Multiple endocrine neoplasia type 2A (MEN 2A) is an autosomal dominant syndrome caused by activating germline mutations in the RET (REarranged during Transfection) proto-oncogene. MEN 2A has a strong (>95%) and age-dependent (5-25 years) clinical penetrance of medullary thyroid carcinoma (MTC). Several major studies have analyzed the predictive and prognostic factors for MEN 2A to find indicators that predict the optimal timing of prophylactic thyroidectomy. The aims of this study were to describe all known RET positive MEN 2A patients diagnosed in Norway and to evaluate the clinical course of MTC, as well as its predictive and prognostic factors.
This nationwide retrospective cohort study included data for 65 (14 index and 51 screening patients) out of a total of 67 MEN 2A patients with the RET gene mutation who were diagnosed in Norway since 1974. Data were collected by reviewing patient files. The variables analyzed were genotype, phenotype, preoperative basal calcitonin, age at thyroid surgery, central lymph node dissection and nodal status at primary surgery, number of surgical procedures, and biochemical cure. Of the 65 patients, 60 had undergone thyroid surgery. The median follow-up period was 9.9 years. The patients were divided into pre-RET-and RET-era, which included patients who had thyroid surgery before January 1, 1994, and after, respectively.
In index and screening patients, MTC was found, respectively, in 100% and 45% of cases, central lymph node dissection at primary surgery was done for 64% and 52% of patients, and the median total number of surgical procedures was two (range 1-6) and one (range 1-4). At primary surgery, all patients (n?=?13) with lymph node metastases had preoperative basal calcitonin levels =68?pg/mL, and all patients (n?=?17) without central lymph node dissection and preoperative basal calcitonin
Congenital hypothyroidism (CH) is defined as the lack of thyroid hormones at birth. Mutations in at least 15 different genes have been associated with this disease. While up to 20% of CH cases are hereditary, the majority of cases are sporadic with unknown etiology. Apart from a monogenic pattern of inheritance, multigenic mechanisms have been suggested to play a role in CH. The genetics of CH has not been studied in Finland so far. Therefore, multigenic sequencing of CH candidate genes was performed in a Finnish patient cohort with both familial and sporadic CH.
A targeted next-generation sequencing (NGS) panel, covering all exons of the major CH genes, was applied for 15 patients with sporadic and 11 index cases with familial CH.
Among the familial cases, six pathogenic mutations were found in the TPO, PAX8, and TSHR genes. Furthermore, pathogenic NKX2.1 and TG mutations were identified from sporadic cases, together with likely pathogenic variants in the TG, NKX2.5, SLC26A4, and DUOX2 genes. All identified novel pathogenic mutations were confirmed by Sanger-sequencing and characterized in silico and/or in vitro.
In summary, the CH panel provides an efficient, cost-effective, and multigenic screening tool for both known and novel CH gene mutations. Hence, it may be a useful method to identify accurately the genetic etiology for dyshormogenic, familial, or syndromic forms of CH.
Cites: J Med Genet. 2003 Apr;40(4):242-8 PMID 12676893
It has been suggested that moist snuff (snus), a smokeless tobacco product that is high in nicotine and widespread in Scandinavia, increases the risk of Type 2 diabetes. Previous studies are however few, contradictory and, with regard to autoimmune diabetes, lacking. Our aim was to study the association between snus use and the risk of Type 2 diabetes and latent autoimmune diabetes of adulthood (LADA).
Analyses were based on incident cases (Type 2 diabetes, n = 724; LADA, n = 200) and population-based controls (n = 699) from a Swedish case-control study. Additional analyses were performed on cross-sectional data from the Norwegian HUNT study (n = 21 473) with 829 prevalent cases of Type 2 diabetes. Odds ratios (OR) were estimated adjusted for age, BMI family history of diabetes and smoking. Only men were included.
No association between snus use and Type 2 diabetes or LADA was seen in the Swedish data. For Type 2 diabetes, the OR for > 10 box-years was 1.00 [95% confidence interval (CI), 0.47 to 2.11] and for LADA 1.01 (95% CI, 0.45 to 2.29). Similarly, in HUNT, the OR for Type 2 diabetes in ever-users was estimated at 0.91 (95% CI, 0.75 to 1.10) and in heavy users at 0.92 (95% CI, 0.46 to 1.83).
The risk of Type 2 diabetes and LADA is unrelated to the use of snus, despite its high nicotine content. This opens the possibility of the increased risk of Type 2 diabetes seen in smokers may not be attributed to nicotine, but to other substances in tobacco smoke.
Helicopter emergency medical services are an important part of many healthcare systems. Norway has a nationwide physician staffed air ambulance service with 12 bases servicing a country with large geographical variations in population density. The aim of the study was to estimate optimal air ambulance base locations.
