Ing-Liss Bryngelsson

All-cause mortality in 272,186 patients hospitalized with incident atrial fibrillation 1995-2008: a Swedish nationwide long-term case-control study.

Aims To evaluate long-term all-cause risk of mortality in women and men hospitalized for the first time with atrial fibrillation (AF) compared with matched controls. Methods and results A total of 272 186 patients (44% women) ≤85 years at the time of hospitalization with incidental AF 1995–2008 and 544 344 matched controls free of in-hospital diagnosis of AF were identified. Patients were followed via record linkage of the Swedish National Patient Registry and the Cause of Death Registry. Using Cox regression models, the long-term relative all-cause mortality risk, adjusted for concomitant diseases, in women vs. controls was 2.15, 1.72, and 1.44 (P < 0.001) in the age categories ≤65, 65–74, and 75–85 years, respectively. The corresponding figures for men were 1.76, 1.36, and 1.24 (P < 0.001). Among concomitant diseases, neoplasm, chronic renal failure, and chronic obstructive pulmonary disease contributed most to the increased all-cause mortality vs. controls. In patients with AF as the primary diagnosis, the relative risk of mortality was 1.63, 1.46, and 1.28 (P < 0.001) in women and 1.45, 1.17, and 1.10 (P < 0.001) in men. Conclusion Atrial fibrillation was an independent risk factor of all-cause mortality in patients with incident AF. The concomitant diseases that contributed most were found outside the thromboembolic risk scores. The highest relative risk of mortality was seen in women and in the youngest patients compared with controls, and the differences between genders in each age category were statistically significant.

Excess Mortality and Morbidity in Patients with Craniopharyngioma, Especially in Patients with Childhood Onset: A Population-Based Study in Sweden

CONTEXT Craniopharyngiomas (CPs) in adults have been associated with excess mortality. OBJECTIVE The aim of the study was to investigate mortality and morbidity in patients with childhood-onset and adult-onset CP. METHODS PATIENTS with CP were identified and followed in Swedish national health registries, 1987 through 2011. The inclusion criteria for the CP diagnosis were internally validated against patient records in 28% of the study population. SETTINGS This was a nationwide population-based study. PATIENTS A total of 307 patients (151 men and 156 women) were identified and included (mean follow-up, 9 years; range, 0-25 years). The inclusion criteria had a positive predictive value of 97% and a sensitivity of 92%. INTERVENTION There were no interventions. MAIN OUTCOME MEASURES Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) with 95% confidence intervals were calculated using the Swedish population as the reference. RESULTS During the study, 54 patients died compared with the expected number of 14.1, resulting in an SMR of 3.2 (2.2-4.7) for men and 4.9 (3.2-7.2) for women. PATIENTS with childhood-onset (n = 106) and adult-onset (n = 201) CP had SMRs of 17 (6.3-37) and 3.5 (2.6-4.6), respectively. PATIENTS with hypopituitarism (n = 250), diabetes insipidus (n = 110), and neither of these (n = 54) had SMRs of 4.3 (3.1-5.8), 6.1 (3.5-9.7), and 2.7 (1.4-4.6), respectively. The SMR due to cerebrovascular diseases was 5.1 (1.7-12). SIRs were 5.6 (3.8-8.0) for type 2 diabetes mellitus, 7.1 (5.0-9.9) for cerebral infarction, 0.7 (0.2-1.7) for myocardial infarction, 2.1 (1.4-3.0) for fracture, and 5.9 (3.4-9.4) for severe infection. The SIR for all malignant tumors was 1.3 (0.8-2.1). CONCLUSIONS This first nationwide population-based study of patients with CP demonstrated excess mortality that was especially marked in patients with childhood-onset disease and among women. Death due to cerebrovascular diseases was increased 5-fold. Hypopituitarism and diabetes insipidus were negative prognostic factors for mortality and morbidity. PATIENTS with CP had increased disease burden related to type 2 diabetes mellitus, cerebral infarction, fracture, and severe infection.

Risk of Cancer Among Workers Exposed to Trichloroethylene: Analysis of Three Nordic Cohort Studies

