More than time: travel time to the delivery ward and maternal outcomes - onset of labour, postpartum haemorrhage and obstetric anal sphincter injury.

BACKGROUND: Closing delivery units increases travel time for some women. Whether increased travel time is associated with maternal outcomes is important for understanding the consequences of such closures. Previous studies are limited in measuring travel time and restricted to the outcome of caesarean section. METHODS: Our population-based cohort includes data from the Swedish Pregnancy Register for women giving birth between 2014 and 2017 (N = 364,630). We estimated travel time from home to the delivery ward using coordinate pairs of actual addresses. The association between travel time and onset of labour was modelled using multinomial logistic regression, and logistic regression was used for the outcomes postpartum haemorrhage (PPH) and obstetric anal sphincter injury (OASIS). FINDINGS: Over three-quarters of women had ≤30 min travel time (median 13.9 min). Women who travelled ≥60 min arrived to care sooner and laboured there longer. Women with further to travel had increased adjusted odds ratio (aOR) of having an elective caesarean section (31-59 min aOR 1.11; 95% confidence interval [CI] 1.07-1.16; ≥60 min aOR 1.25; 95% CI 1.16-1.36) than spontaneous onset of labour. Women (at full term with spontaneous onset) living ≥60 min away had reduced odds of having a PPH (aOR 0.84; 95% CI 0.76-0.94) or OASIS (aOR 0.79; 95% CI 0.66-0.94). INTERPRETATION: Longer travel time increased the odds of elective caesarean section. Women with furthest to travel arrived sooner and spent more time in care; although they had a lower risk of PPH or OASIS, they also tended to be younger, have a higher body mass index and were Nordic born.

The changing epidemiology of community-acquired pneumonia: nationwide register-based study in Sweden.

BACKGROUND: There is limited evidence on the impact of pneumococcal conjugate vaccine childhood immunization programmes (PCV-CIP) on community-acquired pneumonia (CAP) in individuals with underlying diseases. METHODS: A nationwide cohort study using Swedish health registers to assess the incidence of hospitalization with all-cause (AC-CAP) and pneumococcal or lobar (PL-CAP) CAP between 2005 and 2015, in relation to PCV-CIP introduction in 2007-09. RESULTS: In total, 303 691 episodes of AC-CAP occurred, of which 14 225 were PL-CAP. Comparing before (2005-06) with after (2014-15) PCV-CIP, relative incidence reductions were 36% (95% Confidence Interval 32-40), 20% (14-25) and 16% (11-22) of AC-CAP for age groups < 2, 2-4 and 5-17 years, respectively, with similar reductions in young children with and without comorbidities. The reductions were more pronounced for PL-CAP. In the age groups 40-64, 65-74, 75-84 and ≥85 years there were relative increases of 11% (8-14), 18% (15-22), 15% (12-17) and 30% (27-34) of AC-CAP, respectively, but these increases were attenuated after adjustment for admittance practices using four control conditions. In adults with comorbidities, there was an increase in incidence of AC-CAP, and PL-CAP, in contrast to adults without reported underlying diseases where the incidence was stable or diminished for some age groups. Over the study period, there was an increased proportion of pneumonia patients with underlying diseases in all ages. CONCLUSION: This emphasizes that direct preventive interventions should be targeted towards individuals with underlying diseases. Future studies should investigate reasons for the observed increased risk in adults with comorbidities, for example due to pneumococcal nonvaccine serotypes, or other pathogens, preferentially affecting subjects with underlying diseases.

A coordinated cross-disciplinary research initiative to address an increased incidence of narcolepsy following the 2009-2010 Pandemrix vaccination programme in Sweden.

