Evaluation of an artificial intelligence-based decision support for the detection of cutaneous melanoma in primary care: a prospective real-life clinical trial.

BACKGROUND: Use of artificial intelligence (AI), or machine learning, to assess dermoscopic images of skin lesions to detect melanoma has, in several retrospective studies, shown high levels of diagnostic accuracy on par with - or even outperforming - experienced dermatologists. However, the enthusiasm around these algorithms has not yet been matched by prospective clinical trials performed in authentic clinical settings. In several European countries, including Sweden, the initial clinical assessment of suspected skin cancer is principally conducted in the primary healthcare setting by primary care physicians, with or without access to teledermoscopic support from dermatology clinics. OBJECTIVES: To determine the diagnostic performance of an AI-based clinical decision support tool for cutaneous melanoma detection, operated by a smartphone application (app), when used prospectively by primary care physicians to assess skin lesions of concern due to some degree of melanoma suspicion. METHODS: This prospective multicentre clinical trial was conducted at 36 primary care centres in Sweden. Physicians used the smartphone app on skin lesions of concern by photographing them dermoscopically, which resulted in a dichotomous decision support text regarding evidence for melanoma. Regardless of the app outcome, all lesions underwent standard diagnostic procedures (surgical excision or referral to a dermatologist). After investigations were complete, lesion diagnoses were collected from the patients' medical records and compared with the app's outcome and other lesion data. RESULTS: In total, 253 lesions of concern in 228 patients were included, of which 21 proved to be melanomas, with 11 thin invasive melanomas and 10 melanomas in situ. The app's accuracy in identifying melanomas was reflected in an area under the receiver operating characteristic (AUROC) curve of 0.960 [95% confidence interval (CI) 0.928-0.980], corresponding to a maximum sensitivity and specificity of 95.2% and 84.5%, respectively. For invasive melanomas alone, the AUROC was 0.988 (95% CI 0.965-0.997), corresponding to a maximum sensitivity and specificity of 100% and 92.6%, respectively. CONCLUSIONS: The clinical decision support tool evaluated in this investigation showed high diagnostic accuracy when used prospectively in primary care patients, which could add significant clinical value for primary care physicians assessing skin lesions for melanoma.

Are People Generous When the Financial Stakes Are High?

How generous are people when making consequential financial decisions in the real world? We took advantage of a rare opportunity to examine generosity among a diverse sample of adults who received a gift of U.S. $10,000 from a pair of wealthy donors, with nearly no strings attached. Two-hundred participants were drawn from three low-income countries (Indonesia, Brazil, and Kenya) and four high-income countries (Australia, Canada, the United Kingdom, and the United States) as part of a preregistered study. On average, participants spent over $6,400 on purchases that benefited others, including nearly $1,700 on donations to charity, suggesting that humans exhibit remarkable generosity even when the stakes are high. To address whether generosity was driven by reputational concerns, we asked half the participants to share their spending decisions publicly on Twitter, whereas the other half were asked to keep their spending private. Generous spending was similar between the groups, in contrast to our preregistered hypothesis that enhancing reputational concerns would increase generosity.

Establishment and Utility of SwedAD: A Nationwide Swedish Registry for Patients with Atopic Dermatitis Receiving Systemic Pharmacotherapy.

SwedAD, a Swedish nationwide registry for patients with atopic dermatitis receiving systemic pharmacotherapy, was launched on 1 September 2019. We describe here the establishment of a user-friendly registry to the benefit of patients with atopic dermatitis. By 5 November 2022, 38 clinics had recorded 931 treatment episodes in 850 patients with an approximate national coverage rate of 40%. Characteristics at enrolment included median Eczema Area and Severity Index (EASI) 10.2 (interquartile range 4.0, 19.4), Patient-Oriented Eczema Measure (POEM) 18.0 (10.0, 24.0), Dermatology Life Quality Index (DLQI) 11.0 (5.0, 19.0) and Peak Itch Numerical Rating Scale-11 (NRS-11) 6.0 (3.0, 8.0). At 3 months, median EASI was 3.2 (1.0, 7.3) and POEM, DLQI, and NRS-11 were improved. Regional coverage varied, reflecting the distribution of dermatologists, the ratio of public to private healthcare, and difficulties in recruiting certain clinics. This study highlights the importance of a nationwide registry when managing systemic pharmacotherapy of atopic dermatitis.