BACKGROUND Trichloroethylene (TCE) is a widely used chlorinated solvent with demonstrated carcinogenicity in animal assays. Some epidemiologic studies have reported increased risk of cancer of the kidney, cervix, liver and biliary passages, non-Hodgkin lymphoma, and esophageal adenocarcinoma. METHODS We established a pooled cohort, including 5553 workers with individual documented exposure to TCE in Finland, Sweden, and Denmark. Study participants were monitored for the urinary TCE metabolite trichloroacetic acid from 1947 to 1989 and followed for cancer. Standardized incidence ratios (SIRs) were calculated based on cancer incidence rates in the three national populations. Cox proportionate hazard analyses were used for internal comparisons. Tests of statistical significance are two-sided. RESULTS Overall, 997 cases of cancer (n = 683 in men; n = 314 in women) were identified during 154 778 person-years of follow-up. We observed statistically significant elevated standardized incidence ratios for primary liver cancer (1.93; 95% confidence interval [CI] = 1.19 to 2.95) and cervical cancer (2.31; 95% CI = 1.32 to 3.75). The standardized incidence ratio for kidney cancer was 1.01 (95% CI = 0.70 to 1.42) based on 32 cases; we did not observe a statistically significant increased risk of non-Hodgkins lymphoma (SIR = 1.26; 95% CI = 0.89 to 1.73) or esophageal adenocarcinoma (SIR = 1.84; 95% CI = 0.65 to 4.65). Tobacco- and alcohol-associated cancers were not statistically significantly increased. CONCLUSIONS Our results suggest TCE exposure is possibly associated with an increased risk for liver cancer. The relationship between TCE exposure and risks of cancers of low incidence and those with confounding by lifestyle and other factors not known in our cohort require further study.

Excess Mortality in Women and Young Adults With Nonfunctioning Pituitary Adenoma: A Swedish Nationwide Study

CONTEXT Patients with hypopituitarism of various etiologies have excess mortality. The mortality in patients with nonfunctioning pituitary adenoma (NFPA), regardless of pituitary function, is less well studied. OBJECTIVE Our aim was to investigate mortality in patients with NFPA and to examine whether age at diagnosis, gender, tumor treatments, or hormonal deficiencies influence the outcome. DESIGN NFPA patients were identified and followed up in nationwide health registries in Sweden, 1987-2011. The criteria for identification were tested and validated in a subpopulation of the patients. SETTINGS This was a nationwide, population-based study. PATIENTS A total of 2795 unique patients with NFPA (1502 men, 1293 women) were identified and included in the study. Mean age at diagnosis was 58 years (men, 60 y; women, 56 y) and mean follow-up time was 7 years (range 0-25 y). INTERVENTION There were no interventions. MAIN OUTCOME MEASURES Standardized mortality ratios (SMRs) and annual incidence rates were calculated using the Swedish population as reference and presented with 95% confidence intervals. RESULTS Annual incidence of NFPA was 20.3 (18.8-21.9) cases per 1 million inhabitants. During the observation period, 473 patients died against an expected 431, resulting in an SMR of 1.10 (1.00-1.20). Patients diagnosed at younger than 40 years of age had an increased SMR of 2.68 (1.23-5.09). The SMR for patients with hypopituitarism (n = 1500) was 1.06 (0.94-1.19), and for patients with diabetes insipidus (n = 145), it was 1.71 (1.07-2.58). The SMR was increased in women with NFPA (1.29; 1.11-1.48) but not in men (1.00; 0.88-1.12). Women, but not men, with a diagnosis of hypopituitarism and/or diabetes insipidus also had an increased mortality ratio. SMRs due to cerebrovascular (1.73; 1.34-2.19) and infectious diseases (2.08; 1.17-3.44) were increased, whereas the SMR for malignant tumors was decreased (0.76; 0.61-0.94). CONCLUSIONS This nationwide study of patients with NFPA showed an overall excess mortality in women and in patients with a young age at diagnosis. Increased mortality was seen for cerebrovascular and infectious diseases.

Exposure to Wood Dust, Resin Acids, and Volatile Organic Compounds During Production of Wood Pellets

The main aim of this study was to investigate exposure to airborne substances that are potentially harmful to health during the production of wood pellets, including wood dust, monoterpenes, and resin acids, and as an indicator of diesel exhaust nitrogen dioxide. In addition, area measurements were taken to assess background exposure levels of these substances, volatile organic compounds (VOCs), and carbon monoxide. Measurements were taken at four wood pellet production plants from May 2004 to April 2005. Forty-four workers participated in the study, and a total of 68 personal measurements were taken to determine personal exposure to wood dust (inhalable and total dust), resin acids, monoterpenes, and nitrogen dioxide. In addition, 42 measurements of nitrogen dioxide and 71 measurements of total dust, resin acids, monoterpenes, VOCs, and carbon monoxide were taken to quantify their indoor area concentrations. Personal exposure levels to wood dust were high, and a third of the measured levels of inhalable dust exceeded the Swedish occupational exposure limit (OEL) of 2 mg/m 3 . Parallel measurements of inhalable and total dust indicated that the former were, on average, 3.2 times higher than the latter. The data indicate that workers at the plants are exposed to significant amounts of the resin acid 7-oxodehydroabietic acid in the air, an observation that has not been recorded previously at wood processing and handling plants. The study also found evidence of exposure to dehydroabietic acid, and exposure levels for resin acids approached 74% of the British OEL for colophony, set at 50 μg/m 3 . Personal exposure levels to monoterpenes and nitrogen dioxide were low. Area sampling measurements indicated that aldehydes and terpenes were the most abundant VOCs, suggesting that measuring personal exposure to aldehydes might be of interest. Carbon monoxide levels were under the detection limit in all area measurements. High wood dust exposure levels are likely to have implications for worker health; therefore, it is important to reduce exposure to wood dust in this industry.

