The socio-economic status of families experiencing the sudden unexpected death of an infant - Is it possibly related to a higher rate of non-natural deaths among them.

Low socio-economic status is recognized as one of the risk factors for SIDS. In this study we have pointed out the similarities between families that have SIDS cases and families in which infant non-accidental injury has been proven, as well as the differences between them and the general population. This study was conducted in Montenegro, comparing 30 cases of SIDS with 25 cases of known infanticides and with a control group (60 cases) consisting of live newborns and their mothers from the general population, randomly selected from hospital-born newborns without exclusion criteria. We combined and compared the infant characteristics and mother characteristics between the above cases. There were significant similarities between the SIDS group and the infanticide group in terms of the following characteristics: the education level of the mothers (p = 0.086); maternal employment (p = 0.278); and place of residence (p = 0.269); while there were differences between the two groups regarding hospital birth (p = 0.027) and marital status (p = 0.011). The SIDS and infanticide groups, combined, had higher incidences of: out-of-hospital deliveries (p < 0.001); uneducated mothers (p < 0.001); unemployed mothers (p < 0.001); low socio-economic status (p < 0.001); and cases outside of marriage (p < 0.001), compared to the control groups. This study indicated a possible higher incidence of non-natural death among SIDS cases, as reflected by low socio-economic status and linked attributes, which is explained by their similarities with the infanticide groups and differences with the control groups.

Chronic urticaria in the real-life clinical practice setting in the UK: results from the noninterventional multicentre AWARE study.

BACKGROUND: Chronic urticaria (CU) is a skin condition characterized by repeated occurrence of itchy weals and/or angio-oedema for > 6 weeks. AIM: To provide data demonstrating the real-life burden of CU in the UK. METHODS: This UK subset of the worldwide, prospective, noninterventional AWARE study included patients aged 18-75 years diagnosed with H1-antihistamine (H1-AH)-refractory chronic spontaneous urticaria (CSU) for > 2 months. Baseline characteristics, disease activity, treatments, comorbidities and healthcare resource use were documented. Quality of life (QoL), work productivity and activity impairment were assessed. RESULTS: Baseline analysis included 252 UK patients. Mean age and body mass index were 45.0 years and 29.0 kg/m2 , respectively. Most patients were female (77.8%) and had moderate/severe disease activity (mean Urticaria Activity Score over 7 days was 18.4) and a 'spontaneous' component to their CU (73.4% CSU; 24.6% CSU and chronic inducible urticaria). Common comorbidities included depression/anxiety (24.6%), asthma (23.8%) and allergic rhinitis (12.7%). A previous treatment was recorded for 57.9% of patients. Mean Dermatology Life Quality Index score was 9.5, and patients reported impairments in work productivity and activity. Healthcare resource use was high. Severity of CSU was associated with female sex, obesity, anxiety and diagnosis. Only 28.5% of patients completed all nine study visits, limiting analysis of long-term treatment patterns and disease impact. CONCLUSIONS: Adult H1-AH-refractory patients with CU in the UK reported high rates of healthcare resource use and impairment in QoL, work productivity and activity at baseline. The differing structures of UK healthcare may explain the high study discontinuation rates versus other countries.

'Warning: allergic to penicillin': association between penicillin allergy status in 2.3 million NHS general practice electronic health records, antibiotic prescribing and health outcomes.

