| 1. |
- Alfredson, Håkan, et al.
(författare)
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Chronic Achilles tendinosis : recommendations for treatment and prevention.
- 2000
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Ingår i: Sports Medicine. - 0112-1642 .- 1179-2035. ; 29:2, s. 135-146
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Tidskriftsartikel (refereegranskat)abstract
- Chronic Achilles tendinosis is a condition with an unknown aetiology and pathogenesis that is often, but not always, associated with pain during loading of the Achilles tendon. Histologically, there are no inflammatory cells, but increased amounts of interfibrillar glycosaminoglycans and changes in the collagen fibre structure and arrangement are seen. In situ microdialysis has confirmed the absence of inflammation. It is a condition that is most often seen among recreational male runners aged between 35 and 45 years, and it is most often considered to be associated with overuse. However, this condition is also seen in patients with a sedentary lifestyle. Chronic Achilles tendinosis is considered a troublesome injury to treat. Nonsurgical treatment most often includes a combination of rest, NSAIDs, correction of malalignments, and stretching and strengthening exercises, but there is sparse scientific evidence supporting the use of most proposed treatment regimens. It has been stated that, in general, nonsurgical treatment is not successful and surgical treatment is required in about 25% of patients. However, in a recent prospective study, treatment with heavy load eccentric calf muscle training showed very promising results and may possibly reduce the need for surgical treatment of tendinosis located in the midportion of the Achilles tendon. The short term results after surgical treatment are frequently very good, but in the few studies with long term follow-up there are signs of a possible deterioration with time. Calf muscle strength takes a long time to recover and, furthermore, a prolonged progressive calcaneal bone loss has been shown on the operated side up to 1 year after surgical treatment.
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| 2. |
- Benedicks, Michael, et al.
(författare)
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Markov extensions and decay of correlations for certain Henon maps
- 2000
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Ingår i: Astérisque. - 0303-1179. ; :261, s. 13-56
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Tidskriftsartikel (refereegranskat)abstract
- Henon maps for which the analysis in [BC2] applies are considered. Sets with good hyperbolic properties and nice return structures are constructed and their return time functions are shown to have exponentially decaying tails. This sets the stage for applying the results in [Y]. Statistical properties such as exponential decay of correlations and central limit theorem are proved.
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| 3. |
- Lubenow, Norbert, et al.
(författare)
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Heparin-induced thrombocytopenia : recommendations for optimal use of recombinant hirudin.
- 2000
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Ingår i: BioDrugs. - 1173-8804 .- 1179-190X. ; 14:2, s. 109-25
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Tidskriftsartikel (refereegranskat)abstract
- Recombinant hirudins have a definite role in the treatment of patients with heparin-induced thrombocytopenia (HIT). The most important adverse effects are haemorrhages and the induction of antihirudin antibodies. Major haemorrhages were not significantly increased in patients with HIT compared with a historical control group, but prospective data comparing hirudin and heparinoids such as danaparoid are lacking. The definition of the optimal method for monitoring and the availability of an antidote for hirudin would probably increase safety with this drug. To date, haemofiltration using high-flux filter systems is the only way to remove an overdosage of hirudin from the circulation. In patients with renal impairment requiring hirudin treatment, it therefore seems safer to start with a low dose that is subsequently adjusted according to the activated partial prothromboplastin time or ecarin clotting time. Even in special circumstances, such as cardiopulmonary bypass or dialysis, hirudins can be applied successfully if care is taken to monitor their effects meticulously. There are many other indications in which hirudins have shown feasibility (e.g. acute coronary syndromes) but available data preclude definite conclusions.
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| 4. |
- Winqvist, Ola, et al.
