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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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- Andersson, C, et al.
(författare)
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The three ZNT8 autoantibody variants together improve the diagnostic sensitivity of childhood and adolescent type 1 diabetes
- 2011
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Ingår i: Autoimmunity. - : Taylor & Francis. - 0891-6934 .- 1607-842X. ; 44:5, s. 394-405
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Tidskriftsartikel (refereegranskat)abstract
- Aims: We tested whether autoantibodies to all three ZnT8RWQ variants, GAD65, insulinoma-associated protein 2 (IA-2), insulin and autoantibodies to islet cell cytoplasm (ICA) in combination with human leukocyte antigen (HLA) would improve the diagnostic sensitivity of childhood type 1 diabetes by detecting the children who otherwise would have been autoantibody-negative.Methods: A total of 686 patients diagnosed in 1996–2005 in Skåne were analyzed for all the seven autoantibodies [arginin 325 zinc transporter 8 autoantibody (ZnT8RA), tryptophan 325 zinc transporter 8 autoantibody (ZnT8WA), glutamine 325 Zinc transporter 8 autoantibody (ZnT8QA), autoantibodies to glutamic acid decarboxylase (GADA), Autoantibodies to islet-antigen-2 (IA-2A), insulin autoantibodies (IAA) and ICA] in addition to HLA-DQ genotypes.Results: Zinc transporter 8 autoantibody to either one or all three amino acid variants at position 325 (ZnT8RWQA) was found in 65% (449/686) of the patients. The frequency was independent of age at diagnosis. The ZnT8RWQA reduced the frequency of autoantibody-negative patients from 7.5 to 5.4%—a reduction by 28%. Only 2 of 108 (2%) patients who are below 5 years of age had no autoantibody at diagnosis. Diagnosis without any islet autoantibody increased with increasing age at onset. DQA1-B1*X-0604 was associated with both ZnT8RA (p = 0.002) and ZnT8WA (p = 0.01) but not with ZnT8QA (p = 0.07). Kappa agreement analysis showed moderate (>0.40) to fair (>0.20) agreement between pairs of autoantibodies for all combinations of GADA, IA-2A, ZnT8RWQA and ICA but only slight ( < 0.19) agreement for any combination with IAA.Conclusions: This study revealed that (1) the ZnT8RWQA was common, independent of age; (2) multiple autoantibodies were common among the young; (3) DQA1-B1*X-0604 increased the risk for ZnT8RA and ZnT8WA; (4) agreement between autoantibody pairs was common for all combinations except IAA. These results suggest that ZnT8RWQA is a necessary complement to the classification and prediction of childhood type 1 diabetes as well as to randomize the subjects in the prevention and intervention of clinical trials.
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- Kanatsuna, N, et al.
(författare)
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Doubly reactive INS-IGF2 autoantibodies in children with newly diagnosed autoimmune (type 1) diabetes
- 2015
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Ingår i: Scandinavian Journal of Immunology. - : Wiley-Blackwell. - 0300-9475 .- 1365-3083. ; 82:4, s. 361-369
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Tidskriftsartikel (refereegranskat)abstract
- The splice variant INS-IGF2 entails the preproinsulin signal peptide, the insulin B-chain, eight amino acids of the C-peptide and 138 unique amino acids from an ORF in the IGF2 gene. The aim of this study was to determine whether levels of specific INS-IGF2 autoantibodies (INS-IGF2A) were related to age at diagnosis, islet autoantibodies, HLA-DQ or both, in patients and controls with newly diagnosed type 1 diabetes. Patients (n = 676), 0-18 years of age, diagnosed with type 1 diabetes in 1996-2005 and controls (n = 363) were analysed for specific INS-IGF2A after displacement with both cold insulin and INS-IGF2 to correct for non-specific binding and identify double reactive sera. GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, ZnT8QA and HLA-DQ genotypes were also determined. The median level of specific INS-IGF2A was higher in patients than in controls (P < 0.001). Irrespective of age at diagnosis, 19% (126/676) of the patients had INS-IGF2A when the cut-off was the 95th percentile of the controls (P < 0.001). The risk of INS-IGF2A was increased among HLA-DQ2/8 (OR = 1.509; 95th CI 1.011, 2.252; P = 0.045) but not in 2/2, 2/X, 8/8, 8/X or X/X (X is neither 2 nor 8) patients. The association with HLA-DQ2/8 suggests that this autoantigen may be presented on HLA-DQ trans-heterodimers, rather than cis-heterodimers. Autoantibodies reactive with both insulin and INS-IGF2A at diagnosis support the notion that INS-IGF2 autoimmunity contributes to type 1 diabetes.
