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The U.S. Food and Drug Administration (FDA) guidelines S7B mandate the measurement of inhibition of the human ether-a-go-go-related (hERG) ion channel by new drug candidates as it has been found that drug inhibition of the hERG channel can be associated with cardiac action potential (AP) prolongation and lethal cardiac arrhythmias. However, hERG is only one of multiple ion channels involved in forming the cardiac AP and therefore direct measurement of the cardiac AP has the potential to detect the effects of the candidate drug on multiple ion channels potentially affected. Stem cell-derived cardiomyocytes (SC-CM) or induced pluripotent stem cells (iPS-CM) have many of the phenotypic properties of authentic cardiomyocytes e.g. realistic ventricular action potentials. In this work we show how the QPatch can trigger action potentials using rapid switching from voltage to current clamp during recordings on the iPS-CM. We demonstrate that the current clamp recordings made on this automated patch clamp device are comparable to results obtained on standard manual patch clamp rigs. The integrated low volume glass flow channels of the QPatch minimize the consumption of iPS-CM cells - a valuable and often limiting "consumable". Parallel recordings from up to 48 iPS-CM were made on the QPatch HT with full analysis of action potential parameters including action potential duration and upstroke velocity. We measured assay success rates, the stability of action potentials and pharmacological profiles of reference compounds. Current clamp measurements of these cardiomyocytes offer important information to the understanding of the complex pharmacological effect of compounds on ion channels involved in the AP. Our data presented here clearly demonstrate how automated patch clamp on QPatch can augment the throughput of current clamp to meet new demands in drug discovery.

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.

Until recently, expectant management of localised prostate cancer was the routine strategy in Denmark.

Objective: Most published series on tracheal cancer reflect single institution experiences. We used the nationwide Danish Cancer Registry to report on characteristics and treatment of tracheal cancers in Denmark. Methods: One hundred and nine cases of primary tracheal cancers were extracted from the registry in the period 1978‐1995. The clinical data, histological distribution and treatment modalities were analyzed. The cancers were staged in four groups (stage I‐IV) according to size, location and spread. Results: Seventeen cases were diagnosed at autopsy. Ninety-two cases were diagnosed in vivo and 84% of these within 3 months after the first consultation. Sixty-three percent of the cancers were squamous cell carcinomas and only 7% were adenoid cystic carcinomas. The disease was at stage I in 21%, stage II in 23%, stage III in 6% and stage IV in 50%. The majority of the patients received radiotherapy as single treatment. Only nine patients were offered surgery (six were resected and three were found inoperable). The overall survival rates for cases diagnosed in vivo were 1-year 32%, 2-year 20% and 5-year 13%. For the resected patients the 5- and 15-year survival rates were 50%. Conclusions: Tracheal cancers were rare and adenoid cystic carcinomas not as frequent as generally believed. Surgery was rarely offered. A resectability rate of only 10% is not adequately explained by selection bias and indicates a nihilistic attitude based on ignorance about surgical treatment of tracheal cancers. A more dedicated and aggressive approach with centralized workup and radical treatment is strongly recommended. q 2001 Elsevier Science B.V. All rights reserved.

Purpose: We studied the need for hospital care of patients 74 years old or younger with clinically localized prostate cancer managed by deferred endocrine therapy. Materials and Methods: Our series included all cases of newly diagnosed, clinically localized prostate cancer reported to the Danish Cancer Registry from 1977 to 1992. Information on the number of hospitalizations and operations performed from 1977 to 1994 was obtained from the Danish Hospital Discharge Registry. Results: Our study included 4,790 men 37 to 74 years old with clinically localized prostate cancer. During the year of diagnosis and once a year of the following 9 years patients were hospitalized an average of 2.2 and 1 times and remained hospitalized an average of 22 and 10 days, and prostate cancer accounted for approximately 80% and 67% of hospitalizations the year of diagnosis and once a year subsequently. Nearly 90% of patients underwent transurethral prostatic resection within the year of diagnosis and in 30% repeat resection was necessary. A third of the patients underwent orchiectomy during the study period. Median time from the diagnosis to orchiectomy was 23 months. The estimated probability of surviving 5 and 10 years without orchiectomy was 39% and 17%, respectively. Conclusions: Patients diagnosed with clinically localized prostate cancer managed expectantly had a substantial need for hospital care in the years after the diagnosis. When evaluating outcome and quality of life after treatment of localized prostate cancer, the cost and impact of associated morbidity must be considered as well as patient survival.

