Congo, but broader application of this dose-sparing strategy is still not recommended. In this review, important knowledge gaps that hamper this application such as long-term protection after fractional-dose vaccination, safety, comparability across different genetic backgrounds and different World Health Organization-licensed yellow fever vaccines and immunogenicity in infants are addressed.Main findings: Recently, published results on long-term protection after fractional-dose vaccination in healthy young volunteers indicate that if a person mounts a protective response shortly after vaccination, the protective response will persist for 10 years and possibly longer. It also appears that fractional-dose vaccination does not elicit more serious adverse events than standard dose vaccination. Short-term immunogenicity studies are currently underway in specific populations (infants, human immunodeficiency virus (HIV)-infected persons and healthy adults living in Uganda and Kenya), of which the results will become available in 2021-22.Conclusions: Available results on long-lasting immunogenicity of fractional-dose yellow fever vaccination are encouraging, although confirmation is required in larger populations including young children living in yellow fever endemic areas. [ABSTRACT FROM AUTHOR]

Background Confirming the efficacy of dolutegravir/lamivudine in clinical practice solidifies recommendations on its use. Methods Prospective cohort study (DUALING) in 24 human immunodeficiency virus (HIV) treatment centers in the Netherlands. HIV RNA–suppressed cases were on triple-drug antiretroviral regimens without prior virological failure or resistance and started dolutegravir/lamivudine. Cases were 1:2 matched to controls on triple-drug antiretroviral regimens by the use of dolutegravir-based regimens, age, sex, transmission route, CD4+ T-cell nadir, and HIV RNA zenith. The primary endpoint was the treatment failure rate in cases versus controls at 1 year by intention-to-treat and on-treatment analyses with 5% noninferiority margin. Results The 2040 participants were 680 cases and 1380 controls. Treatment failure in the 390 dolutegravir-based cases versus controls occurred in 8.72% and 12.50% (difference: −3.78% [95% confidence interval {CI}, −7.49% to.08%]) by intention-to-treat and 1.39% and 0.80% (difference: 0.59% [95% CI, –.80% to 1.98%]) by on-treatment analyses. The treatment failure risk in 290 non-dolutegravir-based cases was also noninferior to controls. Antiretroviral regimen modifications unrelated to virological failure explained the higher treatment failure rate by intention-to-treat. A shorter time on triple-drug antiretroviral therapy and being of non-Western origin was associated with treatment failure. Treatment failure, defined as 2 consecutive HIV RNA >50 copies/mL, occurred in 4 cases and 5 controls but without genotypic resistance detected. Viral blips occured comparable in cases and controls but cases gained more weight, especially when tenofovir-based regimens were discontinued. Conclusions In routine care, dolutegravir/lamivudine was noninferior to continuing triple-drug antiretroviral regimens after 1 year, supporting the use of dolutegravir/lamivudine in clinical practice. Clinical Trials Registration NCT04707326. [ABSTRACT FROM AUTHOR]

Introduction: Taking consecutive antibiotic use into account is of importance to obtain insight in treatment within disease episodes, use of 2nd- and 3rd-choice antibiotics, therapy failure and/or side effects. Nevertheless, studies dealing with consecutive antibiotic use are scarce. We aimed at evaluating switch patterns in antibiotic use in the outpatient setting in the Netherlands.Methods: Outpatient antibiotic dispensing data was processed to antibiotic treatment episodes consisting of single prescriptions or consecutive prescriptions (2006 to 2014). Consecutive prescriptions were categorised into prolongations and switches. Switches were further analysed to obtain antibiotic switch percentages and trends over time. Outcomes were compared with recommendations of Dutch guidelines.Results: A total of 43,179,867 antibiotic prescriptions were included in the analysis, consisting of single prescriptions (95%), prolongations (2%) and switches (3%). The highest switch percentages were found for trimethoprim (7.6%) and nitrofurantoin (5.4%). For fosfomycin, ciprofloxacin, flucloxacillin and trimethoprim we found the highest yearly increase in switching. Amoxicillin/clavulanic acid was most often used as second antibiotic in a switch. A surprisingly high number of 2nd- and 3rd-choice antibiotics are prescribed as first antibiotic in a treatment.Conclusions: Although the actual reason for a switch is unknown, switch patterns can reveal problems concerning treatment failure and guideline adherence. In general, switch percentages of antibiotics in the Netherlands are low. The data contributes to the knowledge regarding antibiotic switch patterns in the outpatient setting. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article immunoabsorption in patients with haemolytic uraemic syndrome in the September 24 2011 issue.

