| 1. |
- Frisk, Pia, et al.
(author)
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Patients' experiences with generic substitution-a Swedish pharmacy survey
- 2010
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In: Pharmacy World & Science. - : Springer. - 0928-1231 .- 1573-739X. ; 32:5, s. 681-
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Journal article (other academic/artistic)abstract
- Background and objective Generic substitution for reimbursed drugs was introduced in Sweden 1 of October 2002. Concerns have been expressed that generic substitution may compromise patient safety. This study aimed to evaluate how Swedish drug consumers experience generic substitution, more than 5 year after implementation. Design Survey study with an electronic questionnaire, offered to 1551 pharmacy customers/patients presenting with a prescription on one of the 2688 drugs included. The selected drugs constituted 75% of the total volume of dispensed drugs subjected to generic substitution in August 2007.Setting Fifty-eight Swedish community pharmacies. Main outcome measures Positive experiences with generic substitution; problems and their degree of seriousness; and the reported incidence of medication errors. Consumers’ suggestions of improvements to the generic substitution system were also captured. Results Of 1551 respondents (602 male, 949 female), 35% (n = 536) reported one or more positive experiences, the most common being the lower drug price. Sixty percent (n= 932) claimed they had not experienced any problems. Forty percent reported at least one problem related to substitution. Seven percent (n=109) reported medication errors attributed to generic substitution. Twenty-two percent (n=342) of the respondents offered suggestions for improvement. The most common suggestions were to revise the criteria for assessing interchangeability between brand-name and generic alternatives and to abolish substitution.Conclusions A majority of respondents do not experience any problems related to generic substitution. A sizeable minority experience problems, partly resulting in medication errors. Over- and undermedication, lack of compliance, and intake of wrong drug or of both the original and the generic were the problems most often reported. Future system changes should consider the importance of revised criteria for generic and brand name interchangeability.
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| 2. |
- Frisk, Tony
(author)
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Molecular genetic studies of human thyroid tumors
- 2001
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Doctoral thesis (other academic/artistic)abstract
- Tumors of the thyroid gland are common among the general population, but only a small proportion is malignant. The vast majority of thyroid tumors are benign, so called follicular adenomas. Sometimes subtypes such as atypical adenomas and adenomas with oxyphil, i.e. Hurthle cell differentiation, are detected. In Sweden 400 malignant thyroid tumors are diagnosed each year, representing 1% of all cancers reported. Thyroid carcinomas are divided into four different variants: papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC), the latter being undifferentiated. In absence of clear signs of metastases or invasive growth, it is preoperatively impossible to separate benign from malignant follicular tumors. Therefore, virtually all patients with a follicular tumor are operated on. FTCs are generally sporadic tumors but can be found in patients with Cowden disease (CD), an inherited tumor syndrome characterized by multiple hamartomas and an increased risk of developing breast and thyroid cancer. PTEN is the disease gene for CD and is thereby also a candidate gene for the oncogenesis of sporadic FTC. To study the role of PTEN in sporadic FTC development, 95 benign and malignant thyroid tumors of different types were investigated by loss of heterozygosity (LOH) and by direct sequencing of PTEN (paper 1). Structural mutations of PTEN were found in I I cases only. As PTEN, despite the rare structural alterations, may be involved in thyroid tumorigenesis via other mechanisms, expression of PTEN was studied in 87 thyroid tumors by reverse transcriptase polymerase chain reaction (RT- PCR) and restriction enzyme cleavage (paper ll). Fourteen of the tumors showed reduced PTEN expression, but only few of these were differentiated tumors. In contrast, the ATCs had a significantly reduced expression. PTEN seems to be involved in the development of some thyroid tumors, and may contribute to the progression towards the undifferentiated ATC. To detect chromosomal regions potentially harboring tumor suppressor genes or oncogenes, comparative genomic hybridization (CGH) was used to screen 21 follicular tumors (paper 111). Chromosomal aberrations were detected equally often in the benign variants as in the malignant variants, indicating that there is no stepwise progression from adenomas to carcinomas. FTCs with Hurthle cell differentiation all had deletions of chromosome 9q13-21.3. This genomic region may thus harbor a tumor suppressor gene important for these tumors. MTC is sporadic in 75% of the cases. In the remaining ones, MTC is part of multiple endocrine neoplasia type 2 (MEN 2) and its variants. The RET proto-oncogene is the disease gene in the familial cases, but mutations of RET have also been detected in a proportion of sporadic MTCs. RET encodes for a receptor tyrosine kinase and several ligands are known to activate RET. By using mRNA in situ hybridization, the expression of RET and its ligand complexes were analyzed in 15 MTCs with or without the RET M918T mutation (paper IV). All MTCs showed expression of RET, and the majority also expressed the ligand complexes. The mRNA expression was verified by RT-PCR. A strong expression of the genes was seen in tumor cells adjacent to the stroma. in 7 MTCs, indicating that not only mutations, but also the expression level of RET and its ligand complexes are of importance in the development and progression of MTC. CGH was performed on 24 MTCs with or without the RET M918T mutation(paper V). MTC seems to be a genetically relatively stable tumor, with fewer alterations found in the tumors without the RET mutation. The tumors from patients who died from their MTC all showed a gain of chromosome 11cq12. In summary these studies show that although thyroid tumors are genetically relatively stable, specific genes and chromosomal regions are involved in their development and presumably also in their progression. This work emphasizes that the identification of such genetic alterations are crucial for the understanding of the variable clinical features of these tumors, and the need for a more individualized treatment.