We studied the outcome in patients with early and probably organ confined prostate cancer who were considered candidates for curative therapy and treated expectantly.The study included 2,570 patients with newly diagnosed prostate cancer reported to the Danish Cancer Registry from 1943 to 1986 and surviving for 10 years or longer. Mortality and causes of death were analyzed and stratified by stage, age and time of diagnosis. Excess mortality was calculated from life expectancy tables for the general population.An overall excess mortality (standard mortality ratio 1.58, 95% confidence interval [95% CI] 1.51 to 1.65) was found. Young age and advanced clinical stage at diagnosis entailed a higher risk of death from prostate cancer. Overall 42.7 and 19.1% of the patients who died had prostate cancer as the direct or contributing cause of death, respectively. Of the annual deaths 13% were attributable to prostate cancer. In 1,326 patients 55 to 64 and 65 to 74 years old with clinically localized prostate cancer at diagnosis the excess mortality was still significant (standard mortality ratio 1.72, 95% CI 1.54 to 1.93 and 1.50, 95% CI 1.39 to 1.62, respectively). Prostate cancer was the primary or contributing cause of death in 42.9% of the younger group and 21.5% of the older group. In these patients 15% of the annual deaths were related to prostate cancer.Patients with clinically localized prostate cancer for 10 years or longer, who were likely candidates for curative therapy when diagnosed, had significant excess mortality when treated expectantly.

To compare the morbidity in patients with newly diagnosed clinically localized prostate cancer managed conservatively with the morbidity in a randomly selected age-matched background population with no history of prostate cancer. Patients younger than 75 y at diagnosis with newly diagnosed clinically localized prostate cancer reported to the Danish Cancer Registry in the period 1977–1992. Morbidity in patients and age-matched controls was extracted from The Danish Hospital Discharge Registry. Admissions were stratified by discharge diagnosis. Overall 4744 patients were hospitalized for 251,695 days within the first 10 y following diagnosis compared with 74,563 days in 4774 age-matched controls. The patients were admitted 6.7 (6.4–7.1) times more often than controls in the year following diagnosis, and 2.7 (2.6–2.8) times more often in the following 9 y. Excess morbidity declined over time. When prostate cancer-related admissions were excluded, the relative risk of admission was reduced to 1.35 (1.3–1.4) and 0.86 (0.83–0.89), respectively. The estimated costs associated with deferred therapy in patients with clinically localized prostate cancer exceeded the estimated cost in age-matched controls by approximately US$88 million, equivalent to an average extra cost per patient of approximately US$18,500. Patients with clinically localized prostate cancer managed conservatively had a significantly higher morbidity than age-matched controls due to admissions associated with prostate cancer. In future comparisons of treatment strategies, morbidity following treatment and impact on quality of life have to be included when evaluating the outcome.

Objective: To investigate the risk of neurologic disease among women with silicone breast implants. Background: Since 1992, several case series reported an association between silicone breast implants and neurologic diseases. Methods: Between 1977 and 1992, 1,135 women received cosmetic silicone breast implants, and 7,071 women had breast reduction surgery, as identified by the Danish National Register of Patients (NRP). NRP files provided information on numbers and types of subsequent neurologic disorders at hospital discharge, which were compared with expected numbers, calculated on the basis of national hospital discharge rates. Results: In the two study cohorts, hospital discharge rates for neurologic diseases were raised by some 60% to 70% compared with Danish women in general. Among women with silicone breast implants, 13 subsequently developed a neurologic disorder compared with 7.7 expected; whereas in the comparison group, 63 observed versus 39.1 expected disorders were recorded. These results indicate that relative to the comparison cohort, women with implants had no excessive levels of definite neurologic disease. Furthermore, medical record reviews revealed that the majority of women with implants discharged with a neurologic diagnosis had either symptoms before implant surgery or neurologic symptoms secondary to degenerative diseases. Conclusions: Our findings do not support the hypothesis of silicone-induced neurologic disease. The reasons for the elevated rates of neurologic disease in both the exposed and comparison cohorts remain unclear, but may reflect selection processes associated with these women seeking medical care more often than the general population.

