Pituitary dysfunction following mild traumatic brain injury in female athletes.

Objective: Pituitary dysfunction following mild traumatic brain injury can have serious physical and psychological consequences, making correct diagnosis and treatment essential. To the best of our knowledge, this study is the first to study the prevalence of pituitary dysfunction following mild traumatic brain injury in an all-female population following detailed endocrinological work-up after screening for pituitary dysfunction in female athletes. Design: This is a retrospective cohort study. Methods: Hormone screening blood tests, including serum blood values for thyroid-stimulating hormone, free thyroxin, insulin-like growth factor 1, prolactin, cortisol, follicle-stimulating hormone, luteinizing hormone, estrogen and progesterone, were taken in 133 female athletes. Results were repeatedly outside the reference value in 88 women necessitating further endocrinological evaluation. Two of those were lost to follow-up, and further endocrinological evaluation was performed in 86 participants. Results: Six women (4.6%, n = 131) were diagnosed with hypopituitarism, four (3.1%) with central hypothyroidism and two with growth hormone deficiency (1.5%). Ten women (7.6%) had hyperprolactinemia, and four (3.1%) of them had prolactinoma. Medical treatment was initiated in 13 (9.9%) women. Significant prognostic factors were not found. Conclusions: As 12.2% of female athletes with a history of mild traumatic brain injury had pituitary dysfunction (hypopituitarism 4.6%, hyperprolactinemia 7.6%), we conclude that pituitary dysfunction is an important consideration in post-concussion care. Hyperprolactinemia in the absence of prolactinoma may represent pituitary or hypothalamic injury following mild traumatic brain injury. Significance statement: Mild traumatic brain injury (mTBI) has become a growing public health concern as 50 million people worldwide sustain a traumatic brain injury annually, with mTBI being the most common (70-90%). As studies on mTBI have focused on mostly male populations this study aims to explore pituitary dysfunction (PD) in female athletes following mTBI. To the best of our knowledge, it is the first all-female study on PD following mTBI. The study found that 12.2% of the participating women had PD after mTBI. Six (4.6%) had hypopituitarism and ten (7.6%) had hyperprolactinemia. These findings suggest that PD following mTBI is an important consideration that endocrinologists and other medical staff working with athletes need to be aware of.

Screening for possible hypopituitarism following mild traumatic brain injury: The first all-female study. Who do we need to evaluate further?

BACKGROUND: Studies on hypopituitarism (HP) following mild traumatic brain injury (mTBI) have focused on male populations although women may be more susceptible to the sequelae of mTBI. This is, to the best of our knowledge, the first all-female study screening for HP following mTBI. OBJECTIVE: Screening for possible HP in female athletes reporting a history of one or more mTBI. METHODS: Pituitary hormone screening blood tests (SBT) were performed in 133 of the 151 female athletes included. Repeated results outside the reference value (O-RV) were considered abnormal necessitating further endocrinological evaluation. RESULTS: Repeated SBT were O-RV in 88 women (66.2%). Decreased levels of serum insulin growth factor 1 (S-IGF1) were found in 55.6% of participants and elevated levels of serum prolactin (S-prolactin) in 22.6%. Serum cortisol levels were below the RV in 6.0% and thyroid hormonal levels in 11.3%. Lower age and increased number of mTBI symptoms correlated significantly with the risk of hormonal results O-RV. CONCLUSION: The majority of the study population had SBT O-RV, warranting further workup of possible HP. Decreased levels of S-IGF1 were most commonly observed followed by elevated S-prolactin possibly indicating hypothalamic-pituitary impairment. Lower age and increased number of symptoms of mTBI may indicate the need to screen for HP.

Monitoring iron stores in Icelandic blood donors from 1997 through 2019.

