Reliable test of clinicians' mastery in skin cancer diagnostics.

Differentiating between benign and malignant skin lesions can be very difficult and should only be done by sufficiently trained and skilled clinicians. To our knowledge there are no validated tests for reliable assessments of clinicians' ability to perform skin cancer diagnostics. To develop and gather validity evidence for a test in skin cancer diagnostics, a multiple-choice questionnaire (MCQ) was developed based on informal interviews with seven content experts from five skin cancer centers in Denmark. Validity evidence for the test was gathered from May until July 2019 using Messick's validity framework (content, response process, internal structure, relationship to other variables and consequences). Item content was revised through a Delphi-like review process and then piloted on 36 medical students and 136 doctors using a standardized response process. Results enabled an analysis of the internal structure and relationship to other variables of the test. Finally, the contrasting groups method was used to investigate the test's consequences (pass-fail standard). The initial 90-item MCQ was reduced to 40 items during the Delphi-like review process. Item analysis revealed that 25 of the 40 selected items were level I-III quality items with a high internal consistency (Cronbach's α = 0.83) and highly significant (P ≤ 0.0001) differences in test scores between participants with different occupations or levels of experience. A pass-fail standard of 12 (48%) correct answers was established using the contrasting groups' method. The skin cancer diagnostics MCQ developed in this study can be used for reliable assessments of clinicians' competencies.

Hand eczema­prognosis and consequences: a 7-year follow-up study.

BACKGROUND: Hand eczema is recognized as a long-lasting disease with personal and societal repercussions. Long-term studies are required to generate information on factors contributing to a poor outcome. OBJECTIVES: The aims of this 7-year follow-up study were to evaluate the clinical course of patients with hand eczema, the occupational consequences and to identify risk factors associated with a poor prognosis. MATERIALS AND METHODS: In all, 536 patients with hand eczema participated and were examined by a dermatologist. The clinical severity was assessed at baseline and 7 years later using a self-administrated photographic guide. Additional information was obtained from a questionnaire. RESULTS: Based on the photographic guide, 73% experienced a clinical improvement. Notably, 20% had moderate to very severe hand eczema at follow-up. Severe hand eczema or frequent eruptions at baseline and eczema in other body locations during the follow-up period were risk factors of a poor prognosis. The same factors, as well as being a woman, were associated with occupational consequences and low health-related quality of life. Of those with persistent hand eczema only 40% had visited a dermatologist during the follow-up period and 7% had oral treatment. CONCLUSIONS: The disease had improved 7 years later; nevertheless, many patients continued to have considerable symptoms. Patients with a greater risk of a poor outcome are characterized by frequent eruptions, severe hand eczema and more widespread eczema. It should be questioned if more aggressive therapy and closer medical follow-up would be beneficial.

Delay in medical attention to hand eczema: a follow-up study.

BACKGROUND: Hand eczema often runs a chronic course but early medical intervention may be assumed to improve the prognosis. OBJECTIVES: To follow patients with hand eczema for 6 months after seeing a dermatologist to investigate if delay in medical attention would impair the prognosis. METHODS: Study participants were 333 patients with hand eczema from nine dermatological clinics in Denmark. Severity of hand eczema was assessed by the patients at baseline and at the 6-month follow up using a self-administered photographic guide. Additional information was obtained by self-administered questionnaires. RESULTS: Median patient delay (defined as the period from onset of symptoms until seeing a general practitioner) was 3 months [interquartile range (IQR) 1.5-8.0]. The median healthcare delay (defined as the period from the first visit to a general practitioner until seeing a dermatologist) was 3 months (IQR 1-8). In a logistic regression model, the odds ratio of a poor prognosis increased by a factor of 1.11 [95% confidence interval (CI) 1.02-1.21] per month of patient delay and by 1.05 (95% CI 1.00-1.10) per month of healthcare delay. CONCLUSIONS: A poorer prognosis of hand eczema was associated with longer delay before medical attention.

Clinical severity and prognosis of hand eczema.