We have evaluated the reproducibility and relative validity of a semiquantitative food frequency questionnaire (FFQ) used in a prospective study of risk factors for cervical neoplasia. The questionnaire is a modified version of one developed and evaluated in a middle-aged Danish population. In the present study, 122 women from the general population of Copenhagen, aged 20–29 years, completed the FFQ twice at a 1-year interval, and provided three 4-day dietary records during the intervening year. The mean nutrient intakes calculated from the first and second questionnaire were similar and, for most nutrients, close to those obtained from the dietary records. The Pearson correlation coefficients between the mean nutrient intakes from the two questionnaires ranged from 0.53 (95% CI, 0.39–0.65) for vitamin E to 0.76 (95% CI, 0.67–0.83) for vitamin B12 (median, 0.67 [95% CI, 0.56–0.76]). In comparisons between the second FFQ and the dietary records, the correlations ranged from 0.24 (95% CI, 0.07–0.40) for vitamin D to 0.63 (95% CI, 0.51–0.73) for sucrose (median, 0.42 [95% CI, 0.26–0.56]). The correlations between FFQ and dietary records were generally higher after adjustment for energy intake (median, 0.53 [95% CI, 0.39–0.65]) and within-person variability (median, 0.64 [95% CI, 0.52–0.73]). On average, 71% of the women were classified in the same (± 1) quintile in the second FFQ and the dietary records. An average of 3.8% of the women were grossly misclassified into the highest and lowest quintiles by the dietary records. The relative validity of the FFQ in this population was similar to that reported earlier. It is concluded that the FFQ is reproducible and provides a useful scale for categorizing individuals according to their intake of energy and nutrients.

In this paper, we demonstrate recordings of the ion channel activity across the cell membrane in a biological cell by employing the so-called patch clamping technique on an injection-molded polymer microfluidic device. The findings will allow direct recordings of ion channel activity to be made using the cheapest materials and production platform to date and with the potential for very high throughput. The employment of cornered apertures for cell capture allowed the fabrication of devices without through holes and via a scheme comprising master origination by dry etching in a silicon substrate, electroplating in nickel and injection molding of the final part. The most critical device parameters were identified as the length of the patching capillary and the very low surface roughness on the inside of the capillary. The cross-sectional shape of the orifice was found to be less critical, as both rectangular and semicircular profiles seemed to have almost the same ability to form tight seals with cells with negligible leak currents. The devices were functionally tested using human embryonic kidney cells expressing voltage-gated sodium channels (Nav1.7) and benchmarked against a commercial state-of-the-art system for automated ion channel recordings. These experiments considered current–voltage (IV) relationships for activation and inactivation of the Nav1.7 channels and their sensitivity to a local anesthetic, lidocaine. Both IVs and lidocaine dose–response curves obtained from the injection-molded polymer device were in good agreement with data obtained from the commercial system.

Background and objectives Until recently, syphilis was considered a major cause of penis cancer. The possible role of syphilis was discarded without much debate with the detection of certain of human papillomaviruses centrally involved in the etiology of penis cancer. Goals To reevaluate the association between syphilis and penis cancer by using truly population-based cancer and syphilis data and to generate a more sound basis for judging the possible role of syphilis in the etiology of penis cancer. Study design Patients with epidermoid cancer of the penis, totalling 1,523, were diagnosed and reported to the Danish Cancer Registry from 1943 to 1990. Through linkage with the Danish Syphilis Registry, the impact of prior syphilis infection was evaluated in a case-control design using patients with colon cancer or stomach cancer as controls. Results Depending on the criteria used to assess prior syphilis status, 3% to 5% of patients with penis cancer had had syphilis before the cancer diagnosis. The corresponding proportions were 2% to 4% among patients with colon cancer and 2% to 5% among patients with stomach cancer. Logistic regression showed that patients with penis cancer did not have a syphilis history significantly more often than control cancer patients. Conclusion Syphilis should be removed from the list of possible causes of penis cancer.