OBJECTIVES: To estimate the frequency of iron deficiency (ID) and anaemia in blood donors in Iceland and the impact of serum ferritin (SF) testing policy change. BACKGROUND: Blood donations contribute to ID and/or anaemia in whole blood donors (WBD). SF may be used to monitor blood donor iron stores. MATERIALS AND METHODS: The study included WBD and new donors (ND) in the Icelandic Blood Bank in 1997-2019. SF was measured for ND and intermittently for WBD until October 2017, but thereafter for all WBD and ND at every visit. In January 2018, the SF threshold increased from 14 to 16 µg/L for ND and from 8 to 10 µg/L for WBD. RESULTS: The study included 85 370 SF results from 243 369 visits of 32 910 donors. Median SF was higher for males than females, both for ND (88.0 vs. 31.2 µg/L, p < 0.001) and WBD (before 2018: 43.0 vs. 22.0 µg/L, p < 0.001). After the policy change in 2018, median SF increased for both male WBD (to 45.2 µg/L, p < 0.001) and female WBD (to 25.7 µg/L, p < 0.001). ID (SF <15 µg/L) was present in 10.6% of female ND and 0.5% of male ND. After policy change, the proportion of WB donations associated with ID decreased for males (from 6.4% to 4.0%) and females (from 18.9% to 14.1%). ID anaemia was present at some time in 3.7% of female WBD and 1.2% of male WBD. CONCLUSION: This nationwide study showed that ID in WB donors is common, especially among females, but monitoring SF may improve donor management.

Eleven genomic loci affect plasma levels of chronic inflammation marker soluble urokinase-type plasminogen activator receptor.

Soluble urokinase-type plasminogen activator receptor (suPAR) is a chronic inflammation marker associated with the development of a range of diseases, including cancer and cardiovascular disease. The genetics of suPAR remain unexplored but may shed light on the biology of the marker and its connection to outcomes. We report a heritability estimate of 60% for the variation in suPAR and performed a genome-wide association meta-analysis on suPAR levels measured in Iceland (N = 35,559) and in Denmark (N = 12,177). We identified 13 independently genome-wide significant sequence variants associated with suPAR across 11 distinct loci. Associated variants were found in and around genes encoding uPAR (PLAUR), its ligand uPA (PLAU), the kidney-disease-associated gene PLA2R1 as well as genes with relations to glycosylation, glycoprotein biosynthesis, and the immune response. These findings provide new insight into the causes of variation in suPAR plasma levels, which may clarify suPAR's potential role in associated diseases, as well as the underlying mechanisms that give suPAR its prognostic value as a unique marker of chronic inflammation.

Autoimmune disease is associated with a lower risk of progression in monoclonal gammopathy of undetermined significance.

OBJECTIVES AND METHODS: We conducted a population-based study including 19 303 individuals diagnosed with MGUS in Sweden from 1985 to 2013, with the aim to determine whether a prior history of autoimmune disease, a well-described risk factor for MGUS is a risk factor for progression of MGUS to multiple myeloma (MM) or lymphoproliferative diseases (LPs). Using the nationwide Swedish Patient registry, we identified MGUS cases with versus without an autoimmune disease present at the time of MGUS diagnosis and estimated their risk of progression. RESULTS: A total of 5612 (29.1%) MGUS cases had preceding autoimmune diseases. Using Cox proportional hazards models, we found the risk of progression from MGUS to MM (HR = 0.83, 95% CI 0.73-0.94) and LPs (HR = 0.84, 95% CI 0.75-0.94) to be significantly lower in MGUS cases with prior autoimmune disease (compared to MGUS cases without). CONCLUSIONS: In this large population-based study, a history of autoimmune disease was associated with a reduced risk of progression from MGUS to MM/other LPs. Potential underlying reason is that MGUS caused by chronic antigen stimulation is biologically less likely to undergo the genetic events that trigger progression. Our results may have implications in clinical counseling for patients with MGUS and underlying autoimmune disease.

Computerized algorithms compared with a nephrologist's diagnosis of acute kidney injury in the emergency department.