Abstract: The neutralising antibody response after the yellow fever vaccine (YF-17D) skin test was measured in 7 egg allergic persons in whom further vaccination was abandoned because of a strong local urticarial reaction to the YF-17D vaccine test dose. We found that this test dose of 0.1mL of YF-17D vaccine was sufficient to induce a protective antibody response in all 7 subjects. Intradermal injection of 1/5th dose of the yellow fever vaccine appears to be sufficient, in non-allergic as well as allergic persons, and non-inferior to the subcutaneous full dose. [Copyright &y& Elsevier]

Background: A multitude of diagnostic and predictive algorithms have been designed for COVID-19. However, currently no score can accurately quantify and track day-to-day disease severity in hospitalised patients with COVID-19. We aimed to design such a score to improve pathophysiological insight in COVID-19. Methods: Development of the Severity of COronavirus Disease Assessment (SCODA) score was based on the 4C Mortality score but patient demographic variables that remain constant during admission were excluded. Instead, parameters associated with breathing and oxygenation were added to reflect the daily condition. The SCODA score was subsequently applied to the BEAT-COVID cohort to describe COVID-19 severity over time and to determine the timing of clinical recovery for each patient, an important marker in pathophysiological studies. The BEAT-COVID study included patients with PCR confirmed COVID-19 who were hospitalized between April 2020 and March 2021 in the Leiden University Medical Center, The Netherlands. Results: The SCODA score consists of 6 clinical and 2 routine lab parameters. 191 patients participated in the BEAT-COVID study. Median age was 66, and 74.4% was male. The modal timepoint at which recovery was clinically initiated occurred on days 8 and 24 since symptom onset for non-ICU and ICU-patients, respectively. Conclusions: We developed a daily score which can be used to track disease severity of patients admitted due to COVID-19. This score is useful for improving insight in COVID-19 pathophysiology, its clinical course and to evaluate interventions. In a future stage this score can also be used in other (emerging) infectious respiratory diseases. [ABSTRACT FROM AUTHOR]

We report a case of disseminated cutaneous Mycobacterium chelonae infection in a patient who was treated with chemotherapy for acute myeloid leukemia. We discuss the clinical manifestations, diagnosis, and treatment of this unusual infection in neutropenic patients. [ABSTRACT FROM PUBLISHER]

The article discusses the case of a 46-year-old man who presented with fleshy pink-orange lesion, located temporarily on the iris of his left eye, diagnosed with primary Ewing sarcoma of the iris, the first report, and whose treatment include six cycles of vincristin, ifosfamide, and doxorubicin.

