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.

Diagnostic accuracy and interobserver concordance: teledermoscopy of 600 suspicious skin lesions in Southern Denmark.

BACKGROUND: Skin cancer incidences are increasing and early diagnosis, especially of malignant melanoma, is crucial. Teledermatology including teledermoscopy (TDS) can be used to triage referrals of suspicious skin lesions, however, this is not currently recommended in Denmark. OBJECTIVES: To evaluate diagnostic accuracy, sensitivity, specificity and interobserver concordance of TDS, and to evaluate the number of incidental lesions potentially missed by TDS. METHODS: Fifty general practices were invited to send images of suspicious skin lesions for evaluation using smartphone TDS. Simultaneously, the patient was referred for a face-to-face (FTF) consultation. Images for TDS were independently evaluated by two dermatologists; a third dermatologist performed the FTF consultation. Diagnosis, management plan and level of diagnostic confidence were noted. For TDS photo quality was rated, and for FTF any incidental findings were described. RESULTS: Six hundred lesions in 519 patients were included. The diagnostic accuracy was significantly higher on FTF evaluation than on TDS (P < 0.01). However, this was associated with a significant difference in specificity (P ≤ 0.012) whereas no significant difference was found in sensitivity. The concordance between FTF and TDS, and the interobserver concordance of two TDS evaluations was moderate to substantial (AC1 = 0.57-0.71). Incidental melanomas were found in 0.6% of patients on FTF evaluation, adding an extra 13% of melanomas. However, on TDS these patients' photographed lesions all warranted FTF follow-up, where these melanomas would have been identified. CONCLUSION: In this large prospective study, no significant difference in sensitivity was observed between FTF and TDS, but specificity was lower on TDS than FTF. Taking management plans into account, we would, however, potentially have dismissed 2 of 23 melanomas, if only TDS had been used for assessment. One of these was a melanoma located on the scalp, an anatomic region less suitable for TDS.

Pregnancy outcome in four women with inflammatory bowel disease treated with budesonide MMX.

BACKGROUND: Maintaining disease remission throughout pregnancy in women with inflammatory bowel disease is of the utmost importance to decrease the risk of adverse outcome. In general, corticosteroids are safe to use during pregnancy, but no data exist in the specific use of budesonide MMX. We report four cases of budesonide MMX in pregnancy and pregnancy outcome. METHODS: Four women with inflammatory bowel disease experienced disease activity during pregnancy. They were treated with budesonide MMX in an attempt to obtain clinical remission. Disease activity was assessed through physician's global assessment as well as lower endoscopy. RESULTS: Budesonide MMX proved effective in achieving remission in three out of four women. One woman had an uncomplicated colectomy in the second trimester. All children were born normal for gestational age, with no congenital abnormalities and have reached all their developmental milestones. The four children have received vaccines according to the national immunization program without complications. CONCLUSION: No adverse pregnancy outcomes were reported after the use of budesonide MMX. To our knowledge, this is the first report on the safety of budesonide MMX treatment in pregnant women with inflammatory bowel disease.

Anaesthesia care with and without tracheal intubation during emergency endoscopy for peptic ulcer bleeding: a population-based cohort study.

BACKGROUND: Emergency upper gastrointestinal bleeding is a common condition with high mortality. Most patients undergo oesophagogastroduodenoscopy (OGD), but no universally agreed approach exists to the type of airway management required during the procedure. We aimed to compare anaesthesia care with tracheal intubation (TI group) and without airway instrumentation (monitored anaesthesia care, MAC group) during emergency OGD. METHODS: This was a prospective, nationwide, population-based cohort study during 2006-13. Emergency OGDs performed under anaesthesia care were included. End points were 90 day mortality (primary) and length of stay in hospital (secondary). Associations between exposure and outcomes were assessed in logistic and linear regression models, adjusted for the following potential confounders: shock at admission, level of anaesthetic expertise present, ASA score, Charlson comorbidity index score, BMI, age, sex, alcohol use, referral origin (home or in-hospital), Forrest classification, ulcer localization, and postoperative care. RESULTS: The study group comprised 3580 patients under anaesthesia care: 2101 (59%) for the TI group and 1479 (41%) for the MAC group. During the first 90 days after OGD, 18.9% in the TI group and 18.4% in the MAC group died, crude odds ratio=1.03 [95% confidence interval (CI)=0.87-1.23, P=0.701], adjusted odds ratio=0.95 (95% CI=0.79-1.15, P=0.590). Patients in the TI group stayed slightly longer in hospital [mean 8.16 (95% CI=7.63-8.60) vs 7.63 days (95%=CI 6.92-8.33), P=0.108 in adjusted analysis]. CONCLUSIONS: In this large population-based cohort study, anaesthesia care with TI was not different from anaesthesia care without airway instrumentation in patients undergoing emergency OGD in terms of 90 day mortality and length of hospital stay.

Gender differences in randomised, controlled trials in intensive care units.

