Validation of smartwatch electrocardiogram intervals in children compared to standard 12 lead electrocardiograms.

Lay people are now able to obtain one-lead electrocardiograms (ECG) using smartwatches, which facilitates documentation of arrhythmias. The accuracy of smartwatch derived ECG intervals has not been validated in children though. Home-based monitoring of ECG intervals using a smartwatch could improve monitoring of children, e.g. when taking QTc prolonging medications. The aim of this study was to validate the ECG intervals measured by smartwatch in comparison to standard 12-lead ECGs in children and adolescents. Prospective study of children (age 5-17 years) at the outpatient clinic of a national pediatric heart center. Patients underwent a smartwatch ECG (ScanWatch, Withings) and a simultaneous standard 12-lead ECG. ECG intervals were measured both automatically and manually from the smartwatch ECG and the 12-lead ECG. Intraclass correlation coefficients and Bland-Altman plots were performed. 100 patients (54% male, median age 12.9 (IQR 8.7-15.6) were enrolled. The ICC calculated from the automated smartwatch and automated 12-lead ECG were excellent for heart rate (ICC 0.97, p < 0.001), good for the PR and QT intervals (ICC 0.86 and 0.8, p < 0.001), and moderate for the QRS duration and QTc interval (ICC 0.7 and 0.53, p < 0.001). When using manual measurements for the smartwatch ECG, validity was improved for the PR interval (ICC 0.93, p < 0.001), QRS duration (ICC 0.92, p < 0.001), QT (ICC 0.95, p < 0.001) and QTc interval (ICC 0.84, p < 0.001). CONCLUSION: Automated smartwatch intervals are most reliable measuring the heart rate. The automated smartwatch QTc intervals are less reliable, but this may be improved by manual measurements. WHAT IS KNOWN: In adults, smartwatch derived ECG intervals measured manually have previously been shown to be accurate, though agreement for automated QTc may be fair. WHAT IS NEW: In children, automated smartwatch QTc intervals are less reliable than RR, PR, QRS and uncorrected QT interval. Accuracy of the QTc can be improved by peroforming manual measurements.

Impact of Underweight, Overweight, and Obesity on Health-Related Quality of Life in Children with Tetralogy of Fallot Variants.

Traditional cardiovascular risk factors put patients with congenital heart disease (CHD) at increased risk for cardiovascular morbidity and mortality. The aim of this study was to evaluate whether body mass index (BMI) is associated with health-related quality of life (HRQoL) in patients with variants of Tetralogy of Fallot (TOF). Patients and parents of children with variants of TOF-CHD were asked to fill out the PedsQL 4.0 questionnaire and provide weight and length. Patients were categorized into low, normal, and high BMI percentiles. Other demographic data were obtained from the Swedish national registry for congenital heart disease (SWEDCON). Statistical analyses included non-parametric Mann-Whitney U test, Fisher exact, and Chi-square tests. Eighty-five patients were included. Twelve were overweight or obese, 57 had a normal BMI, and 16 were underweight. There was a significant difference in age and gender between the groups. Comparing overweight/obese children to those with normal BMI, physical and social functioning were impaired, while emotional and school function were comparable between the groups. This applied to both child and parental assessment. When comparing underweight to normal weight children, school functioning assessed by the parent was the only domain significantly different from patients with a normal BMI. Children with variants of TOF and overweight/obesity have lower HRQoL, particularly in physical and social functioning, while underweight children may have impaired school functioning. We suggest that preventive measures aimed at maintaining a normal weight should be taken early in life to reduce long-term cardiovascular risk in the CHD population.

"The only thing I wonder is when I will have surgery again": everyday life for children with right ventricle outflow tract anomalies during assessment for heart surgery.