The vertebrate Ets transcriptional repressor Tel (ETV6) and its invertebrate orthologue, Yan, are both indispensable for development, and they orchestrate cell growth and differentiation by binding to DNA, thus inhibiting gene expression. To trigger cell differentiation, these barriers to transcriptional activation must be relieved, and it is established that posttranslational modifications, such as phosphorylation and sumoylation, can specifically impair the repressive functions of Tel and Yan and are crucial for modulating their transcriptional activity. To date, however, relatively little is known about the control of Tel and Yan protein degradation. In recent years, there has been a concentrated effort to assign functions to the large number of F-box proteins encoded by both vertebrate and invertebrate genomes. Here, we report the identification and characterization of a previously unreported, evolutionarily conserved F-box protein named Fbl6. We isolated both human and Drosophila melanogaster fbl6 cDNA and show that the encoded Fbl6 protein binds to both Tel and Yan via their SAM domains. We demonstrate that both Tel and Yan are ubiquitinated, a process which is stimulated by Fbl6 and leads to proteasomal degradation. We recently established that the sumoylation of Tel on lysine 11 negatively regulates its repressive function and that the sumoylation of Tel monomers, but not that of Tel oligomers, may sensitize Tel for proteasomal degradation. Here, we found that Fbl6 regulates Tel/Yan protein stability and allows appropriate spatiotemporal control of gene expression by these repressors. [ABSTRACT FROM AUTHOR]

Cell proliferation and differentiation are governed by a finely controlled balance between repression and activation of gene expression. The vertebrate Ets transcriptional repressor Tel (ETV6) and its invertebrate orthologue Yan, play pivotal roles in cell fate determination although the precise mechanisms by which repression of gene expression by these factors is achieved are not clearly defined. Here, we report the identification and characterization of the primary site of sumoylation of Tel, lysine 11 (K11), which is highly conserved in vertebrates (except Danio rerio). We demonstrate that in cells PIAS3 binds to Tel and stimulates sumoylation of K11 in the nucleus. Both Tel monomers and oligomers are efficiently sumoylated on K11 in vitro; but in cells only Tel oligomers are found conjugated with SUMO, whereas sumoylation of Tel monomers is transitory and appears to sensitize them for proteasomal degradation. Mechanistically, sumoylation of K11 inhibits repression of gene expression by full-length Tel. In accordance with this observation, we found that sumoylation impedes Tel association with DNA. By contrast, a Tel isoform lacking K11 (TelM43) is strongly repressive. This isoform results from translation from an alternative initiation codon (M43) that is common to all Tel proteins that also contain the K11 sumoylation consensus site. We find that PIAS3 may have a dual, context-dependent influence on Tel; it mediates Tel sumoylation, but it also augments Tel's repressive function in a sumoylation-independent fashion. Our data support a model that suggests that PIAS-mediated sumoylation of K11 and the emergence of TelM43 in early vertebrates are linked and that this serves to refine spatiotemporal control of gene expression by Tel by establishing a pool of Tel molecules that are available either to be recycled to reinforce repression of gene expression or are degraded in a regulated fashion. [ABSTRACT FROM AUTHOR]

Systemic immunosuppressive therapy (IS) renders patients with inflammatory bowel disease (IBD) vulnerable to fulminant hepatitis B virus (HBV) infection. Seroprotection against HBV through a full vaccination scheme is preferably obtained before IS is initiated, but often conflicts with the clinical need to initiate therapy rapidly. Consequently, the vast majority of patients will use IS during booster vaccinations. In this retrospective cohort study, we examined the serological response after a modified vaccination schedule which includes an initial double dose of Fendrix in patients with IBD and compared the results with the serological responses of patients with IBD who received the standard schedule. Seroprotection rates were 86.2 % and 88.9 % in the modified and standard schedule groups respectively. One-third of patients obtained seroprotection after only one double dose vaccine. A double dose may be considered in patients with IBD at high short-term risk of HBV infection when a rapid protective response is warranted. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic increases healthcare worker (HCW) absenteeism. The bacillus Calmette-Guérin (BCG) vaccine may provide non-specific protection against respiratory infections through enhancement of trained immunity. We investigated the impact of BCG vaccination on HCW absenteeism during the COVID-19 pandemic. HCWs exposed to COVID-19 patients in nine Dutch hospitals were randomized to BCG vaccine or placebo in a 1:1 ratio, and followed for one year using a mobile phone application. The primary endpoint was the self-reported number of days of unplanned absenteeism for any reason. Secondary endpoints included documented COVID-19, acute respiratory symptoms or fever. This was an investigator-funded study, registered at ClinicalTrials.gov (NCT03987919). In March/April 2020, 1511 HCWs were enrolled. The median duration of follow-up was 357 person-days (interquartile range [IQR], 351 to 361). Unplanned absenteeism for any reason was observed in 2.8% of planned working days in the BCG group and 2.7% in the placebo group (adjusted relative risk 0.94; 95% credible interval, 0.78–1.15). Cumulative incidences of documented COVID-19 were 14.2% in the BCG and 15.2% in the placebo group (adjusted hazard ratio (aHR) 0.94; 95% confidence interval (CI), 0.72–1.24). First episodes of self-reported acute respiratory symptoms or fever occurred in 490 (66.2%) and 443 (60.2%) participants, respectively (aHR: 1.13; 95% CI, 0.99–1.28). Thirty-one serious adverse events were reported (13 after BCG, 18 after placebo), none considered related to study medication. During the COVID-19 pandemic, BCG-vaccination of HCW exposed to COVID-19 patients did not reduce unplanned absenteeism nor documented COVID-19. [ABSTRACT FROM AUTHOR]

