Cross sectional observational study on the societal costs of Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) is one of the most important causes of morbidity and functional decline among the elderly and gives rise to substantial costs for society. There is today limited data on resource utilization and quality of life in AD, in particular in the severe stage of disease. AIMS & METHODS: The objectives of this study were to estimate the relationship between costs, patient and caregiver quality of life, and disease severity. For 233 patients in Sweden and their caregivers cross-sectional data on cognitive function (MMSE), ADL ability, behavioral disturbances, formal and informal resource use and health related quality of life (HRQoL) were collected by questionnaires to caregivers and to the treating physician. Patients were stratified into the disease stages mild, moderate and severe AD based on MMSE-scores. RESULTS: The mean annual total cost in 2007 USD was 23,400 in mild, 56,800 in moderate and 71,400 in severe AD. Special forms of accommodation accounted for the majority of costs. Costs were higher for patients with lower cognitive function, lower ADL ability and more behavioral disturbances, with ADL ability being the most consistent predictor of costs. There were significant differences in HRQoL between the disease stages: health utility scores were 0.64 in mild, 0.39 in moderate and 0.24 in severe AD. CONCLUSIONS: The societal costs of AD are very high, especially for patients with moderate and severe AD. This implies that treatments with the ability to delay progression of the disease into more severe stages have the potential to save large costs for society.

Multidisciplinary examination of patients with illness attributed to dental fillings.

OBJECTIVE AND METHODS: In 1993, a special Amalgam Clinic was established at Huddinge University Hospital. Residents in the Stockholm County area with morbidity attributed to dental fillings ('amalgam disease'), were referred to this clinic. Patients were examined by a dentist (n 428), a physician (n 379), and a psychologist (n 360). Sixty-nine per cent were women and 31% men; the mean patient age was 46 years. RESULTS: Oral symptoms included tender or aching teeth (60%), metallic taste (54%), sore mouth (43%) and dry mouth (43%). Signs of moderate or severe temporomandibular joint dysfunction were found in 81 cases, glossitis in 30 and oral lichen in 26 cases. Common general symptoms included diffuse pain (78%), general weakness (75%), extreme fatigue (68%) and dizziness (68%). Seven per cent of the patients suffered from previously undiagnosed medical conditions (thyroid dysfunction, anaemia, cardiopathy, renal disease, cancer). In 26 subjects, skin patch testing revealed allergy to mercury, gold or palladium. The median concentration of mercury was 10 nmol L-1 in whole blood, 3 nmol L-1 in plasma and 10 nmol L-1 in urine, i.e. normal levels. Earlier mental trauma was common, and in the psychological questionnaire SCL-90, clear tendencies to somatization were found. Only a few cases of severe psychiatric illness were observed. No positive correlation was found between the amount of amalgam and somatic symptoms or psychological effect parameters. CONCLUSIONS: The results do not support the hypothesis that release of mercury from amalgam fillings is the cause of 'amalgam disease', but suggest that there may be various explanations for the patient's complaints.

Acute health effects common during graffiti removal.

OBJECTIVE: The aim of this study was to identify possible health effects caused by different cleaning agents used in graffiti removal. METHODS: In 38 graffiti removers working 8-h shifts in the Stockholm underground system, the exposure to organic solvents was assessed by active air sampling, biological monitoring, and by interviews and a questionnaire. Health effects were registered, by physical examinations, porta7ble spirometers and self-administered questionnaires. The prevalence of symptoms was compared with 49 controls working at the underground depots, and with 177 population controls. RESULTS: The 8-h time-weighted average exposures (TWA) were low, below 20% of the Swedish permissible exposure limit value (PEL) for all solvents. The short-term exposures occasionally exceeded the Swedish short-term exposure limit values (STEL), especially during work in poorly ventilated spaces, e.g. in elevators. The graffiti removers reported significantly higher prevalence of tiredness and upper airway symptoms compared with the depot controls, and significantly more tiredness, headaches and symptoms affecting airways, eyes and skin than the population controls. Among the graffiti removers, some of the symptoms increased during the working day. On a group basis, the lung function registrations showed normal values. However, seven workers displayed a clear reduction of peak expiratory flow (PEF) over the working shift. CONCLUSIONS: Though their average exposure to organic solvents was low, the graffiti removers reported significantly higher prevalence of unspecific symptoms such as fatigue and headache as well as irritative symptoms from the eyes and respiratory tract, compared with the controls. To prevent adverse health effects it is important to inform the workers about the health risks, and to restrict use of the most hazardous chemicals. Furthermore, it is important to develop good working practices and to encourage the use of personal protective equipment.