Transseptal puncture during catheter ablation associated with higher radiation exposure.

BACKGROUND: Electroanatomic mapping systems are increasingly used during ablations to decrease the need for fluoroscopy and therefore radiation exposure. For left-sided arrhythmias, transseptal puncture is a common procedure performed to gain access to the left side of the heart. We aimed to demonstrate the radiation exposure associated with transseptal puncture. METHODS: Data were retrospectively collected from the Catheter Ablation with Reduction or Elimination of Fluoroscopy registry. Patients with left-sided accessory pathway-mediated tachycardia, with a structurally normal heart, who had a transseptal puncture, and were under 22 years of age were included. Those with previous ablations, concurrent diagnostic or interventional catheterisation, and missing data for fluoroscopy use or procedural outcomes were excluded. Patients with a patent foramen ovale who did not have a transseptal puncture were selected as the control group using the same criteria. Procedural outcomes were compared between the two groups. RESULTS: There were 284 patients in the transseptal puncture group and 70 in the patent foramen ovale group. The transseptal puncture group had a significantly higher mean procedure time (158.8 versus 131.4 minutes, p = 0.002), rate of fluoroscopy use (38% versus 7%, p < 0.001), and mean fluoroscopy time (2.4 versus 0.6 minutes, p < 0.001). The acute success and complication rates were similar. CONCLUSIONS: Performing transseptal puncture remains a common reason to utilise fluoroscopy in the era of non-fluoroscopic ablation. Better tools are needed to make non-fluoroscopic transseptal puncture more feasible.

Intrarater and Interrater Reliability of Radiographic Characteristics in Skeletally Immature Patients With Anterior Cruciate Ligament Tears: A PLUTO Study Group Reliability Study.

BACKGROUND: Radiographic measurements of limb alignment in skeletally immature patients with anterior cruciate ligament (ACL) tears are frequently used for surgical decision-making, preoperative planning, and postoperative monitoring of skeletal growth. However, the interrater and intrarater reliability of these radiographic characteristics in this patient population is not well documented. HYPOTHESIS: Excellent reliability across 4 raters will be demonstrated for all digital measures of length, coronal plane joint orientation angles, mechanical axis, and tibial slope in skeletally immature patients with ACL tears. STUDY DESIGN: Cohort study (diagnosis). METHODS: Three fellowship-trained orthopaedic surgeons and 1 medical student performed 2 rounds of radiographic measurements on digital imaging (lateral knee radiographs and long-leg radiographs) of skeletally immature patients with ACL tears. Intrarater and interrater reliability for continuous radiographic measurements was assessed with intraclass correlation coefficients (ICCs) across 4 raters with 95% CIs for affected and unaffected side measurements. Interrater reliability analysis used an ICC (2, 4) structure and intrarater reliability analysis used an ICC (2, 1) structure. A weighted kappa coefficient was calculated for ordinal variables along with 95% CIs for both interrater and intrarater reliability. Agreement statistic interpretations are based on scales described by Fleiss, and Cicchetti and Sparrow: <0.40, poor; 0.40 to 0.59, fair; 0.60 to 0.74, good; and >0.74, excellent. RESULTS: Radiographs from a convenience sample of 43 patients were included. Intrarater reliability was excellent for nearly all measurements and raters. Interrater reliability was also excellent for nearly all reads for all measurements. CONCLUSION: Radiographic reliability of long-leg radiographs and lateral knee x-rays in skeletally immature children with ACL tears is excellent across nearly all measures and raters and can be obtained and interpreted as reliable and reproducible means to measure limb length and alignment. LEVEL OF EVIDENCE: Level III.

Non-Invasive, Topical Sampling of Potential, Low-Molecular Weight, Skin Cancer Biomarkers: A Study on Healthy Volunteers.