(författare)
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Autoimmune adrenal insufficiency : recognition and management
- 2000
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Ingår i: BioDrugs. - 1173-8804 .- 1179-190X. ; 13:2, s. 107-114
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Tidskriftsartikel (refereegranskat)abstract
- The main cause of Addison's disease is an autoimmune organ-specific destruction of the cells in the adrenal cortex by an autoreactive process of activated immune cells directed against the steroid-synthesising enzyme 21-hydroxylase. The diagnosis of Addison's disease is suspected in a patient presenting with symptoms of fatigue, bodyweight loss, anorexia, salt craving, and signs of low blood pressure and hyperpigmentation of the skin. Laboratory findings include electrolyte disturbances, and typically an elevated serum potassium level and sometimes a low serum sodium level is found together with low plasma levels of basal and corticotropin-stimulated hydrocortisone (cortisol). An aetiological diagnosis can rapidly be made using commercially available assays demonstrating the presence of autoantibodies directed against 21-hydroxylase. Determination of 21-hydroxylase autoantibodies also permits early diagnosis before a complete adrenocortical destruction has occurred. Thus, a window of opportunity for an early immunomodulatory intervention therapy may exist. Patients presenting with an acute adrenocortical crisis should be treated with 100mg of hydrocortisone and saline intravenously without awaiting laboratory results. Maintenance therapy includes substitution of glucocorticoid and mineralocorticoid steroids, using divided and lower total dosages of glucocorticoids than previously used.
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| 5. |
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| 6. |
- Concolino, P, et al.
(författare)
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CAH-X Syndrome: Genetic and Clinical Profile
- 2022
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Ingår i: Molecular diagnosis & therapy. - : Springer Science and Business Media LLC. - 1179-2000 .- 1177-1062. ; 26:3, s. 293-300
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Tidskriftsartikel (refereegranskat)
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| 7. |
- Hedenström, Per, et al.
(författare)
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Pretreatment Tumor DNA Sequencing of KIT and PDGFRA in Endosonography-Guided Biopsies Optimizes the Preoperative Management of Gastrointestinal Stromal Tumors
- 2020
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Ingår i: Molecular Diagnosis & Therapy. - : Springer Science and Business Media LLC. - 1177-1062 .- 1179-2000.
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Tidskriftsartikel (refereegranskat)abstract
- Background Neoadjuvant tyrosine kinase inhibitor (TKI) therapy increases the chance of organ-preserving, radical resection in selected patients with gastrointestinal stromal tumors (GISTs). We aimed to evaluate systematic, immediate DNA sequencing of KIT and PDGFRA in pretreatment GIST tissue to guide neoadjuvant TKI therapy and optimize preoperative tumor response. Methods All patients who were candidates for neoadjuvant therapy of a suspected GIST [the study cohort (SC)] were prospectively included from January 2014 to March 2018. Patients were subjected to pretreatment endosonography-guided fine-needle biopsy (EUS-FNB) or transabdominal ultrasound-guided needle biopsy (TUS-NB), followed by immediate tumor DNA sequencing (< 2 weeks). A historic (2006-2013) reference cohort (RC) underwent work-up without sequencing before neoadjuvant imatinib (n = 42). The rate of optimal neoadjuvant therapy (Therapy(OPTIMAL)) was calculated, and the induced tumor size reduction (Tumor Regression(MAX), %) was evaluated by computed tomography (CT) scan. Results The success rate of pretreatment tumor DNA sequencing in the SC (n = 81) was 77/81 (95%) [EUS-FNB 71/74 (96%); TUS-NB 6/7 (86%)], with mutations localized in KIT (n = 58), PDGFRA (n = 18), or neither gene, wild type (n = 5). In patients with a final indication for neoadjuvant therapy, the Therapy(OPTIMAL) was higher in the SC compared with the RC [61/63 (97%) versus 33/42 (79%), p = 0.006], leading to a significantly higher Tumor Regression(MAX) in patients treated with TKI (27% vs. 19%, p = 0.015). Conclusions Pretreatment endosonography-guided biopsy sampling followed by immediate tumor DNA sequencing of KIT and PDGFRA is highly accurate and valuable in guiding neoadjuvant TKI therapy in GIST. This approach minimizes maltreatment with inappropriate regimens and leads to improved tumor size reduction before surgery.
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| 8. |
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| 9. |
- Keshavan, A., et al.