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- Bernhardsson, Susanne, 1958, et al.
(författare)
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Digital physiotherapy assessment vs conventional face-to-face physiotherapy assessment of patients with musculoskeletal disorders: A systematic review.
- 2023
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Ingår i: PloS One. - : Public Library of Science (PLoS). - 1932-6203. ; 18:3
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Forskningsöversikt (refereegranskat)abstract
- This systematic review aimed to assess the certainty of evidence for digital versus conventional, face-to-face physiotherapy assessment of musculoskeletal disorders, concerning validity, reliability, feasibility, patient satisfaction, physiotherapist satisfaction, adverse events, clinical management, and cost-effectiveness.Eligibility criteria: Original studies comparing digital physiotherapy assessment with face-to-face physiotherapy assessment of musculoskeletal disorders. Systematic database searches were performed in May 2021, and updated in May 2022, in Medline, Cochrane Library, Cinahl, AMED, and PEDro. Risk of bias and applicability of the included studies were appraised using the Quality Assessment of Diagnostic Accuracy Studies-2 tool and the Quality Appraisal of Reliability Studies tool. Included studies were synthesised narratively. Certainty of evidence was evaluated for each assessment component using GRADE.Ten repeated-measures studies were included, involving 193 participants aged 23-62 years. Reported validity of digital physiotherapy assessment ranged from moderate/acceptable to almost perfect/excellent for clinical tests, range of motion, patient-reported outcome measures (PROMs), pain, neck posture, and management decisions. Reported validity for assessing spinal posture varied and was for clinical observations unacceptably low. Reported validity and reliability for digital diagnosis ranged from moderate to almost perfect for exact+similar agreement, but was considerably lower when constrained to exact agreement. Reported reliability was excellent for digital assessment of clinical tests, range of motion, pain, neck posture, and PROMs. Certainty of evidence varied from very low to high, with PROMs and pain assessment obtaining the highest certainty. Patients were satisfied with their digital assessment, but did not perceive it as good as face-to-face assessment.Evidence ranging from very low to high certainty suggests that validity and reliability of digital physiotherapy assessments are acceptable to excellent for several assessment components. Digital physiotherapy assessment may be a viable alternative to face-to-face assessment for patients who are likely to benefit from the accessibility and convenience of remote access.The review was registered in the PROSPERO database, CRD42021277624.
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- Lindmark, Ulrika, 1965-, et al.