BACKGROUND: The prevalence of reported penicillin allergy (PenA) and the impact these records have on health outcomes in the UK general population are unknown. Without such data, justifying and planning enhanced allergy services is challenging. OBJECTIVES: To determine: (i) prevalence of PenA records; (ii) patient characteristics associated with PenA records; and (iii) impact of PenA records on antibiotic prescribing/health outcomes in primary care. METHODS: We carried out cross-sectional/retrospective cohort studies using patient-level data from electronic health records. Cohort study: exact matching across confounders identified as affecting PenA records. Setting: English NHS general practices between 1 April 2013 and 31 March 2014. Participants: 2.3 million adult patients. Outcome measures: prevalence of PenA, antibiotic prescribing, mortality, MRSA infection/colonization and Clostridioides difficile infection. RESULTS: PenA prevalence was 5.9% (IQR = 3.8%-8.2%). PenA records were more common in older people, females and those with a comorbidity, and were affected by GP practice. Antibiotic prescribing varied significantly: penicillins were prescribed less frequently in those with a PenA record [relative risk (RR)  = 0.15], and macrolides (RR = 4.03), tetracyclines (RR = 1.91) nitrofurantoin (RR = 1.09), trimethoprim (RR = 1.04), cephalosporins (RR = 2.05), quinolones (RR = 2.10), clindamycin (RR = 5.47) and total number of prescriptions were increased in patients with a PenA record. Risk of re-prescription of a new antibiotic class within 28 days (RR = 1.32), MRSA infection/colonization (RR = 1.90) and death during the year subsequent to 1 April 2013 (RR = 1.08) increased in those with PenA records. CONCLUSIONS: PenA records are common in the general population and associated with increased/altered antibiotic prescribing and worse health outcomes. We estimate that incorrect PenA records affect 2.7 million people in England. Establishing true PenA status (e.g. oral challenge testing) would allow more people to be prescribed first-line antibiotics, potentially improving health outcomes.

Stability, antioxidant activity, in vivo safety and efficacy of creams with standardized wild apple fruit extract: a comparison of conventional and biodegradable emulsifiers.

OBJECTIVE: The aim of the study was in vitro and in vivo characterization of cosmetic cream with 6% of standardized wild apple fruit extract, stabilized by conventional non-ionic emulsifier-CEW, in order to determine the influence of emulsifiers (conventional vs. biodegradable) on the characteristics of creams and their effects on the skin. METHODS: Organoleptic and physico-chemical (pH values and electrical conductivity) analysis was performed, determination of fruit acids-FAs content (using HPLC analysis) and estimation of its antioxidant activity-AA (using DPPH test) during 180 days. In vivo study included following examinations: screening of safety profile (after creams application under occlusion during 24 h at human skin); skin moisturizing potential, transepidermal water loss-TEWL, skin pH after 28 days of cream application and hypopigmentation efficacy 7 days of cream application at artificially induced skin hyperpigmentation. RESULTS: Investigated cosmetic cream-CEW showed satisfactory organoleptic, physico-chemical characteristics, stability, FAs content (0.13%) and AA (19.25 ± 0.67 %RSC) after preparation, which remained unchanged over the study period. In vivo investigation revealed absence of skin irritation after CEW's application under occlusion. An increase of skin moisturization (after 14 days ΔEC was 18.52 ± 11.51 and after 28 days of applications 16.52 ± 9.36) during 28 day-study, with unchanged TEWL and skin pH values was shown. Decrease of melanin index was revealed, too (after 7 days ΔMI was -31.40 ± 16.50). CONCLUSION: Cosmetic cream stabilized by conventional emulsifier showed better antioxidant potential and weaker moisturizing and hypopigmentation effects related to the cream with same composition but stabilized by biodegradable emulsifiers. Based on all mentioned above, investigated cosmetic cream might be considered for potential use as modern, stable, safe and efficient cosmetic product in the prevention and/or treatment of oxidative stress-related skin changes and/or damages, for moisturization of dry, even irritated skin as well as for lightening of hyperpigmented skin. RÉSUMÉ: OBJECTIF Le but de l'étude était la caractérisation in vitro et in vivo d'une crème cosmétique contenant 6 % d'extrait normalisé de pomme sauvage, stabilisée par un émulsifiant non ionique conventionnel-CEW, afin de déterminer l'influence des émulsifiants (conventionnels vs biodégradables) sur les caractéristiques des crèmes et les effets sur la peau. MÉTHODES: Des analyses organoleptiques et physico-chimiques (pH et conductivité électrique) ont été effectuées, la détermination de la teneur en acides de fruits et en acides gras polyinsaturés (par CLHP), et l'estimation de sa teneur en activité antioxydante (AA) (à l'aide du test DPPH) pendant 180 jours. L'étude in vivo comprenait les examens suivants : dépistage du profil d'innocuité (après application de crèmes sous occlusion pendant 24 h sur la peau humaine); potentiel d'hydratation de la peau, perte d'eau transépidermique (PETE), pH de la peau après 28 jours d'application de la crème et efficacité de l'hypopigmentation après 7 jours d'application de la crème sur une hyperpigmentation de la peau induite artificiellement. RÉSULTATS: La crème cosmétique-CEW étudiée a montré des caractéristiques organoleptiques, physico-chimiques, une stabilité, une teneur en AG (0,13 %) et en AA (19,25 ± 0,67 % RSC) satisfaisantes après préparation, qui sont demeurées inchangées au cours de la période de l'étude. L'étude in vivo a révélé l'absence d'irritation cutanée après l'application de CEW sous occlusion. Une augmentation de l'hydratation de la peau (après 14 jours de DEC était de 18,52 ± 11,51 et après 28 jours d'applications de 16,52 ± 9,36) pendant l'étude de 28 jours, avec une PETE et des valeurs de pH cutané inchangées, a été démontrée. Une diminution de l'indice de mélanine a été mise en évidence également (après 7 jours, ΔMI était de 31,40 ± 16,50). CONCLUSION: La crème cosmétique stabilisée par un émulsifiant conventionnel a montré un meilleur potentiel antioxydant et des effets d'hydratation et d'hypopigmentation plus faibles par rapport à la crème de même composition mais stabilisée par des émulsifiants biodégradables. D'après les données précédentes, la crème cosmétique étudiée pourrait être considérée comme un produit cosmétique moderne, stable, sûr et efficace dans la prévention et/ou le traitement des changements et/ou dommages cutanés liés au stress oxydatif, pour l'hydratation de la peau sèche, voire irritée, ainsi que pour éclaircir la peau hyperpigmentée.

