Scoring systems for prediction of malaria and dengue fever in non-endemic areas among travellers arriving from tropical and subtropical areas.

BACKGROUND: Fever is a common symptom among travellers returning from tropical/subtropical areas to Europe, and promptly distinguishing severe illnesses from self-limiting febrile syndromes is important but can be challenging due to non-specific clinical presentation. METHODS: A cross-sectional study enrolled adults and children who sought care during 2015-2020 at Karolinska University Hospital, Stockholm, Sweden with fever within 2 months after returning from travel to a tropical/subtropical area. Data on symptoms and laboratory parameters were prospectively and retrospectively collected. Two separate scoring systems for malaria and dengue were developed based on backward elimination regressions. RESULTS: In total, 2113 adults (18-94 years) and 202 children (1-17 years) were included, with 112 (4.8%) confirmed malaria by blood thick smear and 90 (3.9%) PCR/serology dengue-positive cases. Malaria was more likely in a patient who had visited sub-Saharan Africa and presented with combination of thrombocytopenia, anaemia and fever ≥39.5°C. Leucopenia, muscle pain and rash after travelling to Asia or South/Latin America indicated high probability of dengue. Two scoring systems with points between 0 and 7 for prediction of malaria or dengue were created based on the above predictors. Scores ≥3 indicated >80% sensitivity and specificity for malaria and >90% specificity for dengue in children and adults (area under the curve (AUC) for dengue: 0.92 in adults (95% CI 0.90 to 0.95) and 0.95 in children (95% CI 0.88 to 1.0); AUC for malaria: 0.93 in adults (95% CI 0.91 to 0.96) and 0.88 in children (95% CI 0.78 to 0.99)). Internal validation of optimism and overfitting was managed with bootstrap. CONCLUSION: The presented scoring systems provide novel tools for structured assessment of patients with tropical fever in a non-endemic area and highlight clinical signs associated with a potential severe aetiology to direct the need for microbial investigation.

The accuracy of fully-automated algorithms for the surveillance of central venous catheter-related bloodstream infection in hospitalised patients.

BACKGROUND: Continuous surveillance for healthcare-associated infections such as central venous catheter-related bloodstream infections (CVC-BSI) is crucial for prevention. However, traditional surveillance methods are resource-intensive and prone to bias. This study aimed to develop and validate fully-automated surveillance algorithms for CVC-BSI. METHODS: Two algorithms were developed using electronic health record data from 1000 admissions with a positive blood culture (BCx) at Karolinska University Hospital from 2017: (1) Combining microbiological findings in BCx and CVC cultures with BSI symptoms; (2) Only using microbiological findings. These algorithms were validated in 5170 potential CVC-BSI-episodes from all admissions in 2018-2019, and results extrapolated to all potential CVC-BSI-episodes within this period (n = 181,354). The reference standard was manual record review according to ECDC's definition of microbiologically confirmed CVC-BSI (CRI3-CVC). RESULTS: In the potential CVC-BSI-episodes, 51 fulfilled ECDC's definition and the algorithms identified 47 and 49 episodes as CVC-BSI, respectively. Both algorithms performed well in assessing CVC-BSI. Overall, algorithm 2 performed slightly better with in the total period a sensitivity of 0.880 (95%-CI 0.783-0.959), specificity of 1.000 (95%-CI 0.999-1.000), PPV of 0.918 (95%-CI 0.833-0.981) and NPV of 1.000 (95%-CI 0.999-1.000). Incidence according to the reference and algorithm 2 was 0.33 and 0.31 per 1000 in-patient hospital-days, respectively. CONCLUSIONS: Both fully-automated surveillance algorithms for CVC-BSI performed well and could effectively replace manual surveillance. The simpler algorithm, using only microbiology data, is suitable when BCx testing adheres to recommendations, otherwise the algorithm using symptom data might be required. Further validation in other settings is necessary to assess the algorithms' generalisability.

Clinical presentation and diagnosis of imported strongyloidiasis at a tertiary hospital, Stockholm, Sweden.

