High target attainment for ß-lactam antibiotics in intensive care unit patients when actual minimum inhibitory concentrations are applied.

Patients in the intensive care unit (ICU) are at risk for suboptimal levels of ß-lactam antibiotics, possibly leading to poor efficacy. Our aim was to investigate whether the actual minimum inhibitory concentration (MIC) compared to the more commonly used arbitrary epidemiological cut-off values (ECOFFs) would affect target attainment in ICU patients on empirical treatment with broad-spectrum ß-lactam antibiotics and to identify risk factors for not reaching target. In a prospective, multicenter study, ICU patients ≥18 years old and treated with piperacillin/tazobactam, meropenem, or cefotaxime were included. Clinical and laboratory data were recorded. Serum trough antibiotic levels from three consecutive days were analyzed by liquid chromatography-mass spectrometry (LC-MS). The target was defined as the free trough concentration above the MIC (100% fT>MIC). MICECOFF was used as the target and, when available, the actual MIC (MICACTUAL) was applied. The median age of the patients was 70 years old, 52% (58/111) were males, and the median estimated glomerular filtration rate (eGFR) was 48.0 mL/min/1.73 m2. The rate of patients reaching 100% fT > MICACTUAL was higher (89%, 31/35) compared to the same patients using MICECOFF (60%, p = 0.002). In total, 55% (61/111) reached 100% fT > MICECOFF. Increased renal clearance was independently associated to not reaching 100% fT > MICECOFF. On repeated sampling, >77% of patients had stable serum drug levels around the MICECOFF. Serum concentrations of ß-lactam antibiotics vary extensively between ICU patients. The rate of patients not reaching target was markedly lower for the actual MIC than when the arbitrary MIC based on the ECOFF was used, which is important to consider in future studies.

Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease.

BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology. METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls. RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10-15 , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex. CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.

Long-term persistence of a multi-resistant methicillin-susceptible Staphylococcus aureus (MR-MSSA) clone at a university hospital in southeast Sweden, without further transmission within the region.

The objective of this study was to characterise isolates of methicillin-susceptible Staphylococcus aureus (MSSA) with resistance to clindamycin and/or tobramycin in southeast Sweden, including the previously described ECT-R clone (t002) found in Östergötland County, focusing on clonal relatedness, virulence determinants and existence of staphylococcal cassette chromosome (SCC) mec remnants. MSSA isolates with resistance to clindamycin and/or tobramycin were collected from the three county councils in southeast Sweden and investigated with spa typing, polymerase chain reaction (PCR) targeting the SCCmec right extremity junction (MREJ) and DNA microarray technology. The 98 isolates were divided into 40 spa types, and by microarray clustered in 17 multi-locus sequence typing (MLST) clonal complexes (MLST-CCs). All isolates with combined resistance to clindamycin and tobramycin (n = 12) from Östergötland County and two additional isolates (clindamycin-R) were designated as spa type t002, MREJ type ii and were clustered in CC5, together with a representative isolate of the ECT-R clone, indicating the clone's persistence. These isolates also carried several genes encoding exotoxins, Q9XB68-dcs and qacC. Of the isolates in CC15, 83% (25/30) were tobramycin-resistant and were designated spa type t084. Of these, 68% (17/25) were isolated from new-borns in all three counties. The persistence of the ECT-R clone in Östergötland County, although not found in any other county in the region, carrying certain virulence factors that possibly enhance its survival in the hospital environment, highlights the fact that basic hygiene guidelines must be maintained even when MRSA prevalence is low.

Detection and characterisation of SCCmec remnants in multiresistant methicillin-susceptible Staphylococcus aureus causing a clonal outbreak in a Swedish county.