Monitoring of low-molecular weight cancer biomarkers, such as tryptophan (Trp) and its derivative kynurenine (Kyn), might be advantageous to non-invasive skin cancer detection. Thus, we assessed several approaches of topical sampling of Trp and Kyn, in relation to phenylalanine (Phe) and tyrosine (Tyr), on the volar forearm of six healthy volunteers. The sampling was performed with three hydrogels (made of agarose or/and chitosan), hydrated starch films, cotton swabs, and tape stripping. The biomarkers were successfully sampled by all approaches, but the amount of collected Kyn was low, 20 ± 10 pmol/cm2. Kyn quantification was below LOQ, and thus, it was detected only in 20% of topical samples. To mitigate variability problems of absolute amounts of sampled amino acids, Tyr/Trp, Phe/Trp, and Phe/Tyr ratios were assessed, proving reduced inter-individual variation from 79 to 45% and intra-individual variation from 42 to 21%. Strong positive correlation was found between Phe and Trp, pointing to the Phe/Trp ratio (being in the 1.0-2.0 range, at 95% confidence) being least dependent on sampling materials, approaches, and sweating. This study leads to conclusion that due to the difficulty in quantifying less abundant Kyn, and thus the Trp/Kyn ratio, the Phe/Trp ratio might be a possible, alternative biomarker for detecting skin cancers.

Why is it so difficult to study magnetic compass orientation in murine rodents?

A magnetic compass sense has been demonstrated in all major classes of vertebrates, as well as in many invertebrates. In mammals, controlled laboratory studies of mice have provided evidence for a robust magnetic compass that is comparable to, or exceeds, the performance of that in other animals. Nevertheless, the vast majority of laboratory studies of spatial behavior and cognition in murine rodents have failed to produce evidence of sensitivity to magnetic cues. Given the central role that a magnetic compass sense plays in the spatial ecology and cognition of non-mammalian vertebrates, and the potential utility that a global/universal reference frame derived from the magnetic field would have in mammals, the question of why responses to magnetic cues have been so difficult to demonstrate reliably is of considerable importance. In this paper, we review evidence that the magnetic compass of murine rodents shares a number of properties with light-dependent compasses in a wide variety of other animals generally believed to be mediated by a radical pair mechanism (RPM) or related quantum process. Consistent with the RPM, we summarize both published and previously unpublished findings suggesting that the murine rodent compass is sensitive to low-level radio frequency (RF) fields. Finally, we argue that the presence of anthropogenic RF fields in laboratory settings, may be an important source of variability in responses of murine rodents to magnetic cues.

Treatment Patterns among Patients with Atopic Dermatitis in Secondary Care: A National, Observational, Non-interventional, Retrospective Study in Sweden.

This non-interventional, observational, longitudinal study describes treatment patterns of atopic dermatitis (AD) in Sweden. Data from 3 Swedish registries were merged, and included patients who received an AD diagnosis (during the period 1997 to 2019) and had AD treatment prescribed (during the period 2006 to 2020). Treatment persistence, treatment sequencing, time-to-event analysis, and 12-month prevalence were analysed. Overall, data for 99,885 patients with AD were included, of whom 4,086 (4.1%) received systemic treatments. Median persistence rates were 12.6 (95% CI 11.9, 13.4) months for methotrexate, 10.8 (9.1, 13.0) months for azathioprine, 5.6 (3.8, 6.2) months for mycophenolate, 5.1 (4.4, 5.7) months for alitretinoin and 3.4 (3.2, 3.7) months for cyclosporine. Median (Q1, Q3) time from first secondary care visit for AD to first systemic treatment was 5.8 (2.2, 11.0) years overall and 4.4 (1.3, 9.1) years in the Stockholm region. Methotrexate was a prominent first- and second-line treatment used during the period 2006 to 2020. Dupilumab was introduced during the study period and was increasingly used as first- or second-line therapy over time. The 12-month prevalence of AD generally remained steady, with a gradual increase observed over time for the overall population. A steep increase was observed in Stockholm from 2011. This study shows that a small proportion of patients with AD are offered systemic treatments in Sweden, with long periods in secondary care prior to systemic treatments and low persistence on systemic treatments. Regional differences highlight a need for national treatment guidelines.

Treatment Patterns and Clinical Outcomes of Chronic Urticaria: Two-year Follow-up Results from the Scandinavian AWARE Study.