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| 3. |
- Hansson, Tony, et al.
(author)
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Silent coeliac disease is over-represented in children with type 1 diabetes and their siblings
- 2015
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In: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 104:2, s. 185-191
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Journal article (peer-reviewed)abstract
- AimThis study measured autoantibodies against tissue transglutaminase (anti-tTG) to detect untreated coeliac disease in children with type 1 diabetes and their siblings. MethodsAnti-tTG was measured in prospectively collected sera from 169 children at the onset of diabetes, 88 of their siblings and 96 matched control children. Coeliac disease was confirmed with a small intestinal biopsy. ResultsCoeliac disease was diagnosed in five children before diabetes onset. A further 12 children were diagnosed after diabetes onset, without any gastrointestinal symptoms, and 11 of these had anti-tTG at the onset of diabetes, with the remaining child showing seroconversion within 6months. Hence, all the children with both diseases had anti-tTG at or before diabetes diagnosis, and the prevalence of coeliac disease was 10.1%. Moreover, 6.8% of the siblings and 3.1% of the control children had elevated levels of anti-tTG. None of the siblings reported any coeliac-related symptoms, despite being positive for anti-tTG, and coeliac disease has so far been biopsy confirmed in 4.5%. ConclusionSilent coeliac disease is over-represented in children with type 1 diabetes and their siblings. All diabetes children and their siblings should be tested and followed for the presence of anti-tTG and coeliac disease.
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| 4. |
- Jarvis, Kirsten B., et al.
(author)
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Asymptomatic Right Atrial Thrombosis After Acute Lymphoblastic Leukemia Treatment
- 2021
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In: Journal of pediatric hematology/oncology (Print). - : Lippincott Williams & Wilkins. - 1077-4114 .- 1536-3678. ; 43:4, s. E564-E566
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Journal article (peer-reviewed)abstract
- Right atrial thrombosis is a rare, but potentially serious complication of acute lymphoblastic leukemia treatment. We conducted a retrospective multicenter study to assess the incidence, treatment, and outcome of asymptomatic right atrial thrombosis detected at routine echocardiography of children after acute lymphoblastic leukemia treatment in the Nordic and Baltic countries. Eleven (2.7%, 95% confidence interval, 1.4-4.9) of 406 patients had asymptomatic right atrial thrombosis, ranging from 10 to 25 mm at detection. Three patients were treated with anticoagulation. None of the thromboses affected cardiac function, and they showed neither sign of progress nor spontaneous or treatment-related regress at follow-up.
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| 5. |
- Majeed, Ammar, et al.
(author)
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Management of rivaroxaban- or apixaban-associated major bleeding with prothrombin complex concentrates : a cohort study
- 2017
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In: Blood. - : AMER SOC HEMATOLOGY. - 0006-4971 .- 1528-0020. ; 130:15, s. 1706-1712
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Journal article (peer-reviewed)abstract
- There is uncertainty regarding the effectiveness and occurrence of thromboembolic events in patients treated with prothrombin complex concentrates (PCCs) for the management of major bleeding events (MBEs) onrivaroxabanor apixaban. We investigated the effectiveness of PCCs given for the management of MBEs in patients on rivaroxaban or apixaban. Between 1 January 2014 and 1 October 2016, we prospectively included patients on rivaroxaban or apixaban treated with PCCs for the management of MBEs. The effectiveness of PCCs was assessed by using the International Society of Thrombosis and Hemostasis Scientific and Standardization Subcommittee criteria for the assessment of the effectiveness of major bleeding management. The safety outcomes were thromboembolic events and all-cause mortality with in 30 days after treatmentwith PCCs. Atotal of 84 patients received PCCs for the reversal of rivaroxaban or apixaban due to a MBE. PCCs were given at amedian (interquartile range) dose of 2000 IU (1500-2000 IU). Intracranial hemorrhage (ICH) was themost common site of bleeding requiring reversal (n = 5 59; 70.2%), followed by gastrointestinal bleeding in 13 (15.5%) patients. Management with PCCs was assessed as effective in 58 (69.1%) patients and ineffective in 26 (30.9%) patients. Most patients with ineffective hemostasis with PCCs had ICH (n 5 16; 61.5%). Two patients developed an ischemic stroke, occurring 5 and 10 days after treatment with PCC. Twenty seven (32%) patients died within 30 days after a MBE. The administration of PCCs for the management of MBEs associated with rivaroxaban or apixaban is effective inmost cases and is associated with a low risk of thromboembolism. Our findings are limited by the absence of a control group in the study.