The purpose of this study was to investigate if multiresistant methicillin-susceptible Staphylococcus aureus (MR-MSSA) causing a clonal outbreak in Östergötland County, Sweden, were derived from methicillin-resistant S. aureus (MRSA) by carrying remnants of SCCmec, and, if so, to characterise this element. A total of 54 MSSA isolates with concomitant resistance to erythromycin, clindamycin and tobramycin from 49 patients (91% clonally related, spa type t002) were investigated with the BD GeneOhm MRSA assay and real-time polymerase chain reaction (PCR) targeting the SCCmec integration site/SCCmec right extremity junction. DNA sequencing of one isolate representing the MR-MSSA outbreak clone was performed by massive parallel 454 pyrosequencing. All isolates that were part of the clonal outbreak carried SCCmec remnants. The DNA sequencing revealed the carriage of a pseudo-SCC element 12 kb in size, with a genomic organisation identical to an SCCmec type ΙΙ element, except for a 41-kb gap. This study demonstrates the presence of a pseudo-SCC element resembling SCCmec type II among MR-MSSA, suggesting possible derivation from MRSA. The presence of SCCmec remnants should always be considered when SCCmec typing is used for MRSA detection, and may not be suitable in locations with a high prevalence of MR-MSSA, since this might give a high number of false-positive results.

In vitro activity of beta-lactam antibiotics against CTX-M-producing Escherichia coli.

Beta-lactam antibiotics have been discussed as options for the treatment of infections caused by multiresistant extended-spectrum beta-lactamase (ESBL)-producing bacteria if the minimum inhibitory concentration (MIC) is low. The objective of this study was to investigate the in vitro activity of different beta-lactam antibiotics against CTX-M-producing Escherichia coli. A total of 198 isolates of E. coli with the ESBL phenotype were studied. Polymerase chain reaction (PCR) amplification of CTX-M genes and amplicon sequencing were performed. The MICs for amoxicillin-clavulanic acid, aztreonam, cefepime, cefotaxime, ceftazidime, ceftibuten, ertapenem, imipenem, mecillinam, meropenem, piperacillin-tazobactam, and temocillin were determined with the Etest. Susceptibility was defined according to the breakpoints of the European Committee on Antimicrobial Susceptibility Testing (EUCAST). MIC(50) and MIC(90) values were calculated. Isolates from CTX-M group 9 showed higher susceptibility to the beta-lactam antibiotics tested than isolates belonging to CTX-M group 1. More than 90% of the isolates belonging to CTX-M group 9 were susceptible to amoxicillin-clavulanic acid, ceftazidime, ceftibuten, piperacillin-tazobactam, and temocillin. The susceptibility was high to mecillinam, being 91%, regardless of the CTX-M group. All isolates were susceptible to imipenem and meropenem, and 99% to ertapenem. This study shows significant differences in susceptibility to different beta-lactam antibiotics among the CTX-M-producing E. coli isolates and a significant difference for many antibiotics tested between the CTX-M-producing groups 1 and 9. The good in vitro activity of other beta-lactam antibiotics compared to carbapenems indicate that clinical studies are warranted in order to examine the potential role of these beta-lactam antibiotics in the treatment of infections caused by multiresistant ESBL-producing E. coli.

Risk of autoimmune diabetes in APECED: association with short alleles of the 5'insulin VNTR.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autoimmune disease causing a wide spectrum of autoimmune dysfunction potentially including diabetes of an autoimmune etiology. We have previously described a pair of discordant APECED siblings and pointed to a possible role of 5'insulin variable number of tandem repeats (VNTR) locus IDDM2 in the appearance of diabetes within this disease. In vitro studies have previously suggested that class I VNTR alleles were associated with decreased fetal thymic insulin expression. We genotyped the 5'INS VNTR locus and several flanking 11p15.5 markers in 50 Finnish APECED subjects and explored the possible contribution of IDDM2 in the development of diabetes. The shorter 5'INS VNTR class I alleles (<35 repeats) were more prevalent in the diabetic Finnish APECED subjects than in non-diabetic APECED subjects. Logistic regression analysis revealed that having 1 short (<35) VNTR allele did not increase the risk of developing diabetes (95% CI 0.6-27.0), whereas having 2 short alleles conferred a 43.5-fold increased risk (95% CI 3.0-634.6). We conclude that short 5'INS VNTR class I alleles play a role in susceptibility to autoimmune diabetes in the context of APECED.

