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Skin care education and individual counselling versus treatment as usual in healthcare workers with hand eczema: randomised clinical trialBMJ 2012; 345 doi: https://doi.org/10.1136/bmj.e7822 (Published 12 December 2012) Cite this as: BMJ 2012;345:e7822
- Kristina Sophie Ibler, registrar12,
- Gregor B E Jemec, professor1,
- Thomas L Diepgen, professor of dermatology3,
- Christian Gluud, head4,
- Jane Lindschou Hansen, clinical research consultant4,
- Per Winkel, senior researcher4,
- Simon Francis Thomsen, registrar2,
- Tove Agner, professor2
- 1Department of Dermatology, Roskilde Hospital, Health Science Faculty, Køgevej 7-13, 4000 Roskilde, Denmark
- 2Department of Dermatology, Bispebjerg Hospital, Health Science Faculty, Copenhagen, Denmark
- 3Department of Social Medicine, Occupational and Environmental Dermatology, University of Heidelberg, Germany
- 4Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Denmark
- Correspondence to: K S Ibler kristinaibler{at}hotmail.com
- Accepted 31 October 2012
Objective To evaluate the effect of a secondary prevention programme with education on skin care and individual counselling versus treatment as usual in healthcare workers with hand eczema.
Design Randomised, observer blinded parallel group superiority clinical trial.
Setting Three hospitals in Denmark.
Participants 255 healthcare workers with self reported hand eczema within the past year randomised centrally and stratified by profession, severity of eczema, and hospital. 123 were allocated to the intervention group and 132 to the control group.
Interventions Education in skin care and individual counselling based on patch and prick testing and assessment of work and domestic related exposures. The control was treatment as usual.
Main outcome measures The primary outcome was clinical severity of disease at five month follow-up measured by scores on the hand eczema severity index. The secondary outcomes were scores on the dermatology life quality index, self evaluated severity of hand eczema, skin protective behaviours, and knowledge of hand eczema from onset to follow-up.
Results Follow-up data were available for 247 of 255 participants (97%). At follow-up, the mean score on the hand eczema severity index was significantly lower (improved) in the intervention group than control group: difference of means, unadjusted −3.56 (95% confidence interval −4.92 to −2.14); adjusted −3.47 (−4.80 to −2.14), both P<0.001 for difference. The mean score on the dermatology life quality index was also significantly lower (improved) in the intervention group at follow-up: difference of means: unadjusted −0.78, non-parametric test P=0.003; adjusted −0.92, −1.48 to −0.37). Self evaluated severity and skin protective behaviour by hand washings and wearing of protective gloves were also statistically significantly better in the intervention group, whereas this was not the case for knowledge of hand eczema.
Conclusion A secondary prevention programme for hand eczema improved severity and quality of life and had a positive effect on self evaluated severity and skin protective behaviour by hand washings and wearing of protective gloves.
Trial registration ClinicalTrials.gov NCT01012453.
Eczema of the hand is common among healthcare workers; in 2007 almost one third of healthcare workers in a Danish hospital reported having had hand eczema during the past year.1 In 2009 skin disorders accounted for one third of the recognised occupational diseases in Denmark, and the costs to society are extensive. Preventive programmes have been introduced in some work places and are known to be effective as primary prevention for wet work occupations—that is, healthcare workers, hairdressers, gut cleaners in abattoirs, and cheese dairy workers.2 3 4 5 6 7 8 9 10 11 The evidence for secondary prevention programmes is more limited, however, perhaps because of the complexity of the necessary intervention.12 Multidisciplinary intervention programmes with several clinic visits have been introduced in the secondary prevention of hand eczema in healthcare workers, but these programmes are not based on evidence from randomised clinical trials or systematic reviews of such trials.13 14 15
We evaluated the effect of a simple secondary preventive programme consisting of skin care education and individual counselling on work and domestic related exposures and contact allergies among healthcare workers.
We randomised participants in three geographically close hospitals in Denmark between October 2009 and February 2010. Participants provided informed written consent. The trial design is published in detail elsewhere.16
The participants were identified from a survey of 3181 healthcare workers in the three hospitals. The inclusion criteria were an affirmative answer to the question "Have you had hand eczema during the past 12 months?" and informed consent. The question has been formerly validated in a Swedish study in car mechanics, dentists, and office workers.17 Exclusion criteria were pregnancy, systemic use of immunosuppressive drugs or retinoids, psoriatic lesions on the hands, and any serious medical condition that could influence the results.
In March 2009 we distributed a self administered questionnaire to all the nurses, doctors, nursing aids, and laboratory technicians at the three hospitals; in total 3181 staff.
The questionnaire investigated the prevalence of hand eczema and its relation to exposures and risk factors, hospital wards, duty hours, and professions. The participants used a validated photographic guide to measure the severity of their disease. A multiple choice test was used to measure knowledge of skin protection. We also explored domestic related exposures, allergies, and the presence of atopic skin disease. Overall, 2269 people responded to the questionnaire (71.3%), and among the respondents 21% reported having hand eczema within the past year.18 19
The participants were examined clinically at study entry and a trained nurse obtained information on baseline variables immediately before randomisation. The examination included scoring the severity of the disease, self reported assessment of severity (using a photographic guide), quality of life, number of eruptions during the past three months, use of preventive measures (protective gloves, moisturisers, and disinfectants), and knowledge of hand eczema. After the examination, participants were randomised individually to the intervention group or control group (treatment as usual). The participants in the intervention group were subsequently patch and prick tested. A trained doctor read the test three days later and provided individual counselling. The participants in the intervention group were offered usual treatment if needed. The participants in the control group received no further treatment in the trial but were offered usual treatment if needed. Treatment as usual covered standard practice for general practitioners in Denmark.20 No restrictions were applied to past or future management of hand eczema.
At the five month follow-up, the nurse who carried out the initial clinical examination obtained the outcome measures in an observer blinded fashion.
According to the protocol, follow-up was planned at six months from study entry. For logistical and seasonal reasons, however, the actual follow-up time was five months. This was because the inclusion of participants took longer than expected and because we wanted to avoid confounding from the spontaneous improvement of eczema from increased exposure to ultraviolet radiation and humidity during summertime.
