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.

Narrow-spectrum ß-lactam monotherapy in hospital treatment of community-acquired pneumonia: a register-based cohort study.

OBJECTIVES: To assess the clinical effect of empirical treatment with narrow-spectrum ß-lactam monotherapy (NSBM) versus broad-spectrum ß-lactam monotherapy (BSBM) in non-severe community-acquired pneumonia (CAP). METHODS: Hospitalized patients ≥18 years with CAP who received initial NSBM or BSBM, with a severity score according to CRB-65≤2 (C=confusion, R=respiratory rate >30/min, B=systolic blood pressure <90 mmHg or diastolic blood pressure ≤60 mmHg, 65= ≥65 years), in the Swedish Pneumonia Register from 2008 to 2011 were included. Primary outcome was 30-day mortality. Secondary outcomes were 90-day mortality, treatment at intensive care unit (ICU), and length of stay (LOS). Propensity score matching was performed to account for differences in baseline characteristics. RESULTS: There were 5961 patients with CRB-65≤1 and 1344 patients with CRB-65=2. In the propensity score matched cohorts the 30-day mortality was 40/1827 (2.2%) with NSBM and 56/1827 (3.1%) with BSBM in CRB-65≤1, and 57/524 (10.9%) and 51/524 (9.7%), respectively, in CRB-65=2. No significant differences in 30-day mortality were observed between NSBM and BSBM in patients with CRB-65≤1 or CRB-65=2, OR 1.41 (95% CI 0.94-2.14) and 0.88 (95% CI 0.59-1.32), respectively. There was no significant difference in 90-day mortality. Patients who received BSBM were more often treated at ICU and had longer LOS. CONCLUSIONS: Empirical NSBM appears to be effective in the majority of hospitalized immunocompetent adults with non-severe CAP and should be further evaluated in randomized trials.

Soluble CD27 induces IgG production through activation of antigen-primed B cells.

OBJECTIVES: High levels of soluble CD27 (sCD27), a marker of immune activation, are found in several infectious [including human immunodeficiency virus type-I (HIV-1)] and autoimmune diseases; however, a direct biological effect of sCD27 on B cells has not been established. The aim of this study was to investigate whether sCD27, by binding to CD70, can induce immunoglobulin G (IgG) production from B cells. METHODS: B cells from healthy and HIV-1-infected individuals were cultured with recombinant human sCD27 (rhsCD27), and IgG production was measured. The role of rhsCD27 in inducing the expression of transcription factors involved in plasma cell differentiation was evaluated. Furthermore, we investigated the impact of different cytokines on the modulation of CD70 expression on B cells and the relationship between levels of IgG and sCD27 in serum from healthy and HIV-1-infected individuals. RESULTS: We demonstrated that rhsCD27 induced IgG production from antigen-primed (CD27+) B cells. This effect was mediated by rhsCD27 binding to CD70 on B cells leading to activation of Blimp-1 and XBP-1, transcription factors associated with plasma cell differentiation. We found a significant correlation between levels of serum sCD27 and IgG in HIV-1-infected individuals and healthy controls. CONCLUSIONS: sCD27 may act to enhance immunoglobulin production and differentiation of activated memory or recently antigen-experienced B cells, thus providing an activation signal to antigen-experienced B cells. This mechanism may operate during autoimmune and chronic infectious diseases, situations in which continuous immune activation leads to upregulation of CD70 expression and increased sCD27 cleavage.

The effect of polymer adsorption on the wetting properties of partially hydrophobized magnetite.

Upon reverse flotation of iron ore, the surface of the iron ore concentrate may become partially hydrophobized due to adsorption of flotation collector, which is facilitated by the calcium ions present in the process water. Hydrophobic areas on the concentrate surface may introduce problems in subsequent pelletization of the concentrate. A possible way to restore the wettability of the surface could be by modifying the surface with a hydrophilic polymer. The effect of hydrophilic polymers of different types, viz. cationic, anionic, and non-ionic, on the wettability of the magnetite surface after adsorption of a surfactant was investigated. Although all the polymers could adsorb on magnetite at pH 8.5, the contact angle measurements revealed that only anionic ammonium polyacrylate could decrease the contact angle of synthetic magnetite after surfactant adsorption to a level close to that of as-synthesized magnetite. Such effect was probably achieved due to shielding of the hydrophobic surfactant chains from the aqueous phase by hydrophilic polyacrylate molecules. The fact that polyacrylate adsorption on magnetite occurred via calcium ions makes polyacrylate suitable for application in calcium-rich process water. The results presented in this work illustrate that ammonium polyacrylate could be successfully used to improve the wettability of magnetite after adsorption of surfactants.

