Long-term health outcomes in patients with Prader-Willi Syndrome: a nationwide cohort study in Denmark.

BACKGROUND: Prader-Willi syndrome (PWS) is a rare congenital disease that affects growth, sexual development, cognitive function and behavior. Individuals exhibit food preoccupation and hyperphagia, which may lead to obesity with premature morbidity and mortality. The aim of this work was to evaluate the risk of venous thromboembolisms (VTEs), myocardial infarction, pulmonary hypertension, sleep apnea, depression, anxiety and all-cause mortality among persons with PWS as compared with an age- and sex-matched general-population cohort. METHODS: All persons diagnosed with PWS (n=155) were identified in the Danish Health Registries; an age- and sex-matched comparison group was selected from the general population of Denmark (n=15 500); diseases of interest were identified through the health registry and cause of death register. Follow-up began on date of birth or first medical record availability through to first occurrence of an outcome of interest; follow-up ceased at emigration from Denmark or end of study. Incidence rates (IRs) were calculated and Cox's proportional hazards models were used to understand the relative risk (RR) of disease. RESULTS: The IRs for VTE among patients with PWS was 144 (60-347) per 100 000 person-years. Risks for VTE events and all-cause mortality were 9.4 times (95% confidence interval (CI): 3.7-23.5) and 11.0 times (95% CI: 5.7-21.1) higher, respectively, for patients with PWS versus the general population. Increased risks were also found individually for deep venous thromboses (DVTs) (RR: 9.1; 95% CI: 3.2-25.2), pulmonary embolisms (RR: 11.0; 95% CI: 1.4-86.9), myocardial infarction (RR: 7.2; 95% CI: 1.7-30.2) and anxiety (RR: 2.8; 95% CI: 1.0-7.5). No cases of pulmonary hypertension, sleep apnea or depressive disorders were identified within this PWS cohort. CONCLUSIONS: Multiple cardiovascular and behavioral illnesses are more likely to occur among patients with PWS than within the general population. These increased risks may provide an impetus for enhanced disease prevention, screening, diagnosis and treatment.

Hospitalisation for venous thromboembolism in cancer patients and the general population: a population-based cohort study in Denmark, 1997-2006.

BACKGROUND: Venous thromboembolism (VTE) frequently complicates cancer. Data on tumour-specific VTE predictors are limited, but may inform strategies to prevent thrombosis. METHODS: We computed incidence rates (IRs) with 95% confidence intervals (CIs) for VTE hospitalisation in a cohort of cancer patients (n=57,591) and in a comparison general-population cohort (n=287,476) in Denmark. The subjects entered the study in 1997-2005, and the follow-up continued through 2006. Using Cox proportional-hazards regression, we estimated relative risks (RRs) for VTE predictors, while adjusting for comorbidity. RESULTS: Throughout the follow-up, VTE IR was higher among the cancer patients (IR=8.0, 95% CI=7.6-8.5) than the general population (IR=4.7, 95% CI=4.3-5.1), particularly in the first year after cancer diagnosis (IR=15.0, 95% CI=13.8-16.2, vs IR=8.6, 95% CI=7.6-9.9). Incidence rates of VTE were highest in patients with pancreas (IR=40.9, 95% CI=29.5-56.7), brain (IR=17.7, 95% CI=11.3-27.8) or liver (IR=20.4, 95% CI=9.2-45.3) tumours, multiple myeloma (IR=22.6, 95% CI=15.4-33.2) and among patients with advanced-stage cancers (IR=27.7, 95% CI=24.0-32.0) or those who received chemotherapy or no/symptomatic treatment. The adjusted RR (aRR) for VTE was highest among patients with pancreas (aRR=16.3, 95% CI=8.1-32.6) or brain cancer (aRR=19.8 95% CI=7.1-55.2), multiple myeloma (aRR=46.1, 95% CI=13.1-162.0) and among patients receiving chemotherapy, either alone (aRR=18.5, 95% CI=11.9-28.7) or in combination treatments (aRR=16.2, 95% CI=12.0-21.7). CONCLUSIONS: Risk of VTE is higher among cancer patients than in the general population. Predictors of VTE include recency of cancer diagnosis, cancer site, stage and the type of cancer-directed treatment.

Use of NSAIDs, smoking and lung cancer risk.

