[Anxiety in times of COVID-19 and other health crises]. / Ängste in Zeiten von COVID-19 und anderen Gesundheitskrisen.

BACKGROUND: Epidemics and pandemics and the measures taken to contain their spread are accompanied by numerous stressors, which can lead in particular to severe anxiety. OBJECTIVE: This article describes the components and determinants of these anxiety symptoms, potential resilience and risk factors and appropriate recommendations for action. METHODS: The article presents an overview of research results regarding COVID-19 and previous epidemics and pandemics (e.g., HIV, SARS, MERS, Ebola and swine flu). Furthermore, official recommendations for action are presented. RESULTS: Anxiety symptoms frequently occur in epidemics and pandemics, especially in the early phase and usually decrease in the further course. Although other aspects of different infectious diseases vary, the associated fears are similar and include e.g. the fear of health-related, social and economic consequences. Resilience and risk factors in various epidemics and pandemics are comparable. Self-efficacy expectation, tolerance of uncertainty, normalization, routines, safety and social support usually have a protective effect. In contrast, excessive media consumption, female gender, work in a medical context, suppression, pre-existing diseases, unhealthy behavior and closer exposure to the virus are often accompanied by more severe anxiety. CONCLUSION: Fears should be observed and addressed in order to reduce pathological processes, especially in vulnerable groups. It is advisable to promote resilience factors and to counteract risk factors with preventive and therapeutic measures. For this purpose, the development and empirical testing of specific interventions as well as further longitudinal studies are needed.

Type 1 diabetes in children born after assisted reproductive technology: a register-based national cohort study.

STUDY QUESTION: Do children born after assisted reproductive technology (ART) have an increased risk of developing type 1 diabetes? SUMMARY ANSWER: Children born after ART were found to have an increased risk of type 1 diabetes in the unadjusted analysis, while after adjustment this association was only significant in children born after frozen embryo transfer. WHAT IS KNOWN ALREADY?: Some studies raise concerns as to whether fertility treatments may influence long-term morbidity in children born after ART. Elevated blood pressure and altered glucose metabolism have been found after ART in a few studies. STUDY DESIGN, SIZE, DURATION: A register-based national cohort study that included all children born in Sweden between 1985 and 2015-in total, 3 138 540 children-was carried out. PARTICIPANTS/MATERIAL, SETTING, METHODS: The study was population-based and all live-born singleton children born after ART (n = 47 938) or spontaneous conception (SC) (n = 3 090 602) were included. The ART cohort comprised 36 727 children born after fresh embryo transfer and 11 211 children born after frozen embryo transfer. Several national registries were used together with data from Statistics Sweden. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 202 children born after ART and 17 916 children born after SC developed type 1 diabetes, corresponding to 43.4 and 35.5 per 100 000 person-years at risk (hazard ratio [HR] 1.23; 95% confidence interval [CI], 1.07 to 1.42). Mean follow-up was 9.7 (SD 6.4) years for ART children and 16.3 (SD 9.2) years for SC children. After adjustment for calendar year of birth, HR for type 1 diabetes was 1.13; 95% CI, 0.98-1.30. After further adjustment for sex, maternal age, country of birth, educational level, smoking and parental diabetes, HR was 1.07; 95% CI, 0.93-1.23. In subgroup analyses, an association was found between frozen embryo transfer and type 1 diabetes (adjusted HR 1.52; 95% CI, 1.08-2.14 and 1.41; 95% CI, 1.05-1.89 for frozen versus fresh and frozen versus SC, respectively). When comparing intracytoplasmic sperm injection to in vitro fertilization, no difference was found (adjusted HR 1.08; 95% CI, 0.77-1.51). LIMITATIONS, REASONS FOR CAUTION: Limitations were the missing data and residual confounding caused by unknown confounders. Furthermore, the control group consisted of all children not conceived by ART and not non-ART children from subfertile mothers. The study was also performed in only singletons and not in the total ART population. WIDER IMPLICATIONS OF THE FINDINGS: Type 1 diabetes is a serious disease, affecting human life in several ways, including risk of serious complications, reduced life span and a life-long treatment. Our results are generally reassuring, showing no increase in diabetes in ART children compared to children born after SC after adjustment for relevant confounders. The observation of an association between children born after frozen embryo transfer and type 1 diabetes, although based on subgroup analyses with a limited number of children and modest in size, is however a reason for concern. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by Nordforsk 71450, the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement 70940, and the Hjalmar Svensson Foundation. The authors have no competing interests. TRIAL REGISTRATION NUMBER: ISRCTN 11780826.

