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- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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- Gudnadottir, Gunnhildur, et al.
(författare)
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Indirect costs related to caregivers' absence from work after paediatric tonsil surgery
- 2017
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Ingår i: European Archives of Oto-Rhino-Laryngology. - : Springer Science and Business Media LLC. - 0937-4477 .- 1434-4726. ; 274:6, s. 2629-2636
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Tidskriftsartikel (refereegranskat)abstract
- Tonsillotomy has gradually replaced tonsillectomy as the surgical method of choice in children with upper airway obstruction during sleep, because of less postoperative pain and a shorter recovery time. The aim of this study was to examine the costs related to caregivers' absenteeism from work after tonsillectomy (TE) and tonsillotomy (TT). All tonsillectomies and tonsillotomies in Sweden due to upper airway obstruction during 1 year, reported to the National Tonsil Surgery Register in children aged 1-11 were included, n = 4534. The number of days the child needed analgesics after surgery was used as a proxy to estimate the number of work days lost for the caregiver. Data from the Social Insurance Agency (Forsakringskassan) regarding the days the parents received temporary parental benefits in the month following surgery were also analysed. The indirect costs due to the caregivers' absenteeism after tonsillectomy vs tonsillotomy were calculated, using the human capital method. The patient-reported use of postoperative analgesic use was 77% (n = 3510). Data from the Social Insurance Agency were gathered for all 4534 children. The mean duration of analgesic treatment was 4.6 days (indirect cost of EUR 747). The mean number of days with parental benefits was 2.9 (EUR 667). The indirect cost of tonsillectomy was 61% higher than that of tonsillotomy (EUR 1010 vs EUR 629). The results show that the choice of surgical method affects the indirect costs, favouring the use of tonsillotomy over tonsillectomy for the treatment of children with SDB, due to less postoperative pain.
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- Ho, Alan L., et al.
(författare)
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Selumetinib Plus Adjuvant Radioactive Iodine in Patients with High-Risk Differentiated Thyroid Cancer : A Phase III, Randomized, Placebo-Controlled Trial (ASTRA)
- 2022
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 40:17, s. 1870-1878
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSESelumetinib can increase radioactive iodine (RAI) avidity in RAI-refractory tumors. We investigated whether selumetinib plus adjuvant RAI improves complete remission (CR) rates in patients with differentiated thyroid cancer (DTC) at high risk of primary treatment failure versus RAI alone.METHODSASTRA (ClinicalTrials.gov identifier: NCT01843062) is an international, phase III, randomized, placebo-controlled, double-blind trial. Patients with DTC at high risk of primary treatment failure (primary tumor > 4 cm; gross extrathyroidal extension outside the thyroid gland [T4 disease]; or N1a/N1b disease with ≥ 1 metastatic lymph node(s) ≥ 1 cm or ≥ 5 lymph nodes [any size]) were randomly assigned 2:1 to selumetinib 75 mg orally twice daily or placebo for approximately 5 weeks (no stratification). On treatment days 29-31, recombinant human thyroid-stimulating hormone (0.9 mg)-stimulated RAI (131I; 100 mCi/3.7 GBq) was administered, followed by 5 days of selumetinib/placebo. The primary end point (CR rate 18 months after RAI) was assessed in the intention-to-treat population.RESULTSFour hundred patients were enrolled (August 27, 2013-March 23, 2016) and 233 randomly assigned (selumetinib, n = 155 [67%]; placebo, n = 78 [33%]). No statistically significant difference in CR rate 18 months after RAI was observed (selumetinib n = 62 [40%]; placebo n = 30 [38%]; odds ratio 1.07 [95% CI, 0.61 to 1.87]; P =.8205). Treatment-related grade ≥ 3 adverse events were reported in 25/154 patients (16%) with selumetinib and none with placebo. The most common adverse event with selumetinib was dermatitis acneiform (n = 11 [7%]). No treatment-related deaths were reported.CONCLUSIONPostoperative pathologic risk stratification identified patients with DTC at high risk of primary treatment failure, although the addition of selumetinib to adjuvant RAI failed to improve the CR rate for these patients. Future strategies should focus on tumor genotype-tailored drug selection and maintaining drug dosing to optimize RAI efficacy.
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- Oyen, W J G, et al.