The Copenhagen Trial Unit randomised participants individually and centrally using a computer generated allocation sequence with a block size of 10. The allocation sequence and block size were concealed from the clinical investigators. Randomisation was stratified according to clinical site (the three hospitals), profession (doctors or nurses, nursing aids, and biotechnicians), and severity of disease (scores <8 or ≥8 on hand eczema severity index at study entry). Once participants had given verbal and written informed consent to take part in the study, they were irrevocably included. About half an hour later the investigators telephoned the Copenhagen Trial Unit and were told the allocated intervention.
A trained nurse who was blinded to treatment allocation obtained the outcome measurements. It was not possible to blind the participants or the doctors to treatment allocation. The blinded nurse carried out double data entry and a blinded statistician analysed the data. To reduce the risk of information bias, the participants were individually requested not to share information.
The primary outcome was the score on the hand eczema severity index at follow-up. This validated scoring system grades the intensity of erythema, induration, papules, vesicles, fissures, scaling, and oedema for five areas of each hand (fingertips, fingers (except the tips), palms, back of hands, wrists) on a scale from 0 to 3, with the scores added up for each of the areas. The extent of affected skin in each area is graded from 0 to 4. The intensity and extent of the eczema are multiplied and the total score ranges from 0 to 360 (the higher the score, the more symptoms are present).21 The score for even severe disease (as applied to atopic dermatitis) is often considerably lower than the highest possible score.22 The score is based on clinical practice, although studies have not yet defined the difference necessary for clinically important change.
The secondary outcomes were scores on the dermatology life quality index at follow-up, self evaluated severity of disease at follow-up, the number of eruptions during the past three months, skin protective behaviours (preventive measures), and knowledge of skin protection at follow-up. We chose to use the dermatology life quality index scoring system, a validated quality of life instrument designed for skin diseases in general, as no quality of life instrument is specifically designed for people with hand eczema. The index comprises a 10 item questionnaire, with a total score ranging from 0 to 30 points when the scores for each question are summed. The higher the score, the poorer the quality of life.23 Self evaluated disease severity was measured with a validated photographic guide.24 Skin protective behaviour was measured as instances of daily hand washing and hand disinfection and use of protective gloves and moisturisers at work and at home. Knowledge of skin protection was measured as the total number of points achieved in a repeated multiple choice questionnaire with four questions on skin protection. Scores ranged from 0 to a maximum of 10 if all answers were correct.
Intervention group
At study entry participants in the intervention group were patch tested (Thin Layer Rapid Use Epicutaneous Patch Test; SmartPractice, Phoenix, AZ; standard series panel 1 and 2 supplemented by chlorhexidine digluconate 0.5%, primin 0.01%, sesquiterpene lactone mix 0.1%, budesonide 0.01%, tixocortol pivalate 0.1%, hydroxyisohexyl-3-cyclohexene carboxaldehyde 5%, methyldibromo glutaronitrile 0.5%, and fragrance mix II 14%) and prick tested (ALK-Abello Pharmaceuticals, Mississauga, Ontario, Canada; soluprick standard series, chlorhexidine 0.5%, latex). The patch test was used as recommended by the manufacturer.25 Adhesive panels of allergens were applied to the back and were removed by the recipient after 48 hours. A trained doctor evaluated the skin 72 hours after application. The prick test was carried out according to the manufacturer's recommendations.26 A drop of allergen extract was placed on the arm, and the skin was pierced through the drop with a lancet, ensuring the allergen penetrated the skin. Histamine was used as a positive control and prick testing without allergen as a negative control. The skin was evaluated after 20 minutes and any weal measuring 3 mm or more was considered a positive reaction.
We obtained a history of work related and domestic exposures. The participants were given instructions on how to avoid relevant allergens and how to protect their skin at work and at home. The participants applied a fluorescent emollient to their hands; we used ultraviolet radiation to determine whether it had been successfully applied. The doctor observed hand washing and advised the participants to use cold or lukewarm water, to wet their hands before using the detergent, and to dry their hands carefully with paper wipes.27 The wearing of rings was discouraged. The doctor instructed the participants according to a skin protection programme and handed out a written version of the advice.3 The participants were encouraged to use disinfectants instead of washing their hands when the skin was not visibly dirty (according to workplace recommendations) and to use a lipid-rich moisturiser free of fragrances at least three times daily during working hours (on arrival, before lunch, and before leaving) and at bedtime. Protective gloves were recommended to be worn during wet work and while handling drugs, cleaning, and cooking (handling of vegetables, raw meat, and fish). When the gloves were expected to be worn for more than five minutes, cotton gloves were recommended to be worn underneath. The time spent on reading the patch test and individual counselling was 20 to 30 minutes per participant.
Participants in the intervention group with severe hand eczema requiring medical treatment were advised to consult their general practitioner or dermatologist.
Control group
Participants in the control group received no intervention. If they had severe hand eczema that needed medical treatment, they were advised to consult their general practitioner or dermatologist.
Sample size calculation
In this superiority trial we planned to include a minimum of 262 participants. The sample size calculation was based on the expected mean difference of 4 points on the hand eczema severity index between the intervention group and control group at follow-up (10 v 14).28 The α error level was 5% and the β error level was 20%. We determined that, with a standard deviation of 13 on the hand eczema severity index score, 131 participants would be required in each intervention group.29
Statistical analysis
We carried out an intention to treat analysis, with a two sided level of significance set at 0.05.
For continuous variables we used the general linear univariate model, with the intervention indicator included as the independent variable. We repeated this analysis with the baseline value and included the three prespecified stratification variables as covariates. If the assumptions of the model were violated in both analyses, we used the Mann Whitney test to compare the intervention groups.
Where the intervention indicator was included as a covariate we analysed ordinal outcomes using the proportional odds model. We repeated the analysis with the baseline value and included the prespecified stratification variables as covariates. If the P value of the score test of the proportional odds assumption was <0.05 in both analyses, we used a non-parametric test (Mann Whitney) to compare the groups.
We considered the data from the unadjusted analyses as the primary results. If, however, the model assumption was significantly violated in the unadjusted but not the adjusted analysis, we used the data from the adjusted analysis as the primary results.