From high to low malaria transmission in Zanzibar-challenges and opportunities to achieve elimination.

BACKGROUND: Substantial global progress in the control of malaria in recent years has led to increased commitment to its potential elimination. Whether this is possible in high transmission areas of sub-Saharan Africa remains unclear. Zanzibar represents a unique case study of such attempt, where modern tools and strategies for malaria treatment and vector control have been deployed since 2003. METHODS: We have studied temporal trends of comprehensive malariometric indices in two districts with over 100,000 inhabitants each. The analyses included triangulation of data from annual community-based cross-sectional surveys, health management information systems, vital registry and entomological sentinel surveys. RESULTS: The interventions, with sustained high-community uptake, were temporally associated with a major malaria decline, most pronounced between 2004 and 2007 and followed by a sustained state of low transmission. In 2015, the Plasmodium falciparum community prevalence of 0.43% (95% CI 0.23-0.73) by microscopy or rapid diagnostic test represented 96% reduction compared with that in 2003. The P. falciparum and P. malariae prevalence by PCR was 1.8% (95% CI 1.3-2.3), and the annual P. falciparum incidence was estimated to 8 infections including 2.8 clinical episodes per 1000 inhabitants. The total parasite load decreased over 1000-fold (99.9%) between 2003 and 2015. The incidence of symptomatic malaria at health facilities decreased by 94% with a trend towards relatively higher incidence in age groups > 5 years, a more pronounced seasonality and with reported travel history to/from Tanzania mainland as a higher risk factor. All-cause mortality among children < 5 years decreased by 72% between 2002 and 2007 mainly following the introduction of artemisinin-based combination therapies whereas the main reduction in malaria incidence followed upon the vector control interventions from 2006. Human biting rates decreased by 98% with a major shift towards outdoor biting by Anopheles arabiensis. CONCLUSIONS: Zanzibar provides new evidence of the feasibility of reaching uniquely significant and sustainable malaria reduction (pre-elimination) in a previously high endemic region in sub-Saharan Africa. The data highlight constraints of optimistic prognostic modelling studies. New challenges, mainly with outdoor transmission, a large asymptomatic parasite reservoir and imported infections, require novel tools and reoriented strategies to prevent a rebound effect and achieve elimination.

[Selective mutism]. / Selektiver Mutismus.

Selective mutism was first described in the medical literature 140 years ago. The diagnosis came into the focus of adult psychiatry with the appearance of DSM-5. Henceforth, selective mutism during infancy, adolescence and also adulthood is specified as an independent anxiety disorder. It often begins in early childhood with a kind of speechlessness in certain situations. A diagnostic clarification often only takes place after school enrolment. Very often comorbid anxiety disorders, especially social phobia and depression also occur. The course is very variable and with some affected persons regression of the pathology occurs suddenly and completely and with others there is a slow regression of the symptoms. Equally the disorder can persist until adulthood. Whilst formerly a traumatic genesis was assumed, a multifactorial etiology with genetic, psychological and language-associated effects is nowadays presumed. The therapy is supported through psychotherapy, speech therapy and psychopharmacology.

Time trends of technology mediated communication with friends among bullied and not bullied children in four Nordic countries between 2001 and 2010.