We investigated the risk of lung cancer in relation to non-steroidal anti-inflammatory drugs (NSAIDs) among 573 cases and 857 sex- and age-matched controls for whom we had information on use of NSAIDs, from a prescription database covering all pharmacies in Denmark since 1995, and self-reported NSAID use, smoking habits and other potential confounders. Associations were expressed as odds ratios, assessed by logistic regression in unmatched analyses. After controlling for smoking habits, length of education and concomitant use of acetaminophen, we found a slightly decreased relative risk of 0.86 (95% confidence intervals, 0.65-1.14) for lung cancer associated with any use of NSAIDs. The risk decreased significantly (P=0.02) with increasing numbers of dispensed prescriptions per year during the 1-3 years before the index date with a relative risk of 0.49 (0.28-0.84) among those with four or more prescriptions per year during this period. Our findings suggest that regular use of NSAIDs is associated with a slightly or moderately reduced risk for lung cancer.

Parkinson's disease and other basal ganglia or movement disorders in a large nationwide cohort of Swedish welders.

INTRODUCTION: Although it has been hypothesised that metal welding and flame cutting are associated with an increased risk for Parkinson's disease due to manganese released in the welding fume, few rigorous cohort studies have evaluated this risk. METHODS: The authors examined the relation between employment as a welder and all basal ganglia and movement disorders (ICD-10, G20-26) in Sweden using nationwide and population based registers. All men recorded as welders or flame cutters (n = 49,488) in the 1960 or 1970 Swedish National Census were identified and their rates of specific basal ganglia and movement disorders between 1964 and 2003 were compared with those in an age and geographical area matched general population comparison cohort of gainfully employed men (n = 489,572). RESULTS: The overall rate for basal ganglia and movement disorders combined was similar for the welders and flame cutters compared with the general population (adjusted rate ratio (aRR) = 0.91 (95% CI 0.81 to 1.01). Similarly, the rate ratio for PD was 0.89 (95% CI 0.79 to 0.99). Adjusted rate ratios for other individual basal ganglia and movement disorders were also not significantly increased or decreased. Further analyses of Parkinson's disease by attained age, time period of follow up, geographical area of residency, and educational level revealed no significant differences between the welders and the general population. Rates for Parkinson's disease among welders in shipyards, where exposures to welding fumes are higher, were also similar to the general population (aRR = 0.95; 95% CI 0.70 to 1.28). CONCLUSION: This nationwide record linkage study offers no support for a relation between welding and Parkinson's disease or any other specific basal ganglia and movement disorders.

A cohort study of antihypertensive treatments and risk of renal cell cancer.

We studied 335,682 county residents, of whom 113,298 had been prescribed antihypertensive treatment (AHT), in the period 1989-2002 in North Jutland County, Denmark to examine the relation between different AHTs and the risk of renal cell carcinoma (RCC). An internal comparison was performed among the different classes of AHT users with users of beta blockers as the reference, in order to address potential confounding and bias. The average follow-up was 10 years (range 0-13). Use of any AHT was associated with RCC (relative rate (RR)=1.6, 95% confidence interval (CI) 1.3-1.9) compared with nonusers in the general population. Specific classes of AHTs were nonsignificantly associated with RCC, but compared with users of beta blockers, the numbers observed were close to expectation. Analyses by duration of follow-up and number of prescriptions revealed no clear trends for any antihypertensive agent and after 5-years of follow-up, the RRs for all classes of AHT decreased. The elevated RRs for RCC among users of AHTs compared with the general population are unlikely to be causal, but rather reflect confounding due to failure to control for pre-existing hypertension, and protopathic bias, due to the presence of hypertension as an early sign of kidney disease.

Energy, macronutrients and laryngeal cancer risk.

BACKGROUND: A role for diet in laryngeal carcinogenesis has been suggested, but only a few studies have examined the potential relationship with a wide variety of macronutrients. PATIENTS AND METHODS: A case-control study was conducted between 1992 and 2000 in Italy and Switzerland, including 527 incident cases of laryngeal cancer, and 1297 controls hospitalized for acute, non-neoplastic conditions. The subjects' usual diet was investigated through a validated food frequency questionnaire, including 78 foods and beverages. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional multiple logistic regression models. RESULTS: Cases reported higher energy intake than controls. The continuous OR for 100 kcal/day was 1.16 (95% CI 1.12-1.21) for alcohol energy, and 1.02 (95% CI 1.01-1.04) for non-alcohol energy. A significantly increased risk of laryngeal cancer was observed for animal protein (continuous OR = 1.21, 95% CI 1.03-1.41), polyunsaturated fats other than linoleic and linolenic fatty acids (OR = 1.43, 95% CI 1.19-1.70), and cholesterol intake (OR = 1.43, 95% CI 1.19-1.71). Laryngeal cancer risk was slightly reduced with increasing vegetable protein (OR = 0.75, 95% CI 0.62-0.91), sugar (OR = 0.84, 95% CI 0.71-1.00) and monounsaturated fatty acid intake (OR = 0.83, 95% CI 0.70-0.99). CONCLUSIONS: Laryngeal cancer cases have a higher energy intake than control subjects, and report a higher intake of animal protein and cholesterol.