Suspected allergic reactions after mRNA COVID-19 vaccination withheld multiple individuals from getting fully vaccinated during the pandemic. We vaccinated adults who had experienced possible allergic symptoms after their first intramuscular dose of a COVID-19 mRNA vaccine with a 1/5th fractional intradermal test dose of the mRNA-1273 (Moderna) COVID-19 vaccine. No anaphylactic reactions were observed after intradermal vaccination (n = 56). Serum anti-S1 IgG concentrations were measured using a bead-based multiplex assay four weeks after vaccinations. Antibody concentrations were compared with a previously collected nationwide cohort that had received two intramuscular doses of mRNA-1273. Antibody responses in all subjects tested (n = 47) were comparable to standard of care intramuscular dosing. Fractional intradermal dosing of mRNA COVID-19 vaccines may provide a pragmatic solution that is safe, time efficient compared to skin prick testing, dose sparing and immunogenic in individuals with suspected vaccine allergy. [ABSTRACT FROM AUTHOR]

Objectives To report and analyse trends in antibiotic use in Dutch university hospitals, large teaching hospitals and general hospitals over the period 2003 to 2009. Methods Data on the use of antibiotics and hospital resource indicators were obtained by distributing a questionnaire to all Dutch hospital pharmacies. Antibiotic use was expressed as the number of defined daily doses (DDDs) per 100 patient-days, per 100 admissions and per 1000 inhabitants per day. The latter was achieved by extrapolating sample data by means of imputation and up-scaling. Results From 2003 to 2009, the mean length of hospital stay decreased from 6.27 to 4.50 days (−28%). Total systemic antibiotic use significantly increased from 52.3 to 69.8 DDDs per 100 patient-days (P < 0.001). Despite the overall constant use when expressed in DDDs per 100 admissions, we found a significant increase in the total use of piperacillin/tazobactam, cefazolin, ceftriaxone, meropenem, azithromycin, gentamicin, ciprofloxacin and vancomycin. Mean total systemic use expressed in DDDs per 1000 inhabitants per day gradually increased by 38% from 0.73 in 2003 to 1.01 in 2009. Conclusions Total hospital antibiotic consumption is still low in the Netherlands compared with other European countries. Also, between 2003 and 2009 the use of antibiotics in individual hospitalized patients remained stable. However, since they remained in the hospital for a shorter period of time, the number of DDDs per 100 patient-days increased. This results in an intensification of antibiotic treatment per hospital bed, leading to a possible increase in selection pressure towards resistance. This may create a problem for future patients. To limit the emergence and transmission of antimicrobial-resistant bacteria, effective antibiotic stewardship is essential. [ABSTRACT FROM PUBLISHER]

