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| 2. |
- Albertsson-Wikland, Kerstin, et al.
(författare)
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Mortality Is Not Increased in Recombinant Human Growth Hormone-treated Patients When Adjusting for Birth Characteristics
- 2016
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : ENDOCRINE SOC. - 0021-972X .- 1945-7197. ; 101:5, s. 2149-2159
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aimed to investigate whether reported high mortality in childhood recombinant human GH (rhGH)-treated patients was related to birth-characteristics and/or rhGH treatment. Design and Setting: We sought to develop a mortality model of the Swedish general population born between 1973 and 2010, using continuous-hazard functions adjusting for birth characteristics, sex, age intervals, and calendar year to estimate standardized mortality ratio (SMR) and to apply this model to assess expected deaths in Swedish rhGH-treated patients with idiopathic isolated GH deficiency (IGHD), idiopathic short stature (155) or born small for gestational age (SGA). Participants:The general population: Swedish Medical Birth Register (1973-2010: 1 880 668 males; 1 781 131 females) and Cause of Death Register (1985-2010). Intervention Population: Three thousand eight hundred forty-seven patients starting rhGH treatment between 1985 and 2010 and followed in the National GH Register and/or in rhGH trials diagnosed with IGHD (n = 1890), ISS (n = 975), or SGA (n=982). Main Outcome Measures: Death. Results: Using conventional models adjusting for age, sex, and calendar-year, the SMR was 1.43 (95% confidence interval, 0.89-2.19), P = .14, observed/expected deaths 21/14.68. The rhGH population differed (P amp;lt; .001) from the general population regarding birth weight, birth length, and congenital malformations. Application of an Advanced Model: When applying the developed mortality model of the general population, the ratio of observed/expected deaths in rhGH-treated patients was 21/21.99; SMR = 0.955 (0.591-1.456)P = .95. Model Comparison: Expected number of deaths were 14.68 (14.35-14.96) using the conventional model, and 21.99 (21.24-22.81) using the advanced model, P amp;lt; .001, which had at all ages a higher gradient of risk per SD of the model, 24% (range, 18-42%; P amp;lt; .001). Conclusions: Compared with the general Swedish population, the ratio of observed/expected deaths (21/21.99) was not increased in childhood rhGH-treated IGHD, ISS, and SGA patients when applying an advanced sex-specific mortality model adjusting for birth characteristics.
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| 3. |
- Borgström, F, et al.
(författare)
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The cost-effectiveness of risedronate in the UK for the management of osteoporosis using the FRAX(R).
- 2009
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965.
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Tidskriftsartikel (refereegranskat)abstract
- The study estimated the cost-effectiveness of risedronate compared to no treatment in UK women using the FRAX algorithm for fracture risk assessment. A Markov cohort model was used to estimate the cost-effectiveness. Risedronate was found cost-effective from the age of 65 years, assuming a willingness to pay for a QALY of pound30,000. INTRODUCTION: The aim of this study was to assess the cost-effectiveness of risedronate for the prevention and treatment in a UK setting using the FRAX(R) algorithm for fracture risk assessment. A further aim was to establish intervention thresholds with risedronate treatment. METHODS: The cost-effectiveness of risedronate was compared to no treatment in post-menopausal women with clinical risk factors for fracture using a Markov cohort model populated with data relevant for the UK. The model incorporated the features of FRAX(R) (the WHO risk assessment tool). The analysis had a health care perspective and quality adjusted life years was used as the main outcome measure. RESULTS: Treatment was cost-effective from the age of 65 years, assuming a willingness to pay for a QALY of pound30,000. Treatment was also cost-effective at all ages in women who had previously sustained a fragility fracture or in women with a parental history of hip fracture with a bone mineral density set at the threshold of osteoporosis. At the pound30,000 threshold value for a QALY, risedronate was on average found to cost-effective below the 10-year probability of a major osteoporotic fractures of 13.0%. CONCLUSIONS: Risedronate is a cost-effective agent for the treatment of established osteoporosis (osteoporosis and a prior fragility fracture) in women from the age of 50 years and older and above 65 years in women with osteoporosis alone. The results support the treatment recommendations in recent UK guidelines for osteoporosis.
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| 4. |
- Borgström, F, et al.
(författare)
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The cost-effectiveness of strontium ranelate in the UK for the management of osteoporosis.
- 2010
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 21:2, s. 339-49
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Tidskriftsartikel (refereegranskat)abstract
- The cost-effectiveness of strontium ranelate was compared to no treatment in UK women using the FRAX algorithm for fracture risk assessment. At a willingness-to-pay of pound 30,000 per quality-adjusted life-year (QALY), strontium ranelate was generally cost-effective in women with prior fracture at the threshold of osteoporosis from an age of 65 years. INTRODUCTION: The objectives of the study were to estimate the cost-effectiveness of strontium ranelate in the UK for the treatment of osteoporosis and to establish intervention thresholds for treatment using the FRAX tool. METHODS: The cost-effectiveness of strontium ranelate was compared to no treatment in postmenopausal women with clinical risk factors for fracture using a lifetime simulation model based on Markov cohort methodology that incorporated the features of FRAX. RESULTS: At a threshold of pound 30,000 per QALY, strontium ranelate was generally cost-effective in women from an age of 65 years with prior fracture at the threshold of osteoporosis (i.e., a T-score of -2.5 SD) and in women with a prior fracture (and no information on bone mineral density) from the age of 65 years. At a threshold of pound 20,000, strontium ranelate became cost-effective at a 10-year fracture probability of 25.7% and at 16.9% with a threshold of pound 30,000 for a QALY. CONCLUSIONS: Strontium ranelate is a cost-effective agent for the treatment of established osteoporosis in women over the age of 65 years. Cost-effective scenarios were also found for the prevention and treatment of fractures associated with osteoporosis, in younger women with additional clinical risk factors.
