| 1. |
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| 2. |
- Agreus, L., et al.
(författare)
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Significant over- and misuse of PPIs
- 2021
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Ingår i: Lakartidningen. - 1652-7518. ; 118
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Tidskriftsartikel (refereegranskat)abstract
- PPIs (Proton-pump inhibitors) offers the best treatment for acid related diseases. The predominant indications for PPI prescription are: GERD eradication of H. pylori-infection in combination with antibiotics H. pylori-negative peptic ulcer healing of and prophylaxis against NSAID/COXIB--induced gastroduodenal lesions acid hypersecretory states such as Zollinger-Ellisons syndrome. The market for PPIs continues to expand in most countries. A significant over- and misuse of PPIs prevails in hospital care as well as in general practice. The predominant reasons for and mechanisms behind the over- and misuse of PPIs are well recognised. The most important consequences of this overprescription of PPIs are increasing medical costs and risk for long-term adverse side effects. Continued education and dedicated information are key factors to guide physicians, medical personnel and patients to adopt to generally accepted principles for and balanced use of PPIs.
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| 3. |
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| 6. |
- Johannesson, M., et al.
(författare)
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The cost of screening for hypercholesterolaemia- results from a clinical trial in Swedish primary health care
- 1993
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Ingår i: Scandinavian journal of clinical and laboratory investigation. - : Informa UK Ltd. - 1502-7686 .- 0036-5513. ; 53:7, s. 725-732
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Tidskriftsartikel (refereegranskat)abstract
- A convenience sample of the population was screened for inclusion in a study of the effectiveness of a lipid lowering programme. Included in the study were adults 30-59 years of age with a S-Cholesterol of 6.50 7.79 mmol 1_1 at randomization, plus two previous values ≥ 6.50 mmol 1_1 at screening and selection, with at least two other cardiovascular risk factors. In total 447 persons were screened and 37 were randomized into the lipid lowering programme. The mean cost per randomized person was estimated at about SEK 7500 (Swedish Crowns). An analysis of different inclusion criteria for treatment was also carried out. The cost of finding a patient to treat in the clinical trial was estimated to be more than three times as high with a total cholesterol cut-off point of 7.80 mmol 1−1 compared with a cut-off point of 5.20mmol 1−1.
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| 7. |
- Polley, Mei-Yin C, et al.
(författare)
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An international study to increase concordance in Ki67 scoring.
- 2015
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Ingår i: Modern Pathology. - : Elsevier BV. - 1530-0285 .- 0893-3952. ; 28:6, s. 778-786
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Tidskriftsartikel (refereegranskat)abstract
- Although an important biomarker in breast cancer, Ki67 lacks scoring standardization, which has limited its clinical use. Our previous study found variability when laboratories used their own scoring methods on centrally stained tissue microarray slides. In this current study, 16 laboratories from eight countries calibrated to a specific Ki67 scoring method and then scored 50 centrally MIB-1 stained tissue microarray cases. Simple instructions prescribed scoring pattern and staining thresholds for determination of the percentage of stained tumor cells. To calibrate, laboratories scored 18 'training' and 'test' web-based images. Software tracked object selection and scoring. Success for the calibration was prespecified as Root Mean Square Error of scores compared with reference <0.6 and Maximum Absolute Deviation from reference <1.0 (log2-transformed data). Prespecified success criteria for tissue microarray scoring required intraclass correlation significantly >0.70 but aiming for observed intraclass correlation ≥0.90. Laboratory performance showed non-significant but promising trends of improvement through the calibration exercise (mean Root Mean Square Error decreased from 0.6 to 0.4, Maximum Absolute Deviation from 1.6 to 0.9; paired t-test: P=0.07 for Root Mean Square Error, 0.06 for Maximum Absolute Deviation). For tissue microarray scoring, the intraclass correlation estimate was 0.94 (95% credible interval: 0.90-0.97), markedly and significantly >0.70, the prespecified minimum target for success. Some discrepancies persisted, including around clinically relevant cutoffs. After calibrating to a common scoring method via a web-based tool, laboratories can achieve high inter-laboratory reproducibility in Ki67 scoring on centrally stained tissue microarray slides. Although these data are potentially encouraging, suggesting that it may be possible to standardize scoring of Ki67 among pathology laboratories, clinically important discrepancies persist. Before this biomarker could be recommended for clinical use, future research will need to extend this approach to biopsies and whole sections, account for staining variability, and link to outcomes.Modern Pathology advance online publication, 20 February 2015; doi:10.1038/modpathol.2015.38.
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| 8. |
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| 9. |
- Agreus, L, et al.
(författare)
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The cost of gastro-oesophageal reflux disease, dyspepsia and peptic ulcer disease in Sweden
- 2002
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Ingår i: PharmacoEconomics (Auckland). - 1170-7690 .- 1179-2027. ; 20:5, s. 347-355
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: Dyspepsia, peptic ulcer disease (PUD) and gastro-oesophageal reflux disease (GORD) involve a substantial cost to Swedish society. There is a lack of up-to-date nationwide cost estimates after 1985. This study was conducted to present a comprehensive and updated cost analysis and study the change over time of the national cost of these disorders. Design and setting: Primarily, data from National Swedish databases and secondly, data from databases from the County of Uppsala for 1997 were used for the calculations and estimations. Perspective: Swedish societal perspective. Results: The total cost to Swedish society of dyspepsia, PUD and GORD in 1997 was $US424 million, or $US63 per adult. Direct costs totalled $US258 million (61%) while indirect costs totalled $US166 million (39%). The highest proportions of costs were due to drugs and sick leave, these being 37 and 34%, respectively. Conclusions: The cost of dyspepsia and GORD is substantial for patients, health providers and society. Since 1985, drug costs have increased substantially while the cost of sick leave has decreased.