Background. Despite significant morbidity and mortality among business travelers due to malaria, very little has been published on knowledge, attitudes, and practices (KAP) toward malaria risk. The aim of this study was to assess KAP among frequent international business travelers (FBT) and to identify recommendations for improving malaria prevention that could be applied to the wider FBT community in occupational health. Methods. A retrospective web-based survey was conducted in 2005 among self-registered FBT of an oil and gas company based in the Netherlands. Results. The survey was completed by 328 of the 608 self-registered FBT (54%). Fifty-four percent of respondents had visited a high-risk area for malaria. Most respondents (96%) were experienced travelers; the majority (71%) sought health advice before their trip and made use of a company health resource. Fever was recognized as a malaria symptom by all FBT; travel to high-risk malaria areas was correctly identified by 96%, and 99% of these travelers adhered to use of adequate personal protective measures. The proportion of travelers carrying appropriate anti-malaria drug regimen was positively associated with receiving company advice among FBT traveling to high-risk destinations (RR = 2.10, 95% CI: 1.21-3.67), but not for those traveling to low- or no-risk destinations. Only 8% (14) of those going to a high-risk area were not carrying malaria prophylaxis. One in five of FBT traveling to no-risk areas were unnecessarily carrying malaria prophylaxis. Conclusions. The majority of KAP results were excellent. We postulate that a company culture with a strong focus on health, safety, security, and environment can positively contribute to high KAP scores. Notwithstanding the excellent findings, this study also provides a cautionary tale for company health functions against overprescribing of malaria prophylaxis. It demonstrates the need for constant review and audit of adherence to quality criteria. [ABSTRACT FROM AUTHOR]

Background: In 2013, the World Health Organization (WHO) revised their position on yellow fever vaccination, in which revaccination every 10 years was no longer required, and that a single-dose provided life-long protection. However, research data on the immunogenicity of YF vaccine in people aged 60 years and over are scarce. Indeed, immunosenescence may result in lower virus neutralizing antibody titers after primary vaccination and a more rapid waning immunity. Therefore, we tested the hypothesis that older travelers, vaccinated at 60 years or older are more likely to become seronegative in comparison to young adults 10 years after primary YF vaccination.Methods: This is a 10-year follow-up study of an earlier prospective controlled cohort study. In the original trial, the neutralizing antibody response was measured in older travelers (aged 60-81 years, N = 28) and young adults (aged 18-28 years, N = 30) up to 28 days after a primary yellow fever vaccination. Ten years later, we collected serum samples of 22/28 (78%) elderly (71-85 years) and 14/30 (47%) controls (29-40 years), and determined their neutralizing antibody titers by plaque reduction neutralization test (PRNT80). Seropositivity was defined as plaque formation reduction of 80% at a serum dilution of 10 or more (PRNT80 ≥ 10).Results: All participants (36/36) were still seropositive 10 years after primary vaccination. The geometric mean concentrations were not statistically different between the older and younger participants (6.7 IU/mL vs. 8.6 IU/mL, P = 0.5).Conclusions: All older travelers were seropositive, 10 years after a primary YF vaccination at the age of ≥60 years. These data suggest that in older travelers a single vaccination is sufficient to convey long-lasting immunity for at least 10 years, and is in support the position of the WHO on a single-dose yellow fever vaccination. [ABSTRACT FROM AUTHOR]