Abstract 3689 Introduction: An increased risk of alk-negative T- cell anaplastic large cell lymphoma (T-ALCL) in women with silicone breast implants has recently been suggested. Several small series and case-reports have been published, but, so far, only one analytical epidemiological population-based study has specifically addressed this hypothesis (de Jong et al, JAMA, 2008). Methods: We identified a nationwide cohort of Danish women, who underwent breast implant surgery for any reason (cosmetic or reconstruction) at public hospitals or in private clinics. Data including civil registry number and date of surgery were obtained from the Danish National Hospital Register (1977–2009) and from The Danish Registry for Plastic Surgery of the Breast (1999–2009) and eight private clinics of plastic surgery (1973–1995). The civil registry number, assigned to all Danish citizens by the Central Population Registry (CPR), encodes gender and date of birth, and secures valid linkage to population-based registries in Denmark. Identification of lymphoma cases was performed by combined linkages to the Danish Cancer Registry and the Danish Lymphoma Group (LYFO). This combined strategy was applied in order to maximize catchment of incident lymphoma cases (capture-recapture analysis). Results: We identified a cohort of 18,356 women, who underwent breast implant surgery between 1973–2009. The vast majority of breast implants were silicone gel-filled implants. Among study-subjects, 11,380 underwent surgery for strictly cosmetic reasons, while 6,976 received breast implants as part of a breast reconstruction secondary to breast cancer. The number of non-Hodgkin lymphoma (NHL) and T-ALCL cases expected in the general female population of Denmark was 350/year and 10/year in the study period. The total person-years for the study-cohort (162699,5 years)were multiplied by the estimated incidence rates for T-ALCL in the breast (3/100.000.000 person-years)to ascertain the expected number (0,005) of ALCL in the breast among cohort members. The total number of NHL cases observed was 60. There were no cases of ALCL in the study-cohort and none had an implant-near localization. Conclusion: This is a comprehensive epidemiologic study addressing the specific issue of the possible association between T-ALCL and breast implants. Our large nationwide cohort study does not support a major association between T-ALCL lymphomas and breast implants either implanted for cosmetic reasons in otherwise healthy recipients or for reconstructive purposes in women previously treated for breast cancer. Due to the rarity of this condition, additional population-based analyses are needed to further evaluate potential biological procedure-related or implant-specific associations. An extended analysis of pooled data from different Nordic countries is ongoing. Disclosures: No relevant conflicts of interest to declare.

Urban and rural cancer incidence in Denmark in 1943–1987 was analysed. A consistent urban excess was found for all sites combined for individuals of each sex, irrespective of age at diagnosis. The capital:rural incidence ratio was 1.42 for men and 1.25 for women, and these ratios were not affected to any great extent using another definition of urban areas. Urban:rural ratios were highest for cancers of the respiratory, urinary and upper digestive tracts. The differences cannot be explained by tobacco and alcohol consumption alone. Other risk factors linked to urbanisation may contribute importantly to the “urban factor”, and analytical studies of data at an individual level are required to establish their relative importance. Our findings contradict the generally accepted view that there is no urban-rural difference in cancer incidence in the relatively small, homogeneous population of Denmark.

To clarify the role of previous lung diseases (PLDs) (chronic bronchitis, emphysema, pneumonia, tuberculosis, asbestosis and silicosis) in the development of lung cancer we conducted a pooled analysis in the International Lung Cancer Consortium (ILCCO). Data from 16 studies (9 population based case-control, 4 hospital based case-control, 2 mixed case-control and 1 cohort - 10 from North America, 5 from Europe and 1 from Asia) were pooled, including 24044 cases and 81256 controls. Study-specific effect estimates were derived using logistic regression models for case-control studies and Cox proportional hazards models for cohort studies adjusted for age, sex, education and pack-years of smoking. Effect estimates were then pooled using random effects models where summary effects for each of the PLDs were evaluated separately. Stratified analyses were conducted based on smoking status, histology and study design or control source. Heterogeneity was evaluated using the Cochrane Q statistic and Galbraith plots, and publication bias was evaluated using funnel plots as well as the Begg test. A previous history of emphysema conferred a relative risk (RR) of 2.17, 95% confidence interval (CI): 1.67-2.82 (from 15 studies, p-het Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4826.

Transient receptor potential (TRP) channels are non-selective cationic channels that are widely distributed in mammalian tissues. Their specific physiological functions are largely unknown. Proposed functions include responses to pain, temperature, touch, osmolarity, pheromones, and taste. But due to the lack of specific blockers and the full understanding of their mechanisms of activation studies of TRP channels have been difficult and unexpectedly slow.The emergence of automated patch clamp (APC) systems has increased the number of new targets available for ion channel drug development and has augmented throughput.In order to facilitate tests of large compounds libraries on e.g. TRP targets, we have recently developed two multi-hole APC systems: QPatch HTX and QPatch 16X. The multi-hole technology allows the simultaneous recording of 10 cells in parallel per recording site thereby increasing the signal to noise ratio and the success rate.In this study, we have validated several TRP channels for their activation by their appropriate agonist e.g. Menthol, Capsaicin and temperature. We have found that using the QPatch in multi-hole mode significantly increased the volume of electrophysiology data that can be generated. Our results demonstrate that the QPatch multi-hole systems are capable of generating high quality data from a wide range of the channels belonging to the TRP family of receptors.We believe that the combination of high throughput and high quality data in a single system has more than a “transient potential” to advance the understanding of the complex mechanisms of action exhibited by difficult targets such as the TRP channels.

