Defining and measuring 'eczema control': an international qualitative study to explore the views of those living with and treating atopic eczema.

BACKGROUND: Atopic eczema (also known as eczema) is a chronic, inflammatory skin condition that often afflicts patients' health and well-being. The Harmonising Outcome Measures for Eczema (HOME) initiative recommends that 'long-term control of eczema' is measured in all clinical trials 3 months or longer in duration. However, little has been published on what eczema control means to those living with or treating atopic eczema. OBJECTIVES: To (i) develop understanding of what eczema control means to patients, carers and clinicians and (ii) explore the feasibility and acceptability of different ways of measuring eczema control in the long term. METHODS: Online focus groups explored patients/carers experiences in the UK, the United States, the Netherlands, France, Sweden and Japan, and an international online survey gathered views of clinicians. The framework method was used to analyse the focus groups, and thematic analysis was used to analyse survey data. All findings were integrated into a theoretical framework to create overarching themes that cut across these diverse groups. RESULTS: Eight focus groups with patients (16 years+) and eight groups with carers of children took place (N = 97). Sixty-two people took part in the survey. Eczema control was described as a multifaceted construct involving changes in disease activity, the treatment and management of the condition and psychological, social and physical functioning. Patient/carer measurement allows personal accounts and frequent measurement, whilst clinician measurement was deemed less subjective. The burden on patients/carers and issues for analysing and interpreting data should be considered. CONCLUSIONS: This study formed the basis of judging the content validity and feasibility of measurement instruments/methods to assess control of eczema in clinical trials. This online approach to an international qualitative study is an example of how core outcome set developers with limited resources can engage with multiple stakeholder groups on an international basis to inform consensus meeting discussions.

Dynamic loading, matrix maintenance and cell injection therapy of human intervertebral discs cultured in a bioreactor.

Low back pain originating from intervertebral disc (IVD) degeneration affects the quality of life for millions of people, and it is a major contributor to global healthcare costs. Long-term culture of intact IVDs is necessary to develop ex vivo models of human IVD degeneration and repair, where the relationship between mechanobiology, disc matrix composition and metabolism can be better understood. A bioreactor was developed that facilitates culture of intact human IVDs in a controlled, dynamically loaded environment. Tissue integrity and cell viability was evaluated under 3 different loading conditions: low 0.1-0.3, medium 0.1-0.3 and high 0.1-1.2 MPa. Cell viability was maintained > 80 % throughout the disc at low and medium loads, whereas it dropped to approximately 70 % (NP) and 50 % (AF) under high loads. Although cell viability was affected at high loads, there was no evidence of sGAG loss, changes in newly synthesised collagen type II or chondroadherin fragmentation. Sulphated GAG content remained at a stable level of approximately 50 µg sGAG/mg tissue in all loading protocols. To evaluate the feasibility of tissue repair strategies with cell supplementation, human NP cells were transplanted into discs within a thermoreversible hyaluronan hydrogel. The discs were loaded under medium loads, and the injected cells remained largely localised to the NP region. This study demonstrates the feasibility of culturing human IVDs for 14 days under cyclic dynamic loading conditions. The system allows the determination a safe range-of-loading and presents a platform to evaluate cell therapies and help to elucidate the effect of load following cell-based therapies.

Acute mechanical injury of the human intervertebral disc: link to degeneration and pain.

Excessive mechanical loading or acute trauma to intervertebral discs (IVDs) is thought to contribute to degeneration and pain. However, the exact mechanisms by which mechanical injury initiates and promotes degeneration remain unclear. This study investigates biochemical changes and extracellular matrix disruption in whole-organ human IVD cultures following acute mechanical injury. Isolated healthy human IVDs were rapidly compressed by 5% (non-injured) or 30% (injured) of disc height. 30% strain consistently cracked cartilage endplates, confirming disc trauma. Three days post-loading, conditioned media were assessed for proteoglycan content and released cytokines. Tissue extracts were assessed for proteoglycan content and for aggrecan integrity. Conditioned media were applied to PC12 cells to evaluate if factors inducing neurite growth were released. Compared to controls, IVD injury caused significant cell death. Injury also caused significantly reduced tissue proteoglycan content with a reciprocal increase of proteoglycan content in culture media. Increased aggrecan fragmentation was observed in injured tissue due to increased matrix metalloproteinase and aggrecanase activity. Injured-IVD conditioned media contained significantly elevated interleukin (IL)-5, IL-6, IL-7, IL-8, MCP-2, GROα, and MIG, and ELISA analysis showed significantly increased nerve growth factor levels compared to non-injured media. Injured-disc media caused significant neurite sprouting in PC12 cells compared to non-injured media. Acute mechanical injury of human IVDs ex vivo initiates release of factors and enzyme activity associated with degeneration and back pain. This work provides direct evidence linking acute trauma, inflammatory factors, neo-innervation and potential degeneration and discogenic pain in vivo.