In response to the 2009-2010 influenza A(H1N1)pdm09 pandemic, a mass vaccination programme with the AS03-adjuvanted influenza A(H1N1) vaccine Pandemrix was initiated in Sweden. Unexpectedly, there were a number of narcolepsy cases amongst vaccinated children and adolescents reported. In this review, we summarize the results of a joint cross-disciplinary national research effort to investigate the adverse reaction signal from the spontaneous reporting system and to better understand possible causative mechanisms. A three- to fourfold increased risk of narcolepsy in vaccinated children and adolescents was verified by epidemiological studies. Of importance, no risk increase was observed for the other neurological and autoimmune diseases studied. Genetic studies confirmed the association with the allele HLA-DQB1*06:02, which is known to be related to sporadic narcolepsy. Furthermore, a number of studies using cellular and molecular experimental models investigated possible links between influenza vaccination and narcolepsy. Serum analysis, using a peptide microarray platform, showed that individuals who received Pandemrix exhibited a different epitope reactivity pattern to neuraminidase and haemagglutinin, as compared to individuals who were infected with H1N1. Patients with narcolepsy were also found to have increased levels of interferon-gamma production in response to streptococcus-associated antigens. The chain of patient-related events and the study results emerging over time were subjected to intense nationwide media attention. The importance of transparent communication and collaboration with patient representatives to maintain public trust in vaccination programmes is also discussed in the review. Organizational challenges due to this unexpected event delayed the initiation of some of the research projects, still the main objectives of this joint, cross-disciplinary research effort were reached, and important insights were acquired for future, similar situations in which a fast and effective task force may be required to evaluate vaccination-related adverse events.

Knowledge and understanding of antibiotic resistance and the risk of becoming a carrier when travelling abroad: a qualitative study of Swedish travellers.

BACKGROUND: Increasing globalisation, with the migration of people, animals and food across national borders increases the risk of the spread of antibiotic-resistant bacteria. To avoid becoming a carrier of antibiotic-resistant bacteria when travelling, knowledge about antibiotic resistance is important. MATERIALS AND METHODS: We aimed to describe the knowledge and understanding of antibiotic-resistant bacteria, and of the risk for becoming a carrier of such bacteria, among Swedish travellers before their travel to high-risk areas. A questionnaire with three open-ended questions was distributed to 100 individuals before departure. RESULTS: The travellers' answers were analysed using content analysis, resulting in the theme 'To be an insecure traveller who takes control over one's own journey'. Our results showed that the travellers were aware of what the term 'antimicrobial resistance' meant, but did not understand its real significance, nor the consequences for the individual nor for society. They also distanced themselves from the problem. Few thought that their travel would entail a risk of becoming a carrier of resistant bacteria. The lack of knowledge caused an uncertainty among the travellers, whom tried to master the situation by using coping strategies. They proposed a number of measures to prevent carriership. The measures were general and primarily aimed at avoiding illness abroad, particularly acute gastro-intestinal infection. CONCLUSIONS: In health care and vaccination clinics, there is a need for improved information for persons intending to travel to high-risk areas, both about the risks of contracting antibiotic-resistant bacteria and about effective preventive measures.

Individual maternal and child exposure to antibiotics in hospital - a national population-based validation study.

AIM: Exposure to antibiotics in early life may affect future health. Most antibiotics are prescribed in outpatient care, but inpatient exposure is also important. We estimated how specific diagnoses in hospitals corresponded to individual antibiotic exposure. METHODS: All pregnant women and children from birth to 5 years of age with infectious diseases and common inpatient diagnoses between July 2005 and November 2011 were identified from the Swedish National Patient Register. Random samples of individuals from predefined groups were drawn, and medical records received from the clinics were manually reviewed for antibiotics. RESULTS: Medical records for 4319 hospital visits were requested and 3797 (88%) were received. A quarter (25%) of children diagnosed as premature had received antibiotics, and in children from one to 5 years of age, diagnoses associated with bacterial infections were more commonly treated with antibiotics (62.4-90.6%) than those associated with viruses (6.3-22.2%). Pregnant women who had undergone a Caesarean section were more likely to be treated with antibiotics than those who had had a vaginal delivery (40.1% versus 11.1%). CONCLUSION: This study defines the proportion of new mothers and young children who received individual antibiotic treatment for specific inpatient diagnoses in Sweden and provides a useful basis for future studies focusing on antibiotic use.

Prevailing effectiveness of the 2009 influenza A(H1N1)pdm09 vaccine during the 2010/11 season in Sweden.

