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.

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.

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.

Chromosome aberrations in workers exposed to arsenic.

The occurrence of chromosome aberrations was studied in short-term cultured lymphocytes from nine workers exposed to arsenic at the Rönnskär smeltery in northern Sweden. In the smelter workers, 87 aberrations were found in 819 mitoses. The number of aberrations varied individually from 0 to 25 aberrations per 100 cells. In a control material 13 aberrations were found in 1012 mitoses. The frequency of chromosome aberrations was significantly increased among the smelter workers, but due to the simultaneous exposure to other agents the effect of arsenic per se can not be assessed with certainty.

Transferrin C2, metal binding and Alzheimer's disease.

Significant associations between the transferrin (TF) variant C2 and a number of disorders suspected to be caused by oxygen free radicals have been reported. Thus an increased frequency of the TFC2 variant has been found in patients with Alzheimer's disease (AD), and it has been hypothesized that AD is caused by free radical damage due to defective binding of iron and aluminium by TFC2. In a study of 64 patients with AD from northern Sweden we were able to confirm the association between TFC2 and AD, but there were no significant differences between TFC2 and other TF variants with respect to the binding of iron and aluminium.

Factors affecting the consistent use of barrier methods of contraception.

OBJECTIVES: To discuss the major issues involved in the consistent and effective use of barrier methods of contraception. DATA SOURCES: Major research and review articles on barrier methods published within the last 10 years were considered. One major source of articles was Family Planning Perspectives. METHODS OF STUDY SELECTION: This paper is a focused review and integration of recent literature rather than a comprehensive literature review. Only selected articles published since 1986 that are pertinent to the issues raised are included. TABULATION, INTEGRATION, AND RESULTS: All barrier methods have common characteristics that influence their patterns of use. The correct and consistent use of such methods is determined by the complex interaction of characteristics of the methods themselves, characteristics of users, and the situational context. Method characteristics include the extent of interference with sexual spontaneity and enjoyment, the amount of partner cooperation required, and the ability of the method to protect against human immunodeficiency virus and other sexually transmitted diseases. User characteristics include motivation to avoid unintended pregnancy, ability to plan, comfort with sexuality, and previous contraceptive use. Stage of sexual career, relationship characteristics, and physical and sexual abuse are important situational influences. CONCLUSIONS: Even though most barrier methods can be obtained without a prescription from a provider, clinicians have an extremely important role in promoting effective and consistent method use. Four major ways to improve the use of barrier methods currently available include: 1) improve method characteristics and the distribution systems; 2) change consumers' perceptions of method attributes; 3) train consumers to use methods correctly and overcome-perceived negative characteristics of the methods; and 4) change values about the perceived importance of method characteristics. There also is an urgent need for the development of better barrier methods.

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.

Effects of social interaction and children's relative inputs on older women's psychological well-being.

This study examines the influence of social interaction and relative inputs of parent and children (as perceived by the other) on older women's social and psychological well-being and their satisfaction with their children. The sample consisted of 719 Anglo-American women between the ages of 60 and 75. Half of the women were widows and the other half were currently married and were living with a spouse. For each marital status group the sample was further stratified so that approximately half of the women selected were childless and half had living children. Multiple regression analysis of survey results revealed that contact with other relatives, friends, and associates was more important for older women's well-being than was contact with children and that well-being was enhanced by quality, as compared to quantity, of interaction. Perceived quality of child contact also appeared to be influenced by the women's perceptions of other social relationships. Weak support for equity theory explanations of relationship satisfaction was found: If children provided much better input to the relationship than did the parent, distress and dissatisfaction were likely to exist for the parent. Finally, whereas for women with children amount of interaction appeared unimportant (perhaps because most parents had a certain level of minimal contact with others), for childless women amount, as well as quality, of contact with others was positively related to well-being.

The contraceptive sponge: factors in initiation and discontinuation of use.

This study examined characteristic of the contraceptive sponge that were important in women's decisions to use the contraceptive sponge and reasons why women discontinued sponge use. A sample of 385 current sponge users and 407 former sponge users participated in a national telephone survey on sponge use. Important reasons for trying the sponge were effectiveness, comfort, convenience and ease of use and it "would not interfere with sexual pleasure." The media and physicians were of considerable influence in women's decisions to initiate sponge use, but sexual partners, friends, parents and relatives exerted little influence. The most important reasons for discontinuing use of the sponge were pregnancy, both planned and accidental, and irritation, discomfort or vaginal infection. Women may decide to use the sponge because they have unrealistically positive perceptions of sponge characteristics.

Health care provider and contraceptive care setting: the relationship to contraceptive behavior.

This study examines contraceptive delivery characteristics and their association with contraceptive behavior. Data were collected in telephone interviews from a national sample of 1057 women who were using female contraceptives. The overwhelming majority of the sample obtained contraceptive services from gynecologists and other physician specialists and were seen in private facilities. Whereas nearly half of the providers recommended use of specific methods, only one-fourth discouraged use of particular methods. The pill was both the most frequently recommended and most commonly discouraged method. With regards to the provision of contraceptive information, practitioners were most likely to discuss the effectiveness of a method. In three of the four categories examined, a higher percentage of non-MDs than MDs gave information to their patients. Although the majority of women reported they were satisfied with the quality of care, mean satisfaction ratings were higher for female providers compared to male providers.