The link between obesity and low circulating 25-hydroxyvitamin D concentrations: considerations and implications.

Obesity and vitamin D deficiency have both been recognized as major public health issues worldwide, and there is growing evidence that they are related, although the cause-effect relationship remains unclear. Could obesity be contributing to low circulating 25-hydroxyvitamin D concentrations? Alternatively, could low vitamin D status predispose to obesity? In this review, the relationship between low circulating 25-hydroxyvitamin D and obesity, and possible underlying reasons from both perspectives, is presented. One potential mechanism by which obesity could contribute to low serum 25-hydroxyvitamin D is adipose sequestration of vitamin D. On the other hand, adipose tissue has both the vitamin D receptor and the ability to synthesize 1,25-dihydroxyvitamin D, and there is evidence that vitamin D may regulate adipose tissue mass, differentiation and metabolism in ways that might contribute to obesity. Of particular interest, vitamin D deficiency is common both before and after bariatric surgery, and is often difficult to treat, particularly with the more malabsorptive procedures. Additional research is needed to elucidate the complex and multifaceted factors underlying the association between low circulating 25-hydroxyvitamin D and obesity, and to identify optimal treatment approaches in obese individuals and in bariatric surgical patients both before and after surgery.

Overexpression of c-erbB-2 is related to a higher expression of vascular endothelial growth factor (VEGF) and constitutes an independent prognostic factor in primary node-positive breast cancer after adjuvant systemic treatment.

The aim of this study was to investigate possible associations between the expression of c-erbB-2 and the angiogenic factors vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), p53 status, routine breast cancer prognostic factors and survival. Expression of c-erbB-2, VEGF, bFGF, and p53 protein was determined with an enzyme-linked immunosorbent assay (ELISA) in 656 patients with primary breast cancer (median follow-up time of 83 months). In 60 cases, we also used immunohistochemistry (IHC) for c-erbB-2 evaluation, to be used as a reference for the ELISA. Overexpression of c-erbB-2 was significantly related to a higher expression of VEGF, lower bFGF content, negative steroid receptor status, and a high S-phase fraction. In multivariate analysis, c-erbB-2 was an independent prognostic factor for relapse-free survival (RFS) and overall survival (OS) in all patients, and in node-positive patients, irrespective of the adjuvant systemic therapy. Combined survival analyses regarding c-erbB-2 and VEGF yielded additional prognostic information.

Influence of oscillatory mixing on the injectability of three acrylic and two calcium-phosphate bone cements for vertebroplasty.

Injecting acrylic and, increasingly, calcium-phosphate cements into the porous bone structure is an emerging procedure, referred to as vertebroplasty, for the augmentation of osteoporotic vertebrae. Despite the benefits of vertebroplasty, it has limitations. The limitations of interest in this study are the injectability of bone cements and their mixing variability (i.e., low reproducibility of resulting viscosity). The objective of this study is to investigate the effect of oscillatory versus manual mixing on cement viscosity and mixing variability. Five cements are tested: (a) Vertebroplastic, (b) DP-Pour, (c) Antibiotic Simplex, (d) chronOS Inject, and (e) Biopex. Compared to manual mixing, oscillatory mixing significantly decreased the mean viscosity and the mixing variability, which was inferred from the coefficient of variation. For example, under oscillatory mixing, the viscosity and the variability for Vertebroplastic decreased to one-third of the corresponding values for manual mixing. Similar results were obtained for the other cements. The decrease in viscosity is attributed to the pseudo-plastic behavior of bone cements. The decrease in the variability of cement viscosity was attributed to greater dispersive mixing of the cement components under oscillatory mixing. The decrease in viscosity eases the injection by reducing the pressure required. The decrease in the variability of cement viscosity increases reproducibility of the cement injection. Oscillatory mixing appears to have the potential to contribute to improving vertebroplasty.

The frequency of C282Y and H63D mutations in Hemochromatosis gene in native Estonians.

