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- Jester, S., et al.
(författare)
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Haploidentical stem cell transplantation in two children with mucopolysaccharidosis VI: clinical and biochemical outcome
- 2013
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Ingår i: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 8:134
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mucopolysaccharidosis VI (MPS VI) is an autosomal recessive progressive multiorgan disorder due to mutation in the gene encoding the enzyme Arylsulfatase B (ARSB). Dysfunctional ARSB causes lysosomal accumulation of glycosaminoglycans (GAG). Currently, enzyme replacement therapy (ERT) is preferred to hematopoietic stem cell transplantation (SCT) due to the treatment-related risks of the latter. However, ERT constitutes an expensive life-long treatment. Increased experience and safety of SCT-procedures in recent years suggest that SCT should be further explored as a treatment option. This is the first report on haploidentical SCT in patients with MPS VI. The primary objective was to assess the treatment safety and clinical and biochemical outcome. Patients and methods: Two siblings diagnosed with MPS VI at 10 months of age and at birth with genotype p. C192R, reported as mild to intermediate phenotype, underwent unrelated umbilical cord blood transplantation pre-symptomatic. Due to graft failure, both patients were urgently re-transplantated with haploidentical SCT with the father as donor. Continuous clinical and biochemical status was monitored and concluded 3.8 and 4.6 years after the haploidentical SCT. Results: Haploidentical SCT resulted in prompt and sustained engraftment. Complete donor chimerism was achieved in both patients, apart from mixed B cells chimerism in patient 2. ARSB activity in leukocytes post transplant increased from 0.0 to 19.0 mu kat/kg protein (patient 1) and from 3.6 to 17.9 mu kat/kg protein (patient 2) (ref. 17-40). Total urinary GAG normalized in both patients, although patient 2's values slightly exceed normal range since 6 months. However, dermatan sulfaturia was substantially normalized since 16 months and 12 months post-SCT, respectively. Height was -1.85 SD and -1.27 SD at follow-up. Patient 1 had impaired visual acuity and discrete hepatomegaly. Patient 2 had elevated intraocular pressure and X-ray revealed steep acetabular angles and slightly flattened lumbar vertebrae. Conclusion: This study demonstrates that young children with MPS VI tolerate haploidentical SCT. Normalization of enzyme production and dermatan sulfaturia indicates correction of the inborn error of metabolism and coincide with no obvious symptoms of progressive MPS VI up to 4.6 years post-SCT.
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| 5. |
- Persson, F., et al.
(författare)
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The risk of symptomatic knee osteoarthritis after arthroscopic meniscus repair vs partial meniscectomy vs the general population
- 2018
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 26:2, s. 195-201
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare consultation rate for knee osteoarthritis (OA) after meniscus repair, arthroscopic partial meniscectomy (APM), and in general population, respectively. Method: We identified patients aged 16-45 years having had meniscus surgery due to traumatic meniscus tear in 1998-2010 in southern Sweden by a healthcare register. Patients were followed from surgery until a diagnosis of knee OA, relocation, death, or December 31st, 2015. We studied the consultation rate for knee OA compared to the general population. Results: We identified 2,487 patients diagnosed with traumatic meniscus tear (mean [SD] age 30.5 [8.6] years); 229 (9.2%) of them had had meniscus repair. The absolute risk of having consulted for knee OA during the study was 17% after APM, 10.0% after meniscus repair, and 2.3% in the general population. Hazard ratio (HR) (95% confidence interval (CI)) for knee OA after repair vs APM was: 0.74 (0.48, 1.15). Excluding cases with OA within 2 years post-surgery, yielded the HR of 0.51 (0.27, 0.96). The consultation rate for knee OA standardized to the general population was then 42 per 10,000 person-years (95% CI 12, 71) in the meniscus repair group, 118 per 10,000 person-years (95% CI 101, 135) after APM, and 20 per 10,000 person-years (95% CI 19.9, 20.1) in the general population. Conclusion: The point estimates suggests about 25-50% lower risk of consultation for knee OA after meniscus repair as compared to APM. However, the consultation rate for knee OA after repair was still at least two times higher as compared to the general population.
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| 6. |
- Svensson, F., et al.