There is a male dominance among patients in intensive care units (ICUs). Potentially, this will increase the risk of a skewed male/female distribution in randomised, controlled trials (RCTs). We have evaluated if this has in fact happened when randomising and whether the authors have been aware of that. We performed a systematic search on PubMed from 1 January 2011 to 31 May 2012 using the mesh terms 'randomized controlled trial' and 'intensive care unit'. Twenty-five RCTs with a total of 12,788 patients met the inclusion criteria, with an overall male dominance of 63.6% (P < 0.0001). Eighteen of the 25 papers had an individually statistically significant gender difference in their total trial population. None of the 18 trials with a significant gender difference in their overall trial population had calculated the P-value for this overall difference. In the randomised groups, there was a significant gender difference in five papers. Seventeen had no significant gender difference in the randomised groups, and three papers did not state gender in the randomised groups. This study show that there is a marked male dominance in RCTs conducted in ICUs. We recommend that when planning future RCTs, the authors contemplate if their results can be used indiscriminately among ICU patients if the distribution of males and females is much skewed. It is relevant to determine if ones endpoint can be influenced by gender differences and if there is a risk of gender influence on data, proportional allocation or stratification should be considered.

An audit of thiopurine methyltransferase genotyping and phenotyping before intended azathioprine treatment for dermatological conditions.

BACKGROUND: Determining thiopurine methyltransferase (TPMT) genotype and phenotype before azathioprine treatment predicts which patients are most likely to develop myelosuppression. AIM: To evaluate the course of azathioprine treatment in people with TPMT heterozygosity and whether this deterred clinicians in prescribing the drug. METHODS: This was a retrospective analysis on patients who had TPMT assays undertaken with the intention of treating their skin disorder with azathioprine. Primary outcome measurements were: (i) whether or not azathioprine was started, (ii) azathioprine dosage, and (iii) duration of treatment. Secondary outcome measures were the effect of the drug, any reported side-effects and reasons for not starting azathioprine. RESULTS: TPMT assays were undertaken in 212 patients, of whom 90.6% were TPMT wild type and the remaining 9.4% were TPMT heterozygous. None of the patients was TPMT homozygous. Of the 192 wild-type patients, 103 (53.6%) received azathioprine, as did 7 (35%) of the 20 heterozygotes (P = 0.16). Mean azathioprine dose was 84.1 mg/day for wild-type patients and 64.3 mg/day for heterozygotes (P = 0.10). Mean treatment duration was 21.4 and 22.7 weeks for wild-type and heterozygotes, respectively (P = 0.52). Azathioprine treatment was stopped in 4 of 7 heterozygotes and 54 of 103 wild-type patients, because of side-effects, lack of effect or a combination of both. The commonest reason for not starting azathioprine treatment in heterozygous patients was their heterozygosity. For wild-type patients, the reasons were remission of disease or the patient's lack of interest in the treatment. CONCLUSIONS: TPMT heterozygosity was a deterring factor for the prescription of azathioprine in our department, and the dose for wild-type patients was lower than recommended guidelines. Treatment duration and occurrence of adverse effects were similar for heterozygotes and wild-type patients.

Etiology of common childhood acute lymphoblastic leukemia: the adrenal hypothesis.

The pattern of infections in the first years of life modulates our immune system, and a low incidence of infections has been linked to an increased risk of common childhood acute lymphoblastic leukemia (ALL). We here present a new interpretation of these observations--the adrenal hypothesis--that proposes that the risk of childhood ALL is reduced when early childhood infections induce qualitative and quantitative changes in the hypothalamus-pituitary-adrenal axis that increase plasma cortisol levels. This may directly eliminate leukemic cells as well as preleukemic cells for the ALL subsets that dominate in the first 5-7 years of life and may furthermore suppress the Th1-dominated proinflammatory response to infections, and thus lower the proliferative stress on pre-existing preleukemic cells.

Fecal calprotectin: assessment of a rapid test.

BACKGROUND: Calprotectin, a protein found mainly in neutrophil granulocytes, is used as an inflammatory marker, while the fecal concentration of the protein is used to detect gastrointestinal (GI) inflammation. MATERIAL AND METHODS: Fecal calprotectin in 100 stool samples was measured by the ELISA method and by a new rapid test. Eighty-two patients had fecal calprotectin measured for clinical reasons and delivered 95 stool samples. The rest were delivered by healthy volunteers. RESULTS: The association between the two tests was statistically significant (p<0.0001, chi(2) test). With calprotectin values <15 microg/g, the sensitivity and specificity of the new rapid test was 96 % (95 % confidence interval (CI), 87-100 %) and 70 % (CI, 55-83 %), respectively, with a negative predictive value of 94 % (CI, 81-99 %). With values >15 microg/g, the rapid test was less accurate, thus rendering results in this range difficult to interpret. CONCLUSIONS: The new rapid test is useful as a screening test for excluding GI inflammation when the cut-off of 15 microg/g is used. With fecal calprotectin concentrations >15 microg/g, the rapid test should be supplemented by quantitative measurement.