For the primary outcome we imputed missing values to obtain a worst case scenario. To achieve this we imputed missing values by the maximum value found in the material in the group showing a beneficial effect and by the minimum value found in the material in the other group.
In the survey, 397 healthcare workers gave an affirmative answer to the question "Have you had hand eczema during the past 12 months." Of these, 255 (64%) agreed to participate in the trial and no further recruitment was possible. Of the 142 healthcare workers contacted by email and telephone to ask about reasons for not participating, 103 (72%) responded: 66 did not want to participate, 15 were pregnant, 13 had changed job or moved, 4 could not spare the time, 3 were taking immunosuppressive drugs, 1 was on long term sick leave, and 1 had died. Overall, 123 participants were randomised to the intervention group and 132 to the control group (figure⇓). Randomisation was stratified according to hospital, profession, and clinical scoring of disease severity.
Table 1⇓ shows the characteristics of the participants in the two groups. One participant in the intervention group and two participants in the control group required treatment as usual for severe eczema. They were prescribed topical corticosteroids.
Dropouts and missing values
Follow-up data were available for 247 of the 255 (97%) participants. In the intervention group, 122 of 123 participants received the intervention as planned; one did not attend. Two participants were excluded at follow-up because they were pregnant and one did not attend. In the control group one participant was excluded because systemic corticosteroids had been prescribed and three participants did not attend follow-up.
Table 2⇓ shows the absolute and percentage distribution of missing values for the outcome measures. Only for the outcome use of moisturisers at work was the percentage of missing values significantly related to the intervention (Fisher's exact test P=0.034). Otherwise the differences in percentage of missing values between the intervention groups were not significant. In five instances more than 5% of the values were missing.
Disease severity, quality of life, knowledge of hand eczema, and skin protection
Table 3⇓ shows the distribution of scores on the hand eczema severity index (the primary outcome), scores on the dermatology life quality index, and scores on knowledge of hand eczema and skin protection. The intervention group had significantly lower mean scores on the hand eczema severity index than the control group: difference of means: unadjusted −3.56 (95% confidence interval −4.92 to −2.14); adjusted −3.47 (−4.80 to −2.14), in both cases P<0.001 for difference. After the missing values had been imputed to obtain the worst case scenario the means of the groups still differed significantly (5.57 v 8.01, parametric test P=0.003). Since the assumptions of the parametric test were not quite fulfilled, a non-parametric test was also carried out after the imputation (Mann Whitney test P<0.001).
The intervention group also had significantly lower mean scores on the dermatology life quality index than the control group: difference of means: unadjusted −0.78, non-parametric test P=0.003; adjusted −0.92 (−1.48 to −0.37). Knowledge of hand eczema and skin protection at follow-up was not statistically significantly different between the groups.
Self evaluated disease severity and skin protective behaviour
Table 4⇓ shows the results of the ordinal regression analyses. Self evaluated disease severity was lower in the intervention group than in the control group (P=0.001). This may be assessed from table 5,⇓ which shows the estimated probability of each answer in the intervention groups for those outcomes showing a significant difference in answer profiles between the two groups. Thus the intervention group had a higher probability of self reporting "mild" disease than the control group (62.0% v 41.5%). By contrast the probabilities of self reporting "moderate" and "severe" were both higher in the control group. The groups also differed significantly for scores on hand washing at work (P=0.0047) and use of protective gloves during wet work (P=0.048), cooking (P<0.0005), and cleaning (P=0.0065). The estimated probabilities showed that in all cases the beneficial effect was associated with the intervention group (table 5).
The two groups did not differ significantly for use of disinfectants (P=0.12) or moisturisers at work (P=0.20).
Number of eruptions
Differences in the number of eruptions could not be calculated. Forty one participants reported having "constant" hand eczema instead of providing the number of eruptions.
In the present randomised clinical trial with blinded outcome assessment of healthcare workers with hand eczema, a simple intervention of skin care education and individual counselling on work and home related exposures and contact allergies had a statistically significantly positive effect on severity of disease and quality of life as well as on self reported severity and skin protective behaviour by hand washings and wearing of protective gloves at the five month follow-up. We carried out 13 tests of significance and used Holm's adjustment for multiple testing.30 Variables that were still significant at the 0.05 level after correction were scores on the hand eczema severity index and on the dermatology life quality index, self evaluated disease severity, use of protective gloves while cooking, and hand washing at work.
Interpretation of results
In studies on people with hand eczema referred to hospital units the mean hand eczema severity index scores are reported to be in the range 17 to 20.28 31 The lower score observed in the present trial was expected as the participants were recruited from their work place and not from a dermatological clinic, and indicates that the hand eczema was mild to moderate in severity.
For our primary outcome, we observed a highly significant 3.56 difference in score on the hand eczema severity index between intervention and control groups at follow-up. In two recent studies examining the effect of soaps and moisturisers on the skin of the hand, differences in scores of 1 or 2 points between groups have been reported.32 33 In these studies the change in score was accompanied by a change in transepidermal water loss, reflecting impairment of the skin's barrier function, further confirming the clinical significance of even minor changes in scores.
In a study of people with hand eczema referred to hospital units or dermatology practice, the mean score on the hand eczema severity index was reported to decrease from 19.9 to 11.2 after dermatological treatment.28 This decrease should be interpreted in the light of more severe cases of hand eczema. By using the intervention programme in the present trial, cases of mild to moderate hand eczema changed in the direction of less severe or no eczema. Early intervention and treatment of hand eczema is known to significantly improve the prognosis and therefore the improvement in hand eczema obtained in the present trial is of clinical importance.34
The minimal, clinically significant difference in scores on the hand eczema severity index has not been investigated or estimated systematically. For our sample size calculation we considered a difference of 4 points in follow-up scores between the two groups to be clinically relevant. Our sample size estimation turned out to be larger than necessary because we used a greater standard deviation in the calculation than observed in the trial population (13 v 6.12). The included population had milder eczema and the condition was more homogeneous than in the population in the study from which the standard deviation calculations were based.29
The difference between the two groups of 3.56 points in scores on the hand eczema severity index was close to the expected 4 points. The change from baseline to follow-up was on average 3.97 in the intervention group (44% improvement) compared with 0.87 (9.3% improvement) in the control group. Even though the control group seemed to have a higher disease severity at baseline, this had no significant effect on the findings as a similar intervention effect was observed in the sensitivity analysis including baseline disease severity as a covariate. The result was not related to atopic skin disease, since neither current nor previous atopic skin disease was associated with improvement in scores on the hand eczema severity index.
