Migraine patients have lower systolic but higher diastolic blood pressure compared with controls in a population-based study of 21,537 subjects. The Reykjavik Study

Several studies have explored a possible association between migraine and hypertension, with contradictory results. Because of this uncertainty the relation between blood pressure (BP) and migraine was studied in 10,366 men and 11,171 women in a population-based longitudinal study. A modified version of the 1988 International Headache Society criteria was used for diagnosis of migraine. Logistic regression analysis was used. The crude 1-year prevalence of migraine was 5.2% among men and 14.1% among women. No significant association was found between hypertension and migraine. For a one standard deviation (SD) increase in diastolic BP the probability of having migraine increased 14% (P = 0.11) for men and 30% (P < 0.0001) for women. For a 1-SD increase in systolic BP the probability of having migraine decreased 19% (P = 0.007) for men and 25% (P < 0.0001) for women. It was also found that for a 1-SD increase in pulse pressure the probability of having migraine decreased 13% (P = 0.005) for men and 14% (P < 0.0001) for women. In a population-based study of men and women it was found that subjects with migraine had lower pulse pressure, lower systolic BP and higher diastolic BP compared with controls.     

Self vs expert assessment of technical and non-technical skills in high fidelity simulation

Background

Accurate assessment is imperative for learning, feedback and progression. The aim of this study was to examine whether surgeons can accurately self-assess their technical and nontechnical skills compared with expert faculty members' assessments.

Methods

Twenty-five surgeons performed a laparoscopic cholecystectomy (LC) in a simulated operating room. Technical and nontechnical performance was assessed by participants and faculty members using the validated Objective Structured Assessment of Technical Skills (OSATS) and the Non-Technical Skills for Surgeons scale (NOTSS).

Results

Assessment of technical performance correlated between self and faculty members' ratings for experienced (median score, 30.0 vs 31.0; ρ = .831; P = .001) and inexperienced (median score, 22.0 vs 28.0; ρ = .761; P = .003) surgeons. Assessment of nontechnical skills between self and faculty members did not correlate for experienced surgeons (median score, 8.0 vs 10.5; ρ = −.375; P = .229) or their more inexperienced counterparts (median score, 9.0 vs 7.0; ρ = −.018; P = .953).

Conclusions

Surgeons can accurately self-assess their technical skills in virtual reality LC. Conversely, formal assessment with faculty members' input is required for nontechnical skills, for which surgeons lack insight into their behaviours.     

Current practice in Staphylococcus aureus screening and decolonization

We surveyed infectious disease physicians to determine their preoperative Staphylococcus aureus screening and decolonization practices. Sixty percent reported preoperative screening for S. aureus. However, specific screening and decolonization practices are highly variable, are focused almost exclusively on methicillin-resistant S. aureus, and do not include testing for mupirocin or chlorhexidine resistance.     

Growth hormone deficiency in adults with hypopituitarism—What are the risks and can they be eliminated by therapy?

Growth hormone (GH) deficiency develops early in patients with hypothalamic-pituitary disorders and is therefore common among these patients. GH deficiency in adults is associated with increased morbidity, increased body fat mass, abdominal obesity, dyslipidaemia, reduced exercise capacity, impaired cardiac function as well as reduced self-reported well-being and impaired quality of life. Since recombinant human GH became available as replacement therapy more than 25 years ago, randomised controlled trials and long-term studies, together with meta-analyses, have shown improved outcomes in adult patients with hypopituitarism receiving GH. Many of the features associated with GH deficiency in adults improve, or even normalize, and the safety profile is reassuring. The increased interest in GH deficiency in adults with hypothalamic-pituitary disorders has also contributed to the identification of other factors of importance for an outcome such as the replacement of other pituitary hormone deficiencies, and the management of the underlying hypothalamic-pituitary disease, most commonly a pituitary tumour. In this narrative review, we summarize the burden of GH deficiency in adults with hypopituitarism, the impact of GH replacement on the outcome, as well as safety. Based on currently available data, GH replacement should be considered routine management of adults with hypopituitarism.     