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| 10. |
- Agudo, Antonio, et al.
(författare)
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Impact of Cigarette Smoking on Cancer Risk in the European Prospective Investigation into Cancer and Nutrition Study
- 2012
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 30:36, s. 4550-4557
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Our aim was to assess the impact of cigarette smoking on the risk of the tumors classified by the International Agency for Research on Cancer as causally associated with smoking, referred to as tobacco-related cancers (TRC). Methods The study population included 441,211 participants (133,018 men and 308,193 women) from the European Prospective Investigation Into Cancer and Nutrition. We investigated 14,563 participants who developed a TRC during an average follow-up of 11 years. The impact of smoking cigarettes on cancer risk was assessed by the population attributable fraction (AF(p)), calculated using the adjusted hazard ratios and 95% CI for current and former smokers, plus either the prevalence of smoking among cancer cases or estimates from surveys in representative samples of the population in each country. Results The proportion of all TRC attributable to cigarette smoking was 34.9% (95% CI, 32.5 to 37.4) using the smoking prevalence among cases and 36.2% (95% CI, 33.7 to 38.6) using the smoking prevalence from the population. The AF(p) were above 80% for cancers of the lung and larynx, between 20% and 50% for most respiratory and digestive cancers and tumors from the lower urinary tract, and below 20% for the remaining TRC. Conclusion Using data on cancer incidence for 2008 and our AF(p) estimates, about 270,000 new cancer diagnoses per year can be considered attributable to cigarette smoking in the eight European countries with available data for both men and women (Italy, Spain, United Kingdom, the Netherlands, Greece, Germany, Sweden, Denmark).
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| 11. |
- Ali, Alaa M. G., et al.
(författare)
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Alcohol Consumption and Survival after a Breast Cancer Diagnosis: A Literature-Based Meta-analysis and Collaborative Analysis of Data for 29,239 Cases
- 2014
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755 .- 1055-9965. ; 23:6, s. 934-945
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence for an association of alcohol consumption with prognosis after a diagnosis of breast cancer has been inconsistent. We have reviewed and summarized the published evidence and evaluated the association using individual patient data from multiple case cohorts. Methods: A MEDLINE search to identify studies published up to January 2013 was performed. We combined published estimates of survival time for "moderate drinkers" versus nondrinkers. An analysis of individual participant data using Cox regression was carried out using data from 11 case cohorts. Results: We identified 11 published studies suitable for inclusion in the meta-analysis. Moderate postdiagnosis alcohol consumption was not associated with overall survival [HR, 0.95; 95% confidence interval (CI), 0.85-1.05], but there was some evidence of better survival associated with prediagnosis consumption (HR, 0.80; 95% CI, 0.73-0.88). Individual data on alcohol consumption for 29,239 cases with 4,839 deaths were available from the 11 case cohorts, all of which had data on estrogen receptor (ER) status. For women with ER-positive disease, there was little evidence that pre-or postdiagnosis alcohol consumption is associated with breast cancer-specific mortality, with some evidence of a negative association with all-cause mortality. On the basis of a single study, moderate postdiagnosis alcohol intake was associated with a small reduction in breast cancer-specific mortality for women with ER-negative disease. There was no association with prediagnosis intake for women with ER-negative disease. Conclusion: There was little evidence that pre- or post-diagnosis alcohol consumption is associated with breast cancer-specific mortality for women with ER-positive disease. There was weak evidence that moderate post-diagnosis alcohol intake is associated with a small reduction in breast cancer-specific mortality in ER-negative disease. Impact: Considering the totality of the evidence, moderate postdiagnosis alcohol consumption is unlikely to have a major adverse effect on the survival of women with breast cancer. (C) 2014 AACR.
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| 12. |
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| 13. |
- Barrdahl, Myrto, et al.
(författare)
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A comprehensive analysis of polymorphic variants in steroid hormone and insulin-like growth factor-1 metabolism and risk of in situ breast cancer : Results from the Breast and Prostate Cancer Cohort Consortium
- 2018
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 142:6, s. 1182-1188
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Tidskriftsartikel (refereegranskat)abstract
- We assessed the association between 1,414 single nucleotide polymorphisms (SNPs) in genes involved in synthesis and metabolism of steroid hormones and insulin-like growth factor 1, and risk of breast cancer in situ (BCIS), with the aim of determining whether any of these were disease specific. This was carried out using 1,062 BCIS cases and 10,126 controls as well as 6,113 invasive breast cancer cases from the Breast and Prostate Cancer Cohort Consortium (BPC3). Three SNPs showed at least one nominally significant association in homozygous minor versus homozygous major models. ACVR2A-rs2382112 (ORhom=3.05, 95%CI=1.72-5.44, Phom=1.47 × 10-4), MAST2-rs12124649 (ORhom=1.73, 95% CI =1.18-2.54, Phom=5.24 × 10-3), and INSR-rs10500204 (ORhom=1.96, 95% CI=1.44-2.67, Phom=1.68 × 10-5) were associated with increased risk of BCIS; however, only the latter association was significant after correcting for multiple testing. Furthermore, INSR-rs10500204 was more strongly associated with the risk of BCIS than invasive disease in case-only analyses using the homozygous minor versus homozygous major model (ORhom=1.78, 95% CI=1.30-2.44, Phom=3.23 × 10-4). The SNP INSR-rs10500204 is located in an intron of the INSR gene and is likely to affect binding of the promyelocytic leukemia (PML) protein. The PML gene is known as a tumor suppressor and growth regulator in cancer. However, it is not clear on what pathway the A-allele of rs10500204 could operate to influence the binding of the protein. Hence, functional studies are warranted to investigate this further.