Air and biological monitoring of solvent exposure during graffiti removal.

OBJECTIVE: The principal aim of the study was to estimate the level of exposure to organic solvents of graffiti removers, and to identify the chemicals used in different cleaning agents. A secondary objective was to inform about the toxicity of various products and to optimise working procedures. METHODS: Exposure to organic solvents was determined by active air sampling and biological monitoring among 38 graffiti removers during an 8-h work shift in the Stockholm underground system. The air samples and biological samples were analysed by gas chromatography. Exposure to organic solvents was also assessed by a questionnaire and interviews. RESULTS: Solvents identified were N-methylpyrrolidone (NMP), dipropylene glycol monomethyl ether (DPGME), propylene glycol monomethyl ether (PGME), diethylene glycol monoethyl ether (DEGEE), toluene, xylene, pseudocumene, hemimellitine, mesitylene, ethylbenzene, limonene, nonane, decane, undecane, hexandecane and gamma-butyrolactone. The 8-h average exposures [time-weighted average (TWA)] were below 20% of the Swedish permissible exposure limit value (PEL) for all solvents identified. In poorly ventilated spaces, e.g. in elevators etc., the short-term exposures exceeded occasionally the Swedish short-term exposure limit values (STEL). The blood and urine concentrations of NMP and its metabolites were low. Glycol ethers and their metabolites (2-methoxypropionic acid (MPA), ethoxy acetic acid (EAA), butoxy acetic acid (BAA), and 2-(2-methoxyethoxy) acetic acid (MEAA)) were found in low concentrations in urine. There were significant correlation between the concentrations of NMP in air and levels of NMP and its metabolites in blood and urine. The use of personal protective equipment, i.e. gloves and respirators, was generally high. CONCLUSIONS: Many different cleaning agents were used. The average exposure to solvents was low, but some working tasks included relatively high short-term exposure. To prevent adverse health effects, it is important to inform workers about the health risks and to restrict the use of the most toxic chemicals. Furthermore, it is important to develop good working procedures and to encourage the use of personal protection equipment.

Mercury inductions in persons with subjective symptoms alleged to dental amalgam fillings.

This study was carried out to determine whether health disturbances alleged to mercury release from dental amalgam fillings, i.e. "amalgam disease", may be caused by an increased sensitivity to mercury (Hg). In the form of a double-blind test, 39 volunteers who themselves suspected "amalgam disease" inhaled small doses of mercury vapour (0.6-10 microg) or pure air in a random sequence. After the induction procedure, the test persons assessed whether they reacted or not, i.e. experienced increased illness or not. The test persons also registered the daily intensity of their various symptoms. Calculated on the whole population, there was no statistically significant difference between the number of reactions after inhalation of mercury vapour compared with after inhalation of air. Two subjects, however, reacted significantly more often to mercury vapour than to air. The results do not support that short-term exposure to low doses of Hg vapour in general promotes clinical illness in subjects who themselves suspect "amalgam disease". The deviating reactions presented by two test persons, however, may support the theory that occasional individuals can be sensitive to very low doses of Hg.

Mercury in biological fluids after amalgam removal.