Background: Serological non-response can be present after hepatitis B vaccination in healthy adults. We aimed to establish which of three revaccination regimens is most effective at inducing protective immunity METHODS: Healthy adults (aged 18-80 years) from 16 Dutch centres (13 public health services, two university hospitals, and one travel clinic) were included in this multicentre, parallel group, randomised, controlled, superiority trial. The inclusion criterion was vaccine non-response (hepatitis B surface antibody [anti-HBs] titre <10 IU/L) after a primary series with three doses of one type of recombinant vaccine against hepatitis B virus (either HBVaxPro-10 or Engerix-B at months 0, 1, and 6). Participants were individually randomly assigned (1:1:1:1) to a vaccination series of repeated initial vaccination (HBVaxPro 10 μg or Engerix-B 20 μg) as the control, or to Twinrix 20 μg, Fendrix 20 μg, or HBVaxPro 40 μg. We used a web-based randomisation programme, stratified by centre, with a block size of four. Participants and centres were unmasked to assignment after randomisation. Laboratory staff and investigators were masked to vaccine-group assignment. All revaccination schedules were identical, with intramuscular vaccinations at 0, 1, and 2 months. Anti-HBs was measured at 0, 1, 2, and 3 months. The primary outcome was the percentage of responders (anti-HBs titres ≥10 IU/L) at 3 months. Immunogenicity and safety analyses were based on an intention-to-vaccinate analysis, the immunogenicity analysis with last observation carried forward for missing data, and the Bonferroni and the Benjamini-Hochberg method were applied to correct for multiple testing. The trial was registered in the Dutch National Trial Register and inclusion has been stopped (identifier NL3011; EudraCT-number 2011-005627-40).Findings: The participants were recruited between Nov 1, 2012, and Sept 1, 2017. 480 participants were randomly assigned and included in intention-to-vaccinate analyses: 124 (26%) to control, 118 (25%) to Twinrix, 114 (24%) to HBVaxPro-40, and 124 (26%) to Fendrix. At month 3 the percentage of responders was 83 (67%) of 124 (95% CI 57·9-75·1 in the control group, 94 (80%) of the 118 (71·3-86·5) in the Twinrix group, 95 (83%) of 114 (75·2-89·7) in the HBVaxPro-40 group, and 108 (87%) of 124 (79·9-92·4) in the Fendrix group. Compared with the control group, the percentage of responders was superior for the HBVaxPro-40 group (adjusted difference 21·6% [95% CI 10·4-32·7], p=0·0204 [Bonferroni corrected p value]) and the Fendrix group (26·3% [15·4-37·3], p=0·0006), but not the Twinrix group (25·0% [13·0-37·0]; p=0·0846). One serious adverse event occurred (herpes zoster ophthalmicus) in the Fendrix group, which was not attributed to the vaccine.Interpretation: Revaccinating healthy non-responders with Fendrix or HBVaxPro-40 resulted in significantly higher proportions of responders and therefore indication for these vaccines should be expanded to enable revaccination of non-responders.Funding: National Institute for Public Health and the Environment. [ABSTRACT FROM AUTHOR]

• This study is the first to describe the safety and immunogenicity of a nanoporous microneedle array for SARS-CoV-2 vaccination with the mRNA-1273 vaccine in healthy participants as a booster vaccination. • Nanoporous microneedle array for SARS-CoV-2 vaccination with 20 µg mRNA-1273 was safe but failed to induce an anamnestic antibody response, which is probably due to the used vaccine loading technique resulting in a very low amount of loaded vaccine on the microneedle tips. • As microneedle patch immunisation is a promising vaccination technique; it is worth to evaluate this novel technology further to be better prepared for pandemics in the future. Nanoporous microneedle arrays (npMNA) are being developed as skin patches for vaccine delivery. As alternative for needle-based immunisation, they may potentially result in higher vaccine acceptance, which is important for future mass vaccination campaigns to control outbreaks, such as COVID-19, and for public vaccination in general. In this study we investigated the safety and immunogenicity of needle-free intradermal delivery of a fractional third or fourth dose of mRNA-1273 vaccine by npMNA. This study was an open-label, randomised-controlled, proof-of-concept study. Healthy adults were eligible if they had received a primary immunisation series against SARS-CoV-2 with two doses of mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) mRNA vaccine. A history of a COVID-19 infection or booster vaccination with mRNA-1273 or BNT162b2 was allowed if it occurred at least three months before inclusion. Participants were randomised in a 1:1 ratio to receive 20 µg mRNA-1273 vaccine, either through npMNA patch applied on the skin (ID-patch group), or through intramuscular (IM) injection (IM-control group). Primary outcomes were reactogenicity up to two weeks after vaccination, and fold-increase of SARS-CoV-2 spike S1-specific IgG antibodies 14 days post-vaccination. In April 2022, 20 participants were enroled. The geometric mean concentration (GMC) did not increase in the ID-patch group after vaccination, in contrast to the IM-control group (GMC was 1,006 BAU/mL (95% CI 599–1,689), 3,855 (2,800–5,306), and 3,513 (2,554–4,833) at day 1, 15 and 29, respectively). In addition, SARS-CoV-2-specific T cell responses were lower after ID vaccination through npMNA. Needle-free delivery of 20 µg mRNA-1273 vaccine by npMNA failed to induce antibody and T cell responses. As this is a potentially very useful vaccination method, it is important to determine which adjustments are needed to make this npMNA successful. NCT05315362. [ABSTRACT FROM AUTHOR]