BACKGROUND: The aim of this study was to examine acute kidney injury (AKI) diagnosis based on different computerized algorithms compared with a nephrologist's diagnosis in patients visiting an emergency department (ED) of a university hospital. METHODS: In this retrospective study, we used electronic medical records at the University Hospital in Reykjavik to identify all patients aged ≥18 years, who presented to the ED in the year 2010 with an elevated serum creatinine (SCr) level. All SCr values were reviewed and a nephrologist determined whether AKI was present using the KDIGO SCr criteria and clinical data. Computerized algorithms based on the KDIGO SCr criteria, accounting for various time intervals for baseline SCr and changes in follow-up SCr, were constructed using the statiscal software R. RESULTS: At 53,816 ED visits, SCr was measured in 15,588 patients for a total of 21,559 measurements. Elevated SCr was observed in 2878 (18.4%) patients. Strict adherence to the KDIGO SCr criteria yielded a 79% sensitivity, 94% specificity, 68% positive predictive value (PPV) and 96% negative predictive value (NPV) for the diagnosis of AKI. Allowing for a longer time frame (>365 days) for baseline SCr, resulted in 93% sensitivity, 96% specificity, 80% PPV and 99% NPV. The algorithms which included a decrease in SCr from the index ED value yielded a sensitivity of 97% but lower specificity, 74% and 80%. CONCLUSIONS: The algorithms that perform best yield excellent sensitivity and specificity and could be used to identify patients with AKI in the ED to enhance early diagnosis and treatment.

Ara h 1 and Ara h 6 Sensitization Causes Clinical Peanut Allergy in Ara h 2-Negative Individuals.

BACKGROUND: Of the major peanut allergens, sensitivity to Ara h 2 has the highest prediction for clinical allergy. In this study, we evaluated sensitization to peanut components in Iceland and related Ara h 2-negative sensitization to clinical allergy. METHODS: Ara h 1, Ara h 2, Ara h 3, Ara h 8, and Bet v 1 IgEs were measured (ImmunoCAP) in 220 peanut IgE (Pn-IgE)-positive serum samples. Ara h 2 IgE-negative individuals were invited to an open peanut challenge and evaluated for Ara h 6 and 9 sensitization (ISAC microarray). RESULTS: The Ara h 2 IgE-negative group (52.3%, 115/220) was older (p = 0.04) and more likely to have a history of pollen allergy than the Ara h 2-positive group (p < 0.001). Of the Ara h 2-negative participants, 24.3% were already consuming peanuts and 38.3% were unavailable. Of the 43 who underwent an open peanut challenge, 79% were negative, 14% were positive, and 7% were inconclusive. Those who reacted to peanuts had a higher Ara h 1 IgE than that of the tolerant participants, and 3 were positive to Ara h 6 IgE, and 2 of those subjects were monosensitized. Ara h 8 may have caused a positive reaction, while Ara h 9 did not. CONCLUSIONS: Half of the peanut-sensitized individuals in Iceland were not sensitized to the major allergen Ara h 2. Ara h 1, Ara h 3, and Ara h 6 sensitizations resulted in a positive open peanut challenge and they are therefore clinically important for individuals with a peanut allergy in Iceland.

[Views of Icelandic women towards genetic counseling - and testing of BRCA2 mutations].

