Exposure to organic solvents has been suggested to cause or exacerbate renal disease, but methodologic concerns regarding previous studies preclude firm conclusions. We examined the role of organic solvents in a population-based case-control study of early-stage chronic renal failure (CRF). All native Swedish residents aged 18 to 74 yr, living in Sweden between May 1996 and May 1998, formed the source population. Incident cases of CRF in a pre-uremic stage (n = 926) and control subjects (n = 998), randomly selected from the study base, underwent personal interviews that included a detailed occupational history. Expert rating by a certified occupational hygienist was used to assess organic solvent exposure intensity and duration. Relative risks were estimated by odds ratios (OR) in logistic regression models, with adjustment for potentially important covariates. The overall risk for CRF among subjects ever exposed to organic solvents was virtually identical to that among never-exposed (OR, 1.01; 95% confidence interval [CI], 0.81 to 1.25). No dose-response relationships were observed for lifetime cumulative solvent exposure, average dose, or exposure frequency or duration. The absence of association pertained to all subgroups of CRF: glomerulonephritis (OR, 0.96; 95% CI, 0.68 to 1.34), diabetic nephropathy (OR, 1.02; 95% CI, 0.74 to 1.41), renal vascular disease (OR, 1.16; 95% CI, 0.76 to 1.75), and other renal CRF (OR, 0.92; 95% CI, 0.66 to 1.27). The results from a nationwide, population-based study do not support the hypothesis of an adverse effect of organic solvents on CRF development, in general. Detrimental effects from subclasses of solvents or on specific renal diseases cannot be ruled out.
Although many studies have investigated the possible association between analgesic use (acetaminophen and aspirin) and the development of chronic kidney disease (CKD), the effect of analgesics on the progression of established CKD of any cause has not yet been investigated.
In this population-based Swedish cohort study, we investigated the decline over 5-7 years in estimated glomerular filtration rate (eGFR) among 801 patients with incident, advanced CKD (serum creatinine >3.4 mg/dL for men, >2.8 mg/dL for women for the first time) and with different analgesic exposures. Lifetime analgesic use and current regular use were ascertained through in-person interviews at inclusion while data on analgesic use during the follow-up was abstracted from the medical records at the end of the study period. A linear regression slope, based on their eGFR values during the follow-up, provided a summary of within-individual change. In the final multivariate analyses, a linear mixed effects model was implemented to assess the relation of analgesic use and change in eGFR over time.
The progression rate for regular users of acetaminophen was slower than that for non-regular users (regular users progressed 0.93 mL/min/1.73 m(2) per year slower than non-regular users; 95% CI 0.03, 1.8). For regular users of aspirin, the progression rate was significantly slower than that for non-regular users (regular users progressed 0.80 mL/min/1.73 m(2) per year slower than non-regular users; 95% CI 0.1, 1.5). Different levels of lifetime cumulative dose of acetaminophen and aspirin did not significantly affect the progression rate.
We suggest that single substance acetaminophen and aspirin may be safe to use by patients with diagnosed advanced CKD stage 4-5 without an adverse effect on the progression rate of the disease.
PURPOSE: Several studies have found an increased risk of myocardial infarction among depressed patients. Selective serotonin reuptake inhibitors (SSRIs) appear to lack the arrhythmic adverse effects of tricyclic antidepressants, and are thought to inhibit platelet aggregation. We examined whether use of different antidepressant classes is associated with a lower risk of first-time hospitalization for myocardial infarction, as compared with nonuse. METHODS: We identified 8887 cases of first-time hospitalization for myocardial infarction and 88,862 age- and sex-matched population-based controls during 1994-2002, using data from North Jutland County, Denmark. Cases and controls were stratified according to history of cardiovascular disease. All prescriptions for antidepressants before hospitalization for myocardial infarction were identified using a prescription database. Conditional logistic regression was used to estimate odds ratios of myocardial infarction associated with antidepressant use, adjusted for possible confounding factors. RESULTS: In patients with a history of cardiovascular disease, we found indications of a lower risk of myocardial infarction among those who used SSRIs (adjusted odds ratio [OR] = 0.85; 95% confidence interval [CI]: 0.62 to 1.16), nonselective serotonin reuptake inhibitors (adjusted OR = 0.83; 95% CI: 0.50 to 1.38), and other antidepressants (adjusted OR = 0.55; 95% CI: 0.31 to 0.97). There were no such associations among persons without a history of cardiovascular disease. CONCLUSION: Antidepressant use may be associated with a decreased risk of hospitalization for myocardial infarction among persons with a history of cardiovascular disease, although it remains uncertain whether there are differences by class of antidepressant.