The introduction of high throughput planar automated electrophysiology systems has brought the potential of ion channels as targets for pharmacological modulation to the forefront. Sophion Biosciences QPatch systems are fully automated electrophysiology platforms generating high resistance seals with resultant ion channel biophysical and pharmacological properties similar to conventional patch clamp recordings. In this study, using a CHO cell line stably expressing the TRPM2 channel, the performance of the QPatch HTX, which records from a population of 10 cells per recording site, was evaluated against the QPatch HT which records from a single cell per recording site.TRPM2 can be challenging to measure, particularly when determining inhibitor potencies, due to poor recording stability characterised by current rundown. A compound set was screened against TRPM2 on the QPatch HT and HTX to assess their relative performances. There was a good correlation between the IC50 values generated on the two systems (r2 = 0.91). The current rundown on the QPatch HTX was considerably reduced compared to the QPatch HT (19.5 ± 1.5% and 37.5 ± 3.0% respectively, mean ± SEM, n = 4 experiments, 767 cells profiled). This resulted in an increase in the number of successful recordings obtained from 51.6 ± 7.1% for HT to 83.1 ± 4.5% for HTX (Mean ± SEM, n = 4 experiments, 912 cells profiled) for a 5 point IC50 assay and from 67.2 ± 8.9% for HT to 98.6 ± 1.4% for HTX (Mean ± SEM, n = 3-4 experiments, 480 cells profiled) for a single concentration assay.The QPatch HT has made a significant impact on the volume of high quality electrophysiology data that can be generated. This preliminary study suggests that the QPatch HTX system can further enhance throughput, particularly with channels where current stability is problematic.

Background Clinical reports have raised concern about local complications following breast implantation used in reconstructive or cosmetic surgery, but there is a shortage of epidemiological studies in this area. Objective To assess in a prospective epidemiological manner the occurrence of short-term local complications in a nationwide implantation registry. Design, Setting, and Participants The Danish Registry for Plastic Surgery of the Breast prospectively collects preoperative, perioperative, and postoperative information on Danish women undergoing breast augmentation. Through the registry, we collected data on short-term local complications among 574 women who underwent postmastectomy reconstruction with breast implants from June 1, 1999, through July 24, 2003. Main Outcome Measures Complication incidence rates. Results Thirty-one percent of the women who underwent initial implantation developed at least 1 adverse event. Forty-nine percent of the adverse events occurred within 3 months after implantation and 67% within 6 months. Surgical intervention was required after initial implantation among 21% of women, most frequently because of capsular contracture, asymmetry, or displacement of the implant. Thirty-six percent of women who underwent subsequent implantation experienced at least 1 adverse event, and 21% underwent surgical intervention to treat definitive complications or to optimize cosmetic result. Conclusions Women who undergo postmastectomy breast implantation frequently experience short-term local complications. Surgical or medical intervention is commonly required during the reconstructive course, but reconstruction failure (loss of implant) is rare. However, when weighing benefits and risks associated with reconstruction, the patient should consider that breast reconstruction is a process involving planned and unplanned supplementary surgical correction to achieve the desired result.

Dear Sir, We did not report results for melanoma in our study because of limited statistical precision. Prompted by the letter by Kirsner et al., we calculated relative risk estimates for melanoma among the 12,251 statin users ( 2 prescriptions) in North Jutland County, Denmark, during the study period 1989–2002. The adjusted rate ratio for malignant melanoma among statin users was 0.78 (95% CI 5 0.42– 1.47) compared with nonusers (based on 10 cases among statin users), which is consistent with a 20% lower incidence of melanoma among statin users. As with other sitespecific cancers in our study, stratification by duration of follow-up or number of prescriptions revealed no clear trends. The small number of users of nonstatin lipid-lowering drugs (n 5 1,257) did not allow analysis of melanoma risk. Larger and longer-term studies are needed to evaluate the potential chemopreventive effects of statins against melanoma and other cancers. Yours sincerely, Soren FRIIS