Introduction The aim of this study was to explore the attitudes of Icelandic women towards existing genetic information, genetic counseling and genetic testing for BRCA mutations which dramatically increase risk for aggressive cancers. Materials and methods Women attending the cancer prevention clinic in Reykjavik, capital of Iceland, from October 12th until November 20th 2015 received an invitation to participate. Participation involved answering a short online questionnaire about background, family history of cancer as well as attitudes towards genetic counseling, BRCA testing and preventive use of such information. Descriptive statistics and chi-square tests were used to describe differences in attitudes towards those questions between subgroups of women. Results 1129 women (69% response rate) answered the questionnaire. Mean age was 47 years (span 21-76 years). Around half (47%) had heard fairly much about the mutations. Independent of family history of cancer, the majority of women were positive towards receiving genetic counseling (79%) and to undergo genetic testing (83%) for BRCA mutation with younger women being more interested than older women. On the other hand, only 4% of the women had already received genetic counseling and 7% undergone genetic testing. Women with family history of cancer were more knowledgeable about BRCA mutations (p<0.0001) and were less afraid of the consequence of being a mutation carrier (p<0.0001) compared to those with little or no family history. Regardless of family history, half (49%) worried that results from genetic testing could influence their health insurance. Almost all, or 97% of the women, were positive or very positive toward using existing genetic information obtained through scientific work, to inform affected indi-viduals of their mutation status. Conclusion Icelandic women are positive towards genetic counseling and testing for BRCA mutations although half of them worry that a positive result might affect their health insurance. Nevertheless, almost all women believe that existing genetic information should be used to inform carriers for preventive purposes.

Variations in elderly peoples' visits to the emergency departments in Iceland: A five-year population study.

INTRODUCTION: Elderly people visiting emergency departments (ED) are a non-homogenous group. Gender and other socio-demographic variations in emergency care might be present. However, gender-specific ED-data is scarce. METHODS: We retrieved retrospective data on all ED-visits, by 67years and older from 2008 to 2012, and calculated incidence of visits applying population registries. The relationship of age-categories, marital status, health and residence with outcomes were analyzed descriptively by Chi-square tests. Regression models were built to analyze gender-specific variations. RESULTS: Of the total ED-visits, 20% were from the elderly population (n=66,141), at a mean 3.1 visits per individual. Men (n=30.269) had higher incidence of visits in all age-categories. They were mostly married (69%) and women widowed (43%), although the incidence of partnered visitors underrepresented population-data while widowed and single living overrepresented. Women had more often co-morbidities, their most common causes of visits were musculoskeletal (20%) and men circulatory causes (14%). Men were more likely to be admitted (OR: 1.23; 95% CI 1.16-1.30) and had more unplanned ED-revisits (HR: 1.20; 95% CI 1.06-1.35) within 30 days. DISCUSSION: Elderly men visiting the ED were more often married than women. Gender differences were found in causes of visits and outcomes. In clinical practice, gender may be considered when identifying risk and planning adequate care related elderly ED-visits.

[Fast diagnostic track for suspected lung cancer: A patient centered approach].

INTRODUCTION: The aim of this study is to describe the characteristics of patients who underwent a fast diagnostic track (FDT) due to suspected lung cancer at Landspitali University Hospital, Iceland. MATERIAL AND METHODS: Hospital records were reviewed on background characteristics, diagnosis, staging, waiting times and survival of all 550 patients (mean age 68.1 years, 57% female) that participated in the FDT from February 1, 2008 to January 31, 2015. Adjusting for clinical characteristics in a multivariate analysis, overall survival was compared for patients diagnosed with lung cancer within or outside the FDT in Iceland in 2014 (n=167, mean age 69.3 years, 61.7% female). RESULTS: Of the 550 FDT patients, 426 were diagnosed with lung cancer (77.5%); 346 of the non-small cell type (NSCLC) (81.2%). The proportion of patients receiving lung cancer diagnosis through the FDT increased from 23.3% in 2008 to 47.9% in 2014 (p<0.001). The waiting time from referral to diagnosis was 10 days median and 19 days from diagnosis to initiation of treatment. More patients with advanced disease were diagnosed outside the FDT (70.1% vs. 37.5%, p<0.05). When ad-- justed for age, sex, histology, stage at diagnosis and therapy, patients diagnosed with lung cancer outside the FDT had higher risk of all-cause mortality (HR 1.60; 95% CI: 0.95 - 2.71) although the difference was not statistically significant. CONCLUSION: An increasing proportion of lung cancer diagnosis in Iceland is made through a fast diagnostic track with potential benefits for patients. The waiting time from referral to diagnosis and treatment is in line with international guidelines. Key words: lung cancer, non-small cell lung cancer, diagnostic track, waiting times, survival. Correspondence: Hronn Hardardottir, hronnh@landspitali.is.