We used high resolution population data for Norway from 2015, dividing Norway into >300 000 1 km×1 km cells. Inhabited cells had a median (5-95 percentile) of 13 (1-391) inhabitants. Optimal helicopter base locations were estimated using the maximal covering location problem facility location optimisation model, exploring the number of bases needed to cover various fractions of the population for time thresholds 30 and 45 min, both in green field scenarios and conditioning on the current base structure. We reanalysed on municipality level data to explore the potential information loss using coarser population data.
For a 45 min threshold, 90% of the population could be covered using four bases, and 100% using nine bases. Given the existing bases, the calculations imply the need for two more bases to achieve full coverage. Decreasing the threshold to 30 min approximately doubles the number of bases needed. Results using municipality level data were remarkably similar to those using fine grid information.
The whole population could be reached in 45 min or less using nine optimally placed bases. The current base structure could be improved by moving or adding one or two select bases. Municipality level data appears sufficient for proper analysis.
Cites: Injury. 2014 Jan;45(1):23-30 PMID 23915491
Cites: Air Med J. 2015 Mar-Apr;34(2):98-103 PMID 25733116
Alaska Native children experience high rates of respiratory infections and conditions. Household crowding, indoor smoke, lack of piped water, and poverty have been associated with respiratory infections. We describe the baseline household characteristics of children with severe or chronic lung disease participating in a 2012-2015 indoor air study. We monitored indoor PM2.5, CO2 , relative humidity %, temperature, and VOCs and interviewed caregivers about children's respiratory symptoms. We evaluated the association between reported children's respiratory symptoms and indoor air quality indicators using multiple logistic regression analysis. Compared with general US households, study households were more likely overcrowded 73% (62%-82%) vs 3.2% (3.1%-3.3%); had higher woodstove use as primary heat source 16% (9%-25%) vs 2.1% (2.0%-2.2%); and higher proportion of children in a household with a smoker 49% (38%-60%) vs 26.2% (25.5%-26.8%). Median PM2.5 was 33 µg/m3 . Median CO2 was 1401 ppm. VOCs were detectable in all homes. VOCs, smoker, primary wood heat, and PM2.5>25 µg/m3 were associated with higher risk for cough between colds; VOCs were associated with higher risk for wheeze between colds and asthma diagnosis. High indoor air pollutant levels were associated with respiratory symptoms in household children, likely related to overcrowding, poor ventilation, woodstove use, and tobacco smoke.
This study considered the possibility of using plant community phytomass for the assessment of soil pollution with heavy metals (HM) from industrial wastes. The three-year-long field experiment was run under the regional natural meadow vegetation; the polymetallic galvanic slime was used as an industrial waste contaminant. It is shown that soil contamination primarily causes decrease of phytomass in the growing phytocenosis. The vegetation experiments determined nonlinear dependence of cultivated and wild plant biomass on the level of soil contamination; it is described by the equations of logistic and Gaussian regression. In the absence of permanent contaminants, the soil is self-cleaned over time. It reproduces phytomass mainly due to the productivity increase of the most pollution-tolerant species in the remaining phytocenosis. This phenomenon is defined as environmental hysteresis. Soil pollution by industrial waste leads to the loss of plant biodiversity. The research shows that the study of the HM impact on ecosystems is expedient given the consideration of the "soil-phytocenosis-pollutant" complex in the "dose-response" aspect. The reaction of phytocenosis on HM showing decline in phytomass leads to serious limitations in the choice of accumulating plants, because the adsorbed HM are rejected through phytomass.
The management of multidrug-resistant tuberculosis (MDR-TB) is strictly regulated in Norway. However, nationwide studies of the epidemic are lacking.
To describe the MDR-TB epidemic in Norway over two decades.
Retrospective analysis of data on MDR-TB cases in Norway, 1995-2014, obtained from the national registry, patient records and the reference laboratory, with genotyping and cluster analysis data. Data for non-MDR-TB cases were collected from the national registry.
Of 4427 TB cases, 89 (2.0%) had MDR-TB, 7% of whom had extensively drug-resistant TB (XDR-TB) and 24% pre-XDR-TB. Of the 89 MDR-TB cases, 96% were immigrants, mainly from the Horn of Africa or the former Soviet Union (FSU); 37% had smear-positive TB; and 4% were human immunodeficiency virus co-infected. Of the 19% infected in Norway, the majority belonged to a Delhi/Central Asian lineage cluster in a local Somali community. Among the MDR-TB cases, smear-positive TB and FSU origin were independent risk factors for XDR/pre-XDR-TB. Treatment was successful in 66%; 17% were lost to follow-up, with illicit drug use and adolescence being independent risk factors. Forty-four per cent of patients treated with linezolid discontinued treatment due to adverse effects.
MDR-TB is rare in Norway and is predominantly seen in immigrants from the Horn of Africa and FSU. Domestic transmission outside immigrant populations is minimal.
Crime rates are high in substance-using populations; therefore, investigation of factors associated with crime in these populations is highly relevant. We describe crime prevalence and associations between crime, pattern of substance use and psychosocial factors, such as self-control and social network.