Sixty per cent of the Swedish population received the monovalent AS03-adjuvanted pandemic influenza vaccine in the autumn of 2009. We assessed the age-specific effectiveness of this pandemic vaccine against hospitalisation with laboratory-confirmed influenza A(H1N1)pdm09 during the season 2010/11, in the age group from six months to 64 years in Sweden. The screening method was applied to available surveillance data. Our results suggest a prevailing effectiveness of 72% (95% confidence interval (CI): 63­80%) with the highest effectiveness among children, six months to nine years-old (92%, 95%CI: 80­97%). However, there were limitations in data quality and study design due to the lack of systematic recording of administered vaccinations, which underline the importance of preparing for an evaluation when planning for large public health actions. Despite these limitations, we believe the results reflect true, high prevailing vaccine effectiveness. Indeed, there were fewer deaths caused by influenza and the impact of influenza on intensive care units was less severe during the 2010/11 season in Sweden than in countries with lower pandemic vaccination coverage. The association between the pandemic vaccine and narcolepsy has increased the importance of assessing the risks and benefits of the vaccination; studies on the effectiveness and the duration of protection are needed for this.

Fetal growth and risk of childhood asthma and allergic disease.

INTRODUCTION: Early genetic and environmental factors have been discussed as potential causes for the high prevalence of asthma and allergic disease in the western world, and knowledge on fetal growth and its consequence on future health and disease development is emerging. OBJECTIVE: This review article is an attempt to summarize research on fetal growth and risk of asthma and allergic disease. Current knowledge and novel findings will be reviewed and open research questions identified, to give basic scientists, immunologists and clinicians an overview of an emerging research field. METHODS: PubMed-search on pre-defined terms and cross-references. RESULTS: Several studies have shown a correlation between low birth weight and/or gestational age and asthma and high birth weight and/or gestational age and atopy. The exact mechanism is not yet clear but both environmental and genetic factors seem to contribute to fetal growth. Some of these factors are confounders that can be adjusted for, and twin studies have been very helpful in this context. Suggested mechanisms behind fetal growth are often linked to the feto-maternal circulation, including the development of placenta and umbilical cord. However, the causal link between fetal growth restriction and subsequent asthma and allergic disease remains unexplained. New research regarding the catch-up growth following growth restriction has posited an alternative theory that diseases later on in life result from rapid catch-up growth rather than intrauterine growth restriction per se. Several studies have found a correlation between a rapid weight gain after birth and development of asthma or wheezing in childhood. CONCLUSION AND CLINICAL RELEVANCE: Asthma and allergic disease are multifactorial. Several mechanisms seem to influence their development. Additional studies are needed before we fully understand the causal links between fetal growth and development of asthma and allergic diseases.

Guidelines for the management of adult lower respiratory tract infections--summary.

This document is an update of Guidelines published in 2005 and now includes scientific publications through to May 2010. It provides evidence-based recommendations for the most common management questions occurring in routine clinical practice in the management of adult patients with LRTI. Topics include management outside hospital, management inside hospital (including community-acquired pneumonia (CAP), acute exacerbations of COPD (AECOPD), acute exacerbations of bronchiectasis) and prevention. The target audience for the Guideline is thus all those whose routine practice includes the management of adult LRTI.

Guidelines for the management of adult lower respiratory tract infections--full version.

This document is an update of Guidelines published in 2005 and now includes scientific publications through to May 2010. It provides evidence-based recommendations for the most common management questions occurring in routine clinical practice in the management of adult patients with LRTI. Topics include management outside hospital, management inside hospital (including community-acquired pneumonia (CAP), acute exacerbations of COPD (AECOPD), acute exacerbations of bronchiectasis) and prevention. Background sections and graded evidence tables are also included. The target audience for the Guideline is thus all those whose routine practice includes the management of adult LRTI.

Impaired fetal growth decreases the risk of childhood atopic eczema: a Swedish twin study.