Background Epidemiologic studies indicate that women with cosmetic breast implants have a significantly increased risk of suicide. Our objectives were to examine mortality among Danish women who underwent cosmetic breast implant surgery and to evaluate the baseline prevalence of psychopathological disorders as measured by admission to a psychiatric hospital among women seeking cosmetic surgery. Methods Cohort study of 2761 women who underwent cosmetic breast implant surgery at private clinics of plastic surgery or public hospitals, 7071 women who underwent breast reduction surgery at public hospitals, and 1736 women who attended private clinics for cosmetic surgery other than breast implantation, between 1973 and 1995. Causes of death through 1999 were identified through the Danish Mortality Files. Information on admission to psychiatric hospitals prior to cosmetic surgery was obtained from the Danish Psychiatric Central Register. Results Women with cosmetic breast implants had significantly elevated standardized mortality ratios (SMRs) for death overall (SMR, 1.4; 95% confidence interval [CI], 1.1-1.7), nonmalignant lung disease (3.4; 95% CI, 1.4-6.9), and suicide (SMR, 3.1; 95% CI, 1.7-5.2). Women who underwent breast reduction exhibited low SMRs for death overall (0.7; 95% CI, 0.7-0.8) and several specific causes, including breast cancer (0.4; 95% CI, 0.2-0.6), whereas death from suicide was moderately above expectation (SMR, 1.6; 95% CI, 1.0-2.5). The prevalence of psychiatric admission prior to cosmetic surgery was higher among women who underwent cosmetic breast implant surgery (8.0%; 95% CI, 7.0%-9.0%) than among women who underwent breast reduction (4.7%; 95% CI, 4.2%-5.2%) or other cosmetic procedures (5.5%; 95% CI, 4.5%-6.7%). When compared with all control groups, women with cosmetic implants had an odds ratio for prior psychiatric admission of 1.7 (95% CI, 1.4-2.0). Conclusions Danish women with cosmetic breast implants experienced higher overall mortality compared with women in the general population owing in part to a 3-fold increase in suicide. Women with breast reduction had a low total and cause-specific mortality but a moderate excess risk of suicide. For the first time, to our knowledge, we found evidence of an increased prevalence of mental illness as measured by admission to a psychiatric hospital prior to implant surgery among women receiving cosmetic breast implants. Studies are needed to clarify the underlying reasons for the consistently reported 2- to 3-fold excess of suicide among women with cosmetic breast implants.

Objective To use a new immunologic assay to evaluate antipolymer antibody (APA) levels among women with silicone breast implants (SBIs). Methods Women (n = 186) were identified through Danish population-based registers and categorized into six groups defined by prior breast surgery (silicone breast implantation/breast reduction/no breast surgery) and by the presence or absence of a prior hospital diagnosis of soft-tissue rheumatism (muscular rheumatism, ICD-8 codes 717.90 and 717.99). The women underwent blood tests, including an APA test, a clinical examination, and an interview focusing on rheumatic complaints. Blood samples were tested blindly. The severity of rheumatic symptoms/signs was scored from 1 (none) to 5 (severe) based on the clinical examination and interview. Results Women with SBIs did not have higher levels of APA than women without SBIs. The majority of women with SBIs had mild rheumatic complaints, and the severity of their symptoms was not related to APA levels. Among women who had previously been hospitalized because of soft-tissue rheumatism, there were more fibromyalgia cases, and their symptoms were more severe compared with those women without prior soft-tissue rheumatism; however, APA levels were not higher among these women. There was a significant difference in APA measurements resulting from between-kit variation (p less 0.01). Conclusions Our data did not demonstrate higher APA levels among women with SBIs compared with controls. The large variation observed between the individual plates in the APA test should be evaluated in future studies.

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.

Objectives. To review the trends in prostate cancer (PC) incidence and mortality rates in Denmark during a 50-year period. Methods. A population-based register study was performed of all new cases of PC recorded in the Danish Cancer Registry from 1943 to 1992. Results. The age-standardized incidence rate for PC increased from 11.5/100,000 in 1943 to 1947 to 30.9/100,000 in 1988 to 1992. Age-specific incidence rates increased in all age groups over 50 years of age. Mortality rates increased from 13.5/100,000 in 1953 to 1957 to 17.8/100,000 in 1988 to 1992. No major changes in the distribution of age, stage at the time of diagnosis, or in diagnostic procedures were found, indicating that the observed change in incidence rates was not caused by attempted early detection or changes in diagnostic strategy. Conclusions. Our data suggest that the increased PC incidence observed during the period of cancer registration in Denmark represents a true increase in the number of patients with clinical PC.

During a randomized clinical trial concerning alternative methods of intrapartum fetal surveillance (electronic fetal monitoring (EFM) and auscultation (AUS)) an investigatory interview was carried out. Out of 655 expecting mothers the antepartum preference of EFM was 39.5%, of AUS 32.3% and 28.1% were undecided (UD). EFM was especially preferred by obstetrical high-risk patients. Reasons for preference of AUS were a natural childbirth, a non-technological milieu, and the lack of supposed discomfort from sensors and belts. The pregnant women found as major advantages of EFM continuous observation and the possibility of quick intervention. Postpartum 385 patients were again interviewed. The majority upheld the original preference if that method was used. If the non-preferred method had been applied many would stick to the primary preference although a tendency to prefer the experienced method was seen. The patients who antepartum preferred AUS, but had EFM, became more positive toward the method, and a significantly increased number were positively influenced by the EFM signal/trace and found the method promoting their partner's involvement in labor. Enforced immobility, however, was a major disadvantage as well as the technical milieu. If EFM is to be accepted by a majority of women giving birth it is necessary to increase the pregnant women's knowledge of the method and to take milieu factors into consideration in order to reduce the intrinsic depersonalization of EFM.