The AWARE (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) study investigated outcomes in patients with chronic urticaria refractory to H1-antihistamine. The objective of the current study was to analyse the effects of treatment on patients' symptoms and quality of life for a period of up to 2 years. Over the 2 years, there was clear improvement in the high rates of disease burden from baseline, as evidenced by lower scores for disease severity scales, better quality of life, and a decreasing rate of medical resource utilization. However, this is the result of treatment adherence to the guidelines in highly specialized Scandinavian urticaria centres, and has its basis in the relatively low treatment intensity and control at enrolment. There is a need for greater adherence to the treatment guidelines and better management of antihistamine-refractory chronic urticaria.

Micropuncture closure following high density microarray patch application in healthy subjects.

BACKGROUND: The high-density microarray patch (HD-MAP) promises to be a robust vaccination platform with clear advantages for future global societal demands for health care management. The method of action has its base not only in efficient delivery of vaccine but also in the reliable induction of a local innate physical inflammatory response to adjuvant the vaccination process. The application process needs to induce levels of reactivity, which are acceptable to the vaccine, and from which the skin promptly recovers. MATERIALS AND METHODS: 1 × 1 cm HD-MAP patches containing 5000, 250-µm long microprojections were applied to the skin in 12 healthy volunteers. The return of skin barrier function was assessed by transepidermal water loss (TEWL) and reaction to topical histamine challenge. RESULTS: Skin barrier recovery by 48 h was confirmed for all HD-MAP sites by recovered resistance to the effects of topical histamine application. CONCLUSIONS: Our previous observation, that the barrier disruption indicator TEWL returns to normal by 48 h, is supported by this paper's demonstration of return of skin resistance to topical histamine challenge in twelve healthy subjects.

Utilising electroanatomic mapping during ablation in patients with CHD to reduce radiation exposure.

BACKGROUND: Patients with CHD can be exposed to high levels of cumulative ionising radiation. Utilisation of electroanatomic mapping during catheter ablation leads to reduced radiation exposure in the general population but has not been well studied in patients with CHD. This study evaluated the radiation sparing benefit of using three-dimensional mapping in patients with CHD. METHODS: Data were retrospectively collected from the Catheter Ablation with Reduction or Elimination of Fluoroscopy multi-institutional registry. Patients with CHD were selected. Those with previous ablations, concurrent diagnostic or interventional catheterisation and unknown arrhythmogenic foci were excluded. The control cohort was matched for operating physician, arrhythmia mechanism, arrhythmia location, weight and age. The procedure time, rate of fluoroscopy use, fluoroscopy time, procedural success, complications, and distribution of procedures per year were compared between the two groups. RESULTS: Fifty-six patients with congenital heart disease and 56 matched patients without CHD were included. The mean total procedure time was significantly higher in patients with CHD (212.6 versus 169.5 minutes, p = 0.003). Their median total fluoroscopy time was 4.4 minutes (compared to 1.8 minutes), and their rate of fluoroscopy use was 23% (compared to 13%). The acute success and minor complication rates were similar and no major complications occurred. CONCLUSIONS: With the use of electroanatomic mapping during catheter ablation, fluoroscopy use can be reduced in patients with CHD. The majority of patients with CHD received zero fluoroscopy.

Robotic Assistance for Posterior Approach Total Hip Arthroplasty Is Associated With Lower Risk of Revision for Dislocation When Compared to Manual Techniques.

BACKGROUND: Robotic-assistance total hip arthroplasty (RA-THA) and computer navigation THA (CN-THA) have been shown to improve accuracy of component positioning compared to manual techniques; however, controversy exists regarding clinical benefit. Moreover, these technologies may expose patients to risks. The purpose of this study is to compare rates of intraoperative fracture and complications requiring reoperation within 1 year for posterior approach RA-THA, CN-THA, and THA with no technology (Manual-THA). METHODS: In total, 13,802 primary, unilateral, elective, posterior approach THAs (1770 RA-THAs, 3155 CN-THAs, and 8877 Manual-THAs) were performed at a single institution between 2016 and 2020. Intraoperative fractures and reoperations within 1 year of the index procedure were identified. Cohorts were balanced using inverse probability of treatment weight based on age, gender, body mass index, femoral cementation, history of spine fusion, and Charlson Comorbidity Index. Logistic regression was performed to create odds ratios for complications. Additional regression analysis for dislocation was performed, adjusting for dual mobility and femoral head size. RESULTS: There were no differences in intraoperative fracture and postoperative complication rates between the groups (P = .521). RA-THA had a 0.3 odds ratio (95% confidence interval 0.1-0.9, P = .046) compared to Manual-THA for reoperation due to dislocation. CN-THA had an odds ratio of 3.0 for reoperation due to dislocation (95% confidence interval 0.8-11.3, P = .114) compared to RA-THA. The remaining complication odds ratios, including those for infection, loosening, dehiscence, and "other" were similar between the groups. CONCLUSION: RA-THA is associated with lower risk of revision for dislocation within 1 year of index surgery, when compared to Manual-THA performed through the posterior approach.