Although the collective epidemiologic literature does not support an association between silicone breast implants and any well-defined or atypical connective tissue disease, a recent study raised concern regarding an increased risk for fibromyalgia among women with extracapsular ruptured implants. In this review, we examine the results of 6 epidemiologic studies which have evaluated the occurrence of fibromyalgia among women with breast implants. Two large nationwide follow-up studies of women with breast implants in Sweden and Denmark reported relative risks for fibromyalgia of 1.0 (95% confidence interval [CI] 0.3 to 3.0) and for unspecified rheumatism (including fibromyalgia and myalgia) of 1.2 (95% CI 0.9 to 1.5), respectively. Similarly, both a case-control and a cross-sectional study conducted within rheumatic disease clinics reported no association between silicone breast implants and the subsequent development of fibromyalgia. The single positive finding, that of a greater than 2-fold excess of self-reported fibromyalgia among women with magnetic resonance imaging-diagnosed extra-capsular ruptures in one study, can be explained by selection bias and the use of an inappropriate reference group in the analyses. In the most recent study of indefinite connective tissue disease (including fibromyalgia) by rupture status, no association was found among unselected Danish women with ruptured implants (relative risk 1.0; 95% CI 0.3 to 3.0), and none of the women with extracapsular rupture reported fibromyalgia. Thus, the weight of the epidemiologic evidence is remarkably consistent and reassuring in failing to support an association between breast implants and subsequent fibromyalgia.
The available epidemiologic evidence does not support a carcinogenic effect of silicone breast implants on breast or other cancers. Data on cancer risk other than breast cancer are limited and few studies have assessed cancer risk beyond 10-15 years after breast implantation. We extended follow-up of our earlier cohort study of Danish women with cosmetic breast implants by 7 years, yielding 30 years of follow-up for women with longest implant duration. The study population consisted of women who underwent cosmetic breast implant surgery at private clinics of plastic surgery (n = 1,653) or public hospitals (n = 1,110), and a control group of women who attended private clinics for other plastic surgery (n = 1,736), between 1973-95. Cancer incidence through 2002 was ascertained using the Danish Cancer Registry. Risk evaluation was based on computation of standardized incidence ratios (SIR) and Cox proportional hazards models, adjusting for age, calendar period and reproductive history. We observed 163 cancers among women with breast implants compared to 136.7 expected based on general population rates (SIR = 1.2; 95% confidence interval [CI] = 1.0-1.4), during a mean follow-up period of 14.4 years (range = 0-30 years). Women with breast implants experienced a reduced risk of breast cancer (SIR = 0.7; 95% CI = 0.5-1.0), and an increased risk of non-melanoma skin cancer (SIR = 2.1; 95% CI = 1.5-2.7). Stratification by age at implantation, calendar year at implantation and time since implantation showed no clear trends, however, the statistical precision was limited in these analyses. When excluding non-melanoma skin cancer, the SIR for cancer overall was 1.0 (95% CI = 0.8-1.2). With respect to other site-specific cancers, no significantly increased or decreased SIR were observed. Similar results were found when directly comparing women who had implants at private clinics with women who attended private clinics for other plastic surgery, with rate ratios for cancer overall, breast cancer and non-melanoma skin cancer of 1.1 (95% CI = 0.8-1.6), 0.7 (95% CI = 0.4-1.3) and 1.5 (95% CI = 0.8-2.7), respectively. In conclusion, our study lends further support to the accumulating evidence that silicone breast implants are not carcinogenic. Reasons for the consistently reported deficit of breast cancer among women with breast implants remain unclear, whereas increased exposure to sunlight may explain the excess occurrence of non-melanoma skin cancer. We found no indication of delayed diagnosis of breast cancer due to the presence of breast implants.