The low scores on the dermatology life quality index at enrolment suggests the disease has a small effect on patients' quality of life.35 A score of 7 to 9 was reported in a recent study of people with hand eczema referred to hospital units.29 36 In a study of patients recruited from a patch test clinic with a dermatology life quality index score of 5, scores decreased by 3 after a positive patch test result compared with 1.5 after a negative result, and this difference between groups was interpreted to be clinically relevant.37 In the present trial the difference in dermatology life quality index score of 0.78 between groups at follow-up was highly significant. According to a previous study investigating the clinical relevance of scores in general patients in dermatology, the disease in the intervention group in the present trial changed from "having a small impact on a patient's life" to "having no impact on a patient's life."35 However, although statistically significant, the 0.78 difference in score is small and the clinical impact of this change remains uncertain.
The minimal clinically important difference in score on the dermatology life quality index has been investigated in more generalised skin diseases, with change in score ranging from 2.2 to 3.2 points.38 39 40 Scores are generally lower in more localised disease, however, and these figures therefore can not be directly translated to people with hand eczema. Caution has been urged in the interpretation of results on the dermatology life quality index for people with hand eczema, as the scores do not seem to cover all the impaired aspects of life and therefore owing to sensitivity problems the mean scores may be falsely low.41
In the healthcare sector the demand for frequent hand washing is often high. Frequent hand washing is known to be strongly associated with hand eczema.18 19 However, when hands are not visibly contaminated hand washings can be replaced by use of disinfectants.12 In the present study, hand washings at work were statistically significantly more frequent in the intervention group at follow-up as was use of protective gloves during wet work and cleaning, indicating better skin care and a lower risk of hand eczema. The intervention as such was effective on most outcomes. We cannot, however, distinguish the effect of the single components of the intervention (patch or prick testing, advice on hand care, time spent with the nurse or dermatologist). The effect was general and no specific subgroups (people with atopy or contact allergies) responded better than others.
Strengths and weaknesses of the study
This is the first randomised trial of skin care education and individual counselling on hand eczema in healthcare workers. The strengths of the trial include randomisation carried out both centrally and individually, observer blinded assessment of the primary outcome, and only a few participants lost to follow-up (97% completion rate).42 43 44 45 The statistical analyses were done blinded to treatment allocation.
The randomisation was stratified according to profession, hospital, and score on the hand eczema severity index at study entry, which ensured balance between the groups. The intervention had a simple design and included patch and prick testing. Counselling was carried out individually and included exposures both at work and at home.
Sixty six potentially eligible participants did not want to take part in the study and several others were excluded for various reasons. We are unable to know if these groups would have responded differently to the preventive measures.
On the basis of our sample size calculation we estimated that a total of 262 participants would be required for the study, but only 255 were included. Moreover, eight participants dropped out. A worst-best imputation showed that even under such extreme assumptions, prevention compared with treatment as usual led to significant improvements.
We cannot exclude the possibility of contamination of data by unplanned spread of information between participants as both groups were recruited by the same hospitals. To eliminate the risk of differences between the hospitals and to obtain data from a broader perspective for profession, specialty, and wards we preferred individual randomisation over cluster randomisation. Participants were each requested not to share information to prevent information bias. Even with the risk of contamination, the difference in mean score on the hand eczema severity index was statistically significant between the groups at five months. We suggest that elimination of contamination would increase the differences between the groups and strengthen the results even further.
The trial was not monitored by an external authority. However, the blinded observer investigator carried out double data entry, and 50% of the data was checked for errors by an coinvestigator not blinded to treatment allocation.
Meaning of the trial
Some work places have implemented standardised secondary prevention programmes for occupational hand eczema, but they are not sufficiently scientifically evaluated. In Germany, secondary prevention courses on an individual basis have been established in the health and welfare services in cooperation with the Accident Prevention and Insurance Association and are assumed to be effective.15 46 47 However, these programmes have never been evaluated in a randomised setting. Our trial provides high level evidence suggesting that secondary prevention is effective in healthcare workers with mild to moderate hand eczema. This is an important finding because many healthcare workers are affected and the condition can have a major impact on life.13 48 49 50 51 Studies investigating the effect of a similar programme in other types of workers (hairdressers, cleaners, and kitchen assistants) with more severe eczema would be interesting. Our data, together with data from previous observational studies, strongly suggests the efficacy of preventive programmes for hand eczema in healthcare workers.
Implementation of a secondary preventive programme in the healthcare sector may be economically profitable. In this study, in addition to the time spent on patch and prick testing, only one clinic visit of about 30 minutes was required to a trained dermatologist. Studies on the effectiveness and cost effectiveness of preventive programme on sick leave, rehabilitation, and disability pensions are needed.
Our trial provides evidence that a secondary preventive programme of skin care education and individual counselling based on allergy testing is effective. We suggest that such a preventive programme could be implemented in the healthcare sector if future trials support our findings and cost effectiveness is shown.
What is already known on this topic
Hand eczema is a common disease in healthcare workers
In 2009 skin disorders (predominantly hand eczema) accounted for one third of the recognised occupational diseases in Denmark, and the costs to society are extensive
Preventive programmes are known to be effective as primary prevention for wet work occupations
What this study adds
Our trial provides evidence that a secondary preventive programme of skin care education and individual counselling based on allergy testing is effective in healthcare workers with mild to moderate hand eczema
We suggest that a secondary preventive programme as ours should be implemented in the healthcare sector if future trials support our findings and cost effectiveness is shown
Cite this as: BMJ 2012;345:e7822
Contributors: KSI, TA, and GBJ planned and implemented the trial at different sites. KSI was the main investigator and was responsible for the database. CG and JLH contributed to the original design and were responsible for randomisation and active in the interpretation of the results. TD contributed to the original design of the trial. PW was responsible for the statistical analyses. SFT was helpful in the use of SPSS. KSI drafted the manuscript, which was reviewed by all authors. All authors have approved the final report. KSI, TA, and GBJ are the guarantors of the study.