BACKGROUND: Children with right ventricle outflow tract anomalies require repeated heart surgeries, thereby needing regular preoperative assessments throughout their lifetime. This situation puts a heavy burden on these children. Thus, the aim of this study was to explore how children diagnosed with right ventricle outflow tract anomalies experience their heart disease and their everyday life during the preoperative assessment and after the decision on whether to perform a new cardiac surgery. METHODS: Individual interviews were conducted with nine children between 9 to 17 years of age on three occasions from 2014 to 2016. In total there were 27 interviews which all were analyzed with thematic analysis. RESULTS: The analysis yielded three themes and eight subthemes. The theme Me and my heart disease concerns children's experiences of the heart disease. Almost all described symptoms and how they adapt in their everyday life. The theme Being me concerns the children's sense of self, where their heart disease was not prominent. The theme Being placed in someone else's hands describes how the assessment was more of a safety net at least until the decision of heart surgery. CONCLUSION: The children's symptoms, their experiences during the assessment, their future surgeries and how the heart disease affects their everyday life could be better understood as elements of their adaptation to the heart disease. In order to achieve individualized support based on the child's experiences and to ensure that these children are involved in their own care a child-centered approach is recommended.

The Extracellular Protease AprX from Pseudomonas and its Spoilage Potential for UHT Milk: A Review.

The negative effects of proteases produced by psychrotrophic bacteria on dairy products, especially ultra-high-temperature (UHT) milk, are drawing increasing attention worldwide. These proteases are especially problematic, because it is difficult to control psychrotrophic bacteria during cold storage and to inactivate their heat-resistant proteases during dairy processing. The predominant psychrotrophic species with spoilage potential in raw milk, Pseudomonas, can produce a thermostable extracellular protease, AprX. A comprehensive understanding of AprX on the aspects of its biological properties, regulation, proteolytic potential, and its impact on UHT milk can contribute to finding effective approaches to minimize, detect, and inactivate AprX. AprX also deserves attention as a representative of all extracellular metalloproteases produced by psychrotrophic bacteria in milk. The progress of current research on AprX is summarized in this review, including a view on the gap in current understanding of this enzyme. Reducing the production and activity of AprX has considerable potential for alleviating the problems that arise from the instability of UHT milk during shelf-life.

Swedish population-based study of pupils showed that foster children faced increased risks for ill health, negative lifestyles and school failure.

AIM: This population-based study explored whether foster children faced a higher risk of health problems than children of the same age who were not in foster care. METHODS: Data for 13 739 pupils aged 10, 13 and 16 years were obtained from the Pupil Health Database in the county of Värmland, Sweden, for the school years 2012/2013 and 2013/2014. These included data on school performance, health, lifestyle and social relationships, based on children's interviews with school nurses. RESULTS: Of all the pupils, 171 (1.2%) were in foster care. Children in foster care were generally unhealthier than other children. Both girls and boys were at higher risk of chronic health problems, daily smoking, use of drugs and school failure. When the girls in foster care were compared to other girls, we found that they faced a higher risk of psychological and psychosomatic symptoms. This difference was not found for boys. Foster children were also more likely to express a more negative view on life. CONCLUSION: We confirmed earlier studies that children in foster care tended to have inferior health and well-being than other children. These findings emphasise that health, risky behaviour and school performance should be considered together when assessing foster children.

Health-related quality of life in children with surgery for CHD: a study from the Swedish National Registry for Congenital Heart Disease.