BACKGROUND: Since Strongyloides can persist in its host for decades, and cause life threatening infections data on prevalence, the burden and risk factors for infection is crucial in migrant populations. METHODS: In this observational retrospective cohort study, we describe the epidemiological, clinical, and microbiological characteristics of imported strongyloidiasis diagnosed at the Karolinska University Hospital, Stockholm, Sweden, during 2010-2021. RESULTS: We identified 98 individuals with strongyloidiasis, 89 (90.8%) born in endemic and 9 (9.2%) in non-endemic countries. Sub-Saharan Africa was the most common origin among the group born in endemic countries (62, 69.7%), (p < 0.005). There were 22 individuals with an underlying immunosuppressive condition. Gastrointestinal symptoms (53/98, 54.1%) were the symptoms most frequently described, and were more frequent in adults (57.0%) vs children (0%) (p = 0.013). Eosinophilia was detected in 74 (75.5%), being more frequent in the endemic-borne group (79.8% vs 33.3%, p = 0.002). Eight persons developed complications of strongyloidiasis because of either hyperinfection or disseminated disease. No people living with HIV with CD4 <500/mm3 (n = 6) developed severe strongyloidiasis. CONCLUSION: A limited number of strongyloidiasis cases was identified, with few complicated cases in immunosuppressed patients. Further studies focusing on identifying and exploring the risk of complicated strongyloidiasis in immunosuppressed patients are needed.

Nosocomial SARS-CoV-2 Infections and Mortality During Unique COVID-19 Epidemic Waves.

Importance: Quantifying the burden of nosocomial SARS-CoV-2 infections and associated mortality is necessary to assess the need for infection prevention and control measures. Objective: To investigate the occurrence of nosocomial SARS-CoV-2 infections and associated 30-day mortality among patients admitted to hospitals in Region Stockholm, Sweden. Design, Setting, and Participants: A retrospective, matched cohort study divided the period from March 1, 2020, until September 15, 2022, into a prevaccination period, early vaccination and pre-Omicron (period 1), and late vaccination and Omicron (period 2). From among 303 898 patients 18 years or older living in Region Stockholm, 538 951 hospital admissions across all hospitals were included. Hospitalized admissions with nosocomial SARS-CoV-2 infections were matched to as many as 5 hospitalized admissions without nosocomial SARS-CoV-2 by age, sex, length of stay, admission time, and hospital unit. Exposure: Nosocomial SARS-CoV-2 infection defined as the first positive polymerase chain reaction test result at least 8 days after hospital admission or within 2 days after discharge. Main Outcomes and Measures: Primary outcome of 30-day mortality was analyzed using time-to-event analyses with a Cox proportional hazards regression model adjusted for age, sex, educational level, and comorbidities. Results: Among 2193 patients with SARS-CoV-2 infections or reinfections (1107 women [50.5%]; median age, 80 [IQR, 71-87] years), 2203 nosocomial SARS-CoV-2 infections were identified. The incidence rate of nosocomial SARS-CoV-2 infections was 1.57 (95% CI, 1.51-1.64) per 1000 patient-days. In the matched cohort, 1487 hospital admissions with nosocomial SARS-CoV-2 infections were matched to 5044 hospital admissions without nosocomial SARS-CoV-2 infections. Thirty-day mortality was higher in the prevaccination period (adjusted hazard ratio [AHR], 2.97 [95% CI, 2.50-3.53]) compared with period 1 (AHR, 2.08 [95% CI, 1.50-2.88]) or period 2 (AHR, 1.22 [95% CI, 0.92-1.60]). Among patients with nosocomial SARS-CoV-2 infections, 30-day AHR comparing those with 2 or more doses of SARS-CoV-2 vaccination and those with less than 2 doses was 0.64 (95% CI, 0.46-0.88). Conclusions and Relevance: In this matched cohort study, nosocomial SARS-CoV-2 infections were associated with higher 30-day mortality during the early phases of the pandemic and lower mortality during the Omicron variant wave and after the introduction of vaccinations. Mitigation of excess mortality risk from nosocomial transmission should be a strong focus when population immunity is low through implementation of adequate infection prevention and control measures.