Optical properties of the South pole ice at depths between 0.8 and 1 kilometer.

The optical properties of the ice at the geographical South Pole have been investigated at depths between 0.8 and 1 kilometer. The absorption and scattering lengths of visible light ( approximately 515 nanometers) have been measured in situ with the use of the laser calibration setup of the Antarctic Muon and Neutrino Detector Array (AMANDA) neutrino detector. The ice is intrinsically extremely transparent. The measured absorption length is 59 +/- 3 meters, comparable with the quality of the ultrapure water used in the Irvine-Michigan-Brookhaven and Kamiokande proton-decay and neutrino experiments and more than twice as long as the best value reported for laboratory ice. Because of a residual density of air bubbles at these depths, the trajectories of photons in the medium are randomized. If the bubbles are assumed to be smooth and spherical, the average distance between collisions at a depth of 1 kilometer is about 25 centimeters. The measured inverse scattering length on bubbles decreases linearly with increasing depth in the volume of ice investigated.

Phene Plate (PhP) biochemical fingerprinting. A screening method for epidemiological typing of enterococcal isolates.

Pulsed-field gel electrophoresis (PFGE) is currently considered the gold standard for genotyping of enterococci. However, PFGE is both expensive and time-consuming. The purpose of this study was to investigate whether the PhP system can be used as a reliable clinical screening method for detection of genetically related isolates of enterococci. If so, it should be possible to minimize the number of isolates subjected to PFGE typing, which would save time and money. Ninety-nine clinical enterococcal isolates were analysed by PhP (similarity levels 0.90-0.975) and PFGE (similarity levels < or =3 and < or =6 bands) and all possible pairs of isolates were cross-classified as matched or mismatched. We found that the probability that a pair of isolates (A and B) belonging to the same type according to PhP also belong to the same cluster according to PFGE, i.e. p(A(PFGE)=B(PFGE) * A(PhP)=B(PhP)), and the probability that a pair of isolates of different types according to PhP also belong to different clusters according to PFGE, i.e. p(A(PFGE) not equalB(PFGE) * A(PhP) not equalB(PhP)), was relatively high for E. faecalis (0.86 and 0.96, respectively), but was lower for E. faecium (0.51 and 0.77, respectively). The concordance which shows the probability that PhP and PFGE agree on match or mismatch was 86%-93% for E. faecalis and 54%-66% for E. faecium, which indicates that the PhP method may be useful for epidemiological typing of E. faecalis in the current settings but not for E. faecium.

A descriptive study of childbirth education provided by midwives in Sweden.

OBJECTIVE: to describe the content, modes of working and reaction/interaction of childbirth education provided by midwives in Sweden. DESIGN: qualitative, using non-participant observation to collect the data. Grounded theory approach was used. SETTING: antenatal classes provided in the community in Sweden. PARTICIPANTS: twelve midwives with varying lengths of experience in teaching antenatal classes, and the prospective parents who attended these classes. MEASUREMENTS AND FINDINGS: three perspectives on the content and three modes of working were found. Combinations of the differing perspectives and working modes provided differing interactions within the classes. KEY CONCLUSIONS: the confirming/mixed model resulted in dialogue in the classes. It was assumed that this model would contribute to an increased understanding of the coming experience of giving birth. IMPLICATIONS FOR PRACTICE: the findings provide midwives with a basis for reflection on their experiences as leaders in the childbirth preparation part of education for parenthood.

Women's perceptions of childbirth and childbirth education before and after education and birth.

