The physical and mental impact of surviving sepsis - a qualitative study of experiences and perceptions among a Swedish sample.

BACKGROUND: Sepsis is a critical illness with high morbidity and mortality rates. Each year, sepsis affects about 48.9 million people all over the world. This study aims to illuminate how sepsis survivors experience sepsis and the impact of sepsis, as well as the health-related quality of life thereafter. METHODS: An interview study with eight sepsis survivors was carried out in Sweden with an inductive qualitative method. The data were analyzed with content analysis. RESULTS: Four themes were identified during the analysis; The experience of health care and being a sepsis patient, New circumstances´ impact on life, Family and social interactions, and The psychological impact on life. The lack of information about how sepsis can impact the survivors' lives and what to expect can lead to prolonged agony. The long recovery time comes as an unexpected and unpleasant surprise to those affected. Initially, the sepsis survivors are almost euphoric that they have survived, which can later lead to chock and trauma when they realize that they could have died. This insight needs to be processed in order to reach reconciliation with life after sepsis. CONCLUSION: Sepsis has a huge impact on both physical and mental aspects of life. Many survivors suffer from persistent residual symptoms of varying degrees, to which they have to adapt. The sepsis survivors need individually adjusted information about the sepsis recovery trajectory, and what to expect during and after the hospital stay.

"You just need to leave the room when you breastfeed" Breastfeeding experiences among obese women in Sweden - A qualitative study.

BACKGROUND: The benefits of breastfeeding for the infant as well for the mother are well-known. It is recognized that obese (Body Mass Index ≥30 kg/m2) women may have less antenatal intention to breastfeed, and shortened duration of breastfeeding compared with normal-weight women. This may result in adverse short- and long-term health for both mother and child, such as a shortened lactational amenorrhoea and decreased protection against breast cancer for the women, and an increased risk for infectious diseases and overweight/obesity among the children. Therefore, it is important to gain more knowledge and understanding of obese women's experiences of breastfeeding in order to attain good health care. Hence, the aim of this study was to identify and describe obese women's experiences of breastfeeding. METHODS: This is an explorative study. Data was collected 2 - 18 months after childbirth through semi-structured face-to-face interviews with 11 obese women with breastfeeding experience. The interviews were recorded and transcribed verbatim. Thematic analysis was used. RESULTS: Three themes emerged from the data analysis: Breastfeeding - a part of motherhood, the challenges of breastfeeding, and support for breastfeeding. The women described an antenatal hope for breastfeeding, the body's ability to produce milk fascinated them, and the breast milk was seen as the best way to feed the child and also as promoting the attachment between mother and child. Breastfeeding was described as a challenge even though it is natural. The challenges concerned technical difficulties such as the woman finding a good body position and helping the child to achieve an optimum grip of the nipple. Another challenge was the exposure of the body connected to public breastfeeding. Support of breastfeeding was described as the importance of being confirmed as an individual behind the obesity, rather than an individual with obesity, and to obtain enough professional breastfeeding support. CONCLUSIONS: Breastfeeding was experienced as a natural part of being a mother. There were practical challenges for obese women concerning how to manage breastfeeding and how to handle the public exposure of the body. There was a need for realistic information about breastfeeding concerning both the child and the woman.

Levels of brominated flame retardants and other pesistent organic pollutants in breast milk samples from Limpopo Province, South Africa.

The non-occupational exposure to brominated flame retardants, and other persistent organic pollutants (POPs) was studied by collecting human breast milk samples from mothers residing in Thohoyandou area, a rural district in the Limpopo Province, northern part of South Africa (SA). Of all collected samples to be analysed (n=28), those with large enough milk volumes, (n=14) were quantified for polybrominated diphenyl ethers (PBDEs) (9 congeners: BDE-28, 47, 66, 99, 100, 138, 153, 154, and 183) and hexabromocyclododecane (HBCD) on a GC equipped with dual capillary columns and dual electron-capture detectors (ECD). The levels of PBDE congeners (median sumBDE 1.3 ng/g of lipids) and of HBCD were not far from levels generally found in European studies, and this study may be the first report on the presence of PBDEs and HBCD in SA breast milk. On a congener basis, the finding of comparably high BDE-183 levels suggests a specific PBDE usage, or contamination situation in SA. Apart from BFRs, the high DDT levels found in the breast milk from this area (median and maximum sumDDT levels of about 4600 and over 20,000 ng/g of lipids, respectively; n=28) have earlier been reported. In addition, other POPs (PCBs, HCB and HCHs) were found in SA breast milk, at relatively low levels. To conclude, measurable levels of PBDEs and HBCD, and a specific BDE congener pattern, were found in breast milk from the Limpopo province, SA. A number of other POPs, including DDTs in high levels, were also present.