The augmented value of using clinical notes in semi-automated surveillance of deep surgical site infections after colorectal surgery.

BACKGROUND: In patients who underwent colorectal surgery, an existing semi-automated surveillance algorithm based on structured data achieves high sensitivity in detecting deep surgical site infections (SSI), however, generates a significant number of false positives. The inclusion of unstructured, clinical narratives to the algorithm may decrease the number of patients requiring manual chart review. The aim of this study was to investigate the performance of this semi-automated surveillance algorithm augmented with a natural language processing (NLP) component to improve positive predictive value (PPV) and thus workload reduction (WR). METHODS: Retrospective, observational cohort study in patients who underwent colorectal surgery from January 1, 2015, through September 30, 2020. NLP was used to detect keyword counts in clinical notes. Several NLP-algorithms were developed with different count input types and classifiers, and added as component to the original semi-automated algorithm. Traditional manual surveillance was compared with the NLP-augmented surveillance algorithms and sensitivity, specificity, PPV and WR were calculated. RESULTS: From the NLP-augmented models, the decision tree models with discretized counts or binary counts had the best performance (sensitivity 95.1% (95%CI 83.5-99.4%), WR 60.9%) and improved PPV and WR by only 2.6% and 3.6%, respectively, compared to the original algorithm. CONCLUSIONS: The addition of an NLP component to the existing algorithm had modest effect on WR (decrease of 1.4-12.5%), at the cost of sensitivity. For future implementation it will be a trade-off between optimal case-finding techniques versus practical considerations such as acceptability and availability of resources.

External validation of semi-automated surveillance algorithms for deep surgical site infections after colorectal surgery in an independent country.

BACKGROUND: Automated surveillance methods that re-use electronic health record data are considered an attractive alternative to traditional manual surveillance. However, surveillance algorithms need to be thoroughly validated before being implemented in a clinical setting. With semi-automated surveillance patients are classified as low or high probability of having developed infection, and only high probability patients subsequently undergo manual record review. The aim of this study was to externally validate two existing semi-automated surveillance algorithms for deep SSI after colorectal surgery, developed on Spanish and Dutch data, in a Swedish setting. METHODS: The algorithms were validated in 225 randomly selected surgeries from Karolinska University Hospital from the period January 1, 2015 until August 31, 2020. Both algorithms were based on (re)admission and discharge data, mortality, reoperations, radiology orders, and antibiotic prescriptions, while one additionally used microbiology cultures. SSI was based on ECDC definitions. Sensitivity, specificity, positive predictive value, negative predictive value, and workload reduction were assessed compared to manual surveillance. RESULTS: Both algorithms performed well, yet the algorithm not relying on microbiological culture data had highest sensitivity (97.6, 95%CI: 87.4-99.6), which was comparable to previously published results. The latter algorithm aligned best with clinical practice and would lead to 57% records less to review. CONCLUSIONS: The results highlight the importance of thorough validation before implementation in other clinical settings than in which algorithms were originally developed: the algorithm excluding microbiology cultures had highest sensitivity in this new setting and has the potential to support large-scale semi-automated surveillance of SSI after colorectal surgery.

Association Between Time to Appropriate Antimicrobial Treatment and 30-day Mortality in Patients With Bloodstream Infections: A Retrospective Cohort Study.