BACKGROUND: As survival of children with CHD needing surgery has improved significantly, the need for follow-up in terms of health-related quality of life has become increasingly important. In this study, we sought to describe health-related quality of life in children with CHD in relation to cardiac surgery. METHODS: A retrospective Swedish National Registry for Congenital Heart Disease survey measured using DISABKIDS chronic generic measure-short version included 337 children (age 9-17 years; 39% girls). The majority (n=319, 95%) of children had a biventricular heart, whereas the remaining had a univentricular heart. Cardiac surgery was performed in 197 (58%) children. Health-related quality of life was expressed as total score (100 highest) and given as medians and 10-90th percentiles. RESULTS: The overall total score was 95 (88-100). Children with a biventricular heart who had undergone three or more surgeries (n=31; 9%) had the lowest total score of 81 (61-97; p<0.001). Children with two or more surgeries and those with univentricular heart were classified in NYHA II more frequently than children with one or no cardiac surgery (p=0.005 and <0.001, respectively). Children with three or more surgeries and those with univentricular heart needed more help at school (p<0.001). Compared with children with other chronic diseases, children with CHD had a high total score except for children with three or more surgeries who had comparable total scores with children with other chronic diseases. CONCLUSION: Children with three or more cardiac surgeries and those with a univentricular heart appear to have lower health-related quality of life, cognitive ability, and NYHA classification.

Multiple psychosomatic symptoms can indicate child physical abuse - results from a study of Swedish schoolchildren.

AIM: To examine whether children with self-reported experiences of either physical abuse alone or combined with intimate partner violence report more psychosomatic symptoms than other children and to explore whether these possible associations are enhanced by school-related factors, chronic condition and demographic factors. METHODS: A national cross-sectional study of 2771 pupils in grades 4, 6 and 9 from 44 schools in Sweden was carried out in 2006 (91% response rate). Data were analysed with univariate tests (chi-square), multiple logistic regression analyses and stratified logistic regression analyses, expressed as crude odds ratio (OR) and adjusted odds ratio (AOR) with 95% confidence intervals. RESULTS: There was a strong association between reported physical abuse and multiple (three or more) psychosomatic symptoms among schoolchildren (AOR 2.12). Chronic condition was the only determinant that had an obvious enhancing effect on the association between physical abuse and psychosomatic symptoms in childhood. CONCLUSION: This study shows that multiple psychosomatic symptoms are associated with child physical abuse. Health professionals therefore need to pay special attention to schoolchildren who complain about the co-occurrence of psychosomatic symptoms and pattern of symptoms, which could not be easily explained by other causes.

Chronic conditions in children increase the risk for physical abuse - but vary with socio-economic circumstances.

AIM: To explore whether children (age 10, 12 and 15 years) with self-reported chronic conditions are at higher risk of physical abuse and/or exposure to intimate-partner violence than other children, while considering the importance of demographic factors. METHODS: A national cross-sectional study of 2771 pupils in grades 4, 6 and 9 from 44 schools in Sweden (91% response rate). Conflict Tactic Scales were used to measure physical abuse and separate questions measured exposure to intimate-partner violence. A list of 13 diagnoses was used to estimate chronic conditions. RESULTS: Children with chronic conditions had an increased risk for physical abuse (CPA) only (OR 1.67) as well as in combination with exposure to intimate-partner violence (IPV) (OR 2.54), but not to IPV only, compared to children without chronic conditions. Furthermore, when chronic conditions were combined with country of birth other than Sweden and living in low-income areas, the risk for CPA increased even more, indicating interactive effects. CONCLUSIONS: A wide range of chronic health conditions in children increased the risk for physical abuse. This indicates that certain factors unite this group of children, irrespective of the type of disability or degree of severity, but where a combination with socio-economic circumstances is of importance.

Persistence strategies of Bacillus cereus spores isolated from dairy silo tanks.

Survival of Bacillus cereus spores of dairy silo tank origin was investigated under conditions simulating those in operational dairy silos. Twenty-three strains were selected to represent all B. cereus isolates (n = 457) with genotypes (RAPD-PCR) that frequently colonised the silo tanks of at least two of the sampled eight dairies. The spores were studied for survival when immersed in liquids used for cleaning-in-place (1.0% sodium hydroxide at pH 13.1, 75 degrees C; 0.9% nitric acid at pH 0.8, 65 degrees C), for adhesion onto nonliving surfaces at 4 degrees C and for germination and biofilm formation in milk. Four groups with different strategies for survival were identified. First, high survival (log 15 min kill < or =1.5) in the hot-alkaline wash liquid. Second, efficient adherence of the spores to stainless steel from cold water. Third, a cereulide producing group with spores characterised by slow germination in rich medium and well preserved viability when exposed to heating at 90 degrees C. Fourth, spores capable of germinating at 8 degrees C and possessing the cspA gene. There were indications that spores highly resistant to hot 1% sodium hydroxide may be effectively inactivated by hot 0.9% nitric acid. Eight out of the 14 dairy silo tank isolates possessing hot-alkali resistant spores were capable of germinating and forming biofilm in whole milk, not previously reported for B. cereus.