Treatment as Prevention for Hepatitis C (TraP Hep C) – a nationwide elimination programme in Iceland using direct‐acting antiviral agents

A nationwide programme for the treatment of all patients infected with hepatitis C virus (HCV) was launched in Iceland in January 2016. By providing universal access to direct‐acting antiviral agents to the entire patient population, the two key aims of the project were to (i) offer a cure to patients and thus reduce the long‐term sequelae of chronic hepatitis C, and (ii) to reduce domestic incidence of HCV in the population by 80% prior to the WHO goal of HCV elimination by the year 2030. An important part of the programme is that vast majority of cases will be treated within 36 months from the launch of the project, during 2016–2018. Emphasis is placed on early case finding and treatment of patients at high risk for transmitting HCV, that is people who inject drugs (PWID), as well as patients with advanced liver disease. In addition to treatment scale‐up, the project also entails intensification of harm reduction efforts, improved access to diagnostic tests, as well as educational campaigns to curtail spread, facilitate early detection and improve linkage to care. With these efforts, Iceland is anticipated to achieve the WHO hepatitis C elimination goals well before 2030. This article describes the background and organization of this project. Clinical trial number: NCT02647879.     

Genome-wide search for breast cancer linkage in large Icelandic non-BRCA1/2 families

Introduction:

A significant proportion of high-risk breast cancer families are not explained by mutations in known genes. Recent genome-wide searches (GWS) have not revealed any single major locus reminiscent of BRCA1 and BRCA2, indicating that still unidentified genes may explain relatively few families each or interact in a way obscure to linkage analyses. This has drawn attention to possible benefits of studying populations where genetic heterogeneity might be reduced. We thus performed a GWS for linkage on nine Icelandic multiple-case non-BRCA1/2 families of desirable size for mapping highly penetrant loci. To follow up suggestive loci, an additional 13 families from other Nordic countries were genotyped for selected markers.

Methods:

GWS was performed using 811 microsatellite markers providing about five centiMorgan (cM) resolution. Multipoint logarithm of odds (LOD) scores were calculated using parametric and nonparametric methods. For selected markers and cases, tumour tissue was compared to normal tissue to look for allelic loss indicative of a tumour suppressor gene.

Results:

The three highest signals were located at chromosomes 6q, 2p and 14q. One family contributed suggestive LOD scores (LOD 2.63 to 3.03, dominant model) at all these regions, without consistent evidence of a tumour suppressor gene. Haplotypes in nine affected family members mapped the loci to 2p23.2 to p21, 6q14.2 to q23.2 and 14q21.3 to q24.3. No evidence of a highly penetrant locus was found among the remaining families. The heterogeneity LOD (HLOD) at the 6q, 2p and 14q loci in all families was 3.27, 1.66 and 1.24, respectively. The subset of 13 Nordic families showed supportive HLODs at chromosome 6q (ranging from 0.34 to 1.37 by country subset). The 2p and 14q loci overlap with regions indicated by large families in previous GWS studies of breast cancer.

Conclusions:

Chromosomes 2p, 6q and 14q are candidate sites for genes contributing together to high breast cancer risk. A polygenic model is supported, suggesting the joint effect of genes in contributing to breast cancer risk to be rather common in non-BRCA1/2 families. For genetic counselling it would seem important to resolve the mode of genetic interaction.     