Acetaminophen, aspirin, and chronic renal failure.

BACKGROUND: Several epidemiologic studies have demonstrated an association between heavy consumption of nonnarcotic analgesics and the occurrence of chronic renal failure, but it is unclear which is the cause and which is the effect METHODS: In a nationwide, population-based, case-control study of early-stage chronic renal failure in Sweden, face-to-face interviews were conducted with 926 patients with newly diagnosed renal failure and 998 control subjects, of whom 918 and 980, respectively, had complete data. We used logistic-regression models to estimate the relative risks of disease-specific types of chronic renal failure associated with the use of various analgesics RESULTS: Aspirin and acetaminophen were used regularly by 37 percent and 25 percent, respectively, of the patients with renal failure and by 19 percent and 12 percent, respectively, of the controls. Regular use of either drug in the absence of the other was associated with an increase by a factor of 2.5 in the risk of chronic renal failure from any cause. The relative risks rose with increasing cumulative lifetime doses, rose more consistently with acetaminophen use than with aspirin use, and were increased for most disease-specific types of chronic renal failure. When we disregarded the recent use of analgesics, which could have occurred in response to antecedents of renal disease, the associations were only slightly attenuated CONCLUSIONS: Our results are consistent with the existence of exacerbating effects of acetaminophen and aspirin on chronic renal failure. However, we cannot rule out the possibility of bias due to the triggering of analgesic consumption by predisposing conditions.

Capsular contracture after cosmetic breast implant surgery in Denmark.

The authors investigated the association between the occurrence of capsular contracture and implant and patient characteristics. All women with breast implants from 1977 to 1997 were identified from the files of two private plastic surgery clinics in Denmark. Information on implant and patient characteristics, surgical procedure, and complications was obtained through medical records and self-administered questionnaires. Of 754 women (1,572 implants), average age at implantation was 32 years. Implant types were silicone double lumen, textured, 31.2%; silicone single lumen, textured, 27.8%; silicone single lumen, smooth, 24.5%; silicone double lumen, smooth, 0.8%; and other or missing, 15.7%. Placement was submuscular for more than 90% of implants. Capsular contracture occurred in 7.9% of implanted breasts, on an average of 621 days postoperatively, with 51.6% being bilateral. Overall, 66.1% of capsular contractures were recorded within the first 12 months postoperatively, and 79.0% were recorded within 24 months. Double-lumen implants were associated with a significantly (p < 0.01) reduced occurrence of capsular contracture. In summary, capsular contracture typically occurs within the first 2 years of implantation. Host factors may be important because more than half the capsular contractures in the current study were bilateral. Occurrence of capsular contracture did not appear to be associated with implant surface or placement, occurrence of local complications, or patient characteristics, although these findings should be interpreted cautiously.

Nationwide study of cancer risk among hip replacement patients in Sweden.

BACKGROUND: Orthopedic implants and their fixatives contain materials with carcinogenic potential. Whether these implants are linked to subsequent cancer development remains unknown, mainly because large-scale, long-term follow-up data are scarce. METHODS: We conducted a nationwide cohort study in Sweden to examine cancer incidence among 116,727 patients who underwent hip replacement surgery during the period from 1965 through 1994. Through record linkage to the Swedish Cancer Register, we identified all incident cancers through 1995 in this population (693,954 person-years of observation). For each cancer type, the observed number of cases was divided by that expected in the general Swedish population to produce standardized incidence ratios (SIRs). RESULTS: Relative to the general population, the cohort had no overall cancer excess (SIR = 1.01; 95% confidence interval [CI] = 0.99 to 1.03). However, we observed elevated SIRs for prostate cancer (SIR = 1.16; 95% CI = 1.11 to 1.22) and melanoma (SIR = 1.15; 95% CI = 1.01 to 1.30) and a reduction in stomach cancer risk (SIR = 0.83; 95% CI = 0.75 to 0.92). Long-term follow-up (>or=15 years) revealed an excess of multiple myeloma (SIR = 1.86; 95% CI = 1.01 to 3.11) and a statistically nonsignificant increase in bladder cancer (SIR = 1.42; 95% CI = 0.98 to 1.99). There was no material increase in risk for bone or connective tissue cancer for either men or women in any follow-up period. CONCLUSIONS: In this, the largest study to date, hip implant patients had similar rates of most types of cancer to those in the general population. Although the excesses of melanoma, multiple myeloma, and prostate and bladder cancers may be due to chance, confounding, or detection bias and should be interpreted cautiously, they warrant further investigation because of the ever-increasing use of hip implants at younger ages.