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| 6. |
- Måseide, Ragnhild J., et al.
(author)
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Haemophilia early arthropathy detection with ultrasound and haemophilia joint health score in the moderate haemophilia (MoHem) study
- 2021
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In: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 27:2
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Journal article (peer-reviewed)abstract
- Introduction: Detection of early arthropathy is crucial for the management of haemophilia, but data on moderate haemophilia are limited. Therefore, we evaluated joint health and treatment modalities in Nordic patients with moderate haemophilia A (MHA) and B (MHB). Aim: To explore and compare the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) and Haemophilia Joint Health Score (HJHS) to detect early arthropathy in moderate haemophilia. Methods: A cross-sectional, multicentre study covering Nordic patients with MHA and MHB. Arthropathy was evaluated by HEAD-US and HJHS 2.1. Results: We assessed 693 joints in 118 patients. HEAD-US scores (medians [interquartile ranges]) were as follows: elbows 0 points (0–0), knees 0 (0–0) and ankles 0 (0–1). Respectively, by HJHS: elbows 0 (0–1), knees 0 (0–1) and ankles 0 (0–1). Cartilage (14%) and bone (13%) were most commonly affected by HEAD-US. Frequent HJHS findings were crepitus on motion in knees (39%), and loss of flexion (23%) and extension (13%) in ankles. HEAD-US correlated strongly with HJHS (elbows r =.70, knees r =.60 and ankles r =.65), but 24% had discordant scores. Joints with HJHS zero points, 5% captured HEAD-US ≥1 point. Moreover, 26% had HJHS findings without HEAD-US pathology. Notably, 31% of knees had crepitus on motion and normal HEAD-US. Conclusion: Overall, the joints attained low scores implying good joint health. HEAD-US correlated strongly with HJHS. In 5%, HEAD-US detected subclinical pathology. Crepitus on motion was frequently reported despite normal HEAD-US, thus not necessarily reflecting arthropathy. HEAD-US therefore improves the joint assessment in moderate haemophilia.
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| 7. |
- Måseide, Ragnhild J., et al.
(author)
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Health-related quality of life and physical activity in Nordic patients with moderate haemophilia A and B (the MoHem study)
- 2023
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In: Haemophilia. - 1351-8216. ; 30:1, s. 98-105
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Journal article (peer-reviewed)abstract
- Introduction: The impact of moderate haemophilia on health-related quality of life (HRQoL) and physical activity (PA) is not well known. In previous studies, persons with factor VIII/factor IX activity (FVIII/FIX:C) below 3 IU/dL were associated with a more severe bleeding phenotype than predicted. Aim: To explore HRQoL and PA in patients with moderate haemophilia A (MHA) and B (MHB). Methods: A cross-sectional, multicentre study covering patients with MHA and MHB in Sweden, Finland, and Norway. HRQoL was assessed with the EuroQoL 5-Dimensions (EQ-5D) form and PA with the International Physical Activity Questionnaire among participants aged ≥15 years. Results: We report on 104 patients aged 15–84 years from the MoHem study. Overall, EQ-5D utility was.85 (median) (Q1–Q3 0.73–1.0) with corresponding visual analogue scale (VAS) 80 (70–90), which were similar regardless of treatment modality, FVIII/FIX:C, and MHA or MHB. Pain and mobility were most frequently affected dimensions. Utility (r = -.54), VAS (r = -.42), and PA (r = -.32) correlated negatively with arthropathy (HJHS). Only patients aged 41–50 years displayed lower utility (p =.02) and VAS (p <.01) than the Norwegian population norm. Patients on prophylaxis aged 35–54 years reported higher PA than those treated on-demand (p =.01). Conclusion: Haemophilic arthropathy had negative impact on HRQoL and PA in Nordic patients with moderate haemophilia. Middle-aged patients captured lower utility and VAS than observed in the general population. Tailored prophylaxis and improved joint health may influence positively on HRQoL and PA also in moderate haemophilia.
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| 8. |
- Måseide, Ragnhild J., et al.