Funding: This study was funded by Region Zealand's Research Fund and the Danish Working Environment Research Fund.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: GBJ is on the advisory board of Abbott Laboratories and Pfizer, Coloplast and Leo Pharma, in speakers bureau of Galderma and Novartis, and investigator of Actelion, Janssen Pharma and Abbott Laboratories. TD has been a consultant for Spirig Pharma, Basilea Pharmaceutica, Firmenich, Novartis, Procter & Gamble, and Evanik Industries, and in the speakers bureau of Actelion Pharmaceuticals, Almirall, Basilea Pharmaceutica, Leo Pharma, Spirig Pharma, and Astellas. TA is in the speakers bureau of Abbott, Basilea Pharmaceutica, and Leo Pharma. KSI, CG, JLH, PW, and SFT have no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: This study was approved by the Danish Research Ethics Committee System for Region Zealand (registration No SJ 126).
Data sharing: No additional data available.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

subset: commoncrawl


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While most of the top quarterbacks in a muddled class will be working out fully next week in Indianapolis, one of them won't be able to.
According to Daniel Jeremiah of NFL Network, Zac Dysert from Miami (Ohio) suffered a slight hamstring tear while training, and will be sidelined three or four weeks.
Dysert's working out at the IMG Academy in Florida, alongside West Virginia's Geno Smith and Arkansas' Tyler Wilson.
Dysert didn't impress during Senior Bowl week, and figures to fall somewhere in the middle of a quarterback class that it's hard to glean a consensus on.
He'll have to rely on his pro day workout in late March to impress scouts, playing from behind a bit since the others are going to be on display next week at the Combine.


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RAQQA, Syria, Aug. 26 (UPI) -- Media reports have focused on "Jihadi John," a British-born rapper, as James Foley's executioner, but another jihadist may have carried out the deed.
Attention in the U.K. has honed in on "Jihadi John" Abdel-Majed Abdel Bary, a 23-year-old British-born rapper who flew to Syria several months ago. He is the son of alleged al-Qaida mastermind Adel Abdul Bary, 53, who was extradited to the U.S. last year and is accused of planning the bombings of U.S. embassies in Africa in 1998.
But experts analyzing the video believe the execution may have been staged for the video, speculating the mask-clad speaker and the executioner are actually two different people.
An unnamed international forensic science company, conducting analysis for the The Times in London, noticed a "blip" in the footage indicating Foley may have had to repeat portions of a scripted statement, later edited together using "slick post-production techniques."
The expert said the video shows no blood on Foley's neck as the knife was drawn across his neck at least six times.
"I think it has been staged," one of the forensic experts told the news organization. "My feeling is that the execution may have happened after the camera was stopped."
Ross Patel, a forensics expert, told CNN there were "noticeable changes in their build, their physical appearance" between the speaker and the apparent actual executioner. The knife held by the speaker appears to be different than the one left next to Foley's body, and while the speaker has his pistol holstered on his left side -- indicating right-handedness -- the executioner appears to be left-handed.
The Islamic State is believed to have kidnapped Foley near the Turkey-Syria border nearly two years ago, reportedly holds a number of Western hostages.
The group, formerly associated with al-Qaida, has taken over large swaths of Iraq and has become Bashar al-Assad's principle antagonist in Syria.
In the week since Foley's death, another IS video has surfaced showing the execution of an Iraqi soldier, with the video in Arabic. The Foley video was in English and conducted by an executioner experts believe is British, a deliberate message to the U.S. and Great Britain.
FBI and British authorities believe they are close to identifying the executioner, whom Prime Minister David Cameron has said is likely to be a British citizen.
U.S. federal investigators also believe they have identified the social media account used to post the video, a "key part of the forensic" trail that would lead to Foley's killers.
They say the account belongs to a jihadist who is part of a group close to IS leadership and regularly posts images of the leadership's activities. A counterterrorism analyst told Fox News the account's proximity to IS leadership likely means Foley's kidnapping and execution likely came at the behest, or with the approval, of top IS brass.
Media learning of the name of the account have been asked not to publish it, to avoid tipping off its owner. Many within the group are already moving away from their regular social media patterns to evade detection.


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Manchester United drew 1-1 with Swansea in their first draw of the season
Manchester United were held to their first draw of the season as Swansea claimed a 1-1 stalemate at the Liberty Stadium.
Last Updated: 24/12/12 6:53am
Patrice Evra gave United an early lead, but Michu drew Swansea level before the half hour mark with his 13th goal of the campaign.
United dominated the second half and twice hit the crossbar, but Swansea defended brilliantly to pick up a share of the spoils.
After a bright start from Swansea it was United who created the first noteworthy effort of the game on 13 minutes when Wayne Rooney saw his swerving shot kept out by a smart save from Michel Vorm.
Vorm came to Swansea's rescue again a minute later when he produced a smart reaction save to keep out Ashley Young's shot inside the box after Carrick played the winger in on goal with a fine pass.
United made the breakthrough on 16 minutes with Evra heading home his third Premier League goal of the season after rising highest to meet Robin van Persie's whipped in corner with the ball going in off the far post past Leon Britton on the line.
Swansea came roaring back into the game and they drew level just before the hour mark with Michu netting his 13th goal of the season.
Wayne Routledge slipped in Jonathan de Guzman inside the box and his shot across goal could only be palmed out by David de Gea to the grateful Michu who tapped home the rebound from close-range.
United had a great chance to restore their lead just before the break when Evra got in down the left and pulled the back for the unmarked Rooney 12 yards from goal, but the England man could only fire his shot straight at Vorm.
Swansea started the brighter of the two sides at the start of the second half and De Gea was twice called into the action to keep out efforts from Kemy Agustien and Wayne Routledge.
Ashley Williams produced a superb block to deny Young inside the box after van Persie teed up the winger for a shot on goal.