Cryo-SEM method for the observation of entrapped bubbles and degree of water filling in large wet powder compacts.

There are generally two problems associated with cryogenic scanning electron microscopy (cryo-SEM) observations of large wet powder compacts. First, because water cannot be vitrified in such samples, formation of artefacts is unavoidable. Second, large frozen samples are difficult to fracture but also to machine into regular pieces which fit in standard holders, especially if made of hard materials like ceramics. In this article, we first describe a simple method for planning hard cryo-samples and a low-cost technique for cryo-fracture and transfer of large specimens. Subsequently, after applying the entire procedure to green pellets of iron ore produced by balling, we compare the influence of plunge- and unidirectional freezing on large entrapped bubbles throughout the samples as well as the degree of water filling at the outer surface of the pellets. By carefully investigating the presence of artefacts in large areas of the samples and by controlling the orientation of the sample during freezing and preparation, we demonstrate that unidirectional freezing enables the observation of large entrapped bubbles with minimum formation of artefacts, whereas plunge freezing is preferable for the characterization of the degree of water filling at the outer surface of wet powder compacts. The minimum formation of artefacts was due to the high packing density of the iron ore particles in the matrix.

The effect of calcium ions and sodium silicate on the adsorption of a model anionic flotation collector on magnetite studied by ATR-FTIR spectroscopy.

Previous studies have shown that agglomeration of the magnetite concentrate after reverse flotation of apatite is negatively affected by the collector species adsorbed on the surface of magnetite. In this work, the effect of ionic strength, calcium ions and sodium silicate on the unwanted adsorption of a model anionic flotation collector on synthetic magnetite was studied in situ using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). The amount of collector adsorbed was found to increase with increasing ionic strength at pH 8.5 providing evidence to the contribution of electrostatic forces to the adsorption of the collector. Adding sodium silicate to the system resulted in a threefold decrease in the amount of collector adsorbed compared to when no sodium silicate was added, confirming the depressing activity of sodium silicate on magnetite. Calcium ions were shown to increase the adsorption of both the collector and sodium silicate on magnetite. The depressing effect of sodium silicate on collector adsorption was completely suppressed in the presence of calcium ions under the conditions studied. Furthermore, the amount of collector adsorbed on magnetite from the silicate-collector solution increased 14 times upon addition of calcium ions suggesting that calcium ions in the process water may increase undesired adsorption of the collector on the iron oxide.

Change of colloidal and surface properties of Mytilus edulis foot protein 1 in the presence of an oxidation (NaIO4) or a complex-binding (Cu2+) agent.

Quartz crystal microbalance with dissipation monitoring (QCM-D) was used to study the viscoelastic properties of the blue mussel, Mytilus edulis, foot protein 1 (Mefp-1) adsorbed on modified hydrophobic gold surfaces. The change in viscoelasticity was studied after addition of Cu2+ and Mn2+, which theoretically could induce metal complex formation with 3,4-dihydroxyphenylalanine (DOPA) moieties. We also used NaIO4, a nonmetal oxidative agent known to induce di-DOPA formation. Reduction in viscoelasticity of adsorbed Mefp-1 followed the order of NaIO4 > Cu2+ > buffer control > Mn2+. We also studied the formation of molecular aggregates of Mefp-1 in solution with the use of dynamic light scattering (DLS). We found that addition of Cu2+, but not Mn2+, induced the formation of larger DLS-detectable aggregates. Minor aggregate formation was found with NaIO4. With the analytical resolution of small angle X-ray scattering (SAXS), we could detect differences in the molecular structure between NaIO4- and Cu2+-treated Mefp-1 aggregates. We concluded from this study that Cu2+ could participate in intermolecular cross-linking of the Mefp-1 molecule via metal complex formation. Metal incorporation in the protein most likely increases the abrasion resistance of the Mefp-1 layer. NaIO4, on the other hand, resulted in mainly intramolecular formation of di-DOPA, but failed to induce larger intermolecular aggregation phenomena. The described methodological combination of surface sensitive methods, like QCM-D, and bulk sensitive methods, like DLS and SAXS, generates high resolution results and is an attractive platform to investigate intra- and intermolecular aspects of assembly and cross-linking of the Mefp proteins.