Health-Related Quality of Life in Children With Earlier Surgical Repair for Right Ventricular Outflow Tract Anomalies and the Agreement Between Children and Their Parents.

Background: Children diagnosed with right ventricle outflow tract (RVOT) anomalies require surgical repair early in life, reoperations and lifelong follow-up. The aim is to comprehensively describe their health related quality of life (HRQoL) and to assess the agreement in this regard between children and parents. Methods and Results: Child- and parent-reported HRQoL was assessed in 97 children aged 8-18 years using three different HRQoL questionnaires. The mean age was 12.9 ± 3 years. The mean total score for the child report was lower in the PedsQL Cardiac Module than in the PedsQL 4.0 and DISABKIDS (p ≤ 0.001). The mean score for each domain in PedsQL Cardiac Module ranged between 67 (cognitive function) and 79 (physical appearance), and between 72 (school function) and 82 (physical and social function) in PedsQL 4.0. Nearly half of the children reported problems with shortness of breath during physical activity. In the PedsQL Cardiac Module the child-parent agreement was strong for 13 of 22 items. Conclusion: HRQoL problems as perceived by children with RVOT anomalies are best identified with the PedsQL Cardiac Module and relate mostly to cognitive and physical functioning. The agreement findings suggest the need to take into account both child- and parent reports in the assessment of HRQoL.

New concepts for transdermal delivery of oxygen based on catalase biochemical reactions studied by oxygen electrode amperometry.

The development of formulation concepts for improved skin tissue oxygenation, including methods for measuring oxygen (O2) transport across biological barriers, are important research topics with respect to all processes that are affected by the O2 concentration, such as radiation therapy in oncology treatments, wound healing, and the general health status of skin. In this work we approach this topic by a novel strategy based on the antioxidative enzyme catalase, which is naturally present in the skin organ where it enables conversion of the reactive oxygen species hydrogen peroxide (H2O2) into O2. We introduce various applications of the skin covered oxygen electrode (SCOE) as an in-vitro tool for studies of catalase activity and function. The SCOE is constructed by placing an excised skin membrane directly on an O2 electrode and the methodology is based on measurements of the electrical current generated by reduction of O2 as a function of time (i.e. chronoamperometry). The results confirm that a high amount of native catalase is present in the skin organ, even in the outermost stratum corneum (SC) barrier, and we conclude that excised pig skin (irrespective of freeze-thaw treatment) represents a valid model for ex vivo human skin for studying catalase function by the SCOE setup. The activity of native catalase in skin is sufficient to generate considerable amounts of O2 by conversion from H2O2 and proof-of-concept is presented for catalase-based transdermal O2 delivery from topical formulations containing H2O2. In addition, we show that this concept can be further improved by topical application of external catalase on the skin surface, which enables transdermal O2 delivery from 50 times lower concentrations of H2O2. These important results are promising for development of novel topical or transdermal formulations containing low and safe concentrations of H2O2 for skin tissue oxygenation. Further, our results indicate that the O2 production by catalase, derived from topically applied S. epidermidis (a simple model for skin microbiota) is relatively low as compared to the O2 produced by the catalase naturally present in skin. Still, the catalase activity derived from S. epidermidis is measurable. Taken together, this work illustrates the benefits and versatility of the SCOE as an in vitro skin research tool and introduces new and promising strategies for transdermal oxygen delivery, with simultaneous detoxification of H2O2, based on native or topically applied catalase.