BACKGROUND: Effective antimicrobial treatment is key for survival in bloodstream infection (BSI), but the impact of timing of treatment remains unclear. Our aim was to assess the association between time to appropriate antimicrobial treatment and 30-day mortality in BSI patients. METHODS: This was a retrospective cohort study using electronic health record data from a large academic center in Sweden. Adult patients admitted between the years 2012 and 2019, with onset of BSI at the emergency department or general wards, were included. Pathogen-antimicrobial drug combinations were classified as appropriate or inappropriate based on reported in vitro susceptibilities. To avoid immortal time bias, the association between appropriate therapy and mortality was assessed with multivariable logistic regression analysis at pre-specified landmark times. RESULTS: We included 10 628 BSI-episodes, occurring in 9192 unique patients. The overall 30-day mortality was 11.8%. No association in favor of a protective effect between appropriate therapy and mortality was found at the 1, 3 and 6 hours landmark after blood culture collection. At 12 hours, the risk of death increased with inappropriate treatment (adjusted odds ratio 1.17 [95% confidence interval {CI}, 1.01-1.37]) and continued to increase gradually at 24, 48, and 72 hours. Stratifying by high or low SOFA score generated similar odds ratios, with wider confidence intervals. CONCLUSIONS: Delays in appropriate antimicrobial treatment were associated with increased 30-day mortality after 12 hours from blood culture collection, but not at 1, 3, and 6 hours, in BSI. These results indicate a benchmark for providing rapid microbiological diagnostics of blood cultures.

The accuracy of fully automated algorithms for surveillance of healthcare-onset Clostridioides difficile infections in hospitalized patients.

We developed and validated a set of fully automated surveillance algorithms for healthcare-onset CDI using electronic health records. In a validation data set of 750 manually annotated admissions, the algorithm based on International Classification of Disease, Tenth Revision (ICD-10) code A04.7 had insufficient sensitivity. Algorithms based on microbiological test results with or without addition of symptoms performed well.

SARS-CoV-2 testing in patients with low COVID-19 suspicion at admission to a tertiary care hospital, Stockholm, Sweden, March to September 2020.

BackgroundUniversal SARS-CoV-2 testing at hospital admission has been proposed to prevent nosocomial transmission.AimTo investigate SARS-CoV-2 positivity in patients tested with low clinical COVID-19 suspicion at hospital admission.MethodsWe characterised a retrospective cohort of patients admitted to Karolinska University Hospital tested for SARS-CoV-2 by PCR from March to September 2020, supplemented with an in-depth chart review (16 March-12 April). We compared positivity rates in patients with and without clinical COVID-19 suspicion with Spearman's rank correlation coefficient. We used multivariable logistic regression to identify factors associated with test positivity.ResultsFrom March to September 2020, 66.9% (24,245/36,249) admitted patient episodes were tested; of those, 61.2% (14,830/24,245) showed no clinical COVID-19 suspicion, and the positivity rate was 3.2% (469/14,830). There was a strong correlation of SARS-CoV-2 positivity in patients with low vs high COVID-19 suspicion (rho = 0.92; p < 0.001).From 16 March to 12 April, the positivity rate was 3.9% (58/1,482) in individuals with low COVID-19 suspicion, and 3.1% (35/1,114) in asymptomatic patients. Rates were higher in women (5.0%; 45/893) vs men (2.0%; 12/589; p = 0.003), but not significantly different if pregnant women were excluded (3.7% (21/566) vs 2.2% (12/589); p = 0.09). Factors associated with SARS-CoV-2 positivity were testing of pregnant women before delivery (odds ratio (OR): 2.6; 95% confidence interval (CI): 1.3-5.4) and isolated symptoms in adults (OR: 3.3; 95% CI: 1.8-6.3).ConclusionsThis study shows a relatively high SARS-CoV-2 positivity rate in patients with low COVID-19 suspicion upon hospital admission. Universal SARS-CoV-2 testing of pregnant women before delivery should be considered.

Impact of the COVID-19 pandemic on the incidence and mortality of hospital-onset bloodstream infection: a cohort study.