(författare)
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Blood Biomarkers for Alzheimer's Disease: Much Promise, Cautious Progress
- 2017
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Ingår i: Molecular Diagnosis & Therapy. - : Springer Science and Business Media LLC. - 1177-1062 .- 1179-2000. ; 21:1, s. 13-22
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Tidskriftsartikel (refereegranskat)abstract
- Biomarkers in Alzheimer's disease (AD) have the potential to allow early and more accurate diagnosis, predict disease progression, stratify individuals and track response to candidate therapies in drug trials. The first fluid biomarkers reflecting aspects of AD neuropathology were identified in cerebrospinal fluid (CSF) in the 1990s. Three CSF biomarkers (amyloid-beta 1-42, total tau and phospho-tau) have consistently been shown to have diagnostic utility and are incorporated into the new diagnostic criteria for AD. These markers have also been shown in longitudinal studies to predict conversion of mild cognitive impairment to AD. However, a key issue with the use of CSF biomarkers as a screening test is the invasiveness of lumbar puncture. Over the last 20 years there has been an active quest for blood biomarkers, which could be easily acquired and tested repeatedly throughout the disease course. One approach to identifying such markers is to attempt to measure candidates that have already been identified in CSF. Until recently, this approach has been limited by assay sensitivity, but newer platforms now allow single molecule-level detection. Another approach is identification of candidates in large multiplex panels that allow for multiple analytes to be quantified in parallel. While both approaches show promise, to date no blood-based biomarker or combination of biomarkers has sufficient predictive value to have utility in clinical practice. In this review, an overview of promising blood protein candidates is provided, and the challenges of validating and converting these into practicable tests are discussed.
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| 10. |
- Paterson, Ross W, et al.
(författare)
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Biomarker Modelling of Early Molecular Changes in Alzheimer's Disease.
- 2014
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Ingår i: Molecular diagnosis & therapy. - : Springer Science and Business Media LLC. - 1179-2000 .- 1177-1062. ; 18:2, s. 213-227
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Forskningsöversikt (refereegranskat)abstract
- The preclinical phase of Alzheimer's disease (AD) occurs years, possibly decades, before the onset of clinical symptoms. Being able to detect the very earliest stages of AD is critical to improving understanding of AD biology, and identifying individuals at greatest risk of developing clinical symptoms with a view to treating AD pathophysiology before irreversible neurodegeneration occurs. Studies of dominantly inherited AD families and longitudinal studies of sporadic AD have contributed to knowledge of the earliest AD biomarkers. Here we appraise this evidence before reviewing novel, particularly fluid, biomarkers that may provide insights into AD pathogenesis and relate these to existing hypothetical disease models.
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| 11. |
- Pisanu, Claudia, et al.
(författare)
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The Role of Pharmacogenomics in Bipolar Disorder : Moving Towards Precision Medicine
- 2018
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Ingår i: Molecular Diagnosis & Therapy. - : Springer Science and Business Media LLC. - 1177-1062 .- 1179-2000. ; 22:4, s. 409-420
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Forskningsöversikt (refereegranskat)abstract
- Bipolar disorder (BD) is a common and disabling psychiatric condition with a severe socioeconomic impact. BD is treated with mood stabilizers, among which lithium represents the first-line treatment. Lithium alone or in combination is effective in 60% of chronically treated patients, but response remains heterogenous and a large number of patients require a change in therapy after several weeks or months. Many studies have so far tried to identify molecular and genetic markers that could help us to predict response to mood stabilizers or the risk for adverse drug reactions. Pharmacogenetic studies in BD have been for the most part focused on lithium, but the complexity and variability of the response phenotype, together with the unclear mechanism of action of lithium, limited the power of these studies to identify robust biomarkers. Recent pharmacogenomic studies on lithium response have provided promising findings, suggesting that the integration of genome-wide investigations with deep phenotyping, in silico analyses and machine learning could lead us closer to personalized treatments for BD. Nevertheless, to date none of the genes suggested by pharmacogenetic studies on mood stabilizers have been included in any of the genetic tests approved by the Food and Drug Administration (FDA) for drug efficacy. On the other hand, genetic information has been included in drug labels to test for the safety of carbamazepine and valproate. In this review, we will outline available studies investigating the pharmacogenetics and pharmacogenomics of lithium and other mood stabilizers, with a specific focus on the limitations of these studies and potential strategies to overcome them. We will also discuss FDA-approved pharmacogenetic tests for treatments commonly used in the management of BD.