The Vasomotor Response to Dopamine Is Altered in the Rat Model of l-dopa-Induced Dyskinesia.

BACKGROUND: Levodopa (l-dopa) is the frontline treatment for motor symptoms of Parkinson's disease. However, prolonged use of l-dopa results in a motor complication known as levodopa-induced dyskinesia (LID) in ~50% of patients over 5 years. OBJECTIVES: We investigated neurovascular abnormalities in a rat model of LID by examining changes in angiogenesis and dopamine-dependent vessel diameter changes. METHODS: Differences in striatal and nigral angiogenesis in a parkinsonian rat model (6-OHDA lesion) treated with 2 doses of l-dopa (saline, 2, and 10 mg/kg/day subcutaneous l-dopa treatment for 22 days) by 5-bromo-2'-deoxyuridine (BrdU)-RECA1 co-immunofluorescence. Difference in the vasomotor response to dopamine was examined with 2-photon laser scanning microscopy and Dodt gradient imaging. RESULTS: We found that the 10 mg/kg l-dopa dosing regimen induced LID in all animals (n = 5) and induced significant angiogenesis in the striatum and substantia nigra. In contrast, the 2 mg/kg treatment induced LID in 6 out of 12 rats and led to linearly increasing LID severity over the 22-day treatment period, making this a promising model for studying LID progression longitudinally. However, no significantly different level of angiogenesis was observed between LID versus non-LID animals. Dopamine-induced vasodilatory responses were exaggerated only in rats that show LID-like signs compared to the rest of groups. Additionally, in juvenile rats, we showed that DA-induced vasodilation is preceded by increased Ca2+ release in the adjacent astrocytes. CONCLUSION: This finding supports that astrocytic dopamine signaling controls striatal blood flow bidirectionally, and the balance is altered in LID. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Microvascular effects of microneedle application.

BACKGROUND: The efficiency of transdermal drug delivery may be increased by pretreating the skin with microneedles, but distinct effects of microneedles and the microneedle-enhanced delivery of vasoactive drugs on the skin microvasculature are still not well investigated. MATERIALS AND METHODS: In eight healthy human subjects, we measured the microvascular response to microneedle-induced microtraumas in the skin microvasculature using polarized light spectroscopy imaging (Tissue Viability imaging, TiVi). The microvascular response was assessed for up to 48 hours for three microneedle sizes (300 µm, 500 µm, and 750 µm) and for different pressures and application times. RESULTS: In our results, microneedle application increased the local red blood cell (RBC) concentration for up to 24 hours dependent on the needle lengths, applied time, and force. CONCLUSION: Optimization of microneedles size, pressure, and application time should be taken into account for future protocols for drug delivery and experimental provocations.

Acute outcomes of three-dimensional mapping for fluoroscopy reduction in paediatric catheter ablation for supraventricular tachycardia.