(författare)
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Targeted therapy in nuclear medicine current status and future prospects
- 2007
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 18:11, s. 1782-1792
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, a number of new developments in targeted therapies using radiolabeled compounds have emerged. New developments and insights in radioiodine treatment of thyroid cancer, treatment of lymphoma and solid tumors with radiolabeled monoclonal antibodies (mAbs), the developments in the application of radiolabeled small receptor-specific molecules such as meta-iodobenzylguanidine and peptides and the position of locoregional treatment in malignant involvement of the liver are reviewed. The introduction of recombinant human thyroid-stimulating hormone and the possibility to enhance iodine uptake with retinoids has changed the radioiodine treatment protocol of patients with thyroid cancer. Introduction of radiolabeled mAbs has provided additional treatment options in patients with malignant lymphoma, while a similar approach proves to be cumbersome in patients with solid tumors. With radiolabeled small molecules that target specific receptors on tumor cells, high radiation doses can be directed to tumors in patients with disseminated disease. Radiolabeled somatostatin derivatives for the treatment of neuroendocrine tumors are the role model for this approach. Locoregional treatment with radiopharmaceuticals of patients with hepatocellular carcinoma or metastases to the liver may be used in inoperable cases, but may also be of benefit in a neo-adjuvant or adjuvant setting. Significant developments in the application of targeted radionuclide therapy have taken place. New treatment modalities have been introduced in the clinic. The concept of combining therapeutic radiopharmaceuticals with other treatment modalities is more extensively explored.
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| 7. |
- Prompers, L, et al.
(författare)
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Delivery of care to diabetic patients with foot ulcers in daily practice: results of the Eurodiale Study, a prospective cohort study
- 2008
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Ingår i: Diabetic Medicine. - : Wiley. - 1464-5491 .- 0742-3071. ; 25:6, s. 700-707
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Tidskriftsartikel (refereegranskat)abstract
- Aims To determine current management and to identify patient-related factors and barriers that influence management strategies in diabetic foot disease. Methods The Eurodiale Study is a prospective cohort study of 1232 consecutive individuals presenting with a new diabetic foot ulcer in 14 centres across Europe. We determined the use of management strategies: referral, use of offloading, vascular imaging and revascularization. Results Twenty-seven percent of the patients had been treated for > 3 months before referral to a foot clinic. This varied considerably between countries (6-55%). At study entry, 77% of the patients had no or inadequate offloading. During follow-up, casting was used in 35% (0-68%) of the plantar fore- or midfoot ulcers. Predictors of use of casting were male gender, large ulcer size and being employed. Vascular imaging was performed in 56% (14-86%) of patients with severe limb ischaemia; revascularization was performed in 43%. Predictors of use of vascular imaging were the presence of infection and ischaemic rest pain. Conclusion Treatment of many patients is not in line with current guidelines and there are large differences between countries and centres. Our data suggest that current guidelines are too general and that healthcare organizational barriers and personal beliefs result in underuse of recommended therapies. Action should be undertaken to overcome these barriers and to guarantee the delivery of optimal care for the many individuals with diabetic foot disease.
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| 9. |
- Tennvall, G R, et al.
(författare)
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Costs of deep foot infections in patients with diabetes mellitus
- 2000
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Ingår i: PharmacoEconomics. - 1170-7690. ; 18:3, s. 225-238
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To calculate costs for the management of deep foot infections and to identify the most important factors related to treatment costs. Design: Costs for in-hospital care, surgery, investigations, antibacterials, visits to the foot-care team, orthopaedic appliances and topical treatment were calculated retrospectively from diagnosis until healing or death. Multiple regression analysis was used to identify factors that independently affect costs. Setting: A multidisciplinary foot-care team. Patients: 220 prospectively followed patients with diabetes mellitus and deep foot infections who were referred to the team from 1986 to 1995. Main Outcome Measures and Results: Total cost for healing without amputation was Swedish kronor (SEK) 136 600 per patient, while the corresponding cost for healing with minor amputation was SEK260 000 and with major amputation was SEK234 500. All costs were quoted in SEK at 1997 price levels (£1 sterling and $US1 equalled approximately SEK12.50 and SEK7.64, respectively). The cost of antibacterials was 4% of total costs. The cost of topical treatment was 51% of total costs and related to wound healing time. Number of weeks between diagnosis of deep foot infection and healing, and number of surgical procedures were variables that explained 95% of costs in the multiple regression analysis. It was not possible to find any parameters present at diagnosis that could contribute to an explanation of total treatment costs. Conclusions: Topical treatment accounted for the largest proportion of total costs and the most important cost driving factors were wound healing duration and repeated surgery. Costs of antibacterials should not be used as an argument in the choice between early amputation and conservative treatment.
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