(author)
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Joint health and treatment modalities in Nordic patients with moderate haemophilia A and B – The MoHem study
- 2020
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In: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 26:5, s. 891-897
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Journal article (peer-reviewed)abstract
- Introduction: The prevalence of arthropathy in moderate haemophilia A (MHA) and B (MHB) is not well known. Aim: We evaluated joint health in Nordic patients in relation to their treatment modality. Methods: A cross-sectional, multicentre study covering MHA and MHB in Sweden, Finland and Norway. Arthropathy was evaluated by ultrasound (HEAD-US) and Haemophilia Joint Health Score (HJHS). Results: We report on 145 patients: median age 28 years (IQR 13-52) and 61% MHA. Baseline factor VIII/factor IX activity (FVIII/FIX:C) was 2 IU/dL (median) (IQR 2-4): lower for MHB (2 IU/dL, IQR 1-2) than MHA (3 IU/dL, IQR 2-4) (P <.01). Eighty-five per cent of MHA and 73% MHB had a history of haemarthrosis (P =.07). Age at first joint bleed was lower for MHA (5 years [median], IQR 3-7) than MHB (7 years, IQR 5-12) (P =.01). Thirty-eight per cent received prophylaxis, started at median 10 years of age (IQR 4-24). Median joint bleeds and serious other bleeds during the last 12 months were both zero (IQR 0-1). Total HEAD-US captured 0/48 points (median) (IQR 0-2) and HJHS 4/120 points (IQR 1-10) with strong correlation between them (r =.72). FVIII/FIX:C ≤ 3 IU/dL was associated with higher HJHS (P =.04). Fifteen per cent had undergone orthopaedic surgery. Conclusion: The current joint health in Nordic moderate haemophilia patients was rather good, but a subgroup had severe arthropathy. FVIII/FIX:C ≤ 3 IU/dL and MHA were associated with a more severe bleeding phenotype. We suggest primary prophylaxis to all patients with FVIII/FIX:C ≤ 3 IU/dL.
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| 9. |
- Ranta, Susanna, et al.
(author)
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Cerebral sinus venous thromboses in children with acute lymphoblastic leukaemia - a multicentre study from the Nordic Society of Paediatric Haematology and Oncology
- 2015
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In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 168:4, s. 547-552
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Journal article (peer-reviewed)abstract
- We present a prospective multicentre cohort of 20 children with acute lymphoblastic leukaemia (ALL) and cerebral sinus venous thrombosis (CSVT). The study covers a period of 5years and comprises 1038 children treated according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL 2008 protocol. The cumulative incidence of CSVT was 2%. Sixteen of the thromboses were related to asparaginase and 16 to steroids. Most CSVTs occurred in the consolidation phase. Nearly all were treated with low molecular weight heparin without bleeding complications. Mortality related to CSVT directly or indirectly was 10%, emphasizing the importance of this complication.
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| 10. |
- Tesi, Bianca, et al.
(author)
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Diagnostic yield and clinical impact of germline sequencing in children with CNS and extracranial solid tumors : a nationwide, prospective Swedish study
- 2024
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In: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 39
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Journal article (peer-reviewed)abstract
- BackgroundChildhood cancer predisposition (ChiCaP) syndromes are increasingly recognized as contributing factors to childhood cancer development. Yet, due to variable availability of germline testing, many children with ChiCaP might go undetected today. We report results from the nationwide and prospective ChiCaP study that investigated diagnostic yield and clinical impact of integrating germline whole-genome sequencing (gWGS) with tumor sequencing and systematic phenotyping in children with solid tumors.MethodsgWGS was performed in 309 children at diagnosis of CNS (n = 123, 40%) or extracranial (n = 186, 60%) solid tumors and analyzed for disease-causing variants in 189 known cancer predisposing genes. Tumor sequencing data were available for 74% (227/309) of patients. In addition, a standardized clinical assessment for underlying predisposition was performed in 95% (293/309) of patients.FindingsThe prevalence of ChiCaP diagnoses was 11% (35/309), of which 69% (24/35) were unknown at inclusion (diagnostic yield 8%, 24/298). A second-hit and/or relevant mutational signature was observed in 19/21 (90%) tumors with informative data. ChiCaP diagnoses were more prevalent among patients with retinoblastomas (50%, 6/12) and high-grade astrocytomas (37%, 6/16), and in those with non-cancer related features (23%, 20/88), and ≥2 positive ChiCaP criteria (28%, 22/79). ChiCaP diagnoses were autosomal dominant in 80% (28/35) of patients, yet confirmed de novo in 64% (18/28). The 35 ChiCaP findings resulted in tailored surveillance (86%, 30/35) and treatment recommendations (31%, 11/35).InterpretationOverall, our results demonstrate that systematic phenotyping, combined with genomics-based diagnostics of ChiCaP in children with solid tumors is feasible in large-scale clinical practice and critically guides personalized care in a sizable proportion of patients.
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