Consensus clinical scoring for suspected perioperative immediate hypersensitivity reactions.

BACKGROUND: Grading schemes for severity of suspected allergic reactions have been applied to the perioperative setting, but there is no scoring system that estimates the likelihood that the reaction is an immediate hypersensitivity reaction. Such a score would be useful in evaluating current and proposed tests for the diagnosis of suspected perioperative immediate hypersensitivity reactions and culprit agents. METHODS: We conducted a Delphi consensus process involving a panel of 25 international multidisciplinary experts in suspected perioperative allergy. Items were ranked according to appropriateness (on a scale of 1-9) and consensus, which informed development of a clinical scoring system. The scoring system was assessed by comparing scores generated for a series of clinical scenarios against ratings of panel members. Supplementary scores for mast cell tryptase were generated. RESULTS: Two rounds of the Delphi process achieved stopping criteria for all statements. From an initial 60 statements, 43 were rated appropriate (median score 7 or more) and met agreement criteria (disagreement index <0.5); these were used in the clinical scoring system. The rating of clinical scenarios supported the validity of the scoring system. Although there was variability in the interpretation of changes in mast cell tryptase by the panel, we were able to include supplementary scores for mast cell tryptase. CONCLUSION: We used a robust consensus development process to devise a clinical scoring system for suspected perioperative immediate hypersensitivity reactions. This will enable objectivity and uniformity in the assessment of the sensitivity of diagnostic tests.

Penicillin allergy de-labelling ahead of elective surgery: feasibility and barriers.