OBJECTIVE: to illuminate women's perceptions of childbirth and childbirth education before and after education and birth. DESIGN: qualitative, using tape-recorded interviews to collect data. Interpretation was performed from Antonovsky's concept sense of coherence. SETTING: childbirth education, a part of parent education in Sweden. PARTICIPANTS: eleven women expecting their first child, where the pregnancy was planned and normal MEASUREMENTS AND FINDINGS: the development of perceptions of childbirth and childbirth education was described. The women adopted the content of the education in different ways. Fear as well as unreflected knowledge seemed to block acquisition of new knowledge. Factors which contributed to a childbirth experience worse than expected were lack of or inconsistent information. Increased knowledge about childbirth and experiences of confirmation during childbirth contributed to a good or better experience than expected. KEY CONCLUSION: any model of childbirth education which does not take into consideration the individual woman's perceptions of childbirth and childbirth education seems to be inadequate. IMPLICATIONS FOR PRACTICE: the findings stress the importance of individual assessment of expectations of and experiences of childbirth education. Consistency in information given before and during childbirth supports a sense of comprehensibility, manageability and meaningfulness.

Swedish fathers' involvement in and experiences of childbirth preparation and childbirth.

OBJECTIVE: To discover the expectations and experiences of childbirth preparation and childbirth of Swedish men in order to contribute to a basis of reflections in the midwifery profession. DESIGN: Three tape-recorded interviews were performed: before and after childbirth preparation, and between one and three weeks after the baby was born. SETTING: Swedish maternity care. PARTICIPANTS: Eleven men who participated with their partners in antenatal classes. MEASUREMENTS AND FINDINGS: The interviews were analysed in several steps and included co-assessments by co-workers. Finally, an interpretation based on the concept 'vital involvement' was undertaken. Indications of vital involvement as well as various levels of involvement or distance were found. The participation in childbirth was more demanding than expected for the eleven men. They felt unprepared for an unpredictable process, the experience of time and pain, the woman's action, and their own reactions. The men who were regarded by the authors as vitally involved seemed to manage overwhelming feelings of helplessness during childbirth, to support the women, and experience the meeting with the baby positively. KEY CONCLUSION: It seems important for midwives to meet men individually, design childbirth preparation from men's perspective, follow up interpretations of the content, discuss expectations with regard to the men's role, and assess their experiences during the birth process.

A 5-year clinical review of bond failure with a light-cured resin adhesive.

The purpose of this study was to investigate the time to first failure of stainless steel orthodontic brackets (Ormco Corp, Glendora, Calif) bonded with a light-cured resin adhesive (Transbond, 3M Unitek, Monrovia, Calif) and assess whether time to failure was related to the patient's age at the start of treatment or sex, the proficiency of the individual placing the brackets, or the presenting malocclusion. Data on 548 patients with 7118 bonded brackets were analyzed. Survival analysis was carried out on a single bracket per patient. In each patient, the first bracket to fail was studied. In cases where no brackets failed, the bracket with the shortest follow-up time was analyzed and handled as a censored observation in the formal analysis. Median time until first bracket failure was 442 days, and an overall failure rate of 6% was recorded. There were no significant differences in time to first failure of brackets with respect to the sex or age of the patient at the start of treatment (p = 0.168, and p = 0.261, respectively), operator proficiency in placing brackets (p = 0.189), or presenting malocclusion (p = 0.052). Performance of brackets bonded with Transbond does not appear to vary significantly according to the variables examined.

A clinical retrospective evaluation of 2 orthodontic band cements.