BACKGROUND: Hand eczema (HE) is a frequent, long-lasting disease with both personal and societal repercussions. Consequently, more information is needed on factors that maintain symptoms. OBJECTIVES: In this study, patients with HE were followed for 6 months from the first visit to a dermatologist to identify factors associated with severe disease and a poor prognosis. METHODS: Study participants were 799 patients with HE from nine dermatological clinics in Denmark. Severity assessment of the HE was done at baseline and at the 6-month follow-up using the Hand Eczema Severity Index (HECSI) and by patients using a self-administered photographic guide. Additional information was obtained from a baseline questionnaire. RESULTS: At baseline, 60.3% assessed their HE as moderate to very severe using the self-administered photographic guide compared with 36.1% at follow-up. The mean HECSI value decreased from 19.9 points at baseline to 11.2 points at follow-up (P < 0.001). In a multivariable logistic regression analysis, statistically significant associations with severe HE at baseline were older age (P < 0.001), atopic dermatitis (P = 0.01) and > or = 1 positive patch test (P < 0.001). Being an unskilled worker was a predictor for a poor prognosis at follow-up (P = 0.04), and the presence of frequent symptoms during the previous 12 months was associated with severe initial disease (P = 0.02) and a poor prognosis (P = 0.04). CONCLUSIONS: Overall, the disease had improved 6 months after the dermatological examination: nevertheless, many patients continued to have significant symptoms. Dermatologists should pay special attention to patients with frequent eruptions and to unskilled workers.

Medical consultations in relation to severity of hand eczema in the general population.

BACKGROUND: Hand eczema is a common disease with a wide severity spectrum. Little information exists concerning the association between the severity of hand eczema and medical consultations. OBJECTIVES: To describe the self-rated severity of hand eczema in a general population and the relationship to seeking medical attention. METHODS: A questionnaire on self-reported hypersensitivity including two questions on hand eczema was sent to a random sample of 6000 individuals, aged 18-69 years, living in Copenhagen, Denmark. A total of 4242 individuals (71%) answered the questionnaire. All individuals who reported hand eczema (n = 752) within the previous 12 months received a more detailed questionnaire focused on hand eczema and a previously validated photographic guide with four groups of severity ranging from almost clear to very severe. RESULTS: Five hundred and sixty-four individuals (75%) returned the second questionnaire. The 1-year period prevalence of hand eczema was estimated to be 14% in the population. Twenty-three per cent rated their hand eczema as moderate to very severe. In total, 67% had consulted their general practitioner and 44% had consulted a dermatologist because of hand eczema. Multivariate analysis showed a positive association (P < 0.05) between severity of hand eczema and medical consultations. Of those individuals (n = 102) who had not consulted a dermatologist 26% had experienced moderate to very severe hand eczema within the previous 12 months. CONCLUSIONS: A considerable proportion of individuals with moderate to very severe hand eczema in the general population miss out on the potential benefit of a dermatological examination, patch testing and a thorough-going exploration of environmental factors.

Severity of hand eczema assessed by patients and dermatologist using a photographic guide.

BACKGROUND: The severity of hand eczema is of interest in epidemiological studies. Ideally, as no validated methods of self-assessment exist, a dermatologist should examine all subjects. However, this is very resource intensive. OBJECTIVES: To examine if severity grading performed by patients with hand eczema using a self-administered photographic guide was in agreement with the assessment performed by a trained dermatologist. Furthermore, to measure the correlation between the severity of hand eczema expressed on a visual analogue scale (VAS) and the clinical severity assessment, using the photographic guide. METHODS: Fifty-three consecutive outpatients with hand eczema were included, a number based on a prestudy statistical calculation. The patients were asked to grade current severity of their hand eczema by choosing one of four groups of photographs representing differing severities of hand eczema. On the same day all patients were examined by an experienced dermatologist, who graded the severity using the same photographic guide. The photographic guide was a modified version of a validated guide for use by physicians. In addition, the patients rated the severity of their hand eczema on a VAS. RESULTS: Fifty-one of the respondents completed the full questionnaire. For 37 of the 51 patients (73%) the clinical severity assessments of patient and dermatologist were identical. The measure of agreement, Cohen's kappa coefficient, was 0.61, indicating good inter-rater agreement. The correlation between the dermatologist-rated severity and the corresponding score by the patients on the VAS was only moderate (Spearman's rank correlation coefficient rho = 0.52). CONCLUSIONS: The photographic guide for the self-assessment of hand eczema is an easy instrument to use, and for research purposes can be a reliable tool for patients with hand eczema to grade severity. A VAS can only be considered as a mediocre tool for estimation of the dermatologist-rated clinical severity, but should be validated as an independent instrument to assess severity of hand eczema.