Tenderness of pork muscles as influenced by chilling rate and altered carcass suspension.

Tenderness improvements in porcine muscles (M. longissimus dorsi, LD; M. semimembranosus, SM; M. biceps femoris, BF) were evaluated in a total of 72 carcasses by using combinations of three different chilling rates (fast, delayed fast, slow) and two different suspension methods (Achilles tendon, pelvic bone). Tenderness was improved by fast chilling in LD, SM and BF by the pelvic suspension as compared to conventional suspension in the Achilles tendon (P < 0·05). The lengthening of the sarcomeres in SM and BF as produced by pelvic suspension exceeded those found in LD, without having proportional additional effect on the tenderness. While the pelvic-induced tenderization did not change significantly by delayed fast chilling, additional tenderization in BF and SM was obtained by combining pelvic suspension with slow chilling. In conventionally suspended sides, tenderness was unaffected by delayed fast chilling-with slow chilling, however, improvements were observed in LD and SM to a similar extent as obtained by the pelvic suspension. In the LD muscle, the tenderizing effect produced by treatments was largest in muscles having pH values 45 min post stunning above 6·1 (P < 0·05).

Effect of delay time before chilling on toughness in pork with high or low initial pH.

Paired M. longissimus dorsi muscles from 56 carcasses of Danish Landrace and Yorkshire breeds, slaughtered at approximately 90 kg live weight, were utilized to study the potential of cold induced toughness in pork. Based upon the pH value 45 min post stunning, the carcasses were divided in two groups: a low (5·7 ≤ pH < 6·1) and a high one (6·1 ≤ pH ≤ 6·5). The effects on Warner-Bratzler shear force, sarcomere length and myofibril fragmentation of inserting a delay time of 0, 2 and 4 h before carcasses entered the chilling tunnel (operating at -28°C to -22°C) were investigated on early excised muscles as well as on muscles removed 30 h post stunning. The left LD muscle from each carcass served as a control while all right sides were used for treatments. pH and temperature measurements obtained from LD muscles left on carcasses during chilling showed that LD muscles belonging to the high pH group involve a risk of cold shortening even when a 2 h delay was used before passing in to the chilling tunnel. Comparing pH groups, however, sarcomere lengths did not differ in control sides whereas the Warner-Bratzler shear force values were significantly higher in LD muscles taken from the high pH group. Early excision of the LD muscle resulted in shorter sarcomere lengths and increased WB shear force only for carcasses belonging to the high pH group, which, however, could be avoided by introducing a 4 h delay time before rapid chilling. The effect of delay time on tenderness from muscles excised from the carcass 30 h post stunning was much less but a 4 h delay did significantly (P < 0·05) improve tenderness in carcasses with high initial pH. Coefficient of correlation between Warner-Bratzler shear force and sarcomere length was -0·12 and nonsignificant in the low pH group, whereas it was -0·57 and highly significant in the high pH group.

Effects of altered carcass suspension during rigor mortis on tenderness of pork loin.

A total of 32 porcine carcasses from Danish Landrace and Yorkshire breeds, slaughtered at approximately 90 kg live weight, were utilised in two experiments (replicates) to evaluate the effect of altered carcass suspension on Warner-Bratzler (WB) shear force, sarcomere length, myofibrillar fragmentation and cooking loss in the longissimus dorsi (LD). Carcasses used in the experiments all showed pH(1) values above 6·0 and ultimate pH below 5·8. From each replicate, the two sides of 16 carcasses were suspended by one of two methods: conventional suspension from the Achilles tendon or pelvic suspension from the obturator foramen. WB values were measured at three locations taken from the posterior section of the LD muscle. Pelvic suspension decreased WB values (p < 0·001) and increased sarcomere lengths (p < 0·001) whereas cooking loss was unaffected by method of suspension. The significant interactions between suspension and replicate (p < 0·01) and between suspension and sample location (p < 0·001) revealed that the tenderising effect of pelvic suspension increased with increasing WB level in the conventional suspended carcass sides. Myofibril fragmentation showed inconsistent response to suspension method.

Location on the chromosome of Escherichia coli of genes governing purine metabolism. Adenosine deaminase (add), guanosine kinase (gsk) and hypoxanthine phosphoribosyltransferase (hpt).

Genes coding for enzymes functioning in purine salvage pathways have been located on the chromosome of Escherichia coli. The gene add encoding adenosine deaminase was located by transduction at 31 min, the gene order was established to be man-uidA-add-aroD. A deletion covering man-uidA-add was obtained. The gene gsk encoding guanosine kinase was cotransducible with purE and shown to be located at 13 min. The gene hpt encoding hypoxanthine phosphoribosyltransferase was cotransducible with tonA indicating a location at 3 min. The location of the gene gpt encoding guanine (xanthine) phosphoribosyltransferase in the proA-proB region was confirmed.