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| 12. |
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| 13. |
- Shipitsyna, Elena, et al.
(författare)
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Quantitation of all Four Gardnerella vaginalis Clades Detects Abnormal Vaginal Microbiota Characteristic of Bacterial Vaginosis More Accurately than Putative G. vaginalis Sialidase A Gene Count
- 2019
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Ingår i: Molecular Diagnosis & Therapy. - : Adis International Ltd.. - 1177-1062 .- 1179-2000. ; 23:1, s. 139-147
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Tidskriftsartikel (refereegranskat)abstract
- Background: Bacterial vaginosis (BV) is a vaginal disorder characterized by a depletion of the normal lactobacillus-dominant microbiota and overgrowth of mainly anaerobic bacteria.Objectives: The study aimed to evaluate the distribution and abundance of the Gardnerella vaginalis clades and sialidase A gene in vaginal samples from Russian women, and investigate if the G. vaginalis sialidase A gene count detects an abnormal vaginal microbiota characteristic of BV more accurately than G. vaginalis load.Methods: Vaginal samples from 299 non-pregnant patients of gynecological clinics were examined using Nugent scores and G. vaginalis clade and sialidase A gene quantitative real-time polymerase chain reactions (PCRs). Discriminatory power for BV microbiota was evaluated with receiver operating characteristic (ROC) analysis.Results: The vaginal microbiota was characterized by Nugent scores as normal, intermediate, and BV microbiota in 162, 58, and 79 women, respectively. G. vaginalis clades 1, 2, 3, 4, and the sialidase A gene were detected in 56% (51-62%), 40% (34-45%), 20% (16-25%), 94% (91-96%), and 70% (64-75%) of vaginal samples, respectively. The frequency and abundance of clades 1, 2, 4, and the sialidase A gene as well as clade multiplicity were significantly associated with abnormal microbiota. The sialidase A gene was present in all multi-clade samples, in all single-clade samples comprising clades 1, 2, and 3, and in four of 84 (5% [2-12%]) samples comprising clade 4 only. Total G. vaginalis load showed significantly higher discriminatory power for abnormal microbiota than sialidase A gene count (areas under ROC curves 0.933 vs. 0.881; p = 0.0306).Conclusions: Quantifying all four G. vaginalis clades discriminates between BV microbiota and normal microbiota more accurately than measuring G. vaginalis sialidase A gene. Clade 4 is strongly associated with BV microbiota, despite most clade 4 strains lacking the sialidase A gene.
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| 14. |
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| 15. |
- Daniels, Pablo P., et al.
(författare)
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A new species and a new combination of Rhodophana (Entolomataceae, Agaricales) from Africa
- 2017
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Ingår i: Phytotaxa. - : Magnolia Press. - 1179-3155 .- 1179-3163. ; 306:3, s. 223-233
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Tidskriftsartikel (refereegranskat)abstract
- Multiple collections of a new member of the Entolomataceae were found in W National Park of Niger during a survey of macrofungi. This new species with a dark reddish brown scaly pileus surface and a yellow stipe belongs in the genus Rhodophana of the Rhodocybe-Clitopilus clade in the Entolomataceae. Using a three-gene analysis of the phylogenetic position of Rhodophana flavipes it is most closely related to the recently described Rhodophana squamulosa from India and is a sister taxon to Rhodophana nitellina and R. melleopallens. Micromorphological examination of the type of Rhodocybe fibulata, another African species with a scaly cap, confirms that it belongs in Rhodophana, thus a new combination Rhodophana fibulata is proposed.