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| 14. |
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| 15. |
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| 16. |
- Borgquist, Lars, et al.
(författare)
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The Relationship between Health-state Utilities and the SF-12 in a General Population
- 1999
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Ingår i: Medical decision making. - : SAGE. - 1552-681X .- 0272-989X. ; 19:2, s. 128-140
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Tidskriftsartikel (refereegranskat)abstract
- It would be a major advance if quality-of-life instruments could be translated into health- state utilities. The aim with this study was to investigate the relationship between the SF-12 and health-state utilities, based on responses to a postal questionnaire sent to a random sample of 8,000 inhabitants, aged 20-84 years, in the general population. The questionnaire included the SF-12, a rating-scale (RS) question, and a time-tradeoff (TTO) question; the response rate was 68%. Age, gender, and the 12 items of the SF- 12 were used as explanatory variables in a linear regression analysis of the health- state utilities. The regression models explained about 50% of the variance in the RS answers and about 25% of the variance in the TTO answers. Most of the SF-12 items were related to the health-state utilities in the expected ways, with especially strong results for the RS method. The results suggest that the SF-12 can be converted to health-state utilities, but that further work is needed to reliably estimate the conversion function. Key words: health status; SF-12; rating scale; time-tradeoff; health-related quality of life; health-state utilities; population study. (Med Decis Making 1999;19:128- 140)
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| 17. |
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| 18. |
- Borgquist, Signe, et al.
(författare)
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Oestrogen receptors alpha and beta show different associations to clinicopathological parameters and their co-expression might predict a better response to endocrine treatment in breast cancer.
- 2008
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Ingår i: Journal of Clinical Pathology. - : BMJ. - 1472-4146 .- 0021-9746. ; 61:2, s. 197-202
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The majority of all breast cancers are hormone responsive, traditionally defined by the expression of oestrogen receptor (ER) alpha and/or progesterone receptors. In contrast to ERalpha, the clinical significance of the relatively recently identified ERbeta is still unclear. This study aimed to define the relationship between ERbeta and clinicopathological parameters in a mixed cohort of breast cancer and, furthermore, to investigate the impact of ERbeta expression on disease outcome. METHODS: The immunohistochemical expression of ERalpha and ERbeta was analysed in tissue microarrays containing a total number of 512 tumours with all incident breast cancers diagnosed at the Malmö University Hospital between 1988 and 1992. RESULTS: 78% of the tumours were ERalpha positive and 50% were ERbeta positive. ERbeta correlated positively with ERalpha (p = 0.001). In contrast to ERalpha, ERbeta was not associated with any important clinicopathological variables. Furthermore, no overall prognostic significance could be demonstrated for ERbeta. In the ERalpha-positive subgroup, however, a low expression of ERbeta correlated with a decreased disease-free survival in patients receiving endocrine treatment (p = 0.003). CONCLUSIONS: Although interrelated, ERalpha and ERbeta seem to be differentially associated to clinicopathological parameters, and this would support the fact that they might have different functions in vivo. Furthermore, ERbeta might be a predictive marker of response to endocrine therapy, although this needs to be confirmed in additional studies, preferably randomised trials.
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| 19. |
- Dankiewicz, Josef, et al.
(författare)
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Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest
- 2021
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 384:24, s. 2283-2294
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Tidskriftsartikel (refereegranskat)abstract
- Hypothermia or Normothermia after Cardiac Arrest This trial randomly assigned patients with coma after out-of-hospital cardiac arrest to undergo targeted hypothermia at 33 degrees C or normothermia with treatment of fever. At 6 months, there were no significant between-group differences regarding death or functional outcomes. Background Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. Methods In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33 degrees C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, >= 37.8 degrees C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. Results A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P=0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score >= 4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. Conclusions In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, .)
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| 20. |
- Ericson, Ulrika, et al.
(författare)
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Plasma Folate Concentrations Are Positively Associated with Risk of Estrogen Receptor {beta} Negative Breast Cancer in a Swedish Nested Case Control Study.