The COVID-19 pandemic burdens hospitals, but consequences for quality of care outcomes such as healthcare-associated infections are largely unknown. This cohort included all adult hospital episodes (n=186 945) at an academic centre between January 2018 and January 2021. Data were collected from the hospitals' electronic health record data repository. Hospital-onset bloodstream infection (HOB) was defined as any positive blood culture obtained ≥48 hours after admission classified based on microbiological and hospital administrative data. Subgroup analyses were performed with exclusion of potential contaminant bacteria. The cohort was divided into three groups: controls (prepandemic period), non-COVID-19 (pandemic period) and COVID-19 (pandemic period) based on either PCR-confirmed SARS-CoV-2 infections from respiratory samples or International Classification of Diseases 10th Revision diagnoses U071 and U72 at discharge. Adjusted incidence rate ratios (aIRR) and risk of death in patients with HOB were compared between the prepandemic and pandemic periods using Poisson and logistic regression. The incidence of HOB was increased for the COVID-19 group compared with the prepandemic period (aIRR 3.34, 95% CI 2.97 to 3.75). In the non-COVID-19 group, the incidence was slightly increased compared with prepandemic levels (aIRR 1.20, 95% CI 1.08 to 1.32), but the difference decreased when excluding potential contaminant bacteria (aIRR 1.15, 95% CI 1.00 to 1.31, p=0.04). The risk of dying increased for both the COVID-19 group (adjusted odds ratio (aOR) 2.44, 95% CI 1.75 to 3.38) and the non-COVID-19 group (aOR 1.63, 95% CI 1.22 to 2.16) compared with the prepandemic controls. These findings were consistent also when excluding potential contaminants. In summary, we observed a higher incidence of HOB during the COVID-19 pandemic, and the mortality risk associated with HOB was greater, compared with the prepandemic period. Results call for specific attention to quality of care during the pandemic.

Clinical phenotypes and outcomes of SARS-CoV-2, influenza, RSV and seven other respiratory viruses: a retrospective study using complete hospital data.

BACKGROUND: An understanding of differences in clinical phenotypes and outcomes COVID-19 compared with other respiratory viral infections is important to optimise the management of patients and plan healthcare. Herein we sought to investigate such differences in patients positive for SARS-CoV-2 compared with influenza, respiratory syncytial virus (RSV) and other respiratory viruses. METHODS: We performed a retrospective cohort study of hospitalised adults and children (≤15 years) who tested positive for SARS-CoV-2, influenza virus A/B, RSV, rhinovirus, enterovirus, parainfluenza viruses, metapneumovirus, seasonal coronaviruses, adenovirus or bocavirus in a respiratory sample at admission between 2011 and 2020. RESULTS: A total of 6321 adult (1721 SARS-CoV-2) and 6379 paediatric (101 SARS-CoV-2) healthcare episodes were included in the study. In adults, SARS-CoV-2 positivity was independently associated with younger age, male sex, overweight/obesity, diabetes and hypertension, tachypnoea as well as better haemodynamic measurements, white cell count, platelet count and creatinine values. Furthermore, SARS-CoV-2 was associated with higher 30-day mortality as compared with influenza (adjusted HR (aHR) 4.43, 95% CI 3.51 to 5.59), RSV (aHR 3.81, 95% CI 2.72 to 5.34) and other respiratory viruses (aHR 3.46, 95% CI 2.61 to 4.60), as well as higher 90-day mortality, ICU admission, ICU mortality and pulmonary embolism in adults. In children, patients with SARS-CoV-2 were older and had lower prevalence of chronic cardiac and respiratory diseases compared with other viruses. CONCLUSIONS: SARS-CoV-2 is associated with more severe outcomes compared with other respiratory viruses, and although associated with specific patient and clinical characteristics at admission, a substantial overlap precludes discrimination based on these characteristics.

Infection control link nurses in acute care hospitals: a scoping review.

Background: Involving link nurses in infection prevention and control is a strategy to improve clinical practice that has been implemented in hospitals worldwide. However, little is known about the use, the range and benefits of this strategy. We aimed to identify key concepts of infection control link nurses (ICLN) and ICLN programs, to evaluate the effect of such programs, and to identify gaps in the evidence base. Methods: In a scoping review, we searched PubMed, CINAHL, Google and Google Scholar for manuscripts on ICLN in acute care hospitals. We included research- and opinion-based papers, abstracts, reports and guidelines. Results: We included 29 publications and identified three key concepts: the profile of ICLN, strategies to support ICLN, and the implementation of ICLN programs. The majority of included studies delineates the ICLN profile with accompanying roles, tasks and strategies to support ICLN, without a thorough evaluation of the implementation process or effects. Few studies report on the effect of ICLN programs in terms of patient outcomes or guideline adherence, with positive short term effects. Conclusion: This scoping review reveals a lack of robust evidence on the effectiveness of ICLN programs. Current best practice for an ICLN program includes a clear description of the ICLN profile, education on infection prevention topics as well as training in implementation skills, and support from the management at the ward and hospital level. Future research is needed to evaluate the effects of ICLN on clinical practice and to further develop ICLN programs for maximal impact.