The visitors were beginning to turn the screw and United were inches away from restoring their lead on 67 minutes when out of nothing van Persie saw his instinctive volley from Rooney's cross loop onto the crossbar.
Things threatened to boil over 16 minutes from time when Williams and van Persie were both booked after a melee involving the pair when after being fouled Williams drilled the ball into the Dutchman's head while he was on the ground.
United struck the cross bar for a second time on 78 minutes when Carrick got on the end of van Persie's corner and was unlucky to see his effort come back off the woodwork.
Swansea were defending in numbers and Williams and Davies produced vital blocks inside the box to deny van Persie and Young respectively as United piled on the pressure.
United threw everything at Swansea in the closing stages, but they could not find a way past as they had to settle for a point to move four points clear at the top of the table.


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WOMEN, Politics
Question: People talk about the changing roles of men and women today. For each of the following statements I read out, can you tell me how much you agree with each? Do you agree strongly, agree, disagree, or disagree strongly? On the whole, men make better political leaders than women do.
Source: World Values Surveys
Universe: Country: Uruguay
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In observance of Martin Luther King Jr. Day, the Law Library will closed on Monday, January 20.
The MLK holiday became federal law fifteen years after Martin Luther King, Jr.'s death. The holiday was first observed in 1986, but it took another 17 years for nationwide recognition. In 1994, the holiday was designated a day of service under the direction of the Corporation for National and Community Service. For resources about the life of Dr. Martin Luther King, Jr., visit the King Center Website.


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|March 2011
|OKLAHOMA'S eGOV NEWS REPORT
Welcome to Oklahoma's eGovernment News Report. We hope you enjoy the monthly report providing you with up-to-date information on Oklahoma's eGovernment achievements.
State of Oklahoma Announces Launch of OK.gov Twitter
Follow Oklahoma Government Tweets @okgov
OK.gov, Oklahoma's official website, announced today the creation of an account on the popular social media platform Twitter at http://twitter.com/okgov. Through Twitter, OK.gov will be able to quickly and efficiently notify the public regarding state agency news, Oklahoma government online services, and information affecting Oklahoma citizens during weather related events.
"This is a great opportunity to allow the public to be connected to information regarding Oklahoma government and news from our state agencies," says Alex Pettit, State Chief Information Officer. "This form of technology allows people to become informed conveniently and in a timely manner."
The announcement of an OK.gov Twitter account comes after the announcement that Oklahoma state and local government entities can now use the social media website Facebook. OK.gov plans to open a Facebook account in the near future.
"These two social media platforms provide Oklahomans an opportunity to keep up with developments in state government as the administration of Gov. Mary Fallin pursues a policy of transparency in government on many levels," said Preston Doerflinger, director of the OSF and secretary of finance.
To follow OK.gov's Twitter, visit http://twitter.com/okgov and select the "Follow" button. Once following, citizens will receive real-time access to tweets regarding state agency news and Oklahoma government.
Oklahoma Board of Tests for Alcohol and Drug Influence Launches New Website
The new site, built through OK.gov's Go Gov! Web Management Suite, allows BOT staff to easily build and maintain a website without the knowledge of programming languages. Go Gov! is an online product that is similar to using a combination of an Internet browser and a word processor. The system utilizes the new state agency template, which provides a common look for all Oklahoma's agency websites. This allows website visitors to feel secure that they are visiting an official Oklahoma government website.
The new website will serve as a gateway to the Oklahoma Board of Tests for Alcohol and Drug Influence's existing and future online licensing services. The website and online licensing services are products of a partnership between the Oklahoma Board of Tests for Alcohol and Drug Influence and OK.gov, Oklahoma's Official website.
Visit the Oklahoma Board of Tests for Alcohol and Drug Influence's New Website
Strong & Healthy Oklahoma Showcases Healthy Programs at HealthyPrograms.OK.gov
Search for Programs and Resources Available in your Community
In 2010, Strong & Healthy Oklahoma, a division of the Oklahoma State Department of Health (OSDH), conducted a 12-question survey to capture current physical activity, nutrition, and tobacco programs/resources across the state. The collected information is now available online through an Online Resource Inventory at http://HealthyPrograms.OK.gov.
"The information provided in this resource inventory will help the public find health programs in their community," said Landon Norton, OSDH Nutrition Coordinator. "The information provided in this resource inventory will provide creative ways for individuals and local communities to join in the effort to make Oklahomans healthier. Also, it will support the goals of the Strong & Healthy Oklahoma, the Get Fit Eat Smart OK State Plan, and the Oklahoma Health Improvement Plan, which are designed as guides to encourage healthy behavior changes," Norton said.
The public and interested health partners may search for programs and resources available in the community or look for program examples through the Online Resource Inventory. Types of programs include, but are not limited to, school, afterschool, or childcare-based programs, worksite-based wellness programs, community-based programs focusing on physical activity and/or nutrition.
Strong & Healthy Oklahoma will continually update the program database as new information becomes available to ensure the best possible representation of health programs in the state of Oklahoma. Those interested in adding their program to the Online Resource Inventory may do so by filling out the survey available at: http://www.surveymonkey.com/s/SHOresourceinventory
The Online Resource Inventory is a product of a partnership between Strong & Healthy Oklahoma and OK.gov, Oklahoma's official website.
What's Inside
Employment Security Commission New Hire Reporting
How Do I Sign up for Governor Mary Fallin's email notifications?
Visit the Governor Mary Fallin's Email Notifications Site
How Do I File My Business Taxes Online?
Visit the OuickTax System on the Oklahoma Tax Commission Website
Monday, May 30, 2011
View Upcoming 2011 State Holidays
OKC Home Show
Redbud Classic
OKC Festival of the Arts
Share Your eGov Story
Have an Oklahoma eGovernment story to tell? Want to give us feedback?
About OK.gov
OK.gov is the official website of the state of Oklahoma and a collaborative effort between the Oklahoma Office of State Finance (OSF) and Oklahoma Interactive, LLC to help Oklahoma government entities Web-enable their information services. OSF is responsible for OK.gov. Oklahoma Interactive operates, maintains, and markets OK.gov and is part of eGovernment firm NIC's (NASDAQ: EGOV) family of companies.