Dental amalgam is the major source of inorganic mercury (Hg) exposure in the general population. The objective of the present study was to obtain data on changes in Hg levels in blood, plasma, and urine following removal of all amalgam fillings during one dental session in 12 healthy subjects. The mean number of amalgam surfaces was 18 (range, 13 to 34). Frequent blood sampling and 24-hour urine collections were performed up to 115 days after amalgam removal, and in eight subjects additional samples of plasma and urine were collected up to three years after amalgam removal. A transient increase of Hg concentrations in blood and plasma was observed within 48 hours after amalgam removal. In plasma, the peak concentrations significantly exceeded the pre-removal plasma Hg levels by, on average, 32% (1.3 nmol/L; range, 0.1 to 4.2). No increase in the urinary Hg excretion rate was apparent after amalgam removal. An exponential decline of Hg was seen in all media. Sixty days after the amalgam removal, the Hg levels in blood, plasma, and urine had declined to approximately 60% of the pre-removal levels. In seven subjects, who were followed for up to three years, the half-lives of Hg in plasma and urine were calculated. In plasma, a bi-exponential model was applied, and the half-life was estimated at median 88 days (range, 21 to 121). The kinetics of Hg in urine (nmol/24 hrs) fit a mono-exponential model with a median half-life of 46 days (range, 35 to 67). It is concluded that the process of removing amalgam fillings can have a considerable impact on Hg levels in biological fluids. After removal, there was a considerable decline in the Hg levels of blood, plasma, and urine, which slowly approached those of subjects without any history of amalgam fillings.

Exposure to mercury vapor and impact on health in the dental profession in Sweden.

Possible adverse effects of mercury exposure in dentistry have been discussed in several studies. The objective of the present study was to carry out detailed measurements of mercury exposure in the dental profession in Sweden, and to search for adverse health effects from such exposure. We examined 22 dentists and 22 dental nurses, working in teams, at six Swedish dental clinics. Measurements of air mercury, performed with personal, active air samplers, showed a median air Hg of 1.8 micrograms/m3 for the dentists, and 2.1 micrograms/m3 for the dental nurses. Spot measurements with a direct reading instrument displayed temporarily elevated air Hg, especially during the preparation and application of amalgam. The average concentration of mercury in whole blood (B-Hg) was 18 nmol/L, in plasma (P-Hg) 5.1 nmol/L, and in urine (U-Hg) 3.0 nmol/mmol creatinine. Possible effects on the central nervous system (CNS) were registered with three questionnaires: Q16, Eysenck Personality Inventory (EPI), and the Profile of Mood Scales (POMS). In the Q16, the number of symptoms was statistically significantly higher in the dentistry group compared with an age- and gender-matched control group (n = 44). The urinary excretion of albumin and urinary activity of the tubular enzyme N-acetyl-beta-glucose-aminidase (NAG) did not differ between the two groups. The results confirm that exposure to mercury in the dental profession in Sweden is low. The air Hg levels were mainly influenced by the method of amalgam preparation and inserting, and by the method of air evacuation during drilling and polishing.

Experiences from the amalgam unit at Huddinge hospital--somatic and psychosomatic aspects.

The "amalgam unit" at the Huddinge University Hospital in Sweden examined 379 of 1300 patients referred for health problems which the patients related to amalgam tooth fillings. Toxicologic, clinical, odontological, and psychiatric examinations were performed. More than 30% had medical causes for their complaints; 7% had severe diseases which had been unrecognized. The most common symptoms were diffuse pain, general weakness, fatigue, headache, and difficulties in concentrating. Anxiety and depression were the most prevalent psychiatric complaints. The psychological examination revealed a high prevalence of somatization. The treatment was information about mercury and amalgam, appropriate odontological routines without removal of intact amalgam fillings, medical therapy when necessary, and strengthening of the patients' social networks. Ninety percent were satisfied with the treatment. The results indicate that there are various explanations for the complaints of patients fearing "amalgam disease". No cases of mercury intoxication were found.

A case of high mercury exposure from dental amalgam.

This report describes a patient who suffered from several complaints, which by herself were attributed to her amalgam fillings. Analysis of mercury in plasma and urine showed unexpectedly high concentrations, 63 and 223 nmol/l, respectively. Following removal of the amalgam fillings, the urinary excretion of mercury became gradually normalized, and her symptoms declined.

Minor effects of low exposure to inorganic mercury on the human immune system.