Colonization sites in carriers of ESBL-producing Gram-negative bacteria.

Objective: The distribution of Extended-Spectrum Beta-Lactamase-producing Gram-negative bacteria (ESBL-GNB) colonization sites is relevant for infection control guidelines on detection and follow-up of colonization. We questioned whether it is possible to rely solely on rectal swab culture for follow-up of ESBL-GNB colonization. Methods: We retrospectively assessed ESBL-GNB colonization sites in patients in a tertiary hospital in the Netherlands. The Laboratory Information Management System was queried for all bacterial cultures obtained between January 2012 and August 2016. All patients with one or more cultures positive for ESBL-GNB were identified and the distribution of ESBL-GNB positive sample sites was assessed. A subgroup analysis was performed on patients for whom at least one rectal swab specimen was available. Results: We identified 1011 ESBL-GNB carriers with 16,578 specimens for analysis. ESBL-GNB were most frequently isolated from the rectum (506/1011), followed by the urogenital (414/1011) and respiratory tract (142/1011), and pus (136/1011). For 588 patients at least one rectal swab specimen was available. In this subgroup, ESBL-GNB colonization was detected only in the rectum in 55.4% (326/588) of patients, in 30.6% (180/588) in the rectum and a different culture site, and in 13.9% (82/588) no rectal colonization was detected. Conclusions: Rectal colonization with ESBL-GNB was detected in 86% of ESBL-GNB carriers. However, in 14% of ESBL-GNB carriers we did not detect rectal colonization. Therefore, samples taken for follow-up of colonization with multi-drug resistant Gram-negative bacteria (MDR-GNB) should ideally also include samples from the site where the MDR-GNB was initially found.

Height, zinc and soil-transmitted helminth infections in schoolchildren: a study in Cuba and Cambodia.

Soil-transmitted helminth (STH) infections and zinc deficiency are often found in low- and middle-income countries and are both known to affect child growth. However, studies combining data on zinc and STH are lacking. In two studies in schoolchildren in Cuba and Cambodia, we collected data on height, STH infection and zinc concentration in either plasma (Cambodia) or hair (Cuba). We analyzed whether STH and/or zinc were associated with height for age z-scores and whether STH and zinc were associated. In Cuba, STH prevalence was 8.4%; these were mainly Ascaris lumbricoides and Trichuris trichiura infections. In Cambodia, STH prevalence was 16.8%, mostly caused by hookworm. In Cuban children, STH infection had a strong association with height for age (aB-0.438, p = 0.001), while hair zinc was significantly associated with height for age only in STH uninfected children. In Cambodian children, plasma zinc was associated with height for age (aB-0.033, p = 0.029), but STH infection was not. Only in Cambodia, STH infection showed an association with zinc concentration (aB-0.233, p = 0.051). Factors influencing child growth differ between populations and may depend on prevalences of STH species and zinc deficiency. Further research is needed to elucidate these relationships and their underlying mechanisms.

Impact of periodic selective mebendazole treatment on soil-transmitted helminth infections in Cuban schoolchildren.