Efficacy of partner notification for Chlamydia trachomatis among young adults in youth health centres in Uppsala County, Sweden.

BACKGROUND: The study was conducted to define the contact-tracing success rate of the partner notification services routinely provided by the community-based youth health centres and the county medical officer for communicable disease control (CMO) in Uppsala County, Sweden. OBJECTIVE: The study had three goals, (i) to register the number of sexual partners routinely reported by each diagnosed index case with CT and the success rate in tracing and testing these partners for CT infection. (ii) To analyse the current notification practices in reporting the number of cases of unsuccessful contact tracing to the CMO. (iii) To determine the contact tracing success rate of the partner notification services provided by the CMO. METHODS: Each diagnosed case of CT is obliged by law to participate in the contact-tracing procedure performed by the physician managing the patient or by a specialised sexually transmitted infection (STI) adviser. Successful contact-tracing is defined as the confirmed attendance of a sexual contact within 12 months of the contact with the index case. RESULTS: The number of CT cases diagnosed by the youth health centres during the study period was 463 (299 females and 164 males). The females reported 660 male sexual contacts and the males reported 386 female contacts. Successful partner notification was achieved for 73% of all sexual contacts. 284 (190 females and 94 males) unsuccessful partner notifications were reported to the CMO of whom 98 (52%) of the female contacts and 20 (21%) of the male contacts were successfully notified by the CMO. However, for 134 (71 females and 63 males) partners, personal details given by the index case were insufficient for identification of the partner. CONCLUSIONS: When asymptomatic, genital CT infection spreads among sexually active young adults with multiple, unidentified sexual partners, appropriate methods of partner notification are not sufficient to achieve its aims at the population level.

Medium- and short-chain dehydrogenase/reductase gene and protein families : the MDR superfamily.

The MDR superfamily with ~350-residue subunits contains the classical liver alcohol dehydrogenase (ADH), quinone reductase, leukotriene B4 dehydrogenase and many more forms. ADH is a dimeric zinc metalloprotein and occurs as five different classes in humans, resulting from gene duplications during vertebrate evolution, the first one traced to ~500 MYA (million years ago) from an ancestral formaldehyde dehydrogenase line. Like many duplications at that time, it correlates with enzymogenesis of new activities, contributing to conditions for emergence of vertebrate land life from osseous fish. The speed of changes correlates with function, as do differential evolutionary patterns in separate segments. Subsequent recognitions now define at least 40 human MDR members in the Uniprot database (corresponding to 25 genes when excluding close homologues), and in all species at least 10888 entries. Overall, variability is large, but like for many dehydrogenases, subdivided into constant and variable forms, corresponding to household and emerging enzyme activities, respectively. This review covers basic facts and describes eight large MDR families and nine smaller families. Combined, they have specific substrates in metabolic pathways, some with wide substrate specificity, and several with little known functions.

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.

Molecular mobility of polymeric implants and acute inflammatory response: an experimental study in mice.

An overlooked factor in biomaterial research is the surface molecular flexibility for polymer based implants. The mobility of the polymer chains provides a way for the surface to adapt itself to the environment. This is relevant when the implant comes in contact with a biological fluid and its constituents. By changing the length of the alkyl side chain of poly(alkyl methacrylates) (PAMAs) an interesting opportunity is provided where it is possible to study the surface molecular mobility without changing the surface hydrophobicity, nor does it introduce any additives or any changes in the degree of polymer cross-linking. Four variants of PAMAs were implanted in the peritoneum of Balb/c mice using a well described setup. End points were taken after 18 h and estimations of inflammatory cell recruitment and implant-associated cells were studied. Relationship between surface molecular mobility and inflammatory cell recruitment as well as surface-associated cells was noted.