Association between Daily Hydrogen Sulfide Exposure and Incidence of Emergency Hospital Visits: A Population-Based Study.

BACKGROUND: The adverse health effects of high concentrations of hydrogen sulfide (H2S) exposure are well known, though the possible effects of low concentrations have not been thoroughly studied. The aim was to study short-term associations between modelled ambient low-level concentrations of intermittent hydrogen sulfide (H2S) and emergency hospital visits with heart diseases (HD), respiratory diseases, and stroke as primary diagnosis. METHODS: The study is population-based, using data from patient-, and population-registers from the only acute care institution in the Reykjavik capital area, between 1 January, 2007 and 30 June, 2014. The study population was individuals (≥18yr) living in the Reykjavik capital area. The H2S emission originates from a geothermal power plant in the vicinity. A model was used to estimate H2S exposure in different sections of the area. A generalized linear model assuming Poisson distribution was used to investigate the association between emergency hospital visits and H2S exposure. Distributed lag models were adjusted for seasonality, gender, age, traffic zones, and other relevant factors. Lag days from 0 to 4 were considered. RESULTS: The total number of emergency hospital visits was 32961 with a mean age of 70 years. In fully adjusted un-stratified models, H2S concentrations exceeding 7.00µg/m3 were associated with increases in emergency hospital visits with HD as primary diagnosis at lag 0 risk ratio (RR): 1.067; 95% confidence interval (CI): 1.024-1.111, lag 2 RR: 1.049; 95%CI: 1.005-1.095, and lag 4 RR: 1.046; 95%CI: 1.004-1.089. Among males an association was found between H2S concentrations exceeding 7.00µg/m3, and HD at lag 0 RR: 1.087; 95%CI: 1.032-1.146 and lag 4 RR: 1080; 95%CI: 1.025-1.138; and among those 73 years and older at lag 0 RR: 1.075; 95%CI: 1.014-1.140 and lag 3 RR: 1.072; 95%CI: 1.009-1.139. No associations were found with other diseases. CONCLUSIONS: The study showed an association between emergency hospital visits with HD as primary diagnosis and same day H2S concentrations exceeding 7.00µg/m3, more pronounced among males and those 73 years and older than among females and younger individuals.

[Epidemiology of the two types of gastric adenocarcinoma in Iceland according to the Laurén histological classification 1990-2009].

BACKGROUND: In the mid twentieth century gastric cancer was the most common type of cancer in Iceland. In recent decades, however, the incidence rate of gastric cancer has decreased markedly and currently only represents 2-3% of cancer cases. The Laurén classification system classifies adenocarcinoma into two types, intestinal and diffuse. The main purpose of our study was to describe the epidemiology of the two types of gastric adenocarcinoma in Iceland between the years 1990-2009. METHODS: This is a retrospective cohort study. Information on patients diagnosed with gastric cancer in Iceland between 1990 and 2009 was collected from the population based Cancer Registry. Histological descriptions were reviewed and classified according to the Laurén classification system. The records of patients diagnosed with either having intestinal or diffuse adenocarcinomas were reviewed and epidemiological information gathered. RESULTS: Between 1990 and 2009, 730 patients were diagnosed with gastric adenocarcinoma in Iceland, 447 had intestinal adenocarcinoma and 168 diffuse adenocarcinoma. Patients diagnosed with diffuse adenocarcinoma were significantly younger at diagnosis than those diagnosed with intestinal adenocarcinoma. The sex ratio for intestinal adenocarcinoma was 2.3:1 (M:F) and 1.1:1 (M:F) for diffuse adenocarcinoma. The incidence of intestinal adenocarcinoma decreased more rapidly than that of diffuse adenocarcinoma during this period (0.92/100,000 vs. 0.12/100,000). Median survival rates of intestinal and diffuse adenocarcinomas were 23.7 and 20.6 months, respectively. The difference in survival was found to be statistically significant. The hazard ratio between the two groups was 1.31 (CI 1.03-1.67), corrected for age, sex, stage, year of diagnosis and surgical outcome (radical, non-radical or no operation). CONCLUSION: The overall incidence rate of gastric cancer has decreased dramatically in the past 20 years. However, the reduction is largely limited to the intestinal adenocarcinoma sub-group. We conclude that the Laurén classification predicts prognosis in gastric adenocarcinoma with diffuse adenocarcinoma having worse prognosis. KEY WORDS: gastric cancer, Laurén classification, survival, incidence. Correspondence: Halla Sif Olafsdottir, hsolafsdottir@gmail.com.