BACKGROUND: Friends are important in childhood and adolescence, especially to bullied children. Technology mediated communication (TMC) could be used both to develop and maintain friendship. The present study examined (1) trends in the use of TMC with friends between 2001 and 2010; (2) possible differences between bullied and not bullied children and (3) differences between children with few close friends and children with several close friends. METHODS: Data were obtained from three waves of the serial cross-sectional Health Behaviour in School-Aged Children survey conducted in Denmark, Finland, Iceland and Sweden during 2001/2002, 2005/2006 and 2009/2010. The total sample consisted of 65 953 children aged 11, 13 and 15. RESULTS: Two trends were observed. The first trend showed an increased use of TMC in all countries. Children that were not bullied and/or had several close friends had increased their use of TMC with friends from 2001 to 2010. The second trend was applicable only for bullied children with few close friends; they had not as other children increased their use of TMC and thus remained at the same levels as in 2001/2002. CONCLUSIONS: Bullied children with few close friends were excluded from communication forums that usually allow children to maintain and develop friendships. This is a concern because friends are important during childhood and adolescence, especially for bullied children.

Tick-Borne Encephalitis sequelae at long-term follow-up: a self-reported case-control study.

BACKGROUND: Tick-borne encephalitis (TBE), caused by the TBE virus (TBEV), is a major neurotropic infection throughout Europe and Asia, with a considerable risk of neurological sequelae. Our aim was to study the symptoms in patients with TBE in Western Gotaland between 1997 and 2012 in the acute phase and at follow-up after 2-15 years (median: 5.5 years). METHODS: The medical records of 96 patients with TBE were studied. Phone-based interviews were held with 92 patients and 58 controls, matched by age, gender and residential area. The Encephalitis Support Group Questionnaire (ESGQ) 2000 was used, further developed with dimensions and scoring 1-4, where a high score is related to better outcome. Patients and controls also answered a written survey regarding functional outcome of sleep (FOSQ). RESULTS: Of the patients, 35% had a mild disease, 56% moderate and 7.3% severe disease. At the follow-up, patients scored significantly lower than controls in the dimensions of memory/learning, executive functions, vigilance and physical impairments. In addition, the answers concerning tiredness/fatigue, poor concentration/attention, reduced initiative/motivation, balance disturbances, coordination problems, difficulties with short- and long-term memory, learning difficulties and problems with fine motor skills resulted in significantly lower scores in the patients compared with the controls. The patients scored lower than the controls in the FOSQ dimension social outcome. CONCLUSIONS: At the long-term follow-up, the patients scored significantly lower in a diversity of neurocognitive and motor symptoms, in comparison with controls. These sequelae and their pathogenesis should be further explored and specific neurocognitive assessment tests are needed.

Peripheral venous catheter related complications are common among paediatric and neonatal patients.

AIM: The aims of this study were to describe the characteristics of peripheral venous catheters (PVCs), including dwell time and reasons for removal, and explore predictors for PVC-related complications. METHODS: We included PVCs in 2032 children - 484 neonatal and 1548 paediatric - from 12 inpatient units. Data were retrieved from the patient record system, and predictors for complications were explored using logistic regression analyses. RESULTS: Just over one-third (35.4%) of the PVCs were removed due to complications, in particular infiltration and occlusion (51.9 and 48.4/1000 PVC days, respectively). PVC survival time was shorter in neonatal than paediatric patients (4 versus 5 days), and infiltration was more frequent in neonatal patients (92.8 versus 38.7/1000 PVC days). Infiltration was associated with younger age (odds ratio 0.97) for neonatal patients and with younger age (OR 0.96), insertion in the bend of the arm (OR 1.48) or ankle (OR 2.81) for paediatric patients. Occlusion was, both for neonatal and paediatric patients, associated with longer dwell time (OR 1.32 and 1.22 respectively), insertion in the ankle (OR 5.00 and 3.51) or foot (OR 3.47 and 1.99). CONCLUSION: PVC-related complications, particularly infiltration and occlusion, were more common in hospitalised children but decreased with the child's age.

Differences in prevalence of bullying victimization between native and immigrant children in the Nordic countries: a parent-reported serial cross-sectional study.