Four hundred and forty two adult individuals of Estonian nationality were examined in different regions of Estonia for the C282Y and H63D HFE mutations to determine the allele and genotype frequencies. The sample consisted only of those people whose at least four grandparents were born in Estonia, and have lived settled in the same region. The study was carried out using the PCR technique and restriction analysis for C282Y and H63D mutations respectively. For the C282Y mutation the frequency of heterozygotes was 6.6% and homozygotes 0.2%, giving allele frequency 0.035. The allele frequency for the H63D mutation was 0.136, and the frequency of homo- and hetero-zygotes 1.6% and 24.0% respectively.

Choice of and satisfaction with methods of medical and surgical abortion among U.S. clinic patients.

CONTEXT: Abortion induced by drugs is now a viable alternative to surgically induced abortion for U. S. women. Women's willingness to use these new methods of medical abortion hinges on the extent to which they prove acceptable, however. METHODS: Among 304 women participating in a clinical trial of medical abortion, 186 received a methotrexate-induced abortion and 118 were offered the option of a medical abortion but chose a surgical procedure instead. Study participants completed self-administered questionnaires before the abortion and again at a follow-up visit. RESULTS: Women in the medical and surgical abortion groups did not differ significantly with regard to demographic and other background characteristics: Their mean age was about 27, more than two-thirds were white, and three-quarters were unmarried and worked either part-time or full-time. However, women's ratings of seven attributes of abortion methods were significant predictors of choosing a medical abortion: Women were more likely to choose medical abortion if they placed greater importance on a method that was nonsurgical, one that resembled a miscarriage or one that could take place at home (odds ratios, 2.0-3.3). Conversely, women were less likely to choose medical abortion if they valued methods that were quick, that did not involve painful cramping or seeing blood or blood clots and that needed a doctor or nurse to be present (odds ratios, 0.3-0.5). Compared with those who had a surgical abortion, women who had a methotrexate-induced abortion expected more bleeding (mean scores, 3.5 vs. 3. 1) and reported more pain (3.4 vs. 2.9), heavier bleeding (3.4 vs. 2.5) and bleeding of longer duration (3.3 vs. 2.6). The overwhelming majority of women in the medical and surgical abortion groups reported that they were either very or somewhat satisfied with their abortion method (81% and 82%, respectively), would recommend it to others (82% and 78%) and would choose the method again (89% and 93%). CONCLUSIONS: Factors affecting the choice of abortion method appear to be numerous and complex. Providers need to be sensitive to differences in women's values and life circumstances when counseling them about an abortion method. In particular, providers should incorporate into their counseling sessions what women need to know about the characteristics of abortion methods and help women to identify what is the best option for them.

Emergency contraception: knowledge and attitudes of health care providers in a health maintenance organization.

One hundred sixty-four health care providers in a health maintenance organization were surveyed in 1996 regarding their knowledge of, attitudes toward, and perception of barriers regarding emergency contraceptive pills (ECPs), as well as their ECP prescribing practices. Providers reported primarily positive attitudes regarding ECPs. Only 42% reported having ever prescribed ECPs; those who had prescribed had more positive attitudes about ECPs. Knowledge of ECP provision was incomplete, with 40% believing treatment had to be initiated in 48 hours or less. Barriers identified by providers included lack of a dedicated product, lack of awareness of ECPs among providers, and liability issues.

Haemochromatosis gene mutations in Finns, Swedes and Swedish Saamis.

Frequencies of three different mutant haemochromatosis (HFE) alleles (282Tyr, 63Asp and 65Cys) were studied in three northern European populations, i.e. Finns, Swedes and Swedish Saamis. In Finns and Swedes the allele frequencies were within the range found in other populations from northern and western Europe. The Saamis differed from the Swedes with respect to all mutant alleles. Lower frequencies compared to Swedes were found for the 282Tyr (p = 0.0046) and 63Asp (p = 0.034) alleles, whereas the frequency of the 65Cys allele was higher (p = 0.046) in the Saamis. The total distribution of HFE alleles in Saamis showed a highly significant difference from that in Swedes (chi2 = 16.7, 3 d.f., p = 0.0008). These results further underline the genetic uniqueness of the Saamis.

Changes in providers' views and practices about emergency contraception with education.