Free fatty acid suppositories are as effective as docusate sodium and sorbitol enemas in treating constipation in children.

AIM: A well-documented, clinically proven per rectum treatment for childhood constipation is needed. This phase two clinical trial evaluated the efficacy of suppositories containing free fatty acids (FFA) compared with Klyx docusate sodium and sorbitol enemas. METHODS: A randomised, controlled, single-blind study was undertaken on 77 children aged between one and 17 who presented to an emergency department in Iceland and were diagnosed with constipation. In stage one, 23 patients were randomised to receive lower dose FFA suppositories or Klyx (n = 33). In stage two, 21 different patients were randomised to receive higher dose suppositories and compared with the same Klyx control subjects. RESULTS: The suppositories were effective at bowel emptying in 39% of the group who received the lower FFA doses and 81% of the group receiving higher doses, compared with 88% in the Klyx control group. Symptom relief was obtained in 30% of the group receiving the lower doses and 71% of the group receiving the higher doses, compared with 73% in the control group. CONCLUSION: The higher dose FFA suppositories were as effective as the Klyx enemas with regard to bowel emptying and symptom relief and might provide an important and less invasive alternative for childhood constipation.

Clinical trial: free fatty acid suppositories compared with enema as bowel preparation for flexible sigmoidoscopy.

OBJECTIVES: The purpose of this trial was to evaluate the efficacy and safety of recently developed suppositories containing free fatty acids as a bowel-cleansing agent prior to flexible sigmoidoscopy and compare them with Klyx (docusate sodium/sorbitol). DESIGN: A controlled, non-inferiority, single-blind, randomised study on outpatients undergoing flexible sigmoidoscopy. SETTING: Department of Gastroenterology, Landspitali-University Hospital and endoscopic clinic. PATIENTS: 53 outpatients undergoing flexible sigmoidoscopy. INTERVENTION: Participants were randomised to receive either free fatty acid suppositories (28) or a standard bowel preparation with Klyx enema (25). In the study group, two suppositories were administered the evening before as well as 2 h prior to the sigmoidoscopy. In the control group, Klyx enema (120 mL) was administered the evening before and repeated 2 h prior to the procedure. MAIN OUTCOME MEASUREMENTS: Quality of the bowel cleansing, height of scope insertion and safety. RESULTS: The mean height of scope insertion and bowel cleansing was 43 cm (SD=13.4) in the study group and 48 cm (SD=10.4) in the control group (NS). The investigating physicians were less satisfied with the bowel preparation in the study group compared with the control group with a difference of 20% (p<0.016). The amount of faeces noted in the rectum was similar in both groups with no significant difference (p<0.56). No serious side effects, toxic reaction or irritation were observed. CONCLUSIONS: The suppositories are well tolerated with no significant side effects. The suppositories had distinct bowel emptying effect and as effective as Klyx in rectal cleansing. Although physician's satisfaction was slightly lower, the height of scope insertion was similar. TRIAL REGISTRATION NUMBER: EudraCT nr.: 2010-018761-35.

The effect of SNPs on expression levels in Nimblegen RNA expression microarrays.