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| 16. |
- Lönnell, Niklas
(författare)
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New combinations within the genus Sphagnum (Sphagnaceae, Bryophyta)
- 2018
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Ingår i: Phytotaxa. - : Magnolia Press. - 1179-3155 .- 1179-3163. ; 369, s. 57-58
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Tidskriftsartikel (refereegranskat)abstract
- The genus Sphagnum is known for its morphological variable species, showing plastic responses along environmental gradients (Stenøien et al. 1997). Consequently, species delimitation based on morphological characters is not always straight forward. However, molecular analysis have in some cases pointed to differentiated entities within morphologically recognised taxa, e.g. Sphagnum fuscum (Schimper 1871:63) Klinggräff (1872:4) and Sphagnum magellanicum Bridel (1798:24) (Kyrkjeeide et al. 2015, Yousefi et al. 2017). In other cases, molecular markers have not resolved closely related taxa. A study based on isoenzymes could, for instance, not differentiate Sphagnum viride Flatberg (1988:9) from Sphagnum cuspidatum Ehrh. ex Hoffmann (1796:22) (Hanssen et al. 2000). Moreover, a study based on isoenzymes and RAPD could not differentiate Sphagnum isoviitae Flatberg (1992:2) and Sphagnum brevifolium (Lindb. ex Braithwaite (1878:84)) Röll (1889:340) from Sphagnum fallax (Klinggräff 1872:7) Klinggräff (1880: 128) (Såstad et al. 1999). Hence, the treatment of these taxa at the species level may be questioned. The material used in the studies was limited, and the use of more modern molecular markers might lead to other conclusions. Recognition of the taxa at variety level seems to be a reasonable solution, given our current knowledge. We therefore propose that S. viride, S. isoviitae and S. brevifolium be treated at the variety level while we await more comprehensive genetic studies, which may provide conclusive evidence concerning the status of these taxa.
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| 17. |
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| 18. |
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| 19. |
- Ghatnekar, Ola, et al.
(författare)
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Medical Resource Utilization and Cost of HIV-Related Care in the Highly Active Antiretroviral Therapy Era at a University Clinic in Sweden.
- 2010
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Ingår i: PharmacoEconomics. - : Springer Science and Business Media LLC. - 1179-2027 .- 1170-7690. ; 28:S1, s. 49-57
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Little is known regarding healthcare costs for HIV/AIDS patients in the era of highly active antiretroviral therapy (HAART) and subgroups of patients according to the severity and progression of HIV infection in Sweden. The objective of this study is therefore to describe the direct medical resource use and cost of healthcare for HIV patients at a university clinic in Sweden. Methods: A patient registry database for HIV treatment at the Department of Infectious Diseases, Sahlgrenska University Hospital, between 2000 and 2005 provided information on patient characteristics, antiretroviral drugs and dosages, tests and diagnostic procedures, outpatient visits and inpatient stays. The review used publicly available unit costs with a county council perspective, expressed in 2006 Euros. Results: Two hundred and eighty-five patients with a mean age of 38 years in 2000 (64% men) were followed for 1368 patient-years. They had a mean (median) of 6.3 (0) inpatient days, 4.1 (3.7) physician visits, 4.2 (3.8) nurse visits, 2.6 (0.7) counsellor visits and 11.5 (7.7) tests and diagnostic procedures per patient-year. Only 12 deaths were recorded during the study period, and the proportion of treated patients with successful treatment (HIV-RNA <50copies/mL) increased from 74% to 92% during the period. The mean cost per patient-month amounted to &U20AC;1069. The main cost driver was HIV drugs (51%), followed by inpatient stays (including hospitalizations for opportunistic infections; 22%), outpatient physician, nurse or therapist visits (19%) and diagnostics and tests (7%). All non-drug costs increased with a decreasing CD4 cell count. Conclusions: Overall, approximately half of the direct costs of HIV treatment were not related to antiretroviral treatment. The non-antiretroviral costs were inversely correlated with HIV-induced immune deficiency.
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| 20. |
- Okoye, Chukwuma, et al.