BACKGROUND: Around 10-15% of the in-patient population carry unsubstantiated 'penicillin allergy' labels, the majority incorrect when tested. These labels are associated with harm from use of broad-spectrum non-penicillin antibiotics. Current testing guidelines incorporate both skin and challenge tests; this is prohibitively expensive and time-consuming to deliver on a large scale. We aimed to establish the feasibility of a rapid access de-labelling pathway for surgical patients, using direct oral challenge. METHODS: 'Penicillin allergic' patients, recruited from a surgical pre-assessment clinic, were risk-stratified using a screening questionnaire. Patients at low risk of true, immunoglobulin E (IgE)-mediated allergy were offered direct oral challenge using incremental amoxicillin to a total dose of 500 mg. A 3-day course was completed at home. De-labelled patients were followed up to determine antibiotic use in surgery, and attitudes towards de-labelling were explored. RESULTS: Of 219 patients screened, 74 were eligible for inclusion and offered testing. We subsequently tested 56 patients; 55 were de-labelled. None had a serious reaction to the supervised challenge, or thereafter. On follow-up, 17 of 19 patients received appropriate antimicrobial prophylaxis during surgery. Only three of 33 de-labelled patients would have been happy for the label to be removed without prior specialist testing. CONCLUSION: Rapid access de-labelling, using direct oral challenge in appropriately risk-stratified patients, can be incorporated into the existing surgical care pathway. This provides immediate and potential long-term benefit for patients. Interest in testing is high among patients, and clinicians appear to follow clinic recommendations. Patients are unlikely to accept removal of their allergy label on the basis of history alone. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: AN17/92982.

Management of a surgical patient with a label of penicillin allergy: narrative review and consensus recommendations.

Unsubstantiated penicillin-allergy labels are common in surgical patients, and can lead to significant harm through avoidance of best first-line prophylaxis of surgical site infections and increased infection with resistant bacterial strains. Up to 98% of penicillin-allergy labels are incorrect when tested. Because of the scarcity of trained allergists in all healthcare systems, only a minority of surgical patients have the opportunity to undergo testing and de-labelling before surgery. Testing pathways can be modified and shortened in selected patients. A variety of healthcare professionals can, with appropriate training and in collaboration with allergists, provide testing for selected patients. We review how patients might be assessed, the appropriate testing strategies that can be used, and the minimum standards of safe testing.

British Society for Immunology/United Kingdom Primary Immunodeficiency Network consensus statement on managing non-infectious complications of common variable immunodeficiency disorders.

Common variable immunodeficiency (CVID) represents a heterogeneous group of rare disorders. There is considerable morbidity and mortality as a result of non-infectious complications, and this presents clinicians with management challenges. Clinical guidelines to support the management of CVID are urgently required. The UK Primary Immunodeficiency Network and the British Society for Immunology funded a joint project to address this. A modified Delphi Survey was conducted for the assessment, diagnosis and treatment of the non-infectious blood, respiratory, gut and liver complications of CVID. A steering group of 10 consultant immunologists and one nurse specialist developed and reviewed the survey statements and agreed the final recommendations. In total, 22 recommendations and three areas for research were developed.

Reinforcement of barrier function - skin repair formulations to deliver physiological lipids into skin.

OBJECTIVE: The aim of the study was to develop formulations to deliver physiological lipids into skin in an attempt to repair defective barrier function. METHODS: Physiological cholesterol and linoleic acid were incorporated into basic cream and non-ionic cream to prepare skin repair formulations. Homogeneity and storage stability of the developed creams were examined by polarized light microscopy. Ex vivo evaluation was conducted using lipid-deficient skin samples and confocal Raman microspectroscopy. A 7-day in vivo study was performed on volunteers to study the repairing efficacy. RESULTS: Homogeneous texture was seen in the prepared skin repair formulations. The application of the creams led to substantially increased lipid levels compared to the reference in the lipid-deficient skin in ex vivo study. Twice-a-day application of the skin repair creams provided a reinforcement of the skin barrier as transepidermal water loss (TEWL) was significantly decreased. CONCLUSION: The skin repair creams showed excellent efficacy in skin recovery. They have great potentials for treating impaired skin barrier associated with depletion of lipids in stratum corneum.

The United Kingdom Primary Immune Deficiency (UKPID) registry 2012 to 2017.

This is the second report of the United Kingdom Primary Immunodeficiency (UKPID) registry. The registry will be a decade old in 2018 and, as of August 2017, had recruited 4758 patients encompassing 97% of immunology centres within the United Kingdom. This represents a doubling of recruitment into the registry since we reported on 2229 patients included in our first report of 2013. Minimum PID prevalence in the United Kingdom is currently 5·90/100 000 and an average incidence of PID between 1980 and 2000 of 7·6 cases per 100 000 UK live births. Data are presented on the frequency of diseases recorded, disease prevalence, diagnostic delay and treatment modality, including haematopoietic stem cell transplantation (HSCT) and gene therapy. The registry provides valuable information to clinicians, researchers, service commissioners and industry alike on PID within the United Kingdom, which may not otherwise be available without the existence of a well-established registry.