A comparison of the hairpin stability of the palindromic d(CGCG(A/T)4CGCG) oligonucleotides.

The palindromic deoxyribonucleotides 5'-CGCGA-TATCGCG-3' and 5'-CGCGTTAACGCG-3' have been characterized by 1H NMR spectroscopy. The NMR data identified both B-DNA duplex conformations and hairpin conformations, the latter with loop regions consisting of the four central nucleotides. The resonances of the various conformations were assigned by use of two-dimensional NMR methods. The relative stability of the various conformations was investigated as a function of temperature, ionic strength and nucleotide concentration. The duplexes were found to be stabilized at high ionic strength and at low temperature, while the hairpins were stabilized at low ionic strength and at medium temperature. The thermodynamics of the duplex-hairpin and the hairpin-random coil transitions were examined, and compared to the other two oligonucleotide in the palindromic d(CGCG(A/T)4CGCG) oligonucleotide family. The relative stabilities of the duplex conformations with respect to the random coil conformations are similar for the d(CGCGAATTCGCG), d(CGCGATATCGCG) and d(CGCGTATACGCG) oligonucleotides. The duplex conformation of d(CGCGTTAACGCG) is less stable. The hairpin of d(CGCGTTAACGCG) seems also to be less stable relative to the random coil conformation than in the case of the other oligonucleotides at an equal oligonucleotide concentration. A cruciform intermediate between the duplex and hairpin conformations is suggested to explain some discrepancies observed in this work in case of the d(CGCGTTAACGCG) oligonucleotide. This is similar to what has been reported for the d(CGCGTATACGCG) oligonucleotide.

Hydrogen exchange studies of the Arc repressor: evidence for a monomeric folding intermediate.

The hydrogen exchange rates of the backbone amide and labile side-chain protons of the dimeric Arc repressor have been measured. For the slowly exchanging amides in the alpha-helical regions, these rates show a concentration dependence. To account for this dependence, the role of the monomer-dimer equilibrium was considered. Extrapolating the observed exchange rates to zero dimer concentration provides estimates of these rates in the monomer and shows that they are significantly retarded compared to those of an unfolded polypeptide. This suggests that the monomer is in a structured "molten globule" like state. In particular, the two helices of Arc retain a high degree of their secondary structure and it is proposed that the two amphiphilic helices are packed together with their hydrophobic faces. Evidence for a partially folded structure in the Arc monomer was reported earlier in two other studies [J. L. Silva, C. F. Silveira, A. Correia, Jr., and L. Pontes (1992) Journal of Molecular Biology, Vol. 223, pp. 545-555; X. Peng, J. Jonas, and J. L. Silva (1993) Proceedings of the National Academy of Science USA, Vol. 90, pp. 1776-1780]. By combining the results of these studies and ours, a folding pathway of the dimeric Arc repressor involving four different stages is proposed. Due to the low concentration of Arc repressor in the cell, the protein is present either as a free monomer or it is bound to DNA presumably as a tetramer. Therefore the folding pathway can be regarded as an integral part of the overall DNA binding process.

Sodium-23 and lithium-7 NMR spin-lattice relaxation measurements in the study intercalation in DNA.

Sodium-23 spin-lattice relaxation rate (the reciprocal relaxation time) measurements have been used to study the intercalation of 9-aminoacridine in calf thymus DNA. The results are analyzed by a two state model based on the counterion condensation theory and a theory for the quadrupolar relaxation of counterions in polyelectrolyte solutions. It is shown that change of the solvent from H2O to D2O has a negligible effect on the intercalation process. Furthermore, an attempt is made to analyze the dependence of the 7Li spin-lattice relation rate on intercalation of 9-aminoacridine in LiDNA. It is shown that both quadrupolar and dipolar mechanisms contribute to the bound 7Li relation rate, and that both these contributions are reduced upon intercalation of 9-aminoacridine.