In this paper the effect of SNPs on expression levels in Nimblegen RNA expression microarrays is investigated. A vast number of replicates of probe pairs representing both alleles of SNPs on 14 loci allows accurate estimation of the difference in signal intensities both within and between probe pairs. The majority of probe-pairs with sufficiently high expression have significant differences in expression levels within the pair and the difference shows concordance with the genotype of the samples. With two or more replicates of each probe, the allele-to-allele variance dominates the error in estimating the difference within the probe-pair, ten replicates are needed for adequate power in calling a true difference within a single probe-pair. Using the expression level of the probe within the probe-pair that has the higher value gives more accurate estimates. When using probes at loci containing known SNP's one should use probes containing both alleles of the SNP.

Pregnancy-Induced Hypertensive Disorders before and after a National Economic Collapse: A Population Based Cohort Study.

BACKGROUND: Data on the potential influence of macroeconomic recessions on maternal diseases during pregnancy are scarce. We aimed to assess potential change in prevalence of pregnancy-induced hypertensive disorders (preeclampsia and gestational hypertension) during the first years of the major national economic recession in Iceland, which started abruptly in October 2008. METHODS AND FINDINGS: Women whose pregnancies resulted in live singleton births in Iceland in 2005-2012 constituted the study population (N = 35,211). Data on pregnancy-induced hypertensive disorders were obtained from the Icelandic Medical Birth Register and use of antihypertensive drugs during pregnancy, including ß-blockers and calcium channel blockers, from the Icelandic Medicines Register. With the pre-collapse period as reference, we used logistic regression analysis to assess change in pregnancy-induced hypertensive disorders and use of antihypertensives during the first four years after the economic collapse, adjusting for demographic and pregnancy characteristics, taking aggregate economic indicators into account. Compared with the pre-collapse period, we observed an increased prevalence of gestational hypertension in the first year following the economic collapse (2.4% vs. 3.9%; adjusted odds ratio [aOR] 1.47; 95 percent confidence interval [95%CI] 1.13-1.91) but not in the subsequent years. The association disappeared completely when we adjusted for aggregate unemployment rate (aOR 1.04; 95% CI 0.74-1.47). Similarly, there was an increase in prescription fills of ß-blockers in the first year following the collapse (1.9% vs.3.1%; aOR 1.43; 95% CI 1.07-1.90), which disappeared after adjusting for aggregate unemployment rate (aOR 1.05; 95% CI 0.72-1.54). No changes were observed for preeclampsia or use of calcium channel blockers between the pre- and post-collapse periods. CONCLUSIONS: Our data suggest a transient increased risk of gestational hypertension and use of ß-blockers among pregnant women in Iceland in the first and most severe year of the national economic recession.

The Role of Diagnosis and Clinical Follow-up of Monoclonal Gammopathy of Undetermined Significance on Survival in Multiple Myeloma.