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.

Hard core drinking drivers.

The term "hard core" has been used extensively over the past 15 years to identify persons who drink and drive regularly, typically at high blood alcohol levels. This article discusses how the term arose and clarifies what it means, both as a concept and in practice. It describes the characteristics of hard core drinking drivers and estimates their contribution to drinking driver trips, arrests, and crashes. It summarizes current knowledge and recommendations on the most effective means to affect their behavior and reduce their drinking and driving.

Additive preventive effect of influenza and pneumococcal vaccines in elderly persons.

In 1999, all individuals > or = 65 yrs of age (n=258,754) in Stockholm County, Sweden, were offered influenza and pneumococcal vaccination in a prospective study on the effectiveness of these vaccines in reducing the need for hospital treatment and death due to influenza, pneumonia and invasive pneumococcal disease (IPD). Data on hospitalisation and mortality during 1 yr were obtained from the administrative database in Stockholm County Council. Vaccination was performed in 124,702 (48%) subjects; 72,107 had both vaccines, 29,346 only had the influenza vaccine and 23,249 only had the pneumococcal vaccine. Compared with the unvaccinated cohort, a lower incidence of hospitalisation for all endpoint diagnoses was seen in vaccinated persons. An additive effectiveness of vaccination was seen when both vaccines were given, with a reduction of hospital admissions for influenza (37%), pneumonia (29%) and IPD (44%). In-hospital mortality for pneumonia was significantly lower in those who received both vaccines, than in unvaccinated persons. To conclude, vaccination with influenza and pneumococcal vaccines together was effective in reducing the need for hospital admission for influenza and pneumonia. There was a strong indication that pneumococcal vaccination alone, was effective not only in the prevention of invasive pneumococcal disease, but also of pneumonia overall, although to a low degree.

Effects of a large-scale intervention with influenza and 23-valent pneumococcal vaccines in elderly people: a 1-year follow-up.

To assess the effectiveness of influenza and pneumococcal vaccination in reducing hospitalisation and deaths in elderly people, the population aged > or =65 years in Stockholm County, Sweden (n = 259627) were invited to take part in a vaccination campaign with influenza and 23-valent pneumococcal vaccine (PV). A no. of persons (100,242) (vaccinated cohort) were vaccinated with one or both vaccines during the campaign. The incidence of hospital admissions during 1 year after the vaccination campaign, adjusted for sex and age, was significantly lower in the vaccinated than in the unvaccinated cohort for influenza (relative risk [RR] 0.68), pneumonia (RR 0.78), and invasive pneumococcal disease (RR 0.46). In the vaccinated cohort, the in-hospital mortality was lower for pneumonia (RR 0.55), COPD (RR 0.53) and cardiac failure (RR 0.72).

Dynamics of penicillin-susceptible clones in invasive pneumococcal disease.

In a 10-year period, 1987-1997, there was a >4-fold increase in the rate of pneumococcal bacteremia in Sweden. Invasive pneumococcal isolates (n=1136), which were obtained from 18 Swedish clinical microbiology laboratories from 1987 through 1997, and other national and international isolates were serotyped, and their clonal relationships were determined by molecular typing. The increase in invasive pneumococcal disease in Sweden during this period was associated particularly with an increase in isolates of serotypes 1 and 14. A 3-fold increase of type 14 was seen from 1987 through 1992, and a 10-fold increase of type 1 occurred from 1992 through 1997. One dominating penicillin-susceptible clone of type 14 was responsible for the increase of type 14 during the first 5 years. This clone also was found in Canada and the United States and was shown by multilocus sequence typing to correspond to a previously identified hyper-virulent clone. A novel penicillin-susceptible clone of type 1, which was not found among invasive isolates from 1987 or 1992, was responsible for the increase of serotype 1 during the last 5 years. These results illustrate the ability of virulent penicillin-susceptible pneumococcal clones to emerge and spread rapidly within a country.

Negligible adjuvant effect for antibody responses and frequent adverse events associated with IL-12 treatment in humans vaccinated with pneumococcal polysaccharide.