To address concerns about the potential carcinogenicity of pacemakers, we launched the first epidemiologic study of cancer incidence among pacemaker recipients. A nationwide cohort of 16,357 pacemaker recipients in Denmark from 1982 through 1996 was identified. The Danish Cancer Registry was used to identify all incident cancers within the cohort, with almost 75,000 person-years of observation. The cohort had a slight excess of cancer overall (SIR = 1.19, 95% confidence interval [95% CI, 1.1-1.2]). This was largely caused by an elevated SIR for multiple myeloma among men (SIR = 1.78,95% CI, 1.1-2.8), which increased to 2.60 (95% CI, 0.9-5.7) 5-9 years after implantation, and to a similarly increased SIR for kidney cancer among women (SIR = 2.05, 95% CI, 1.3-3.0), which increased to 3.39 (95% CI, 1.6-6.2) after a latency period of 5-9 years. An excess of urinary bladder cancer was also seen after 10 years. No excess risk was observed for breast cancer or sarcomas, although the SIRs for sarcomas tended to increase over time, based on small numbers. Our results are largely reassuring but, as pacemakers become more common and are implanted at earlier ages and as survival following implantation improves, the excesses of bladder cancer, multiple myeloma among men, and kidney cancer among women with long-term followup warrant further investigation.
Comment In: J Long Term Eff Med Implants. 2002;12(4):251-312627786
Trichloroethylene is an animal carcinogen with limited evidence of carcinogenicity in humans. Cancer incidence between 1968 and 1997 was evaluated in a cohort of 40,049 blue-collar workers in 347 Danish companies with documented trichloroethylene use. Standardized incidence ratios for total cancer were 1.1 (95% confidence interval (CI): 1.04, 1.12) in men and 1.2 (95% CI: 1.14, 1.33) in women. For non-Hodgkin's lymphoma and renal cell carcinoma, the overall standardized incidence ratios were 1.2 (95% CI: 1.0, 1.5) and 1.2 (95% CI: 0.9, 1.5), respectively; standardized incidence ratios increased with duration of employment, and elevated standardized incidence ratios were limited to workers first employed before 1980 for non-Hodgkin's lymphoma and before 1970 for renal cell carcinoma. The standardized incidence ratio for esophageal adenocarcinoma was 1.8 (95% CI: 1.2, 2.7); the standardized incidence ratio was higher in companies with the highest probability of trichloroethylene exposure. In a subcohort of 14,360 presumably highly exposed workers, the standardized incidence ratios for non-Hodgkin's lymphoma, renal cell carcinoma, and esophageal adenocarcinoma were 1.5 (95% CI: 1.2, 2.0), 1.4 (95% CI: 1.0, 1.8), and 1.7 (95% CI: 0.9, 2.9), respectively. The present results and those of previous studies suggest that occupational exposure to trichloroethylene at past higher levels may be associated with elevated risk for non-Hodgkin's lymphoma. Associations between trichloroethylene exposure and other cancers are less consistent.
The use of paracetamol has been associated with increased risks for urinary tract cancers and decreased risk for ovarian cancer, although results have been inconsistent. We conducted a population-based cohort study using data from the Prescription Database of North Jutland County and the Danish Cancer Registry. Cancer incidence among 39,946 individuals receiving prescriptions for paracetamol was compared with expected incidence based on the North Jutland population who did not receive paracetamol prescriptions, during a 9-year follow-up period. Standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (95% CIs) were calculated for cancers overall and at selected sites. Overall, 2,173 cancers were observed with 1,973 expected, yielding a SIR of 1.10 (95% CI, 1.06-1.15). Significantly elevated SIRs were found for cancers of the esophagus (1.9; 95% CI, 1.3-2.8) and lung (1.6; 95% CI, 1.4-1.7). Nonsignificantly increased SIRs were observed for cancers of the liver (1.5; 95% CI, 0.96-2.2), renal parenchyma (1.3; 95% CI, 0.9-1.7) and renal pelvis/ureter (1.6; 95% CI, 0.96-2.6), whereas the SIR for cancer of the urinary bladder was close to unity (1.1; 95% CI, 0.9-1.4). For ovarian cancer, the SIR was close to expectation (0.9; 95% CI, 0.6-1.2) with no evidence of trends with duration of follow-up or number of prescriptions. A similar risk pattern was observed after exclusion of person-time experience following prescription for aspirin or other nonsteroidal antiinflammatory drugs in the study cohort and reference population. Our results do not support a major role for paracetamol in the development of cancers of the urinary tract, and we found little evidence of a protective effect of paracetamol against ovarian cancer. The elevated risks for cancers of the esophagus, lung and liver are most likely a result of confounding variables, but may warrant further investigation.