Prevalence of silicone breast implant rupture among Danish women.

The durability of silicone gel-filled breast implants is of concern, but there are few epidemiological studies on this issue. To date, most of the relevant findings are derived from studies of explantation, which suffer from bias by including women with symptoms or concerns about their implants. As part of a long-term magnetic resonance imaging study of the incidence of rupture, this study involved 271 women with 533 cosmetic breast implants who were randomly selected from among women who underwent cosmetic breast implantation from 1973 through 1997 at one public and three private plastic-surgery clinics in Denmark. The prevalence of rupture was determined from the first magnetic resonance screening. The images were evaluated by four independent readers, using a standardized, validated form. The outcomes under study were rupture, possible rupture, and intact implant. Ruptures were categorized as intracapsular or extracapsular. Overall, 26 percent of implants in 36 percent of the women examined were found to be ruptured, and an additional 6 percent were possibly ruptured. Of the ruptured implants, 22 percent were extracapsular. In multiple regression analyses, age of implant was significantly associated with rupture among second- and third-generation implants, with a 12-fold increased prevalence odds ratio for rupture of implants that were between 16 and 20 years of age, compared with implants between 3 and 5 years of age. Surgitek implants (Medical Engineering Corporation, Racine, Wis.) had a significantly increased prevalence odds ratio of 2.6 for rupture, compared with the reference implants. No significant association was found with the position (subglandular or submuscular) or the type of implant (single- or double-lumen). Extracapsular ruptures were significantly associated with a history of closed capsulotomy (p = 0.001). In the future, the authors plan to examine the women in their cohort with a second magnetic resonance imaging scan to establish the incidence of rupture, a parameter unknown to date in the literature, and to further characterize those factors associated with the actual risk of rupture.

Cancer mortality in relation to environmental chromium exposure.

From the 1950s to the 1980s, hexavalent chromium compounds were used as additives at certain water-cooling towers at three southern California gas compressor facilities. Claims of potential residential chromium exposure prompted the examination of age-adjusted mortality rates during 1989 to 1998 for lung cancer, all cancer, and all deaths for neighborhoods near versus distant from the plants. Differences in the rates between areas tended to be small and not statistically significant. The only significant difference was a lower, rather than higher, rate of total cancer among women in the potentially exposed areas. Study limitations preclude a definitive assessment of risk, but similar to previous investigations of cancer in relation to environmental chromium exposure in other locations, this study found no evidence of a cancer hazard among residents living near these California gas compressor facilities.

Comparison of surrogate with self-respondents regarding medical history and prior medication use.

BACKGROUND: The self-report of medical history and medication use is a common feature of epidemiological research. METHODS: In a unique re-interview study, we evaluated the concordance of medical conditions and past medication use reported in two similar interviews 5 years apart. RESULTS: In 196 re-interviews with the subjects themselves, and in 107 with next-of-kin of subjects who died after the first interview, agreement was good or excellent (kappa > or =0.40) for 90% (9/10) of the conditions asked about in the personal medical history for both next-of-kin and self-respondents. Agreement was excellent (kappa >0.75) for two conditions, high blood pressure and hysterectomy, among self-respondents. Self- and surrogate respondents also showed similar reproducibility for prescription medications, but next-of-kin respondents tended to have poor agreement (kappa <0.40) for over-the-counter (OTC) medications such as antacids, antihistamines, and analgesics. Next-of-kin also less reliably reported a family history of cancer. When analyses were stratified by type of surrogate respondent, concordance between the two interviews was generally higher for spouses than for other surrogate respondents. CONCLUSIONS: This research demonstrates that personal medical history and prescription medication use may be as reliably reported by next-of-kin as self-respondents, but suggests that additional information may be needed to validate measures of OTC medication use and family history of cancer for next-of-kin respondents, possibly through the review of hospital records.