BACKGROUND: Bullying among children is a problem with severe consequences for the victim. The present study examined parent-reported bullying victimization among children in the Nordic countries at two points in time, 1996 and 2011, and studied differences in prevalence of bullying victimization between immigrant and native children. METHODS: Data came from the parent-reported NordChild, carried out in the Nordic countries in 1996 and 2011. NordChild is a serial cross-sectional comparative study. A total of 7107 children aged 7-13 were included in the analyses. RESULTS: The prevalence of bullying victimization in the total Nordic countries was lower in 2011 (19.2%) than 1996 (21.7%). Difference in prevalence of bullying victimization was found both between native and immigrant children, and between countries. The largest difference in prevalence of bullying victimization was measured in Sweden 2011, where 8.6% of the native children were bullied, to be compared with the 27.8% of the immigrant children. Immigrant children had higher odds to be bullied than native children in Norway, Sweden and in the total Nordic countries at both measurements, also when adjusted for potentially confounding factors. CONCLUSIONS: The higher prevalence of bullying victimization among immigrant children should be taken into consideration in the design and development of preventive work against bullying.

Using rumen probes to examine effects of conjugated linoleic acids and dietary concentrate proportion on rumen pH and rumen temperature of periparturient dairy cows.

The study aimed to examine the influence of supplemented conjugated linoleic acids (CLA) to periparturient cows receiving different concentrate proportions antepartum on rumen pH (RpH) and rumen temperature (RT). Twenty pregnant German Holstein cows were equipped with rumen probes for continuous RpH and RT measurement in a frequency of 15 min to investigate effects of dietary concentrate and CLA around parturition and the impact of parturition itself on RpH and RT. Cows had ad libitum access to partial mixed rations, 3 weeks prior to calving until day 7 post-partum. Antepartum, cows received 100 g/day control fat (CON) or CLA supplement, either in low (20%; CON-20, CLA-20) or high concentrate diet (60%; CON-60, CLA-60). Post-partum, concentrate proportion was adjusted to 50% while fat supplementation continued. Compared with adapted feeding, high concentrate proportions antepartum tended to increase DMI and reduced RpH. Groups CON-60 and CLA-60 spent more than 4 h per day below RpH 5.6 during late pregnancy, indicating the presence of subacute rumen acidosis (SARA). The RT remained unaffected antepartum. Before calving, cows spent less time below RpH 5.6 and SARA could be detected in each group post-partum. Mean RpH increased slightly antepartum, whereas few hours before parturition a sharp decrease in RpH could be observed, accompanied with increased RT. Overall, it seems that CLA supplementation influences RpH and RT. Bearing in mind that rumen parameters fluctuate during day and herd level must be known, rumen probes for continuous RpH and RT measurement could be a useful management tool for animal health surveillance and may also help to predict parturition.

The EC-COMPASS: Long-term, multi-centre surveillance of Enterobacter cloacae complex - a clinical perspective.

BACKGROUND: Enterobacter cloacae complex (ECCO) comprises closely related Enterobacterales, causing a variety of infections ranging from mild urinary tract infections to severe bloodstream infections. ECCO has emerged as a significant cause of healthcare-associated infections, particularly in neonatal and adult intensive care. AIM: The Enterobacter Cloacae COMplex PASsive Surveillance (EC-COMPASS) aims to provide a detailed multi-centre overview of ECCO epidemiology and resistance patterns detected in routine microbiological diagnostics in four German tertiary-care hospitals. METHODS: In a sentinel cluster of four German tertiary-care hospitals, all culture-positive ECCO results between 1st January 2020 and 31st December 2022, were analysed based on Hybase® laboratory data. FINDINGS: Analysis of 31,193 ECCO datasets from 14,311 patients revealed a higher incidence in male patients (P<0.05), although no significant differences were observed in ECCO infection phenotypes. The most common sources of ECCO were swabs (42.7%), urine (17.5%), respiratory secretions (16.1%), blood cultures (8.9%) and tissue samples (5.6%). The annual bacteraemia rate remained steady at approximately 33 cases per hospital. Invasive ECCO infections were predominantly found in oncology and intensive care units. Incidences of nosocomial outbreaks were infrequent and limited in scope. Notably, resistance to carbapenems was consistently low. CONCLUSION: EC-COMPASS offers a profound clinical perspective on ECCO infections in German tertiary-healthcare settings, highlighting elderly men in oncology and intensive care units as especially vulnerable to ECCO infections. Early detection strategies targeting at-risk patients could improve ECCO infection management.