Dehydration affects drug transport over nasal mucosa.

Formulations for nasal drug delivery often rely on water sorption to adhere to the mucosa, which also causes a higher water gradient over the tissue and subsequent dehydration. The primary aim of this study was therefore to evaluate mucosal response to dehydration and resolve the hypothesis that mucoadhesion achieved through water sorption could also be a constraint for drug absorption via the nasal route. The effect of altering water activity of the vehicle on Xylometazoline HCl and 51Cr-EDTA uptake was studied separately ex vivo using flow through diffusion cells and excised porcine mucosa. We have shown that a modest increase in the water gradient over mucosa induces a substantial decrease in drug uptake for both Xylometazoline HCl and 51Cr-EDTA. A similar result was obtained when comparing two different vehicles on the market; Nasoferm® (Nordic Drugs, Sweden) and BLOX4® (Bioglan, Sweden). Mucoadhesion based on water sorption can slow down drug uptake in the nasal cavity. However, a clinical study is required to determine whether prolonged duration of the vehicle in situ or preventing dehydration of the mucosa is the most important factor for improving bioavailability.

Ecological diversification in the Bacillus cereus Group.

The Bacillus cereus Group comprises organisms that are widely distributed in the environment and are of health and economic interest. We demonstrate an 'ecotypic' structure of populations in the B. cereus Group using (i) molecular data from Fluorescent Amplified Fragment Length Polymorphism patterns, ribosomal gene sequences, partial panC gene sequences, 'psychrotolerant' DNA sequence signatures and (ii) phenotypic and descriptive data from range of growth temperature, psychrotolerance and thermal niches. Seven major phylogenetic groups (I to VII) were thus identified, with ecological differences that provide evidence for a multiemergence of psychrotolerance in the B. cereus Group. A moderate thermotolerant group (VII) was basal to the mesophilic group I, from which in turn distinct thermal lineages have emerged, comprising two mesophilic groups (III, IV), an intermediate group (V) and two psychrotolerant groups (VI, II). This stepwise evolutionary transition toward psychrotolerance was particularly well illustrated by the relative abundance of the 'psychrotolerant' rrs signature (as defined by Pruss et al.) copies accumulated in strains that varied according to the phylogenetic group. The 'psychrotolerant' cspA signature (as defined by Francis et al.) was specific to group VI and provided a useful way to differentiate it from the psychrotolerant group II. This study illustrates how adaptation to novel environments by the modification of temperature tolerance limits has shaped historical patterns of global ecological diversification in the B. cereus Group. The implications for the taxonomy of this Group and for the human health risk are discussed.

Electrochemical monitoring of native catalase activity in skin using skin covered oxygen electrode.

A skin covered oxygen electrode, SCOE, was constructed with the aim to study the enzyme catalase, which is part of the biological antioxidative system present in skin. The electrode was exposed to different concentrations of H2O2 and the amperometric current response was recorded. The observed current is due to H2O2 penetration through the outermost skin barrier (referred to as the stratum corneum, SC) and subsequent catalytic generation of O2 by catalase present in the underlying viable epidermis and dermis. By tape-stripping the outermost skin layers we demonstrate that SC is a considerable diffusion barrier for H2O2 penetration. Our experiments also indicate that skin contains a substantial amount of catalase, which is sufficient to detoxify H2O2 that reaches the viable epidermis after exposure of skin to high concentrations of peroxide (0.5-1mM H2O2). Further, we demonstrate that the catalase activity is reduced at acidic pH, as compared with the activity at pH 7.4. Finally, experiments with often used penetration enhancer thymol shows that this compound interferes with the catalase reaction. Health aspect of this is briefly discussed. Summarizing, the results of this work show that the SCOE can be utilized to study a broad spectrum of issues involving the function of skin catalase in particular, and the native biological antioxidative system in skin in general.