Familial risk of pancreatic cancer.

BACKGROUND: Pancreatic cancer is the fifth leading cause of cancer-related mortality in the United STATES: Although smoking and age are known risk factors for pancreatic cancer, several case reports and case-control studies have suggested that there is also a familial risk. We evaluated whether a family history of pancreatic cancer increases the risk of pancreatic cancer in first-degree relatives and whether smoking and younger age at cancer diagnosis further increase this risk. METHODS: We conducted in-person interviews with 247 patients ("case probands") with pancreatic cancer and 420 population-based control probands to collect risk factor data and pancreatic cancer family history for 1816 first-degree relatives of the case probands and 3157 first-degree relatives of the control probands. We analyzed the data by unconditional logistic regression models, with adjustment for correlated data by use of generalized estimating equations. All statistical tests were two-sided. RESULTS: A positive family history of pancreatic cancer (i.e., being related to a case proband) or ever-smoking cigarettes approximately doubled the risk of pancreatic cancer (relative risk [RR] = 2.49; 95% confidence interval [CI] = 1.32 to 4.69; RR = 2.04; 95% CI = 1.09 to 3.83, respectively). The RR increased to 8.23 (95% CI = 2.18 to 31.07) for relatives who ever smoked and were related to a case proband who was diagnosed before age 60 years. CONCLUSION: Routine questioning of patients about a family history of pancreatic cancer, the age of onset of this cancer in their relatives, and the patient's smoking status may identify individuals at high risk of pancreatic cancer. Future research exploring the genetic and environmental interactions associated with the risk of pancreatic cancer is critically important.

Risks of fracture of Björk-Shiley 60 degree convexo-concave prosthetic heart valves: long-term cohort follow up in the UK, Netherlands and USA.

BACKGROUND AND AIM OF THE STUDY: Approximately 82,000 Björk-Shiley convexo-concave (BSCC) 60 degree prosthetic heart valves were implanted in patients worldwide between 1979 and 1986. Outlet strut fractures (OSF) of some of the valves were first reported shortly after their introduction. Here, the determinants of OSF are examined, and the between-country variation and long-term risk are assessed. METHODS: Cohorts of patients in the UK, Netherlands and USA with 15,770 BSCC 60 degree heart valves were followed up to 18 years for the occurrence of OSF. RESULTS: Crude rates of OSF were highest in the UK (0.18% per year), intermediate in the Netherlands (0.13%), and lowest in the USA (0.06%), although risk factor adjustment reduced the inter-country differences. Furthermore, in the UK and Netherlands, OSF rates (particularly for mitral valves) declined with time since implantation, and between-country differences were considerably diminished 10 or more years post implantation. The risk of OSF decreased steadily with advancing patient age. Fracture rates were lower among women than men, and also varied significantly with valve size and position and OSF status of other valves in the same shoporder. CONCLUSION: This long-term follow up of BSCC 60 degree heart valve patients indicates that risk factors for valve fracture are generally similar in the UK, Netherlands and USA. It also identifies a strong association between fracture risk and age, newly reveals gender-related differences, and shows that the risk of valve fracture persisted, albeit at a reduced rate, into the 1990s.

Offspring health risk after cosmetic breast implantation in Sweden.

Case reports have suggested that children born to women with silicone breast implants may have an excess risk of rheumatic disease and/or esophageal disorders. In Sweden, the authors conducted a retrospective cohort study of 5,874 children born to women with cosmetic breast implants and 13,274 children born to women who had breast reduction surgery. Using national registers, they computed hospitalization rates for rheumatic and esophageal disorders, incidence rates for cancer, and prevalence rates for congenital malformations and perinatal death. Relative to children of women who had breast reduction surgery, children born to women who had cosmetic breast implants were not at excess risk of rheumatic disease (relative risk [RR] = 1.1; 95% confidence interval [95% CI], 0.2-5.3), esophageal disorders (RR = 1.0; 95% CI, 0.7-1.6), cancer (RR = 0.3; 95% CI, 0.0-2.5), congenital malformations in total (RR = 1.0; 95% CI, 0.6-1.5), or specifically involving the digestive organs (RR = 0.5; 95% CI, 0.2-1.3) or perinatal death (RR = 0.9; 95% CI, 0.5-1.8). The rates of these health outcomes among children born after a mother's implant surgery were also not significantly higher than among children born before a mother's implant surgery. This study provides no evidence that certain hypothesized health outcomes are more likely among the children of women with cosmetic breast implants.