To assess whether co-administration of recombinant human IL-12 (rhIL-12) and 23-valent pneumococcal polysaccharide vaccine (PPV) enhances the antibody response to this T cell-independent antigen, healthy immunocompetent volunteers (n=34, 55-65 years old) were vaccinated intramusculary with PPV and concurrently-treated subcutaneously with either rhIL-12 (1 or 4 microg) or placebo. The increases of total anti-pneumococcal IgG antibodies were numerically higher among the rhIL-12 recipients compared with placebo recipients, but the difference was not significant. The rhIL-12 recipients had a high incidence of local and systemic side effects. Given the lack of convincing evidence that rhIL-12 enhances the antibody response to PPV, the frequency and severity of the side effects was unacceptable.

Effects of a large-scale intervention with influenza and 23-valent pneumococcal vaccines in adults aged 65 years or older: a prospective study.

BACKGROUND: The effectiveness of influenza and pneumococcal vaccination in the prevention of hospital admissions and death has not been assessed prospectively. We have therefore examined the effects of influenza and pneumococcal vaccination in individuals aged 65 years and older in a 3-year prospective study, between Dec 1, 1998 and May 31, 1999. METHODS: All individuals in Stockholm County aged 65 years or older (259,627) were invited to take part in a vaccination campaign against influenza and pneumococcal infection. We recorded for all vaccine recipients (100,242) name, and date of birth, and whether they had been given both or one of the vaccines. All individuals (> or = 65 years) admitted to hospital in Stockholm County with influenza and pneumonia related diagnoses were identified between Dec 1, 1998, and May 31, 1999. FINDINGS: The incidence (per 100,000 inhabitants per year) of hospital treatment was lower in the vaccinated than in the unvaccinated cohort for all diagnoses: 263 versus 484 (-46% [95% CI 34-56]) for influenza; 2199 versus 3097 (-29% [24-34)) for pneumonia; 64 versus 100 (-36% [3-58]) for pneumococcal pneumonia; and 20 versus 40 (-52% [1-77]) for invasive pneumococcal disease. The total mortality was 57% (55-60) lower in vaccinated than in unvaccinated individuals (15.1 vs 34.7 deaths per 1000 inhabitants). INTERPRETATION: These findings show that general vaccination leads to substantial health benefits and to a reduction of mortality from all causes in this age group.

Changes in serotype distribution may hamper efficacy of pneumococcal conjugate vaccines in children.

During the last 10 y we have observed an increased incidence of pneumococcal bacteremia in Sweden. In order to study the serotype distribution over time we collected 1136 invasive pneumococcal isolates from 1987, 1992 and 1997 from Swedish microbiological laboratories. Currently, new pneumococcal conjugate vaccines are being considered for introduction in the general childhood vaccination program in several countries, including Sweden. We studied the potential vaccine coverage rate for the new conjugate vaccines among our Swedish invasive isolates. We found that the serotype distribution fluctuated with time and observed a surprisingly low potential coverage rate for the 7-valent vaccine in Sweden, in contrast to other countries. Therefore we argue that pneumococcal conjugate vaccines have to be tailored to suit current, local serotype patterns and most likely will need to be changed over time.

Recurrence of pneumonia in relation to the antibody response after pneumococcal vaccination in middle-aged and elderly adults.

We have recently studied the efficacy of pneumococcal vaccine in preventing pneumonia recurrences after hospital treatment for community-acquired pneumonia in non-immunocompromised patients aged 50-85 y. Among these patients, we have now compared the antibody response to the pneumococcal vaccine between patients who developed pneumonia (n = 50) and patients without pneumonia recurrences (n = 100), during a mean follow-up period of 32 months after vaccination. The antibody levels of 5 pneumococcal serotypes were measured before, and 4 weeks, 1 y and 3 y after vaccination. A lower risk of pneumonia recurrences was seen in patients with antibody fold increases (FIs) > 4 from pre-vaccination to post-vaccination compared with patients with lower FIs (p = 0.02). The results suggest that in this patient category, the antibody response to pneumococcal vaccination is of importance for the risk of pneumonia recurrence.