- 2010
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Ingår i: Journal of Nutrition. - : Elsevier BV. - 1541-6100 .- 0022-3166. ; 140:9, s. 1661-1668
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Tidskriftsartikel (refereegranskat)abstract
- Folate's role in breast cancer development is controversial. Not only estrogen receptor (ER) alpha status, but also ERbeta status of tumors may have confounded results from previous epidemiological studies. We aimed to examine associations between plasma folate concentration and postmenopausal breast cancer defined by ER status. This nested case-control study, within the Malmö diet and cancer cohort, included 204 incident breast cancer cases with information on ERalpha and ERbeta status determined by immunochemistry on tissue micro-array sections. Plasma folate concentration was analyzed for the cases and 408 controls (matched on age and blood sample date). Odds ratios (OR) for ER-defined breast cancers in tertiles of plasma folate concentration were calculated with unconditional logistic regression. All tests were 2-sided. Women in the third tertile of plasma folate concentration (>12 nmol/L) had higher incidence of ERbeta- breast cancer than women in the first tertile (OR: 2.67; 95% CI: 1.44-4.92; P-trend = 0.001). We did not observe significant associations between plasma folate concentration and other breast cancer subgroups defined by ER status. We observed a difference between risks for ERbeta+ and ERbeta- cancer (P-heterogeneity = 0.003). Our findings, which indicate a positive association between plasma folate and ERbeta- breast cancer, highlight the importance of taking ERbeta status into consideration in studies of folate and breast cancer. The study contributes knowledge concerning folate's multifaceted role in cancer development. If replicated in other populations, the observations may have implications for public health, particularly regarding folic acid fortification.
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| 21. |
- Grodzinsky, Ewa, 1958-, et al.
(författare)
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Point-of-care testing has a limited effect on time to clinical decision in primary health care
- 2004
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 64:6, s. 547-551
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the clinical logistics of laboratory routines at primary health care centres (PHCs). Design and methods: Prospective registration was carried out for each PHC using questionnaires during 2-week intervals between the end of November 2001 and mid-January 2002. The study included 9 PHCs in the county of Östergötland and 4 in the county of Jönköping, Sweden, with different numbers of blood tests analysed using point-of-care testing (POCT). Data for B-glucose, HbA1c, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), thyroid-stimulating hormone (TSH), T4, cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides were collected. Main outcome measures were median time from sampling to available test result (TATa) and median time from sampling to clinical decision (TATd), and the proportion of patients informed of the outcome of the blood test in question during the sampling occasion. Results: A total of 3542 samples were collected. The median TATa showed that B-glucose, ESR and CRP were immediately analysed at all 13 PHCs. For the other tests, TATa varied from immediately to about two days. The median TATd varied from immediately to about a week. When POCT was used, 30% of the patients were informed about the outcome of the test during the sampling occasion. Conclusion: POCT has a limited effect on the clinical logistics in PHCs.
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| 22. |
- He, W., et al.
(författare)
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CYP2D6 genotype predicts tamoxifen discontinuation and drug response : a secondary analysis of the KARISMA trial
- 2021
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 32:10, s. 1286-1293
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Tidskriftsartikel (refereegranskat)abstract
- Background: Guidelines regarding whether tamoxifen should be prescribed based on women's cytochrome P450 2D6 (CYP2D6) genotypes are conflicting and have caused confusion. This study aims to investigate if CYP2D6 metabolizer status isa associated with tamoxifen-related endocrine symptoms, tamoxifen discontinuation, and mammographic density change. Patients and methods: We used data from 1440 healthy women who participated the KARISMA dose determination trial. Endocrine symptoms were measured using a modified Functional Assessment of Cancer Therapy – Endocrine Symptoms (FACT-ES) questionnaire. Change in mammographic density was measured and used as a proxy for tamoxifen response. Participants were genotyped and categorized as poor, intermediate, normal, or ultrarapid CYP2D6 metabolizers. Results: The median endoxifen level per mg oral tamoxifen among poor, intermediate, normal and ultrarapid CYP2D6 metabolizers were 0.18 ng/ml, 0.38 ng/ml, 0.56 ng/ml and 0.67 ng/ml, respectively. Ultrarapid CYP2D6 metabolizers were more likely than other groups to report a clinically relevant change in cold sweats, hot flash, mood swings, being irritable, as well as the overall modified FACT-ES score, after taking tamoxifen. The 6-month tamoxifen discontinuation rates among poor, intermediate, normal, and ultrarapid CYP2D6 metabolizers were 25.7%, 23.6%, 28.6%, and 44.4%, respectively. Among those who continued and finished the 6-month tamoxifen intervention, the mean change in dense area among poor, intermediate, normal, and ultrarapid CYP2D6 metabolizers were −0.8 cm2, −4.5 cm2, −4.1 cm2, and −8.0 cm2 respectively. Conclusions: Poor CYP2D6 metabolizers are likely to experience an impaired response to tamoxifen, measured through mammographic density reduction. In contrast, ultrarapid CYP2D6 metabolizers are at risk for exaggerated response with pronounced adverse effects that may lead to treatment discontinuation.
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| 23. |
- Hermann, Silke, et al.
(författare)
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The association of education with body mass index and waist circumference in the EPIC-PANACEA study
- 2011
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 11:1, s. 169-
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine the association of education with body mass index (BMI) and waist circumference (WC) in the European Prospective Investigation into Cancer and Nutrition (EPIC).METHOD: This study included 141,230 male and 336,637 female EPIC-participants, who were recruited between 1992 and 2000. Education, which was assessed by questionnaire, was classified into four categories; BMI and WC, measured by trained personnel in most participating centers, were modeled as continuous dependent variables. Associations were estimated using multilevel mixed effects linear regression models.RESULTS: Compared with the lowest education level, BMI and WC were significantly lower for all three higher education categories, which was consistent for all countries. Women with university degree had a 2.1 kg/m2 lower BMI compared with women with lowest education level. For men, a statistically significant, but less pronounced difference was observed (1.3 kg/m2). The association between WC and education level was also of greater magnitude for women: compared with the lowest education level, average WC of women was lower by 5.2 cm for women in the highest category. For men the difference was 2.9 cm.CONCLUSION: In this European cohort, there is an inverse association between higher BMI as well as higher WC and lower education level. Public Health Programs that aim to reduce overweight and obesity should primarily focus on the lower educated population.