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| 5. |
- Eberhardson, Michael, et al.
(författare)
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Randomised, Double-blind, Placebo-controlled Trial of CCR9-targeted Leukapheresis Treatment of Ulcerative Colitis Patients.
- 2017
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Ingår i: Journal of Crohn's & colitis. - : Oxford University Press (OUP). - 1876-4479 .- 1873-9946. ; 11:5, s. 534-542
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Tidskriftsartikel (refereegranskat)abstract
- Ulcerative colitis patients display increased numbers of circulating pro-inflammatory monocyte human leukocyte antigen-DR [HLA-DRhi] monocytes expressing high levels of the gut-homing C-C chemokine receptor 9 [CCR9] and tumour necrosis factor [TNF]-α. The aim of this first-in-human, double-blind, randomised, placebo-controlled trial was to evaluate selective removal of circulating CCR9-expressing monocytes by leukapheresis in patients with moderate to severe ulcerative colitis, with regards to safety, tolerability, and immunological response.Patients with ulcerative colitis were treated every second day with leukapheresis during five sessions with a C-C chemokine ligand 25 [CCL25; CCR9 ligand] column or a placebo column.No major safety concerns were raised and the procedure was well tolerated. Pro-inflammatory HLA-DRhi cells decreased significantly in the active treatment group [p = 0.0391] whereas no statistically significant change was seen in the placebo group [p = 0.4688]. There was a significant decrease of HLA-DRhi monocytes in the active group compared with the placebo group when corrected for the imbalance in weight between the groups [p = 0.0105]. Mayo score decreased in the active group [p = 0.0156] whereas the change in the placebo group was not significant [p = 0.1250]. Mayo score ≤ 3 was observed in five out of 14 patients [35.7%] in the active group compared with one out of eight [12.5%] receiving placebo. The number of responders in the active treatment group was eight out of 14 patients [57.1%], whereas in the corresponding placebo group three out of eight patients [37.5%] responded to placebo. A dose-response correlation was observed between the blood volume processed and clinical outcome.This clinical induction trial using CCL25-tailored leukapheresis demonstrates a safe and effective removal of activated monocytes with a clinical effect in patients with ulcerative colitis.
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| 6. |
- Gjertsson, Peter, 1961, et al.
(författare)
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Diagnostic and referral delay in patients with aortic stenosis is common and negatively affects outcome
- 2007
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Ingår i: Scand Cardiovasc J. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 41:1, s. 12-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Aortic stenosis (AS) patients are often severely symptomatic at the time of aortic valve replacement (AVR). We wanted to investigate doctors' delay and its impact on outcome. DESIGN: AS patients undergoing AVR (n = 422) were included. Clinical and echocardiographic data at the time of diagnosis and preoperatively were noted. The risk of death after AVR was estimated using Poisson regression, incorporating age, gender, coronary artery disease, NYHA III/IV and time on the waiting list for AVR. RESULTS: The age (mean+/-SD) was 71+/-8.6 years, 45% were women, and 48% were in NYHA III/IV. 55% underwent AVR within one year of diagnosis, indicating late diagnosis. The time from referral to AVR (median, range) was 112 (1-803) days. NYHA III/IV independently predicted mortality (hazard ratio 1.76, 95% CI 1.28-2.43, p = 0.0005). The time from referral to AVR influenced the risk of death immediately after operation (p = 0.0083). CONCLUSION: Late diagnosis and late referral for AVR are common, and negatively influence outcome in patients with AS. Delay in surgery after referral increase the mortality immediately after AVR.
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| 7. |
- Jedel, Elizabeth, 1962, et al.
(författare)
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Impact of electroacupuncture and exercise on hyperandrogenism and oligo/amenorrhoea in women with polycystic ovary syndrome: A randomized controlled trial.