BACKGROUND: Studies have found associations between birth weight and risk of atopic eczema or allergic rhinitis (AR), although this could be due to confounding. OBJECTIVE: We sought to evaluate associations between fetal growth and the risk of atopic eczema or AR in childhood, controlling for gestational age (GA), shared (familial) environmental and genetic factors. METHODS: Data on atopic eczema, AR, birth characteristics and confounders were collected from registers and telephone interviews with the parents of 9- and 12-year-old twins. Firstly, cohort analyses on all twins (eczema n=10 132 and AR n=10 896) were performed. Secondly, to control for genetic and shared environment, co-twin-control analyses were performed in twin pairs discordant for atopic eczema (n=480) and AR (n=332). RESULTS: The rate of atopic eczema increased with birth weight, from 12.6% in twin children <2000 g to 17.3% in children >or=3500 g. The rate of AR varied between 7.8% and 8.8%. In the cohort analyses, the odds ratio (OR) for atopic eczema was 1.62 (95% CI: 1.27-2.06) for 500 g increase in birth weight and 1.00 (95% CI: 0.75-1.33) for AR. In co-twin-control analyses on atopic eczema, OR was 3.93 (95% CI: 1.55-9.98) for 500 g increase in birth weight, with no significant difference between monozygotic and dizygotic twins (P=0.84). CONCLUSIONS: We found a positive association between fetal growth and childhood atopic eczema, but not AR, independent of GA, shared environmental and genetic factors. This indicates fetal growth affects the immune system, and supports further studies on early mechanisms.

Validity of routine surveillance data: a case study on Swedish notifications of methicillin-resistant Staphylococcus aureus.

Surveillance of communicable diseases is a public health corner stone. Routine notification data on communicable diseases are used as a basis for public health action as well as for policy making. While there are agreed standards for evaluating the performance of surveillance systems, it is rarely possible to analyse the validity of the data entered into these systems. In this study we compared data on all Swedish cases of methicillin-resistant Staphylococcus aureus (MRSA) routinely notified between 2000 and 2003 with follow-up information collected for each of these cases as part of a public health project. The variables Reason for testing (clinical sample, contact tracing, screening of risk group), Clinical presentation (disease, colonisation), Transmission setting (healthcare-acquired, community-acquired), Country of acquisition (Sweden, abroad) and Risk-occupation (yes, no) were analysed for sensitivity, positive predictive value and completeness of answers. The sensitivity varied between 23% and 83%, the positive predictive values were generally higher (55% to 97%), while missing answers varied from 11% to 59%. The proportion of community-acquired cases was markedly higher when excluding either cases of MRSA colonisation or cases found through public health-initiated activities (contact tracing or screening of risk groups). We conclude that the quality of routine surveillance data may be inadequate for in-depth epidemiological analyses. This should be taken into account when interpreting routine surveillance figures. Whether or not the case definition includes cases of MRSA colonisation may have a significant impact on population-wide estimates of MRSA occurrence.

Severity of illness scoring systems in patients with bacteraemic pneumococcal pneumonia: implications for the intensive care unit care.

Severity of illness scoring systems are useful for decisions on the management of patients with community-acquired pneumonia (CAP), including assessing the need for intensified therapy and monitoring, or for intensive care unit (ICU) admission. We compared the accuracy of the Pneumonia Severity Index (PSI), the CURB-65 and CRB-65 score, the modified-American Thoracic Society score (ATS), the IDSA/ATS guidelines and the Pitt Bacteraemia score (PBS) in evaluating severity of illness in 766 patients with bacteraemic pneumococcal pneumonia. We evaluated the sensitivity and specificity, the positive predictive value (PPV) and the negative predictive value (NPV) and the accuracy of the classification in predicting 14-day mortality. The PSI and the IDSA/ATS guidelines were the most sensitive whereas the PBS and modified-ATS scoring systems were the most specific in predicting mortality. The NPV was comparable for all four scoring systems (all above 90%), but the PPV was highest for PBS (54.2%) and lowest for PSI (23.2%). The predictive accuracy and discriminating power as measured by the receiver-operating characteristic (ROC) curve was highest for the PBS. Both the modified-ATS and the PBS scoring systems identified those patients who might benefit most from intensified care and monitoring. The PBS and modified-ATS proved superior to the IDSA/ATS guidelines, CURB-65 and CRB-65 with respect to their specificity and PPV. The low PPV of the PSI rendered it not usable as a parameter for decision-making in severely-ill patients with pneumococcal bacteraemia.