Toxin gene profiling of enterotoxic and emetic Bacillus cereus.

Very different toxins are responsible for the two types of gastrointestinal diseases caused by Bacillus cereus: the diarrhoeal syndrome is linked to nonhemolytic enterotoxin NHE, hemolytic enterotoxin HBL, and cytotoxin K, whereas emesis is caused by the action of the depsipeptide toxin cereulide. The recently identified cereulide synthetase genes permitted development of a molecular assay that targets all toxins known to be involved in food poisoning in a single reaction, using only four different sets of primers. The enterotoxin genes of 49 strains, belonging to different phylogenetic branches of the B. cereus group, were partially sequenced to encompass the molecular diversity of these genes. The sequence alignments illustrated the high molecular polymorphism of B. cereus enterotoxin genes, which is necessary to consider when establishing PCR systems. Primers directed towards the enterotoxin complex genes were located in different CDSs of the corresponding operons to target two toxin genes with one single set of primers. The specificity of the assay was assessed using a panel of B. cereus strains with known toxin profiles and was successfully applied to characterize strains from food and clinical diagnostic labs as well as for the toxin gene profiling of B. cereus isolated from silo tank populations.

Emetic toxin-producing strains of Bacillus cereus show distinct characteristics within the Bacillus cereus group.

One hundred representative strains of Bacillus cereus were selected from a total collection of 372 B. cereus strains using two typing methods (RAPD and FT-IR) to investigate if emetic toxin-producing hazardous B. cereus strains possess characteristic growth and heat resistance profiles. The strains were classified into three groups: emetic toxin (cereulide)-producing strains (n=17), strains connected to diarrheal foodborne outbreaks (n=40) and food-environment strains (n=43), these latter not producing the emetic toxin. Our study revealed a shift in growth limits towards higher temperatures for the emetic strains, regardless of their origin. None of the emetic toxin-producing strains were able to grow below 10 degrees Celsius. In contrast, 11% (9 food-environment strains) out of the 83 non-emetic toxin-producing strains were able to grow at 4 degrees Celsius and 49% at 7 degrees Celsius (28 diarrheal and 13 food-environment strains). non-emetic toxin-producing strains. All emetic toxin-producing strains were able to grow at 48 degrees Celsius, but only 39% (16 diarrheal and 16 food-environment strains) of the non-emetic toxin-producing strains grew at this temperature. Spores from the emetic toxin-producing strains showed, on average, a higher heat resistance at 90 degrees Celsius and a lower germination, particularly at 7 degrees Celsius, than spores from the other strains. No difference between the three groups in their growth kinetics at 24 degrees Celsius, 37 degrees Celsius, and pH 5.0, 7.0, and 8.0 was observed. Our survey shows that emetic toxin-producing strains of B. cereus have distinct characteristics, which could have important implication for the risk assessment of the emetic type of B. cereus caused food poisoning. For instance, emetic strains still represent a special risk in heat-processed foods or preheated foods that are kept warm (in restaurants and cafeterias), but should not pose a risk in refrigerated foods.

Block-copolymer micro-emulsion with solvent-induced segregation.

Reverse micelle formation of the poly(ethylene oxide)/poly(propylene oxide) block-copolymer (EO)13(PO)30(EO)13 (L64) in p-xylene was investigated as a function of water content and copolymer content, using small-angle neutron scattering (SANS). PEO/PPO block-copolymers are generally soluble in xylene but without forming aggregates. However, the effective block segregation increases dramatically upon addition of small amounts of water, and micelles form. The SANS data were analyzed using an absolute scale model fitting approach. This way, a detailed quantitative description of the system in terms of unimer concentration, micelle structure, and aggregation number as well as particle-particle interactions can be obtained. This approach throws light on very atypical features of the system as compared to standard amphiphilic systems. Data from samples measured along water-swelling lines with fixed EO/p-xylene-d10 molar ratios show that reverse micelles are formed at the water/EO molar ratio, W0 congruent with 0.2, independent of copolymer concentration. The majority of the block-copolymers are on a free monomer state (unimer state) at this W0. Increasing W0 above 0.2 only has a small effect on the micelle size. However, it does induce a strong increase of the total number of micelles and induce a corresponding decrease of the unimer concentration. On the other hand, increasing the overall copolymer concentration at fixed W0 gives rise to a significant decrease of the micelle size in terms of the micellar aggregation number. This observed behavior is totally different from what is normally observed for binary surfactant-solvent systems and droplet micro-emulsion systems, respectively. We believe that the atypical behavior is a result of the unusually weak segregation in the system, and we are not aware of previous discussions of the phenomenon for reverse micellar systems.