Connective tissue disease and other rheumatic conditions following cosmetic breast implantation in Denmark.

OBJECTIVE: To examine the occurrence of connective tissue diseases (CTDs) as well as ill-defined and other rheumatic conditions among Danish women with cosmetic silicone breast implants. PATIENTS AND METHODS: A total of 2761 women with breast implants and 8807 control subjects were identified from plastic surgery private clinics and from public hospital plastic surgery departments. Women operated on at plastic surgery private clinics were identified through the files of each clinic, while women operated on at public hospitals were identified using the nationwide Danish National Registry of Patients. The control group consisted of women who underwent cosmetic surgery other than breast implantation or who only had a consultation. All women were followed up from January 1, 1977, through December 31, 1996, through the Danish National Registry of Patients for the occurrence of CTD as well as ill-defined and other rheumatic conditions. For the study period January 1, 1977, through December 31, 1994, the Danish National Registry of Patients contains information on hospitalization only, whereas data on outpatient visits are included from 1995 on, thus improving the sensitivity of the data. The implant and control groups were compared with the Danish population rates for CTD and ill-defined and other rheumatic conditions, and a direct comparison between the implant and control groups was also performed. RESULTS: When compared with rates from the general population, no excess of definite CTD was observed in the implant cohorts. For ill-defined and other rheumatic conditions, statistically significant excesses of unspecified rheumatism were observed in both the implant and control cohorts when compared with national rates. A direct comparison between the implant and control cohorts found no material differences between the groups. CONCLUSIONS: The findings of this study support previous investigations and independent review panel conclusions that an association between silicone breast implants and definite CTDs is unlikely. The observation of an excess of unspecified rheumatism among women with implants and among control women suggests that women undergoing cosmetic plastic surgery have hospitalization rates for this condition in excess of those from the general population.

Self-reported symptoms among women after cosmetic breast implant and breast reduction surgery.

A retrospective cohort study was performed in Sweden to evaluate the possibility that an individual symptom or constellation of illness symptoms related to silicone occurs in women after breast implant surgery. A random sample (n = 2500) of all women in the Swedish national implant registry who underwent breast augmentation surgery with alloplastic breast implants during the years 1965 through 1993 was compared with a sample (n = 3500) of women who underwent breast reduction surgery during the same period, frequency matched to the implant patients for age and calendar year at the time of surgery. In total, 65 percent of the breast implant patients (n = 1546) and 72 percent of the breast reduction patients (n = 2496) completed a self-administered questionnaire covering 28 rheumatologic and other symptoms and lifestyle and demographic factors. Practically all of the 28 symptoms inquired about were reported more often by women in the breast implant cohort, with 16 (57 percent) significantly more common in breast implant recipients. In contrast, few significant differences or consistent patterns were observed in the length of time since the implant and in the type (silicone or saline) or volume of the implant. Although women with breast implants report a multitude of symptoms more often than women who have breast reduction surgery, the lack of specificity and absence of dose-response relationships suggest that the excess of reported symptoms is not causally related to cosmetic implants.

Local complications and subsequent symptom reporting among women with cosmetic breast implants.

Epidemiologic studies have found no association between breast implants and cancer or well-defined connective tissue diseases. However, women with cosmetic breast implants continue to report specific as well as nonspecific physical and psychological symptoms after receiving their implants. In an attempt to determine whether local complications of implantation may contribute to this excess of symptom reporting, the authors studied a large cohort of women in Sweden with cosmetic breast implants (n = 1280) and a comparison cohort of women who had cosmetic breast reduction surgery (n = 2211). Both groups of women had operations between 1969 and 1996. Medical record reviews of local complications revealed that approximately 31 percent of the women with cosmetic breast implants had an implant change, implant leakage, or a capsulotomy. Capsulotomies occurred more often in women who were age 35 or older at the time of the operation, had ever smoked, and had implants with a smooth surface. On self-administered questionnaires, symptoms were reported more often by the women who had implants regardless of whether they had local complications. Twenty of the 28 symptoms occurred more frequently among women with local complications and breast implants, compared with the women in the breast reduction comparison group or the women with breast implants but no local complications. This study suggests that local complications, particularly capsular contractures as indicated by capsulotomy, may be an important factor to consider when studying symptom reporting among women with breast implants.