(författare)
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Health-promoting factors in higher education for a sustainable working life : protocol for a multicenter longitudinal study
- 2020
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Ingår i: BMC Public Health. - London : BioMed Central. - 1471-2458. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The World Health Organization has highlighted the importance of health promotion for health service providers in order to ensure sustainable working life for individuals involved in providing health services. Such sustainability begins when students are preparing to manage their own future health and welfare in working life. It has been suggested that universities, employees and trainee health professionals should adopt or follow a salutogenic approach that not only complements the providing of information on known health risks but also favors health promotion strategies. This paper describes the study design and data collection methods in a planned study aiming to explore health-promoting factors for a sustainable working life among students in higher education within healthcare and social work. METHODS: This protocol describes a multicenter longitudinal study involving Swedish students on higher education programs in the healthcare and social work sectors. In 2018, the study invited students on seven education programs at six universities to participate. These programs were for qualification as: biomedical laboratory scientists (n = 121); dental hygienists (n = 87); nurses (n = 1411); occupational therapists (n = 111); physiotherapists (n = 48); radiographers (n = 60); and, social workers (n = 443). In total, 2283 students were invited to participate. Participants completed a baseline, a self-reported questionnaire including six validated instruments measuring health-promoting factors and processes. There are to be five follow-up questionnaires. Three while the students are studying, one a year after graduating, and one three years after graduating. Each questionnaire captures different health-promoting dimensions, namely: health-promoting resources (i.e. sense of coherence); occupational balance; emotional intelligence; health and welfare; social interaction; and work and workplace experiences/perceptions. DISCUSSION: This study focuses on the vastly important aspect of promoting a sustainable working life for healthcare and social work employees. In contrast to previous studies in this area, the present study uses different, validated instruments in health promotion, taking a salutogenic approach. It is hoped that, by stimulating the implementation of new strategies, the study's findings will lead to education programs that prepare students better for a sustainable working life in healthcare and social work.
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- Andersson, Cecilia K, et al.
(författare)
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The three ZNT8 autoantibody variants together improve the diagnostic sensitivity of childhood and adolescent type 1 diabetes.
- 2011
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Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 44, s. 394-405
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Tidskriftsartikel (refereegranskat)abstract
- Aims: We tested whether autoantibodies to all three ZnT8RWQ variants, GAD65, insulinoma-associated protein 2 (IA-2), insulin and autoantibodies to islet cell cytoplasm (ICA) in combination with human leukocyte antigen (HLA) would improve the diagnostic sensitivity of childhood type 1 diabetes by detecting the children who otherwise would have been autoantibody-negative. Methods: A total of 686 patients diagnosed in 1996-2005 in Skåne were analyzed for all the seven autoantibodies [arginin 325 zinc transporter 8 autoantibody (ZnT8RA), tryptophan 325 zinc transporter 8 autoantibody (ZnT8WA), glutamine 325 Zinc transporter 8 autoantibody (ZnT8QA), autoantibodies to glutamic acid decarboxylase (GADA), Autoantibodies to islet-antigen-2 (IA-2A), insulin autoantibodies (IAA) and ICA] in addition to HLA-DQ genotypes. Results: Zinc transporter 8 autoantibody to either one or all three amino acid variants at position 325 (ZnT8RWQA) was found in 65% (449/686) of the patients. The frequency was independent of age at diagnosis. The ZnT8RWQA reduced the frequency of autoantibody-negative patients from 7.5 to 5.4%-a reduction by 28%. Only 2 of 108 (2%) patients who are below 5 years of age had no autoantibody at diagnosis. Diagnosis without any islet autoantibody increased with increasing age at onset. DQA1-B1(*)X-0604 was associated with both ZnT8RA (p = 0.002) and ZnT8WA (p = 0.01) but not with ZnT8QA (p = 0.07). Kappa agreement analysis showed moderate (>0.40) to fair (>0.20) agreement between pairs of autoantibodies for all combinations of GADA, IA-2A, ZnT8RWQA and ICA but only slight ( < 0.19) agreement for any combination with IAA. Conclusions: This study revealed that (1) the ZnT8RWQA was common, independent of age; (2) multiple autoantibodies were common among the young; (3) DQA1-B1(*)X-0604 increased the risk for ZnT8RA and ZnT8WA; (4) agreement between autoantibody pairs was common for all combinations except IAA. These results suggest that ZnT8RWQA is a necessary complement to the classification and prediction of childhood type 1 diabetes as well as to randomize the subjects in the prevention and intervention of clinical trials.
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- Bornhoft, Lena, et al.
(författare)
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Monitoring handgrip strength to motivate lifestyle choices for patients with diabetes type 2-a pragmatic randomised controlled trial
- 2024
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Ingår i: SCANDINAVIAN JOURNAL OF PRIMARY HEALTH CARE. - 0281-3432 .- 1502-7724.