[Treatment of rheumatoid arthritis (RA) with anti-TNF-alpha antibody (Remicade). Individual monitoring of bioavailability and immunogenicity--secondary publication]. / Behandling af reumatoid artrit med anti-tumornekrosefaktor-alpha-antistof. Individuel monitorering af biotilgaengelighed og immunogenicitet-- sekundaerpublikation.

Remicade/infliximab is effective in rheumatoid arthritis (RA), but response failure is frequent. Sera from 106 RA patients were monitored using an RIA for functional infliximab and an RIA for anti-infliximab antibody (Ab). S-infliximab varied considerably, e.g. 0-22 microg/ml before the 3rd infusion, and 44% were Ab-positive after 6 months. Low s-infliximab was associated with Ab development and later therapeutic failure, and high Ab levels could be related to dose increases, side-effects and cessation of therapy. Pharmacological monitoring should help optimize anti-TNF therapies.

Plasma PBDE and thyroxine levels in rats exposed to Bromkal or BDE-47.

In experimental models, polybrominated diphenyl ethers (PBDEs), a group of brominated flame retardants, have caused effects in a number of biological end-points, including neurobehavioural effects, disturbances in thyroid and steroid hormone homeostasis, and other steroid-related effects. Almost exclusively, only external dose metrics (dose per body weight basis) have been studied in connection to the observed effects. In this study we report on new analyses of plasma PBDE levels in surplus samples from earlier studies on thyroid hormones (TH) in exposed rodents. Female, 7-week old Sprague-Dawley rats were given either Bromkal 70-5 DE (Study I; 18 or 36 mg/kg bw/day) or BDE-47 (Study II; 1, 6 or 18 mg/kg bw/day) daily by gavage for two weeks. At an external dose of 18 mg/kg bw/day significant TH effects (decreased plasma free thyroxin levels) were observed in both studies, corresponding to an internal (plasma) dose of 463 microg sumPBDE/g lipid (Study I) or 421 microg BDE-47/g lipid (Study II). If we compare the contribution of different BDE congeners to the total BDE level in rat plasma after Bromkal exposure (Study II), and in the Bromkal mixture itself, the most important congener in the Bromkal mixture were also found in plasma. However, the relative concentration of BDE-99 was lower, and that of BDE-153 was higher, than that of the mixture, indicating selectivity in uptake, metabolism and/or excretion of the individual BDE congeners. Explicitly, the possible in vivo conversion of BDE-99 to BDE-47, and of BDE-154 to BDE-153 could not be excluded. The internal dose in the present rat study could be compared to reported human serum doses of PBDE. Human serum/blood levels have a wide range, from 3 to 6 ng sumPBDE/g lipid in background samples from Europe, about 10 times higher in US sample, and up to 100 times higher (300-600 ng/g lipid) in upper-end levels in collected samples from USA. As a consequence, the margin between effects levels in the rat and exposure levels in man varies widely, with a quotient roughly from 1000 to 100,000. Generally, it could be expected that this margin is lower than if external dose metrics would be used. An even lower margin could be expected as recent studies have shown effects in offspring at lower doses than those giving effects in our studies. Lastly, it should be noted that humans are already exposed to a mixture of chemicals in daily life, a fact that complicates this kind of comparison.

Individualized monitoring of drug bioavailability and immunogenicity in rheumatoid arthritis patients treated with the tumor necrosis factor alpha inhibitor infliximab.