Background Use of statins has been suggested to protect against renal cell carcinoma (RCC); however, studies have typically been underpowered, and the results are conflicting. Objective To determine whether the use of statins is associated with a reduced risk of RCC using high-quality registry data. Design, setting, and participants We conducted a nationwide case–control study based on all histologically verified cases of RCC in Denmark between 2002 and 2012 ( n =4606) matched 1:10 to cancer-free controls. Data on drug use, comorbidity, and educational level were obtained from Danish nationwide prescription, patient, and demographic registries. Outcome measurements and statistical analysis Odds ratios (ORs) and 95% confidence intervals (CIs) for RCC associated with long-term use (≥5 yr) of statins were estimated using conditional logistic regression, adjusting for potential confounders. Results and limitations The adjusted OR for RCC associated with long-term use of statins was 1.06 (95% CI, 0.91–1.23). Analyses stratified by duration of statin use, type of statin, and patient characteristics all yielded ORs close to unity, except for a slightly increased OR for RCC associated with long-term statin use among women (OR: 1.25; 95% CI, 0.96–1.62). The main limitation of our study was lack of information on lifestyle factors, notably obesity, which may have biased the risk estimates upward. Conclusions Our study does not support an important chemopreventive effect of long-term statin use against RCC. The marginally increased and statistically insignificant risk estimates can readily be interpreted as a null finding, considering the lack of control for obesity and other lifestyle risk factors. Patient summary Previous studies have shown that the use of cholesterol-lowering drugs (statins) may protect against renal cancer. In a large study including all Danish renal cancers during an 11-yr period, we found no evidence of such an effect.

Eva Bjerre Ostenfeld,1,2 Trine Frøslev,1 Søren Friis,3 Per Gandrup,2 Mogens Rørbæk Madsen,4 Mette Søgaard1,51Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Surgery A, Aarhus University Hospital, Aalborg, Denmark; 3Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark; 4Department of Surgery A, Herning Regional Hospital, Herning, Denmark; 5Department of Clinical Microbiology, Aarhus University Hospital, Aalborg, DenmarkObjective: To explore the completeness of tumor, node, metastasis (TNM) staging for colon and rectal cancer in the Danish Cancer Registry.Material and methods: From the Danish Cancer Registry, we retrieved data on TNM stage, year of diagnosis, sex, and age for 15,976 and 8292 patients, respectively, with first diagnoses of colon or rectal cancer during the 2004–2009 period. From the Danish National Patient Register, we retrieved data on comorbidity (computed as Charlson Comorbidity Index scores). We calculated the completeness of TNM staging overall, by each stage component, and according to a stage algorithm allowing some missing stage components. Analyses were stratified by sex, age, year of diagnosis, and Charlson Comorbidity Index score.Results: For colon and rectal cancer, overall TNM completeness was 67.8% (95% confidence interval [CI]: 67.0%–68.5%) and 68.1% (95% CI: 67.0%–69.1%), respectively. For both cancers, completeness decreased with increasing age and level of comorbidity, whereas differences between the sexes were minor. Over the study period, TNM completeness for colon cancer decreased from 71.3% (95% CI: 69.5%–73.0%) to 64.8% (95% CI: 63.0%–66.6%), whereas the completeness for rectal cancer remained stable over time. When using the stage algorithm, the completeness rose markedly, to 81.1% for colon cancer and 79.0% for rectal cancer.Conclusion: One-third of colon and rectal cancer cases in the Danish Cancer Registry had missing TNM stage information, which varied with age and level of comorbidity. Cancer cases with unknown staging warrant serious consideration of the methodological implications in future epidemiological studies monitoring cancer incidence and outcomes.Keywords: colorectal neoplasm, neoplasm staging, TNM, registries, epidemiology, cancer