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Tidskriftsartikel (refereegranskat)abstract
- Physical strength can be an important parameter to monitor for patients with diabetes mellitus type 2 (T2DM) to promote healthy lifestyle choices. Functional measurements can contribute to healthcare advice and possibly motivate more active lifestyles. The aim of the study was to investigate whether adding measurement and feedback concerning handgrip strength (HGS) to the parameters measured for patients with T2DM at annual check-ups leads to change in physical activity (PA) level, HGS, HbA1c or waist circumference.MethodsMeasurement of HGS with Jamar dynamometers was added to annual check-ups for patients with T2DM by diabetes nurses in primary care with feedback about normal values for age and sex in the intervention group. The control group had standard check-ups. Change in self-reported PA level was measured with questionnaires.ResultsSeven clinics and 334 patients participated. The intervention led to similar effects on PA in both groups. Patients with T2DM had comparable HGS to the general public. Regression analyses showed statistically significantly higher HGS in the intervention group than in the control group at follow-up and no improvement in PA, HbA1c, or waist circumference. Increased HGS was found for older people, men, and people with normal-to-high inclusion HGS, while patients with low inclusion HGS reduced their strength levels.ConclusionsMeasuring HGS and giving feedback to patients with T2DM can lead to increased HGS but does not seem to affect general PA level, HbA1c, or waist circumference. People over 65 years, men, and people with normal-to-high HGS were influenced positively by the intervention. Patients with low HGS may need personalised support to increase physical activity and improve function.ClinicalTrials registration: NCT03693521ConclusionsMeasuring HGS and giving feedback to patients with T2DM can lead to increased HGS but does not seem to affect general PA level, HbA1c, or waist circumference. People over 65 years, men, and people with normal-to-high HGS were influenced positively by the intervention. Patients with low HGS may need personalised support to increase physical activity and improve function.
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- Bornhöft, Lena, et al.
(författare)
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Development and feasibility of a function-based preventive intervention for lifestyle-related disorders
- 2024
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Ingår i: BMC PUBLIC HEALTH. - 1471-2458. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe enormous effect of lifestyle-related disorders on health of the global population warrants the development of preventive interventions. Focusing on musculoskeletal health and physical activity may be a way to encourage necessary lifestyle changes by making them more concrete and understandable. The aims of the current study were to develop a function-based preventive intervention aimed at lifestyle-related disorders in physically inactive 40-year-old people and to investigate the feasibility of the intervention. The feasibility study aimed to solve practical and logistical challenges and to develop the intervention based on the experiences of participants and involved clinical personnel according to defined criteria.MethodsDevelopment of the standardised functional examination was based on literature-validated tests and clinical reasoning. Development of a risk profile was based on the functional examination and similar profiles which have already proved feasible. The feasibility of the functional examination and risk profile, together with function-based lifestyle counselling was tested on 27 participants in a pilot study with two physiotherapist examinations over a four-month period. Practical results and feedback from participants and collaborating personnel were examined.ResultsThe functional examination consists of 20 established tests not requiring specialised equipment or training which were deemed relevant for a middle-aged population and a sub-maximal ergometer test. The risk profile consists of seven functional dimensions: cardiovascular fitness, strength in upper extremity, lower extremity and trunk, mobility, balance and posture, and three non-functional dimensions: weight, self-assessed physical activity and pain. Each dimension contains at least two measures. The participants appreciated the intervention and found it motivating for making lifestyle changes. They found the tests and risk profile understandable and could see them as tools to help achieve concrete goals. The examination required 60-75 min for one physiotherapist. The recruitment rate was low and recruited participants were highly motivated to making lifestyle changes.ConclusionThis project developed a functional test battery and risk profile aimed at inactive 40-year-olds which fulfilled our feasibility criteria. Functional screening and lifestyle counselling were found to be of value to a sub-group of inactive 40-year-olds who were already motivated to improve their health situations.
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