The article cites a research study that describes the use of thoracolumbar lordotic intervention (TLI) technique in a brace of adolescent scoliosis and kyphosis patients. It demonstrates that restoration of natural lordosis at the thoracolumbar junction corrects scoliotic curves. Lifestyle factors and knowledge on growth forces are crucial for the etiology of adolescent scoliosis and kyphosis.

Objective The objective of this study was to show good compliance and satisfaction in wearing a corrective brace with TLI (Thoracolumbar Lordotic Intervention) technique and highlight the important dynamic parts in this type of treatment. Background Former rigid non dynamic TLSO braces are known for their troublesome compliance and poor patient satisfaction. Dynamic braces can have good compliance but do not easily reach evident corrections. A solution was found in a short rigid brace with evident dynamic aspects by concentrating forces in a symmetric natural way at the thoracolumbar joint. Methods and results In a group of 91 adolescents with kyphotic and scoliotic deformities with earlier presented results in radiologic correction, a questionnaire was administered after at least one year (mean 1.6 years) wearing the brace. Bracing alterations were also performed during the times the brace could be adapted towards more corrective lordosis and extension. Outcome Compliance was estimated by physician and parents and scored poorly in 5.5%, fair in 30.8%, and good in 61% (Unknown 2%). Progressive alterations in shape by adding pads to increase lordosis at the TL joint and bending the sternal support backward were done a mean of 5.1 times by the orthotist. No skin sores were reported. 58.2% and 26.4% were respectively satisfied or very satisfied with the whole treatment course. The ease of brace wearing scored very good in 11%, good in 46.2%, and fair in 25.3%. With respect to overall satisfaction of perceived results, 34.1% were very satisfied, 45.1% were satisfied, 9.9% were neutral, and 6.6% were unsatisfied. Different subgroups were studied and will be presented (figure 1). Conclusion TLI braces are accepted very well by children with spinal deformities. Improved radiographic results were not the primary motivation for the compliance, but rather the fact that good compliance was rewarded with gradually improved posture and regained mobility provided by the dynamic philosophy behind the bracing technique. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Use of a Patch Containing Heat Labile Toxin From Escheria Coli Against Traveller's Diarrhea: A Phase II Randomised, Double Blind, Placebo Controlled Field Trial" by S. A. Frech, H. L. Dupont and A. L. Bourgeois in the June 14, 2008 issue.