OBJECTIVE: To assess changes in the prescribing practices, knowledge, attitudes, and perceptions of health care providers after an educational program about emergency contraception. METHODS: Health care providers completed self-administered questionnaires before and 1 year after full implementation of the project. The 102 providers who completed both questionnaires were physicians (64%) and mid-level professionals from 13 San Diego County Kaiser Permanente medical offices working in departments such as obstetrics and gynecology, primary care, and emergency medicine. RESULTS: The frequency of prescription for emergency contraceptive pills increased significantly from baseline to follow-up. There was an increase of almost 20% in the percentage who prescribed emergency contraception at least once a year. Knowledge also improved significantly, and perceptions of barriers to prescribing emergency contraceptive pills within the health maintenance organization decreased significantly. In contrast, attitudes about emergency contraception showed little change. CONCLUSION: This study suggests that providers who participate in in-service training and other aspects of a demonstration project show changes in perceptions, knowledge, and behavior. However, findings also suggest that significant gaps remain in knowledge about medications, side effects, and mode of action. It is likely that many providers in other health care settings also need additional information and training concerning protocols of emergency contraception provision and its modes of action and effects.

Geographical, linguistic, and cultural influences on genetic diversity: Y-chromosomal distribution in Northern European populations.

We analyzed 10 Y-chromosomal binary markers in 363 males from 8 populations in Northern Europe and 5 Y microsatellites in 346 of these individuals. These populations can be grouped according to cultural, linguistic, or geographical criteria, and the groupings are different in each case. We can therefore ask which criterion best corresponds to the distribution of genetic variation. In an AMOVA analysis using the binary markers, 13% of the Y variation was found between populations, indicating a high level of differentiation within this small area. No significant difference was seen between the traditionally nomadic Saami and the neighboring, historically farming, populations. When the populations were divided into Uralic speakers and Indo-European speakers, 8% of the variation was found between groups, but when they were divided according to geographical location, 14% of the variation was between groups. Geographical factors have thus been the most important in limiting gene flow between these populations, but linguistic differences have also been important in the east.

Interaction between haemochromatosis and transferrin receptor genes in hepatocellular carcinoma.

In hepatocellular carcinoma (HCC) iron has been implicated as a risk factor primarily in patients with hereditary haemochromatosis (HH) and cirrhosis. The wild-type HH (HFE) protein complexes with the transferrin receptor (TFR), and two HFE mutations (Cys282Tyr and His63Asp) have been found to increase the affinity of the TFR for transferrin resulting in an increased cellular uptake of iron. In previous studies we found an interaction between HFE and TFR genotypes in multiple myeloma and breast and colorectal carcinomas. In the present investigation we have studied HFE and TFR genotypes in 54 Swedish patients with HCC, using DNA from archival samples of paraffin wax blocks. The same HFE-TFR interaction as in the previously studied neoplastic disorders was found. Individuals carrying the HFE282Tyr allele (homo- and heterozygotes) in combination with homozygosity for the TFR Ser allele showed an increased risk for HCC (OR = 3.5; 95% confidence interval, CI = 1.3-9.3), which was further increased in HFE Tyr homozygotes and compound (Tyr/Asp) heterozygotes in combination with TFR 142Ser homozygosity (OR = 17.2; 95% CI = 1.8-168.9). The presence of liver cirrhosis could only be assessed in part of the patient material. In patients with verified liver cirrhosis the risk figures were substantially increased: for HFE 282 Tyr carriers in combination with TFR 142 Ser/Ser OR = 7.2; 95% CI = 2.0-25.5 and for HFE 282Tyr homozygotes and compound heterozygotes in combination with TFR 142Ser homozygosity, OR = 62.8; 95% CI = 6.1-642.5.

The genetic legacy of Paleolithic Homo sapiens sapiens in extant Europeans: a Y chromosome perspective.

A genetic perspective of human history in Europe was derived from 22 binary markers of the nonrecombining Y chromosome (NRY). Ten lineages account for >95% of the 1007 European Y chromosomes studied. Geographic distribution and age estimates of alleles are compatible with two Paleolithic and one Neolithic migratory episode that have contributed to the modern European gene pool. A significant correlation between the NRY haplotype data and principal components based on 95 protein markers was observed, indicating the effectiveness of NRY binary polymorphisms in the characterization of human population composition and history.

Y-chromosomal diversity in Europe is clinal and influenced primarily by geography, rather than by language.