(författare)
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Discontinuation of Loop Diuretics in Older Patients with Chronic Stable Heart Failure : A Narrative Review
- 2023
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Ingår i: Drugs & Aging. - 1170-229X .- 1179-1969. ; 40, s. 981-990
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Forskningsöversikt (refereegranskat)abstract
- Loop diuretics (LDs) represent the cornerstone treatment for relieving pulmonary congestion in patients with heart failure (HF). Their benefit is well-recognized in the short term because of their ability to eliminate fluid retention. However, long term, they could adversely influence prognosis due to activation of the neurohumoral mechanism, particularly in older, frail patients. Moreover, the advent of new drugs capable of improving outcomes and reducing pulmonary and systemic congestion signs in HF emphasizes the possibility of a progressive reduction and discontinuation of LD treatment. Nevertheless, few studies were aimed at investigating the safety of LDs withdrawal in older patients with chronic stable HF. This current review aims to approach current evidence regarding the safety and effectiveness of LDs discontinuation in patients with chronic stable HF, and is based on the material obtained via the PubMed and Scopus databases from January 2000 to November 2022. Our search yielded five relevant studies, including two randomized controlled trials. All participants presented stable HF at the time of study enrolment. Apart from one study, all the investigations were conducted in patients with HF with reduced ejection fraction. The most common outcomes examined were the need for diuretic resumption or the event of death and rehospitalization after diuretic withdrawal. As a whole, although based on a few investigations with a low grade of evidence, diuretic therapy discontinuation might be a safe strategy that deserves consideration for patients with stable HF. However, extensive investigations in older adults, accounting for frailty status, are warranted to confirm these data in this peculiar class of patients.
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| 21. |
- Wu, Yunjiao, et al.
(författare)
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Pre- and Postnatal Maturation are Important for Fentanyl Exposure in Preterm and Term Newborns : A Pooled Population Pharmacokinetic Study
- 2022
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Ingår i: Clinical Pharmacokinetics. - : Springer Science and Business Media LLC. - 0312-5963 .- 1179-1926. ; 61:3, s. 401-412
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objective: Fentanyl is an opioid commonly used to prevent and treat severe pain in neonates; however, its use is off label and mostly based on bodyweight. Given the limited pharmacokinetic information across the entire neonatal age range, we characterized the pharmacokinetics of fentanyl across preterm and term neonates to individualize dosing. Methods: We pooled data from two previous studies on 164 newborns with a median gestational age of 29.0 weeks (range 23.9–42.3), birthweight of 1055 g (range 390–4245), and postnatal age (PNA) of 1 day (range 0–68). In total, 673 plasma samples upon bolus dosing (69 patients; median dose 2.1 μg/kg, median 2 boluses per patient) or continuous infusions (95 patients; median dose 1.1 μg/kg/h for 30 h) with and without boluses were used for population pharmacokinetic modeling in NONMEM® 7.4. Results: Clearance in neonates with birthweight of 2000 and 3000 g was 2.8- and 5.0-fold the clearance in a neonate with birthweight of 1000 g, respectively. Fentanyl clearance at PNA of 7, 14, and 21 days was 2.7-fold, 3.8-fold, and 4.6-fold the clearance at 1 day, respectively. Bodyweight-based dosing resulted in large differences in fentanyl concentrations. Depending on PNA and birthweight, fentanyl concentrations increased slowly after the start of therapy for both intermittent boluses and continuous infusion and reached a maximum concentration at 12–48 h. Conclusions: As both prenatal and postnatal maturation are important for fentanyl exposure, we propose a birthweight- and PNA-based dosage regimen. To provide rapid analgesia in the first 24 h of treatment, additional loading doses need to be considered.
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| 22. |
- Jönsson, Anna K., et al.
(författare)
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Venous Thromboembolism in Recipients of Antipsychotics : Incidence, Mechanisms and Management
- 2012
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Ingår i: CNS Drugs. - : Adis. - 1172-7047 .- 1179-1934. ; 26:8, s. 649-662
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Forskningsöversikt (refereegranskat)abstract
- Since chlorpromazine was introduced to the market in the early 1950s, theuse of antipsychotic drugs has been associated with venous thromboembolism(VTE) in a number of reports. During the last decade the evidence hasbeen strengthened with large epidemiological studies. Whether all antipsychoticsincrease the risk for VTE or the risk is confined to certain drugs is stillunclear. The aim of this article is to present an updated critical reviewfocusing on the incidence, mechanisms and management of VTE in users ofantipsychotics. After searching the databases PubMed and Scopus for relevantarticles we identified 12 observational studies, all of which were publishedafter the year 2000. In most of these studies an elevated risk of VTE wasobserved for antipsychotic drugs, with the highest risk for clozapine, olanzapineand low-potency first-generation antipsychotics. The risk seems to becorrelated with dose. The elderly, who mainly use lower doses, do not showan increased risk of VTE to the same extent as younger subjects.The underlying biological mechanisms explaining the association betweenantipsychotic medication and VTE are to a large extent unknown. Severalhypotheses have been proposed, such as body weight gain, sedation, enhancedplatelet aggregation, increased levels of antiphospholipid antibodies,hyperprolactinaemia and hyperhomocysteinaemia. The risk of VTE in schizophreniaand other psychotic disorders may also be related to the underlyingdisease rather than the medication.Very limited evidence exists to guide how cases of VTE in subjects usingantipsychotics should be handled. An attempt to compile an algorithm wherethe patients’ individual risk of VTE is assessed and preventive clinical measuresare suggested has been published recently. Strong consideration shouldbe given to discontinuation of the offending antipsychotic drug in patientsexperiencing a VTE, and another antipsychotic drug with a presumably lowerrisk should be chosen if antipsychotic drug treatment is still indicated. It isessential that physicians and patients are aware that VTE may be an adversedrug reaction to the antipsychotic treatment so the condition is identifiedearly and treated appropriately.