- 2011
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Ingår i: American Journal of Physiology - Endocrinology and Metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 300:1, s. E37-45
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Tidskriftsartikel (refereegranskat)abstract
- Background: Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenism, oligo/amenorrhea, and polycystic ovaries. We aimed to determine whether low-frequency electro-acupuncture (EA) decreases hyperandrogenism and improves oligo/amenorrhea more effectively than physical exercise or no intervention. Methods: We randomized 84 women with PCOS, aged 18-37 years, to 16 weeks of low-frequency EA, physical exercise, or no intervention. The primary outcome measure-changes in the concentration of total testosterone (T) at week 16 determined by gas and liquid chromatography/mass spectrometry-was analyzed by intention-to treat. Secondary outcome measures were changes in menstrual frequency; concentrations of androgens, estrogens, androgen precursors, glucuronidated androgen metabolites; and acne and hirsutism. Outcomes were assessed at baseline, after 16 weeks of intervention, and after a 16-week follow-up. Results: After 16 weeks of intervention, circulating T decreased by -25%, androsterone glucuronide by -30%, and androstane-3α, 17β-diol-3glucuronide by -28% in the EA group (P=0.038, 0.030, and 0.047, respectively vs. exercise); menstrual frequency increased to 0.69/month from 0.28 at baseline in the EA group (P=0.018 vs. exercise). After the 16-week follow-up, the acne score decreased by -32% in the EA group (P=0.006 vs. exercise). Both EA and exercise improved menstrual frequency and decreased the levels of several sex steroids at week 16 and at the 16-week follow-up, compared to no intervention. Conclusion/Significance: Low-frequency EA and physical exercise improved hyperandrogenism and menstrual frequency more effectively than no intervention in women with PCOS. Low-frequency EA was superior to physical exercise and may be useful for treating hyperandrogenism and oligo/amenorrhea.
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| 8. |
- Kanis, John A, et al.
(författare)
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Assessment of fracture risk.
- 2005
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Ingår i: Osteoporosis international. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 16:6, s. 581-9
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Tidskriftsartikel (refereegranskat)abstract
- The diagnosis of osteoporosis is based on the measurement of bone mineral density (BMD). There are a number of clinical risk factors that provide information on fracture risk over and above that given by BMD. The assessment of fracture risk thus needs to be distinguished from diagnosis to take account of the independent value of the clinical risk factors. These include age, a prior fragility fracture, a parental history of hip fracture, smoking, use of systemic corticosteroids, excess alcohol intake and rheumatoid arthritis. The independent contribution of these risk factors can be integrated by the calculation of fracture probability with or without the use of BMD. Treatment can then be offered to those identified to have a fracture probability greater than an intervention threshold.
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| 9. |
- Kanis, J A, et al.
(författare)
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Case finding for the management of osteoporosis with FRAX--assessment and intervention thresholds for the UK.
- 2008
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Ingår i: Osteoporosis international. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 19:10, s. 1395-408
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Tidskriftsartikel (refereegranskat)abstract
- SUMMARY: Assessment and intervention thresholds are developed and proposed in men aged over 50 years and postmenopausal women for the UK based on fracture probability from the WHO fracture risk assessment tool (FRAX). INTRODUCTION: The FRAX tool has recently become available to compute the 10-year probability of fractures in men and women from clinical risk factors (CRFs) with or without the measurement of femoral neck bone mineral density (BMD). The aim of this study was to develop a case-finding strategy for men and women from the UK at high risk of osteoporotic fracture by delineating the fracture probabilities at which BMD testing or intervention should be recommended. METHODS: Fracture probabilities were computed using the FRAX tool calibrated to the epidemiology of fracture and death in the UK. The relationship between cost effectiveness and fracture probability used the source data from a prior publication that examined the cost effectiveness of generic alendronate in the UK. An intervention threshold was set by age in men and women, based on the fracture probability equivalent to that of women with a history of a prior osteoporosis related fracture. In addition, assessment thresholds for the use of BMD testing were explored. Assessment thresholds for the measurement of BMD followed current practice guidelines where individuals were considered to be eligible for assessment in the presence of one or more CRF. An upper assessment threshold (i.e. a fracture probability above which patients could be treated without recourse to BMD) was based on optimisation of the positive predictive value of the assessment tool. The consequences of assessment and intervention thresholds on the requirement for BMD test and interventions were assessed using the distribution of clinical risk factors and femoral neck BMD for women in the source cohorts used for the development of the FRAX models RESULTS: Treatment was cost effective at all ages when the 10-year probability of a major fracture exceeded 7%. The intervention threshold at the age of 50 years corresponded to a 10-year probability of a major osteoporotic fracture of 7.5%. This rose progressively with age to 30% at the age of 80 years, so that intervention was cost effective at all ages. Assessment thresholds for testing with BMD (6-9% at the age of 50 years) also rose with age (18-36% at the age of 80 years). The use of these thresholds in a case-finding strategy would identify 6-20% of women as eligible for BMD testing and 23-46% as eligible for treatment, depending on age. The same threshold can be used in men. CONCLUSION: The study provides a method of developing management algorithms for osteoporosis from the estimation of fracture probabilities, rather than those based on BMD alone or BMD with single or multiple CRFs.
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| 10. |
- Kanis, John A, et al.
(författare)
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FRAX and its applications to clinical practice
- 2009
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 44:5, s. 734-43
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of the WHO FRAX algorithms has facilitated the assessment of fracture risk on the basis of fracture probability. FRAX integrates the influence of several well validated risk factors for fracture with or without the use of BMD. Its use in fracture risk prediction poses challenges for patient assessment, the development of practice guidelines, the evaluation of drug efficacy and reimbursement, as well as for health economics which are the topics outlined in this review.
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