(författare)
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Scrutinizing the cut-off for “pathological” meniscal body extrusion on knee MRI
- 2019
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 29:5, s. 2616-2623
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Medial meniscal body extrusion ≥ 3 mm on MRI is often considered “pathologic.” The aims of this study were to (1) assess the adequacy of 3 mm as cut-off for “pathological” extrusion and (2) find an optimal cut-off for meniscal extrusion cross-sectionally associated with radiographic knee osteoarthritis, bone marrow lesions (BMLs), and cartilage damage. Methods: Nine hundred fifty-eight persons, aged 50–90 years from Framingham, MA, USA, had readable 1.5 T MRI scans of the right knee for meniscal body extrusion (measured in mm). BMLs and cartilage damage were read using the whole organ magnetic resonance imaging score (WORMS). Knee X-rays were read according to the Kellgren and Lawrence (KL) scale. We evaluated the performance of the 3-mm cut-off with respect to the three outcomes and estimated a new cut-off maximizing the sum of sensitivity and specificity. Results: The study persons had mean age of 62.2 years, 57.0% were women and the mean body mass index was 28.5 kg/m2. Knees with radiographic osteoarthritis, BMLs, and cartilage damage had overall more meniscal extrusion than knees without. The 3-mm cut-off had moderate sensitivity and low specificity for all three outcomes (sensitivity between 0.68 [95% CI 0.63–0.73] and 0.81 [0.73–0.87], specificity between 0.49 [0.45–0.52] and 0.54 [0.49–0.58]). Using 4 mm maximized the sum of sensitivity and specificity and improved the percentage of correctly classified subjects (from between 54 and 61% to between 64 and 79%). Conclusions: The 4-mm cut-off may be used as an alternative cut-off for denoting pathological meniscal extrusion. Key Points: • Medial meniscal body extrusion is strongly associated with osteoarthritis. • The 3-mm cut-off for medial meniscal body extrusion has high sensitivity but low specificity with respect to bone marrow lesions, cartilage damage, and radiographic osteoarthritis. • The 4-mm cut-off maximizes the sensitivity and specificity with respect to all three osteoarthritis features.
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| 7. |
- Thorlund, J. B., et al.
(författare)
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Inappropriate opioid dispensing in patients with knee and hip osteoarthritis : a population-based cohort study
- 2020
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 28:2, s. 146-153
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To estimate inappropriate opioid dispensing in patients with knee or hip osteoarthritis (OA) defined as (1) dispensing of opioids within the first year of diagnosis or (2) long-term opioid use. Design: Data from Skåne Healthcare Register was linked with the Swedish Prescribed Drug Register. Incidence proportion of dispensed opioids within first year of incident knee or hip OA diagnosis was determined in knee (n = 399,670) and hip (413,216) OA cohorts without a history of OA. The 1-year period prevalence of long-term opioid dispensing was determined in a prevalence cohort (n = 48,574 with knee and/or hip OA and n = 457,587 without OA). The proportion of OA patients with excess opioid dispensing attributable to OA was estimated using inverse probability weighted regression adjustment. Results: In the incident cohorts, 5866 and 2359 developed knee and hip OA, respectively. Within the first year after OA diagnosis 14.7% patients with knee OA and 20.7% with hip OA had an opioid dispensed. The estimated inappropriate dispensing attributable to OA was 7.4% (95% CI 6.5–8.4) for knee OA and 12.8% (95% CI 11.1–14.4) for hip OA. Among persons with prevalent knee, hip or knee and hip OA inappropriate, long-term opioid use attributable to OA was 1.3%, 2.0% and 2.4% of, respectively. Conclusions: More than half the incident opioid dispensations to patients within their first year after knee or hip OA diagnosis are inappropriate according to current treatment guidelines. Furthermore, 2% of patients with prevalent knee or hip OA have inappropriate long-term dispensing of opioids.
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| 8. |
- Thorlund, J. B., et al.
(författare)
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Opioid use in knee or hip osteoarthritis : a region-wide population-based cohort study
- 2019
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 27:6, s. 871-877
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To quantify opioid use in knee and hip osteoarthritis (OA) patients, and to estimate the proportion of opioids in the population attributable to OA patients. Design: Population-based cohort study. Methods: We included 751,579 residents in southern Sweden, aged ≥35 years in 2015. Doctor-diagnosed knee or hip OA between 1998 and 2015 was the exposure. Dispensed weak and strong opioids were identified between November 2013 and October 2015 from the Swedish Prescribed Drug Register (SPDR). We determined age- and sex-standardized 12-month period prevalence of opioid use from November 2014 until October 2015 and calculated prevalence ratios and incidence rate ratios adjusted for age, sex, and other socio-demographic variables. We estimated the population attributable fraction (PAF) of incident opioid use attributable to OA patients. Results: The 12-month prevalence of opioid use among OA patients was 23.7% [95% confidence intervals (CI) 23.3–24.2], which was two-fold higher compared to individuals without knee or hip OA: prevalence ratio: 2.1 [95% CI 2.1–2.1]. Similarly, OA patients were more likely to have an incident opioid dispensation, especially for strong opioids (incidence rate ratio: 2.6 [95% CI 2.5–2.7]). Population attributable tractions (PAF) of incident opioid use attributable to OA patients was 12%, 9% for weak and 17% for strong opioids. Conclusions: Every fourth patient with knee or hip OA has opioids dispensed over a 1-year period, and 12% of incident opioid dispensations are attributable to OA and/or its related comorbidities. These results highlight that patients with knee and hip OA constitute a group of patients with an alarmingly high use of opioids.
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