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| 23. |
- Verrest, Luka, et al.
(författare)
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Lack of Clinical Pharmacokinetic Studies to Optimize the Treatment of Neglected Tropical Diseases : A Systematic Review.
- 2017
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Ingår i: Clinical Pharmacokinetics. - : Springer Science and Business Media LLC. - 0312-5963 .- 1179-1926. ; 56:6, s. 583-606
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Forskningsöversikt (refereegranskat)abstract
- INTRODUCTION: Neglected tropical diseases (NTDs) affect more than one billion people, mainly living in developing countries. For most of these NTDs, treatment is suboptimal. To optimize treatment regimens, clinical pharmacokinetic studies are required where they have not been previously conducted to enable the use of pharmacometric modeling and simulation techniques in their application, which can provide substantial advantages.OBJECTIVES: Our aim was to provide a systematic overview and summary of all clinical pharmacokinetic studies in NTDs and to assess the use of pharmacometrics in these studies, as well as to identify which of the NTDs or which treatments have not been sufficiently studied.METHODS: PubMed was systematically searched for all clinical trials and case reports until the end of 2015 that described the pharmacokinetics of a drug in the context of treating any of the NTDs in patients or healthy volunteers.RESULTS: Eighty-two pharmacokinetic studies were identified. Most studies included small patient numbers (only five studies included >50 subjects) and only nine (11 %) studies included pediatric patients. A large part of the studies was not very recent; 56 % of studies were published before 2000. Most studies applied non-compartmental analysis methods for pharmacokinetic analysis (62 %). Twelve studies used population-based compartmental analysis (15 %) and eight (10 %) additionally performed simulations or extrapolation. For ten out of the 17 NTDs, none or only very few pharmacokinetic studies could be identified.CONCLUSIONS: For most NTDs, adequate pharmacokinetic studies are lacking and population-based modeling and simulation techniques have not generally been applied. Pharmacokinetic clinical trials that enable population pharmacokinetic modeling are needed to make better use of the available data. Simulation-based studies should be employed to enable the design of improved dosing regimens and more optimally use the limited resources to effectively provide therapy in this neglected area.
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| 24. |
- Aagaard, Lise, et al.