Clinal patterns of autosomal genetic diversity within Europe have been interpreted in previous studies in terms of a Neolithic demic diffusion model for the spread of agriculture; in contrast, studies using mtDNA have traced many founding lineages to the Paleolithic and have not shown strongly clinal variation. We have used 11 human Y-chromosomal biallelic polymorphisms, defining 10 haplogroups, to analyze a sample of 3,616 Y chromosomes belonging to 47 European and circum-European populations. Patterns of geographic differentiation are highly nonrandom, and, when they are assessed using spatial autocorrelation analysis, they show significant clines for five of six haplogroups analyzed. Clines for two haplogroups, representing 45% of the chromosomes, are continentwide and consistent with the demic diffusion hypothesis. Clines for three other haplogroups each have different foci and are more regionally restricted and are likely to reflect distinct population movements, including one from north of the Black Sea. Principal-components analysis suggests that populations are related primarily on the basis of geography, rather than on the basis of linguistic affinity. This is confirmed in Mantel tests, which show a strong and highly significant partial correlation between genetics and geography but a low, nonsignificant partial correlation between genetics and language. Genetic-barrier analysis also indicates the primacy of geography in the shaping of patterns of variation. These patterns retain a strong signal of expansion from the Near East but also suggest that the demographic history of Europe has been complex and influenced by other major population movements, as well as by linguistic and geographic heterogeneities and the effects of drift.

Expanding the applicability of ISA TR84.02 in the field.

The ANSI/ISA S84.01 standard was released in 1996. The companion technical report TR84.02 is in the process of being completed. The latter document is intended to provide the methodology to implement the safety performance requirements of the standard for the safety system. In this document, three techniques are presented; these being Simplified Equations, Fault Tree Analysis and Markov Modeling. Of the three, only the Simplified Equations approach would reasonably be utilized in the field by plant personnel. The Simplified Equations provided as part of TR84.02 comprehend common cause failures, systematic failures, and second failure prior to repair scenarios. They do not however comprehend the use of redundant field devices which are dissimilar, and as such have different failure rates. This situation is quite common in practice, and simple to manage using enhanced equations for the computation of PFDavg. A set of these equations for typical redundant architectures in the field, and several examples of their applications in safety loop analysis are derived and presented in this paper.

Experiences and satisfaction with providing methotrexate-induced abortions among US providers.

OBJECTIVE: This study examined the acceptability of and experiences with methotrexate as an abortifacient among health care providers in the United States. METHODS: Seventy-six telephone interviews were conducted with providers (28% physicians, 13% midlevel providers, 29% administrators, and 30% counselors/other medical staff) of methotrexate-induced abortions during May and June of 1997. We examined provider satisfaction and several key operational issues relative to medical abortion, including: time spent with patients and staffing, training, and space needs. RESULTS: The majority of providers agreed that overall, more time was spent with methotrexate than with surgical abortion patients. Most agreed that the number of staff needed was the same for both methods, and that methotrexate required less office space. There were differing views on whether methotrexate required more, an equal amount of, or less training than surgical. Overall, providers were satisfied with methotrexate as an abortifacient. CONCLUSION: These data suggest that as knowledge of the method spreads, more providers will add this technique to their services.

Acceptability of suction curettage and mifepristone abortion in the United States: a prospective comparison study.

OBJECTIVE: We sought to compare the acceptability of suction curettage abortion with that of medical abortion with mifepristone and misoprostol in American women. STUDY DESIGN: We performed a prospective, serially enrolled, cohort analysis. The study population consisted of 152 subjects receiving mifepristone and misoprostol and 174 subjects undergoing suction curettage abortion aged > or =18 years with intrauterine pregnancies of up to 63 days' estimated gestation. Questionnaires regarding expectations and experiences were administered before the abortion and at the 2-week follow-up visit. RESULTS: Subjects undergoing medical abortions reported significantly greater satisfaction than those undergoing surgical abortions (mean rank, 121 vs 149; P <.01) but were no more likely to recommend the method they had just experienced to a friend (97% vs 93.3%). If a future abortion was required, however, 41.7% of subjects undergoing surgical abortions indicated they would opt for a medical abortion, whereas only 8.6% of subjects receiving medical abortions would choose a surgical abortion (P <.001). Failure of the abortion decreased satisfaction in the medical group and increased the likelihood of choosing a surgical abortion for a subsequent procedure (P <.001). Surgical subjects who experienced more anxiety than expected during the abortion were more likely to choose a medical procedure for a subsequent abortion (P <.01). CONCLUSION: Women receiving mifepristone and misoprostol were more satisfied with their method and more likely to choose the same method again than were subjects undergoing surgical abortion. Failure of a medical abortion and increased anxiety during surgical abortion were associated with preference for the alternative technique in a future procedure.