BACKGROUND: Catheter ablation is a safe and effective therapy for the treatment of supraventricular tachycardia in children. Current improvements in technology have allowed progressive reduction in radiation exposure associated with the procedure. To assess the impact of three-dimensional mapping, we compared acute procedural results collected from the Catheter Ablation with Reduction or Elimination of Fluoroscopy registry to published results from the Prospective Assessment after Pediatric Cardiac Ablation study. METHODS: Inclusion and exclusion criteria from the Prospective Assessment after Pediatric Cardiac Ablation study were used as guidelines to select patient data from the Catheter Ablation with Reduction or Elimination of Fluoroscopy registry to compare acute procedural outcomes between cohorts. Outcomes assessed include procedural and fluoroscopy exposure times, success rates of procedure, and complications. RESULTS: In 786 ablation procedures, targeting 498 accessory pathways and 288 atrioventricular nodal reentrant tachycardia substrates, average procedural time (156.5 versus 206.7 minutes, p < 0.01), and fluoroscopy time (1.2 versus 38.3 minutes, p < 0.01) were significantly shorter in the study group. Success rates for the various substrates were similar except for manifest accessory pathways which had a significantly higher success rate in the study group (96.4% versus 93.0%, p < 0.01). Major complication rates were significantly lower in the study group (0.3% versus 1.6%, p < 0.01). CONCLUSIONS: In a large, multicentre study, three-dimensional systems show favourable improvements in clinical outcomes in children undergoing catheter ablation of supraventricular tachycardia compared to the traditional fluoroscopic approach. Further improvements are anticipated as technology advances.

Actinic Keratosis Diagnosis and Increased Risk of Developing Skin Cancer: A 10-year Cohort Study of 17,651 Patients in Sweden.

Actinic keratosis is the most common actinic lesion in fair-skinned populations. It is accepted as an indicator of actinic skin damage and as an occasional precursor of squamous cell carcinoma. The aim of this study was to investigate, in a cohort of patients with a diagnosis of actinic keratosis, the relative risk of developing skin cancer during a follow-up period of 10 years. This registry-based cohort study compared a cohort of 2,893 individuals in south-eastern Sweden, who were diagnosed with actinic keratosis during the period 2000 to 2004, with a matched-control cohort of 14,668 individuals without actinic keratosis during the same inclusion period. The subjects were followed for 10 years to identify skin cancer development in both cohorts. Hazard ratios with 95% confidence intervals (95% CI) were used as risk measures. Individuals in the actinic keratosis cohort had a markedly higher risk for all skin cancer forms compared with the control cohort (hazard ratio (HR) 5.1, 95% CI 4.7-5.6). The relative risk was highest for developing squamous cell carcinoma (SCC) (HR 7.7, 95% CI 6.7-8.8) and somewhat lower for basal cell carcinoma (BCC) (HR 4.4, 95% CI 4.1-5.0) and malignant melanoma (MM) (HR 2.7 (2.1-3.6). Patients with a diagnosis of actinic keratosis were found to be at increased risk of developing SCC, BCC and MM in the 10 years following diagnosis of actinic keratosis. In conclusion, a diagnosis of actinic keratosis, even in the absence of documentation of other features of chronic sun exposure, is a marker of increased risk of skin cancer, which should be addressed with individually directed preventive advice.

Man versus machine: comparison of naked-eye estimation and quantified capillary refill.

BACKGROUND: Capillary refill (CR) time is traditionally assessed by 'naked-eye' inspection of the return to original colour of a tissue after blanching pressure. Few studies have addressed intra-observer reliability or used objective quantification techniques to assess time to original colour. This study compares naked-eye assessment with quantified CR (qCR) time using polarisation spectroscopy and examines intra-observer and interobserver agreements in using the naked eye. METHOD: A film of 18 CR tests (shown in a random fixed order) performed in healthy adults was assessed by a convenience sample of 14 doctors, 15 nurses and 19 secretaries (Department of Emergency Medicine, Linköping University, September to November 2017), who were asked to estimate the time to return to colour and characterise it as 'fast', 'normal' or 'slow'. The qCR times and corresponding naked-eye time assessments were compared using the Kruskal-Wallis test. Three videos were shown twice without observers' knowledge to measure intra-observer repeatability. Intra-observer categorical assessments were compared using Cohen's Kappa analysis. Interobserver repeatability was measured and depicted with multiple-observer Bland-Altman plotting. Differences in naked-eye estimation between professions were analysed using ANOVA. RESULTS: Naked-eye assessed CR time and qCR time differ substantially, and agreement for the categorical assessments (naked-eye assessment vs qCR classification) was poor (Cohen's kappa 0.27). Bland-Altman intra-observer repeatability ranged from 6% to 60%. Interobserver agreement was low as shown by the Bland-Altman plotting with a 95% limit of agreement with the mean of ±1.98 s for doctors, ±1.6 s for nurses and ±1.75 s for secretaries. The difference in CR time estimation (in seconds) between professions was not significant. CONCLUSIONS: Our study suggests that naked-eye-assessed CR time shows poor reproducibility, even by the same observers, and differs from an objective measure of CR time.