Learn more about Oklahoma's eGov News Report and view past issues
405.524.3468 or Toll Free at 1.800.955.3468


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The util_strcasecmp function performs a comparison of two alphanumeric strings and returns a -1, 0, or 1 to signal which string is larger or the strings are identical.
The comparison is not case sensitive.
int util_strcasecmp(const char *s1, const char *s2);
1 if s1 is greater than s2.
0 if s1 is equal to s2.
-1 if s1 is less than s2.
char *s1 is the first string.
char *s2 is the second string.


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The majority of Mitsubishi vehicles have a number of different limiters on them. Speed can be limited in a number of ways. Some limiters will slow you down based on the throttle position, limp mode, sensor failures, RPM and actual speed travelled. While all limiters can be disabled globally, we feel that disabling only specific sets is a better approach as limiting the maximum speed can be a good idea when certain hardware failures have occurred or the computer detects that a transmission is overheating.
While we do not advocate exceeding posted speed limits on public roads, there are sometimes situations where users would rather not have the factory speed limiter engaged. While racing on closed roads or race tracks many vehicles are certainly capable of exceeding the factory programmed limits. We leave the details and safety considerations up to the end users but there are also a few ways you can verify that your speed limiters have properly been removed.
We normally do our testing on a chassis dynomometer. With this, the wheels rest on rollers and the vehicle can be safely run at very high speeds without the vehicle physically moving.
Disabling Mitsubishi Speed Limiters
UVTune & FastWorks support for Mitsubishi vehicles
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Just Say It Like It Is
As I lay napping in my recliner the other evening with the TV on, I was rudely awakened by this loud obnoxious announcer guy trying to make me believe – in a raucous voice better suited to be announcing the Friday Night cage fights – that "Sellum, Bilkum and Cheetum" was the only auto dealer in the world from which (whom?) to buy a new car.
He promised "thousands of dollars in instant cash rebates, no financing charges for the next millennium", and I thought I heard mention of a free glow-in-the-dark Hula Hoop with every pickup purchase. But maybe I just imagined that part ... or did I?
Seems these days, companies will promise anything in their advertisements to get you to buy their product. Buy one get one free gimmicks, mail in rebates – which go in my file of all time un-favorites – cash incentives, glorious weekend getaway vacations, a free puppy and whooda thunk it, a free pop-up toaster.
What about the guy who talks a mile a minute with a disclaimer that tells the real story, but who can understand him? And what's with all that unreadable gibberish at the bottom of the page or on TV? Who reads that stuff? Who CAN read it? And what does it all mean?
I'll tell you what it means.
It says, in lawyer-ese, that all you have read in the large print or heard with your very own "hears" is pure Double D Bull! It says "Ya gotta read the fine print, Sonny, to get the real Rest of the Story. And in most cases the fine print is the killer.
That's where you find all the "therefores," "where-ofs," therebys" and "whatnots" that almost completely negate the feel good, warm-fuzzy commercial you just read or heard.
It's the harsh reality friends and you had best get out your Genuine Dick Tracy Spy Glass and Decoder Ring and peruse the fine print before you sign on the dotted line.
And have you ever REALLY read all the fine print in the "You have been Pre-Approved" credit card applications every one of us gets in the mail? Yikes! Nightmare on Credit Street!
I sent a credit card pre-approved application back to the company with the words "You gotta be Kidding! Have YOU read the Fine Print? Would YOU agree to this?" written in large Magic Marker.
I haven't received another application from that particular company for at least two years.
I tried Free Credit Report.com ( "Get your Free credit report Free") only to find that the word "Free" does not actually apply.
See, here's how that particular scam works. After you have punched in all the required info including your hat size and the number of dead house plants in your home, and have hit the "continue" button, up comes this screen that reads, "Your account will be charged a returnable fee of one dollar if you wish to continue."
(In a fit of total mental collapse I typed in my debit card number. I guess you could say I'm related to that famous writer of "The Count of Monte Cristo,",Alexander Dumass. Pronounced Dewmaw, according to Alex Trebek, but in my case he could be wrong).
The dollar fee enabled me to "be eligible" to read my full credit report and score, all I had to do was give them another (non-refundable) $17.85.
At this point I declined and escaped from their web page.
A few days later I had occasion to check my bank account and found that not only had they absconded with the refundable' dollar, but they had also stolen the non-refundable $17.85 that I had not authorized.
After 45 minutes on the phone trying to understand what foreign accent I was trying to understand, I finally got them to credit my account with both the $1 AND the non-refundable $17.85.
I guess that old adage "the squeaky wheel gets the worm" really works.
That's it for now folks. Thanks for listening.


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WiMax Finally Available... In 2008... In Baltimore
from the took-'em-long-enough deptFor years and years we used to make fun of the press and analysts for either saying that WiMax existed when it did not or for predicting huge uptake before the tech was even ready. Plenty of companies offered wireless broadband, but it was not WiMax, no matter what they (or the press) called it. Back in 2003, we even made a pretty clear prediction: WiMax would not be ready for prime time until 2008, going against plenty of analysts who insisted it would be the big thing in 2004. And 2005. And 2006. And 2007. So, it's nice to see Sprint squeeze in the launch of its WiMax Xohm service before the end of 2008, and make our prediction accurate. Of course, those analysts who predicted huge WiMax success stories in 2004 have moved on and have already declared WiMax dead, and now LTE is the huge success story to watch out for. Let's wait and see on that one as well. There's just something about wireless technologies that make the press and analysts assume that what is being talked about at the tech level will take the world by storm immediately. These things take time.
Filed Under: baltimore, wimax, wireless, xohm
Companies: sprint


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OKLAHOMA CITY (Reuters) - A 33-year-old Oklahoma man has been charged with killing his stepfather by giving him an "atomic wedgie," that caused the victim to suffocate on his own underwear.
Brad Lee Davis was charged with murder in the death of 58-year-old Denver St. Clair in a drunken family fight at a residence just east of Oklahoma City, the Pottawatomie County Sheriff's Office said in an arrest affidavit obtained on Wednesday.