Emetic toxin formation of Bacillus cereus is restricted to a single evolutionary lineage of closely related strains.

An in-depth polyphasic approach was applied to study the population structure of the human pathogen Bacillus cereus. To assess the intraspecific biodiversity of this species, which is the causative agent of gastrointestinal diseases, a total of 90 isolates from diverse geographical origin were studied by genetic [M13-PCR, random amplification of polymorphic DNA (RAPD), multilocus sequence typing (MLST)] and phenetic [Fourier transform Infrared (FTIR), protein profiling, biochemical assays] methods. The strain set included clinical strains, isolates from food remnants connected to outbreaks, as well as isolates from diverse food environments with a well documented strain history. The phenotypic and genotypic analysis of the compiled panel of strains illustrated a considerable diversity among B. cereus connected to diarrhoeal syndrome and other non-emetic food strains, but a very low diversity among emetic isolates. Using all typing methods, cluster analysis revealed a single, distinct cluster of emetic B. cereus strains. The isolates belonging to this cluster were neither able to degrade starch nor could they ferment salicin; they did not possess the genes encoding haemolysin BL (Hbl) and showed only weak or no haemolysis. In contrast, haemolytic-enterotoxin-producing B. cereus strains showed a high degree of heterogeneity and were scattered over different clusters when different typing methods were applied. These data provide evidence for a clonal population structure of cereulide-producing emetic B. cereus and indicate that emetic strains represent a highly clonal complex within a potentially panmictic or weakly clonal background population structure of the species. It may have originated only recently through acquisition of specific virulence factors such as the cereulide synthetase gene.

Erythropoietin treatment in metastatic breast cancer--effects on Hb, quality of life and need for transfusion.

Erythropoietin is an effective treatment for anemia in patients with various types of cancers, but few studies have evaluated the benefit of treatment in advanced breast cancer. In this multicenter study, we investigated the influence of two different doses of epoetin-beta on the level of hemoglobin, the need for blood transfusion, quality of life and safety aspects in patients with metastatic breast cancer. A total of 180 patients were randomized to receive either 1000 IE or 5000 IE epoetin-beta subcutaneously three times per week for 24 weeks. An increase of 20 g/L was defined as a positive hemoglobin response. Blood transfusions were given, if clinically indicated. Additional laboratory values and adverse events were recorded. Quality of life was measured with the aid of the EORTC QLQ-C30 questionnaire. Hemoglobin levels increased significantly in both groups. In the high-dose group, the initial mean Hb value was 98 g/L (64-110), which increased to 121 g/L (83-165) by week 24. In the low-dose group, the mean Hb value was 99 g/L (77-110.5) and by week 24 it was 116 g/L (81-144). The majority of patients who responded to treatment did so during the first four weeks. After 4 weeks, 7 patients in the low-dose group and 24 patients in the high-dose group had increased their Hb values by more than 20 g/L. The need for transfusion was low and did not differ between the groups. Quality of life was significantly enhanced in both groups, and there was no difference in the global quality of life between the two study arms. Epoetin-beta is a well-tolerated, safe and effective treatment of anemia in patients with metastatic breast cancer. There were significant improvements in Hb levels and quality of life in both groups.