The Nordic prescription databases as a resource for pharmacoepidemiological research--a literature review.

PURPOSE: All five Nordic countries have nationwide prescription databases covering all dispensed drugs, with potential for linkage to outcomes. The aim of this review is to present an overview of therapeutic areas studied and methods applied in pharmacoepidemiologic studies using data from these databases. METHODS: The study consists of a Medline-based structured literature review of scientific papers published during 2005-2010 using data from the prescription databases in Denmark, Finland, Iceland, Norway, and Sweden, covering 25 million inhabitants. Relevant studies were analyzed in terms of pharmacological group, study population, outcomes examined, type of study (drug utilization vs. effect of drug therapy), country of origin, and extent of cross-national collaboration. RESULTS: A total of 515 studies were identified. Of these, 262 were conducted in Denmark, 97 in Finland, 4 in Iceland, 87 in Norway, and 61 in Sweden. Four studies used data from more than one Nordic country. The most commonly studied drugs were those acting on the nervous system, followed by cardiovascular drugs and gastrointestinal/endocrine drugs. A total of 228 studies examined drug utilization and 263 focused on the effects and safety of drug therapy. Pregnant women were the most commonly studied population in safety studies, whereas prescribers' adherence to guidelines was the most frequent topic of drug utilization studies. CONCLUSIONS: The Nordic prescription databases, with their possibility of record-linkage, represent an outstanding resource for assessing the beneficial and adverse effects of drug use in large populations, under routine care conditions, and with the potential for long-term follow-up.

Factors associated with switching and combination use of antidepressants in young Swedish adults.

AIMS: Little is known on factors associated with switching and combination use of antidepressants. Our aim was to describe such use and to analyse the association with socioeconomic factors and level of care in Swedish adults aged 20-34 years. METHODS: Individuals, aged 20-34 years, who purchased an antidepressant in January-June 2006, and who had not purchased any antidepressant in the preceding 6 months (n = 24,897) were followed from 6 up to 12 months. Among those who purchased ≥ 2 antidepressant substances, switchers were defined as those who did not fulfil the requirements for combination use. Data on purchased antidepressants and socioeconomic characteristics were obtained from the Swedish Prescribed Drug Register and Statistics Sweden. The association between (i) ≥ 2 antidepressants or (ii) switching, respectively, and socioeconomic factors as well as level of care was analysed with multiple logistic regression. RESULTS: A total of 4254 individuals (17%) purchased ≥ 2 antidepressant substances, and the remaining 20,643 (83%) purchased one antidepressant. The adjusted odds ratio (OR) for purchase of ≥ 2 antidepressants (vs. purchase of one antidepressant only) was higher among those who started on mirtazapine compared with selective serotonin re-uptake inhibitors: 2.23 (95% confidence interval: 1.93-2.57), and lower in individuals with high education: 0.64 (0.54-0.75), and shorter length of follow-up: 0.73 (0.62-0.85). Among those with ≥ 2 antidepressants, 71.6% were classified as switchers. The adjusted OR for switching (vs. combination use) were higher among divorced/widows/widowers: 1.61 (1.05-2.49), and lower among individuals with short university education: 0.58 (0.43-0.78), those starting on mirtazapine: 0.78 (0.62-0.97), and when treatment was initiated in psychiatric care: 0.75 (0.63-0.88). CONCLUSIONS: One of six new users purchased at least two antidepressants, the majority were classified as switchers. Purchase patterns were associated with socioeconomic characteristics, in particular level of education, type of first purchased antidepressant, and level of care initiating treatment.

Feasibility of the FINDRISC questionnaire to identify individuals with impaired glucose tolerance in Swedish primary care. A cross-sectional population-based study.