(författare)
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Global Patterns of Adverse Drug Reactions Over a Decade Analyses of Spontaneous Reports to VigiBase (TM)
- 2012
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Ingår i: Drug Safety. - : Adis. - 0114-5916 .- 1179-1942. ; 35:12, s. 1171-1182
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although systems to collect information about suspected adverse drug reactions (ADRs) were established in many countries and by the WHO in the 1960s, few studies have examined reported ADRs related to national income. Objective: The aim of the study was to characterize ADRs reported to the WHO-ADR database, VigiBase (TM), and to relate data to national income. Methods: We analysed ADR reports submitted to VigiBase (TM) from 2000 to 2009 with respect to reporting rate, age and sex of patient, type, seriousness and medications. Reports were also analysed with respect to national income level, classified in accordance with the World Bank definition: low, lower-middle, upper-middle and high. Results: We analysed 1 359 067 ADR reports including 3 013 074 ADRs. Overall, 16% of reports were serious and 60% were reported for females. High-income countries had the highest ADR reporting rates (range 3-613 reports/million inhabitants/year) and low-income countries the lowest (range 0-21). Distribution of ADRs across income groups with respect to age group, seriousness and sex was non-significant. Overall, the majority of ADRs were reported for nervous system medications, followed by cardiovascular medicines. Low-income countries reported relatively more ADRs for antiinfectives for systemic use than high-income countries, and high-income countries reported more ADRs for antineoplastic and immunomodulating agents than lower-income groups. Conclusion: This study showed that high-income countries had the highest ADR reporting rates and low-income countries the lowest, with large variations across countries in each group. Significant differences in ADR reporting rates were only found for ADRs of the type skin and subcutaneous tissue disorders and for the therapeutic groups antiinfectives for systemic use and antineoplastic and immunomodulation agents. To strengthen ADR reporting rates, especially in low-income countries, more research is needed about the impact of organizational structures and economic resources of national pharmacovigilance centres and ADR reporting practices on the large variations in ADR reporting rates within income groups.
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| 25. |
- Tregunno, Philip Michael, et al.
(författare)
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Performance of Probabilistic Method to Detect Duplicate Individual Case Safety Reports
- 2014
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Ingår i: Drug Safety. - : Springer Science and Business Media LLC. - 0114-5916 .- 1179-1942. ; 37:4, s. 249-258
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Tidskriftsartikel (refereegranskat)abstract
- Individual case reports of suspected harm from medicines are fundamental for signal detection in postmarketing surveillance. Their effective analysis requires reliable data and one challenge is report duplication. These are multiple unlinked records describing the same suspected adverse drug reaction (ADR) in a particular patient. They distort statistical screening and can mislead clinical assessment. Many organisations rely on rule-based detection, but probabilistic record matching is an alternative. The aim of this study was to evaluate probabilistic record matching for duplicate detection, and to characterise the main sources of duplicate reports within each data set. vigiMatch (TM), a published probabilistic record matching algorithm, was applied to the WHO global individual case safety reports database, VigiBase(A (R)), for reports submitted between 2000 and 2010. Reported drugs, ADRs, patient age, sex, country of origin, and date of onset were considered in the matching. Suspected duplicates for the UK, Denmark, and Spain were reviewed and classified by the respective national centre. This included evaluation to determine whether confirmed duplicates had already been identified by in-house, rule-based screening. Furthermore, each confirmed duplicate was classified with respect to the likely source of duplication. For each country, the proportions of suspected duplicates classified as confirmed duplicates, likely duplicates, otherwise related, and unrelated were obtained. The proportions of confirmed or likely duplicates that were not previously known by the national organisation were determined, and variations in the rates of suspected duplicates across subsets of reports were characterised. Overall, 2.5 % of the reports with sufficient information to be evaluated by vigiMatch were classified as suspected duplicates. The rates for the three countries considered in this study were 1.4 % (UK), 1.0 % (Denmark), and 0.7 % (Spain). Higher rates of suspected duplicates were observed for literature reports (11 %) and reports with fatal outcome (5 %), whereas a lower rate was observed for reports from consumers and non-health professionals (0.5 %). The predictive value for confirmed or likely duplicates among reports flagged as suspected duplicates by vigiMatch ranged from 86 % for the UK, to 64 % for Denmark and 33 % for Spain. The proportions of confirmed duplicates that were previously unknown to national centres ranged from 89 % for Spain, to 60 % for the UK and 38 % for Denmark, despite in-house duplicate detection processes in routine use. The proportion of unrelated cases among suspected duplicates were below 10 % for each national centre in the study. Probabilistic record matching, as implemented in vigiMatch, achieved good predictive value for confirmed or likely duplicates in each data source. Most of the false positives corresponded to otherwise related reports; less than 10 % were altogether unrelated. A substantial proportion of the correctly identified duplicates had not previously been detected by national centre activity. On one hand, vigiMatch highlighted duplicates that had been missed by rule-based methods, and on the other hand its lower total number of suspected duplicates to review improved the accuracy of manual review.
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