Background. Immunocompromised travelers to developing countries are thought to have symptomatic infectious diseases more often and longer than non-immunocompromised travelers. Evidence for this is lacking. This study evaluates whether immunocompromised short-term travelers are at increased risk of diseases. Methods. A prospective study was performed between October 2003 and May 2010 among adult travelers using immunosuppressive agents (ISA) and travelers with inflammatory bowel disease (IBD), with their non-immunocompromised travel companions serving as matched controls with comparable exposure to infection. Data on symptoms of infectious diseases were recorded by using a structured diary. Results. Among 75 ISA, the incidence of travel-related diarrhea was 0.76 per person-month, and the number of symptomatic days 1.32 per month. For their 75 controls, figures were 0.66 and 1.50, respectively ( p > 0.05). Among 71 IBD, the incidence was 1.19, and the number of symptomatic days was 2.48. For their 71 controls, figures were 0.73 and 1.31, respectively ( p > 0.05). These differences also existed before travel. ISA had significantly more and longer travel-related signs of skin infection and IBD suffered more and longer from vomiting. As for other symptoms, no significant travel-related differences were found. Only 21% of immunocompromised travelers suffering from diarrhea used their stand-by antibiotics. Conclusions. ISA and IBD did not have symptomatic infectious diseases more often or longer than non-immunocompromised travelers, except for signs of travel-related skin infection among ISA. Routine prescription of stand-by antibiotics for these immunocompromised travelers to areas with good health facilities is probably not more useful than for healthy travelers. [ABSTRACT FROM AUTHOR]

The present study applied T2- and diffusion-weighted magnetic resonance imaging to examine if mild cerebral edema and subsequent brain swelling are implicated in the pathophysiology of acute mountain sickness (AMS). Twenty-two subjects were examined in normoxia (21% O2), after 16 hours passive exposure to normobaric hypoxia (12% O2) corresponding to a simulated altitude of 4,500 m and after 6 hours recovery in normoxia. Clinical AMS was diagnosed in 50% of subjects during hypoxia and corresponding headache scores were markedly elevated (P<0.05 versus non-AMS). Hypoxia was associated with a mild increase in brain volume (+7.0±4.8 ml, P<0.05 versus pre-exposure baseline) that resolved during normoxic recovery. Hypoxia was also associated with an increased T2 relaxation time (T2rt) and a general trend toward an increased apparent diffusion coefficient (ADC). During the normoxic recovery, brain volume and T2rt recovered to pre-exposure baseline values, whereas a more marked reduction in ADC in the splenium of the corpus callosum (SCC) was observed (P<0.05). While changes in brain volume and T2rt were not selectively different in AMS, ADC values were consistently lower (P<0.05 versus non-AMS) and associated with the severity of neurologic symptoms. Acute mountain sickness was also characterized by an increased brain to intracranial volume ratio (P<0.05 versus non-AMS). These findings indicate that mild extracellular vasogenic edema contributes to the generalized brain swelling observed at high altitude, independent of AMS. In contrast, intracellular cytotoxic edema combined with an anatomic predisposition to a ‘tight-fit’ brain may prove of pathophysiologic significance, although the increase in brain volume in hypoxia was only about 0.5% of total brain volume. [ABSTRACT FROM AUTHOR]

Abstract: Adoptive transfer of Epstein Barr virus (EBV) specific cytotoxic T lymphocytes (CTLs) has been successfully applied in the treatment of EBV associated post-transplant lymphoproliferative disease (PTLD). In most studies EBV transformed B cells (LCLs) have been used for the induction of EBV specific T cell lines. Application of this approach to other EBV associated tumors is difficult, because LCLs focus T cell expansion toward immunodominant EBV antigens that are not expressed in EBV associated Hodgkin’s lymphoma and nasopharyngeal carcinoma. Therefore, we compared dendritic cells (DCs) with LCLs for CD8+ T cell stimulation against dominant and subdominant EBV antigens. DCs expanded tenfold more EBNA3A and LMP2 specific CD8+ T cells than LCL and also stimulated EBV specific CTL from PTLD patients. Both, DCs and LCLs stimulations led to the expansion of high affinity T cells, capable to target EBV transformed B cells. While LCLs and DCs expressed MHC class I and II products at similar levels, DCs showed a higher expression of costimulatory and adhesion molecules. This resulted in more efficient T cell conjugate formation with DCs than with LCLs. We propose the use of DCs for stimulaton of EBV specific T cells in active or passive immunotherapy of EBV associated malignancies. [Copyright &y& Elsevier]