AIM: To evaluate the performance of the FINDRISC questionnaire as a tool to recruit individuals with impaired glucose tolerance for lifestyle intervention programmes. METHODS: A cross-sectional population-based study in primary Health Care Centres in a middle-sized Swedish town. All 9734 individuals, aged 35-75 years, living within a defined area, were invited by mail to fill in and return the FINDRISC questionnaire. Participants with a risk score ≥ 15 (n = 525) were invited to perform an oral glucose tolerance test while those with known diabetes were excluded. RESULTS: In total, 5452 questionnaires (58%) were returned and revealed a mean risk-score of 8.5 ± 4.5 (mean ± SD). We found that 525 participants had a risk-score ≥ 15 and 302 (58%) were further examined with an oral glucose tolerance testing (OGTT). Among them we detected 11% with previously undiagnosed Type 2 diabetes, 16% with impaired glucose tolerance and 29% with impaired fasting glucose. A FINDRISC score ≥ 15 was associated with a positive predictive value of 55% for impaired glucose metabolism (impaired fasting glucose + impaired glucose tolerance + Type 2 diabetes) and of 16% for impaired glucose tolerance, respectively. The positive predictive value for impaired glucose tolerance did not increase to more than 17% when choosing the cut-point 17, while there was a significant increase in the positive predictive value for impaired glucose metabolism (70%). CONCLUSIONS: The FINDRISC questionnaire is a useful instrument for identification of individuals with impaired glucose metabolism but seems less effective for detection of individuals with impaired glucose tolerance. Strategies to find individuals with impaired glucose tolerance for implementation of lifestyle changes in primary care should therefore be developed further.

Obstetric and perinatal risks after the use of donor sperm: A systematic review and meta-analysis.

Donor sperm is widely used in infertility treatments. The purpose of the study was to investigate, whether use of donor sperm in intrauterine insemination (IUI) or in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatments affect maternal and perinatal risks compared with spontaneously conceived pregnancies or use of partner sperm in IUI, IVF or ICSI. We provide a systematic review and meta-analyses on the most clinically relevant obstetric and perinatal outcomes after use of donor sperm compared with partner sperm: hypertensive disorders of pregnancy, preeclampsia, low birth weight, and preterm birth. Our meta-analyses showed an increased risk for preeclampsia (pooled adjusted odds ratio (aOR) 1.77, 95% CI 1.26-2.48) and hypertensive disorders of pregnancy (pooled aOR 1.55, 95%, CI 1.20-2.00) in pregnancies resulting from IUI with donor sperm compared with IUI with partner sperm. No increased risk was seen for low birth weight or preterm birth after the use of donor sperm in IUI compared with the use of partner sperm in IUI. Subgroup analysis for singletons only did not change these results. The meta-analysis on low birth weight showed a lower risk after in IVF with donor sperm compared with IVF with partner sperm (pooled aOR 0.89, 95% CI 0.83-0.94). For hypertensive disorders of pregnancy, preeclampsia and preterm birth, no difference was found between IVF with donor sperm vs. partner sperm. Patients need to be informed about the moderately increased risk of hypertensive disorders of pregnancy and preeclampsia in pregnancies after IUI with donor sperm.

The Indian and Nepalese programmes of indoor residual spraying for the elimination of visceral leishmaniasis: performance and effectiveness.

Although, when applied under controlled conditions in India and Nepal, indoor residual spraying (IRS) has been found to reduce sandfly densities significantly, it is not known if IRS will be as effective when applied generally in these countries, via the national programmes for the elimination of visceral leishmaniasis. The potential benefits and limitations of national IRS programmes for the control of sandflies were therefore evaluated in the districts of Vaishali (in the Indian state of Bihar), Sarlahi (in Nepal) and Sunsari (also in Nepal). The use of technical guidelines, levels of knowledge and skills related to spraying operations, insecticide bio-availability on the sprayed surfaces, concentrations of the insecticide on the walls of sprayed houses, insecticide resistance, and the effectiveness of spraying, in terms of reducing sandfly densities within sprayed houses (compared with those found in unsprayed sentinel houses or control villages) were all explored. It was observed that IRS programme managers, at district and subdistrict levels in India and Nepal, used the relevant technical guidelines and were familiar with the procedures for IRS operation. The performance of the spraying activities, however, showed important deficiencies. The results of bio-assays and the chemical analysis of samples from sprayed walls indicated substandard spraying and suboptimal concentrations of insecticide on sprayed surfaces. This was particularly obvious at one of the Nepali study sites (Sunsari district), where no significant vector reduction was achieved. Sandfly resistance to the insecticide used in India (DDT) was widespread but the potential vectors in Nepal remained very susceptible towards a pyrethroid similar to the one used there. The overall short-term effectiveness of IRS was found to be satisfactory in two of the three study sites (in terms of reduction in the densities of the sandfly vectors). Unfortunately, the medium-term evaluation, conducted 5 months after spraying, was probably made invalid by flooding or lime plastering in the study areas. Preparation for, and the monitoring of, the IRS operations against sandfly populations in India and Nepal need to be improved.