This is a cross-sectional study including substance users (n?=?549; mean age 34?years; 27% women) entering treatment at 21 treatment centres across Norway (December 2012 to April 2015). Data on demographics, substance use, psychosocial variables and crime in the 6?months prior to treatment were obtained through interviews. Adjusted odds ratios (aOR) with 95% confidence intervals (CI) were estimated through logistic regression.
Sixty-four percent of participants had committed crime in the 6?months prior to treatment. Of these, 93% committed income-generating crime. Several factors were associated with increased likelihood of having committed crime: use of stimulants (aOR?=?1.82, 95% CI 1.04-3.17), use of a higher number of different substances (aOR?=?1.16, 95% CI 1.04-1.31) and spending most of their time with family or friends using addictive substances (aOR?=?2.38, 95% CI 1.10-5.16 and aOR?=?2.22, 95% CI 1.32-3.73). Protective factors associated with decreased likelihood of committing crime were being older (aOR?=?0.95, 95% CI 0.92-0.97) and having higher self-control (aOR?=?0.94, 95% CI 0.91-0.97).
Stimulant use, higher number of different substances used, lower self-control, primarily a substance-using social network and being younger were associated with crime in this substance-using population. Treatment clinics should consider these risk factors for crime, and suitable interventions should be implemented and evaluated. [Skjaervø I, Skurtveit S, Clausen T, Bukten A. Substance use pattern, self-control and social network are associated with crime in a substance-using population. Drug Alcohol Rev 2017;36:245-252].
aUnit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center bDepartment of Obstetrics and Gynecology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark cDepartment of Research, The Cancer Registry of Norway, Oslo, Norway dDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden eMerck & Co. Inc., Kenilworth, New Jersey, USA.
Using a large, population-based survey, we assessed the levels and correlates of human papillomavirus (HPV) awareness among Scandinavian women after introduction of HPV vaccination. In 2011-2012, a random sample of women aged between 18 and 45 years from Denmark, Sweden and Norway received a questionnaire on lifestyle, health and HPV awareness. We included 47?895 women (response rate 60.6%) in our study. Country-specific and age-specific proportions of women who had heard of HPV in 2011-2012 (postvaccination survey) were compared with corresponding proportions in an identical survey from 2004-2005 (prevaccination survey, n=54?079, response rate 71.3%). Correlates of HPV awareness in the postvaccination survey were assessed by logistic regression. In all countries and age groups, awareness of HPV increased from the prevaccination to the postvaccination survey. In the postvaccination survey, HPV awareness was higher in Denmark (75.8%) and Sweden (74.8%) compared with Norway (62.4%), with greatest discrepancy among women aged between 18 and 19 years (Denmark: 74.9%, Sweden: 70.4%, Norway: 39.6%). Variables associated with low HPV awareness included the following: low education [=12 vs. >16 years of schooling: odds ratio (OR)=0.45, 95% confidence interval (CI): 0.42-0.48], being a virgin (vs. nonvirgins: OR=0.74, 95% CI: 0.66-0.83), never having used condoms (vs. ever: OR=0.62, 95% CI: 0.56-0.67), nonuse of contraception at first intercourse (vs. use: OR=0.83, 95% CI: 0.79-0.88) and daily smoking (vs. never: OR=0.86, 95% CI: 0.80-0.92). HPV awareness in Scandinavia has increased since the introduction of HPV vaccination. However, 24-38% of Scandinavian women still have never heard of HPV. Future information efforts should target groups with low HPV awareness.
aCenter for Primary Health Care Research, Department of Clinical Sciences in Malmö, Lund University, Region Skåne, Sweden bSchool of Medicine, Stanford Prevention Research Center, Stanford University, Stanford, California, USA.
Alcohol consumption is associated with squamous cell carcinoma of the esophagus, but little is known about whether alcohol consumption is associated with adenocarcinoma of the esophagus and gastric cancer, which we attempt to clarify in this study. Individuals with alcohol use disorders were identified from the nation-wide Swedish Hospital Discharge Register and Outpatient Register, the Crime Register, and the Prescription Drug Register, and they were linked to the Swedish Cancer Registry to calculate standardized incidence ratios of esophageal and gastric cancers using those without alcohol use disorders (AUDs) as a reference. A total of 14?518 and 73?504 patients were diagnosed with esophageal and gastric cancers, separately, during the study period. The risk of esophageal cancer was significantly increased, with a standardized incidence ratio of 2.24 (95% confidence interval 2.08-2.41) among individuals with AUDs. Both squamous cell carcinoma and adenocarcinoma of the esophagus were increased (2.89 for squamous cell carcinoma and 1.20 for adenocarcinoma). The incidence of gastric cancer was significantly decreased and the decrease was even more prominant for corpus cancer compared with cardia cancer (0.57 vs. 0.82). In this retrospective cohort study, we found that AUDs were associated with an increased risk of both squamous cell carcinoma and adenocarcinoma of the esophagus, whereas individuals with AUDs had a lower risk of gastric cancer, especially for corpus cancer, which may be related to the eradication of Helicobacter pylori infection. However, the underlying mechanisms need to be explored in future studies.