The reliability of self-reported childhood otitis media by adults

OBJECTIVE: To estimate reliability of retrospective questionnaire data on childhood recurrent otitis media, and to identify factors influencing inconsistency in self-report. METHODS: Retrospective questionnaire data from a population-based sample of 4430 Norwegian twins who participated in two questionnaire surveys, 6 years apart, containing identical questions on otitis media. Main outcome measure was individual consistency in reporting of otitis media. The tetrachoric correlation and Cohen's Kappa were used to measure reliability. Inconsistent and consistent responders were compared on medical history and mental distress. The use of twin data made it possible to test whether inconsistent responders represent a group with intermediate levels of otitis media severity. RESULTS: The test-retest tetrachoric correlation was 0.82 and Kappa was 0.53. Inconsistency in response was not associated with mental distress, but related to reported number of otitis media episodes per year, use of medical services and history of ear surgery. CONCLUSION: Retrospective self-reported otitis media is a relatively reliable measure. The study suggests that reporting inconsistency is likely to be associated with less severe disease. The finding that reporting pattern is related to disease severity is in accordance with the proposed need for a uniform agreement on the definition of the term "recurrent otitis media" for research purposes.     

Gene-Network Analysis Identifies Susceptibility Genes Related to Glycobiology in Autism

The recent identification of copy-number variation in the human genome has opened up new avenues for the discovery of positional candidate genes underlying complex genetic disorders, especially in the field of psychiatric disease. One major challenge that remains is pinpointing the susceptibility genes in the multitude of disease-associated loci. This challenge may be tackled by reconstruction of functional gene-networks from the genes residing in these loci. We applied this approach to autism spectrum disorder (ASD), and identified the copy-number changes in the DNA of 105 ASD patients and 267 healthy individuals with Illumina Humanhap300 Beadchips. Subsequently, we used a human reconstructed gene-network, Prioritizer, to rank candidate genes in the segmental gains and losses in our autism cohort. This analysis highlighted several candidate genes already known to be mutated in cognitive and neuropsychiatric disorders, including RAI1, BRD1, and LARGE. In addition, the LARGE gene was part of a sub-network of seven genes functioning in glycobiology, present in seven copy-number changes specifically identified in autism patients with limited co-morbidity. Three of these seven copy-number changes were de novo in the patients. In autism patients with a complex phenotype and healthy controls no such sub-network was identified. An independent systematic analysis of 13 published autism susceptibility loci supports the involvement of genes related to glycobiology as we also identified the same or similar genes from those loci. Our findings suggest that the occurrence of genomic gains and losses of genes associated with glycobiology are important contributors to the development of ASD.     

Poppyfield bleeding: a new dermatoscopic sign and its histopathological background

Dermatoscopy increases the accuracy of diagnosis of melanoma. An atypical vascular pattern may be an indicator of cutaneous malignant melanoma (CMM). During dermatoscopy of certain CMMs numerous ruby droplets of blood appear when the dermatoscope is pressed firmly against the lesion. The aim of this paper was to examine the histopathological background for this observation. CMMs from 8 patients showing the poppyfield sign, i.e. squirts of ruby blood droplets, were paired with 8 CMMs of equal Breslow thickness not showing this sign. The 16 CMMs were placed in an unsystematic sequence and presented to two dermato-pathologists who assessed the lesions independently for confirmation of Breslow thickness, Clark level, ulceration and presence of dilated tumour vessels. There was no disagreement between the pathologists' assessments. Age of the patients and Breslow thickness of the cutaneous malignant melanoma were similar in the two groups. All 8 poppyfield CMMs had dilated tumour vessels compared with 25% (2/8) of the non-poppyfield CMMs (p< 0.007). Histological ulceration was observed in all poppyfield CMMs and none of the non-poppyfield CMMs (p< 0.001). The poppyfield bleeding sign is a dermatoscopic clue to dilated tumour vessels. It may be a dermatoscopic reflection of increased vascular density described in primary CMMs compared with adjacent skin and may also reflect the presence of primitive vessels in CMMs displaying increased fragility.     

Difficulties in avoiding exposure to allergens in cosmetics

The aim of the study is to describe the ability of patients with allergic contact dermatitis to avoid exposure to allergens in cosmetics. The study is a questionnaire survey among 382 patients with contact allergy to preservatives and fragrances, included from 3 dermatological clinics. The questionnaire included questions about the level of difficulty in reading labels of ingredients on cosmetics and about patients' strategies to avoid substances they were allergic to. It also included questions about eczema severity as well as about educational level. 46% of the patients found it difficult or extremely difficult to read the ingredient labelling of cosmetics, and this finding was significantly related to low educational level. Patients allergic to formaldehyde and methyldibromo glutaronitrile experienced the worst difficulties, while patients with fragrance allergy found ingredient label reading easier than patients with preservative allergy. Reading of ingredient labels is a major problem for patients with contact allergy to allergens in consumer products. It is a general problem for all patients and not restricted to a small group with multiple allergies.     

Expression of interleukin‐21 receptor in epidermis from patients with systemic sclerosis

Objective

To examine the expression and regulation of interleukin‐21 (IL‐21) and IL‐21 receptor (IL‐21R) in patients with systemic sclerosis (SSc; scleroderma).

Methods

Skin biopsy specimens were obtained from 23 patients with SSc and 15 healthy controls. IL‐21/IL‐21R messenger RNA (mRNA) was quantified using real‐time polymerase chain reaction (PCR). The expression pattern of IL‐21/IL‐21R was analyzed by in situ hybridization and Western blotting. Stimulation experiments were performed with cultured dermal fibroblasts from patients with SSc and healthy controls as well as with keratinocytes, using IL‐1β, platelet‐derived growth factor BB, monocyte chemoattractant protein 1, transforming growth factor β, and IL‐21. The SCID‐hu skin mouse model was used for in vivo experiments.