The clinical and genetic spectrum of catecholaminergic polymorphic ventricular tachycardia: findings from an international multicentre registry.

Aims: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an ion channelopathy characterized by ventricular arrhythmia during exertion or stress. Mutations in RYR2-coded Ryanodine Receptor-2 (RyR2) and CASQ2-coded Calsequestrin-2 (CASQ2) genes underlie CPVT1 and CPVT2, respectively. However, prognostic markers are scarce. We sought to better characterize the phenotypic and genotypic spectrum of CPVT, and utilize molecular modelling to help account for clinical phenotypes. Methods and results: This is a Pediatric and Congenital Electrophysiology Society multicentre, retrospective cohort study of CPVT patients diagnosed at <19 years of age and their first-degree relatives. Genetic testing was undertaken in 194 of 236 subjects (82%) during 3.5 (1.4-5.3) years of follow-up. The majority (60%) had RyR2-associated CPVT1. Variant locations were predicted based on a 3D structural model of RyR2. Specific residues appear to have key structural importance, supported by an association between cardiac arrest and mutations in the intersubunit interface of the N-terminus, and the S4-S5 linker and helices S5 and S6 of the RyR2 C-terminus. In approximately one quarter of symptomatic patients, cardiac events were precipitated by only normal wakeful activities. Conclusion: This large, multicentre study identifies contemporary challenges related to the diagnosis and prognostication of CPVT patients. Structural modelling of RyR2 can improve our understanding severe CPVT phenotypes. Wakeful rest, rather than exertion, often precipitated life-threatening cardiac events.

Scoring of Hand Eczema: Good Reliability of Hand Eczema Extent Score (HEES).

There is good agreement between dermatological staff and patients using the Hand Eczema Extent Score (HEES). The aim of this study was to assess inter- and intra-observer reliability of the HEES in dermatologists and intra-observer reliability of the HEES in patients with hand eczema. Six dermatologists assessed 18 patients twice. Only the hands of the patients were visible to the assessors. Patients performed a self-assessment twice. Inter- and intra-observer reliability was tested with intraclass correlation coefficient (ICC). The mean HEES score for all dermatologists' assessments was 21.0 (range 3.6-46.3). The corresponding mean scores for all patients' own assessments were 24.9 (range 4.0-54.0). Inter-observer reliability in the dermatologists' observations ICC classification was very good, median value 0.82 (range 0.56-0.92). The overall intra-observer reliability for the 6 dermatologists' ICC classification was very good (range 0.88-0.94). Intra-observer reliability in the patients' 2 self-assessments ICC classification was very good (ICC 0.95). In conclusion, HEES is a reliable tool for both dermatologists and patients to grade the extent of hand eczema.

The Effects of Job Instability and Financial Strain on C-Reactive Protein in a Sample of Mexican Immigrants.

OBJECTIVE: Mexican immigrants have lower cardiovascular disease risk than US citizens, but risk increases with level of acculturation. Our study investigated whether job stress and financial strain would be related to inflammation (C-reactive protein), lipids, and blood pressure, and if they would play a role in the acculturation process in Mexican immigrants. METHODS: A sample of 310 Mexican immigrants living in the United States were studied on measures of job stress, financial strain, acculturation, and cardiovascular disease risk factors (C-reactive protein, lipids, and blood pressure). RESULTS: Job instability, financial strain, and acculturation, were related to inflammation, but psychological demands and decision latitude were not related. Lipids and blood pressure were not related to the variables of interest. Body mass index (BMI) was related to both increased acculturation and inflammation, and when controlling for BMI, acculturation was no longer a significant predictor of inflammation. Job instability and financial strain remained significant predictors of inflammation after controlling for BMI, sex, and age. Job instability and financial strain were not related to acculturation, suggesting that these factors are significant stressors for both newly arrived and more established immigrants. CONCLUSIONS: Job instability and financial strain predict increased inflammation in Mexican immigrants but they do not play a role in the relationship between acculturation and C-reactive protein. The effects of acculturation on inflammation in this study were mediated by BMI.