The Study on Directors’ Duties and Sustainable Corporate Governance (hereinafter ‘The Study’) was published on 30 July 2020 and is accompanied by a Commission Inception Impact Assessment and a consultation deadline of 8 October 2020. The Assessment adds very little to the Study and this response is consequently made to the Study by a group of Nordic company law scholars.Resume of Findings.The Study displays a lack of understanding of the nature of legal discourse and presents a biased, unrepresentative and highly politically motivated survey of literature and empirics.The Study misrepresents fundamental concepts of company law and fails to understand how corporate governance works.The Study exaggerates the problem of climate change and neglects the many other, equally serious, problems facing both company directors and EU legislators in their obligations to their respective constituencies.The policy pursued by the Study contravenes both fundamental concepts of ownership rights inherent in European law and the basic policies that underlie the founding treaties of the European Union and its assumptions are equally incompatible with EU secondary legislation on company law and capital markets.The Study underestimates the many existing measures adopted by EU legislators and their potential to serve as alternatives to its own far-reaching measures in a way that fundamentally would void the principle of subsidiarity and deprive Member States of control with their own economies.The regulatory options recommended by the Study would seriously harm European business and prevent it from continuing to contribute to the sustainable growth and prosperity that the Union needs to fulfil its overall policies.On this basis, we find that the Study cannot serve as the basis for contemplating the proposed regulatory initiatives and that any discussion must proceed on a better informed foundation brought about by a free and unbiased discourse.

BACKGROUND AND PURPOSE: To evaluate the association between the use of azathioprine and risk of cancer in patients with non-thymoma myasthenia gravis (MG) in a nationwide setting. METHODS: Case-control study based on population-based registries. Cases were patients with MG with a first time diagnosis of cancer (except non-melanoma skin cancer) registered during 2000-2009, and controls were patients with MG with no history of cancer. Prior use of azathioprine in cases and controls was assessed through prescription records (1995-2009). We used unconditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for cancer associated with a high cumulative dose [≥ 1000 defined daily doses (DDD)] or long-term use (≥ 5 years) of azathioprine, compared with never use of the drug and adjusted for potential confounders. RESULTS: We identified 89 cases and 873 controls. The prevalence of ever use of azathioprine was similar among cases (39.3%) and controls (39.4%). We observed a slightly elevated OR for cancer overall associated with long-term use of azathioprine (1.22; 95% CI: 0.62-2.40, P = 0.56). The highest ORs were observed for use of 2000 DDD or more of azathioprine; however, these risk estimates were based on small numbers. CONCLUSIONS: Use of azathioprine in patients with non-thymoma MG may be associated with a slightly increased risk of cancer overall. Larger studies are necessary to address the risk of site-specific cancers.

Udgivelsesdato: 2010-Mar-1 ABSTRACT: INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAIDs) prevent the growth of mammary tumours in animal models. Two population-based case-control studies suggest a reduced risk of breast cancer associated with selective cyclooxygenase-2 (sCox-2) inhibitor use, but data regarding the association between breast cancer occurrence and use of non-selective NSAIDs are conflicting. METHODS: We conducted a population-based case-control study using Danish healthcare databases to examine if use of NSAIDs, including sCox-2 inhibitors, was associated with a reduced risk of breast cancer. We included 8,195 incident breast cancer cases diagnosed in 1991 through 2006 and 81,950 population controls. RESULTS: Overall, we found no reduced breast cancer risk in ever users (>2 prescriptions) of sCox-2 inhibitors (odds ratio (OR) = 1.08, 95% confidence interval (95% CI) = 0.99, 1.18), aspirin (OR = 0.98, 95% CI = 0.90-1.07), or non-selective NSAIDs OR = 1.04, (95% CI = 0.98, 1.10)). Recent use (>2 prescriptions within two years of index date) of sCox-2 inhibitors, aspirin, or non-selective NSAIDs was likewise not associated with breast cancer risk (Ors = 1.06 (95% CI = 0.96, 1.18), 0.96 (95% CI = 0.87, 1.06) and 0.99 (95% CI = 0.85, 1.16), respectively). Risk estimates by duration (

We present the successful integration of an electroosmotic flow pump and a patch-clamp orifice in the same package. When experiments are performed the electroosmotic pump is used both to position e.g. a single HEK293 cell on a micron-sized orifice and later to rupture the cell membrane, to bring the cell in the whole-cell configuration. In this configuration we are able to perform high quality electrophysiological ion-channel measurements. In the experiments we have used a sieve geometry for the pump. This design is a particularly promising candidate for such an integration scheme. The sieve pumps have relatively low volumetric flow rats, but are able to supply relatively high stall pressures (>200 mbar), which make the sieve pumps well suited to work on a load with high flow resistance e.g. a patch-clamp orifice. In the following we present a characterisation of such electroosmotic sieve pumps. For our system we were able to determine the zeta-potential of the glass/electrolyte interface of to be well above 10 mV. Furthermore we also present ion-channel measurements performed on this integrated platform.