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| 24. |
- Holtedahl, K., et al.
(författare)
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Abdominal symptoms in general practice: Frequency, cancer suspicions raised, and actions taken by GPs in six European countries. Cohort study with prospective registration of cancer
- 2017
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Ingår i: Heliyon. - : Elsevier BV. - 2405-8440. ; 3:6
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Tidskriftsartikel (refereegranskat)abstract
- Background Abdominal symptoms are diagnostically challenging to general practitioners (GPs): although common, they may indicate cancer. In a prospective cohort of patients, we examined abdominal symptom frequency, initial diagnostic suspicion, and actions of GPs in response to abdominal symptoms. Methods Over a 10-day period, 493 GPs in Norway, Denmark, Sweden, Belgium, the Netherlands, and Scotland, recorded consecutive consultations: sex, date of birth and any specified abdominal symptoms. For patients with abdominal symptoms, additional data on non-specific symptoms, GPs’ diagnostic suspicion, and features of the consultation were noted. Data on all cancer diagnoses among all included patients were requested from the GPs eight months later. Findings Consultations with 61802 patients were recorded. Abdominal symptoms were recorded in 6264 (10.1%) patients. A subsequent malignancy was reported in 511 patients (0.8%): 441 (86.3%) had a new cancer, 70 (13.7%) a recurrent cancer. Abdominal symptoms were noted in 129 (25.2%) of cancer patients (P < 0.001), rising to 34.5% for the 89 patients with cancer located in the abdominal region. PPV for any cancer given any abdominal symptom was 2.1%. In symptomatic patients diagnosed with cancer, GPs noted a suspicion of cancer for 85 (65.9%) versus 1895 (30.9%) when there was no subsequent cancer (P < 0.001). No suspicion was noted in 32 (24.8%) cancer patients. The GP's intuitive cancer suspicion was independently associated with a subsequent new cancer diagnosis (OR 2.11, 95% CI 1.15–3.89). Laboratory tests were ordered for 45.4% of symptomatic patients, imaging for 10.4%, referral or hospitalization for 20.0%: all were more frequent in subsequent cancer patients (P < 0.001). Interpretation Abdominal symptoms pointed to abdominal cancers rather than to other cancers. However, the finding of abdominal symptoms in only one third of patients with an abdominal cancer, and the lack of cancer suspicion in a quarter of symptomatic cancer patients, provide challenges for GPs’ diagnostic thinking and referral practices. © 2017 The Authors
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| 25. |
- Johannesson, Magnus, et al.
(författare)
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The cost effectiveness of lipid lowering in Swedish primary health care
- 1996
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Ingår i: Journal of internal medicine. - : Blackwell Science Ltd. - 1365-2796 .- 0954-6820. ; 240:1, s. 23-29
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To evaluate the cost‐effectiveness of two types of advice (usual and intensive) to lower cardiovascular risk, with or without pharmacological medication aimed at lowering cholesterol levels. Design. Prospective, randomized, controlled clinical study of 18 months' duration. Setting. Thirty‐two primary health care centres in Sweden. Subjects. A total of 384 males, aged 30–59 years, with at least one cardiovascular risk factor in addition to moderate primary hyperlipidaemia; of these, 355 completed the 18‐month follow‐up. Interventions. Intensive advice consisted of group sessions led by a health care professional; the usual level of advice was given at follow‐up visits. The pharmacological intervention consisted of pravastatin. The goal was to achieve a 15% reduction in cholesterol. Main outcome measures. Cost per life‐year gained based on the change in serum cholesterol and the net intervention cost of the four treatment options. Results. The usual level of advice and intensive advice in combination with pharmacological treatment achieved no incremental effects and were not considered in the cost‐effectiveness analysis. The cost per life‐year gained of pharmacological treatment compared with intensive advice decreased. The cost per life‐year gained of pharmacological treatment compared with no treatment was about $61 000, if no adverse consequences on noncardiovascular mortality were assumed. Conclusions. According to the results of the CELL trial, intensive advice is not a cost‐effective strategy compared with lipid‐lowering drug treatment. However, it is also doubtful whether drug treatment as primary prevention is cost‐effective compared with no treatment in the studied patient population.
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| 26. |
- Kaminska, Kamila, et al.
(författare)
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Distinct mechanisms of resistance to fulvestrant treatment dictate level of ER independence and selective response to CDK inhibitors in metastatic breast cancer
- 2021
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Ingår i: Breast cancer research : BCR. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 23:1, s. 26-26
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Resistance to endocrine treatment in metastatic breast cancer is a major clinical challenge. Clinical tools to predict both drug resistance and possible treatment combination approaches to overcome it are lacking. This unmet need is mainly due to the heterogeneity underlying both the mechanisms involved in resistance development and breast cancer itself.METHODS: To study the complexity of the mechanisms involved in the resistance to the selective estrogen receptor degrader (SERD) fulvestrant, we performed comprehensive biomarker analyses using several in vitro models that recapitulate the heterogeneity of developed resistance. We further corroborated our findings in tissue samples from patients treated with fulvestrant.RESULTS: We found that different in vitro models of fulvestrant resistance show variable stability in their phenotypes, which corresponded with distinct genomic alterations. Notably, the studied models presented adaptation at different cell cycle nodes to facilitate progression through the cell cycle and responded differently to CDK inhibitors. Cyclin E2 overexpression was identified as a biomarker of a persistent fulvestrant-resistant phenotype. Comparison of pre- and post-treatment paired tumor biopsies from patients treated with fulvestrant revealed an upregulation of cyclin E2 upon development of resistance. Moreover, overexpression of this cyclin was found to be a prognostic factor determining resistance to fulvestrant and shorter progression-free survival.CONCLUSIONS: These data highlight the complexity of estrogen receptor positive breast cancer and suggest that the development of diverse resistance mechanisms dictate levels of ER independence and potentially cross-resistance to CDK inhibitors.