This study aimed to compare the time to first failure of stainless steel orthodontic first permanent molar bands cemented with either a modified composite (Band-Lok, Reliance Orthodontic Products) or a conventional glass ionomer cement (AquaCem, De Trey Dentsply). The effect of patient sex, patient age at the start of treatment, the presenting malocclusion, treatment mechanics, and the operator proficiency on band survival was also assessed. Data for 219 bands cemented with Band-Lok in 108 patients and for 395 bands cemented with AquaCem in 183 patients were analyzed. For each case, a single molar band, either the band that was first to fail or the band that had the shortest follow-up time, was chosen for analysis. For each cement, whether headgear was used or not, there was no significant difference in time to first band failure (P = .398). Twenty-six percent of patients had at least one band failure with Band-Lok, and 30% of patients had at least one band failure with AquaCem, representing an 18% band failure rate for each cement. There was no significant difference in time to first band failure for either cement with respect to sex of the patient (P = .842), patient age at the start of treatment (P = .257), presenting malocclusion (P = .319), or operator proficiency (P = .062). The use of headgear, however, reduced significantly the time to first band failure irrespective of cement type (P = .0069). Headgear use was identified as a predictor of first permanent molar band survival. Clinical performance of bands cemented with either cement appears to be similar and was influenced significantly by the use of headgear.

Outcome of a scheme for orthodontic care: a comparison of untreated and treated 19-year-olds.

The organization of the orthodontic service within the Public Dental Health Service in the southern part of the county of Halland, Sweden is described, and data for the provision of treatment are presented. The aim of this study was to examine the outcome of this service by studying the prevalence of malocclusion and residual need, as well as attitudes to treatment in previously treated and untreated individuals. Three samples of 19-year-olds were established: patients treated by specialists (n=132), patients treated by general practitioners (GP) (n=132), and untreated individuals (n=492). All samples were examined clinically, and radiographs, photographs, and study casts were obtained from the two treated groups. Attitudes to own teeth and orthodontic treatment were recorded by use of questionnaires. Deviant occlusal traits were recorded, and all the individuals were categorised according to a treatment need index. Generally, good occlusal conditions were observed in all samples. More deviant traits were observed in individuals that had been treated by GPs, and significant differences were observed for overjet, overbite, and crowding compared to the other samples. The majority of individuals belonged to the little/no treatment need index categories. Of those treated by GPs, one third belonged to the moderate (22%) or urgent (11%) need categories. About 10% reported dissatisfaction with their dental appearance, but only 2% expressed a desire for (further) orthodontic treatment.

Cariostatic effect of glass ionomer retained orthodontic appliances. An in vivo study.

The cariostatic effect of a fluoride releasing bonding agent was investigated and compared with a conventional composite based material in connection with bonding of orthodontic brackets in 22 homologous pairs of premolars. All subjects had malocclusions requiring orthodontic treatment with fixed appliances and extraction of at least two premolars. 6-13 weeks prior to extraction, orthodontic brackets were bonded to the labial surfaces of the extraction teeth with either a glass ionomer cement or a bis-GMA resin. Initially, the children were instructed in tooth brushing and the regular use of fluoride. After extraction, the bonded teeth were stained and evaluated in a stereo-microscope regarding the incidence and extension of initial enamel demineralisation. The zone of intact enamel adjacent to the bracket base and bonding material was measured in a stereo-microscope at four predetermined locations with the aid of an electronic ruler and scored according to four categories. The incidence of enamel demineralisation adjacent to glass ionomer bonded and composite bonded brackets was 68% and 77% respectively. In 12 pairs of premolars however, the demineralisation appeared to a lesser extent on the enamel around the brackets was generally wider when glass ionomer cement was used compared to the composite resin. These differences were statistically significant (p < 0.05) mesially and distally, but non-significant cervically and incisally. The results indicate that bonding with glass ionomer cement may have a local cariostatic effect in children requiring fixed orthodontic appliances.

[Effects of the training in integrity-promoting care on the interactions in a long-term ward]. / Auswirkungen der Schulung in integritätsfördernder Pflege auf die zwischenmenschlichen Beziehungsabläufe auf einer Langzeitabteilung.