High risk of in-breast tumor recurrence after BRCA1/2-associated breast cancer

The purpose of the study was to compare breast-conserving therapy (BCT) and mastectomy (M) in BRCA1/2 mutation carriers. Women with invasive breast cancer and a pathogenic mutation in BRCA1 or BRCA2 were included in the study (n = 162). Patients treated with BCT (n = 45) were compared with patients treated with M (n = 118). Endpoints were local recurrence as first recurrence (LR), overall survival (OS), breast cancer death, and distant recurrence. Cumulative incidence was calculated in the presence of competing risks. For calculation of hazard ratios and for multivariable analysis, cause-specific Cox proportional hazards regression was used. Compared to M, BCT was associated with an increased risk of LR in univariable analysis (HR 4.0; 95 % CI 1.6–9.8) and in multivariable analysis adjusting for tumor stage, age, and use of adjuvant chemotherapy (HR 2.9; CI 1.1–7.8). Following M, all local recurrences were seen in the first 5 years after breast cancer diagnosis. Following BCT, the rate of LR continued to be high also after the first 5 years. The cumulative incidence of LR in the BCT group was 15, 25, and 32 % after 5, 10, and 15 years, respectively. There were no significant differences between BCT and M for OS, breast cancer death, or distant recurrence. BRCA1/2 mutation carriers treated with BCT have a high risk of LR, many of which are new primary breast cancers. This must be thoroughly discussed with the patient and is an example of how rapid treatment-focused genetic testing could influence choice of treatment.     

The relation of fatness to insulin is independent of fitness in 9- but not 15-yr-olds

PURPOSE: To explore the relationship between varying aerobic fitness (fitness), fatness, and fasting insulin levels in healthy children. METHODS: A population-based sample of 9-yr-old (9YO, 47 boys, 56 girls) and 15-yr-old (15YO, 53 boys, 51 girls) Icelandic children. Body fatness was evaluated via body mass index, waist circumference adjusted for height (waist adj), and sum of four skinfolds. Fitness was assessed with a graded maximal cycle ergometer test. Fasting insulin was measured using an ECLIA. RESULTS: Fasting insulin correlated to all fatness measures (9YO, r = 0.43-0.46, P < 0.001; 15YO, r = 0.30-0.37, P < 0.003) and fitness (9YO, r = -0.29, P = 0.003; 15YO, r = -0.32, P = 0.001). Adjustment for fitness did not affect the relations between fatness and fasting insulin in 9YO (r = 0.33-0.37, P < 0.001); however, only waist adj remained significantly related to fasting insulin (r = 0.24, P = 0.016) in 15YO. Children in the upper half of fitness and fatness split on the median did not differ in fasting insulin from children in the upper half of fitness but lower half of fatness. Fatness was related to fasting insulin in 9YO (r = 0.51-0.54, P = 0.001) and 15YO (r = 0.31-0.35, P = 0.011-0.028) in the lower half of fitness, but no association was observed in the upper half of fitness in either group. CONCLUSION: Fatness has a greater association with fasting insulin than fitness, especially among 9YO; however, fitness attenuates the adverse relation of fatness to fasting insulin in 15YO but does not change it in 9YO. In both age groups, being fitter and fatter does not result in greater fasting insulin than being fitter and leaner, and fatness is primarily associated with fasting insulin in lower-fit children.     

Enzyme-amplified immunoassays

The sensitivity of enzyme immunoassays may be enhanced by the use of enzyme-amplification. This technique uses the enzyme label in the immunoassay to provide a trigger substance for a secondary system that can generate a large quantity of coloured product. Two examples of enzyme amplifiers are described, using either a substrate cycle with phosphorylated hexose sugars, or a redox cycle involving the coenzyme NAD⁺. The redox enzyme-amplifier has a detection limit of less than one attomole for the enzyme label, alkaline phosphatase.

The limited dynamic range of enzyme-amplified immunoassays may be overcome by kinetic analysis of the colour development in the enzyme-amplifier, to add at least a further order of magnitude to the range of directly measured analyte concentrations in the immunoassay. This is illustrated in an enzyme-amplified immunoassay for human thyroid stimulating hormone. Amperometric measurement of the enzyme-amplifier provides a method to extend the dynamic range still further and compares favourably with the performance of a gamma counter, a luminometer or a fluorimeter.