Prevalence and clinical association of gene mutations through multiplex mutation testing in patients with NSCLC: results from the ETOP Lungscape Project.

Background: Reported prevalence of driver gene mutations in non-small-cell lung cancer (NSCLC) is highly variable and clinical correlations are emerging. Using NSCLC biomaterial and clinical data from the European Thoracic Oncology Platform Lungscape iBiobank, we explore the epidemiology of mutations and association to clinicopathologic features and patient outcome (relapse-free survival, time-to-relapse, overall survival). Methods: Clinically annotated, resected stage I-III NSCLC FFPE tissue was assessed for gene mutation using a microfluidics-based multiplex PCR platform. Mutant-allele detection sensitivity is >1% for most of the ∼150 (13 genes) mutations covered in the multiplex test. Results: Multiplex testing has been carried out in 2063 (76.2%) of the 2709 Lungscape cases (median follow-up 4.8 years). FFPE samples mostly date from 2005 to 2008, yet recently extracted DNA quality and quantity was generally good. Average DNA yield/case was 2.63 µg; 38 cases (1.4%) failed QC and were excluded from study; 95.1% of included cases allowed the complete panel of mutations to be tested. Most common were KRAS, MET, EGFR and PIK3CA mutations with overall prevalence of 23.0%, 6.8%, 5.4% and 4.9%, respectively. KRAS and EGFR mutations were significantly more frequent in adenocarcinomas: PIK3CA in squamous cell carcinomas. MET mutation prevalence did not differ between histology groups. EGFR mutations were found predominantly in never smokers; KRAS in current/former smokers. For all the above mutations, there was no difference in outcome between mutated and non-mutated cases. Conclusion: Archival FFPE NSCLC material is adequate for multiplex mutation analysis. In this large, predominantly European, clinically annotated stage I-III NSCLC cohort, none of the mutations characterized showed prognostic significance.

Selective response to omalizumab in a patient with concomitant ncMCAS and POTS: what does it teach us about the underlying disease?

No disponible

[The Paris system for classification of urinary cytology]. / Das Paris-System zur Klassifikation der Urinzytologie.

A uniform classification system for reporting urinary cytology has not been available until recently, although urinary cytology represents an important volume of specimens in cytopathology laboratories and is well-established in the diagnosis and follow-up of patients with urothelial carcinoma. The Paris system is the first internationally accepted classification system, which allows uniform reporting of urinary cytology based on standardized morphological criteria. It emphasizes the detection of potentially life-threatening high-grade urothelial carcinomas and well-defined diagnostic categories have been developed. Notably, it aims at reducing the diagnosis of equivocal atypia and additionally at confining indications for a rational use of ancillary molecular techniques. The Paris system has already gained broad acceptance both in the cytology and urology communities, and promises to enhance the value of diagnostic urinary cytology.

Towards satisfying performance of an O/W cosmetic emulsion: screening of reformulation factors on textural and rheological properties using general experimental design.