The influence of exposure to inorganic mercury on the immune system was examined in 36 workers occupationally exposed to mercury vapor, 14 individuals with skin hypersensitivity to mercury compounds, 21 subjects with health disturbances allegedly caused by dental amalgam fillings ("amalgam disease"), and 39 healthy referents. Concentrations of mercury in blood and urine and some parameters judged to mirror different effects on the immune system were determined. The latter included, white blood cell differential counts, serum immunoglobulins and autoantibodies, and in vitro production of the cytokines interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF alpha). Virtually all of the immunologic parameters were within normal ranges and did not differ significantly between the groups. In the group sensitized to mercury, there was a reduction of the in vitro production of both TNF alpha and IL-1 compared with the reference group's values. No significant correlations were noted between different mercury exposure estimates and the immunologic parameters.

Activity of antioxidative enzymes in erythrocytes and concentration of selenium in plasma related to mercury exposure.

The activity of catalase and glutathione peroxidase (GSH-Px) in erythrocytes and concentration of selenium in plasma and mercury in whole blood, plasma, and urine were analyzed in 36 individuals occupationally exposed to mercury vapor, in 14 individuals with skin hypersensitivity to inorganic mercury, and in 17 individuals with subjective symptoms alleged to result from dental amalgam fillings. The control group consisted of 39 individuals with amalgam fillings, but no occupational exposure to mercury. Selenium in plasma was determined by GFAAS with Zeeman background correction. After exclusion of individuals with reported intake of selenium supplement the median plasma selenium concentration in the group with occupational exposure to mercury was 1.24 mumol/L, in the allergy group 1.22 mumol/L, in the amalgam group 1.25 mumol/L, and in the control group 1.22 mumol/L. The activities of catalase and GSH-Px were similar in all groups. However, in females lower GSH-Px activity was found in the amalgam group compared with females in the control group. GSH-Px activity in smokers was slightly lower than in non-smokers. No correlations were found between concentration of selenium or mercury in plasma and activity of glutathione peroxidase or catalase in erythrocytes.

High exposures to organic solvents among graffiti removers.

The exposure to organic solvents among 12 graffiti removers was studied. Health effects were also assessed by structured interview and a symptom questionnaire. Blood and urine samples were collected at the end of the day of air sampling. The concentrations of dichloromethane, glycol ethers, trimethylbenzenes and N-methyl-2-pyrrolidinone in the breathing zone of each worker were measured during one working day. The 8-h time-weighted average exposure to dichloromethane ranged from 18 to 1200 mg/m3. The Swedish Permissible Exposure Limit value for dichloromethane is 120 mg/m3. The air concentrations of glycol ethers, trimethylbenzenes and N-methyl-2-pyrrolidinone were low or not detectable. No exposure-related deviations in the serum concentrations of creatinine, aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase or hyaluronan or the urine concentrations of alpha 1-microglobulin, beta 2-microglobulin or N-acetyl-beta-glucosaminidase were found. Irritative symptoms of the eyes and upper respiratory tract were more prevalent than in the general population. This study demonstrates that old knowledge about work hazards is not automatically transferred to new professions. Another aspect is that the public is also exposed as the job is performed during daytime in underground stations. At least for short periods, bystanders may be exposed to high concentrations of organic solvent vapours. People with predisposing conditions, e.g. asthmatics, may risk adverse reactions.

Effects of occupational exposure to mercury vapour on the central nervous system.

Possible effects of mercury on the central nervous system (CNS) were examined in a group of chloralkali workers exposed to mercury (n = 89) and compared with a control group (n = 75), by registration of subjective symptoms, personality changes, forearm tremor, and performance on six computerised psychometric tests in the two groups. The groups were similar in age, education, verbal comprehension, and work tasks. In the chloralkali group, median blood mercury concentration (B-Hg) was 55 nmol/l, serum mercury concentration (S-Hg) 45 nmol/l, and urine mercury concentration (U-Hg) 14.3 nmol/mmol creatinine (25.4 micrograms/g creatinine). Corresponding concentrations in the control group were 15 nmol/l, 4 nmol/l, and 1.1 nmol/mmol creatinine (1.9 micrograms/g creatinine) respectively. The number of self reported symptoms, the scores for tiredness and confusion in the profile of mood states (POMS), and the degree of neuroticism in the Eysenck personality inventory (EPI), were significantly higher in the mercury exposed group compared with the controls. Performance on the psychometric tests and tremor frequency spectra did not differ significantly between the two groups. Dose-response calculations showed weak but statistically significant relations between symptom prevalence and current mercury concentrations in both blood and urine. The performance on three of the psychometric tests was negatively correlated with earlier peak exposures. The findings indicate a slight mercury induced effect on the CNS among the chloralkali workers.