In Search of Patient Zero: Visual Analytics of Pathogen Transmission Pathways in Hospitals.

Pathogen outbreaks (i.e., outbreaks of bacteria and viruses) in hospitals can cause high mortality rates and increase costs for hospitals significantly. An outbreak is generally noticed when the number of infected patients rises above an endemic level or the usual prevalence of a pathogen in a defined population. Reconstructing transmission pathways back to the source of an outbreak - the patient zero or index patient - requires the analysis of microbiological data and patient contacts. This is often manually completed by infection control experts. We present a novel visual analytics approach to support the analysis of transmission pathways, patient contacts, the progression of the outbreak, and patient timelines during hospitalization. Infection control experts applied our solution to a real outbreak of Klebsiella pneumoniae in a large German hospital. Using our system, our experts were able to scale the analysis of transmission pathways to longer time intervals (i.e., several years of data instead of days) and across a larger number of wards. Also, the system is able to reduce the analysis time from days to hours. In our final study, feedback from twenty-five experts from seven German hospitals provides evidence that our solution brings significant benefits for analyzing outbreaks.

Reducing costs and operational constraints of dengue vector control by targeting productive breeding places: a multi-country non-inferiority cluster randomized trial.

OBJECTIVES: To test the non-inferiority hypothesis that a vector control approach targeting only the most productive water container types gives the same or greater reduction of the vector population as a non-targeted approach in different ecological settings and to analyse whether the targeted intervention is less costly. METHODS: Cluster randomized trial in eight study sites (Venezuela, Mexico, Peru, Kenya, Thailand, Myanmar, Vietnam, Philippines), with each study area divided into 18-20 clusters (sectors or neighbourhoods) of approximately 50-100 households each. Using a baseline pupal-demographic survey, the most productive container types were identified which produced >or=55% of all Ae. aegypti pupae. Clusters were then paired based on similar pupae per person indices. One cluster from each pair was randomly allocated to receive the targeted vector control intervention; the other received the 'blanket' (non-targeted) intervention attempting to reach all water holding containers. RESULTS: The pupal-demographic baseline survey showed a large variation of productive container types across all study sites. In four sites the vector control interventions in both study arms were insecticidal and in the other four sites, non-insecticidal (environmental management and/or biological control methods). Both approaches were associated with a reduction of outcome indicators in the targeted and non-targeted intervention arm of the six study sites where the follow up study was conducted (PPI, Pupae per Person Index and BI, Breteau Index). Targeted interventions were as effective as non-targeted ones in terms of PPI. The direct costs per house reached were lower in targeted intervention clusters than in non-targeted intervention clusters with only one exception, where the targeted intervention was delivered through staff-intensive social mobilization. CONCLUSIONS: Targeting only the most productive water container types (roughly half of all water holding container types) was as effective in lowering entomological indices as targeting all water holding containers at lower implementation costs. Further research is required to establish the most efficacious method or combination of methods for targeted dengue vector interventions.

Pharmacogenomics of CYP2A6, CYP2B6, CYP2C19, CYP2D6, CYP3A4, CYP3A5 and MDR1 in Vietnam.