Police arrested Davis on Tuesday. The affidavit said he "grabbed St. Clair's underwear and gave him an 'atomic wedgie.' Davis allegedly pulled the elastic waistband of St. Clair's underwear over his head and around his neck."
Oklahoma Medical Examiner spokeswoman Amy Elliott said the cause of death was asphyxiation and blunt force trauma.
Pottawatomie County Sheriff Deputy Travis Palmer said Davis and St. Clair were drinking beer on the night of December 21 at the older man's residence when St. Clair began speaking ill about his wife, who is Davis' mother.
Investigators said St. Clair's elastic waistband was stretched over his head and that it left ligature marks around his neck. Blood splatter was also found in the kitchen, the living room and on the living room ceiling.
Davis was being held in Pottawatomie County without bond. His lawyer was not immediately available for comment.
Editing by Jon Herskovitz and David Gregorio


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GLAAD Media Awards: Grey's Anatomy, Supergirl and Transparent Land Nominations
Jan 31, 2017 10:17 AM EST
Nominees for the 28th annual GLAAD Media Awards, which recognize fair, accurate and inclusive depictions of LGBTQ stories, were announced Wednesday. Television nominees include Grey's Anatomy, Crazy Ex-Girlfriendand Supergirl. "At a time when progres… Read more


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There are many blogs out there that offer great lists of tips on how to write a good query letter and how to survive the agent hunt with the least possible amount of bodily harm and psychological trauma. I don't want to waste your time by repeating their advice. (But in case you want to check out Nathan Bransford's one-stop shop for topnotch query advice, swing by HERE.)
I will offer you this one little suggestion though: WATCH THIS.
J.J. Abrams, the creator of LOST, Alias, and Cloverfield, talked about the importance of the MYSTERY BOX in television and film. I'm going to stay away from debating about how LOST ended (sigh), but I will take my hat off to Mr. Abrams for the incredible job he did at reeling viewers into the mystery of the show's first season. Who wasn't dying to know what "the numbers" meant or who "the Others" were? He threw in a "smoke monster" and we were hopelessly hooked.
I believe the power of the mystery box applies to query letters as well. An effective query letter is like a good blind date – you give enough away to pique a person's interest, but leave him/her wanting more. Give too much, and kiss a second date good bye. Give too little, and the crickets will break into a chorus. So my humble advice is, dress well, comb your hair, and keep a smoke monster in your pocket at all times.
* Switches to Sir David Attenborough's voice * If you hide quietly behind the bushes and wait patiently, you may just see that rare and elusive creature known as the literatus agentus climb into your carefully laid mystery box.
p.s. I know that the characters from BEFORE EVER AFTER were supposed to stop by this week, but I'm still getting clearance for the excerpts I'll be sharing with you. Stay tuned! But as promised, I did bring chicken wings. The beer's in the fridge. Make yourself at home :-)


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SizeSmall: 300m2 - 500m2Medium: 500m2 - 1000m2Large: >1000m2
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Building TypeFarmaBuild (Rural)EquinaBuild (Equestrian)XpandaBuild (Commercial)StrongaBuild (Industrial)COLABuild (Education)DesinaBuild (Custom)HangaBuild (Aviation)SmartaBuild (Backyard Shed/Garage)
Unfortunately, we're located in Victoria and unable to travel interstate for small builds.
Wide span sheds with large spans are a specialty of Central Steel Build.
Hay sheds to fit any size and amount of hay bales
Protect your valuable farm machinery, vehicles, tools and equipment.
Versatile and flexible, to help you do the job better.
Trust Central Steel Build for farm sheds that are unmatched in robust construction and personal service.
Efficient and workable buildings that will meet your present and future needs
Individually designed yard covers for all-weather working conditions.
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Ride and train all year round in a dream-come-true indoor horse arena
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Anyway, I'm wondering if the site has a memberlist page? I'm asking because the way this navigation is set up is somewhat foreign to me, and I can't find an easy way to find the names of members, either to PM or to view aspects of their profile. In fact, the only way I can view a member's profile, that I know of, is by finding a post of theirs, and then clicking on their name. Any info?
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The Department of Chemical Engineering guarantees an undergraduate research experience to every student before graduating, and 70-90% of recent graduating classes have done research.
We also send students (fully funded) to national research conferences at a rate exceeding all other ChemE programs nationally.
A chemically powered car for Bucknell's entry in the American Institute of Chemical Engineers' "ChemE" Car Competition.
Learn to design and analyze products and systems that transform raw materials chemically, physically or biologically into materials that improve products and enhance lives.
You will work closely with faculty in the classroom and on independent research projects, and get plenty of hands-on experience that links theory and practice, always keeping the public and the environment in mind. Upper-level design students work on real-world projects. The curriculum also offers study-abroad opportunities, preparation for graduate study, specialized technical tracks or premedical training.
Each year, about 25 percent of our junior year engineering students study overseas at such locations as the United Kingdom, Australia and Spain.
A number of graduating seniors in chemical engineering pursue advanced degrees. In addition to the master's degree program which students may enter once their bachelor's degree is completed, we offer an accelerated 3-2 program leading to both a bachelor of science and a master of science.
More than 75% of our students work with faculty on independent study research projects at Bucknell.
Students can tailor the curriculum to their interests, which may include study abroad, pre-medical training, preparation for graduate study or pursuit of a concentration within the major (biological, environmental, materials, process).
Average number of majors per class year: 25-30
"I expect my students to pursue their work with academic rigor and do a quality work of which they can be proud."More about Professor Maneval
"Trying to study this thing on the nanoscale is really trying to help the world on a global scale."More about Professor Raymond
"The students here are the main focus. They take an active part in research, write up their papers and, in many cases, present them at national conferences themselves."More about Professor Wakabayashi
Students often participate in research projects with faculty mentors. Recent projects include:
Each year, about 25 percent of our junior year engineering students study overseas at such locations as the United Kingdom, Australia and Spain.
Bucknell provides opportunities for students to find summer employment in industry, government or academia.
Make an online gift to support the Department of Chemical Engineering.
ABET: Bucknell's chemical engineering degree program is accredited by the Engineering Accreditation Commission of ABET, www.abet.org.
323 Dana Engineering Bldg
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