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| 27. |
- Leung, Samuel CY, et al.
(författare)
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Analytical validation of a standardized scoring protocol for Ki67 immunohistochemistry on breast cancer excision whole sections: an international multicenter collaboration
- 2019
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Ingår i: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 75:2, s. 225-235
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The nuclear proliferation marker Ki67 assayed by immunohistochemistry has multiple potential uses in breast cancer, but an unacceptable level of interlaboratory variability has hampered its clinical utility. The International Ki67 in Breast Cancer Working Group has undertaken a systematic programme to determine whether Ki67 measurement can be analytically validated and standardised among laboratories. This study addresses whether acceptable scoring reproducibility can be achieved on excision whole sections.Methods and results: Adjacent sections from 30 primary ER+ breast cancers were centrally stained for Ki67 and sections were circulated among 23 pathologists in 12 countries. All pathologists scored Ki67 by two methods: (i) global: four fields of 100 tumour cells each were selected to reflect observed heterogeneity in nuclear staining; (ii) hot‐spot: the field with highest apparent Ki67 index was selected and up to 500 cells scored. The intraclass correlation coefficient (ICC) for the global method [confidence interval (CI) = 0.87; 95% CI = 0.799–0.93] marginally met the prespecified success criterion (lower 95% CI ≥ 0.8), while the ICC for the hot‐spot method (0.83; 95% CI = 0.74–0.90) did not. Visually, interobserver concordance in location of selected hot‐spots varies between cases. The median times for scoring were 9 and 6 min for global and hot‐spot methods, respectively.Conclusions: The global scoring method demonstrates adequate reproducibility to warrant next steps towards evaluation for technical and clinical validity in appropriate cohorts of cases. The time taken for scoring by either method is practical using counting software we are making publicly available. Establishment of external quality assessment schemes is likely to improve the reproducibility between laboratories further.
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| 28. |
- Lundberg, Lena, et al.
(författare)
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Effects of user charges on the use of prescription medicines in different socio-economic groups
- 1998
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Ingår i: Health policy (Amsterdam). - : Elsevier Ireland Ltd. - 1872-6054 .- 0168-8510. ; 44:2, s. 123-134
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Tidskriftsartikel (refereegranskat)abstract
- This study examined the sensitivity towards increases in user charges for different types of drugs and among different socio-economic groups. It was based on responses by 2008 consumers of prescription drugs to a self-administered postal questionnaire sent to a random sample of 8000 inhabitants in Uppsala County in Sweden. The questionnaire included a question about whether the respondents would use fewer prescription drugs if the user charges increased by a specific amount. The increase in user charges was varied between 9 and 150% in five different subsamples. Logistic regression analysis was used to estimate the probability that a respondent would reduce consumption of prescription drugs as a function of the size of the user charges increase, socio-economic characteristics and the type of drug used. Results showed that the price sensitivity decreased with increasing age, income, education and self-rated health status. Price sensitivity was highest for antitussives and lowest for climacteric drugs. If the user charges doubled, 40% of antitussives users would reduce their consumption whereas only 11% of climacteric drugs users would reduce their consumption. It is concluded that sensitivity to increases in user charges varied greatly between different types of drugs and between socio-economic groups. The young, those with poor health status, low education and low income are most likely to decrease consumption of prescription drugs when user charges increase.
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| 29. |
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| 30. |
- Lundberg, Lena, et al.
(författare)
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Health-state utilities in a general population in relation to age, gender and socioeconomic factors
- 1999
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Ingår i: European journal of public health. - : Oxford University Press. - 1464-360X .- 1101-1262. ; 9:3, s. 211-217
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study examined health-related quality of life in a general population in relation to different socioeconomic variables. Method: The study was cross-sectional and was conducted in Uppsala county, Sweden, which had approximately 290,000 inhabitants in 1995. The study was based on a self-administered postal questionnaire sent to a random sample of 8,000 inhabitants aged 20–84 years, with a response rate of 68%. Health-related quality of life was measured on a 0 (dead) to 1 (full health) cardinal scale by two methods used to measure health-state utilities in economic evaluations, i.e. the rating scale method and the time trade-off method. Results: The mean age was 46 years and approximately 54% were women. Almost 70% were married or cohabitors. Approxiamtely 33% of the respondents had less than high-school education and 26% had a university degree. The mean income was SEK 13,000 per month and the proportion unemployed was 4.5%. The proportions of blue-collar workers, white-collar workers and self-employed were 40, 50 and 10% respectively. With the rating scale method, the mean health-state utility decreased from 0.86 in the youngest age group (20–29 years) to 0.63 (80–years) in the oldest age group and from 0.94 to 0.61 with the time trade-off method. Quality of life increased with income, education and social group and decreased with being single and unemployed. Conclusion: These methods are useful in assessing health-related quality of life in the general population and that quality of life varies substantially among different sodoeconomic groups.