A training programme in integrity-promoting care was given the staff of a long-term ward and practised during a three months intervention period. The effects were analysed in different parameters and compared with a control ward. This report describes analysis of video-recorded interactions (12 hs) during social activities between demented patients and caregivers and changes induced by the programme. The video-recorded episodes, containing mainly music and coffee sessions were interpreted from a model on interaction with demented patients suggested by Athlin and Norberg. The results indicate that the training programme and the guidance during the intervention resulted in increased understanding of demented patients' situation among the staff. They became more sensitive, adapted their cues and made the environment easier to interpret for the patients. This in turn led to the fact that the patients appeared more sensitive and clear in their cues. A positive circle developed.

Effects of three different swallow maneuvers analyzed by videomanometry.

PURPOSE: To evaluate the manometric effects of three different swallow maneuvers on healthy volunteers. MATERIAL AND METHODS: Ten healthy volunteers with no history of swallowing complaints were evaluated with simultaneous videoradiography and pharyngeal manometry (videomanometry). Three different swallow maneuvers were evaluated (supraglottic swallow, super-supraglottic swallow, and Mendelsohn's maneuver) and seven manometric and two videoradiographic variables were analyzed. RESULTS: The supraglottic swallow showed a significantly weaker peak contraction of the upper esophageal sphincter (UES). The super-supraglottic swallow had a significantly higher UES relaxation pressure and the Mendelsohn maneuver a significantly higher UES peak contraction. With the Mendelsohn maneuver, there was also a significantly longer duration of the pharyngeal contraction and a significantly weaker UES peak contraction. Both the super-supraglottic and the Mendelsohn maneuver had a significantly longer bolus transit time. CONCLUSION: Our study did not show any significant difference in the relaxation duration of any of the swallowing maneuvers compared to a control swallow. With the Mendelsohn maneuver, we found that both the pharyngeal peak contraction and contraction duration were increased, which might result in an improved propulsion of bolus into the esophagus.

Rapid decrease of free vancomycin in dense staphylococcal cultures.

Bacterial numbers in broth cultures were determined by bioluminescence assay of intracellular bacterial ATP. Broth MICs for strains of Staphylococcus epidermidis (ATCC 14990 and 35984) and Staphylococcus aureus (ATCC 25923, 29213 and 6538) were determined for cultures with different inocula (10(5)-10(8) bacteria/ml) after 24 h of incubation in supplemented Mueller-Hinton broth containing vancomycin. All of the tested strains except one were susceptible to methicillin, and all of the strains were susceptible to vancomycin. Free vancomycin concentrations in the broth cultures of all strains were determined with an agar well bioassay after 24 h of incubation. Free vancomycin concentrations and bacterial numbers of ATCC 35984 and ATCC 29213 were also determined after 0.5, 2, 4, and 8 h. In a low inoculum (10(5) bacteria/ml), the broth MICs were 1-4 microg/ml. In a high inoculum (approximately 10(8) bacteria/ml), the broth MICs increased two- to fourfold to 4-8 microg/ml. In dense inocula ( approximately 10(9)-10(10) bacteria/ml), the concentrations of free vancomycin in the broth were reduced, in most cases below the detection limit of the bioassay (

Salivary fluoride concentrations in children with glass ionomer cemented orthodontic appliances.

Salivary fluoride concentrations were determined in 10 children (mean age 12.0 years) undergoing fixed orthodontic therapy. The orthodontic appliances, a minimum of 4 bands and 8 brackets, were cemented with a glass ionomer cement. Unstimulated whole saliva was collected 4 times a day before (baseline value) and at 1, 7, 14 and 28 days after cementation. The samples of saliva were centrifuged and the supernatants were analyzed with a fluoride-sensitive electrode. At baseline, the mean salivary fluoride concentration was 0.85 mumol/l. There was a significant increase during the day after cementation (1.88 mumol/l). After 7, 14 and 28 days, salivary fluoride levels were slightly elevated, but not statistically different from the baseline values. The ingested fluoride dose during the 1st day was estimated to be 0.02 mg. It is concluded that in orthodontic treatment with fixed appliances, a slow release of fluoride from glass ionomer cements could exert a local cariostatic effect on adjacent caries-susceptible enamel.