Medical Yoga for Patients with Stress-Related Symptoms and Diagnoses in Primary Health Care: A Randomized Controlled Trial

An increasing number of patients are suffering from stress-related symptoms and diagnoses. The purpose of this study was to evaluate the medical yoga treatment in patients with stress-related symptoms and diagnoses in primary health care. A randomized controlled study was performed at a primary health care centre in Sweden from March to June, 2011. Patients were randomly allocated to a control group receiving standard care or a yoga group treated with medical yoga for 1 hour, once a week, over a 12-week period in addition to the standard care. A total of 37 men and women, mean age of 53 ± 12 years were included. General stress level (measured using Perceived Stress Scale (PSS)), burnout (Shirom-Melamed Burnout Questionnaire (SMBQ)), anxiety and depression (Hospital Anxiety and Depression Scale (HADS)), insomnia severity (Insomnia Severity Index (ISI)), pain (visual analogue scale (VAS)), and overall health status (Euro Quality of Life VAS (EQ-VAS)) were measured before and after 12 weeks. Patients assigned to the Yoga group showed significantly greater improvements on measures of general stress level (P < 0.000), anxiety (P < 0.019), and overall health status (P < 0.018) compared to controls. Treatment with medical yoga is effective in reducing levels of stress and anxiety in patients with stress-related symptoms in primary health care.

Quartz and Dust Exposure in Swedish Iron Foundries

Exposure to respirable quartz continues to be a major concern in the Swedish iron foundry industry. Recommendations for reducing the European occupational exposure limit (EU-OEL) to 0.05 mg/m 3 and the corresponding ACGIH® threshold limit value (ACGIH-TLV) to 0.025 mg/m 3 prompted this exposure survey. Occupational exposure to respirable dust and respirable quartz were determined in 11 Swedish iron foundries, representing different sizes of industrial operation and different manufacturing techniques. In total, 436 respirable dust and 435 respirable quartz exposure measurements associated with all job titles were carried out and are presented as time-weighted averages. Our sampling strategy enabled us to evaluate the use of respirators in certain jobs, thus determining actual exposure. In addition, measurements using real-time dust monitors were made for high exposure jobs. For respirable quartz, 23% of all the measurements exceeded the EU-OEL, and 56% exceeded the ACGIH-TLV. The overall geometric mean (GM) for the quartz levels was 0.028 mg/m 3 , ranging from 0.003 to 2.1 mg/m 3 . Fettler and furnace and ladle repair operatives were exposed to the highest levels of both respirable dust (GM = 0.69 and 1.2 mg/m 3 ; range 0.076–31 and 0.25–9.3 mg/m 3 and respirable quartz (GM = 0.041 and 0.052 mg/m 3 ; range 0.004–2.1 and 0.0098–0.83 mg/m 3 . Fettlers often used respirators and their actual quartz exposure was lower (range 0.003–0.21 mg/m 3 , but in some cases it still exceeded the Swedish OEL (0.1 mg/m 3 . For furnace and ladle repair operatives, the actual quartz exposure did not exceed the OEL (range 0.003–0.08 mg/m 3 , but most respirators provided insufficient protection, i.e., factors less than 200. In summary, measurements in Swedish iron foundries revealed high exposures to respirable quartz, in particular for fettlers and furnace and ladle repair workers. The suggested EU-OEL and the ACGIH-TLV were exceeded in, respectively, 23% and 56% of all measurements regardless of the type of foundry. Further work on elimination techniques to reduce quartz concentrations, along with control of personal protection equipment, is essential.

Inflammatory markers and exposure to occupational air pollutants

Objectives: To study the possible relationship between inhalation of airborne particles in the work environment and inflammatory markers in blood. Methods: Total dust was sampled in the breathing zone of 73 subjects working with welding, cutting, grinding and in foundries such as iron, aluminium, and concrete. Stationary measurements were used to study different size fractions of particles including respirable dust, particulate matter (PM)10 and PM2.5, the particle number concentration, the number of particles deposited in the alveoli, and total particle surface area concentration. Inflammatory markers such as interleukin-6 (IL-6), C-reactive protein (CRP), fibrinogen, d-dimer, and urate were measured in plasma or serum before the first shift after the summer vacation and after the first, second, and fourth shift. Results: The mean level of total dust in the breathing zone was 0.93 mg/m3. The proxies for mean respirable dust fraction was 0.27 mg/m3, PM10 0.60 mg/m3, and PM2.5 was 0.31 mg/m3. The IL-6 values increased by 50% after the first day, but decreased after shift on the second and fourth day. CRP did not increase after the first shift but increased by 17% after the second shift. Other biomarkers were unaffected. A multiple linear regression analysis of a subgroup of 47 subjects showed a statistically significant positive relationship between particle exposure and post-shift IL-6. Conclusion: This study supports previous investigations observing increases of IL-6 at air concentrations of PM10 or PM2.5 between 0.13 and 0.3 mg/m3 among healthy subjects. This increase of IL-6 may indicate an increased risk of coronary heart disease.