OBJECTIVE: To evaluate the impact of periodic selective treatment with 500 mg mebendazole on soil-transmitted helminth (STH) infections in Cuban schoolchildren. METHODS: We followed up a cohort of 268 STH-positive schoolchildren, aged 5-14 years at baseline, at six-month intervals for two years and a final follow-up after three years. Kato-Katz stool examination was used to detect infections with Ascaris lumbricoides, Trichuris trichiura and hookworm. Common risk factors related to STHs were assessed by parental questionnaire. RESULTS: A significant reduction in the number of STH infections was obtained after three years with the highest reduction for T. trichiura (87.8%) and the lowest for hookworm (57.9%). After six months, cure rates (CRs) were 76.9% for A. lumbricoides, 67.4% for T. trichiura and 44.4% for hookworm. After two treatment rounds, more than 75% of all STH-positive children at baseline were cured, but with important differences between STH species (95.2% for A. lumbricoides, 80.5% for T. trichiura and 76.5% for hookworm). At the end of the study, these cumulative CRs were almost 100% for all three STHs. Risk factors for STHs were sex, sanitary disposal and habit of playing in the soil. CONCLUSIONS: Our results indicate that periodic selective treatment with 500 mg mebendazole is effective in reducing the number of STH infections in Cuban schoolchildren. Although important differences were found between helminth species, two rounds of treatment appeared sufficient to obtain substantial reductions.

Childhood atopic diseases and early life circumstances: an ecological study in Cuba.

BACKGROUND: Children are especially vulnerable during periods of resource shortage such as economic embargoes. They are likely to suffer most from poor nutrition, infectious diseases, and other ensuing short-term threats. Moreover, early life circumstances can have important consequences for long-term health. We examined the relationship between early childhood exposure to the Cuban economic situation in the nineties and the occurrence of atopic diseases later in childhood. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional study of 1321 primary schoolchildren aged 4-14 was conducted in two Cuban municipalities. Asthma, allergic rhinoconjunctivitis and atopic dermatitis were diagnosed using the International Study of Asthma and Allergies in Childhood questionnaire. Children were divided into three groups of exposure to the economic situation in the nineties according to birth date: (1) unexposed; (2) exposed during infancy; (3) exposed during infancy and early childhood. Associations were assessed using multiple logistic regression models. Exposure during infancy had a significant inverse association with the occurrence of asthma (OR 0.56, 95%CI 0.33-0.94) and allergic rhinoconjunctivitis (OR 0.46, 95%CI 0.25-0.85). The associations were stronger after longer exposure, i.e. during infancy and early childhood, for asthma (OR 0.40, 95% CI 0.17-0.95) and allergic rhinoconjunctivitis (OR 0.29, 95%CI 0.11-0.77). No significant associations were found for atopic dermatitis. CONCLUSIONS/SIGNIFICANCE: Exposure to the economic situation in the nineties during infancy and early childhood was inversely associated with asthma and allergic rhinoconjunctivitis occurrence later in childhood. We hypothesize that factors related to this period, such as infectious diseases and undernutrition, may have an attenuating effect on atopic disease development. The exact cause and underlying mechanisms need to be further elucidated.

Age is of influence on midazolam requirements in a paediatric intensive care unit.

AIM: To test that age is of influence on midazolam requirements during prolonged mechanical ventilation in critically ill children. METHODS: Retrospective observational study of children (28 days-18 year) admitted between January 1st 2002 and January 1st 2005 who needed controlled mechanical ventilation for 5 days and initial sedation with midazolam were included. Exclusion criteria were psychomotor retardation, therapeutic use of midazolam, ventilator weaning within 5 days, kidney or liver failure. RESULTS: A total of 1186 children were admitted, of which 58 children were included. The children were divided into three age groups: 28 days-1 year (n = 28), 1-4 years (n = 16) and older than 4 years (n = 14). Within 2 days the children age 1-4 years received the maximum midazolam dosage (0.3 mg/kg/h). In addition, the mean total dose of midazolam was higher at all days for this age group. At day 5 none of the children between 1 and 4 years could be sedated with midazolam alone. CONCLUSIONS: Our data showed that children between 1 and 4 years needed higher doses of midazolam as compared to children who were younger and older. Furthermore, we observed that midazolam alone is a poor sedative for all age groups. The influence of and mechanisms for possible age related effects on midazolam requirements remain to be elucidated, as well as the position of midazolam as a first line drug for PICU sedation.