PIP: This study examines contraceptive delivery characteristics and their association with contraceptive behavior. Data were collected in telephone interviews from a national sample of 1057 women who were using female contraceptives. The overwhelming majority of the sample obtained contraceptive services from gynecologists and other physician specialists and were seen in private facilities. Whereas nearly half of the providers recommended use of specific methods, only 1/4 discouraged use of particular methods. The pill was both the most frequently recommended and most commonly discouraged method. With regards to the provision of contraceptive information, practitioners were most likely to discuss the effectiveness of a method. In 3 of the 4 categories examined, a higher percentage of non-MD's than MD's gave information to their patients. Although the majority of women reported they were satisfied with the quality of care, mean satisfaction ratings were higher for female providers compared to male providers.

Experience and acceptability of medical abortion with mifepristone and misoprostol among U.S. women.

PIP: The acceptability of medical abortion (mifepristone and misoprostol) among US women was investigated in a 1995 survey of 262 women seeking this method of pregnancy termination at 3 clinics in Oregon, Washington, and Vermont. The abortion patients' mean age was 27 years; mean gestational age was 49.5 days. 51.1% of respondents had experienced at least one prior abortion. Women completed a questionnaire at their initial clinic visit and again two weeks after the procedure. Participants chose medical abortion to avoid surgery (62.8%) or because they perceived it to be less invasive (56.3%), more natural (40.5%), and associated with a lesser risk of infection or damage to the uterus (35.1%) than vacuum aspiration, and could be performed earlier in pregnancy (27.2%). 49.8% indicated they preferred to wait for abortion to occur with a partner, friend, or family member, while 30.6% preferred to be alone; only 17.6% wanted to wait with other women undergoing the same procedure. Comparison of pre- and post-abortion questionnaires indicated women expected significantly more discomfort than they actually experienced and underestimated the number of days of bleeding. 72.8% of respondents were very satisfied with their medical abortion and 15.5% were somewhat satisfied. Women in the somewhat satisfied group had experienced significantly more abortion-related discomfort and anxiety than those who were very satisfied. Prior abortion experience and demographic characteristics did not influence satisfaction. 94% stated they would recommend medical abortion to a friend and 87% would select medical abortion if they had to terminate another pregnancy. Medical abortion has the potential to increase access to abortion among underserved groups of US women. Appropriate educational materials should be developed to help women choose between abortion methods.^ieng

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.

Listening and learning from women about mifepristone: implications for counseling and health education.

The careful, reflective, and honest way in which the women in the study analyzed, questioned, and explored the benefits and disadvantages of a mifepristone abortion compared with vacuum aspiration yielded an extensive list of information needed by women to make informed choices as well as an understanding of the diverse social contexts in which choices are made. Needed information identified by this study included technical information about the drugs themselves and their mechanisms of action, roles and responsibilities of health personnel, and descriptions of other women's experiences with mifepristone. A multiplicity of factors entered the decision-making process, demonstrating at the same time a complexity and flexibility of thought. In their hypothetical evaluation of mifepristone, women weighed such factors as experience with childbirth, spontaneous abortion and vacuum aspiration, specific issues for teenagers, lack of a support system, experience with herbal emenagogues and nonprescription drugs intended as abortifacients, and the relative dependence on health care providers. Social, personal, and cultural factors entered into women's interpretation of the different options. These socio-cultural contexts can profoundly influence decisions and potentially affect clinical outcomes. If health care professionals are not proactive, do not fully provide answers to questions (even if unasked), and fail to probe for specific life circumstances, then poor choices and poor outcomes may follow with long term negative consequences for clients.(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: Focus group discussions proved to be an effective modality for identifying potential barriers to mifepristone/misoprostol-induced abortion as well as special informational and counseling needs. The eight focus groups, conducted in 1994 in New York, Oregon, and California, included a total of 73 nonpregnant White, Black, and Hispanic women recruited from local family planning clinics. The mean age of respondents was 25.8 years; 63% had been pregnant and 45% reported a prior abortion. Respondents were asked to identify the information they would need to make an informed choice between vacuum aspiration and mifepristone/misoprostol abortion. Their questions centered around the drugs and their mechanisms of action, the abortion process (especially pain and the appearance of the expelled products of conception), postabortion fertility, and the role of health care staff. Discussions identified several factors--e.g., the length of time a woman requires to make a decision to abort, the degree of control she wants to exert over the abortion process, religious beliefs, and support from significant others--that can help counselors to identify women for whom vacuum aspiration may be a more feasible alternative. Overall, the group discussions highlighted the importance of a woman's unique life circumstances to reproductive health decisions.

Chromosome aberrations in cultured human lymphocytes exposed to trivalent and pentavalent arsenic.

Cultured human lymphocytes were exposed to trivalent (NaASO2) and pentavalent (Na2HAsO4) arsenic in concentrations comparable to the arsenic levels found in the urine of copper smelter workers. Significantly increased frequencies of chromosome aberrations (gaps, chromatid breaks, chromatid exchanges and chromosome breaks) were found after exposure to trivalent but not pentavalent arsenic. This effect was not found when nonstimulated (GO) lymphocytes were exposed to trivalent arsenic and then cultured. The rate of sister chromatid exchanges was also found to be increased after exposure to trivalent arsenic. Thus results suggest that trivalent arsenic is more genotoxic than pentavalent arsenic and that arsenic exerts its effect mainly during cell division.

A study of chromosomal aberrations in miners exposed to diesel exhausts.

A study was made of chromosome aberrations in cultured lymphocytes from a group of 14 miners exposed to diesel exhausts and a reference group of office employees and construction workers. No increased frequency of chromosomal aberrations was observed. The frequency of chromosomal aberrations (both gaps and breaks) was, however, found to be associated with smoking.

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.