Association of serotypes of Streptococcus pneumoniae with disease severity and outcome in adults: an international study.

BACKGROUND: The introduction of conjugate pneumococcal vaccination for children has reduced the burden of invasive disease due to pneumococcal conjugate vaccine (PCV) types (i.e., serotypes 9V, 14, 6B, 18C, 23F, 19F, and 4) in adults. As nonvaccine serotypes become predominant causes of invasive disease among adults, it is necessary to evaluate the disease severity and mortality associated with infection due to nonvaccine serotypes, compared with PCV serotypes, in adults. METHODS: The association of pneumococcal serotype and host-related variables with disease severity and mortality was statistically examined (with multivariable analysis) in 796 prospectively enrolled, hospitalized adult patients with bacteremia due to Streptococcus pneumoniae. RESULTS: In multivariate analyses of risk in patients with invasive pneumococcal disease, older age (age, > or = 65 years; P = .004), underlying chronic disease (P = .025), immunosuppression (P = .035), and severity of disease (P < .001) were significantly associated with mortality; no association was found between nosocomial infection with invasive serotypes 1, 5, and 7 and mortality. The risk factors meningitis (P = .001), suppurative lung complications (P < or = .001), and preexisting lung disease (P = .051) were significantly associated with disease severity, independent of infecting serotype. No differences were seen in disease severity or associated mortality among patients infected with PCV serotypes, compared with patients infected with nonvaccine serotypes. CONCLUSIONS: Our data support the notion that host factors are more important than isolate serotype in determining the severity and outcome of invasive pneumococcal disease and that these outcomes are unlikely to change in association with nonvaccine serotype infection in the post-conjugate vaccine era.

Hospital-acquired pneumonia guidelines in Europe: a review of their status and future development.

Hospital-acquired pneumonia (HAP) is the most common healthcare-acquired infection contributing to death. Effective management requires accurate diagnosis, administration of a suitable antibiotic regimen early in infection and implementation of prevention strategies. In recent years, there has been a rapid increase in the number of country-specific HAP guidelines in Europe, which vary in their formulation, coverage of different disease aspects and overall recommendations. Development of comprehensive pan-European HAP guidelines would rationalize the conflicting proposals, provide a useful resource and limit guideline proliferation. However, careful consideration needs to be given to the principles of guideline development to ensure that the output is rigorous, broadly applicable and facilitates update as new data becomes available. The use of an evidence-based approach to HAP guideline development is optimal, but is compromised by limitations in the supporting data. The implementation of a formalized evidence grading system is key to introducing consistency into the guideline development process. Pan-European guidelines should provide recommendations on core aspects of HAP common to all treatment settings and locations, and reflect the differing perspectives of the countries involved. Given the different antibiotic susceptibility profiles across Europe, such guidelines should provide general treatment recommendations suitable for local adaptation. The development of such guidelines represents an ideal time to identify priorities for European research, by addressing controversies and identifying previously unconsidered aspects of HAP. Establishing a pan-European consensus on core processes of care should be viewed as an impetus for change to improve clinical practices and should include a suitable implementation strategy.

Influenza vaccination and mortality: prospective cohort study of the elderly in a large geographical area.

The 50% reduced overall mortality previously associated with influenza vaccination among the elderly was based on studies neither fully taking into account systematic differences between individuals who accept or decline vaccination nor encompassing the entire general population. A population-based prospective cohort study was performed in Stockholm County (Sweden), including all persons aged > or =65 yrs (n = approximately 260,000), over three influenza seasons: 1998/1999, 1999/2000 and 2000/2001. The relative risks of mortality among vaccinated versus unvaccinated individuals were estimated using Cox's proportional hazards regression adjusted for, and stratified by, demographic factors and comorbid conditions during the three seasons and the respective following off-seasons. Influenza vaccination was associated with an unadjusted reduction in all-cause mortality during the three seasons of 50, 46 and 42%, respectively, which decreased to 14, 19 and 1%, respectively, following adjustment for confounders and differences in mortality between vaccinated and unvaccinated individuals following the influenza season. The numbers needed to treat to prevent one death, during the three seasons, were 297, 158 and 743, respectively. Vaccination remains the most important measure for prevention of influenza complications in elderly people, although the effectiveness in reducing all-cause mortality in elderly persons is lower than previously thought.