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| 35. |
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| 39. |
- Robertsson, Otto, et al.
(författare)
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Use of unicompartmental instead of tricompartmental prostheses for unicompartmental arthrosis in the knee is a cost-effective alternative. 15,437 primary tricompartmental prostheses were compared with 10,624 primary medial or lateral unicompartmental prostheses
- 1999
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Ingår i: Acta Orthopaedica Scandinavica. - 0001-6470. ; 70:2, s. 170-175
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Tidskriftsartikel (refereegranskat)abstract
- Unicompartmental knee arthroplasty (UKA) is known to have a higher risk of revision than tricompartmental arthroplasty (TKA), while UKA implants are generally less expensive than TKA implants. We estimated the costs of implants and hospital stay of both procedures and related the cost difference at primary operation to the difference in number of revisions to be expected. We compared 15,437 primary TKAs and 10,624 primary medial or lateral UKAs. The operations were all done on patients with arthrosis during 1985-1995. By matching patients in the Swedish Patient Administration System with the Swedish National Knee Arthroplasty Register, the groups could be compared regarding the length of the hospital stay. The cumulative revision rate (CRR) and the relative risk of revision were calculated with survival statistics, as well as the risk of a second revision and the risk of infection. The weighted mean cost of the commonest implants in each group was used as an estimate of the implant cost. We found that the TKA patients were, on average, 2 years older at operation and had a lower CRR than the UKA patients-i.e., 10-year CRR of 12% and 16%, respectively. After adjusting for age, gender and year of operation, UKA patients were found to have a 2-day shorter hospital stay and fewer serious complications than TKA patients. The mean estimated cost of a unicompartmental implant was 57% of that of a tricompartmental implant. We conclude, that by using UKA instead of TKA in appropriate patients, money can be saved, even after taking into account the increased number of revisions to be expected.
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| 40. |
- Schlehofer, B, et al.
(författare)
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Primary brain tumours and specific serum immunoglobulin E : a case-control study nested in the European prospective investigation into cancer and nutrition cohort
- 2011
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 66:11, s. 1434-1441
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: Background: Case-control studies suggest that patients with allergic diseases have a lower risk of developing glioma but not meningioma or schwannoma. However, those data can be differentially biased. Prospective studies with objective measurements of immunologic biomarkers, like immunoglobulin E (IgE), in blood obtained before cancer diagnosis could help to clarify whether an aetiological association exists. Methods: The present case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) measured specific serum IgE as a biomarker for the most common inhalant allergens in 275 glioma, 175 meningioma and 49 schwannoma cases and 963 matched controls using the ImmunoCAP specific IgE test. Subjects with an IgE level ≥0.35 kUA/l (kilo antibody units per litre) were classified as sensitized by allergens. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by adjusted conditional logistic regression models for each tumour subtype. The effect of dose-response relationship was assessed in five increasing IgE level categories to estimate P-values for trend. Results: The risk of glioma was inversely related to allergic sensitization (OR = 0.73; 95% CI 0.51-1.06), especially pronounced in women (OR = 0.53; 95% CI 0.30-0.95). In dose-response analyses, for high-grade glioma, the lowest OR was observed in sera with the highest IgE levels (P for trend = 0.04). No association was seen for meningioma and schwannoma. Conclusion: The results, based on serum samples prospectively collected in a cohort study, provide some support for the hypothesis that individuals with allergic sensitization are at reduced risk of glioma and confirm results from previous case-control studies.
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| 41. |
- Shirazi, L., et al.
(författare)
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Serum vitamin D (25OHD(3)) levels and the risk of different subtypes of breast cancer: A nested case-control study
- 2016
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Ingår i: Breast. - : Elsevier BV. - 0960-9776. ; 28, s. 184-190
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies regarding the association between serum 25-hydroxyvitamin D (25OHD(3)) and breast cancer risk have not been conclusive. The aim of this study was to investigate the potential association between pre-diagnostic serum 25OHD(3) levels and the risk of different subtypes of breast cancer. Materials and methods: The study was based on The Malmo Diet and Cancer Study recruiting 17,035 women from 1991 to 1996. A total of 764 incident breast cancers with matched controls were analysed for 25OHD(3) in samples collected at baseline, before diagnosis. A logistic regression analysis was used to calculate odds ratios with 95% confidence intervals for tertiles of 25OHD(3) in relation to different subtypes of breast cancer, i.e. defined according to tumour type, tumour size, lymph node involvement, histological grade, oestrogen receptor (ER) status, progesterone receptor (PgR) status, Ki67, cyclin D1 and p27. Results: As compared to the 1st tertile of 25OHD(3), the second tertile had a statistically significantly lower risk of ER negative tumours, PgR negative tumours and tumours with a high expression of Ki67, A similar pattern was seen in relation to large tumours (>= 21 mm), grade III tumours, and tumours with low p27 expression, but these associations did not reach statistical significance. The third tertile had a similar risk as the first tertile. Conclusions: We found that women with low levels of 25OHD(3), as compare to women in the middle tertile, had a high risk of breast tumours with an unfavourable prognosis.