Renal and immunological effects of occupational exposure to inorganic mercury.

Seven parameters of renal dysfunction (urinary excretion of albumin, orosomucoid, beta 2-microglobulin, N-acetyl-beta-glucosaminidase (NAG), and copper; serum creatinine concentration, and relative clearance of beta 2-microglobulin) were examined in a group of chloralkali workers exposed to mercury vapour (n = 89) and in an unexposed control group (n = 75). Serum concentrations of immunoglobulins (IgA, IgG, IgM) and auto-antibodies towards glomeruli and other tissues were also determined. The parameters examined were compared between the two groups and related to different exposure parameters. In the chloralkali group median blood mercury concentration (B-Hg) was 55 nmol/l, serum mercury (S-Hg) 45 nmol/l, and urine mercury concentration (U-Hg) 14.3 nmol/mmol creatinine (25.4 micrograms/g creatinine). Corresponding concentrations for the control group were 15 nmol/l, 4 nmol/l, and 1.1 nmol/mmol creatinine (1.9 micrograms/g creatinine) respectively. None of the parameters of renal dysfunction differed significantly between the two groups, but there was a tendency to increased excretion of NAG in the exposed group compared with the controls. Also, a statistically significant relation existed between U-Hg and U-NAG (p less than 0.001). Serum immunoglobulin concentrations did not differ between the groups, and serum titres of autoantibodies (including antiglomerular basement membrane and antilaminin antibodies) were low in both groups. Thus the results gave no evidence of glomerular damage or of a tubular reabsorption defect at the current relatively low exposures. The findings still indicate slight, dose related tubular cell damage in the mercury exposed group. There were no signs of a mercury induced effect on the immune system.

Biological monitoring of environmental and occupational exposure to mercury.

Biological monitoring was used to assess mercury exposure from occupational and environmental sources in a group of chloralkali workers (n = 89) and in a control group (n = 75). In the control group, the median value for blood mercury (B-Hg) was 15 nmol/l, that for serum mercury (S-Hg) was 4 nmol/l and that for urinary mercury (U-Hg) was 1.1 nmol/mmol creatinine. Corresponding levels in the chloralkali group were 55 nmol/l, 45 nmol/l and 14.3 nmol/mmol creatinine, respectively. In the control group, there were statistically significant relationships between fish consumption and both B-Hg and S-Hg values (P less than 0.001), whereas U-Hg correlated best with the individual amalgam burden (P less than 0.01). In the chloralkali group, the mercury levels in blood and urine were significantly related to the type of work (P less than 0.001) but not to the length of employment, to fish consumption or to the quantity of dental amalgam fillings. In both groups there were poor correlations between smoking or alcohol intake and the mercury levels in blood and urine. The results strongly suggest that fish is an important source of methylmercury exposure and that amalgam fillings are probably the most important source of inorganic mercury exposure among occupationally unexposed individuals. In the chloralkali group, mercury exposure from fish and amalgam was overshadowed by occupational exposure to inorganic mercury.

Normal pituitary hormone response to thyrotrophin releasing hormone in dental personnel exposed to mercury.

Basal serum levels of TSH, PRL, T3, T4, cortisol, glucose and calcium were determined in a group of dental personnel (n = 11) exposed to mercury vapour from dental amalgam, and in an occupationally unexposed control group (n = 9). The TSH and PRL responses after injection of 25 micrograms TRH were also analysed. There were no significant group differences in basal hormone levels or in TRH responses. The findings do not indicate a negative influence on the pituitary function at the present low grade, chronic mercury exposure.