Non-response to specific serotypes likely cause for failure to 23-valent pneumococcal polysaccharide vaccine in the elderly.

During a randomised controlled trial with the 23-valent pneumococcal vaccine in older persons, antibody concentrations and opsonophagocytic activity (OPA) were compared between eight patients who developed culture-verified pneumococcal pneumonia and 38 controls, matched for age, sex and vaccination status. Patients who developed pneumococcal pneumonia did not respond with a significant increase of antibody concentration (>1microg/ml) post-vaccination to the infecting serotype, but responded equally well as controls to most other serotypes. Neither was there any significant difference in the OPA post-vaccination between patients and controls. In conclusion, the 23-valent pneumococcal vaccine should be regarded as 23 different vaccines, rather than one. Older persons who fail to respond to one serotype may well be protected against infection by the other 22 serotypes.

Addition of a macrolide to a ss-lactam in bacteremic pneumococcal pneumonia.

In the study presented here, data collected prospectively from 340 adult patients hospitalised in five countries with bacteremic pneumococcal CAP and treated with a ss-lactam +/- a macrolide were analysed retrospectively to evaluate the efficacy of this antimicrobial combination. Univariate and multivariate analyses revealed no significant effect on case fatality rate when a macrolide/ss-lactam regimen was used as initial therapy. Results were not affected by severity of illness, or by excluding patients who died within 2 days of admission. Identified predictors of death in a multivariate regression model were age >65 years (OR=2.6), two or more lung lobes affected (OR=2.2), and severity of disease as estimated using the acute physiology score (APS)>8.

Prognostic score systems and community-acquired bacteraemic pneumococcal pneumonia.

The aim of this study was to evaluate the accuracy of three score systems: the pneumonia severity index (PSI); CURB-65 (confusion; urea >7 mM; respiratory rate > or =30 breaths x min(-1); blood pressure <90 mmHg systolic or < or =60 mmHg diastolic; aged > or =65 yrs old); and modified American Thoracic Society rule for predicting intensive care unit (ICU) need and mortality due to bacteraemic pneumococcal pneumonia. All adult patients (n = 114) with invasive pneumococcal pneumonia at the Karolinska University Hospital, Sweden, 1999-2000, were included in the study. Severity scores were calculated and the independent prognostic importance of different variables was analysed by multiple regression analyses. PSI > or = IV, CURB-65 > or = 2, and the presence of one major or more than one minor risk factor in mATS all had a high sensitivity, but somewhat lower specificity for predicting death and ICU need. The death rate was 12% (13 out of 114). Severity score and treatment in departments other than the Dept of Infectious Diseases were the only factors independently correlated to death. Patients treated in other departments more often had severe underlying illnesses and were more severely ill on admission. However, a significant difference in death rates remained after adjustment for severity between the two groups. In conclusion, all score systems were useful for predicting the need for intensive care unit treatment and death due to bacteremic pneumococcal pneumonia. The pneumonia severity index was the most sensitive, but CURB-65 was easier to use.

Endocarditis and pericarditis complicating pneumococcal bacteraemia, with special reference to the adhesive abilities of pneumococci: results from a prospective study.

The incidence of pneumococcal cardiac infections is unknown and the pathogenicity of such complications is poorly understood. In a prospective, international, observational study, eight of 844 patients hospitalised with Streptococcus pneumoniae bacteraemia developed endocarditis (n = 5) or pericarditis (n = 3). The clinical and microbiological characteristics of these patients were compared with those of control patients. The corresponding incidence of pneumococcal endocarditis was c. 1-3/1 million inhabitants/year. There was no common pattern in the medical history of patients with an infectious cardiac complication. The severity of illness upon admission was comparable with that for patients without infectious cardiac complications, as was the 14-day mortality rate (25% and 17%, respectively). For encapsulated S. pneumoniae, no significant differences were found between patients with infectious cardiac complications and controls in adherence assays. However, non-encapsulated S. pneumoniae showed higher hydrophobicity and increased adherence to human epithelial cells.