AIM: The aim of this study was to obtain pharmacogenetic data in a Vietnamese population on genes coding for proteins involved in the elimination of drugs currently used for the treatment of malaria and human immunodeficiency virus/acquired immunodeficiency syndrome. METHOD: The main polymorphisms on the cytochrome P450 (CYP) genes, CYP2A6, CYP2B6, CYP2C19, CYP2D6, CYP3A4 and CYP3A5, and the multi-drug resistance 1 gene (MDR1) were genotyped in 78 healthy Vietnamese subjects. Pharmacokinetic metrics were available for CYP2A6 (coumarin), CYP2C19 (mephenytoin), CYP2D6 (metoprolol) and CYP3As (midazolam), allowing correlations with the determined genotype. RESULTS: In the CYP2 family, we detected alleles CYP2A6*4 (12%) and *5 (15%); CYP2B6*4 (8%), *6 (27%); CYP2C19*2 (31%) and *3 (6%); CYP2D6*4, *5, *10 (1, 8 and 44%, respectively). In the CYP3A family, CYP3A4*1B was detected at a low frequency (2%), whereas CYP3A5 *3 was detected at a frequency of 67%. The MDR1 3435T allele was present with a prevalence of 40%. Allele proportions in our cohort were compared with those reported for other Asian populations. CYP2C19 genotypes were associated to the S-4'-OH-mephenytoin/S-mephenytoin ratio quantified in plasma 4 h after intake of 100 mg mephenytoin. While CYP2D6 genotypes were partially reflected by the alpha-OH-metroprolol/metoprolol ratio in plasma 4 h after dosing, no correlation existed between midazolam plasma concentrations 4 h post-dose and CYP3A genotypes. CONCLUSIONS: The Vietnamese subjects of our study cohort presented allele prevalences in drug-metabolising enzymes that were generally comparable with those reported in other Asian populations. Deviations were found for CYP2A6*4 compared to a Chinese population (12 vs. 5%, respectively; P = 0.023), CYP2A6*5 compared with a Korean population (15 vs. <1%, respectively; P < 0.0001), a Malaysian population (1%; P < 0.0001) and a Chinese population (1%; P < 0.0001); CYP2B6*6 compared with a Korean population (27 vs. 12%; P = 0.002) and a Japanese population (16%; P = 0.021). Pharmacokinetic metrics versus genotype analysis reinforces the view that the predictive value of certain globally common variants (e.g. CYP2D6 single nucleotide polymorphisms) should be evaluated in a population-specific manner.

Care-seeking in the development of severe community acquired pneumonia in Ugandan children.

BACKGROUND: Improved case management of paediatric pneumonia is recognised as a key strategy for pneumonia control. Since symptoms of pneumonia and malaria often overlap, there are concerns that children with pneumonia are treated with antimalarial drugs. There is a need to describe how children with severe pneumonia have been managed prior to their arrival at hospital, including possible risks of developing more severe disease. METHODS: A case-series study of 140 children, aged 2-59 months, with severe radiologically verified pneumonia at Mulago Hospital, Kampala was undertaken. Caretakers were interviewed about initial symptoms, treatment given and care sought. Using WHO definitions, children were clinically classified as having severe or very severe pneumonia. RESULTS: The children had been ill for a median of 7 days before arrival at hospital, 90/140 (64%) had received treatment at home, and 72/140 (51%) had seen another health-care provider prior to presentation at hospital. Altogether, 32/140 (23%) children had reportedly received antibiotics only prior to admission, 18/140 (13%) had received anti-malarials only and 35/140 (25%) had received both. Being classified as very severe pneumonia was more common among children who had received anti-malarials only (OR 5.5, 1.8-16.4). CONCLUSIONS: Although the majority of caretakers were able to recognise the key symptoms of pneumonia, they did not respond with any immediate care-giving action. Since progression from first recognition of pneumonia symptoms to severe disease is rapid, management guidelines regarding timing of care-seeking need to be clearly defined. The reason why children who sought health facility care failed to improve should be investigated. Meanwhile, there is a need to increase caretakers' and health workers' awareness of the urgency to act promptly when key pneumonia symptoms are observed.