Concern has been raised recently regarding the absence of information on the occurrence and severity of local complications after cosmetic breast implantation. The authors evaluated the occurrence of local complications in a large epidemiological retrospective cohort study of women with cosmetic breast implants in Denmark. All women with breast implants were identified from the files of two private clinics of plastic surgery in Denmark. Information on implant characteristics, surgical procedure, as well as short- and long-term complications was obtained through medical record review. Patient characteristics were obtained through a self-administered questionnaire. A total of 754 women (1,572 implants) had at least one cosmetic implantation performed at the study clinics. Average age at implantation was 32 years. Implant types included silicone double lumen with textured surface, 31.2%; silicone single lumen with textured surface, 27.8%; silicone single lumen with smooth surface, 24.5%; silicone double lumen with smooth surface, 0.8%; and other or missing information, 15.7%. Average implant size was 247 ml (range, 110-630 ml). Placement was submuscular for 91.3% of implants, subglandular for 2.6%, and 6.1% had no available information. Overall, 77.8% of implantations were not followed by complications, 17.8% were followed by one complication, 3.6% were followed by two complications, and 0.8% were followed by three or more complications. In 94.6% of implantations, no additional hospitalizations were recorded as a result of complications. Forty-seven of 57 explantations/reimplantations were secondary to postoperative complications. General complications such as hematoma and infection were rare, occurring in 2.3% and 2.0% of implantations respectively. Capsular contracture remains the most common complication, occurring in 11.4% of implantations. In this investigation, among the first epidemiological studies of local complications, the authors found cosmetic breast implant surgery to be associated with a low frequency of normal surgical complications such as infection, hematoma, and wound dehiscence. Most complications were mild and did not lead to additional hospitalization. The complication that led most frequently to the need for additional surgery/hospitalization was capsular contracture. Kjøller K, Hölmich LR, Jacobsen PH, Friis S, Fryzek J, McLaughlin JK, Lipworth L, Henriksen TF, Jørgensen S, Bittmann S, Olsen JH. Epidemiological investigation of local complications after cosmetic breast implant surgery in Denmark.
The aim of this study was to investigate the exposure of Danish workers to trichloroethylene (TCE) and the factors that affected such exposure. Data from Danish health authorities were evaluated for use in an epidemiological study of possible adverse health effects of TCE. The paper files relating to 1,075 air measurements taken between 1947 and 1989 at 150 companies were examined to extract information about calendar year, company, industry, type of measurement, and worker. Multiple regression models were used to analyze the effects of various factors on the concentration of TCE. TCE concentrations decreased over the four decades studied. The geometric mean was 329 mg/m3 for measurements taken 1947-1959, and 260 mg/m3, 53 mg/m3, and 23 mg/m3, respectively, for the three subsequent decades. Regression analyses showed that 1) TCE concentrations decreased on average 4 percent per year before 1964 and 15 percent per year afterward; 2) area and personal measurements gave similar concentrations (for the same calendar period, industry, and duration of measurement); 3) longer-duration measurements were associated with lower TCE concentrations; 4) high TCE concentrations occurred in the iron and metal industry; and, 5) in this industry men were exposed to concentrations two times those of women. Moreover, this study indicated that both the exposure level and the proportion of exposed workers in Danish companies increased with decreasing number of employees. Epidemiological studies of health effects of TCE may benefit from evaluating potential risk within different strata of calendar time, number of company employees, sex, and type of industry.