Results

IL‐21R mRNA was detected in all biopsy specimens from patients with SSc and controls, with a 4.7‐fold increase observed in SSc samples. In situ hybridization and immunohistochemical analysis showed an up‐regulation of IL‐21R in samples of epidermis from SSc patients, whereas no signal was detected in skin specimens from healthy controls. These results were confirmed in vitro, in that cultured keratinocytes expressed significant levels of IL‐21R, whereas no signal was observed in fibroblasts. Interestingly, mRNA for IL‐21 could not be detected by real‐time PCR and in situ hybridization. Various concentrations of key cytokines in the pathogenesis of SSc did not stimulate the expression of IL‐21R mRNA in cultured keratinocytes and dermal fibroblasts. In the SCID mouse transplantation model, the overexpression of IL‐21R mRNA in SSc keratinocytes remained unchanged after transplantation.

Conclusion

The up‐regulation of IL‐21R in keratinocytes indicates that, similar to fibroblasts and endothelial cells, the expression pattern is altered in SSc. Moreover, the expression of IL‐21R appears to be independent of key cytokines that are operant in SSc.

     

The role of P-glycoprotein in limiting intestinal regional absorption of digoxin in rats.

The objective of this work was to study the role of regional intestinal efflux activity of P-glycoprotein (Pgp) in situ in anesthetized rats in limiting the absorption of digoxin. A 10-cm portion of duodenum or jejunum, or 5-cm of colon was perfused single-pass with saline containing [(3)H]digoxin while the appearance of radioactivity in the blood was measured. Verapamil in the perfusate was used as a modulator of Pgp in the intestinal mucosa. Net water absorption, mucosal integrity, and intestinal motility of the isolated segment were monitored, as well as heart rate and blood pressure. Excretion of i.v. administered unlabelled digoxin, 1 mg/kg, into the intestine while perfusing the duodenum-proximal jejunum region, was studied for comparison. At a perfusate concentration of 1 mM, verapamil caused a dramatic increase in [(3)H]digoxin absorption rate from duodenum and jejunum, while the effect in colon was insignificant. At concentrations of 0.1, 1, and 2.5 mM in the duodenal perfusate, verapamil increased the absorption rate of [(3)H]digoxin in a dose-dependent manner. The lowest concentration almost doubled the rate without having any significant effects on the cardiovascular system, intestinal motility, or net absorption of water. The excretion rate of unlabelled digoxin from the blood into the gut lumen was found to be halved in the presence of 0.5 mM verapamil in the perfusate. Absorption rate of [(3)H]digoxin in the rat is likely limited by Pgp-mediated efflux. The data indicate that Pgp plays an important role for digoxin efflux in the small intestine only.     

Association between early initiation of breastfeeding and reduced risk of respiratory infection: Implications for nonseparation of infant and mother in the COVID‐19 context

Early initiation of breastfeeding, within 1 h of birth, is vital for the health of newborns and reduces morbidity and mortality. Secondary analysis of the 2016 Nepal Demographic and Health Survey (DHS) showed that early initiation of breastfeeding significantly reduced the risk of acute respiratory infection (ARI) in children under 2 years. Early initiation of breastfeeding requires maternal proximity. Separation of infant and mother inhibits early initiation of breastfeeding and increases the risk that infants will suffer from ARIs. However, during the COVID‐19 pandemic, guidance varied, with some recommending that infants and mothers with SARS‐CoV‐2 be isolated from one another. Nepal''s Ministry of Health and Population recommended nonseparation, but the adherence to this guidance was inconsistent. Maternal proximity, nonseparation and early initiation of breastfeeding should be promoted in all birthing facilities.     

First-line trifluridine/tipiracil + bevacizumab in patients with unresectable metastatic colorectal cancer: final survival analysis in the TASCO1 study

Background Therapeutic options are limited in patients with unresectable metastatic colorectal cancer (mCRC) ineligible for intensive chemotherapy. The use of trifluridine/tipiracil plus bevacizumab (TT-B) in this setting was evaluated in the TASCO1 trial; here, we present the final overall survival (OS) results.Methods TASCO1 was an open-label, non-comparative phase II trial. Patients (n = 153) were randomised 1:1 to TT-B (trifluridine/tipiracil 35 mg/m² orally twice daily on days 1–5 and 8–12, and bevacizumab intravenously 5 mg/kg on days 1 and 15 of each 28-day cycle) or capecitabine plus bevacizumab (C-B; capecitabine, 1250 mg/m² orally twice daily on days 1–14 and bevacizumab 7.5 mg/kg intravenously on day 1 of each 21-day cycle). Final OS was analysed when all patients had either died or withdrawn from the study. Adjusted multivariate regression was used to investigate the effects of pre-specified variables on OS.Results At 1 September 2020, median OS was 22.3 months (95% CI: 18.0–23.7) with TT-B and 17.7 months (95% CI: 12.6–19.8) with C-B (adjusted HR 0.78; 95% CI: 0.55–1.10). No variables negatively affected OS with TT-B. Safety results were consistent with prior findings.Conclusions TT-B is a promising therapeutic regimen in mCRC patients ineligible for intensive chemotherapy.Clinical trial information {"type":"clinical-trial","attrs":{"text":"NCT02743221","term_id":"NCT02743221"}}NCT02743221 (clinicaltrials.gov)Subject terms: Colorectal cancer, Colorectal cancer