OBJECTIVE: Infliximab, an anti-tumor necrosis factor alpha (anti-TNFalpha) antibody, is effective in the treatment of several immunoinflammatory diseases. However, many patients experience primary or secondary response failure, suggesting that individualization of treatment regimens may be beneficial. This study was undertaken to investigate whether serologic monitoring of infliximab bioavailability and immunogenicity in individual patients would be useful in optimizing treatment regimens to improve efficacy and tolerability. METHODS: To avoid the use of solid-phase assays, two radioimmunoassays were developed: one for measurement of levels of anti-infliximab antibody, and a functional one for measurement of TNFalpha binding due to infliximab. Sera from 106 randomly selected rheumatoid arthritis patients were tested within 6 months of therapy initiation, and associations between findings of serum assays and disease activity, infusion reactions, and treatment failure occurring within 18 months were assessed. RESULTS: Trough serum infliximab levels after the first 2 intravenous infusions of infliximab at 3 mg/kg varied considerably between patients (range 0-22 microg/ml). At this stage, only 13% of the patients were anti-infliximab antibody positive. With subsequent infusions, the frequency of antibody positivity rose to 30% and 44% (at 3 months and 6 months, respectively), accompanied by diminished trough levels of infliximab. Indeed, low infliximab levels at 1.5 months predicted antibody development and later treatment failure. There were highly significant correlations between high levels of antibodies and later dose increases, side effects, and cessation of therapy. High baseline disease activity, judged by C-reactive protein level and Disease Activity Score, was associated with low levels of infliximab at the early stage of treatment and later development of anti-infliximab antibodies. Cotreatment with methotrexate resulted in slightly reduced antibody levels after 6 months; other disease-modifying antirheumatic drugs and prednisolone had no effect. CONCLUSION: Development of anti-infliximab antibodies, heralded by low preinfusion serum infliximab levels, is associated with increased risk of infusion reaction and treatment failure. Early monitoring may help optimize dosing regimens for individual patients, diminish side effects, and prevent prolonged use of inadequate infliximab therapy.

Predictors of infusion reactions during infliximab treatment in patients with arthritis.

In the present study we evaluated the impact of baseline antinuclear antibody (ANA) status and use of methotrexate on development of infliximab-related infusion reactions in patients with rheumatoid arthritis (RA) or spondylarthropathies (SpAs), including psoriatic arthritis. All patients with RA (n = 213) or SpA (n = 76) treated with infliximab during the period 1999-2005 at the Department of Rheumatology in Lund, Sweden were included. ANAs were present in 28% and 25% of RA and SpA patients, respectively. Because of differences in baseline characteristics, we used a binary logistic regression model to calculate odds ratios (ORs), adjusting for age, sex and prednisolone dosage. Altogether 21% of patients with RA and 13% of patients with SpA developed infusion reactions (P = 0.126). The OR for development of infusion reactions in RA patients with baseline ANA positivity alone was 2.1. Infliximab without methotrexate and infliximab as monotherapy were associated with ORs of 3.1 and 3.6, respectively. Combining infliximab without methotrexate and ANA positivity yielded an OR for infusion reaction of 4.6. Lower age at disease onset and longer disease duration were associated with infusion reactions (P = 0.012 and P = 0.036, respectively), but age, sex, C-reactive protein, erythrocyte sedimentation rate, Health Assessment Questionnaire and Disease Activity Score-28 at baseline were not. No predictors of infusions reactions were identified in SpA patients. RA patients treated with infliximab without methotrexate, and who are positive at baseline for ANAs are at increased risk for developing infliximab-related infusion reactions.

Serum cartilage oligomeric matrix protein (COMP) decreases in rheumatoid arthritis patients treated with infliximab or etanercept.

Changes in serum cartilage oligomeric matrix protein (COMP) were studied during a 6-month period from initiation of treatment of rheumatoid arthritis patients with either infliximab or etanercept, to elucidate whether the favourable results of tissue protection reported in clinical trials are corroborated by changing levels of circulating COMP. Rheumatoid arthritis patients commencing treatment with infliximab (N = 32) or etanercept (N = 17) were monitored in accordance with a structured protocol. Only patients who were not receiving glucocorticoids or who were on a stable dose of oral prednisolone (<10 mg daily) were included. Serum COMP was measured by a sandwich immunoassay based on two monoclonal antibodies against human COMP in samples obtained at treatment initiation and at 3 and 6 months. Serum COMP decreased at 3 months in both infliximab- and etanercept-treated patients (P < 0.001 and <0.005, respectively) and remained low at 6 months. There was no significant correlation between changes in or concentrations of serum COMP and serum C-reactive protein at any time point. A decrease in serum COMP was seen both in ACR20 responders (patients meeting the American College of Rheumatology criteria for 20% improvement) and in nonresponders. The pattern of changes of serum COMP, a marker for cartilage turnover, in these patient groups supports the interpretation that infliximab and etanercept have a joint protective effect. Serum COMP has potential as a useful marker for evaluating tissue effects of novel treatment modalities in rheumatoid arthritis.