Life Expectancy in Patients with Pituitary Adenoma Receiving Growth Hormone Replacement

OBJECTIVE Hypopituitarism has been associated with increased mortality. The excess mortality may be due to untreated growth hormone (GH) deficiency but also due to various underlying disorders. We therefore analysed mortality in patients with only one underlying disorder, non-functioning pituitary adenoma (NFPA), with and without GH replacement therapy (GHRT). DESIGN AND METHOD Patients with NFPA in the western region of Sweden, 1997-2011, were identified through the National Patient Registry and cross-referenced with several National Health Registries. All patient records were reviewed. Standardised mortality ratios (SMRs) with 95% confidence intervals (CIs) were calculated using the general population as reference. Cox-regression models were performed to identify predictors of mortality. RESULTS A total of 426 NFPA patients with 4599 patient-years were included, of whom 207 had used GHRT and 219 had not received GHRT. Median (range) follow-up in patients with and without GHRT was 12.2 (0-25) and 8.2 (0-27) years, respectively. Other pituitary hormone deficiencies were more frequent in the GHRT group than those in the non-GHRT group. SMR was 0.65 (95% CI, 0.44-0.94; P = 0.018) for the GHRT group and 1.16 (0.94-1.42; P = 0.17) for the non-GHRT group. Direct comparison between the groups showed reduced mortality among those who were GH replaced (P = 0.0063). The SMR for malignant tumours was reduced in the GHRT-group (0.29; 0.08-0.73; P = 0.004) but not in untreated patients. CONCLUSIONS Selection bias explaining some of the results cannot be excluded. However, NFPA patients with GHRT had reduced overall mortality compared with the general population, and death due to malignancy was not increased. This suggests that long-term GHRT is safe in adult patients selected for treatment.

Estimating Trends in Quartz Exposure in Swedish Iron Foundries—Predicting Past and Present Exposures

BACKGROUND Swedish foundries have a long tradition of legally required surveys in the workplace that, from the late 1960s onwards, included measurements of quartz. The availability of exposure data spanning almost 40 years presents a unique opportunity to study trends over that time and to evaluate the validity of exposure models based on data from shorter time spans. The aims of this study were (i) to investigate long-term trends in quartz exposure over time, (ii) using routinely collected quartz exposure measurements to develop a mathematical model that could predict both historical and current exposure patterns, and (iii) to validate this exposure model with up-to-date measurements from a targeted survey of the industry. METHODS Eleven foundries, representative of the Swedish iron foundry industry, were divided into three groups based on the size of the companies, i.e. the number of employees. A database containing 2333 quartz exposure measurements for 11 different job descriptions was used to create three models that covered time periods which reflected different work conditions and production processes: a historical model (1968-1989), a development model (1990-2004), and a validation model (2005-2006). A linear mixed model for repeated measurements was used to investigate trends over time. In all mixed models, time period, company size, and job title were included as fixed (categorical) determinants of exposure. The within- and between-worker variances were considered to be random effects. A linear regression analysis was performed to investigate agreement between the models. The average exposure was estimated for each combination of job title and company size. RESULTS A large reduction in exposure (51%) was seen between 1968 and 1974 and between 1975 and 1979 (28%). In later periods, quartz exposure was reduced by 8% per 5 years at best. In the first period, employees at smaller companies experienced ~50% higher exposure levels than those at large companies, but these differences became much smaller in later years. The furnace and ladle repair job were associated with the highest exposure, with 3.9-8.0 times the average exposure compared to the lowest exposed group. Without adjusting for this autonomous trend over time, predicting early historical exposures using our development model resulted in a statistically significant regression coefficient of 2.42 (R(2) = 0.81), indicating an underestimation of historical exposure levels. Similar patterns were seen for other historical time periods. Comparing our development model with our validation model resulted in a statistically significant regression coefficient of 0.31, indicating an overestimation of current exposure levels. CONCLUSION To investigate long-term trends in quartz exposure over time, overall linear trends can be determined by using mixed model analysis. To create individual exposure measures to predict historical exposures, it is necessary to consider factors such as the time period, type of job, type of company, and company size. The mixed model analysis showed systematic changes in concentration levels, implying that extrapolation of exposure estimates outside the range of years covered by measurements may result in underestimation or overestimation of exposure.