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| 42. |
- Sjöblom, J, et al.
(författare)
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Efficacy of primary preventive ICD therapy in an unselected population of patients with reduced left ventricular ejection fraction.
- 2015
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Ingår i: Europace. - : Oxford University Press (OUP). - 1532-2092 .- 1099-5129. ; 17:2, s. 255-261
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Tidskriftsartikel (refereegranskat)abstract
- International guidelines advocate an implantable cardioverter and defibrillator (ICD) in patients with reduced left ventricular ejection fraction (LVEF) to prevent sudden death (SCD). Previous data suggest that the benefit of ICD therapy in real life may be lower than expected from the results of controlled studies and side-effects are not negligible. It is also unclear whether women benefit from treatment to the same extent as men. The aim of this study was to investigate the balance between benefits and complications of ICD therapy in a real-life population of patients with heart failure.
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| 43. |
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| 44. |
- Steffen, Annika, et al.
(författare)
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Meat and Heme Iron Intake and Risk of Squamous Cell Carcinoma of the Upper Aero-Digestive Tract in the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2012
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755 .- 1055-9965. ; 21:12, s. 2138-2148
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence from prospective studies on intake of meat and fish and risk of squamous cell carcinoma (SCC) of the upper aero-digestive tract (UADT) is scarce. We prospectively investigated the association of meat and fish intake with risk of SCC of the UADT and the possible mechanism via heme iron in the large multicenter European Prospective Investigation into Cancer and Nutrition (EPIC) study. Methods: Multivariable proportional hazards models were used to estimate relative risks (RR) of SCC of the UADT in relation to intake of total meat, as well as subtypes of meat, fish, and heme iron among 348,738 individuals from 7 European countries. Results: During an average follow-up of 11.8 years, a total of 682 incident cases of UADT SCC were accrued. Intake of processed meat was positively associated with risk of SCC of the UADT in the total cohort (highest vs. lowest quintile: RR = 1.41; 95% confidence interval (CI) = 1.03-1.941, however, in stratified analyses, this association was confined to the group of current smokers (highest vs. lowest quintile: RR = 1.89; 95% CI = 1.22-2.93). Red meat, poultry, fish, and heme iron were not consistently related to UADT SCC. Conclusion: Higher intake of processed meat was positively associated with KC of the UADT among smokers. Although this finding was stable in various sensitivity analyses, we cannot rule out residual confounding by smoking. Confirmation in future studies and identification of biologic mechanisms is warranted. Impact: Smokers may further increase their risk for SCC of the UADT if they additionally consume large amounts of processed meat. Cancer Epidemiol Biomarkers Prev; 21(12); 2738-48. (C)2012 AACR.
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| 45. |
- Tsilidis, K. K., et al.
(författare)
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Oral contraceptives, reproductive history and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition
- 2010
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 103:11, s. 1755-1759
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Oral contraceptive use and reproductive factors may initiate long-term changes to the hormonal milieu and thereby, possibly influence colorectal cancer risk. METHODS: We examined the association of hormonal and reproductive factors with risk of colorectal cancer among 337 802 women in the European Prospective Investigation into Cancer and Nutrition, of whom 1878 developed colorectal cancer. RESULTS: After stratification for center and age, and adjustment for body mass index, smoking, diabetes mellitus, physical activity and alcohol consumption, ever use of oral contraceptives was marginally inversely associated with colorectal cancer risk (hazard ratio (HR), 0.92; 95% confidence interval (CI), 0.83-1.02), although this association was stronger among post-menopausal women (HR, 0.84; 95% CI: 0.74-0.95). Duration of oral contraceptive use and reproductive factors, including age at menarche, age at menopause, type of menopause, ever having an abortion, parity, age at first full-term pregnancy and breastfeeding, were not associated with colorectal cancer risk. CONCLUSION: Our findings provide limited support for a potential inverse association between oral contraceptives and colorectal cancer risk. British Journal of Cancer (2010) 103, 1755-1759. doi:10.1038/sj.bjc.6605965 www.bjcancer.com Published online 2 November 2010 (C) 2010 Cancer Research UK
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| 46. |
- Öien, Rut, et al.
(författare)
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Pinch grafting in hospital and primary care: a cost analysis
- 2001
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Ingår i: Journal of Wound Care. - 0969-0700. ; 10:5, s. 164-169
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Tidskriftsartikel (refereegranskat)abstract
- The cost of treating venous leg ulcers with pinch grafting was evaluated for 58 consecutive patients: 29 in hospital care and 29 in primary care. The mean age was 76.8 and 74.3 years and the mean ulcer size 15.1 and 13.5 cm2, respectively. The operation technique, pinch grafting, was the same for all patients but primary care patients were not immobilised postoperatively. Healing rate within 12 weeks was the same for patients in hospital care and primary care (31%). Treatment costs for one week pre-operatively and three weeks postoperatively amounted to 5109 Pounds per patient in hospital care and 870 Pounds per patient in primary care (p < 0.001), and the costs for one week pre-operatively and 12 weeks postoperatively were 6738 Pounds and 1806 Pounds, respectively (p < 0.001). Costs for patients whose ulcers healed within 12 weeks were 5552 Pounds for those receiving hospital care and 1676 Pounds for those receiving primary care (p < 0.001). Pinch grafting in primary care was shown to cost 3.3 to 5.9 times less, with the same healing outcome, than pinch grafting in hospital care.
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