OBJECTIVE: Consumers' demand for improved products' performance, alongside with the obligation of meeting the safety and efficacy goals, presents a key reason for the reformulation, as well as a challenging task for formulators. Any change of the formulation, whether it is wanted - in order to innovate the product (new actives and raw materials) or necessary - due to, for example legislative changes (restriction of ingredients), ingredients market unavailability, new manufacturing equipment, may have a number of consequences, desired or otherwise. The aim of the study was to evaluate the influence of multiple factors - variations of the composition, manufacturing conditions and their interactions, on emulsion textural and rheological characteristics, applying the general experimental factorial design and, subsequently, to establish the approach that could replace, to some extent, certain expensive and time-consuming tests (e.g. certain sensory analysis), often required, partly or completely, after the reformulation. METHODS: An experimental design strategy was utilized to reveal the influence of reformulation factors (addition of new actives, preparation method change) on textural and rheological properties of cosmetic emulsions, especially those linked to certain sensorial attributes, and droplet size. RESULTS: The general experimental factorial design revealed a significant direct effect of each factor, as well as their interaction effects, on certain characteristics of the system and provided some valuable information necessary for fine-tuning reformulation conditions. Upon addition of STEM-liposomes, consistency, index of viscosity, firmness and cohesiveness were decreased, as along with certain rheology parameters (elastic and viscous modulus), whereas maximal and minimal apparent viscosities and droplet size were increased. The presence of an emollient (squalene) affected all the investigated parameters in a concentration-dependent manner. Modification of the preparation method (using Ultra Turrax instead of a propeller stirrer) produced emulsions with higher firmness and maximal apparent viscosity, but led to a decrease in minimal apparent viscosity, hysteresis loop area, all monitored parameters of oscillatory rheology and droplet size. CONCLUSION: The study showed that the established approach which combines a general experimental design and instrumental, rheological and textural measurements could be appropriate, more objective, repeatable and time and money-saving step towards developing cosmetic emulsions with satisfying, improved or unchanged, consumer-acceptable performance during the reformulation.

Chlorhexidine allergy in four specialist allergy centres in the United Kingdom, 2009-13: clinical features and diagnostic tests.

We describe an observational survey of diagnostic pathways in 104 patients attending four specialist allergy clinics in the United Kingdom following perioperative hypersensitivity reactions to chlorhexidine reactions. The majority were life-threatening. Men undergoing urological or cardiothoracic surgery predominated. Skin prick testing and specific immunoglobulin (sIg)E testing were the most common tests used for diagnosis. Fifty-three per cent of diagnoses were made on the basis of a single positive test. Where multiple tests were performed the sensitivity of intradermal, basophil activation and skin prick testing was 68% (50-86%), 50% (10-90%) and 35% (17-55%), respectively. Seven per cent were negative on screening tests initially, and 12 cases were only positive for a single test despite multiple testing. Intradermal tests appeared most sensitive in this context. Additional sensitization to other substances used perioperatively, particularly neuromuscular blocking agents (NMBA), was found in 28 patients, emphasizing the need to test for possible allergy to all drugs to which the patient was exposed even where chlorhexidine is positive.

A new model to determine lipophilicity of 1,2-ethanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives with antiproliferative activity by combining shake flask procedure and UHPLC-MS method.

Fourteen compounds representing ester derivatives of (S,S)-1,2-ethanediamine-N,N'-di-2-(3-cyclohexyl) propanoic and (S,S)-1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acids, expressing antiproliferative activity in vitro were examined. The objective of this study was to determinate their lipophilicity data, and also to ensure a mathematical model for prediction lipophilicity data of potential in vivo metabolites and new derivatives of (S,S)-1,2-ethanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid, based on chromatographic parameters. Experimentally, lipophilicity data were obtained by a traditional shake flask procedure and an ultra-high performance liquid chromatographic tandem mass spectrometry (UHPLC-MS) method. A correlation between the partition coefficient n-octanol/water (logD7,4) and chromatographic data (CHI, 0), and also, between logD7,4 and retention time was investigated. A very good correlation (r2=0.8969) was found between lipophilicity parameters 0 and logD7,4 obtained using UHPLC-MS and shake flask methods: logD7,4 = (0.11±0.01)×0 + (1.25±0.20)×Nc - (9.19±1.18); statistical parameter F=47.84; significance of F = 3.74×10-6, Nc=number of C atoms between two amino groups (Nc=2 for 1,2-ethanediamine derivatives and Nc=3 for 1,3-propanediamine derivatives). The model predictivity power was determined by cross validation leave one out (LOO) technique, and expressed by the term Q2, was 0.89. The developed model has good predictivity power for prediction lipophilicity data of potential in vivo metabolites of the investigated compounds, such as novel 1,2-ethanediamine and 1,3-propanediamine N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives. Also, the lipophilicity data obtained in the present study correlated with the antiproliferative activity of the investigated substances shown previously in in vitro studies.