IMPORTANCE: Multiple myeloma (MM) is consistently preceded by the precursor state, monoclonal gammopathy of undetermined significance (MGUS). The average annual risk of progression from MGUS to multiple myeloma is 0.5% to 1.0%. Current guidelines suggest life-long clinical follow-up of individuals diagnosed as having MGUS depending on risk stratification. The impact of diagnosing and conducting clinical follow-up of MGUS on MM survival is unclear. OBJECTIVE: To estimate the impact of prior knowledge of MGUS diagnosis and comorbidities on MM survival. DESIGN, SETTING, AND PARTICIPANTS: We conducted a population-based study including all patients with MM (MM patients) diagnosed in Sweden (n = 14,798) from 1976 to 2005 (with follow-up until 2007); 394 (2.7%) had previously been diagnosed as having MGUS. Information on comorbidities was gathered for all patients. We calculated survival rates from the time of MM diagnosis, comparing patients with vs those without prior knowledge of MGUS. Using Cox proportional hazards models, we calculated hazard ratios (HRs) and 95% CIs for risk factors for death. χ2 Tests were used to evaluate differences in comorbidities. EXPOSURES: Prior knowledge of MGUS among MM patients. In a subanalysis, monoclonal (M)-protein concentration and type were used as exposure. MAIN OUTCOMES AND MEASURES: Risk of death and comorbidities. RESULTS: Patients with MM with prior knowledge of MGUS had significantly (HR, 0.86; 95% CI, 0.77-0.96; P < .01) better overall survival (median survival, 2.8 years) than MM patients without prior knowledge of MGUS (median survival, 2.1 years), although MM patients with (vs without) prior knowledge of MGUS had more comorbidities (P < .001). Among MM patients with prior knowledge of MGUS, low M-protein concentration (<0.5 g/dL) at MGUS diagnosis was associated with poorer MM survival (HR, 1.86; 95% CI, 1.13-3.04; P = .01). CONCLUSIONS AND RELEVANCE: Patients with MM with prior knowledge of MGUS had better MM survival, suggesting that earlier treatment of MM leads to better survival. The observation that a low M-protein concentration at MGUS diagnosis was associated with poorer MM survival may reflect less frequent clinical follow-up. Our observations stress the importance of clinical follow-up in patients with MGUS, regardless of risk stratification.

Hodgkin lymphoma risk following infectious and chronic inflammatory diseases: a large population-based case-control study from Sweden.

Patients with Hodgkin lymphoma (HL) have a well-characterized immune deficiency of T cell function, originally identified by increased susceptibility to certain infections. Epidemiological evidence has long pointed to infectious etiologies in younger HL patients. With the aim of expanding our knowledge on the potential role of pre-existing immune deficiency in HL and an infectious/inflammatory etiology, we conducted a comprehensive population-based case-control study in HL patients diagnosed in Sweden in the period 1965-2004, and their matched controls. In a large population-based study including 7,414 HL patients and 29,240 matched controls, we evaluated the subsequent risk of HL in relation to a broad range of infectious and inflammatory conditions, using unconditional logistic regression. A previous history of any reported infection was associated with an 11 % increased risk of HL (P < 0.05). More specifically, we found sinusitis (odds ratio = 1.81; 95 % confidence interval = 1.06-3.07), tuberculosis (1.76; 1.01-3.07), encephalitis (7.88; 1.97-31.5), and herpes zoster (2.20; 1.11-4.35) to be associated with excess HL risk. A personal prior history of chronic inflammatory condition was not associated with an increased risk of HL (0.94; 0.71-1.14). Our results suggest that underlying immune deficiency is a primary phenomenon in HL. Alternatively, certain infectious agents may be potential HL triggers.

Healing rate and autoimmune safety of full-thickness wounds treated with fish skin acellular dermal matrix versus porcine small-intestine submucosa: a noninferiority study.

A novel product, the fish skin acellular dermal matrix (ADM) has recently been introduced into the family of biological materials for the treatment of wounds. Hitherto, these products have been produced from the organs of livestock. A noninferiority test was used to compare the effect of fish skin ADM against porcine small-intestine submucosa extracellular matrix in the healing of 162 full-thickness 4-mm wounds on the forearm of 81 volunteers. The fish skin product was noninferior at the primary end point, healing at 28 days. Furthermore, the wounds treated with fish skin acellular matrix healed significantly faster. These results might give the fish skin ADM an advantage because of its environmental neutrality when compared with livestock-derived products. The study results on these acute full-thickness wounds might apply for diabetic foot ulcers and other chronic full-thickness wounds, and the shorter healing time for the fish skin-treated group could influence treatment decisions. To test the autoimmune reactivity of the fish skin, the participants were tested with the following ELISA (enzyme-linked immunosorbent assay) tests: RF, ANA, ENA, anti ds-DNA, ANCA, anti-CCP, and anticollagen I and II. These showed no reactivity. The results demonstrate the claims of safety and efficacy of fish skin ADM for wound care.